The importance of set up time and temperature in real-time PCR; an essential reminder.

Abstract:
BACKGROUND
Non-specific amplification can arise in real-time PCR when temperatures are above 4°C during PCR set up. Pressure of high throughput tests, particularly in a clinical setting, can lead to short cuts being taken during PCR set up.

OBJECTIVES
This study set out to evaluate the outcome of exposing a real-time PCR assay to increasing durations of room temperature prior to PCR amplification.

STUDY DESIGN
A real-time PCR assay was exposed to increasing durations of room temperature prior to PCR amplification.

RESULTS
We found that reactions left at room temperature for 30min or more produced non-specific traces in the negative controls which could be mistaken for weak positive traces. In addition we found that the fluorescence of positive control traces was significantly reduced indicating reduced reaction efficiency, however the Ct valves were comparable between all reactions highlighting that control Ct monitoring alone would not have detected this issue.

CONCLUSIONS
This study acts as a reminder for PCR users to set up reactions on ice/chill blocks prior to PCR amplification.

D060888:Real-Time Polymerase Chain Reaction

Temperature
Real-time PCR
Fluorescence
Time-dependent


Regulation of cardiac nitric oxide signaling by nuclear β-adrenergic and endothelin receptors.

Abstract: At the cell surface, βARs and endothelin receptors can regulate nitric oxide (NO) production. β-adrenergic receptors (βARs) and type B endothelin receptors (ETB) are present in cardiac nuclear membranes and regulate transcription. The present study investigated the role of the NO pathway in the regulation of gene transcription by these nuclear G protein-coupled receptors. Nitric oxide production and transcription initiation were measured in nuclei isolated from the adult rat heart. The cell-permeable fluorescent dye 4,5-diaminofluorescein diacetate (DAF2 DA) was used to provide a direct assessment of nitric oxide release. Both isoproterenol and endothelin increased NO production in isolated nuclei. Furthermore, a β3AR-selective agonist, BRL 37344, increased NO synthesis whereas the β1AR-selective agonist xamoterol did not. Isoproterenol increased, whereas ET-1 reduced, de novo transcription. The NO synthase inhibitor l-NAME prevented isoproterenol from increasing either NO production or de novo transcription. l-NAME also blocked ET-1-induced NO-production but did not alter the suppression of transcription initiation by ET-1. Inhibition of the cGMP-dependent protein kinase (PKG) using KT5823 also blocked the ability of isoproterenol to increase transcription initiation. Furthermore, immunoblotting revealed eNOS, but not nNOS, in isolated nuclei. Finally, caged, cell-permeable isoproterenol and endothelin-1 analogs were used to selectively activate intracellular β-adrenergic and endothelin receptors in intact adult cardiomyocytes. Intracellular release of caged ET-1 or isoproterenol analogs increased NO production in intact adult cardiomyocytes. Hence, activation of the NO synthase/guanylyl cyclase/PKG pathway is necessary for nuclear β3ARs to increase de novo transcription. Furthermore, we have demonstrated the potential utility of caged receptor ligands in selectively modulating signaling via endogenous intracellular G protein-coupled receptors.

Vaniotis|George|G|
Glazkova|Irina|I|
Merlen|Clémence|C|
Smith|Carter|C|
Villeneuve|Louis R|LR|
Chatenet|David|D|
Therien|Michel|M|
Fournier|Alain|A|
Tadevosyan|Artavazd|A|
Trieu|Phan|P|
Nattel|Stanley|S|
Hébert|Terence E|TE|
Allen|Bruce G|BG|

nuclear factor kappa-light-chain-enhancer of activated B-cells

quantitative real-time polymerase chain reaction

P P P P P P P P P P P P P P P P P P U U U U U U U U U U U U U P U U U U U U R U U U U U U M U U U U U U U M P R P R M U U U U U R R U U U U M M U P


Neuroanatomical basis of concern-based altruism in virtual environment.

Abstract: Costly altruism entails helping others at a cost to the self and prior work shows that empathic concern (EC) for the well-being of distressed and vulnerable individuals is one of the primary motivators of such behavior. However, extant work has investigated costly altruism with paradigms that did not feature self-relevant and severe costs for the altruist and have solely focused on neurofunctional, and not neuroanatomical, correlates. In the current study, we used a contextually-rich virtual reality environment to study costly altruism and found that individuals who risked their own lives in the virtual world to try to save someone in danger had enlarged right anterior insula and exhibited greater empathic concern than those who did not. These findings add to the growing literature showing the role of caring motivation in promoting altruism and prosociality and its neural correlates in the right anterior insula.

Patil|Indrajeet|I| Zanon|Marco|M| Novembre|Giovanni|G| Zangrando|Nicola|N| Chittaro|Luca|L| Silani|Giorgia|G|

Altruism
Empathic concern
Prosocial
Empathy
Moral
Morphometry


The Role of Hydrophobicity and Surface Receptors at Hyphae of Lyophyllum sp. Strain Karsten in the Interaction with Burkholderia terrae BS001 - Implications for Interactions in Soil.

Abstract: The soil bacterium Burkholderia terrae strain BS001 can interact with varying soil fungi, using mechanisms that range from the utilization of carbon/energy sources such as glycerol to the ability to reach novel territories in soil via co-migration with growing fungal mycelia. Here, we investigate the intrinsic properties of the B. terrae BS001 interaction with the basidiomycetous soil fungus Lyophyllum sp. strain Karsten. In some experiments, the ascomycetous Trichoderma asperellum 302 was also used. The hyphae of Lyophyllum sp. strain Karsten were largely hydrophilic on water-containing media versus hydrophobic when aerial, as evidenced by contact angle analyses (CA). Co-migration of B. terrae strain BS001 cells with the hyphae of the two fungi occurred preferentially along the - presumably hydrophilic - soil-dwelling hyphae, whereas aerial hyphae did not allow efficient migration, due to reduced thickness of their surrounding mucous films. Moreover, the cell numbers over the length of the hyphae in soil showed an uneven distribution, i.e., the CFU numbers increased from minima at the inoculation point to maximal numbers in the middle of the extended hyphae, then decreasing toward the terminal side. Microscopic analyses of the strain BS001 associations with the Lyophyllum sp. strain Karsten hyphae in the microcosms confirmed the presence of B. terrae BS001 cells on the mucous matter that was present at the hyphal surfaces of the fungi used. Cell agglomerates were found to accumulate at defined sites on the hyphal surfaces, which were coined 'fungal-interactive' hot spots. Evidence was further obtained for the contention that receptors for a physical bacterium-fungus interaction occur at the Lyophyllum sp. strain Karsten hyphal surface, in which the specific glycosphingolipid ceramide monohexoside (CMH) plays an important role. Thus, bacterial adherence may be mediated by heterogeneously distributed fungal-specific receptors, implying the CMH moieties. This study sheds light on the physical aspects of the B. terrae BS001 - Lyophyllum sp. strain Karsten interaction, highlighting heterogeneity along the hyphae with respect to hydrophobicity and the presence of potential anchoring sites.

Vila|Taissa|T|
Nazir|Rashid|R|
Rozental|Sonia|S|
Dos Santos|Giulia M P|GM|
Calixto|Renata O R|RO|
Barreto-Bergter|Eliana|E|
Wick|Lukas Y|LY|
van Elsas|Jan Dirk|JD|

Burkholderia terrae
soil fungi
CMH
Lyophyllum sp. Karsten
cerebroside
fungal-bacterial association


Long-Term Safety of Short-Term Administration of Filgrastim (rhG-CSF) and Leukophresis Procedure in Healthy Children: Application of Peripheral Blood Stem Cell Collection in Pediatric Donors.

Abstract: Administration of filgrastim (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) (Neupogen) in healthy donors to mobilize hematopoietic stem cells (HSCs) is a widespread practice in adults. Application of peripheral blood stem cell (PBSC) collection in normal pediatric donors is scarce due to ethical issues. Hence, there are insufficient data on the long-term impact of PBSC procedure in healthy children. This retrospective study aimed to evaluate the early and late adverse effects of PBSC donation in pediatric donors. Bone marrow and PBSC procedures and known adverse events of each technique were completely explained to parents and when applicable to children and written informed consent was obtained. rhG-CSF was administered for 4 days. HSCs were collected on the fifth day through continuous-flow apheresis and donors were followed for 30 days. Manual chart review was performed to collect short-term complications. Donors' health status was assessed via a questionnaire. A total of 145 healthy pediatric donors with a median age of 10 years at the time of donation (2 to 15 years) were followed for a median of 4.8 years (range, 1.2 to 14.2 years). The most frequent symptoms of rhG-CSF administration were fatigue (5%) and headache (3%). Thirty-five (24%) donors experienced hypocalcaemia during apheresis procedure that quickly responded to treatment. Two pregnancies occurred after rhG-CSF administration that resulted in normal births. We did not encounter any serious adverse events, including neoplastic disorders and death in this study. rhG-CSF and leukophresis procedure were well-tolerated in this study and all children completed the donation process without interruption or reduction of rhG-CSF dosage. Our results suggest that rhG-CSF is a safe drug in healthy children for the purpose of HSC mobilization.

Behfar|Maryam|M|
Faghihi-Kashani|Sara|S|
Hosseini|Ashraf Sadat|AS|
Ghavamzadeh|Ardeshir|A|
Hamidieh|Amir Ali|AA|

D019650:Hematopoietic Stem Cell Mobilization

Pediatric donor
Granulocyte colony-stimulating factor
Hematopoietic stem cell transplantation


A Randomized Cross-Over Trial Focused on Clinical Breast Exam Skill Acquisition Using High Fidelity versus Low Fidelity Simulation Models in Rwanda.

Abstract:
OBJECTIVE
Breast cancer incidence is rising for women in low and middle income country (LMIC)s. Growing the health care workforce trained in clinical breast exam (CBE) is critical to mitigating breast cancer globally. We developed a CBE simulation training course and determined whether training on a low-fidelity (LF) simulation model results in similar skill acquisition as training on high-fidelity (HF) models in Rwanda.

DESIGN
A single-center randomized educational crossover trial was implemented. A preintervention baseline exam (exam 1), followed by a lecture series (exam 2), and training sessions with assigned simulation models was implemented (exam 3)-participants then crossed over to their unassigned model (exam 4). The primary outcome of this study determined mean difference in CBE exam scores between HF and LF groups. Secondary outcomes identified any provider level traits and changes in overall scores.

SETTING
The study was implemented at the University Teaching Hospital, Kigali (CHUK) in Rwanda, Africa from July 2014 to March 2015 PARTICIPANTS: Medical students, residents in surgery, obstetrics and gynecology, and internal medicine residents participated in a 1-day CBE simulation training course.

