How nurses are preparing for the revalidation process.

Abstract: As the profession's new system of revalidation goes live, this article brings together the experiences of emergency nurses from revalidation pilot sites in England, Scotland, Wales and Northern Ireland. A total of 19 sites across the UK, including hospital trusts, tested the process between 2014 and 2015. This gave these trusts the opportunity to prepare their staff and help them to get revalidation ready ahead of the official roll-out. This article aims to help nurses working in emergency departments better understand the process and offers tips for dealing with process issues which are pertinent to them.

revalidation
pilot
patient feedback
portfolio


Independent and combined effects of environmental factors and miR-126, miR-143, and miR-145 on the risk of coronary heart disease.

Abstract:
Objective
To evaluate the effects of environmental factors and microRNAs (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease (CHD).

Methods
A frequency-matched case-control study (450 patients, 450 controls) was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, miR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction (PCR) in peripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation.

Results
Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD.

Conclusions
Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.

Lin|Da-Cen|DC| Lin|Jia-Bing|JB| Chen|Zhou|Z| Chen|Rong|R| Wan|Chun-Yu|CY| Lin|Shao-Wei|SW| Ruan|Qi-Shuang|QS| Li|Huang-Yuan|HY| Wu|Si-Ying|SY|


Pain in the Elderly.

Abstract: Pain management in the elderly has increasingly become problematic in the USA as the aged population grows. The proportion of the population over 65 continues to climb and may eclipse 20 % in the next decade. In order to effectively diagnosis and treat these patients, a proper history and physical exam remain essential; pain assessment scales such as the Verbal Descriptor Scales (VDS), the Numerical Rating Scales (NRS), and the Visual Analogue Scales (VAS) often but not always prove beneficial. The conditions most frequently afflicting this population include osteoarthritis, diabetic neuropathy, post-herpetic neuralgia, and lower back pain which include spondylosis and radiculopathies. While the normal aging process does not necessarily guarantee symptoms of chronic pain, elderly individuals are far more likely to develop these painful conditions than their younger counterparts. There are many effective treatment modalities available as potential therapeutic interventions for elderly patients, including but not limited to analgesics such as NSAIDs and opioids, as well as multiple interventional pain techniques. This review will discuss chronic pain in the elderly population, including epidemiology, diagnostic tools, the multitude of co-morbidities, and common treatment modalities currently available to physicians.

Jones|Mark R|MR|
Ehrhardt|Ken P|KP|
Ripoll|Juan G|JG|
Sharma|Bharat|B|
Padnos|Ira W|IW|
Kaye|Rachel J|RJ|
Kaye|Alan D|AD|

Pain
Elderly
Back pain
Chronic pain
NSAIDs
Opioids
Arthritis


Advanced oxidation protein products accelerate bone deterioration in aged rats.

Abstract: Advanced oxidation protein products (AOPPs) are novel markers of oxidation-mediated protein damage, and accumulation of AOPPs is involved in many pathophysiological conditions. Our previous studies demonstrated that the serum level of AOPPs negatively correlated with the age-related change in bone mineral density (BMD) in rats and that AOPPs inhibited rat osteoblast-like cell proliferation and differentiation in vitro. However, whether AOPPs are involved in senile osteoporosis is still largely unknown. The present study aimed to test the hypothesis that accumulation of AOPPs might accelerate bone deterioration in aged rats. Seventy 18-month-old male Sprague Dawley (SD) rats were randomized to intravenous injection of vehicle, native rat serum albumin (RSA), AOPPs-modified RSA (AOPPs-RSA) with or without oral administration of apocynin (a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor), or apocynin alone. After treatment for 8 weeks or 16 weeks, seven rats in each group were sacrificed. Bone and blood samples were harvested for BMD measurement, micro-computed tomographic (micro-CT) imaging, and biochemical analysis of circulating bone biomarkers. Compared to RSA- or vehicle-treated rats, AOPPs-RSA-treated animals displayed significantly decreased total vertebral BMD and deteriorated microstructure in both the tibias and the lumbar vertebral bodies, which were associated with down-regulated plasma bone-specific alkaline phosphatase concentration and up-regulated tartrate-resistant acid phosphatase 5b concentration. These AOPPs-induced perturbations in aged rats could be prevented by the oral administration of apocynin. However, no significant differences in BMD were detected in the femurs or the biomechanical parameters tested between the different treatment groups. These data suggest that accumulation of AOPPs accelerates bone deterioration in aged rats, likely via the activation of NADPH oxidase. This study provides new information toward understanding the pathogenic basis of senile osteoporosis and may provide targets for intervention.

Zeng|Ji-Huan|JH| Zhong|Zhao-Ming|ZM| Li|Xiao-Dan|XD| Wu|Qian|Q| Zheng|Shuai|S| Zhou|Jian|J| Ye|Wen-Bin|WB| Xie|Fang|F| Wu|Xiu-Hua|XH| Huang|Zhi-Ping|ZP| Chen|Jian-Ting|JT|

D062107:Advanced Oxidation Protein Products

Bone deterioration
Aged rats
AOPPs
Senile osteoporosis
Oxidative stress


Propensity score-based comparison of survival and radiation pneumonitis after definitive chemoradiation for esophageal cancer: Intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy.

Abstract:
PURPOSE
To compare survival outcomes and radiation pneumonitis (RP) between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in patients with esophageal cancer (EC) who underwent definitive chemoradiation therapy (CRT).

METHODS
Clinical characteristics and dose-volume histogram parameters were collected for 388 EC patients who received definitive CRT with either IMRT (n = 297) or 3DCRT (n = 91) from 2010 through 2017. Dosimetric parameters, survival end-points, and symptomatic RP (grade ≥2) were compared between groups. Propensity score matching (PSM) was performed to balance potential confounding factors. Univariate and multivariate logistic regression analyses were applied to identify predictors of RP.

RESULTS
Compared with 3DCRT, IMRT was significantly associated with better overall survival (OS; P = 0.001), progression-free survival (PFS; P = 0.008), and distant metastasis-free survival (P = 0.011), but not with locoregional failure-free survival (P = 0.721). Moreover, IMRT demonstrated a remarkably lower risk of RP than 3DCRT (5.4% vs 23.1%, P < 0.001). PSM analysis further confirmed the clinical benefit of IMRT. In the matched cohort, radiation modality was independently correlated with OS and PFS. On multivariate analysis, smoking history (odds ratio [OR]: 4.225, P = 0.002), primary tumor length (OR: 2.764, P = 0.049), radiation modality (OR: 10.760, P < 0.001), planning target volume (OR: 1.004, P < 0.001), and lung V20 (OR: 1.286, P = 0.002) were found to be significant predictors of RP.

CONCLUSIONS
Compared with 3DCRT, IMRT was associated with more favorable survival and a reduced risk of RP after definitive CRT, supporting the routine use of IMRT for EC.

Lan|Kaiqi|K| Zhu|Jinhan|J| Zhang|Jun|J| Zhou|Sha|S| Yang|Yadi|Y| Feng|Zizhen|Z| Zhang|Li|L| Wang|Shi|S| Xi|Mian|M|


Preoperative transcatheter arterial chemotherapy may suppress oxidative stress in hepatocellular carcinoma cells and reduce the risk of short-term relapse.

