Pilot test of a home-based program to prevent perceived insufficient milk.

Abstract:
PROBLEM
Although the World Health Organization and American Academy of Pediatrics recommend exclusive breastfeeding for the first six months, only 22% of U.S. mothers do so. Mothers' perceived insufficient milk (PIM) is the primary reason for breastfeeding discontinuation globally. There are two changeable causes of PIM: (1) mothers' misinterpretation of their infant's behavior, and (2) mothers' lack of confidence in their ability to breastfeed.

AIM
The purpose of this study was to evaluate the short-term effect of a home-based intervention designed to prevent and/or reduce PIM.

METHODS
A mixed-methods, single-group, pretest-midtest-posttest design was used for evaluating a home-based breastfeeding program. The program was implemented during three 1.0- to 1.5-h home intervention sessions at 6, 13, and 27 days postpartum, delivered to 14 dyads of breastfeeding mothers and their full-term singleton infants.

FINDINGS
We found significant increases over time in mothers' sensitivity to infant behavior and breastfeeding self-efficacy as well as significant decreased attribution of infant crying to PIM. Exit interviews indicated that the program was accepted by participating mothers.

DISCUSSION
This is the first intervention study that has directly targeted the causes of PIM. The home-based intervention has the potential to add to maternal competencies both in correctly assessing their infants' behavior, thereby preventing erroneous attribution of infant behavior to PIM, as well as simultaneously bolstering maternal confidence in breastfeeding skills.

CONCLUSION
By building maternal competencies, the home-based intervention has a longer-range potential to prevent breastfeeding discontinuation. Further evaluation is warranted.

Wood|Natsuko K|NK|
Sanders|Elizabeth A|EA|
Lewis|Frances M|FM|
Woods|Nancy F|NF|
Blackburn|Susan T|ST|

Perceived insufficient milk
Exclusive
Breastfeeding
Pilot study


Stress and coping - Perceptions of final year nursing students returning to clinical practice during the COVID-19 pandemic, South Africa.

Abstract:
Background
The novel nature of the coronavirus disease 2019 (COVID-19) pandemic places challenges on nursing students as they try to complete the clinical requirement of their training. Nursing faculties need to understand these challenges to support and equip nursing students to enter the workforce.

Aim
To explore and describe the anticipated and subsequent perceptions of final year Bachelor of Nursing students returning to clinical practice during the COVID-19 pandemic in South Africa.

Setting
The study was conducted at two universities in the Western Cape and KwaZulu-Natal, South Africa. Both universities offer 4-year Bachelor of Nursing programmes accredited by the South African Nursing Council and were in 'hot spot areas' for SARS-CoV-2.

Methods
A qualitative study with focus groups discussions of final year undergraduate nursing students from both universities were conducted. Data were analysed through content analysis using Lazarus and Folkman's Stress Appraisal Coping Model.

Results
Five focus groups discussions with a total of 25 participants were conducted. Three themes with eight sub-themes emerged, the key themes being: primary appraisal and anticipation of returning to clinical practice; contextual influence on primary appraisal and reappraisal to facilitate positive return to clinical practice.

Conclusion
Primary perceptions of returning to clinical practice revolved around uncertainty and stress. However, through preparation and the process of reappraisal, participants were able to adapt and cope with the challenges in returning to clinical practice during the pandemic.

Contribution
It is important to recognise the role of faculty in supporting nursing students' transition into situations of uncertainty such as the pandemic.

stress
coping
nursing students
clinical practice
COVID-19 pandemic


A predictive model and nomogram for predicting return to work at 3 months after cervical spine surgery: an analysis from the Quality Outcomes Database.

Abstract: OBJECTIVEBack pain and neck pain are two of the most common causes of work loss due to disability, which poses an economic burden on society. Due to recent changes in healthcare policies, patient-centered outcomes including return to work have been increasingly prioritized by physicians and hospitals to optimize healthcare delivery. In this study, the authors used a national spine registry to identify clinical factors associated with return to work at 3 months among patients undergoing a cervical spine surgery.METHODSThe authors queried the Quality Outcomes Database registry for information collected from April 2013 through March 2017 for preoperatively employed patients undergoing cervical spine surgery for degenerative spine disease. Covariates included demographic, clinical, and operative variables, and baseline patient-reported outcomes. Multiple imputations were used for missing values and multivariable logistic regression analysis was used to identify factors associated with higher odds of returning to work. Bootstrap resampling (200 iterations) was used to assess the validity of the model. A nomogram was constructed using the results of the multivariable model.RESULTSA total of 4689 patients were analyzed, of whom 82.2% (n = 3854) returned to work at 3 months postoperatively. Among previously employed and working patients, 89.3% (n = 3443) returned to work compared to 52.3% (n = 411) among those who were employed but not working (e.g., were on a leave) at the time of surgery (p < 0.001). On multivariable logistic regression the authors found that patients who were less likely to return to work were older (age > 56-65 years: OR 0.69, 95% CI 0.57-0.85, p < 0.001; age > 65 years: OR 0.65, 95% CI 0.43-0.97, p = 0.02); were employed but not working (OR 0.24, 95% CI 0.20-0.29, p < 0.001); were employed part time (OR 0.56, 95% CI 0.42-0.76, p < 0.001); had a heavy-intensity (OR 0.42, 95% CI 0.32-0.54, p < 0.001) or medium-intensity (OR 0.59, 95% CI 0.46-0.76, p < 0.001) occupation compared to a sedentary occupation type; had workers' compensation (OR 0.38, 95% CI 0.28-0.53, p < 0.001); had a higher Neck Disability Index score at baseline (OR 0.60, 95% CI 0.51-0.70, p = 0.017); were more likely to present with myelopathy (OR 0.52, 95% CI 0.42-0.63, p < 0.001); and had more levels fused (3-5 levels: OR 0.46, 95% CI 0.35-0.61, p < 0.001). Using the multivariable analysis, the authors then constructed a nomogram to predict return to work, which was found to have an area under the curve of 0.812 and good validity.CONCLUSIONSReturn to work is a crucial outcome that is being increasingly prioritized for employed patients undergoing spine surgery. The results from this study could help surgeons identify at-risk patients so that preoperative expectations could be discussed more comprehensively.

Devin|Clinton J|CJ|
Bydon|Mohamad|M|
Alvi|Mohammed Ali|MA|
Kerezoudis|Panagiotis|P|
Khan|Inamullah|I|
Sivaganesan|Ahilan|A|
McGirt|Matthew J|MJ|
Archer|Kristin R|KR|
Foley|Kevin T|KT|
Mummaneni|Praveen V|PV|
Bisson|Erica F|EF|
Knightly|John J|JJ|
Shaffrey|Christopher I|CI|
Asher|Anthony L|AL|

ACDF = anterior cervical discectomy and fusion


Factor 10 Expedience of Monthly Linac Quality Assurance via an Ion Chamber Array and Automation Scripts.

Abstract:
PURPOSE
While critical for safe and accurate radiotherapy, monthly quality assurance of medical linear accelerators is time-consuming and takes physics resources away from other valuable tasks. The previous methods at our institution required 5 hours to perform the mechanical and dosimetric monthly linear accelerator quality assurance tests. An improved workflow was developed to perform these tests with higher accuracy, with fewer error pathways, in significantly less time.

METHODS
A commercial ion chamber array (IC profiler, Sun Nuclear, Melbourne, Florida) is combined with automation scripts to consolidate monthly linear accelerator QA. The array was used to measure output, flatness, symmetry, jaw positions, gated dose constancy, energy constancy, collimator walkout, crosshair centering, and dosimetric leaf gap constancy. Treatment plans were combined with automation scripts that interface with Sun Nuclear's graphical user interface. This workflow was implemented on a standard Varian clinac, with no special adaptations, and can be easily applied to other C-arm linear accelerators.

RESULTS
These methods enable, in 30 minutes, measurement and analysis of 20 of the 26 dosimetric and mechanical monthly tests recommended by TG-142. This method also reduces uncertainties in the measured beam profile constancy, beam energy constancy, field size, and jaw position tests, compared to our previous methods. One drawback is the increased uncertainty associated with output constancy. Output differences between IC profiler and farmer chamber in plastic water measurements over a 6-month period, across 4 machines, were found to have a 0.3% standard deviation for photons and a 0.5% standard deviation for electrons, which is sufficient for verifying output accuracy according to TG-142 guidelines. To minimize error pathways, automation scripts which apply the required settings, as well as check the exported data file integrity were employed.

CONCLUSIONS
The equipment, procedure, and scripts used here reduce the time burden of routine quality assurance tests and in most instances improve precision over our previous methods.

Skinner|Lawrie B|LB|0000-0001-7317-1642
Yang|Yong|Y|
Hsu|Annie|A|
Xing|Lei|L|
Yu|Amy S|AS|0000-0002-9730-5593
Niedermayr|Thomas|T|

quality assurance
automation
IC profiler
linac QA
monthly QA


SIRT3 Protects Against Acute Kidney Injury via AMPK/mTOR-Regulated Autophagy.

Abstract: Acute kidney injury (AKI), which involves the loss of kidney function caused by damage to renal tubular cells, is an important public health concern. We previously showed that sirtuin (SIRT)3 protects the kidneys against mitochondrial damage by inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, attenuating oxidative stress, and downregulating proinflammatory cytokines. In this article, we investigated the role of autophagy, mediated by a mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), in the protective effect of SIRT3, against sepsis-induced AKI, in a mouse model of cecal ligation and puncture (CLP). The AKI in CLP mice was associated with the upregulation of autophagy markers; this effect was abolished in SIRT3- mice in parallel with the downregulation of phospho (p)-AMPK and the upregulation of p-mTOR. Pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) or AMPK inhibitor compound isotonic saline (C), exacerbated AKI. SIRT3 overexpression promoted autophagy, upregulated p-AMPK and downregulated p-mTOR in CLP mice, attenuating sepsis-induced AKI, tubular cell apoptosis, and inflammatory cytokine accumulation in the kidneys. The blockage of autophagy induction largely abolished the protective effect of SIRT3 in sepsis-induced AKI. These findings indicate that SIRT3 protects against CLP-induced AKI by inducing autophagy through regulation of the AMPK/mTOR pathway.

Zhao|Wenyu|W| Zhang|Lei|L| Chen|Rui|R| Lu|Hanlan|H| Sui|Mingxing|M| Zhu|Youhua|Y| Zeng|Li|L|

acute kidney injury
autophagy
cecal ligation and puncture
AMPK/mTOR pathway
sirtuin 3


Endurance training selectively increases high-density lipoprotein-bound sphingosine-1-phosphate in the plasma.