RESULTS
A total of 107 individuals were analyzed in each arm of the study. Mean difference in exam scores between HF and LF models in exam 1 to 4 was not significantly different (exam 1 0.08 standard error (SE) = 0.47, p = 0.42; exam 2 0.86, SE = 0.69, p = 0.16; exam 3 0.03, SE = 0.38, p = 0.66; exam 4 0.10 SE = 0.37, p = 0.29). Overall exam scores improved from pre- to post-intervention.

CONCLUSIONS
Mean difference in exams scores were not significantly different between participants trained with HF versus LF models. LF models can be utilized as cost effective teaching tools for CBE skill acquisition, in resource poor areas.

Murthy|Shilpa Shree|SS|
Ntakiyiruta|Georges|G|
Ntirenganya|Faustin|F|
Ingabire|Allen|A|
Defregger|Sara Kikut|SK|
Reznor|Gally|G|
Lipitz|Stu|S|
Troyan|Susan Lynn|SL|
Raza|Sughra|S|
Dunnington|Gary|G|
Riviello|Robert|R|

Medical Knowledge
Patient Care
Practice-Based Learning and Improvement
Systems-Based Practice


Gender gaps in preschool age: A study of behavior, neurodevelopment and pre-academic skills.

Abstract: Background: Female educational advantage is evident from elementary school and throughout the education system. Understanding the gender differences that precede school entry might provide important insight as to why girls outperform boys later in their educational careers. Aims: The aim of this study was to explore gender differences in early literacy and numeracy skills, as well as a range of neurodevelopmental and behavioral domains between the age of five and six years. Methods: We used questionnaire data from preschool teachers in the Norwegian Mother, Father and Child Cohort Study reported for 7467 children attending the final year in preschool, to explore gender differences and age patterns by fitting flexible regression models predicting pre-academic, behavioral and neurodevelopmental outcomes. Results: We found gender differences favoring girls for all outcomes except internalizing behavior. For neurodevelopment and behavior, differences in adjusted standardized scores ranged from 46% of a standard deviation (95% confidence interval (CI) 0.41, 0.50) in overall school readiness to 31% of a standard deviation difference in externalizing behavior problems (CI 0.21, 0.41). We found gender differences for all literacy skills in favor of girls. The gender gap in naming and adding numbers was small, but in favor of girls. Increasing age was associated with improved pre-academic skills and school readiness, as well as reduction of attention problems and language difficulties, the latter especially for boys.

gender preschool behavior neurodevelopment pre-academic Education literacy MoBa


A group-enhanced sprint interval training program for amateur athletes.

Abstract: Sprint interval training (SIT) can elicit improvements in aerobic and anaerobic capacity. While variations in SIT protocols have been investigated, the influence of social processes cannot be overlooked. As research supports the use of groups to influence individual cognitions and behaviours, the current project assessed the effectiveness of a group-based intervention with participants conducting SIT. Specifically, 53 amateur athletes (age, 21.9 ± 2.9 years; 53% females) took part in a 4-week training program (3 sessions per week, 30-s "all-out" efforts with 4 min active recovery, repeated 4-6 times per session), and were assigned to "true group", aggregate, or individual conditions. Results indicated no significant differences between groups for the physiological measures. With regards to training improvements from baseline for all participants- regardless of condition - significant main effects for time were identified for maximal oxygen uptake (2.5-2.8 mL·kg(-1)·min(-1), p < 0.001, η(2) = 0.03), time-trial performance (14-32 s, p < 0.001, η(2) = 0.37), and anaerobic power (1.1-1.7 k·h(-1), p < 0.001, η(2) = 0.66). With regards to the psychological measures, significant main effects between groups were found for motivation (p = 0.033, η(2) = 0.13), task self-efficacy (p = 0.018, η(2) = 0.15), and scheduling self-efficacy (p = 0.003, η(2) = 0.22). The true group experienced greater improvements in motivation than the individual condition, but the aggregate and individual conditions demonstrated greater increases in task and scheduling self-efficacy. Though the SIT paradigm employed induced training improvements similar to previous work, the group intervention was not able to further these improvements.

Martin|Luc J|LJ|
Anderson|Scott H|SH|
Schmale|Matthew S|MS|
Hallworth|Jillian R|JR|
Hazell|Tom J|TJ|

entraînement par intervalle d’intensité élevée


Self-Healable Supramolecular Vanadium Pentoxide Reinforced Polydimethylsiloxane-Graft-Polyurethane Composites.

Abstract: The self-healing ability can be imparted to the polymers by different mechanisms. In this study, self-healing polydimethylsiloxane-graft-polyurethane (PDMS-g-PUR)/Vanadium pentoxide (V₂O₅) nanofiber supramolecular polymer composites based on a reversible hydrogen bonding mechanism are prepared. V₂O₅ nanofibers are synthesized via colloidal route and characterized by XRD, SEM, EDX, and TEM techniques. In order to prepare PDMS-g-PUR, linear aliphatic PUR having one ⁻COOH functional group (PUR-COOH) is synthesized and grafted onto aminopropyl functionalized PDMS by EDC/HCl coupling reaction. PUR-COOH and PDMS-g-PUR are characterized by ¹H NMR, FTIR. PDMS-g-PUR/V₂O₅ nanofiber composites are prepared and characterized by DSC/TGA, FTIR, and tensile tests. The self-healing ability of PDMS-graft-PUR and composites are determined by mechanical tests and optical microscope. Tensile strength data obtained from mechanical tests show that healing efficiencies of PDMS-g-PUR increase with healing time and reach 85.4 ± 1.2 % after waiting 120 min at 50 °C. The addition of V₂O₅ nanofibers enhances the mechanical properties and healing efficiency of the PDMS-g-PUR. An increase of healing efficiency and max tensile strength from 85.4 ± 1.2% to 95.3 ± 0.4% and 113.08 ± 5.24 kPa to 1443.40 ± 8.96 kPa is observed after the addition of 10 wt % V₂O₅ nanofiber into the polymer.

Berkem|Ali Sabri|AS|
Capoglu|Ahmet|A|
Nugay|Turgut|T|
Sancaktar|Erol|E|
Anac|Ilke|I|

self-healing
vanadium pentoxide
supramolecular polymer
hydrogen bonding
graft copolymer
nanocomposite
polydimethylsiloxane
polyurethane


Acne Scarring-Pathogenesis, Evaluation, and Treatment Options.

Abstract: Acne vulgaris is a ubiquitous problem affecting 80 percent of people ages 11 to 30 years, with many patients experiencing some degree of scarring. This review focuses on atrophic scars, the most common type of acne scar. We briefly address the cellular sequelae that lead to scar formation and the initial evaluation of patients with acne scars. We then discuss an algorithmic approach to the treatment of acne scarring based on the classification of scars into erythematous and atrophic types. Lastly, we discuss the future treatment of acne scars and ongoing clinical trials.

Connolly|Deirdre|D|
Vu|Ha Linh|HL|
Mariwalla|Kavita|K|
Saedi|Nazanin|N|

acne
acne vulgaris
Acne scarring
laser
light devices
resurfacing agents


The potential hepatoprotective effect of royal jelly against cadmium chloride-induced hepatotoxicity in mice is mediated by suppression of oxidative stress and upregulation of Nrf2 expression.

Abstract: This study was aimed at investigating the possible protective mechanism of royal jelly (RJ) against hepatotoxicity induced by cadmium chloride (CdCl2). The study included four groups: the control group received saline (0.9% sodium chloride), CdCl2 group received 6.5 mg/kg CdCl2 for seven days, RJ group received 85 mg/kg standardized RJ containing 6% 10-hydroxy-2-decenoic acid equivalent to 250 mg crude RJ, and finally, the fourth group received RJ 2 h before CdCl2 injection daily for 7 days. Oxidant/antioxidant markers of liver function estimation and histopathology were determined. The results revealed that RJ significantly ameliorated the hepatotoxic side effects of Cd. Furthermore, RJ inhibited oxidative stress, inflammation, and hepatic tissue injury; normalized enzymatic and nonenzymatic antioxidant molecules; and enhanced nuclear-related factor-2 (Nrf-2) expression. Our results provide new insights into the hepatoprotective property of RJ and revealed that RJ prevented hepatic injury, oxidative stress, and inflammation by upregulating Nrf2 and the anti-apoptotic protein Bcl-2. Hence, RJ can be used as a hepatoprotective agent against the toxic effects of CdCl2.

Almeer|Rafa S|RS|
Alarifi|Saud|S|
Alkahtani|Saad|S|
Ibrahim|Shaimaa R|SR|
Ali|Daoud|D|
Moneim|Abdel|A|

D056486:Chemical and Drug Induced Liver Injury

Royal jelly
Cadmium
Mice
Oxidative stress
Liver
Inflammation


Systematic Screening of Different Polyglycerin-Based Dienophile Macromonomers for Efficient Nanogel Formation through IEDDA Inverse Nanoprecipitation.

Abstract: Alternatives for strain-promoted azide-alkyne cycloaddition (SPAAC) chemistries are needed because of the employment of expensive and not easily scalable precursors such as bicyclo[6.1.0]non-4-yne (BCN). Inverse electron demand Diels Alder (iEDDA)-based click chemistries, using dienophiles and tetrazines, offer a more bioorthogonal and faster toolbox, especially in the biomedical field. Here, the straightforward synthesis of dendritic polyglycerin dienophiles (dPG-dienophiles) and dPG-methyl-tetrazine (dPG-metTet) as macromonomers for a fast, stable, and scalable nanogel formation by inverse nanoprecipitation is reported. Nanogel size-influencing parameters are screened such as macromonomer concentration and water-to-acetone ratio are screened. dPG-norbonene and dPG-cyclopropene show fast and stable nanogel formation in the size range of 40-200 nm and are thus used for the coprecipitation of the model protein myoglobin. High encapsulation efficiencies of more than 70% at a 5 wt% feed ratio are obtained in both cases, showing the suitability of the mild gelation chemistry for the encapsulation of small proteins.

D001643:Bridged Bicyclo Compounds
D057930:Click Chemistry
D061565:Cycloaddition Reaction
D006571:Heterocyclic Compounds
D009211:Myoglobin
D000080385:Nanogels
D010316:Particle Size

nanogels
nanoprecipitation
inverse electron demand Diels Alder
protein encapsulation


Consent in escrow: opting to opt in.

Abstract: In this paper, we reply to Taylor's (2015) peer commentary on consent-in-escrow. Specifically, we clarify the utility of this novel approach, the way in which it minimizes risks to participants, and how it differs from existing opt-out methods. We further explore its potential use in fields beyond disaster research.