Abstract: In this study, we aim to investigate oxidative stress in hepatocellular carcinoma (HCC) tissues in patients receiving preoperative transcatheter arterial chemotherapy (TAC) and its association with prognosis. A total of 89 HCC patients enrolled in this study, 39 received preoperative TAC 1 week before surgery (pTAC group) and 50 did not (non-pTAC group). All patients underwent hepatectomy and postoperative TAC and were followed up to 400 weeks. Samples of liver tissue without HCC and hepatitis (n = 15) served as normal controls. Cellular levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), TP53, and p21waf1/cip1 were measured in both cancer and surrounding tissues using an immunohistochemistry assay. Taken together, our data suggested that preoperative TAC might postpone postoperative HCC relapse within 1 year via suppression of tumor cells by induction of high levels of oxidative stress.

Su|Hao|H|
Zhu|Guangzhi|G|
Djaja P|Ketut Indra|KI|
Lin|Yi|Y|
Gong|Yizhen|Y|
Liu|Xiaoguang|X|
Li|Jiaquan|J|
Liu|Zhiming|Z|
Qin|Xiao|X|
Li|Lequn|L|
Liu|Tangwei|T|
Lu|Zili|Z|
Wei|Minyi|M|
Yan|Lunan|L|
Winkler|Cheryl Ann|CA|
O'Brien|Stephen J|SJ|
Li|Jing|J|
Xiao|Kaiyin|K|
Peng|Tao|T|


COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials.

Abstract: Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations.

COVID-19
vaccine
safety
efficacy
herd immunity


HO-1 drives autophagy as a mechanism of resistance against HER2-targeted therapies.

Abstract:
PURPOSE
Targeted therapies have resulted in major advances in the treatment of HER2-positive breast cancers. Despite this, up to 70% of patients will develop resistance to treatment within 2 years and new strategies for targeting resistant disease are needed.

METHODS
To identify potential resistance mechanisms, we used the mouse MMTV-NIC-PTEN+/- spontaneous model of HER2-positive breast cancer and the pan-HER family kinase inhibitor sapatinib. Vehicle and sapatinib-treated tumors were evaluated by immunohistochemistry and proteomic analysis. In vitro studies were carried out to define the role of heme oxygenase 1 (HO-1) and autophagy in resistance to sapatinib and lapatinib, another pan-HER family kinase inhibitor.

RESULTS
Treatment of tumor-bearing MMTV-NIC-PTEN+/- mice with sapatinib resulted in delayed tumor progression and increased survival. However, tumors eventually progressed on treatment. Proteomic analysis identified proteins associated with cellular iron homeostasis as being upregulated in the sapatinib-treated tumors. This included HO-1 whose overexpression was confirmed by immunohistochemistry. Overexpression of HO-1 in HER2-expressing SKBR3 breast cancer cells resulted in reduced sensitivity to both pan-HER family kinase inhibitors sapatinib and lapatinib. This was associated with increased autophagy in the HO-1 over-expressing cells. Furthermore, increased autophagy was also seen in the sapatinib-treated tumors. Treatment with autophagy inhibitors was able to increase the sensitivity of the HO-1 over-expressing cells to both lapatinib and sapatinib.

CONCLUSION
Together these data indicate a role for HO-1-induced autophagy in resistance to pan-HER family kinase inhibitors.


Enterococcus faecium WEFA23 from infants lessens high-fat-diet-induced hyperlipidemia via cholesterol 7-alpha-hydroxylase gene by altering the composition of gut microbiota in rats.

Abstract: Enterococcus faecium WEFA23 is a potential probiotic strain from Chinese infants with the ability to decrease cholesterol levels. Aiming to explore the mechanism of E. faecium WEFA23 in lowering cholesterol in vivo, we examined the gene transcriptions related to cholesterol metabolism, the composition of bile acids in feces, the synthesis of trimethylamine N-oxide (TMAO) in liver, and the composition of the gut microbiota of rats. We found that E. faecium WEFA23 enhanced the synthesis of bile acids by promoting cholesterol excretion, upregulating the genes transcript level relevant to cholesterol decomposition and transportation, and downregulating the genes involved in cholesterol synthesis. In addition, E. faecium WEFA23 not only downregulated the transcript levels of farnesoid X receptor and fibroblast growth factor 15 as well as flavin-containing monooxygenase 3, but also decreased the TMAO production followed by increasing the CYP7A1 transcript level. Furthermore, when orally administered to rats for 35 d, E. faecium WEFA23 improved the gut microbiota diversity of rats fed a high-fat diet. Therein, the ratio of Bacteroidetes to Firmicutes and the abundance of Rikenellaceae increased, whereas the number of Veillonellaceae decreased. These results suggest that reduction of cholesterol level by E. faecium WEFA23 might be related to the changes in the gut microbiota. Our finding provides important information on lowering cholesterol by E. faecium and reveals that Enterococcus spp. might have the potential to decrease the TMAO level.

Huang|Fuqing|F| Zhang|Fen|F| Xu|Di|D| Zhang|Zhihong|Z| Xu|Feng|F| Tao|Xueying|X| Qiu|Liang|L| Wei|Hua|H|

cholesterol 7-alpha-hydroxylase
bile acid
trimethylamine N-oxide
intestinal microbiota


Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

Abstract: Altered synaptic transmission with excess glutamate release has been implicated in the loss of motoneurons occurring in amyotrophic lateral sclerosis (ALS). Hyperexcitability or hypoexcitability of motoneurons from mice carrying the ALS mutation SOD1(G93A) (mSOD1) has also been reported. Here we have investigated the excitability, the ion currents, and the kinetics of the exocytotic fusion pore in chromaffin cells from postnatal day 90 to postnatal day 130 mSOD1 mice, when motor deficits are already established. With respect to wild-type (WT), mSOD1 chromaffin cells had a decrease in the following parameters: 95% in spontaneous action potentials, 70% in nicotinic current for acetylcholine (ACh), 35% in Na(+) current, 40% in Ca(2+)-dependent K(+) current, and 53% in voltage-dependent K(+) current. Ca(2+) current was increased by 37%, but the ACh-evoked elevation of cytosolic Ca(2+) was unchanged. Single exocytotic spike events triggered by ACh had the following differences (mSOD1 vs. WT): 36% lower rise rate, 60% higher decay time, 51% higher half-width, 13% lower amplitude, and 61% higher quantal size. The expression of the α3-subtype of nicotinic receptors and proteins of the exocytotic machinery was unchanged in the brain and adrenal medulla of mSOD1, with respect to WT mice. A slower fusion pore opening, expansion, and closure are likely linked to the pronounced reduction in cell excitability and in the ion currents driving action potentials in mSOD1, compared with WT chromaffin cells.

Calvo-Gallardo|Enrique|E|
de Pascual|Ricardo|R|
Fernández-Morales|José-Carlos|JC|
Arranz-Tagarro|Juan-Alberto|JA|
Maroto|Marcos|M|
Nanclares|Carmen|C|
Gandía|Luis|L|
de Diego|Antonio M G|AM|
Padín|Juan-Fernando|JF|
García|Antonio G|AG|

fusion pore
chromaffin cells
amyotrophic lateral sclerosis
exocytosis
ion channel currents


P16 overexpression in BRAF-mutated gastrointestinal stromal tumors.