Abstract: Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in relatively high concentration in human plasma. Erythrocytes, endothelial cells, and activated platelets are the main sources of circulating S1P. The majority of plasma S1P is transported bound to high-density lipoprotein (HDL) and albumin. In recent years, HDL-bound S1P attracted much attention due to its cardioprotective and anti-atherogenic properties. We have previously found that endurance-trained athletes are characterized by higher plasma S1P concentration compared to untrained individuals. This finding prompted us to examine the effect of endurance training on S1P metabolism in blood. Thirteen healthy, untrained, male subjects completed an 8-week training program on a rowing ergometer. Three days before the first, and 3 days after the last training session, blood samples were drawn from an antecubital vein. We found that total plasma S1P concentration was increased after the training. Further analysis of different plasma fractions showed that the training selectively elevated HDL-bound S1P. This effect was associated with activation of sphingosine kinase in erythrocytes and platelets and enhanced S1P release from red blood cells. We postulate that increase in HDL-bound S1P level is one of the mechanisms underlying beneficial effects of regular physical activity on cardiovascular diseases.

D017853:Phosphotransferases (Alcohol Group Acceptor)

ceramide
dihydrosphingosine
low-density lipoprotein
serum
sphingolipids
thrombocytes


Predicting postoperative atrial fibrillation after myocardial revascularization without cardiopulmonary bypass: A retrospective cohort study.

Abstract:
INTRODUCTION
Considering the threat imposed by postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and the potential benefits of off-pump CABG, the objective of this study was to describe the incidence and identify predictor factors for POAF in patients undergoing CABG without cardiopulmonary bypass (CPB).

METHODS
In this retrospective cohort study, we enrolled patients undergoing CABG without CPB between December 2008 and December 2011. The independent variables evaluated in this study were major patients' characteristics (age, sex, and ethnia), associated comorbidities (systemic arterial hypertension, diabetes mellitus, thyroid dysfunction, chronic renal failure (CRF), chronic obstructive pulmonary disease, and ischemic stroke), and the revascularization approach (the number of grafts used, the revascularized branch, and the choice of vascular graft (arterial or venous). The dependent variable was the onset of atrial fibrillation after the procedure.

RESULTS
Two hundred and eighty patients were included in the present study. The overall incidence of POAF after off-pump CABG was 5.0%. In the univariate analysis, the presence of chronic renal failure (odds ratio [OR], 3.01 [1.00-9.06], P = .049) and the use of venous-origin graft alone (OR, 9.67 [1.15-81.56], P = .037) were associated with an increased risk or POAF. These findings were confirmed after multivariate analysis, for both CRF (OR, 3.31 [1.05-10.46], P = .042) and the use of venous-origin graft alone (OR, 9.81 [1.13-85.35], P = .039).

CONCLUSION
Off-pump coronary artery bypass grafting proved a safe and effective procedure, with low postoperative atrial fibrillation occurrence, for myocardial revascularization. Chronic renal insufficiency and the use of venous-origin graft solely proved to be independent predictor factors for PAOF.

D047549:Coronary Artery Bypass, Off-Pump

postoperative atrial fibrillation
cardiopulmonary bypass
coronary artery bypass grafting


Heavy metal contamination in river water and sediments of the Swarnamukhi River Basin, India: risk assessment and environmental implications.

Abstract: The concentration of heavy metals was analyzed each of 20 river water, suspended sediments and bed sediments along the stretch of Swarnamukhi River Basin. River water is not contaminated with heavy metals except Fe and Mn. Contamination factor in sediments shows considerable to very high degree contamination with Cr, Cu, Pb and Zn. The sources of these metals could be residential wastes, sewer outfall, fertilizers, pesticides (M-45 + carbondine) and traffic activities apart from natural weathering of granitic rocks present in the basin area. Principal component analyses indicate the interaction between metals in different media. The comparison of metals (Cu, Pb and Zn) in bed sediments of Swarnamukhi River with the Indian and world averages indicates that the values obtained in the basin are above the Indian averages and far below to the world averages. Average shale values and sediment quality guidelines point toward the enrichment and contamination of Cu, Cr, Pb and Zn to several fold leading to eco-toxicological risks in basin.

Patel|Priyanka|P|
Raju|N Janardhana|NJ|
Reddy|B C Sundara Raja|BCSR|
Suresh|U|U|
Sankar|D B|DB|
Reddy|T V K|TVK|

D004784:Environmental Monitoring
D019015:Geologic Sediments
D007194:India
D019216:Metals, Heavy
D025341:Principal Component Analysis
D018570:Risk Assessment
D045483:Rivers
D014874:Water Pollutants, Chemical

Heavy metal
Swarnamukhi River
Suspended sediments
Contamination factor
Sediment quality guidelines
Heavy metal pollution index


Retrograde coronary intervention for chronic total occlusion of RCA ostium with anomalous origin: A case report.

Abstract: Chronic total coronary occlusion (CTO) remains one of the most technically challenging clinical scenarios in which to perform interventions. Although the antegrade approach is a general approach for CTO recanalization, a retrograde attempt improves the success rate and its usage has been increasingly adopted in recent years. Congenital coronary anomaly represents another technically challenging factor especially when accompanied with CTO lesions. We report the case of a 43-year-old man with no relevant cardiac history who presented for evaluation of exertional chest discomfort with palpitation. Coronary angiography revealed the existence of CTOs at just ostial of anomalously originating right coronary artery (RCA) with no angiographic ostial dimple in Valsalva sinus. Because it was not possible to engage with the antegrade guiding catheter (GC) at the inlet of the RCA, we decided to perform revascularization using the retrograde approach. Percutaneous coronary intervention (PCI) of such an anomalous RCA, which is chronically occluded, is difficult and is rarely described. Retrograde approach has been used to overcome the impossible placement of antegrade GC to RCA ostium. After successful CTO-PCI, his chest discomfort promptly disappeared. <Learning objective: Percutaneous coronary intervention for chronic total coronary occlusion of anomalous origin of right coronary artery (RCA) patients is difficult and is rarely described. Retrograde approach has been used to overcome the impossible placement of antegrade guiding catheter to RCA ostium.>.

Yamada|Ryotaro|R| Hirohata|Atsushi|A| Kume|Teruyoshi|T| Neishi|Yoji|Y| Uemura|Shiro|S|

Chronic total occlusion
Case report
Percutaneous coronary intervention
Anomalous origin of coronary artery


Exploring the effect of a lifestyle intervention on cancer risk: 43-year follow-up of the randomized Oslo diet and antismoking study.

Abstract:
BACKGROUND/OBJECTIVES
The Oslo diet and antismoking study showed that counselling for a healthy lifestyle reduced lifelong coronary mortality in high-risk men. We explored whether the same counselling reduced also cancer risk.

METHODS
The study randomly allocated males at high coronary risk to either a 5-year intervention for lifestyle changes (cholesterol-lowering dietary changes, weight loss and stopping smoking) or a control group (1 : 1) in 1972/73. We explored the incidence and mortality of all cancers and cancer forms related to smoking, BMI or diet up to 43 years after randomization.

RESULTS
A total of 595 men in the intervention and 621 in the control group were included. At inclusion median age was 45 years, 588 (48.4%) subjects were overweight (BMI > 25 kg m-2 ) and 925 (76.1%) current smokers. The intervention did not reduce the risk of cancer after 43 years (adjusted hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.80-1.15). In the first 25 years of follow-up, among the 1088 (89.5%) men who were overweight/obese and/or smokers, the intervention reduced the incidence of those cancer forms related to smoking, BMI or diet (including carcinoma of the respiratory, digestive and urinary tracts; adjusted HR 0.69; 95% CI 0.49-0.99). The intervention had no significant effect on incidence beyond 25 years, or on mortality.

CONCLUSIONS
The 5-year counselling for a healthy lifestyle did not reduce the overall cancer risk in the very long term. However, in the first 25 years, the counselling reduced the risk of relevant cancer types in overweight/obese subjects and smokers.

Botteri|E|E|
de Lange|T|T|
Tonstad|S|S|
Berstad|P|P|0000-0002-9025-4455

intervention
cancer
diet
smoking
cancer mortality
prevention


Subgroups with typical courses of depressive symptoms in an elderly population during 13 years of observation: Results from the Heinz Nixdorf Recall Study.

Abstract:
BACKGROUND
Depressive symptoms are volatile over time but empirical studies of intra-individual variations of depressive symptoms over longer periods are sparse.

AIMS
We aim to examine fluctuation patterns of depressive symptoms and to investigate the possible influence of age, sex and socioeconomic factors on fluctuation in a population-based sample over a period of 13 years.

METHODS
We used data of 4,251 participants (45-75 years; 51.0% women at baseline) of the Heinz Nixdorf Recall Study with at least two of nine possible measurements obtained in the period between 2000 and 2017. Depressive symptoms were assessed via the Center for Epidemiologic Studies Depression Scale (CES-D) short form. Based on the individual mean values and standard deviation from all measurements, we categorized participants as G1 'stable low', G2 'stable high', G3 'stable around cutoff' and G4 'large fluctuations'.

RESULTS
Most participants (82.3%) showed stable low depressive symptoms (G1), whereas 2.3% performed stable high values (G2), 6.9% stable around the cutoff (G3) and 8.6% large fluctuations (G4).

CONCLUSION
Our longitudinal results reveal that almost 18% (G2, G3 and G4) of the participants have an increased depression score or strong fluctuations at times. According to our classification, a higher proportion of the participants show anomalies with regard to depression compared to a simple classification into depressed and nondepressed, especially if this is based on a single measurement. Thus, longitudinal measurements of depression can prevent misclassification and provide valuable information about the course of depressive symptoms for a better understanding of the changes of depression.

Engel|Miriam|M|0000-0003-0161-0858 Jöckel|Karl-Heinz|KH| Dragano|Nico|N| Engels|Miriam|M| Moebus|Susanne|S|


Comparison of Stroke Codes in the Emergency Room and Inpatient Setting.

Abstract:
BACKGROUND
Outcomes of acute stroke management are time dependent. Intravenous tissue plasminogen activator (t-PA) is indicated within 3-4.5 hours of symptom onset and endovascular intervention within 6 hours. Time to treatment may depend on the patient's location. This study seeks to determine whether there is a difference in the timing of key aspects of stroke codes between the emergency room and the inpatient setting.

METHODS
Stroke codes ending in t-PA administration or endovascular intervention between 2010 and 2013 were included. Emergency room stroke codes were compared with those in the inpatient setting. Data were obtained from the Yarmon Stroke Center log. The variables were time to neurological evaluation, time to computed tomography (CT) scan, time to t-PA administration, time from CT scan to t-PA, and time to endovascular intervention. The variables were compared using the t test.