Van der Loos|Kiah I|KI|
Longstaff|Holly|H|
Virani|Alice|A|
Illes|Judy|J|

Disaster research
informed consent
refugee research
research ethics
vulnerable populations


Managing Massive Splenic Hematoma: Exploratory Laparotomy or Active Surveillance?

Abstract: Splenic hematoma is a known complication of blunt force abdominal trauma. Traditional management of splenic hematomas has been primarily surgical. However, more recently, spleen-sparing management has been favored over surgical management for cases that meet certain criteria, with surgery now reserved for patients with complications. In this report, we present a case of a massive splenic hematoma that was managed conservatively and analyze the challenges faced in clinical decision making.

Otieno|Steve B|SB|
Wellikoff|Saradasri K|SK|
Weir|Alva|A|
Ogbeide|Osarenren|O|

splenic hematoma
abdominal trauma
non-operative management


Report of a case involving novel use of a post-operative esophagogastroduodenoscopy to re-evaluate a duodenal ulcer bleed.

Abstract:
INTRODUCTION
Acute gastrointestinal (GI) bleeding can be a life-threatening condition. This is usually diagnosed and managed by an upper GI tract endoscopy. When treating actively bleeding duodenal ulcers, surgical intervention, or arterial embolization by Interventional Radiology (IR) is warranted in the event of failed initial management. We present a patient with a significant GI bleed and failure of management through endoscopy, necessitating emergent surgical intervention.

PRESENTATION OF CASE
An 87-year-old female presented to the emergency department after a fall. Her hemoglobin level dropped significantly and an esophagogastroduodenoscopy (EGD) revealed a large pool of blood in the stomach but had a limited view of an active bleed. The patient was taken emergently to the operating room (OR) where she underwent an exploratory laparotomy, gastroduodenostomy, suture ligation, and pyloroplasty. The following day, she had increased sanguineous output from her nasogastric (NG) tube. Re-evaluation was done with an EGD in the OR. The patient tolerated all procedures well and was transferred to a facility with IR capabilities for further management.

DISCUSSION
An EGD hours after gastroduodenostomy runs a high risk for perforation and is not the typical course of action. Given the lack of IR availability and concern for rebleeding, this procedure was performed in the OR to minimize risk.

CONCLUSION
A favorable outcome was achieved with this patient and hemostasis was confirmed with the post-operative EGD. Further studies will determine whether this approach is a viable option for facilities without IR until the patient can be transferred.

DeVito|Robert|R| Shoukry|Sameh|S| Arif|Azzan|A| Fullmer|Rhett|R| Simpson|Matthew|M| Kimyaghalam|Ali|A|

Ulcer
Bleeding
Endoscopy
Case report
Duodenum
Repair
Surgery


Clinical outcomes and nephrotoxicity of colistin loading dose for treatment of extensively drug-resistant Acinetobacter baumannii in cancer patients.

Abstract:
BACKGROUND
Colistin is a last-line defense therapy against extensively drug-resistant Acinetobacter baumannii (XDR-AB). Despite a loading dose of colistin being applied in many clinical practices, studies evaluating the effect of the loading dose of colistin in cancer patients remain limited.

PATIENTS AND METHODS
A retrospective cohort study of cancer patients who received either a loading or non-loading dose of colistin for treatment of XDR-AB was conducted. For each group, the clinical response, bacteriological eradication and serum creatinine were recorded. Logistic regression was applied to evaluate the effects of therapy on each of the three aforementioned outcomes.

RESULTS
One hundred and two patients diagnosed with XDR-AB infections between January 2012 and December 2015 were recruited. Only 75 patients were given a loading dose of colistin. There was no significant clinical and microbiological response in patients in the loading dose group or patients in the non-loading dose group. However, 38 (50.67%) patients in the loading dose group and 6 (22.22%) patients in the non-loading dose group developed nephrotoxicity according to the RIFLE criteria (p = 0.013). Multivariate logistic regression analysis showed that independent predictors of clinical response were Charlson score ≥4 and duration of colistin treatment ≥10 days. Septic shock correlated with both poor clinical and microbiological response. Independent predictors for nephrotoxicity were loading dose colistin and patient's age ≥60 years.

CONCLUSION
Administration of colistin loading dose did not significantly increase clinical response, microbiological response or mortality rate compared to non-loading dose in cancer patients with XDR-AB-related infections. However, nephrotoxicity was significantly higher when patients received loading dose colistin.


The arithmetic problem size effect in children: an event-related potential study.

Abstract: This study used for the first time event-related potentials (ERPs) to examine the well-known arithmetic problem size effect in children. The electrophysiological correlates of this problem size effect have been well documented in adults, but such information in children is lacking. In the present study, 22 typically developing 12-year-olds were asked to solve single-digit addition problems of small (sum ≤ 10) and large problem size (sum > 10) and to speak the solution into a voice key while ERPs were recorded. Children displayed similar early and late components compared to previous adult studies on the problem size effect. There was no effect of problem size on the early components P1, N1, and P2. The peak amplitude of the N2 component showed more negative potentials on left and right anterior electrodes for large additions compared to small additions, which might reflect differences in attentional and working memory resources between large and small problems. The mean amplitude of the late positivity component which follows the N2, was significantly larger for large than for small additions at right parieto-occipital electrodes, in line with previous adult data. The ERPs of the problem size effect during arithmetic might be a useful neural marker for future studies on fact retrieval impairments in children with mathematical difficulties.

Van Beek|Leen|L|
Ghesquièr|Pol|P|
De Smedt|Bert|B|
Lagae|Lieven|L|

arithmetic
problem size effect
children
event-related potential (ERP)
verbal production task


Monitoring nutrients fate after digestate spreading in a short rotation buffer area.

Abstract: One of the main sources of reactive nitrogen pollution is animal manure. The disposal of digestate (material remaining after the anaerobic digestion of a biodegradable feedstock) in agricultural soils could solve both the problems of soil fertilization and waste removal, but the fate of digestate in the environment must be assessed carefully before its massive utilization. To investigate whether digestate could be safely employed as a soil fertilizer, an agricultural field located in Monastier di Treviso (Northern Italy) and characterized by the presence of low hydraulic conductivity clay soils, was selected to be amended with bovine digestate. The experimental site was intensively monitored by a three-dimensional array of probes recording soil water content, temperature, and electrical conductivity, to solve the water and bulk mass fluxes in the unsaturated zone. High-resolution soil coring allowed the characterization of soil water composition over two hydrological years. Chloride, found in high concentrations in the digestate, was used as environmental tracer to track the fate of the percolating water. The study concluded that digestate could be confidently employed in short rotation buffer areas at an average rate of 195 ± 26 kg-N/ha/year in low hydraulic conductivity soils not affected by diffuse fracturing during dry periods.

Colombani|Nicolò|N| Boz|Bruno|B| Gumiero|Bruna|B| Mastrocicco|Micòl|M|

Digestate
Hydraulic conductivity
Clay soils
Soil water content
Environmental tracer
Nitrate


Trends in calcium supplementation, National Health and Nutrition Examination Survey (NHANES) 1999-2014.

Abstract:
BACKGROUND
Long-term outcomes of supplemental calcium are inadequately understood. Recent research suggests that calcium from supplements may not be entirely free from unintended health consequences. Consequently, it is important to understand patterns and trends in use of calcium supplements.

OBJECTIVE
To report trends in supplemental calcium intake between 1999 and 2014, using NHANES data, overall and stratified by sex, race/ethnicity and age.

METHODS
A total of 42,038 adult NHANES participants were included in this analysis. For each survey period, we calculated the prevalence of calcium supplement use exceeding the Estimated Average Requirement (EAR) and Tolerable Upper Intake Levels (UL), and mean daily supplemental calcium dose among calcium-containing supplement users. Sample weights were applied. Linear regression was used to examine trends.

RESULTS
Overall, the prevalence of calcium supplement use at a dose ≥EAR increased between 1999 and 2000 and 2013-2014, from 2.5% (95% CI: 1.9-3.3%) to 4.6% (3.8-5.5%). Use ≥EAR peaked in 2003-2004 at 6.7% (5.3-8.5%) (p-quadratic trend<0.001). Mean supplemental calcium intake peaked in 2007-2008, thereafter decreasing (p-quadratic trend<0.001). The overall prevalence of intake ≥UL from supplemental calcium in 2013-2014 was 0.4% (0.2-0.8%). Use of supplemental calcium ≥UL peaked during 2007-2008 at 1.2% (0.7-2.0%). In all time periods, supplemental calcium intake tended to be greater among women, non-Hispanic whites and adults >60years.

CONCLUSIONS
We described the prevalence of U.S. adults consuming supplemental calcium ≥UL and ≥ EAR. While few were consuming supplemental calcium ≥UL, consumption ≥EAR was not uncommon, especially among women, non-Hispanic whites and older adults.

Rooney|Mary R|MR|
Michos|Erin D|ED|
Hootman|Katie C|KC|
Harnack|Lisa|L|
Lutsey|Pamela L|PL|


Spontaneous Trans-Abdominal Expulsion of a Foreign Body: A Rare Occurrence.

Abstract: Large and sharp foreign bodies invariably need surgical removal. A 55-year-old male, had epigastric pain, two weeks after accidental ingestion of wooden tooth brush. Later he developed pain, fever and indurations in left iliac fossa followed by spontaneous expulsion of foreign body through indurated area on the anterior abdominal wall. Contrast enhanced computed tomography revealed an inflammatory tract along the posterior wall of stomach communicating with the anterior abdominal wall. Patient was managed conservatively and made an uneventful recovery.

Sharma|Anil K|AK|
Roat|Rajesh|R|
Gulati|Ajay|A|
Gupta|Vikas|V|


Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System.

Abstract:
OBJECTIVE
The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process.

METHODS
We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma.

RESULTS
Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA.