Abstract:
BACKGROUND
The aims of this study were to analyze the histopathology, immunophenotype, molecular features, and prognosis in cases of BRAF-mutated gastrointestinal stromal tumors (GISTs) and to examine the p16 expression in these tumors, and further discuss its effects on tumor formation and progression.

METHODS
In all, 283 GIST cases (201 KIT mutants, 12 PDGFRA mutants and 70 wild-type) from the 2010 to 2014 surgical pathology files of the Department of Pathology at Nanjing Jinling Hospital were analyzed for mutations in BRAF exon 15. Patient follow-up and clinical data were collected if available in the medical records. To determine the clinicopathological features and potential molecular mechanism, the authors examined 10 BRAF-mutated GIST cases for KIT, DOG1, SMA, desmin, S-100, Ki-67 and p16 expression.

RESULTS
The authors identified 10 cases (3.5%) of BRAF (V600E) mutations in a series of 283 primary GISTs, without KIT (exons 9, 11, 13, 17) or PDGFRA (exons 12, 18) gene mutations. All 10 cases exhibited spindle-cell features, and the morphology and immunophenotype of these cases were no different from those in cases of KIT-mutated GISTs. The clinical results indicated that BRAF-mutated GISTs tended to occur more frequently in females (7/10), older individuals (mean age, 54.9 years) and the stomach (7/10), and that these tumors were low risk and exhibited low recurrence and mortality rates. Two different forms of p16 were identified, which presented with simultaneously strong and diffuse nuclear and cytoplasmic expression patterns.

CONCLUSION
GISTs with the BRAF V600E mutation are relatively benign tumors with a distinctive molecular mechanism. The expression of the nuclear and cytoplasmic forms of p16 represent two independent mechanisms, and both seemed to control proliferation in response to oncogenic stimuli, protecting the cell from malignant transformation in BRAF-mutated GISTs.

Shi|Shan-Shan|SS| Wang|Xuan|X| Xia|Qiu-Yuan|QY| Rao|Qiu|Q| Shen|Qin|Q| Ye|Sheng-Bin|SB| Li|Rui|R| Shi|Qun-Li|QL| Lu|Zhen-Feng|ZF| Ma|Heng-Hui|HH| Zhou|Xiao-Jun|XJ|

D019941:Cyclin-Dependent Kinase Inhibitor p16

D015972:Gene Expression Regulation, Neoplastic

p16
GIST
wild-type
BRAF mutation
immunohistochemistry


Life Span Studies of ADHD-Conceptual Challenges and Predictors of Persistence and Outcome.

Abstract: There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span.

Caye|Arthur|A|
Swanson|James|J|
Thapar|Anita|A|
Sibley|Margaret|M|
Arseneault|Louise|L|
Hechtman|Lily|L|
Arnold|L Eugene|LE|
Niclasen|Janni|J|
Moffitt|Terrie|T|
Rohde|Luis Augusto|LA|

D001289:Attention Deficit Disorder with Hyperactivity

Predictors
Persistence
Outcomes
ADHD
Course
Longitudinal investigations


The Effect of Photodynamic Therapy in the Treatment of Chronic Periodontitis: A Review of Literature.

Abstract: Introduction: Chronic periodontitis is the most common periodontal disease which is related to the chronic accumulation of bacterial plaque. Since mechanical methods are not sufficient in the treatment of this disease, administration of local/systemic antibiotic is recommended following mechanical debridement. However, side effects of antibiotics such as microbial resistance and patient allergy led to development of alternative methods. One of these suggested methods is the antimicrobial photodynamic therapy (aPDT). PDT is a local noninvasive treatment modality without the side effects caused by antibiotics. The aim of this study was to review the articles related to the application of PDT with laser in the treatment of chronic periodontitis. Review of literature: In the present review of literature, the authors used key words such as chronic periodontitis, laser and photodynamic therapy, and conducted a literature search via Google Scholar and PubMed for the period of 1990 to 2015. A total of 47 articles in English were found. The articles that were not associated with the topic of research and review articles were deleted and only clinical trials were evaluated. After reviewing 23 articles' abstracts, the full texts of 16 articles were analyzed. Conclusion: Considering the safety, the lack of side effects and general advantages like more patient compliance, the PDT treatment with scaling and root planing (SRP) is recommended as an efficient adjunctive modality for the treatment of localized chronic periodontitis especially during the maintenance phase in non-surgical treatment.

Meimandi|Mansour|M|
Talebi Ardakani|Mohammad Reza|MR|
Esmaeil Nejad|Azadeh|A|
Yousefnejad|Parisa|P|
Saebi|Khosro|K|
Tayeed|Mohammad Hossein|MH|

Photodynamic therapy
Chronic periodontitis
Laser


Development and Implementation of the Integrative Toolbox for Headache Management.

Abstract: Patients with migraine are interested in integrative therapies and overall wellness. They also suffer from social isolation as they try to manage a chronic medical condition. We implemented a three-part workshop structured as a group visit that teaches multiple integrative therapies from specialists and offers a chance for shared support and learning.

Beaton-Starr|Meredith|M|
Rist|Pamela M|PM|
Connor|Julie P|JP|
Wayne|Peter M|PM|
Osypiuk|Kamila|K|
Bernstein|Carolyn|C|0000-0002-1064-0808

migraine
complementary and integrative health
group-based education


Ventricular remodelling in rabbits with sustained high-fat diet.

Abstract:
AIM
Excess weight gain and obesity are one of the most serious health problems in the western societies. These conditions enhance risk of cardiac disease and have been linked with increased prevalence for cardiac arrhythmias and sudden death. Our goal was to study the ventricular remodelling occurring in rabbits fed with high-fat diet (HFD) and its potential arrhythmogenic mechanisms.

METHODS
We used 15 NZW rabbits that were randomly assigned to a control (n = 7) or HFD group (n = 8) for 18 weeks. In vivo studies included blood glucose, electrocardiographic, and echocardiographic measurements. Optical mapping was performed in Langendorff-perfused isolated hearts.

RESULTS
Body weight (3.69 ± 0.31 vs. 2.94 ± 0.18 kg, P < 0.001) and blood glucose levels (230 ± 61 vs. 141 ± 14 mg dL(-1) , P < 0.05) were higher in the HFD group vs. controls. The rate-corrected QT interval and its dispersion were increased in HFD rabbits vs. controls (169 ± 10 vs. 146 ± 13 ms and 37 ± 11 vs. 9 ± 2 ms, respectively; P < 0.05). Echocardiographic analysis showed morphological and functional alterations in HFD rabbits indicative of left ventricle (LV) hypertrophy. Isolated heart studies revealed no changes in repolarization and propagation properties under conditions of normal extracellular K(+) , suggesting that extrinsic factors could underlie those electrocardiographic modifications. There were no differences in the dynamics of ventricular fibrillation (frequency, wave breaks) in the presence of isoproterenol. However, HFD rabbits showed a small reduction in action potential duration and an increased incidence of arrhythmias during hyperkalaemia.

CONCLUSION
High-fat feeding during 18 weeks in rabbits induced a type II diabetes phenotype, LV hypertrophy, abnormalities in repolarization and susceptibility to arrhythmias during hyperkalaemia.