RESULTS
One hundred twenty-two stroke codes were included (106 from emergency room and 16 from inpatient setting). There was no difference in the time to neurological evaluation (P = .19). The time to CT scan and to t-PA administration was significantly increased in the inpatient group (P ≤ .001 and P = .01, respectively). There was no difference in the time from CT scan to t-PA (P = .09) and in the time to endovascular intervention (P = .21).

CONCLUSIONS
Our results show that in the inpatient setting, there was a significant delay in the time to CT scan and to t-PA administration and that the source of the delay is the time to CT scan.

Garcia-Santibanez|Rocio|R| Liang|John|J| Walker|Amy|A| Matos-Diaz|Ivan|I| Kahkeshani|Kourosh|K| Boniece|Irene|I|

Stroke code
emergency room
inpatient
in-hospital


Accounting for space and uncertainty in real-time location system-derived contact networks.

Abstract: Point data obtained from real-time location systems (RTLSs) can be processed into animal contact networks, describing instances of interaction between tracked individuals. Proximity-based definitions of interanimal "contact," however, may be inadequate for describing epidemiologically and sociologically relevant interactions involving body parts or other physical spaces relatively far from tracking devices. This weakness can be overcome by using polygons, rather than points, to represent tracked individuals and defining "contact" as polygon intersections.We present novel procedures for deriving polygons from RTLS point data while maintaining distances and orientations associated with individuals' relocation events. We demonstrate the versatility of this methodology for network modeling using two contact network creation examples, wherein we use this procedure to create (a) interanimal physical contact networks and (b) a visual contact network. Additionally, in creating our networks, we establish another procedure to adjust definitions of "contact" to account for RTLS positional accuracy, ensuring all true contacts are likely captured and represented in our networks.Using the methods described herein and the associated R package we have developed, called contact, researchers can derive polygons from RTLS points. Furthermore, we show that these polygons are highly versatile for contact network creation and can be used to answer a wide variety of epidemiological, ethological, and sociological research questions.By introducing these methodologies and providing the means to easily apply them through the contact R package, we hope to vastly improve network-model realism and researchers' ability to draw inferences from RTLS data.

contact network
R package
animal behavior
biotelemetry
global positioning system
movement ecology
radio telemetry
real‐time location


Hypoxia-induced downregulation of Sema3a and CXCL12/CXCR4 regulate the formation of the coronary artery stem at the proper site.

Abstract:
BACKGROUND
During the formation of the coronary artery stem, endothelial strands from the endothelial progenitor pool surrounding the conotruncus penetrate into the aortic wall. Vascular endothelial growth factors (VEGFs) as well as CXCL12/CXCR4 signaling are thought to play a role in the formation of the coronary stem. However, the mechanisms regulating how endothelial strands exclusively invade into the aorta remain unknown.

METHODS AND RESULTS
Immunohistochemistry showed that before the formation of endothelial strands, Sema3a was highly expressed in endothelial progenitors surrounding the great arteries. At the onset of/during invasion of endothelial strands into the aorta, Sema3a was downregulated and CXCR4 was upregulated in the endothelial strands. In situ hybridization showed that Cxcl12 was highly expressed in the aortic wall compared with in the pulmonary artery. Using avian embryonic hearts, we established two types of endothelial penetration assay, in which coronary endothelial strands preferentially invaded into the aorta in culture. Sema3a blocking peptide induced an excess number of endothelial strands penetrating into the pulmonary artery, whereas recombinant Sema3a inhibited the formation of endothelial strands. In cultured coronary endothelial progenitors, recombinant VEGF protein induced CXCR4-positive endothelial strands, which were capable of being attracted by CXCL12-impregnated beads. Monoazo rhodamine detected that hypoxia was predominant in aortic/subaortic region in ovo and hypoxic condition downregulated the expression of Sema3a in culture.

CONCLUSION
Results suggested that hypoxia in the aortic region downregulates the expression of Sema3a, thereby enhancing VEGF activity to induce the formation of CXCR4-positive endothelial strands, which are subsequently attracted into the Cxcl12-positive aortic wall to connect the aortic lumen.

Narematsu|Mayu|M| Kamimura|Tatsuya|T| Yamagishi|Toshiyuki|T| Nakajima|Yuji|Y|


Factors predicting Registered Nurses' intentions to leave their organization and profession: A job demands-resources framework.

Abstract:
AIMS
To develop a comprehensive model of nursing turnover intention by examining the effects of job demands, job resources, personal demands and personal resources on burnout and work engagement and subsequently on the intention to leave the organization and profession.

BACKGROUND
The ageing population and a growing prevalence of multimorbidity are placing increasing strain on an ageing nursing workforce. Solutions that address the anticipated nursing shortage should focus on reducing burnout and enhancing the engagement of Registered Nurses (RNs) to improve retention.

DESIGN
A cross-sectional survey design.

METHOD
Data were collected in 2014-2015 via an e-survey from 2,876 RNs working in New Zealand. Data were analysed with structural equation modelling.

RESULTS
Higher engagement results in lower intention to leave the organization and profession. Burnout has significant effects on intentions to leave through lower engagement. While most of the demands and resources' variables (except professional development) have effects on intentions to leave, greater workload and greater work-life interference result in higher burnout and are the strongest predictors of intentions to leave. Greater emotional demands (challenges) and greater self-efficacy also have strong effects in lowering intentions to leave through higher engagement.

CONCLUSIONS
Employee burnout and work engagement play an important role in transmitting the impacts of job demands, job resources, personal demands and personal resources into RN intention to leave the organization and profession. Work-life interference and high workloads are major threats to nursing retention while challenge demands and higher levels of self-efficacy support better retention.

nursing turnover
work engagement
employee burnout
nurse retention
job demands-resources model


Functional Analysis of Recombinant Channels in Host Cells Using a Fast Agonist Application System.

Abstract: A reduced recombinant system provides a unique opportunity to study the biophysical properties of NMDAR channels with known subunit compositions, by using a point mutation approach to analyze the structural determinants of receptor function (Wollmuth and Sobolevsky, Trends Neurosci 27:321-328, 2004). However, in addition to the well-developed repertoire of molecular biological techniques, these types of studies also require electrophysiological methods that allow a wide range of receptor activation protocols that can adequately assess desensitization, inactivation, ion permeability, and other properties of the channels. Currently, one of the most well-developed techniques suitable for addressing these issues is use of the fast agonist application system for rapid activation of ligand gated ion-channels (Colquhoun et al., J Physiol 458:261-287, 1992; Jonas and Sakmann, J Physiol 455:143-171, 1992).

Fast agonist application
Calcium permeability
Kinetics
Magnesium block
Recombinant NMDA Receptors


Rapid response to secukinumab in a 5-year-old with deficiency of the interleukin-36 receptor antagonist (DITRA) with severe scalp and nail involvement.

Abstract: Deficiency of the interleukin-36 receptor antagonist (DITRA) is an autosomal recessive disease caused by mutations of the IL36RN gene. DITRA is characterized by acute generalized pustular psoriasis (GPP), fever, systemic inflammation, and leukocytosis. We report the case of a 5-year-old girl with severe scalp and nail involvement with a rapid response to secukinumab.

Deficiency of interleukin-36 receptor antagonist


Delay prior to expedited carotid endarterectomy: a prospective audit of practice.

Abstract:
OBJECTIVES
To identify reasons for delay before carotid endarterectomy (CEA) in a reconfigured "fast-track" system where patients were admitted from the TIA (transient ischaemic attack) Clinic for urgent CEA.

METHODS
Prospective audit in 89 recently symptomatic patients.

RESULTS
Ten patients (11%) suffered recurrent symptoms between admission and surgery. Two strokes were sufficiently severe that CEA was cancelled. The median delay from index symptom to CEA was 8 days. 74/87 (85%) underwent CEA <14 days from the index symptom; 39/87 (45%) within 7 days. Forty-five (51%) were ready for CEA <24 hours of admission; 74 (83%) <72 hours. The most common reasons for delay to CEA were logistical, especially a failure to plan for access to weekend operating. Two-thirds of the Tuesday/Friday theatre lists that were reserved for urgent CEAs were actually used for CEA; 27 (33%) were not used for CEA but were utilized for another vascular procedure, and five (4%) were cancelled the day before and went unused.

CONCLUSIONS
The vast majority of patients (85%) underwent CEA <14 days from the index symptom, but 11% still suffered recurrent symptoms prior to surgery. Transferring patients directly from the TIA Clinic reduced overall delays, but Vascular Units adopting such an approach might then be vulnerable to criticisms regarding prolonged lengths of pre-operative in-patient stay while patients were worked up for theatre. Protected theatre lists both optimized (and delayed) access to CEA, but the most important cause of delay was that we had not planned for weekend operating using specialist anaesthetic and theatre staff.

D010043:Outcome and Process Assessment, Health Care

D010561:Personnel Staffing and Scheduling

Carotid endarterectomy
TIA
Stroke
Rapid treatment


An experimental study to investigate typical temperature conditions in fuel tanks of European vehicles.

Abstract: Vehicular evaporative emissions have been recognized as an important source of volatile organic compounds to the environment and are of high environmental concern since these compounds have been associated to the formation of surface ozone and secondary organic aerosols. Evaporative emissions occur during any vehicle operation. In Europe, a revised legislative test procedure has been recently introduced to better control evaporative emissions during parking. However, emissions related to normal driving conditions-the so-called running losses-have received less attention compared with the other categories. The current study aims at giving some insights to the prevailing temperature conditions in fuel tanks of typical European vehicles during normal driving operation. The effects of ambient air temperature, trip duration, vehicle speed, and fuel tank level on the temperature reached by the fuel inside the tank under different real-world operating conditions were studied. Tank temperature can exceed 40 °C depending on ambient and driving conditions. Ambient temperature was found to be the most important parameter affecting the tank temperature. Trip duration and driving pattern may also have an influence on the tank temperature particularly when long trips combined with high vehicle speed are examined. Additionally, the difference between tank and ambient temperature was examined during the individual trips and was found to vary between 1 and 10 °C depending on the testing conditions. The most important parameters affecting the delta temperature were found to be the trip duration and the maximum vehicle speed. Finally, the purging strategy of two of the test vehicles was monitored, and the parameters affecting the purging flow rate were investigated. No strong correlation between the canister flow rate with ambient temperature, vehicle speed, or fuel level was observed in either of the tested vehicles. Substantially different canister flow rate levels between the two vehicles point to different purging strategies.

Evaporative emissions
Purging flow rate
Fuel tank temperature
Running losses


Paternal physical exercise demethylates the hippocampal DNA of male pups without modifying the cognitive and physical development.