CONCLUSION
These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

Kim|Hyun Sik|HS|
Park|Young Han|YH|
Lee|Heui Seung|HS|
Kwon|Mi Jung|MJ|
Song|Joon Ho|JH|
Chang|In Bok|IB|

Propranolol Glioblastoma Neuroblastoma Isoproterenol


Detection of Treatment Success after Photodynamic Therapy Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

Abstract: Early evaluation of response to therapy is crucial for selecting the optimal therapeutic follow-up strategy for cancer patients. PDT is a photochemistry-based treatment modality that induces tumor tissue damage by cytotoxic oxygen radicals, generated by a pre-injected photosensitive drug upon light irradiation of tumor tissue. Vascular shutdown is an important mechanism of tumor destruction for most PDT protocols. In this study, we assessed the suitability of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to evaluate treatment efficacy within a day after photodynamic therapy (PDT), using the tumor vascular response as a biomarker for treatment success. Methods: DCE-MRI at 7 T was used to measure the micro-vascular status of subcutaneous colon carcinoma tumors before, right after, and 24 h after PDT in mice. Maps of the area under the curve (AUC) of the contrast agent concentration were calculated from the DCE-MRI data. Besides, tracer kinetic parameters including K were calculated using the standard Tofts-Kermode model. Viability of tumor tissue at 24 h after PDT was assessed by histological analysis. Results: PDT led to drastic decreases in AUC and K or complete loss of enhancement immediately after treatment, indicating a vascular shutdown in treated tumor regions. Histological analysis demonstrated that the treatment induced extensive necrosis in the tumors. For PDT-treated tumors, the viable tumor fraction showed a strong correlation (ρ ≥ 0.85) with the tumor fraction with K > 0.05 min-1 right after PDT. The viable tumor fraction also correlated strongly with the enhanced fraction, the average K , and the fraction with K > 0.05 min-1 at 24 h after PDT. Images of the viability stained tumor sections were registered to the DCE-MRI data, demonstrating a good spatial agreement between regions with K > 0.05 min-1 and viable tissue regions. Finally, 3D post-treatment viability detection maps were constructed for the tumors of three mice by applying a threshold (0.05 min-1) to K at 24 h after PDT. As a proof of principle, these maps were compared to actual tumor progression after one week. Complete tumor response was correctly assessed in one animal, while residual viable tumor tissue was detected in the other two at the locations where residual tumor tissue was observed after one week. Conclusion: This study demonstrates that DCE-MRI is an effective tool for early evaluation of PDT tumor treatment.

Schreurs|Tom J L|TJL|
Jacobs|Igor|I|
Nicolay|Klaas|K|
Prompers|Jeanine J|JJ|
Strijkers|Gustav J|GJ|

Dynamic contrast-enhanced magnetic resonance imaging


Efficacy and safety of short-term administration of recombinant human atrial natriuretic peptide (rhANP) for congestive heart failure: a phase II, multicentre randomized controlled dose-finding study.

Abstract:
WHAT IS KNOWN AND OBJECTIVE
Although the long-term infusion of ANP has proved effective to treat heart failure, no published randomized controlled study has been reported to confirm the efficacy of the short-term ANP infusion in congestive heart failure (CHF) patients. This study was designed to assess the efficacy and safety of short-term infusion of recombinant human atrial natriuretic peptide (rhANP) in CHF patients.

METHODS
A total of 48 patients with CHF were enrolled and randomized into four groups, treated with standard therapy or rhANP (0·05, 0·1 or 0·2 μg/kg/min) for 1-hour infusion in addition to standard therapy. The hemodynamics were assessed for 12 h by Swan-Ganz catheter.

RESULTS AND DISCUSSION
The effect of the 0·05 μg/kg/min rhANP dose group on CO was modest and transient. The 0·2 μg/kg/min rhANP dose group tended to be associated with better effect on SV, CO and dyspnoea improvement, but modest effect on PCWP and more adverse events probably attributed to the study drug. However, the 0·1 μg/kg/min rhANP infusion was well tolerated and effective both on PCWP decrease (maximum:-9·46 ± 5·81 mmHg compared with baseline (P = 0·0002) and -6·75 mmHg compared with standard therapy, the 95% confidential interval [-13·43, -0·06 mmHg] at 1 h) and CO increase (maximum: 1·02 ± 1·43 L/min [P = 0·0308] at 1 h).

WHAT IS NEW AND CONCLUSION
In this small-sample study, 1-hour infusion of rhANP produced beneficial hemodynamic effects in CHF patients compared with standard therapy, and it was well tolerated. 0·1 μg/kg/min may be the optimum dose for short-term rhANP infusion to treat CHF for the further large sample trial before clinical application.

Wang|P|P| Luan|X|X| Wang|G|G| Liu|W|W| Zhang|J|J| Li|W|W| Gao|X|X| Wang|Y|Y| Mao|Y|Y| Sun|X|X| Wang|Q|Q| Zhang|Y|Y| Bai|S|S|

congestive heart failure
dose-finding study
controlled clinical trial


Fear of recurrence among older breast, ovarian, endometrial, and colorectal cancer survivors: Findings from the WHI LILAC study.

Abstract:
OBJECTIVE
To examine the prevalence of and factors associated with fear of recurrence (FCR) following treatment for breast, ovarian, endometrial, and colorectal cancer among older women.

METHODS
Participants were enrolled in the Women's Health Initiative Life and Longevity After Cancer study. Descriptive statistics and multivariate logistic regression models were used to assess the association of demographic, clinical, and quality of life variables with survivors' FCR, dichotomized as <14 (low) or ≥14 (high) using the Cancer Worry Scale.

RESULTS
Out of the 4259 participants, 3124 (73.3%) were diagnosed with breast cancer, 559 (13.1%) with colorectal cancer, 493 (11.6%) with endometrial cancer, and 83 (2%) with ovarian cancer. There were no significant differences in FCR by cancer type (P = .75), with a mean scale score of 10.8 ± 2.87 for all participants combined. Approximately 16% (n = 679) were in the high FCR group. Multivariable analyses indicated that being younger at diagnosis, reporting a symptom score of ≥8, receipt of chemotherapy, and lower self-rated health were significantly associated with high FCR. Women who were widowed or never married were less likely to report high FCR.

CONCLUSIONS
Fear of recurrence was experienced by a small but important proportion of older, long-term cancer survivors and is associated with multiple demographic and clinical variables. These results will better inform researchers and clinicians regarding the individuals who are at risk of FCR.

cancer
cancer survivors
WHI LILAC
older women
fear of cancer recurrence


How to Establish a Minimal Invasive and Stable Carotid Artery Stenosis Rabbit Model? A Simple and Effective Carotid Artery Balloon Strain Technique.

Abstract: Background: The objective of this study is to establish a minimally invasive technique to create a stable carotid artery stenosis rabbit model. This article summarizes the specific methods and key points of this technology. Methods: The experiment studied a rabbit that was anesthetized through the vein. After the femoral artery was exposed, a minimally invasive needle was used to puncture the femoral artery, then the sheath was placed into the artery. We primarily put a catheter in the ascending aorta for angiography and then used a PT2 guidewire for super-selection. The PT2 guidewire was retained, and a balloon was placed in the right common carotid artery (CCA) through a guidewire to inflate it three times. Six rabbits in the 2- (2W) and 4-week (4W) groups were examined at 14 and 28 days, respectively. The rabbits in the control group received angiography at the beginning and 28 days later but without balloon injury. After angiography assessment, specimens of right CCA were dissected. Pathological and immunohistochemical examinations were performed on the collected specimens, and iFlow analysis was performed as well. Results: All the 18 animals which survived were observed. The rabbits in the 2W and 4W groups showed stenosis of the right CCA. Digital subtraction angiography showed the diameter was lower than that in the control group (1.04 ± 0.1, 0.71 ± 0.12, and 1.83 ± 0.08 mm in 2W, 4W, and control group, P < 0.05). Pathology also suggested carotid stenosis and obvious intimal hyperplasia. The results of immunohistochemistry showed that α-smooth muscle actin was highly expressed in the 2W and 4W groups, and the integrated optical density (IOD) value was higher than that in the control group (14,807.11 ± 1,822.3, 22,245.96 ± 1,212.82, and 6,537.16 ± 1,186.62 in the 2W, 4W, and control group, P < 0.05). Meanwhile, a cluster of differentiation 31 (CD31) was low expressed in the 2W and 4W groups, and the IOD value was lower than that in the control group (519.14 ± 44.4, 1,029.64 ± 98.48, and 1,502.05 ± 88.79 in the 2W, 4W, and control group, P < 0.05), which suggested endothelial damage and partial repair. The analysis by iFlow showed that the time-to-peak after balloon strain in the 2W and 4W groups were longer than that in the control group. Conclusion: We established a minimally invasive, effective, and safe method to establish a carotid artery stenosis rabbit model. The highlights of this technology were the application of minimally invasive methods, reducing surgical bleeding, infection, and related complications. This technology avoided the influence of tissue around CCA in the traditional carotid artery balloon injury model, which might lead to more accurate treatment outcomes.

Liu|Zhengli|Z| Gong|Maofeng|M| Zhao|Boxiang|B| Gu|Jianping|J| Su|Haobo|H| Zhou|Yangyi|Y| Fu|Guanqi|G| He|Xu|X| Kong|Jie|J|

rabbit model
balloon strain
injury
common carotid artery stenosis
fluoroscopy guidance


Symmetrical peripheral gangrene: A rare clinical entity.

Abstract: Symmetrical peripheral gangrene (SPG) may present initially with septicemia. Prompt identification and management of the underlying cause of SPG is central for the best outcome. Good management incorporates delaying early surgical intervention, suitable antibiotic therapy, judicious debridement, and skin grafting.

symmetrical peripheral gangrene
septicemia
disseminated intravascular coagulation
purpura fulminans


Developmental stages of cultivated strawberry flowers in relation to chilling sensitivity.

Abstract: Environmental factors affecting flower development may limit the yields of fruiting crops worldwide. In temperate regions, chilling temperatures during flower development can compromise fruit production, but their negative effects vary depending on the differing susceptibilities of each developmental stage. The cultivated strawberry (Fragaria× ananassa Duch.) is widely grown worldwide but financial returns are influenced by sudden shifts to chilling temperatures occurring during the cropping cycle. Despite this important limitation, knowledge of F.× ananassa flower development is lacking, in contrast to the diploid wild-type strawberry (F. vesca). In this study we describe steps in floral development of cultivated strawberry and define their vulnerability to chilling temperatures. To achieve this, flower buds from strawberry plants of cv. 'Camarosa' were labelled and monitored from bud initiation until anthesis. Description of morphological and functional changes during flower development was based on histological sections and scanning electron microscopy. To determine the impact of low temperatures at different developmental stages, plants carrying buds of different sizes were chilled at 2 °C for 24 h. Several parameters related to male and female gametophyte development were later evaluated in flowers as they approached anthesis. Fragaria× ananassa flower development was divided into 16 stages according to landmark events. These stages were similar to those documented for F. vesca but three new additional intermediate stages were described. Timing of developmental processes was achieved by correlating developmental staging with specific bud sizes and days before anthesis. Time to reach anthesis from early bud stages was 17-18 days. During this period, we detected four critical periods vulnerable to low temperatures. These were mostly related to male gametophyte development but also to injury to female organs at late developmental stages. These results provide the essential groundwork on floral biology of cultivated strawberry that is a prerequisite for successful comparative studies of cold tolerance among genotypes during flower formation.

Ariza|Maria Teresa|MT|
Soria|Carmen|C|
Martínez-Ferri|Elsa|E|

flower development
low temperature
Critical periods
Fragaria × ananassa
flower differentiation
pistil
pollen


Periodontal disease: modulation of the inflammatory cascade by dietary n-3 polyunsaturated fatty acids.