Zarzoso|M|M|
Mironov|S|S|
Guerrero-Serna|G|G|
Willis|B Cicero|BC|
Pandit|S V|SV|

ventricle structure and electrophysiology


Field Evaluation of Plant Defense Inducers for the Control of Citrus Huanglongbing.

Abstract: Huanglongbing (HLB) is currently the most economically devastating disease of citrus worldwide and no established cure is available. Defense inducing compounds are able to induce plant resistance effective against various pathogens. In this study the effects of various chemical inducers on HLB diseased citrus were evaluated in four groves (three with sweet orange and one with mandarin) in Florida (United States) for two to four consecutive growing seasons. Results have demonstrated that plant defense inducers including β-aminobutyric acid (BABA), 2,1,3-benzothiadiazole (BTH), and 2,6-dichloroisonicotinic acid (INA), individually or in combination, were effective in suppressing progress of HLB disease. Ascorbic acid (AA) and the nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DDG) also exhibited positive control effects on HLB. After three or four applications for each season, the treatments AA (60 to 600 µM), BABA (0.2 to 1.0 mM), BTH (1.0 mM), INA (0.1 mM), 2-DDG (100 µM), BABA (1.0 mM) plus BTH (1.0 mM), BTH (1.0 mM) plus AA (600 µM), and BTH (1.0 mM) plus 2-DDG (100 µM) slowed down the population growth in planta of 'Candidatus Liberibacter asiaticus', the putative pathogen of HLB and reduced HLB disease severity by approximately 15 to 30% compared with the nontreated control, depending on the age and initial HLB severity of infected trees. These treatments also conferred positive effect on fruit yield and quality. Altogether, these findings indicate that plant defense inducers may be a useful strategy for the management of citrus HLB.


ESTABLISHING A LIVE CARTILAGE-ON-CARTILAGE INTERFACE FOR TRIBOLOGICAL TESTING.

Abstract: Mechano-biochemical wear encompasses the tribological interplay between biological and mechanical mechanisms responsible for cartilage wear and degradation. The aim of this study was to develop and start validating a novel tribological testing system, which better resembles the natural joint environment through incorporating a live cartilage-on-cartilage articulating interface, joint specific kinematics, and the application of controlled mechanical stimuli for the measurement of biological responses in order to study the mechano-biochemical wear of cartilage. The study entailed two parts. In Part 1, the novel testing rig was used to compare two bearing systems: (a) cartilage articulating against cartilage (CoC) and (b) metal articulating against cartilage (MoC). The clinically relevant MoC, which is also a common tribological interface for evaluating cartilage wear, should produce more wear to agree with clinical observations. In Part II, the novel testing system was used to determine how wear is affected by tissue viability in live and dead CoC articulations. For both parts, bovine cartilage explants were harvested and tribologically tested for three consecutive days. Wear was defined as release of glycosaminoglycans into the media and as evaluation of the tissue structure. For Part I, we found that the live CoC articulation did not cause damage to the cartilage, to the extent of being comparable to the free swelling controls, whereas the MoC articulation caused decreased cell viability, extracellular matrix disruption, and increased wear when compared to CoC, and consistent with clinical data. These results provided confidence that this novel testing system will be adequate to screen new biomaterials for articulation against cartilage, such as in hemiarthroplasty. For Part II, the live and dead cartilage articulation yielded similar wear as determined by the release of proteoglycans and aggrecan fragments, suggesting that keeping the cartilage alive may not be essential for short term wear tests. However, the biosynthesis of glycosaminoglycans was significantly higher due to live CoC articulation than due to the corresponding live free swelling controls, indicating that articulation stimulated cell activity. Moving forward, the cell response to mechanical stimuli and the underlying mechano-biochemical wear mechanisms need to be further studied for a complete picture of tissue degradation.

Trevino|Robert L|RL|
Stoia|Jonathan|J|
Laurent|Michel P|MP|
Pacione|Carol A|CA|
Chubinskaya|Susan|S|
Wimmer|Markus A|MA|

cartilage
cartilage mechanics
joint motion simulation
tribology- wear


Education Burnout and Engagement in Occupational Therapy Undergraduate Students and Its Associated Factors.

Abstract:
Introduction
Burnout syndrome has been characterized as a process of chronic responses to occupational stress in certain employee groups. However, this phenomenon has also been reported in other participant groups including university students. The Maslach Burnout Inventory-Student Survey (MBI-SS), composed of the Exhaustion, Cynicism and Efficacy subscales, was used to evaluate burnout in this sample group while the Utrecht Work Engagement Scale (UWES) was used to gather data related to engagement, a positive psychology construct composed of the three factors, namely vigor, dedication, and absorption. To date, no studies considered these factors in relation to occupational therapy students. This begs the question, is there a relationship between occupational therapy students' self-reported levels of burnout and engagement?

Objectives
The study objectives are to (1) ascertain the self-reported levels of burnout and engagement in a sample of Australian Occupational undergraduate therapy students, and (2) analyze the sociodemographic, occupational and academic characteristic associated with these levels.

Methods
Participants were 225 Australian undergraduate occupational therapy students from Monash University completed the MBI-SS and the UWES for students. Descriptive, bivariate and multiple linear regression analyses were performed.

Results
Regarding MBI-SS burnout dimensions, exhaustion was associated with age, year level of enrolment and hours of direct time spent working on occupational therapy studies, explaining 15% of its variance. Cynicism and efficacy were associated with age, year level of enrolment and hours of indirect time, accounting for 16% of its variance. For the UWES engagement dimensions, year level of enrolment and hours of indirect time spent working on occupational therapy studies were significant predictors of vigor, explaining 27% its variance while while age, gender, year level of enrolment, hours of indirect time spent working on occupational therapy studies, and hours spend per week engaged in self-care activities accounted for 23% of the variance of dedication. Finally, age, year level of enrolment, and hours of indirect time spent working on occupational therapy studies explained 27% of the variance of absorption.

Conclusion
The results indicate that a number of demographic and academic study variables are significantly associated with burnout syndrome and education engagement reported by undergraduate occupational therapy students.

Morales-Rodríguez|Francisco Manuel|FM|
Pérez-Mármol|José M|JM|
Brown|Ted|T|

education
burnout
engagement
undergraduate students
academic


Frequency dependent impedimetric cytotoxic evaluation of anticancer drug on breast cancer cell.

Abstract: The present work reports the impedance characteristics of MCF-7 cell lines treated with anticancer drug ZD6474 to evaluate the cytotoxic effect on cellular electrical behaviour using miniature impedance sensors. Four types of impedance sensing devices with different electrode geometries are fabricated by microfabrication technology. The frequency response characteristics of drug treated cells are studied to evaluate cytotoxic effect of ZD6474 and also to assess the frequency dependent sensitivity variation with electrode area. A significant variation in magnitude of measured impedance data is obtained for drug treated samples above 10 µM dose indicating prominent effect of ZD6474 which results in suppression of cell proliferation and induction of apoptosis process. The results obtained by impedimetric method are correlated well with conventional in vitro assays such as flow cytometry, cell viability assays and microscopic imaging. Finally an empirical relation between cell impedance, electrode area and drug dose is established from impedance data which exhibits a negative correlation between drug doses and impedance of cancer cells.