Abstract: Maternal exercise is known to have beneficial effects in progeny development, but the influence of paternal exercise on the offspring still unclear. Since spermatogenesis is a continuous process, the father's life experiences can reprogram epigenetic content of the sperm and somehow interfere on offspring phenotype. This study was designed to evaluate the effects of paternal physical exercise on cognitive and physical development and on hippocampal DNA methylation levels of the offspring. Adult male Wistar rats were divided into two groups: sedentary and exercised. The exercise protocol occurred before mating and consisted of treadmill running, 5 consecutive days/week for 8 weeks (20 min/day). The mothers were not trained. The following developmental parameters were examined in male offspring: body growth, physical and cognitive performance, weights of adrenal glands, gonadal fat and hindlimb muscles, BDNF expression and global DNA methylation at the hippocampus. The progeny of trained and sedentary fathers did not differ in relation to physical parameters and performance, spatial memory and BDNF expression. However, paternal exercise promoted a decrease in offspring´s relative gonadal fat weight and a lower percentage of global hippocampal DNA methylation compared to offspring of sedentary fathers. These results pointed to interference of male physical activity at the time of conception on adiposity and hippocampal epigenetic reprogramming of male offspring. The data reinforces that exercise does not harm the descendant's development and emphasize the benefits to include the practice of physical exercise in a healthier lifestyle of the parents. Nevertheless, future studies are necessary and should investigate further the long-effects of epigenetic mechanisms in order to elucidate the father's contribution in fetal programming.

Mega|Filipe|F|
de Meireles|André Luís Ferreira|ALF|
Piazza|Francele Valente|FV|
Spindler|Christiano|C|
Segabinazi|Ethiane|E|
Dos Santos Salvalaggio|Gabriela|G|
Achaval|Matilde|M|
Marcuzzo|Simone|S|

Paternal
Epigenetics
Memory
Physical activity
Health
Preconception


Finite element analysis of the influence of the posterior tibial slope on mobile-bearing unicompartmental knee arthroplasty.

Abstract:
BACKGROUND
The most common modes of failure reported in unicompartmental knee arthroplasty (UKA) in its first two decades were wear on the polyethylene (PE) insert, component loosening, and progressive osteoarthritis in the other compartment. The rates of implant failure due to poor component positioning in patients who have undergone UKA have been reported. However, the effect of the posterior tibial slope on the biomechanical behavior of mobile-bearing Oxford medial UKA remains unknown.

METHODS
We applied finite element (FE) analysis to evaluate the effects of the posterior tibial slope in mobile-bearing UKA on the contact stresses in the superior and inferior surfaces of PE inserts and articular cartilage as well as the forces exerted on the anterior cruciate ligament (ACL). Seven FE models for posterior tibial slopes of -1°, 1°, 3°, 5°, 7°, 9°, and 11° were developed and analyzed under normal-level walking conditions based on this approach.

RESULTS
The maximum contact stresses on both the superior and inferior surfaces of the PE insert decreased as the posterior tibial slope increased. However, the maximum contact stress on the lateral articular cartilage and the force exerted on the ACL increased as the posterior tibial slope increased.

CONCLUSIONS
Increasing the tibial slope led to a reduction in the contact stress on the PE insert. However, a high contact stress on the other compartment and increased ACL force can cause progressive osteoarthritis in the other compartment and failure of the ACL.

Koh|Yong-Gon|YG|
Park|Kyoung-Mi|KM|
Kang|KiWon|K|
Kim|Paul Shinil|PS|
Lee|Young Han|YH|
Park|Kwan Kyu|KK|
Kang|Kyoung-Tak|KT|

D019645:Arthroplasty, Replacement, Knee
D001696:Biomechanical Phenomena
D003198:Computer Simulation
D020342:Finite Element Analysis
D000077107:Gait Analysis
D006801:Humans
D007719:Knee Joint
D007720:Knee Prosthesis
D008954:Models, Biological
D017755:Prosthesis Fitting
D013314:Stress, Mechanical

Mobile-type unicompartmental knee arthroplasty


Exercise intensities modulate cognitive function in spontaneously hypertensive rats through oxidative mediated synaptic plasticity in hippocampus.

Abstract: Oxidative damage in the brain may lead to cognitive impairments. There was considerable debate regarding the beneficial effects of physical exercise on cognitive functions because exercise protocols have varied widely across studies. We investigated whether different exercise intensities alter performance on cognitive tasks. The experiment was performed on spontaneously hypertensive rats (6 months at the established phase of hypertension) distributed into 3 groups: sedentary, low-intensity exercise and high-intensity exercise. Systolic blood pressure measurements confirmed hypertension in spontaneously hypertensive rats. In comparison to normotensive Wistar-Kyoto rats, sedentary spontaneously hypertensive rats had similar escape latencies and a similar preference for the correct quadrant in the probe trial. Compared to the sedentary group, the low-intensity exercise group had significantly better improvements in spatial memory assessed by Morris water maze. Low-intensity exercise was associated with attenuated reactive oxygen species, as measured by dihydroethidine fluorescence and nitrotyrosine staining in the dentate gyrus of the hippocampus. This was coupled with increased numbers of neurons and dendritic spines as well as a significant upregulation of synaptic density. In contrast, the beneficial effects of low-intensity exercise are abolished in high-intensity exercise as shown by increased free radical levels and an impairment in spatial memory. We concluded that exercise is an effective strategy to improve spatial memory in spontaneously hypertensive rats even at an established phase of hypertension. Low-intensity exercise exhibited better improvement on cognitive deficits than high-intensity exercise by attenuating free radical levels and improving downstream synaptic plasticity.

Lee|Cheng-Che|CC| Wu|De-Yu|DY| Chen|Syue-Yi|SY| Lin|Yi-Pin|YP| Lee|Tsung-Ming|TM|0000-0002-3487-8749

exercise
spontaneously hypertensive rats
synaptic plasticity
Morris water maze
reactive oxygen species


Omalizumab for severe allergic asthma in clinical trials and real-life studies: what we know and what we should address.

Abstract: Randomized clinical trials (RCTs) are the gold standard for the assessment of any therapeutic intervention. Real-life (R-L) studies are needed to verify the provided results beyond the experimental setting. This review aims at comparing RCTs and R-L studies on omalizumab in adult severe allergic asthma, in order to highlight the concurring results and the discordant/missing data. The results of a selective literature research, including "omalizumab, controlled studies, randomized trial, real-life studies" as key words are discussed. Though some similarities between RCTs and R-L studies strengthen omalizumab efficacy and safety outcomes, significant differences concerning study population features, follow-up duration, local adverse events and drop-out rate for treatment inefficacy emerge between the two study categories. Furthermore the comparative analysis between RCTs and R-L studies highlights the need for further research, concerning in particular long-term effects of omalizumab and its impact on asthma comorbidities.

Caminati|Marco|M|
Senna|Gianenrico|G|
Guerriero|Massimo|M|
Dama|Anna Rita|AR|
Chieco-Bianchi|Fulvia|F|
Stefanizzi|Giorgia|G|
Montagni|Marcello|M|
Ridolo|Erminia|E|

D016032:Randomized Controlled Trials as Topic

Omalizumab
Severe allergic asthma
Efficacy
Safety
Effectiveness
Comorbidities


A case of squamous cell carcinoma occurring on a scar of Buruli ulcer in Bouake, Ivory Coast.

Abstract: Buruli ulcer is infectious necrotizing panniculitis due to Mycobacterium ulcerans. Buruli ulcer is healed by leaving dystrophic, fibrous and retractile scars. On these scars can occur long-term squamous cell carcinoma. We report the first case of squamous cell carcinoma occurring on healing of Buruli ulcer. A 32-year-old woman with Buruli ulcer who has been cured for about 10 years is seen for ulcero-bulging knee swelling. The examination had revealed a large swelling of about ten centimeters in diameter, ulcero-budding, with an easily bleeding cauliflower appearance. The diagnosis of squamous cell carcinoma being retained without metastasis, resection of the tumor with scarring after one month without chemotherapy. There was no recurrence after six months of decline. The epidemiology of Buruli ulcer, responsible for scarring, explains the young age of our patient and the localization of carcinoma on the limb. The carcinomatous degeneration of scars, especially the scars of old burns, is constantly reported. The characteristics of Buruli ulcer scars, which bring them closer to burn scars, may explain why they are particularly affected by carcinomatous degeneration. One could also mention the chronicity of the wound in this infection, or wonder if the mycobacteria itself could play a role in carcinogenesis. This observation is, in our opinion, an alarm signal. We must fear an outbreak of cases in the years to come. To this end, preventive measures should already be taken by sensitizing the patients for an early consultation before any modification of their scars. After recovery, Buruli ulcer seems to present a risk of long-term evolution to a cancer. The scars of this condition, which could be considered precancerous lesions.

Diabaté|Almamy|A|
Gbandama|Koffi Kouamé Pacôme|KKP|
Kouabenan|Amon Anderson Stephen|AAS|
Gué|Irenée|I|
Vagamon|Bamba|B|
Aka|Boussou Romain|BR|

squamous cell carcinoma
scar
Buruli ulcer


Functionality During the First Five Years After the Diagnosis of Schizophrenia. A Cohort Study in a Colombian Population.

Abstract:
OBJECTIVE
There is a lack of studies on the natural history of the initial stages of schizophrenia in Colombia. This study aims to assess functionality in the first five years after the diagnosis of schizophrenia.

METHODS
Naturalistic longitudinal study of 50 patients with early schizophrenia evaluated between 2011 and 2014. Data about demographic background, symptoms, introspection, treatment and adverse reactions were collected in all patients every 3 months for at least 3-5 years. Functionality was measured with the Global Assessment of Functioning (GAF) and Personal and Social Performance (PSP) scales.

RESULTS
Patients were followed up for a mean of 174±62.5 weeks and showed moderate difficulties in overall functioning. This functioning was modified by polypharmacy, degree of introspection, changes in antipsychotic regimens, and the number of episodes, relapses and hospitalisations.

CONCLUSIONS
The results suggest that functional outcomes seem to be related to the use of polypharmacy, degree of insight, changes in antipsychotic regimens, and number of episodes, relapses and hospitalisations during the first years of schizophrenia.

Cano|Juan F|JF|
Ortegón-Valencia|Julián|J|
Pedraza-Perez|Carlos|C|
Córdoba-Rojas|Rodrigo|R|
Olarte-Armenta|Ana|A|
Vallejo-Silva|Alexie|A|
González-Díaz|Jairo|J|

Functioning Schizophrenia Colombia Introspection Antipsychotics Antipsicóticos Esquizofrenia Funcionalidad Introspección Recurrence Recurrencia


Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and corona radiata areas.