Abstract: Periodontal disease, including gingivitis and periodontitis, is caused by the interaction between pathogenic bacteria and the host immune system. The ensuing oxidative stress and inflammatory cascade result in the destruction of gingival tissue, alveolar bone and periodontal ligament. This article reviews the underlying mechanisms and host-bacteria interactions responsible for periodontal disease and evidence that nutritional supplementation with fish oil may provide a protective effect. Historical investigations of diet and disease have highlighted an inverse relationship between ingestion of fish oil, which is high in n-3 polyunsaturated fatty acids, and the incidence of typical inflammatory diseases such as arthritis and coronary heart disease. Ingestion of n-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, results in their incorporation into membrane phospholipids, which can alter eicosanoid production after stimulation during the immune response. These eicosanoids promote a reduction in chronic inflammation, which has led to the proposal that fish oil is a possible modulator of inflammation and may reduce the severity of periodontal diseases. Tentative animal and human studies have provided an indication of this effect. Further human investigation is needed to establish the protective effects of fish oil in relation to periodontal disease.

periodontal disease
n-3 polyunsaturated fatty acids
eicosanoids
inflammation


Enhanced Energy Conversion of Z907-Based Solar Cells by Cucurbit[7]uril Macrocycles.

Abstract: A dye-sensitized solar cell was constructed on the basis of encapsulating the ruthenium polypyridyl photosensitizer Z907 in the macrocycle cucurbit[7]uril (CB7). The work focuses on the photophysical properties of the new host-guest complexes in acetonitrile and water (volume ratio 1:9) and on the top of nanocrystalline titanium dioxide (TiO2) electrode prior to the addition of poly(3-hexylthiophene) polymer and gold electrode. Complexation to CB7 in aqueous solutions has decreased the emission intensity and excited-state lifetime for metal-to-ligand charge transfer (MLCT) state at 650 nm by twofold because of collisional quenching, which opens a non-radiative deactivation channel. Similarly, a twofold decrease in the emission intensity and excited-state lifetime of MLCT at 750 nm on the top of TiO2 electrodes was observed with the addition of CB7. Encapsulation of Z907 dye to CB7 host has, also, led to fourfold enhancement in the short circuit current and power conversion efficiency of the final solar cell. The results support the premise that host-guest complexation of CB7 facilitates faster electron injection from Z907 dye into the conduction band of TiO2 electrodes.

Al-Dmour|Hmoud|H|
Alzard|Reem H|RH|
Alblooshi|Hamda|H|
Alhosani|Khaula|K|
AlMadhoob|Shaqra|S|
Saleh|Na'il|N|

solar cell
electron injection
charge recombination and separation
cucurbit (n = 7, 8) uril
metal to ligand charge transfer


Repurposing Methotrexate in Dampening SARS-CoV2-S1-Mediated IL6 Expression: Lessons Learnt from Lung Cancer.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) is associated with uncontrolled inflammatory responses. Loss of pulmonary angiotensin-converting enzyme 2 (ACE2) function has been associated with SARS-CoV-2 infection. The aberrant signalling and dysregulated inflammation characteristic of lung cancer have marked similarities with SARS-CoV-2 infection. Spearman's correlation analysis of The Cancer Genome Atlas (TCGA) datasets indicated an inverse correlation between ACE2 and IL6 in lung adenocarcinoma. qRT-PCR analysis revealed CoV-2-SRBD-mediated diminished ACE2 expression in lung cancer cells that was concomitant with increased IL6 expression. Western blot and qRT-PCR analysis suggested that treatment with methotrexate (MTx) dampened CoV-2-SRBD-mediated increase in JAK1/STAT3 phosphorylation, gp130, IL6, and folate-binding protein (FBP) expressions. MTx also rescued the diminished expression of ACE2 in CoV-2-SRBD transfected cells. As lung tissue injury in severely affected COVID-19 patients is characterised by aberrant inflammatory response, repurposing MTx as an effective therapy against critical regulators of inflammation in SARS-CoV-2 infection warrants investigation.


Comparison of mother, father, and teacher reports of ADHD core symptoms in a sample of child psychiatric outpatients.

Abstract:
OBJECTIVE
To explore the significance of adding father ratings to mother and teacher ratings in the assessment of ADHD symptoms in children.

METHOD
The ADHD Rating Scale-IV, the Child Behavior Checklist, and the Teacher Report Form were filled out by all three informants for a sample of 48 clinically referred children (79% boys) aged 6 to 15 (M = 10.1) years.

RESULTS
Correspondence between father and teacher reports on ADHD-specific symptoms (intraclass correlation coefficient [ICC] = .38) exceeded that between mothers and teachers (ICC = .23). Fathers rated their children as having fewer problems than did mothers and teachers on Total scale scores and the Inattention subscale of the ADHD Rating Scale-IV. Mother ratings were more sensitive to an ADHD diagnosis, whereas father ratings better predicted an ADHD diagnosis requiring the two-setting criterion.

CONCLUSION
The choice of parent informant and informant combination had a considerable impact on parent-teacher concordance and estimates of ADHD symptoms and subtypes in the child.

D001289:Attention Deficit Disorder with Hyperactivity

ADHD
assessment
children
informant agreement


Reflection on modern methods: Dynamic prediction using joint models of longitudinal and time-to-event data.

Abstract: Individualized prediction is a hallmark of clinical medicine and decision making. However, most existing prediction models rely on biomarkers and clinical outcomes available at a single time. This is in contrast to how health states progress and how physicians deliver care, which relies on progressively updating a prognosis based on available information. With the use of joint models of longitudinal and survival data, it is possible to dynamically adjust individual predictions regarding patient prognosis. This article aims to introduce the reader to the development of dynamic risk predictions and to provide the necessary resources to support their implementation and assessment, such as adaptable R code, and the theory behind the methodology. Furthermore, measures to assess the predictive performance of the derived predictions and extensions that could improve the predictions are presented. We illustrate personalized predictions using an online dataset consisting of patients with chronic liver disease (primary biliary cirrhosis).

Andrinopoulou|Eleni-Rosalina|ER|
Harhay|Michael O|MO|0000-0002-0553-674X
Ratcliffe|Sarah J|SJ|
Rizopoulos|Dimitris|D|

dynamic predictions
Joint model
longitudinal outcome
personalized risk predictions
survival outcome


P2X purinoceptors as a link between hyperexcitability and neuroinflammation in status epilepticus.

Abstract: There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".

D058920:Purinergic P2X Receptor Antagonists

Purinoceptor
Adenosine
Epileptogenesis
Hippocampal sclerosis
Super-refractory status epilepticus


PA12 Powder Recycled from SLS for FDM.

Abstract: In this study, Polyamide 12 (PA12) powder recycled after selective laser sintering (SLS) was made into filaments for fused deposition modelling (FDM). Compared with fresh PA12, the melt flow rate (MFR) of the recycled PA12 powder decreased by 77%, but the mechanical properties were only slightly reduced. In FDM, the printing speed and building orientation were changed, and the performance of the printed parts was tested. If the printing speed is too fast or too slow, the mechanical properties of the parts will be affected, and there is an optimal speed range. The tensile strength, flexural modulus, and impact strength of a printed test sample made from recycled powder reached 95%, 85%, and 87% of an x-direction test sample made from fresh PA12, respectively. For test samples printed from different orientations, the mechanical properties of the test samples printed in the x-direction were the best, while the crystallization performance was the opposite. Scanning electron microscope (SEM) images show that the printed test sample had good compactness and mechanical properties, and the delamination phenomenon was basically not observed.


Evaluation of arch forms depending on the angle classification.

Abstract:
It is generally accepted that each individual has his or her own dental arch form. However, during orthodontic treatment, industrially preshaped archwires are widely used. The resulting use of the same arch form for all malocclusions may compromise occlusal stability after orthodontic treatment.

AIM
To determine the average dental arch form of a non-consulting Moroccan population depending on the Angle classification, after digitization of plaster models of the dental arches.

MATERIAL AND METHODS
A sample of 50 dental students aged between 21 and 27 was selected. After digitization of the plaster models to produce a cloud of points, the barycentric method was applied to this representation, enabling all the arch shapes of each series to be superimposed with Photoshop CS 5 software (layer mode) and the average curves for each Angle class to be thereby determined.

RESULTS
The average maxillary and mandibular arch forms were defined for each class: Class I: a normal maxillary form and an ovoid mandibular form; Class II: a tapered maxillary form and a narrow tapered mandibular form; Class III: narrow tapered forms for both upper and lower arches. Globally speaking, in this sample an ovoid mandibular arch form and a normal maxillary arch form are the dominant shapes.

DISCUSSION AND CONCLUSION
The studied population exhibited specific arch form features. This study could serve as the basis for the choice and use of preformed archwires better-adapted to the needs of our patients.

Bourzgui|Farid|F|
Khribchi|Asmaa|A|
Rachdy|Zineb|Z|
Housbane|Sami|S|
Othmani|Mohamed Bennani|MB|

Orthodontics
Angle classes
Dental archforms
Morocco


Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?

Abstract:
BACKGROUND
Longitudinal clinical surveillance by transthoracic echocardiography (TTE) is an established practice in children with repaired tetralogy of Fallot (TOF). Non-Invasive Imaging Guidelines recommends a list of reporting elements that should be addressed during routine TTE in this population. In this study, we assessed the adherence to these recommendations.

METHODS
This was a multi-center (n = 8) retrospective review of TTE reports in children ≤11 years of age who have had complete TOF repair. We included 10 patients from each participating center (n = 80) and scored 2 outpatient follow-up TTE reports on each patient. The adherence rate was based on completeness of TTE reporting elements derived from the guidelines.

RESULTS
We reviewed 160 TTE reports on 80 patients. Median age was 4.4 months (IQR 1.5-6.6) and 3.6 years (IQR 1.3-6.4) at the time of complete surgical repair and first TTE report, respectively. The median adherence rate to recommended reporting elements was 61% (IQR 53-70). Of the 160 reports, 9 (7%) were ≥80% adherent and 40 (25%) were ≥70% adherent. Quantitative measurements of right ventricular outflow tract (RVOT), right ventricular (RV) size and function, and branch pulmonary arteries were least likely to be reported.

CONCLUSIONS
Overall adherence to the most recent published imaging guidelines for surveillance of children with repaired TOF patients was suboptimal, especially for reporting of RVOT, RV size and function, and branch pulmonary arteries. Further studies are needed to explore the barriers to adherence to guidelines and most importantly, whether adherence is associated with clinical outcomes.