Pradhan|Rangadhar|R| Rajput|Shashi|S| Mandal|Mahitosh|M| Mitra|Analava|A| Das|Soumen|S|


Radiometric characterisation of light sources used in analytical chemistry - A review.

Abstract: Light sources are an indispensable component of an overwhelmingly large number of analytical methods. Radiometric characterisation of light sources in analytical chemistry is therefore of fundamental importance. This review presents up to date knowledge on methods to characterise radiometric properties of light sources in terms of radiometric power, irradiance, brightness, luminous efficacy, luminous efficiency and emission spectra, all of which are crucial parameters for their use in analytical chemistry. Special attention is paid to radiometric characterisation of new generations of light sources with focus on miniaturised and low-cost light sources suitable for portable analytical instrumentation. Miniaturised light sources, especially new generations of solid-state light sources including solution processable quantum dot light emitting diodes (QLEDs), organic LEDs (OLEDs) as well as conventional LEDs and lasers, are radiometrically characterised through various spectrophotometric, actinometric as well as new facile radiometric methods. Although the areas of analytical use of new light sources including QLEDs, OLEDs as well as other important light sources such as deep ultraviolet (DUV) and infrared LEDs in analytical chemistry are yet to reach their potential, their radiometric characterisation opens future options for their wider deployment in analytical chemistry.


A meta-analysis of client-therapist perspectives on the therapeutic alliance: Examining the moderating role of type of measurement and diagnosis.

Abstract:
BACKGROUND
Clients and therapists often have different perspectives on their therapeutic alliance (TA), affecting the process and outcome of therapy. The aim of the present meta-analysis was to assess the mean differences between clients' and therapists' estimations of TA among clients with severe disturbances, while focusing on two potential moderators: client diagnosis and alliance instrument.

METHOD
We conducted a systematic literature search of studies examining both client perspective and therapist perspective on TA in psychotherapy among people with schizophrenia spectrum disorders, personality disorders, and substance misuse disorders. We then analyzed the data using a random-effects meta-analytic model with Cohen's d standardized mean effect size.

RESULTS
Heterogeneity analyses (k = 22, Cohen's d = -.46, 95% confidence interval = .31-1.1) produced a significant Q-statistic (Q = 94.96) and indicated high heterogeneity, suggesting that moderator analyses were appropriate.

CONCLUSIONS
Our findings show that the type of TA instrument moderates the agreement on TA between client and therapist, but there was no indication of the client's diagnosis moderating the effect. The agreement between client and therapist estimations seems to be dependent on the instrument that is used to assess TA. Specific setting-related instruments seem to result in higher agreement between clients' and therapists' estimations than do more general instruments that are applied to assess TA.

Igra|Libby|L|0000-0002-1872-4539
Lavidor|Michal|M|
Atzil-Slonim|Dana|D|
Arnon-Ribenfeld|Nitzan|N|
de Jong|Steven|S|0000-0002-0421-3041
Hasson-Ohayon|Ilanit|I|

meta-analysis
therapeutic alliance
Agreement


Prevalence of occupational exposure and its influence on job satisfaction among Chinese healthcare workers: a large-sample, cross-sectional study.

Abstract:
OBJECTIVES
This study had three objectives: (1) describe the prevalence of occupational exposure among Chinese medical personnel in detail, (2) verify the partial mediating role of work environment satisfaction in the relationship between occupational exposure and job satisfaction, and (3) examine if stress symptoms moderate the relationship between occupational exposure and job satisfaction.

DESIGN
A large cross-sectional online survey was conducted in July 2018 in China.

SETTING
A survey was conducted in 54 cities across 14 provinces of China.

PARTICIPANTS
A total of 12 784 questionnaires were distributed, and 9924 healthcare workers (HCWs) completed valid questionnaires. The response rate was 77.63%.

OUTCOME MEASURES
A confidential questionnaire was distributed to HCWs. The relationships among and the mechanisms of the variables were explored using descriptive statistical analyses, Pearson's correlation coefficient and multiple linear regression analysis.

RESULTS
The most common occupational exposures among HCWs in the past 12 months were psychosocial and organisational hazards (85.93%). Overall, physicians (93.7%) and nurses (89.2%) were the main victims of occupational exposure. Occupational exposure correlated negatively with work environment satisfaction and job satisfaction, and positively with stress symptoms. Moreover, work environment satisfaction fully mediated the relationship between occupational exposure and job satisfaction, and stress symptoms moderated the relationship between occupational exposure and job satisfaction.

CONCLUSION
The incidence of occupational exposure among HCWs is generally high. The high frequency of psychosocial and organisational hazards among physicians and nurses should be taken seriously and dealt with in a timely manner by hospital managers. The negative impact of occupational exposure on job satisfaction must be buffered by measures to reduce stress symptoms and enhance working environment satisfaction, ultimately improving the overall quality of life of HCWs and promoting comprehensive development of the medical team.

Shi|Yu|Y|0000-0002-9349-5529 Xue|Haifeng|H| Ma|Yuanshuo|Y| Wang|Licheng|L| Gao|Tian|T| Shi|Lei|L| Wang|Yang|Y| Cui|Mei|M| Wang|Chao|C| Yang|Xi|X| Liu|Ming|M| Fan|Lihua|L| Yan|Guanyun|G|

occupational exposure
job satisfaction
healthcare workers
working environment
stress
occupational health and safety


Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial.

Abstract: Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a nine-month cluster-randomized controlled trial conducted in south-central Côte d'Ivoire. 378 children aged 12-36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (PF < 30 μg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44-66%, and 57-76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on iron deficiency with or without anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).

Glinz|Dominik|D|
Wegmüller|Rita|R|
Ouattara|Mamadou|M|
Diakité|Victorine G|VG|
Aaron|Grant J|GJ|
Hofer|Lorenz|L|
Zimmermann|Michael B|MB|
Adiossan|Lukas G|LG|
Utzinger|Jürg|J|
N'Goran|Eliézer K|EK|
Hurrell|Richard F|RF|

D007227:Infant Nutritional Physiological Phenomena

complementary food
sodium iron EDTA
iron deficiency
anemia
cluster-randomized controlled trial
iron fortification
Plasmodium falciparum
Côte d’Ivoire
infant cereal


Clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenza-associated encephalopathy.

Abstract:
BACKGROUND
Influenza-associated encephalopathy (IAE) is one of the most serious CNS complications of an influenza virus infection, with unclear pathophysiology. Clasmatodendrosis is a complex of morphological changes in astrocytes characterized by fragmentation of the distal processes and swollen cell bodies. Although pathologists in Japan have long been aware of the presence of clasmatodendrosis in IAE brains, no details of the phenomenon have been published to date. We aimed to confirm the existence, and characterize the spatial distribution of clasmatodendrosis in postmortem IAE brains.

METHODS
Autopsied brains from 7 patients with IAE and 8 non-IAE subjects were examined immunohistochemically. In addition, immunofluorescent staining and electron microscopy were performed.

RESULTS
Clasmatodendrosis was present in all examined regions of the IAE brains, but none of the control brains. Fragmented processes of astrocytes in IAE brains were closely adjacent to synapses on the dendritic spines, with the fragmentation especially prominent in the cerebellar molecular layer. In addition, the clasmatodendrotic astrocytes were negative for autophagy markers. Furthermore, whereas aquaporin 4 was predominantly detected in the perivascular endfeet of astrocytes in the control brains, its primary localization site shifted to the fragmented perisynaptic processes in the IAE brains.