Abstract:
BACKGROUND
As a step towards clinical use of AAV-mediated gene therapy, brains of large animals are used to settle delivery parameters as most brain connections, and relative sizes in large animals and primates, are reasonably common. Prior to application in the clinic, approaches that have shown to be successful in rodent models are tested in larger animal species, such as dogs, non-human primates, and in this case, minipigs.

NEW METHOD
We evaluated alternate delivery routes to target the basal ganglia by injections into the more superficial corona radiata, and, deeper into the brain, the thalamus. Anatomically known connections can be used to predict the expression of the transgene following infusion of AAV5. For optimal control over delivery of the vector with regards to anatomical location in the brain and spread in the tissue, we have used magnetic resonance image-guided convection-enhanced diffusion delivery.

RESULTS
While the transduction of the cortex was observed, only partial transduction of the basal ganglia was achieved via the corona radiata. Thalamic administration, on the other hand, resulted in widespread transduction from the midbrain to the frontal cortex COMPARISON WITH EXISTING METHODS: Compared to other methods, such as delivery directly to the striatum, thalamic injection may provide an alternative when for instance, injection into the basal ganglia directly is not feasible.

CONCLUSIONS
The study results suggest that thalamic administration of AAV5 has significant potential for indications where the transduction of specific areas of the brain is required.

Pietersz|K L|KL|
Pouw|S|S|
Klima|J|J|
Ellederova|Z|Z|
Bohuslavova|B|B|
Chrastina|J|J|
Liscak|R|R|
Urgosik|D|D|
Starek|Z|Z|
Crha|M|M|
Lewis|O|O|
Wooley|M|M|
Johnson|D|D|
Brouwers|C C|CC|
Evers|M|M|
Motlik|J|J|
Martens|G J M|GJM|
Konstantinova|P S|PS|
Blits|B|B|


Molecular characterization of B. anthracis isolates from the anthrax outbreak among cattle in Karnataka, India.

Abstract:
BACKGROUND
Anthrax, a zoonotic disease is caused by the Gram positive bacterium Bacillus anthracis. During January 2013, an anthrax outbreak among cattle was reported in Gundlupet Taluk, neighboring Bandipur National Park and tiger reserve, India. The present study aims at the molecular identification and characterization of 12 B. anthracis isolates from this outbreak by 16S rRNA gene sequencing, screening B. anthracis specific prophages and chromosomal markers, protective antigen (pag) gene and canonical single nucleotide polymorphism (canSNP) analysis to subtype the isolates into one of the twelve globally identified clonal sub-lineages of B. anthracis.

RESULTS
These isolates had identical 16S rDNA nucleotide sequences with B. anthracis specific dual peaks showing mixed base pair R (G/A) at position 1139 with visual inspection while the automated basecaller software indicated a G. Alternatively the nucleotide A at 1146 position was indicative of the 16S rDNA type 7. Multiple sequence alignment with additional 170 (16S rDNA) sequences of B. cereus sensu lato group from GenBank database revealed 28 new 16S types in addition to eleven 16S types reported earlier. The twelve B. anthracis isolates were found to harbor the four B. anthracis specific prophages (lambdaBa01, lambdaBa02, lambdaBa03, and lambdaBa04) along with its four specific loci markers (dhp 61.183, dhp 77.002, dhp 73.019, and dhp 73.017). The pag gene sequencing identified the isolates as protective antigen (PA) genotype I with phenylalanine-proline-alanine phenotype (FPA phenotype). However, sequence clustering with additional 34 pag sequences from GenBank revealed two additional missense mutations at nucleotide positions 196 bp and 869 bp of the 2294 bp pag sequence among the 5 B. cereus strains with pXO1 like plasmids. The canSNP analysis showed that the isolates belong to A.Br.Aust94 sub-lineage that is distributed geographically in countries of Asia, Africa, Europe and Australia.

CONCLUSIONS
The analysis of 16S rDNA sequences reiterated the earlier findings that visual inspection of electropherogram for position 1139 having nucleotide R could be used for B. anthracis identification and not the consensus sequence from base caller. The canSNP results indicated that the anthrax outbreak among cattle was caused by B. anthracis of A.Br.Aust94 sub-lineage.

Roonie|Akanxa|A|
Majumder|Saugata|S|
Kingston|Joseph J|JJ|
Parida|Manmohan|M|

B. anthracis
Outbreak
Pag
canSNP
16S rDNA
Anthrax detection


Why chimpanzees carry dead infants: an empirical assessment of existing hypotheses.

Abstract: The study of non-human primate thanatology has expanded dramatically in recent years as scientists seek to understand the evolutionary roots of human death concepts and practices. However, observations of how conspecifics respond to dead individuals are rare and highly variable. Mothers of several species of primate have been reported to carry and continue to interact with dead infants. Such interactions have been proposed to be related to maternal condition, attachment, environmental conditions or reflect a lack of awareness that the infant has died. Here, we tested these hypotheses using a dataset of cases of infant corpse carrying by chimpanzees in Gombe National Park, Tanzania (n = 33), the largest dataset of such cases in chimpanzees. We found that mothers carried infant corpses at high rates, despite behavioural evidence that they recognize that death has occurred. Median duration of carriage was 1.83 days (interquartile range = 1.03-3.59). Using an information theoretic approach, we found no support for any of the leading hypotheses for duration of continued carriage. We interpret these data in the context of recent discussions regarding what non-human primates understand about death.

chimpanzees
non-human primates
thanatology
death responses


Development and efficacy of an online wheelchair maintenance training program for wheelchair personnel.

Abstract:
OBJECTIVES
To develop an online version of the wheelchair maintenance training program (WMTP) and compare learning outcomes from the in-person and online programs using the wheelchair maintenance training questionnaire (WMT-Q), administered before and after the intervention.

DESIGN
Iterative development of an online version of the WMTP and implementation.

SETTING
Online.

PARTICIPANTS
26 graduate and undergraduate students.

INTERVENTION
Web-based training. These results are compared with those from another study of the in-person WMTP with 10 participants.

MAIN OUTCOME MEASURES
Feedback survey and WMT-Q.

RESULTS
The training program was well-received and valued by all 26 participants. A significant increase in all scores after the online training program was found, based on pre-/post-intervention scores. In manual wheelchair open-ended questions, knowledge increased from 16% to 21%, p < .05; in power wheelchair open-ended questions, from 9% to 31%, p < .05; in multiple-choice questions related to knowledge, from 27% to 59%, p < .05; confidence increased from 8% to 80%, p < .05; and capacity from 12% to 88%, p < .05. There was no statistical difference in WMT-Q scores between individuals who participated in the in-person and online programs.

CONCLUSION
This study indicates that there was a similar-increased knowledge for participants, indicating that web-based training may be a viable approach for delivering maintenance training.

education
knowledge translation
mobility
wheeled mobility aids


Intersphincteric resection for very low rectal cancer: clinical outcomes of open versus laparoscopic approach and multidimensional analysis of the learning curve for laparoscopic surgery.

Abstract:
BACKGROUND
Laparoscopic rectal cancer surgery is regarded as more complex because of its technical difficulties in pelvic exposure, dissection, and sphincter preservation. This study therefore aimed to investigate the feasibility of laparoscopic resection for low rectal cancer using intersphincteric resection (ISR) and to assess its short-term oncological outcomes. Further, we intended to analyze the learning curve for laparoscopic surgery and identify the factors influencing the learning curve.

METHODS
Patients with low rectal cancer who received open or laparoscopic ISR were retrospectively chart reviewed. The surgical and oncological outcomes were evaluated. Comparisons of operating time, estimated blood loss, surgical outcomes, and histopathologic status were analyzed. Also, operating time was used as a technical indicator for learning curve analysis.

RESULTS
The mean estimated blood loss was 265 mL (range, 100-800 mL) in the open group and 104 mL (range, 30-250 mL) in the laparoscopic group. There was a significant difference between these two groups (P < 0.001). Operative experience analysis showed that the mean operating time was 402.1 min (range, 210-570 min) in the first stage and 331.4 min (range, 210-450 min) in the second stage, and on pathologic examination the mean number of lymph nodes harvested was 11.1 (range, 5-21) in the first stage and 18.3 (range, 11-31) in the second stage, with statistical differences between these two stages (P = 0.034 and P = 0.004, respectively). Multifactorial analysis showed that operating time was associated with surgeons' experience (<18 or ≥18 cases) (odds ratio = 2.918, 95% CI 1.078-7.902). Protective stoma creation was also associated with surgeons' experience (odds ratio = 3.999, 95% CI 1.153-13.86).

CONCLUSIONS
Our data show that laparoscopic ISR for low rectal cancer is feasible and safe. Surgeons' experience improved operating time and postoperative complications.

Kuo|Li-Jen|LJ| Hung|Chin-Sheng|CS| Wang|Weu|W| Tam|Ka-Wai|KW| Lee|Hung-Chia|HC| Liang|Hung-Hua|HH| Chang|Yu-Jia|YJ| Huang|Ming-Te|MT| Wei|Po-Li|PL|

Intersphincteric resection
Rectal cancer
Learning curve
Laparoscopic surgery
Chemoradiation


White matter abnormalities in long-term anabolic-androgenic steroid users: A pilot study.

Abstract: Recent studies of long-term anabolic-androgenic steroid (AAS) users reported amygdala structural and functional connectivity abnormalities. We assessed white matter microstructure in the inferior-fronto-occipital fasciculus (IFOF), a major associative bundle of the amygdala network. Diffusion weighted images acquired from 9 male long-term AAS users and 8 matched controls aged 36-51 years old were processed using a standardized pipeline (Tract-Based Spatial Statistics). Group differences were examined using linear regression with adjustment for age and current testosterone level. Compared to nonusers, AAS users exhibited significantly higher fractional anisotropy (FA) in the IFOF. Users showed markedly greater FA than nonusers on the left IFOF but only a modest, nonsignificant difference on the right IFOF. Moreover, FA was positively associated with lifetime cumulative AAS dose. Our results suggest that long-term AAS use alters IFOF white matter organization and integrity, which in turn might affect amygdala-related processes such as reward system function. Accordingly, further studies are needed to replicate findings in larger subject groups to determine the functional significance of the FA abnormality.

Seitz|Johanna|J|
Lyall|Amanda E|AE|
Kanayama|Gen|G|
Makris|Nikos|N|
Hudson|James I|JI|
Kubicki|Marek|M|
Pope|Harrison G|HG|
Kaufman|Marc J|MJ|

D038524:Diffusion Magnetic Resonance Imaging


HLA-A*24:07 as a potential biomarker for carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Filipino patients.