Annavajjhala|Vidhya|V|
Valente|Anne Marie|AM|
Lopez|Leo|L|
Sachdeva|Ritu|R|
Glickstein|Julie S|JS|
Natarajan|Shobha S|SS|
Buddhe|Sujatha|S|
Altmann|Karen|K|
Soriano|Brian D|BD|
Colquitt|John L|JL|
Altman|Carolyn A|CA|
Sasaki|Nao|N|
Sakarovitch|Charlotte|C|
Tacy|Theresa A|TA|
Geva|Tal|T|
Selamet Tierney|Elif Seda|ES|

Tetralogy of Fallot
Adherence
Guidelines
Echocardiography


Zinc toxicity to the alga Pseudokirchneriella subcapitata decreases under phosphate limiting growth conditions.

Abstract: Previous studies have suggested that phosphorus (P) deficiency can increase the sensitivity of microalgae to toxic trace metals, potentially due to reduced metal detoxification at low cell P quota. The existing evidence is, however, inconsistent. This study was set up to determine the combined effects of zinc (Zn) and P supplies on Zn and P bioaccumulation and growth of the green microalgae Pseudokirchneriella subcapitata. Zinc toxicity was investigated in (i) a 24h growth rate assay with cells varying in initial cell P quota (0.5-1.7% P on cell dry weight) with no supplemental P during Zn exposure (Expt. 1) and in (ii) a 48h growth assay initiated with cells at the end of a 14-days steady state culture at three P addition rates (RARs) between 0.8 and 1.6day(-1) (Expt.2). The solution Zn concentrations required to reduce final cell density by 10% relative to control (EbC10) were 5-fold (Expt.1) or 2-fold (Expt.2) lower at the highest P supply than at the lowest P supply, i.e. Zn was more toxic at higher P supply, in contrast with the suggestions from previous studies. Cell P quota increased with increasing Zn in the exposure solution (Expt.2), thereby partially overcoming P deficiency under moderate Zn toxicity compared to low Zn exposure. Similarly, cell Zn increased with increasing P supply, potentially induced by Zn-P complexation or precipitation inside the cell. A dynamic growth model accounting for effects of external Zn and internal P on the specific growth rate was calibrated to all data. This model shows that the effect of solution Zn on specific growth rate (ErC50) was statistically unaffected by cell P quota. In contrast, this model predicts that the EbC10 (i.e. EC10 based on cell numbers) varies with P supply because cell P depends on external P and Zn. Moreover, scenario analysis predicts even contrasting trends of the EbC10 with increasing P supply depending on the duration of the growth assay and the P supply scenario. Our data at two experimental scenarios and the prediction under various relevant scenarios suggest a weaker effect of secondary stress factor (Zn) when nutrient deficiency (first stress factor) is prevailing.

Gao|C|C|
De Schamphelaere|K A C|KAC|
Smolders|E|E|

Algae
Exponential addition rate
Solution Zn toxicity
Three-dimensional model
Zn–P interaction


Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent, photoacoustic, and photothermal capabilities.

Abstract:
PURPOSE
The aim of the present study was to develop nanoprobes with theranostic features, including - at the same time - photoacoustic, near-infrared (NIR) optical imaging, and photothermal properties, in a versatile and stable core-shell silica-polyethylene glycol (PEG) nanoparticle architecture.

MATERIALS AND METHODS
We synthesized core-shell silica-PEG nanoparticles by a one-pot direct micelles approach. Fluorescence emission and photoacoustic and photothermal properties were obtained at the same time by appropriate doping with triethoxysilane-derivatized cyanine 5.5 (Cy5.5) and cyanine 7 (Cy7) dyes. The performances of these nanoprobes were measured in vitro, using nanoparticle suspensions in phosphate-buffered saline and blood, dedicated phantoms, and after incubation with MDA-MB-231 cells.

RESULTS
We obtained core-shell silica-PEG nanoparticles endowed with very high colloidal stability in water and in biological environment, with absorption and fluorescence emission in the NIR field. The presence of Cy5.5 and Cy7 dyes made it possible to reach a more reproducible and higher doping regime, producing fluorescence emission at a single excitation wavelength in two different channels, owing to the energy transfer processes within the nanoparticle. The nanoarchitecture and the presence of both Cy5.5 and Cy7 dyes provided a favorable agreement between fluorescence emission and quenching, to achieve optical imaging and photoacoustic and photothermal properties.

CONCLUSION
We obtained rationally designed nanoparticles with outstanding stability in biological environment. At appropriate doping regimes, the presence of Cy5.5 and Cy7 dyes allowed us to tune fluorescence emission in the NIR for optical imaging and to exploit quenching processes for photoacoustic and photothermal capabilities. These nanostructures are promising in vivo theranostic tools for the near future.

Biffi|Stefania|S|
Petrizza|Luca|L|
Garrovo|Chiara|C|
Rampazzo|Enrico|E|
Andolfi|Laura|L|
Giustetto|Pierangela|P|
Nikolov|Ivaylo|I|
Kurdi|Gabor|G|
Danailov|Miltcho Boyanov|MB|
Zauli|Giorgio|G|
Secchiero|Paola|P|
Prodi|Luca|L|

optical imaging
NIR imaging
PEGylated nanoparticles
dye-doped nanoparticles
photoacoustic imaging
photothermal therapy


Utility of postoperative radiography in routine primary total shoulder arthroplasty.

Abstract:
BACKGROUND
The medical relevance and cost-benefit of routine radiographs after primary anatomic total shoulder arthroplasty (TSA) up to a year postoperatively are unknown. This study was performed to assess the medical relevance and cost-benefit of radiography after TSA during the first postoperative year.

METHODS
During the period 2010 to 2015, 160 consecutive patients undergoing anatomic TSA by a single fellowship-trained surgeon had radiographs obtained at 2 weeks, 6 weeks, 4 months, and 1 year postoperatively. Radiographs and clinic notes were assessed to determine if a change in postoperative care happened because of radiographic findings, including postoperative fracture, hardware complication, or any concerning radiographic feature. Cost data and amount billed were obtained.

RESULTS
Patients underwent radiography at 1.8 ± 0.2 weeks, 6.5 ± 1.2 weeks, 14.9 ± 2.9 weeks, and 46.8 ± 19.5 weeks postoperatively. Findings on the radiologist's reading were normal/unremarkable for 100.0%, 96.8%, 95.9%, and 95.2%, respectively, at each visit. Results were documented in the note for 92.5%, 97.4%, 98.0%, and 92.4%, respectively, at each visit. Review of the radiographs yielded no change in management based on these parameters. The amount billed for radiographs was $284,281 ($1776.76 per patient).

CONCLUSIONS
A lack of clinically meaningful impact from routine postoperative radiography does not justify the per-patient expense, as routine imaging did not cause a change in postoperative management. The available data suggest that routine radiographs after primary anatomic TSA may be unnecessary or perhaps the described frequency in which radiographs are obtained is in excess.

Dempsey|Ian J|IJ|
Kew|Michelle E|ME|
Cancienne|Jourdan M|JM|
Werner|Brian C|BC|
Brockmeier|Stephen F|SF|

utility
radiography
Primary total shoulder arthroplasty
X-ray
cost-effectiveness
health care economics


Production of novel palladium nanocatalyst stabilized with sustainable chitosan/cellulose composite and its catalytic performance in Suzuki-Miyaura coupling reactions.

Abstract: In this study, we designed a new palladium nanocatalyst on chitosan/cellulose composite for the first time to increase the use of sustainable polysaccharides, which are cheap, non-toxic, environmental friendly, abundant in nature, and can be used as support materials for metallic nanoparticles. Physicochemical characterization of fabricated palladium nanocatalyst was illuminated with FT-IR, TG/DTG, SEM/EDAX, XRD, and ICP-OES analyses. Pd nanoparticles were found to be almost spherically structured, and the average particle size was 26-30nm. Then catalytic performance of the designed nanocatalyst was investigated in the synthesis of a series of biphenyl compounds via the Suzuki-Miyaura reaction by using the green method which is conducted in a very short-time, under low temperature, and without the presence of any toxic chemical solvents (e.g., 5min treatment in microwave oven at 400W at 50°C). As a result of the tests, palladium nanocatalyst showed excellent catalytic performance with high conversion yields for a wide range of substrates and with a very low catalyst loading for the Suzuki reactions. Sustainability performance of palladium nanocatalyst was also studied, and it is found that the catalyst was able to be recycled for eight successive runs.

Yılmaz Baran|Nuray|N|
Baran|Talat|T|
Menteş|Ayfer|A|

Nanocatalyst Sustainability Composite Polysaccharide Microwave


Minimally Invasive Adnexal Mass Extraction: Considerations and Techniques (With Videos).

Abstract: Adnexal masses are a common indication for surgery in the United States. This article reviews the clinical features that may suggest an underlying malignancy, including ultrasound and biomarkers. The decision regarding how to remove an adnexal mass involves consideration of several factors, including body habitus, intra-abdominal anatomy, concomitant procedures planned, characteristics of the adnexal mass, and concern for underlying malignancy. Minimally invasive techniques for removal of adnexal masses are discussed in detail, with a review of the risk of an unexpected underlying malignancy.

Walsh|Teresa M|TM|
McMillin|Miranda G|MG|
Kho|Kimberly A|KA|

D019060:Minimally Invasive Surgical Procedures

Adnexal mass
Colpotomy
Laparoscopic extraction
Laparoscopic removal
Laparoscopy
Large adnexal masses
Tissue extraction


Production of cellulase from Aspergillus terreus MS105 on crude and commercially purified substrates.

Abstract: Aspergillus terreus MS105 was originally isolated from soil and screened for cellulase production in the presence of various carbon sources including carboxymethyl cellulose (CMC), avicel, sigmacell, filter-paper and salicin. CMC induced the production of endoglucanase (EG) and filter-paperase while the levels of β-glucosidase (BGL) were increased when salicin was present in the medium. Nature of production medium influenced the duration of lag- and log-phase of the growth, rate of fungal dry-mass and enzyme production. The volumetric and specific productivity of cellulase under submerged fermentation of grass were 1.7-20-folds higher than sugarcane-bagasse, corncob and commercially available purified substrates. Nonetheless, solid state fermentation (SSF) of crude substrates also yielded high volumetric productivity of EG and BGL. The studies on characterization of enzymes showed that EG was more thermostable than BGL with an optimum activity at 70 °C and a melting temperature of 76 °C. A 1.2-1.5-folds increase in EG activity was observed in the presence of K+, Ca2+ and Mg2+, whereas, the EG and BGL activities remained unaffected in the presence of EDTA. Both the enzyme activities performed optimally under acidic range of pH.

Sohail|Muhammad|M|
Ahmad|Aqeel|A|
Khan|Shakeel Ahmed|SA|

Aspergillus terreus
Endoglucanase
β-glucosidase
Crude substrates
Solid-state fermentation


Aging and the prudential lifespan account.