CONCLUSION
Clasmatodendrosis was distributed diffusely in the IAE brains in close association with synapses, and was not caused by astrocyte autophagy. Clasmatodendrosis may be a suggestive pathological feature of IAE.

Tachibana|Masaya|M| Mohri|Ikuko|I| Hirata|Ikuko|I| Kuwada|Ayano|A| Kimura-Ohba|Shihoko|S| Kagitani-Shimono|Kuriko|K| Fushimi|Hiroaki|H| Inoue|Takeshi|T| Shiomi|Masashi|M| Kakuta|Yukio|Y| Takeuchi|Makoto|M| Murayama|Shigeo|S| Nakayama|Masahiro|M| Ozono|Keiichi|K| Taniike|Masako|M|

Clasmatodendrosis
Astrocytes
Influenza-associated encephalopathy
Synapses
Autophagy
Aquaporin4


Offering mental health first aid to a person experiencing psychosis: a Delphi study to redevelop the guidelines published in 2008.

Abstract:
BACKGROUND
Psychotic illnesses can have a major impact on those who experience them. Timely treatment for psychosis is important and friends, family members and the public can be a facilitating factor in social support and professional help-seeking. Expert consensus guidelines on how to provide mental health first aid to a person experiencing psychosis were developed in 2008. This Delphi study aimed to redevelop the guidelines to reflect current evidence.

METHODS
The Delphi consensus method was used to determine which helping strategies should be included in the redeveloped guidelines. A systematic search of grey and academic literature was undertaken to identify strategies on how a member of the public can assist someone experiencing psychosis. These strategies were organised into questionnaire statements. Two expert panels-one comprising people with lived experience (Carers and Consumers) and one of professionals-completed three consecutive rounds of online survey questionnaires to rate the importance of each helping statement for inclusion in the guidelines. Statements were included in the guidelines if they were endorsed by at least 80% of each panel.

RESULTS
The expert panels rated 515 statements across three rounds of surveys, with 325 statements meeting the criteria for inclusion in the redeveloped guidelines. 59 panel participants completed all three surveys.

CONCLUSIONS
The redeveloped guidelines outline a general set of strategies for providing initial assistance to a person who is experiencing psychosis. Compared to the original guidelines, these redeveloped guidelines provide more detailed instruction for members of the public on how to provide mental health first aid to assist a person experiencing psychosis. The guidelines are available to the public and will be used to update the Mental Health First Aid courses.

D003697:Delphi Technique
D005392:First Aid
D033062:Friends
D006801:Humans
D008603:Mental Health
D011618:Psychotic Disorders
D011795:Surveys and Questionnaires

Mental health
Mental health first aid
Psychosis
Delphi study
Expert consensus
Community guidelines
Mental illness


Photocatalytic degradation of organic contaminants by g-C3N4/EPDM nanocomposite film: Viable, efficient and facile recoverable.

Abstract: The original metal free graphitic carbon nitride/ethylene propylene diene monomer nanocomposite film (g-C3N4/EPDM NCF) was fabricated by facile solution cast method. g-C3N4/EPDM NCF with diameter (50mm) and thickness (4mm) was investigated towards the photocatalytic degradation of methylene blue (MB) and methyl orange (MO) dye solution under visible light irradiation. The as synthesized g-C3N4/EPDM NCF was exhibited high crystalline nature with the crystalline size of 21.53nm, the smooth surface nature and the particle size was observed from the TEM analysis is 20nm. Furthermore, the influence of operational parameters was carried out which demonstrated that 100mg photocatalyst and 25μM of dye concentration were obtained as an optimized condition for the best photocatalytic degradation results. As a result of scavenger experiment, it was concluded that the hydroxyl radical (OH) was actively involved in the photocatalytic degradation. The g-C3N4/EPDM NCF were recoverable from the photocatalytic reaction system and the present find findings may open up a new platform for the simple handpicked photocatalyst.

Selvam|V|V|
Senthil Kumar|P|P|
Navaneetha Krishnan|G|G|
Senthil Andavan|G T|GT|

D017550:Spectroscopy, Fourier Transform Infrared

Photocatalytic degradation
100% recoverability
Dye contaminant
Handpicking method
Polymer
g-C(3)N(4)/EPDM


Drug Development and Potential Regulatory Paths for Insulin Biosimilars.

Abstract: Under the Biologics Price Competition and Innovation Act (BPCI Act), a biological product may be demonstrated to be "biosimilar" if data show that, among other things, the product is "highly similar" to an already-approved biological product. Biosimilar insulins have the potential to reduce ever growing costs associated with insulin treatment by allowing competition. In this article, we describe the current drug development and regulatory paths for biosimilar insulins. Most likely basis of market approval for biosimilar insulins by the US Food and Drug Administration (FDA) and guidance for developing insulin biosimilars by European Medicines Agency (EMA) are discussed in detail. Currently, no product specific biosimilar FDA guidance for insulin biosimilarity assessment exists. We propose efficient and cost-effective drug development and potential regulatory paths based on scientific justification. In addition, novel trial designs for demonstrating interchangeability between the biosimilar and the reference insulin products are presented.

regulatory insulin biosimilar interchangeability drug-development


Zinc boosts EGCG's hIAPP amyloid Inhibition both in solution and membrane.

Abstract: Amyloid aggregation of human islet amyloid polypeptide (hIAPP) is linked to insulin-producing islet cell death in type II diabetes. Previous studies have shown that zinc (Zn(II)) and insulin, co-secreted with hIAPP, have an inhibition effect on hIAPP aggregation. Lipid membranes have also been shown to significantly influence the aggregation kinetics of hIAPP. An increasing number of studies report the importance of developing small molecule inhibitors to suppress the hIAPP's aggregation and subsequent toxicity. The ability of epigallocatechin-gallate (EGCG) to inhibit aggregation of a variety of amyloid peptide/proteins initiated numerous studies as well as the development of derivative compounds to potentially treat amyloid diseases. In this study, a combination of Thioflavin-T fluorescence kinetics, transmission electron microscopy, isothermal titration calorimetery, circular dicrosim and nucelar magnetic resonance experiments were used to demonstrate a significant enhancement in EGCG's efficiency when complexed with Zn(II). We demonstrate that the Zn-EGCG complex is able to significantly suppress hIAPP's amyloid aggregation both in presence and absence of lipid membrane. Circular dichroism experiments indicate the formation and stabilization of a helical structure of hIAPP in presence of the EGCG:Zn(II) complex. Our results also reveal the ability of EGCG or EGCG:Zn(II) to efficiently suppress hIAPP's cellular toxicity. We believe that the reported results could be useful to develop strategies to trap hIAPP intermediates for further biophysical and structural studies, and also to devise approaches to abolish amyloid aggregation and cellular toxicity.

Lee|Young-Ho|YH|
Lin|Yuxi|Y|
Cox|Sarah J|SJ|
Kinoshita|Misaki|M|
Sahoo|Bikash R|BR|
Ivanova|Magdalena|M|
Ramamoorthy|Ayyalusamy|A|

Amyloid
Membrane
Islet amyloid polypeptide
Type II diabetes
Epigallocatechin-gallate
Protein aggregation


Approaches Towards Professional Studies and Spare-time Activities Among Preclinical and Clinical Year Medical Students.