Abstract: Aim: A case-control study was conducted in Filipino patients to determine the association between HLA alleles and carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Materials & methods: A retrospective review of medical records and data collection were performed. A total of 10 carbamazepine-induced SJS/TEN cases and 40 tolerant controls were recruited. Genomic DNA extracted from saliva samples was genotyped. Statistical analysis was done. Results: The HLA-B75 serotype (p = 0.003; odds ratio [OR] = 13.8; 95% CI = 2.5-76.8), HLA-B*15:21 (p = 0.041; OR = 4.7; 95% CI = 1.1-20.8) and HLA-A*24:07 (p = 0.032; OR = 6; 95% CI = 1.2-30.7) were significantly associated with carbamazepine-induced SJS/TEN. Conclusion: The HLA-B75 serotype, HLA-B*15:21 or HLA-A*24:07 may be used for pharmacogenetic screening prior to prescribing carbamazepine in Filipinos.

HLA-A*24:07
toxic epidermal necrolysis
Filipino
HLA-B75 serotype
HLA-B*15:21
carbamazepine
Stevens–Johnson syndrome
antiepileptic agent
human leukocyte antigen
severe cutaneous adverse drug reactions


Evaluation of COVID-19 vaccine acceptance of healthcare providers in a tertiary Pediatric hospital.

Abstract: Objective: The aim of this study was to reveal the perceptions of healthcare providers who work in a tertiary children's hospital about domestic and foreign COVID-19 vaccines to determine the frequency of hesitancy toward COVID-19 vaccination prior to its availability in Turkey and to elucidate the reasons for its rejection and distrust.Methods: A questionnaire about COVID-19 vaccination was conducted with 343 healthcare providers, including pediatricians, pediatric nurses, and auxiliary health staff. The questionnaire was conducted online. In the survey, participants were asked about sociodemographic characteristics and opinions on domestic and foreign COVID-19 vaccines, and reasons for vaccine refusal.Results: Women were more likely to be reluctant to get a domestic (p < .001) or foreign (p < .001) COVID-19 vaccine than men. There was a significant relationship between age and vaccine acceptance (p = .01). The younger the age of the healthcare provider, the higher the rate of vaccine hesitancy (r = - 0.25). Years of professional experience were correlated with vaccine acceptance (r = 0,19, p < .05), but vaccine rejection and indecision did not change (p > .05). The factors predicting vaccine acceptance were status as a doctor, more than 10 years of professional experience, and male gender.Conclusion: More than half of the healthcare providers were willing to have a COVID-19 vaccine once available. Indecision rates were found to be high, although rejection rates were not. Status as a doctor, more than 10 years of professional experience, and male gender were factors associated with vaccination intention.

D010342:Patient Acceptance of Health Care

COVID-19
vaccine acceptance
healthcare providers
pediatricians


Sport Courage, Worry and Fear in Relation to Success of Alpine Ski Learning.

Abstract: (1) Background: Individuals' psychological traits can influence not just success in sport but also the ability to learn new motor skills. We investigated whether sport courage, worry and fear differ between alpine ski-naive and basic level skiers and how they affect ski learning. (2): A total of 337 students (249 ski-naive and 88 basic level) participated in research consisting of a four-part questionnaire and structured skiing program. (3) Results: For beginners, lower fear (r = -0.30, p < 0.01) and higher Self-efficiency (r = 0.28, p < 0.05) and mastery (r = 0.20, p < 0.01) were associated with better performance; reducing fear and increasing self-efficiency and worry increased performance. Experienced skiers were better in determination, mastery, and self-efficiency (all p < 0.05). In case of lower score in worry (r = -0.28, p < 0.01) and higher in self-efficiency (r = 0.22, p < 0.05) performance was better. Males scored higher in sport courage scale-31 (all p < 0.05). In particular, self-efficiency was associated with better (r = 0.39, p < 0.01), and higher fear with poorer performance (r = -0.33, p < 0.01). Moreover, self-efficiency was a predictor of ski success (p < 0.001). On the other hand, females like ski beginners scored higher in fear (p < 0.001). In females, determination, mastery and self-efficiency had a positive correlation with skiing (r = 0.21, p < 0.05, r = 0.28, p < 0.01, and r = 0.33, p < 0.01, respectively), while association between Fear and skiing (r = -0.46, p < 0.01) was negative, and fear (p < 0.001) was inversely related to success. (4): Conclusions: Psychological factors and gender differences need to be considered during learning phases of alpine skiing. There is a positive association between self-efficiency and performance of male ski beginners, and negative association between fear and achieved results in basic alpine ski school in case of female ski beginners.

Cigrovski|Vjekoslav|V| Radman|Ivan|I|0000-0002-5358-3591 Konter|Erkut|E| Očić|Mateja|M| Ružić|Lana|L|

sport courage
worry
fear
self-efficiency
skiing performance


Impact of GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala polymorphisms on Bofutsushosan response in obese subjects: a randomized, double-blind, placebo-controlled trial.

Abstract: Obesity is known to be influenced by a number of genes, including the β3 subunit of G protein (GNB3), β3-adrenergic receptor (ADRB3), uncoupling protein 2 (UCP2), and peroxisome proliferator activated receptor gamma (PPARγ). The single nucleotide polymorphisms (SNPs) of the above genes, such as GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala, are associated with obesity and body mass index. The present study evaluates the impact of Bofutsushosan, a traditional Eastern Asian herbal medicine with known anti-obesity properties, on obese subjects according to the presence of the above-mentioned SNPs. Upon randomization, the volunteers were allocated to receive Bofutsushosan (n=55) or placebo (n=56) treatments for 8 weeks. Following the treatment schedule, significant reductions in total cholesterol and significant improvement in the Korean version of obesity-related quality of life scale were seen in the Bofutsushosan-treated group, but not in placebo. Bofutsushosan exerted significant anti-obesity effects on a number of parameters in the carriers of the GNB3-825T allele, but only on waist circumference in the GNB3-C/C homozygote. Significant anti-obesity impact of Bofutsushosan was also seen on a number of obesity-indices in both ADRB3-Arg64 carriers and ADRB3-Trp64 homozygotes, as well as in UCP2-D/D carriers, but not in UCP2-D/I+I/I variants. The effect of Bofutsushosan was more pronounced in PPARγ-Pro/Pro genotype compared to PPARγ-Pro/Ala variants. Thus, the results revealed differential responses of the subjects to the anti-obesity effects of Bofutsushosan treatment according to the polymorphism of the vital obesity-related genes. Our study provides new insight into individualized clinical applications of Bofutsushosan for obesity.

Park|Junghyun|J| Bose|Shambhunath|S| Hong|Sun-Woo|SW| Lee|Dong-Ki|DK| Yoo|Jae-Wook|JW| Lim|Chi-Yeon|CY| Lee|Myeongjong|M| Kim|Hojun|H|

Bofutsushosan
obesity
single nucleotide polymorphism
clinical trial


Mechanisms of Neurological Dysfunction in GOSR2 Progressive Myoclonus Epilepsy, a Golgi SNAREopathy.

Abstract: Successive fusion events between transport vesicles and their target membranes mediate trafficking of secreted, membrane- and organelle-localised proteins. During the initial steps of this process, termed the secretory pathway, COPII vesicles bud from the endoplasmic reticulum (ER) and fuse with the cis-Golgi membrane, thus depositing their cargo. This fusion step is driven by a quartet of SNARE proteins that includes the cis-Golgi t-SNARE Membrin, encoded by the GOSR2 gene. Mis-sense mutations in GOSR2 result in Progressive Myoclonus Epilepsy (PME), a severe neurological disorder characterised by ataxia, myoclonus and seizures in the absence of significant cognitive impairment. However, given the ubiquitous and essential function of ER-to-Golgi transport, why GOSR2 mutations cause neurological dysfunction and not lethality or a broader range of developmental defects has remained an enigma. Here we highlight new work that has shed light on this issue and incorporate insights into canonical and non-canonical secretory trafficking pathways in neurons to speculate as to the cellular and molecular mechanisms underlying GOSR2 PME. This article is part of a Special Issue entitled: SNARE proteins: a long journey of science in brain physiology and pathology: from molecular.

Jepson|James E C|JEC|
Praschberger|Roman|R|
Krishnakumar|Shyam S|SS|

GOSR2
progressive myoclonus epilepsy
Golgi
secretory pathway
Membrin


Understanding Normal and Malignant Human Hematopoiesis Using Next-Generation Humanized Mice.

Abstract: Rodent models for human diseases contribute significantly to understanding human physiology and pathophysiology. However, given the accelerating pace of drug development, there is a crucial need for in vivo preclinical models of human biology and pathology. The humanized mouse is one tool to bridge the gap between traditional animal models and the clinic. The development of immunodeficient mouse strains with high-level engraftment of normal and diseased human immune/hematopoietic cells has made in vivo functional characterization possible. As a patient-derived xenograft (PDX) model, humanized mice functionally correlate putative mechanisms with in vivo behavior and help to reveal pathogenic mechanisms. Combined with single-cell genomics, humanized mice can facilitate functional precision medicine such as risk stratification and individually optimized therapeutic approaches.

Saito|Yoriko|Y|
Shultz|Leonard D|LD|
Ishikawa|Fumihiko|F|

human hematopoiesis
humanized mouse
human immunity
xenograft
leukemia


Effect of a Novel, Energy-Dense, Low-Volume Nutritional Food in the Treatment of Superior Mesenteric Artery Syndrome.

Abstract: Superior mesenteric artery syndrome (SMAS) is an intermittent or persistent passage obstruction that occurs in the third portion of the duodenum between the aorta and the superior mesenteric artery. After symptoms stabilize, the nutritional intake is started by ingesting a small amount. Recently, an energy-dense, low-volume nutritional food, Terumeal uplead® (Terumo Corporation, Tokyo, Japan) with an energy density of 4.0 kcal/mL, was launched. We report a case of a postoperative SMAS patient who was successfully treated using Terumeal uplead® through gastrostomy. An 83-year-old man who developed adhesive intestinal obstruction underwent right hemicolectomy, lysis of adhesion, and partial small bowel resection. Gastric distension persisted after surgery; thus, gastrostomy was performed for decompression and enteral nutrition on the 21st postoperative day, and enteral feeding was started on the 23rd postoperative day. However, fluoroscopy showed obstruction in the third portion of the duodenum, which was considered to be SMAS. To reduce the administration volume, enteral nutrition was replaced with Terumeal uplead® from the 28th postoperative day (intermittent administration thrice a day, 300 mL, 1,200 kcal per day). From the 34th postoperative day, the gastrostomy tube was clamped for two hours after administration, and no drainage was observed. Oral intake was resumed from the 36th postoperative day, and it was used in combination with enteral nutrition. Three months later, the patient was discharged home and continued oral ingestion with occasional decompression from the gastrostomy tube. Thus, Terumeal uplead® may be useful during the conservative treatment of SMAS by initiation with small amounts.

superior mesenteric artery syndrome
enteral nutrition
energy intake
oral nutritional supplements
tube feeding


Establishment versus population growth in spatio-temporally varying environments.