Abstract: As individuals grow older, they usually require assistance with the daily tasks of self-care. This type of assistance, ancillary care, is essential to maintaining the health of those who need these services. In his prudential lifespan account, Norman Daniels includes access to such services making his account an attractive proposal given the current demographic shift. In this paper, I examine the prudential lifespan account through the lens of old age and I focus on the two concepts on which the lifespan account relies. I show that these two concepts, normal species functioning and opportunity cannot buttress Daniels's lifespan account; at least it cannot do so for older persons. The tensions that I identify in the prudential lifespan account in relation to aging are instructive for the more recent proposals to include aging in a theory of health and health justice. In addition, my analysis allows me to demonstrate that Daniels's view of opportunity is irreconcilable to capabilities, the latter being more adaptable to the realities of aging. If capabilities appear more promising, it is nonetheless imperative that the specificities of extended care, such as the need for unpaid caregiving, be taken into consideration.

Aging
Prudential lifespan account
Daniels
Normal species functioning
Capabilities


Mechanical Properties of Hybrid Graphene Nanoplatelet-Nanosilica Filled Unidirectional Basalt Fibre Composites.

Abstract: Basalt fibre (BF) is one of the most promising reinforcing natural materials for polymer composites that could replace the usage of glass fibre due to its comparable properties. The aim of adding nanofiller in polymer composites is to enhance the mechanical properties of the composites. In theory, the incorporation of high strength and stiffness nanofiller, namely graphene nanoplatelet (GNP), could create superior composite properties. However, the main challenges of incorporating this nanofiller are its poor dispersion state and aggregation in epoxy due to its high surface area and strong Van der Waals forces in between graphene sheets. In this study, we used one of the effective methods of functionalization to improve graphene's dispersion and also introducing nanosilica filler to enhance platelets shear mechanism. The high dispersive silica nanospheres were introduced in the tactoids morphology of stacked graphene nanosheets in order to produce high shear forces during milling and exfoliate the GNP. The hybrid nanofiller modified epoxy polymers were impregnated into BF to evaluate the mechanical properties of the basalt fibre reinforced polymeric (BFRP) system under tensile, compression, flexural, and drop-weight impact tests. In response to the synergistic effect of zero-dimensional nanosilica and two-dimensional graphene nanoplatelets enhanced the mechanical properties of BFRP, especially in Basalt fibre + 0.2 wt% GNP/15 wt% NS (BF-H0.2) with the highest increment in modulus and strength to compare with unmodified BF. These findings also revealed that the incorporation of hybrid nanofiller contributed to the improvement in the mechanical properties of the composite. BF has huge potential as an alternative to the synthetic glass fibre for the fabrication of mechanical components and structures.

mechanical properties
basalt fibre
graphene nanoplatelets (GNP)
nanosilica
epoxy polymer
hybrid filler


A Blood Flow Volume Linear Inversion Model Based on Electromagnetic Sensor for Predicting the Rate of Arterial Stenosis.

Abstract: This paper presents a mathematical model of measuring blood flow based on electromagnetic induction for predicting the rate of arterial stenosis. Firstly, an electrode sensor was used to collect the induced potential differences from human skin surface in a uniform magnetic field. Then, the inversion matrix was constructed by the weight function theory and finite element method. Next, the blood flow volume inversion model was constructed by combining the induction potential differences and inversion matrix. Finally, the rate of arterial stenosis was predicted based on mathematical relationship between blood flow and the area of arterial stenosis. To verify the accuracy of the model, a uniform magnetic field distribution of Helmholtz coil and a 3D geometric model of the ulnar artery of the forearm with different rates of stenosis were established in COMSOL, a finite element analysis software. Simulation results showed that the inversion model had high accuracy in the measurement of blood flow and the prediction of rate of stenosis, and is of great significance for the early diagnosis of arterial stenosis and other vessel diseases.

Yang|Dan|D|0000-0002-9790-0851 Liu|Yan-Jun|YJ| Xu|Bin|B| Duo|Yun-Hui|YH|

D001158:Arteries
D003198:Computer Simulation
D003251:Constriction, Pathologic
D055590:Electromagnetic Phenomena
D004867:Equipment Design
D020342:Finite Element Analysis
D006801:Humans
D016014:Linear Models
D008955:Models, Cardiovascular
D012039:Regional Blood Flow
D012984:Software
D014652:Vascular Diseases

electromagnetic sensor
artery stenosis
weight function
finite element
COMSOL


Effects of Pup Separation on Stress Response in Postpartum Female Rats.

Abstract: There is a complex collection of neuroendocrine function during the postpartum period. Prolactin (PRL) released by suckling stimulus and its PRL receptors (PRL-R) in the central nervous system (CNS) are involved in hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in lactating mammals including rodents and humans. It is not clear how long it takes to reestablish the attenuated HPA axis activity of lactating rats to a pre-pregnancy state after pup separation. We first tested the hypothesis that HPA axis activity in response to an acute stress in postpartum rats would return to a pre-pregnancy state after pup separation. Restraint stress for 30 min was performed at the end of pup separation as an acute stressor. Plasma levels of corticosterone (CORT) were measured following restraint stress or no-stress (control) in virgin rats and postpartum rats housed with their pups or with pup removal for different periods of time of one hour, 24 h, or eight days. We then tested the hypothesis that circulating PRL level and CNS PRL-R gene expression were involved in mediating the acute stress response in postpartum rats. Plasma levels of PRL and PRL-R mRNA levels in the choroid plexus of the CNS were determined in both no-stress and stress, virgin rats, and postpartum rats housed with their pups or with pup removal for various periods, and their correlation with plasma CORT levels was assessed. The results demonstrated that PRL levels declined to virgin state in all postpartum rats separated from their pups, including the dams with one-hour pup separation. Stress-induced HPA activity dampened in lactating rats housed with pups, and returned to the pre-pregnancy state after 24 h of pup separation when both circulating PRL level and CNS PRL-R expression were restored to a pre-pregnancy state. Additionally, basal plasma CORT and CNS PRL-R expression were significantly correlated in rats with various pup status. This study suggested that stress-induced HPA activation occurred when PRL-R expression was similar to the level of virgin females, indicating that PRL-R upregulation contributes to an attenuated HPA response to acute stress. Understanding neuroendocrine responses to stress during the postpartum period is critical to understand postpartum-related neuropsychiatric illnesses and to maintain mental health in postpartum women.

Kalyani|Manu|M|
Callahan|Phyllis|P|
Janik|James M|JM|
Shi|Haifei|H|

prolactin
lactation
HPA axis
restraint stress
corticosterone
prolactin receptor


Cryptogenic stroke: clinical consideration of a heterogeneous ischemic subtype.

Abstract:
BACKGROUND
Cryptogenic stroke can be subdivided into 3 distinct categories: stroke of no determined cause (CyNC), stroke due to multiple etiologies (Cy >1), and stroke etiology unclear due to incomplete evaluation. Although these subdivisions may be very different from one another with respect to baseline features and outcomes, they are often reported as a composite group in clinical trials.

METHODS
Patients treated at our academic institution between July 2008 and June 2013 for acute ischemic stroke were retrospectively assessed in our prospective registry. CyNC and Cy >1 patients were compared to other Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtypes and to each other using univariate analyses and multivariate logistic regression. The primary outcome of interest was good functional outcome, defined as a discharge modified Rankin Scale score of 0-2.

RESULTS
Of the 1311 included patients, 260 (19.8%) experienced a CyNC and 49 (3.7%) experienced a Cy >1. Cy >1 classification was associated with history of atrial fibrillation (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.16-6.12; P = .001). In comparison to other TOAST classifications, CyNC strokes were more likely to have good functional outcome (OR, 1.97; 95% CI, 1.38-2.82; P < .001) after adjusting for baseline National Institutes of Health Stroke Scale, admission glucose, age, and intravenous tissue plasminogen activator (IV tPA).

CONCLUSIONS
Even after adjusting for higher IV tPA treatment rates, ischemic stroke patients with no identified cause had better outcomes than other TOAST groups. Conversely, patients coded as cryptogenic with more than 1 likely cause represent a different patient subpopulation. These data argue against the consolidation of cryptogenic stroke subcategories in future investigations.

Scullen|Tyler A|TA|
Monlezun|Dominique J|DJ|
Siegler|James E|JE|
George|Alexander J|AJ|
Schwickrath|Melissa|M|
El Khoury|Ramy|R|
Cho|Min Chan|MC|
Martin-Schild|Sheryl|S|

cryptogenic stroke
Ischemic stroke
TOAST
atrial fibrillation
cost
management


Management of multiple tumors in neurofibromatosis type 2 patients.

Abstract:
INTRODUCTION
Neurofibromatosis type 2 is characterized by the presence of bilateral vestibular schwannomas. However, other nervous system tumors may also occur. Therefore, the management of NF2 patients is complex and requires a multidisciplinary discussion in a specialized center.

MATERIALS AND METHODS
All recent articles concerning tumors other than vestibular schwannoma in NF2 disease were reviewed, using PubMed databases.

RESULTS
Intracranial meningiomas occur in 50% of NF2 patients, and are often multiple. Surgery remains the main treatment and should be performed in cases of growing tumors. The role of antiangiogenic therapy is currently under evaluation and the role of radiosurgery still remains to be defined in NF2 disease. Spinal tumors occur in about half of NF2 patients. Surgery should be discussed when radiological tumor progression is demonstrated, even if spinal tumors are asymptomatic, in order to preserve neurological function and good quality of life. As regards lower cranial nerve schwannomas, radiosurgery appears to be a more appropriate treatment for growing tumor with a small volume in order to avoid post-operative complications, especially swallowing disorders. Facial nerve schwannomas may appear, on MRI, like vestibular schwannomas. The diagnosis should be suspected when the facial palsy is an early symptom during cerebello-pontine tumor progression. Trigeminal schwannomas are frequent in NF2 disease and fortunately they are often asymptomatic. Among major neurofibromatosis types, peripheral nerve sheath schwannomas are only present in patients with NF2 disease and schwannomatosis. Surgical resection is required when the cutaneous schwannomas is painful or when tumor progression is observed and causes symptoms.

CONCLUSION
Tumors other than vestibular schwannoma are also associated with a poor prognosis in NF2 patients. Surgery remains the main treatment in most cases. Each treatment decision in NF2 disease requires a complete evaluation of all cranial and spinal locations of the disease in order to establish surgical priorities and strategies.