Abstract: Objective This study aims at a recognition of the differences in the study habits, approach to teaching resources, and spare-time activities of medical students in the preclinical and clinical training periods at King Abdulaziz University (KAU) Jeddah, Saudi Arabia (SA). Methods Study sampling was carried out in 2017 at the Faculty of Medicine, KAU, Jeddah, SA. Students from both genders were included and further subdivided to preclinical (2nd and 3rd years) and clinical groups (4th, 5th, and 6th years). Students were asked to respond to an online questionnaire. SPSS-Version 21 (IBM Corp., Armonk, NY, US) was utilized for statistical analysis of the collected data, Results Of the 347/500 (response rate 69.4%) medical students, 85 (24.5%) were from the preclinical students (2nd and 3rd years), and 262 (64.5%) were enrolled in the clinical group (4th to 6th years of MBBS). The majority of students 330 (94.1%) were unmarried, only 17 of them, i.e., 4.9%, were married. Analysis of the data revealed that medical textbooks, essential versions of basic medical books, online resources, and online version of books were used more frequently by the clinical group as compared to the preclinical students. Teacher-provided lecture handouts and lecture notes taken during classes were being equally used by both groups. There was a significant difference in the opinion on the usefulness of different resources between both groups. Students faced difficulty in understanding the English language, observed more in the pre-clinical years as compared to relatively groomed clinical students. The preclinical group could not understand the teaching material in books due to a weaker understanding of the English language. Social media software was used for keeping both groups busy, but clinical students also used social media for academic purposes. More than half of the participants from the preclinical and almost one-third from the clinical years admitted that their teachers recommended them for relevant medical textbooks. An encouraging trend was observed in most preclinical group students: they found teaching modalities, such as problem-based learning (PBL) and other academic activities, as a trigger to promote book reading. Conclusion Our results show that the students in the clinical phase had a more methodical approach to professional studies and a difference in spare-time activities.

Jameel|Tahir|T|
Baig|Mukhtiar|M|
Gazzaz|Zohair J|ZJ|
Tashkandi|Jawad M|JM|
Al Alhareth|Nasser S|NS|
Khan|Shahida A|SA|
Butt|Nadeem S|NS|

medical students
study habits
social media
basic sciences
clinical sciences
reading resources


Dialkylzinc-mediated cross-coupling reactions of perfluoroalkyl and perfluoroaryl halides with aryl halides.

Abstract: A highly chemoselective perfluoroalkylation reaction of aromatic halides is reported. Thermally stable perfluoroalkylzinc reagents, generated by a rapid halogen-zinc exchange reaction between diorganozinc and perfluoroalkyl halide species, couple with a wide range of aryl halides in the presence of a copper catalyst, in moderate to high yields. Good stability of the perfluoroalkylzinc species was indicated by DFT calculation and the reagents were storable for at least three months under argon without loss of activity. This method is applicable to gram-scale synthesis, and its functional group tolerance compares favorably with reported protocols.

Kato|Hisano|H| Hirano|Keiichi|K| Kurauchi|Daisuke|D| Toriumi|Naoyuki|N| Uchiyama|Masanobu|M|

cross-coupling
perfluoroalkylation
arylation
density functional calculations
organozinc reagents


Quadriceps effort during squat exercise depends on hip extensor muscle strategy.

Abstract: Hip extensor strategy, specifically relative contribution of gluteus maximus versus hamstrings, will influence quadriceps effort required during squat exercise, as hamstrings and quadriceps co-contract at the knee. This research examined the effects of hip extensor strategy on quadriceps relative muscular effort (RME) during barbell squat. Inverse dynamics-based torque-driven musculoskeletal models were developed to account for hamstrings co-contraction. Net joint moments were calculated using 3D motion analysis and force platform data. Hamstrings co-contraction was modelled under two assumptions: (1) equivalent gluteus maximus and hamstrings activation (Model 1) and (2) preferential gluteus maximus activation (Model 2). Quadriceps RME, the ratio of quadriceps moment to maximum knee extensor strength, was determined using inverse dynamics only, Model 1 and Model 2. Quadriceps RME was greater in both Models 1 and 2 than inverse dynamics only at barbell loads of 50-90% one repetition maximum. The highest quadriceps RMEs were 120 ± 36% and 87 ± 28% in Models 1 and 2, respectively, which suggests that barbell squats are only feasible using the Model 2 strategy prioritising gluteus maximus versus hamstrings activation. These results indicate that developing strength in both gluteus maximus and quadriceps is essential for lifting heavy loads in squat exercise.

Bryanton|Megan A|MA|
Carey|Jason P|JP|
Kennedy|Michael D|MD|
Chiu|Loren Z F|LZ|

gluteus maximus
hamstrings
co-contraction
Knee
musculoskeletal modelling


Inference and sample size calculation for clinical trials with incomplete observations of paired binary outcomes.

Abstract: We investigate the estimation of intervention effect and sample size determination for experiments where subjects are supposed to contribute paired binary outcomes with some incomplete observations. We propose a hybrid estimator to appropriately account for the mixed nature of observed data: paired outcomes from those who contribute complete pairs of observations and unpaired outcomes from those who contribute either pre-intervention or post-intervention outcomes. We theoretically prove that if incomplete data are evenly distributed between the pre-intervention and post-intervention periods, the proposed estimator will always be more efficient than the traditional estimator. A numerical research shows that when the distribution of incomplete data is unbalanced, the proposed estimator will be superior when there is moderate-to-strong positive within-subject correlation. We further derive a closed-form sample size formula to help researchers determine how many subjects need to be enrolled in such studies. Simulation results suggest that the calculated sample size maintains the empirical power and type I error under various design configurations. We demonstrate the proposed method using a real application example. Copyright © 2016 John Wiley & Sons, Ltd.

D016032:Randomized Controlled Trials as Topic

sample size
incomplete
paire
binary outcomes


Significant Adhesion Reduction with 4DryField PH after Release of Adhesive Small Bowel Obstruction.

Abstract: Background  Peritoneal adhesions reoccur in up to 100% of cases, possibly causing complications like pain, secondary female infertility, and small bowel obstruction. The latter has a mortality rate of up to 15% during hospitalization. This study investigates if recurrence of peritoneal adhesions can be prevented by prophylactic use of the starch-based medical device 4DryField. Methods  The course of 40 patients with surgery for intestinal obstruction and, partially, second intervention was analyzed. In both operations, adhesion severity and extent were scored 0 (no adhesions) to III (massive/dense and vascular adhesions) and 0 (no adhesions) to III (extensive, covering more than approximately 25 × 25 cm), respectively. To prevent recurrence of adhesions all patients were treated with 4DryField gel (60 mL saline solution per 5 g powder), evenly distributed on the whole impaired intestine (including anastomoses) before abdominal closure. Follow-up was up to 1.5 years in a 3 to 6 months' interval. Results  Eight patients had relaparotomies on postoperative days 1 to 155. In the first operation, median adhesion severity score was III, median adhesion extent II. In redo-surgeries, significantly lower scores were detected (median adhesion severity: 0, p  = 0.0003; median adhesion extent: 0, p  = 0.0009). No adverse events related to the product were observed. One patient had later redo-surgery in another hospital due to recurrence of adhesions, one patient suffered from flatulence. All other patients were free of adhesion-related symptoms during follow-up. Conclusion  Based on the high severity of diseases and the significant reduction of adhesion severity and extent in redo-surgeries, 4DryField gel is a promising adjunct for adhesion prevention in bowel surgery. The favorable results should be confirmed in prospective randomized trials.

intestinal obstruction
adhesion prevention
barrier gel
ileus
modified polysaccharide


A Hybrid DV-Hop Algorithm Using RSSI for Localization in Large-Scale Wireless Sensor Networks.