Abstract: We consider situations where repeated invasion attempts occur from a source population into a receptor population over extended periods of time. The receptor population contains two locations that provide different expected offspring numbers to invaders. There is demographic stochasticity in offspring numbers. In addition, temporal variation causes local invader fitnesses to vary. We show that effects of environmental autocorrelation on establishment success depend on spatial covariance of the receptor subpopulations. In situations with a low spatial covariance this effect is positive, whereas high spatial covariance and/or high migration probabilities between the subpopulations causes the effect to be negative. This result reconciles seemingly contradictory results from the literature concerning effects of temporal variation on population dynamics with demographic stochasticity. We study an example in the context of genetic introgression, where invasions of cultivar plant genes occur through pollen flow from a source population into wild-type receptor populations, but our results have implications in a wider range of contexts, such as the spread of exotic species, metapopulation dynamics and epidemics.

D011157:Population Dynamics
D011158:Population Growth

repeated invasions
environmental autocorrelation
introgression
inhomogeneous branching process
persistence
spatial structure


Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice.

Abstract: A new type of coronavirus has been identified as the causative agent underlying Middle East Respiratory Syndrome (MERS). The MERS coronavirus (MERS-CoV) has spread in the Middle East, but cases originating in the Middle East have also occurred in the European Union and the USA. Eight hundred and thirty-seven cases of MERS-CoV infection have been confirmed to date, including 291 deaths. MERS-CoV has infected dromedary camel populations in the Middle East at high rates, representing an immediate source of human infection. The MERS-CoV spike (S) protein, a characteristic structural component of the viral envelope, is considered as a key target of vaccines against coronavirus infection. In an initial attempt to develop a MERS-CoV vaccine to ultimately target dromedary camels, we constructed two recombinant adenoviral vectors encoding the full-length MERS-CoV S protein (Ad5.MERS-S) and the S1 extracellular domain of S protein (Ad5.MERS-S1). BALB/c mice were immunized with both candidate vaccines intramuscularly and boosted three weeks later intranasally. All the vaccinated animals had antibody responses against spike protein, which neutralized MERS-CoV in vitro. These results show that an adenoviral-based vaccine can induce MERS-CoV-specific immune responses in mice and hold promise for the development of a preventive vaccine that targets the animal reservoir, which might be an effective measure to eliminate transmission of MERS-CoV to humans.

Kim|Eun|E|
Okada|Kaori|K|
Kenniston|Tom|T|
Raj|V Stalin|VS|
AlHajri|Mohd M|MM|
Farag|Elmoubasher A B A|EA|
AlHajri|Farhoud|F|
Osterhaus|Albert D M E|AD|
Haagmans|Bart L|BL|
Gambotto|Andrea|A|

D065207:Middle East Respiratory Syndrome Coronavirus

MERS-CoV S
Adenoviral vaccines
Codon-optimized


Oversensing of the wearable cardioverter defibrillator during bipolar ventricular stimulation.

Abstract: The wearable cardioverter defibrillator (WCD) is a temporary treatment option for patients with potentially reversible risk of sudden cardiac death. This case demonstrates a pitfall during WCD usage in a pacemaker-dependent patient as well as a possible solution allowing continuation of WCD therapy. Bipolar stimulation may lead to double counting of the WCD detection algorithm resulting in false alarm or inappropriate therapy.

D016757:Death, Sudden, Cardiac
D017147:Defibrillators, Implantable
D004554:Electric Countershock
D006801:Humans
D008297:Male
D008875:Middle Aged
D000076251:Wearable Electronic Devices

False alarm
Misdetection
Myocarditis
Pacing
Telemedicine


"You Have Reached Your Destination": A Single Trial EEG Classification Study.

Abstract: Studies have established that it is possible to differentiate between the brain's responses to observing correct and incorrect movements in navigation tasks. Furthermore, these classifications can be used as feedback for a learning-based BCI, to allow real or virtual robots to find quasi-optimal routes to a target. However, when navigating it is important not only to know we are moving in the right direction toward a target, but also to know when we have reached it. We asked participants to observe a virtual robot performing a 1-dimensional navigation task. We recorded EEG and then performed neurophysiological analysis on the responses to two classes of correct movements: those that moved closer to the target but did not reach it, and those that did reach the target. Further, we used a stepwise linear classifier on time-domain features to differentiate the classes on a single-trial basis. A second data set was also used to further test this single-trial classification. We found that the amplitude of the P300 was significantly greater in cases where the movement reached the target. Interestingly, we were able to classify the EEG signals evoked when observing the two classes of correct movements against each other with mean overall accuracy of 66.5 and 68.0% for the two data sets, with greater than chance levels of accuracy achieved for all participants. As a proof of concept, we have shown that it is possible to classify the EEG responses in observing these different correct movements against each other using single-trial EEG. This could be used as part of a learning-based BCI and opens a new door toward a more autonomous BCI navigation system.

EEG
classification
navigation
BCI
neurophysiology
P300
human machine interaction
target recognition


Designer Benzodiazepines: Another Class of New Psychoactive Substances.

Abstract: Benzodiazepines have been introduced as medical drugs in the 1960s. They replaced the more toxic barbiturates, which were commonly used for treatment of anxiety or sleep disorders at the time. However, benzodiazepines show a high potential of misuse and dependence. Although being of great value as medicines, dependence to these drugs is a concern worldwide, in part due to overprescription and easy availability. Therefore, the phenomenon of benzodiazepines sold via Internet shops without restrictions at low prices is alarming and poses a serious threat to public health. Most of these compounds (with the exception of, e.g., phenazepam and etizolam) have never been licensed as medical drugs in any part of the world and are structurally derived from medically used benzodiazepines. Strategies of clandestine producers to generate new compounds include typical structural variations of medically used 1,4-benzodiazepines based on structure-activity relationships as well as synthesis of active metabolites and triazolo analogs of these compounds. As they were obviously designed to circumvent national narcotics laws or international control, they can be referred to as "designer benzodiazepines." The majority of these compounds, such as diclazepam, clonazolam, and nitrazolam, have been described in scientific or patent literature. However, little is known about their pharmacological properties and specific risks related to their use. This chapter describes the phenomenon of designer benzodiazepines and summarizes the available data on pharmacokinetics and pharmacodynamics as well as analytical approaches for their detection.

Designer benzodiazepines
Pharmacokinetics
Analysis
Metabolism
NPS
Toxicology


Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach.

Abstract: Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers.

Shin|Miji|M|
Mun|Sora|S|
Park|Sang Hyun|SH|
Lee|Jiyeong|J|
Kang|Hee-Gyoo|HG|0000-0001-8690-2483

biomarkers
pathogenesis
acute coronary syndrome
proteomics


The safety and efficacy of midlines compared to peripherally inserted central catheters for adult cystic fibrosis patients: a retrospective, observational study.

Abstract:
BACKGROUND
Intravenous antibiotics are the cornerstone of treatment for patients with cystic fibrosis (CF). Midlines are a type of vascular access device (VAD) used exclusively in one treatment facility within Australia, most other centres use peripherally inserted central catheters (PICCs).

OBJECTIVE
To ascertain the safety and efficacy of midlines for CF patients receiving intravenous antibiotics.

DESIGN
Retrospective observational.

SETTING
A large, major metropolitan teaching hospital in Adelaide, South Australia.

PARTICIPANTS
Adult patients with a diagnosis of CF, who had a PICC or midline inserted for the commencement of antibiotic therapy during the period 2004-2010 to treat a respiratory exacerbation.

METHODS
Medical records and hospital reports were used to record rates of adverse events and unexpected removal of VADs. The primary outcome was a composite measure of adverse events (catheter-related blood stream infection, deep vein thrombosis, occlusion, pain, infiltration, bleeding, phlebitis, catheter leakage and dislodgement) and whether the VAD was removed unexpectedly.

RESULTS
There were 231 midlines and 97 PICCs inserted into 64 patients (39 male and 25 female; age range 18-47 years old). Presented as per 1000 VAD days, patients with PICCs and midlines had similar rates of adverse events (14 and 11 adverse events per 1000 VAD days, respectively). Unexpected removal was higher for patients with midlines (6.90 per 1000 VAD days) than for PICCs (2.89 per 1000 VAD days). Incident rate ratios (IRRs) showed that patients with midlines and PICCs had similar rates of adverse events (IRR 1.18, P=0.617, CI 0.62-2.22) although the removal rate of patients with midlines was twice that of patients with PICCs (IRR 2.24, P=0.079, CI 0.91-5.56). As an absolute risk there were only 4.09 more cases of removal for patients with midlines per 1000 VAD days than those with PICCs.

CONCLUSIONS
Midlines may be an alternative to PICCs for adult CF patients although further research is required with a larger sample size to enable definitive conclusions.

Sharp|Rebecca|R| Esterman|Adrian|A| McCutcheon|Helen|H| Hearse|Neville|N| Cummings|Melita|M|

Midlines
Peripherally inserted central catheters
Cystic fibrosis
Observational
Catheterisation-adverse effects
Catheters vascular


Silver Foams with Hierarchical Porous Structures: From Manufacturing to Antibacterial Activity.

Abstract: The development of porous materials with hierarchical porous structures is currently of great interest. These materials exhibit properties representative of different pore scales and thus open up the possibility of being used in new applications. In this paper, a method for the preparation of silver foams with hierarchical porous structures is discussed. Here, the replication method, which is typically used to produce coarse-pore foams, is merged with dealloying, which is commonly used to manufacture small-pore foams. For this purpose, packed NaCl particles (hard template) were infiltrated with 75%Al-25%Ag alloy (whose so-called soft template is the Al-rich phase). Both the hard and soft templates were removed by water dissolution and dealloying with HCl or NaOH solutions, respectively. Extensive characterization of the resulting materials revealed pores ranging from a few nanometers to hundreds of micrometers. The materials were characterized by their antibacterial performance against Gram-positive and Gram-negative bacteria and showed significantly higher activity than both silver foams prepared by sintering pure Ag particles and silver nanofoams produced by chemical dealloying. The combinations of pores of different sizes and the resulting high internal specific surface area have a decisive influence on the antibacterial capacity of these new materials.

silver
foam
hierarchical porous structure
antibacterial
dealloying
silver−aluminum alloy


A close insight to factor VIII inhibitor in the congenital hemophilia A.

Abstract:
INTRODUCTION
Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists.