Aboukais|R|R| Bonne|N-X|NX| Baroncini|M|M| Zairi|F|F| Schapira|S|S| Vincent|C|C| Lejeune|J-P|JP|

Schwannoma
NF2
Meningioma
Spinal tumor
Ependymoma
Méningiome
Schwannome
Tumeur spinale
Épendymome


Stroke Seasonality and Weather Association in a Middle East Country: A Single Tertiary Center Experience.

Abstract: Background: Stroke is a medical condition that leads to major disability and mortality worldwide. Some evidence suggests that weather and seasonal variations could have an impact on stroke incidence and outcome. However, the current evidence is inconclusive. Therefore, this study examines the seasonal variations and meteorological influences on stroke incidence and outcome in the largest city in Saudi Arabia. Methods: From February 2016 to July 2019, we retrospectively reviewed data from all patients with acute ischemic (AIS) or hemorrhagic stroke (HS) admitted to the stroke unit in a tertiary academic center in Saudi Arabia. The corresponding daily meteorological data were obtained for the same period. We considered the months from November to March as the cold season and April to October as the hot season. Results: The final cohort included 1,271 stroke patients; 60.89% (n = 774) cases occurred in the hot season, while 39.1% (n = 497) in the cold season. Males accounted for 69.6% (n = 884) of the cases. The proportion of ischemic stroke was 83.2% [hot season 83.9% (n = 649) vs. cold season 82.3% (n = 409)]. We found no statistically significant difference between seasons (hot or cold) in stroke incidence, severity [National Institutes of Health Stroke Scale (NIHSS)], hospital course (pneumonia, thromboembolism, intensive care stay, or length of stay), or outcome [modified Rankin scale (mRS) on discharge and death]. Conclusions: In Riyadh, Saudi Arabia, our study found no impact of weather or seasonal variations on stroke incidence, hospital course, or outcomes. However, our findings warrant further research in different country regions.

Alghamdi|Saeed A M|SAM|
Aldriweesh|Mohammed A|MA|
Al Bdah|Bayan A|BA|
Alhasson|Muath A|MA|
Alsaif|Sultan A|SA|
Alluhidan|Waleed A|WA|
Almutairi|Faisal M|FM|
Alskaini|Mohammed A|MA|
Alotaibi|Naser|N|
Al Khathaami|Ali M|AM|

weather
Saudi Arabia
hemorrhagic stroke
ischemic stroke
risk factors


Health promotion preparedness for health crises - a 'must' or 'nice to have'? Case studies and global lessons learned from the COVID-19 pandemic.

Abstract: The current COVID-19 pandemic has exposed missing links between health promotion and national/global health emergency policies. In response, health promotion initiatives were urgently developed and applied around the world. A selection of case studies from five countries, based on the Socio-Ecological Model of Health Promotion, exemplify 'real-world' action and challenges for health promotion intervention, research, and policy during the COVID-19 pandemic. Interventions range from a focus on individuals/families, organizations, communities and in healthcare, public health, education and media systems, health-promoting settings, and policy. Lessons learned highlight the need for emphasizing equity, trust, systems approach, and sustained action in future health promotion preparedness strategies. Challenges and opportunities are highlighted regarding the need for rapid response, clear communication based on health literacy, and collaboration across countries, disciplines, and health and education systems for meaningful solutions to global health crises.

health literacy
equity/social justice
health-promoting healthcare
health-promoting schools
mental health literacy
migrant health
vulnerable groups


The decays of (109,111)Pd and (111)Ag following neutron capture by Pd.

Abstract: Improved precisions of the energies and intensities of the γ rays emitted in the decays of (109)Pd and (111g,m)Pd have been obtained based on a high-resolution spectroscopic study of these γ emissions from radioactive samples produced by neutron capture by natural Pd. Correspondingly improved values of the energies and β feedings of the levels in the (109,)(111)Ag daughters have been deduced. More precise energies and intensities have also been determined for the γ rays emitted in the decays of the (111)Pd daughter activities (111g,m)Ag to (111)Cd.


Gas-Phase Ion Fluorescence Spectroscopy of Tailor-made Rhodamine Homo- and Heterodyads: Quenching of Electronic Communication by π-Conjugated Linkers.

Abstract: While many key photophysical features are understood for electronic communication between chromophores in neutral compounds, there is limited information on the effect of charges in practically relevant ionic chromo/fluorophores. Here we have chosen positively charged rhodamines and prepared a selection of homo- and heterodimers with alkyl or π-conjugated, acetylenic bridges. Protonated molecules were transferred as isolated ions to gas phase where there is no solvent screening of charges, and fluorescence spectra were measured with a custom-made ion-trap setup. Our work reveals strong polarization of the π-spacer (induced dipole/quadrupole) when it experiences the electric field from one/ two dyes. Hence, π-spacers provide efficient shielding of charges by reducing the Coulomb interaction, whereas two dye cations polarize each other when connected by an alkyl. The screening influences the Förster resonance energy transfer efficiency that relies on the dipole-dipole interaction.

fluorescence
alkynes
cross-coupling
dyads
gas-phase FRET


Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear.

Abstract: Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here, we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented rats from learning to avoid a lever that was punished with a stimulus that coterminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from reacquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.

medial orbitofrontal cortex
conditioned punishment
Pavlovian conditioned fear
passive avoidance


Artificial intelligence in oncology: Path to implementation.

Abstract: In recent years, the field of artificial intelligence (AI) in oncology has grown exponentially. AI solutions have been developed to tackle a variety of cancer-related challenges. Medical institutions, hospital systems, and technology companies are developing AI tools aimed at supporting clinical decision making, increasing access to cancer care, and improving clinical efficiency while delivering safe, high-value oncology care. AI in oncology has demonstrated accurate technical performance in image analysis, predictive analytics, and precision oncology delivery. Yet, adoption of AI tools is not widespread, and the impact of AI on patient outcomes remains uncertain. Major barriers for AI implementation in oncology include biased and heterogeneous data, data management and collection burdens, a lack of standardized research reporting, insufficient clinical validation, workflow and user-design challenges, outdated regulatory and legal frameworks, and dynamic knowledge and data. Concrete actions that major stakeholders can take to overcome barriers to AI implementation in oncology include training and educating the oncology workforce in AI; standardizing data, model validation methods, and legal and safety regulations; funding and conducting future research; and developing, studying, and deploying AI tools through multidisciplinary collaboration.

Chua|Isaac S|IS|0000-0002-8404-8452
Gaziel-Yablowitz|Michal|M|
Korach|Zfania T|ZT|
Kehl|Kenneth L|KL|0000-0001-5339-9797
Levitan|Nathan A|NA|
Arriaga|Yull E|YE|0000-0002-7229-2028
Jackson|Gretchen P|GP|
Bates|David W|DW|
Hassett|Michael|M|

artificial intelligence
oncology
deep learning
machine learning


Visualization of Needle-Tip Localization by Ultrasound Guidance with Contrast Bubble in Lumbar Selective Nerve Root Block: Clinical Pilot Study.

Abstract:
BACKGROUND
Epidural steroid injection for low back and leg pain has been shown to result in a positive clinical outcome. Lumbosacral selective nerve root block (SNRB) via a transforaminal approach is commonly performed under fluoroscopic guidance. However, ultrasound guidance is an alternative to overcome the radiologic disadvantages. This study examined the accuracy of needle-tip localization under ultrasound guidance with a contrast bubble, compared with fluoroscopic guidance.

OBJECTIVE
The primary objectives were to envisage the needle-tip localization with an air bubble by ultrasound and also to determine the accuracy of needle-tip location in transforaminal lumbar SNRB for low back and leg pain patients who were not surgical candidates.

METHODS
A prospective study of 30 SNRBs was conducted. An air bubble was produced and was used to envisage the needle-tip location under ultrasound guidance. Finally, the needle tip was confirmed by fluoroscopy. The accuracy of needle-tip location was statistically analyzed.

RESULTS
Twenty-four SNRBs were performed at L4-5 and 6 SNRBs at L3-4. The accuracy of needle-tip localization was 80%.

CONCLUSION
In order to avoid radiation exposure during the SNRB procedure, ultrasound guidance might be an alternative. Despite being accepted practice, there is a steep learning curve involved in the use of ultrasound guidance for lumbar SNRB, and proper training is crucial. A contrast bubble is a prospective enhancement for better visualization of ultrasound guidance.

Pain
Needles
Lumbosacral region
Nerve block
Spinal injection
Triamcinolone


Assessing usefulness and researcher satisfaction with consent form templates.

Abstract:
Introduction
We aimed to improve the research consenting process by developing and evaluating simplified consent forms.

Methods
Four templates written at the eighth-tenth grade reading level were developed and trialed by a group of experts in clinical research, health literacy, national regulatory requirements, and end users. Researchers from protocols which had received expedited review were surveyed at 2 time points regarding their use and assessment of the templates.

Results
At baseline 18/86 (20.9%) responding researchers had heard of the templates and 5 (5.8%) reported that they had used them; 2 years later, 54.2% (32/59) had heard of the templates and 87.5% (28/32) had used them (p<0.001).

Conclusions
Consent form templates may be one mechanism to improve patient comprehension of research protocols as well as efficiency of the review process, but require considerable time for development and implementation, and one key to their success is involvement and support from the IRB and technical staff.

Larson|Elaine L|EL|
Teller|Alan|A|
Aguirre|Alejandra N|AN|
Jackson|Jhia|J|
Meyer|Dodi|D|

consent forms
Informed consent
health literacy, bioethics


Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222.

Abstract: BacSp222 is a multifunctional peptide produced by Staphylococcus pseudintermedius 222. This 50-amino acid long peptide belongs to subclass IId of bacteriocins and forms a four-helix bundle molecule. In addition to bactericidal functions, BacSp222 possesses also features of a virulence factor, manifested in immunomodulatory and cytotoxic activities toward eukaryotic cells. In the present study, we demonstrate that BacSp222 is produced in several post-translationally modified forms, succinylated at the ε-amino group of lysine residues. Such modifications have not been previously described for any bacteriocins. NMR and circular dichroism spectroscopy studies have shown that the modifications do not alter the spatial structure of the peptide. At the same time, succinylation significantly diminishes its bactericidal and cytotoxic potential. We demonstrate that the modification of the bacteriocin is an effect of non-enzymatic reaction with a highly reactive intracellular metabolite, i.e., succinyl-coenzyme A. The production of succinylated forms of the bacteriocin depends on environmental factors and on the access of bacteria to nutrients. Our study indicates that the production of succinylated forms of bacteriocin occurs in response to the changing environment, protects producer cells against the autotoxicity of the excreted peptide, and limits the pathogenicity of the strain.

succinylation
bacteriocin
Staphylococcus pseudintermedius
cytotoxic
Krebs/tricarboxylic acids cycle
antibacterial
nuclear magnetic resonance (NMR)
succinyl-coenzyme A