AREAS COVERED
A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

D020022:Genetic Predisposition to Disease

factor VIII inhibitor
Hemophilia A
inhibitor development
environmental risk factor
genetic risk factors


Enhancement of the apoptotic effects of Arctii Fructus extracts on cancer cells by the enzymatic bioconversion of lignans.

Abstract: The fruit of Arctium lappa L. (Arctii Fructus) is one of the most popularly used medicinal plant components in Asia. To enhance the functionality of Arctii Fructus extract, a bioconversion method was developed to produce arctigenin from arctiin. Treatment with β-glucosidase increased the arctigenin content by >5 fold in Arctii Fructus extracts. The bioconversion products enhanced the apoptosis of cancer cells. The cell viabilities of gefitinib-resistant lung cancer HCC827 (HCC827GR) cells and colon cancer cells (DLD1) were decreased by 40% and 35%, respectively. The bioconversion products also decreased anchorage-independent growth of cancer cells. In addition, the increase of apoptosis in cancer cells by bioconversion was confirmed by the flow cytometry analysis. These results indicated that arctigenin exerts anticancer effects on lung and colon cancer cells and that Arctii Fructus can potentially function as a chemopreventive agent. In addition, bioconverted Arctii Fructus extract displayed higher anticancer activity than the same levels of purified arctigenin, indicating the advantage of consuming Arctii Fructus itself as a food or medicinal material.

Arctii Fructus
cancer
bioconversion
arctigenin
apoptosis


Genetic analysis of Iranian family with hereditary cardiac arrhythmias by next generation sequencing.

Abstract:
BACKGROUND
Cardiac arrhythmias are responsible for several cases of syncope and sudden cardiac death annually worldwide. Due to overlapping clinical symptoms in some cardiac arrhythmias genetic studies would help to confirm the primary clinical diagnosis made on the basis of solely clinical findings. In addition clinical management of the patient, family screening and provide appropriate counseling and risk assessment for the family members are other advantages of genetic study.

MATERIALS AND METHODS
Totally nine patients from a family included in this study. The primary diagnosis on the basis of clinical findings was second-degree atrioventricular (AV) block for this family. Mutation in SCN5A gene is frequently reported for second-degree AV block and hence the gene was analyzed using whole gene sequencing but no mutation was detected. Subsequently, the samples were subjected to customized Ampliseq 77 gene panel using next generation sequencing to detect the underlying molecular defects.

RESULTS
We found c. 5570T>A missense mutation in ANK2 gene for this family. Based on the Online Mendelian Inheritance in Man, ANK2 gene and the mutation detected correspond to long QT syndrome type 4.

CONCLUSION
This mutation, although already known in other populations, but is reported for the first time in Iranian patients with cardiac arrhythmias. As the case with this family, genetic analysis of patients with cardiac arrhythmias would be helpful in reassessment of clinical diagnosis and therefore would help for patients' management and in some cases re-evaluation of ongoing treatment may be needed.

Asadi|Marzieh|M|
Foo|Roger|R|
Samienasab|Mohammad Reza|MR|
Salehi|Ahmad Reza|AR|
Kheirollahi|Majid|M|
Khanahmad|Hossein|H|
Salehi|Rasoul|R|

hereditary cardiac arrhythmias
next generation sequencing
Atrioventricular block
congenital long QT syndrome


Utility of oxcarbazepine in the treatment of childhood and adolescent psychiatric symptoms.

Abstract: The primary aims of this study were to determine if oxcarbazepine is a safely tolerated option for treatment of psychiatric symptoms in children and whether its use facilitates dose modification of other psychotropic medications. A retrospective chart review was completed using data extracted from the electronic medical record of a large outpatient child psychiatry clinic. A total of 507 of 740 children prescribed oxcarbazepine for psychiatric indications for 3 months or more had adequate data to assess clinical responses and medication outcomes. Most patients prescribed oxcarbazepine experienced clinically significant control of irritability/anger, mood stabilization, aggressive outbursts, impulsivity, or anxiety, with over 80% achieving at least maintenance symptom control. In all, 51% and 25% fully discontinued second- or third-generation antipsychotic or antidepressant medication, respectively, after starting oxcarbazepine; 8% discontinued oxcarbazepine for nonresponse, while 9% stopped oxcarbazepine because of emergent side effects. In patients fully discontinuing or reducing the second- or third-generation antipsychotic dose by 50% or more, improvements in body mass index were observed. Oxcarbazepine may prove to be an appropriate alternative to antipsychotic and antidepressant medications for treating psychiatric symptoms in children and adolescents. In particular, it may be a more metabolically neutral psychotropic medication.

Morrow|Kyle|K|
Young|Keith A|KA|
Spencer|Shawn|S|
Medina|Edgar Samuel|ES|
Marziale|Michaela A|MA|
Sanchez|Alejandro|A|
Bourgeois|James A|JA|

oxcarbazepine
antipsychotics
Anticonvulsants
child and adolescent psychiatry


Storage stability of commonly used haematological parameters at 33 °C: Electronic supplementary material available online for this article.

Abstract:
Introduction
This study aimed to investigate the analytical bias in haematological parameters induced by storage at 33 ºC.

Materials and methods
Blood from the diversion pouch of 20 blood donors were collected in K  EDTA vials and stored at 33 ºC. Readings from each vial were taken at 0, 4, 6, 12, 24, 48 and 72 hours after collection on the Sysmex XP-100 analyser (Sysmex Corporation, Kobe, Japan). The percent difference from the baseline readings were calculated and subjected to a Wilcoxon signed rank test at a Holm corrected significance level of 0.05. A median percent difference, which was statistically significant and greater than the maximum acceptable bias (taken from studies of biological variation), was taken as evidence of unacceptable shift. If the median shift was lesser than the maximum acceptable bias, two one-sided Wilcoxon signed rank tests for equivalence were used to determine whether the percent differences were significantly lesser than the maximum acceptable bias.

Results
Haemoglobin, red blood cell count, white blood cell count, mean corpuscular haemoglobin and lymphocyte count showed acceptable bias after storage for at least 24 hours at 33 ºC. Haematocrit, mean corpuscular volume, mean corpuscular haemoglobin concentration, platelet count and mean platelet volume showed unacceptable shift in less than 4 hours when stored at 33 ºC.

Conclusions
Since many haematological parameters show unacceptable bias within 4 hours of sample storage at 33 ºC, the recommended limit of time from collection to processing should be revised for areas where high environmental temperatures are common.

Jain|Ashish|A|
Jain|Sanchit|S|
Singh|Neha|N|
Aswal|Priyanka|P|
Pal|Shweta|S|
Meinia|Sushant Kumar|SK|
Chowdhury|Nilotpal|N|

D057205:Automation, Laboratory
D001800:Blood Specimen Collection
D004906:Erythrocyte Count
D004909:Erythrocyte Indices
D064368:Healthy Volunteers
D006400:Hematocrit
D006403:Hematologic Tests
D006454:Hemoglobins
D006358:Hot Temperature
D006801:Humans
D007958:Leukocyte Count
D063847:Mean Platelet Volume
D010976:Platelet Count

platelet count
erythrocyte indices
laboratory errors
pre-analytical error
sample stability


Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis.

Abstract:
BACKGROUND
In obesity, the excessive synthesis of aldosterone contributes to the development and progression of metabolic and cardiovascular dysfunctions. Obesity-induced hyperaldosteronism is independent of the known regulators of aldosterone secretion, but reliant on unidentified adipocyte-derived factors. We hypothesized that the adipokine leptin is a direct regulator of aldosterone synthase (CYP11B2) expression and aldosterone release and promotes cardiovascular dysfunction via aldosterone-dependent mechanisms.

METHODS AND RESULTS
Immunostaining of human adrenal cross-sections and adrenocortical cells revealed that adrenocortical cells coexpress CYP11B2 and leptin receptors. Measurements of adrenal CYP11B2 expression and plasma aldosterone levels showed that increases in endogenous (obesity) or exogenous (infusion) leptin dose-dependently raised CYP11B2 expression and aldosterone without elevating plasma angiotensin II, potassium or corticosterone. Neither angiotensin II receptors blockade nor α and β adrenergic receptors inhibition blunted leptin-induced aldosterone secretion. Identical results were obtained in cultured adrenocortical cells. Enhanced leptin signaling elevated CYP11B2 expression and plasma aldosterone, whereas deficiency in leptin or leptin receptors blunted obesity-induced increases in CYP11B2 and aldosterone, ruling out a role for obesity per se. Leptin increased intracellular calcium, elevated calmodulin and calmodulin-kinase II expression, whereas calcium chelation blunted leptin-mediated increases in CYP11B2, in adrenocortical cells. Mineralocorticoid receptor blockade blunted leptin-induced endothelial dysfunction and increases in cardiac fibrotic markers.

CONCLUSIONS
Leptin is a newly described regulator of aldosterone synthesis that acts directly on adrenal glomerulosa cells to increase CYP11B2 expression and enhance aldosterone production via calcium-dependent mechanisms. Furthermore, leptin-mediated aldosterone secretion contributes to cardiovascular disease by promoting endothelial dysfunction and the expression of profibrotic markers in the heart.

Huby|Anne-Cécile|AC|
Antonova|Galina|G|
Groenendyk|Jake|J|
Gomez-Sanchez|Celso E|CE|
Bollag|Wendy B|WB|
Filosa|Jessica A|JA|
Belin de Chantemèle|Eric J|EJ|

leptin
aldosterone
obesity
CYP11B2
heart
adrenal glands
endothelium


Hepeviridae: an expanding family of vertebrate viruses.

Abstract: The hepatitis E virus (HEV) was first identified in 1990, although hepatitis E-like diseases in humans have been recorded for a long time dating back to the 18th century. The HEV genotypes 1-4 have been subsequently detected in human hepatitis E cases with different geographical distribution and different modes of transmission. Genotypes 3 and 4 have been identified in parallel in pigs, wild boars and other animal species and their zoonotic potential has been confirmed. Until 2010, these genotypes along with avian HEV strains infecting chicken were the only known representatives of the family Hepeviridae. Thereafter, additional HEV-related viruses have been detected in wild boars, distinct HEV-like viruses were identified in rats, rabbit, ferret, mink, fox, bats and moose, and a distantly related agent was described from closely related salmonid fish. This review summarizes the characteristics of the so far known HEV-like viruses, their phylogenetic relationship, host association and proposed involvement in diseases. Based on the reviewed knowledge, a suggestion for a new taxonomic grouping scheme of the viruses within the family Hepeviridae is presented.

Johne|Reimar|R|
Dremsek|Paul|P|
Reetz|Jochen|J|
Heckel|Gerald|G|
Hess|Michael|M|
Ulrich|Rainer G|RG|

Hepeviridae
Hepatitis E virus
Cross-species transmission
Genome organisation
Reservoir