Abstract: With the increasing realization of the Internet-of-Things (IoT) and rapid proliferation of wireless sensor networks (WSN), estimating the location of wireless sensor nodes is emerging as an important issue. Traditional ranging based localization algorithms use triangulation for estimating the physical location of only those wireless nodes that are within one-hop distance from the anchor nodes. Multi-hop localization algorithms, on the other hand, aim at localizing the wireless nodes that can physically be residing at multiple hops away from anchor nodes. These latter algorithms have attracted a growing interest from research community due to the smaller number of required anchor nodes. One such algorithm, known as DV-Hop (Distance Vector Hop), has gained popularity due to its simplicity and lower cost. However, DV-Hop suffers from reduced accuracy due to the fact that it exploits only the network topology (i.e., number of hops to anchors) rather than the distances between pairs of nodes. In this paper, we propose an enhanced DV-Hop localization algorithm that also uses the RSSI values associated with links between one-hop neighbors. Moreover, we exploit already localized nodes by promoting them to become additional anchor nodes. Our simulations have shown that the proposed algorithm significantly outperforms the original DV-Hop localization algorithm and two of its recently published variants, namely RSSI Auxiliary Ranging and the Selective 3-Anchor DV-hop algorithm. More precisely, in some scenarios, the proposed algorithm improves the localization accuracy by almost 95%, 90% and 70% as compared to the basic DV-Hop, Selective 3-Anchor, and RSSI DV-Hop algorithms, respectively.

Cheikhrouhou|Omar|O|
M Bhatti|Ghulam|G|
Alroobaea|Roobaea|R|

DV-Hop RSSI localization IoT WSN multihop


Association Between Vancomycin Area Under the Curve and Nephrotoxicity: a single center, retrospective cohort study in a veteran population.

Abstract:
Background
It is unclear which vancomycin area under the curve (AUC) values are most associated with risk for acute kidney injury (AKI).

Methods
This retrospective cohort study was undertaken to determine if vancomycin AUC >550 is associated with a higher rate of AKI than an AUC <550. Patients treated with vancomycin for at least 4 days at the VA St. Louis Health Care System from 1/1/2016 to 9/31/2018 were included. The primary outcome was AKI (defined as an increase in serum creatinine by 0.3 mg/dL or 50% from baseline). Secondary outcomes included length of stay, readmission in 30 days, and mortality in 30 days. A bivariate analysis was used to determine other potential factors affecting AKI rate, with significant variables (P < .2) to be included in the multivariate logistic regression analysis to determine independent risk for AKI.

Results
Two hundred patients were included in the analysis; 100 patients with an AUC ≥550 and 100 with an AUC <550. Only mean vancomycin dose (1722.50 mg vs 2361.25 mg; P < .05), mean AUC (465.88 vs 696.45; P < .05), and peak SCr (1.22 mg/dL vs 1.48 mg/dL; P = .015) were significantly different between groups (AUC <550 vs AUC ≥550, respectively). AKI occurred in 42% (42/100) of patients with AUC ≥550 compared with 2% (2/100) of patients with AUC <550 (P < .05). Secondary outcomes were not different between the groups. In the bivariate analysis, age ≥70, CrCl <50 mL/min, and AUC ≥550 (odds ratio, 49.5; 95% CI, 10.1-242.3; P < .05) were found to be independently associated with risk for developing AKI.

Conclusions
Patients with a vancomycin AUC ≥550 were found to have a significantly higher rate of AKI compared with those with an AUC <550.

vancomycin
area under the curve
nephrotoxicity
pharmacokinetics


Prediction of Coronary Atherosclerotic Ostial Lesion with a Damping of the Pressure Tracing during Diagnostic Coronary Angiography.

Abstract:
PURPOSE
When performing coronary angiography (CAG), diagnostic catheter intubation to the ostium can cause damping of the pressure tracing. The aim of this study was to determine the predictors of atherosclerotic ostial stenosis in patients showing pressure damping during CAG.

MATERIALS AND METHODS
In total, 2926 patients who underwent diagnostic CAG were screened in this study. Pressure damping was defined as an abrupt decline of the coronary blood pressure with a blunted pulse pressure after engagement of the diagnostic catheter. According to CAG and intravascular ultrasound (IVUS), we divided damped ostia into two groups: atherosclerotic ostial lesion group (true lesion group) and non-atherosclerotic ostium group (false lesion group). Clinical and angiographic characteristics were compared between the two groups.

RESULTS
The overall incidence of pressure damping was 2.3% (68 patients and 76 ostia). Among the pressure damped ostia, 40.8% (31 of 76 ostia) were true atherosclerotic ostial lesions (true lesion group). The true lesion group had more frequent left main ostial damping and more percutaneous coronary interventions (PCIs) performed on non-ostial lesions, compared to the false lesion group. On multivariate logistic regression analysis, left main ostial damping [hazard ratio (HR) 4.11, 95% confidence interval (CI) 1.24-13.67, p=0.021] and PCI on non-ostial lesion (HR 5.34, 95% CI 1.34-21.27, p=0.018) emerged as independent predictors for true atherosclerotic ostial lesions in patients with pressure damping.

CONCLUSION
Left main ostial damping and the presence of a non-ostial atherosclerotic lesion may suggest a significant true atherosclerotic lesion in the coronary ostium.

Her|Ae Young|AY|
Ann|Soe Hee|SH|
Singh|Gillian Balbir|GB|
Kim|Yong Hoon|YH|
Koo|Bon Kwon|BK|
Shin|Eun Seok|ES|

ostial lesion
coronary angiography
Pressure damping
intravascular ultrasound


Stacking geometry between two sheared Watson-Crick basepairs: Computational chemistry and bioinformatics based prediction.

Abstract:
BACKGROUND
Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The A:A w:wC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Its effect is pronounced when the A:A w:wC basepair stacks on Sheared wobble G:U W:WC basepairs.

METHODS
We employed molecular dynamics simulations of three possible double helices with GAG, UAG and GAU sequence motifs at their centers and quantum chemical calculation for non-canonical A:A w:wC basepair stacked on G:U W:WC basepair.

RESULTS
We noticed stable structures of GAG motif with specifically negative Shear of the A:A basepair but stabilities of the other motifs were not found with A:A w:wC basepairing. Hybrid DFT-D and MP2 stacking energy analyses on dinucleotide step sequences, A:A w:wC::G:U W:WC and A:A w:wC::U:G W:WC reveal that viable orientation of A:A::G:U prefers one of the H-bonding modes with negative Shear, supported by crystal structure database. The A:A::U:G dinucleotide, however, prefers structure with only positive Shear.

CONCLUSIONS
The quantum chemical calculations explain why MD simulations of GAG sequence motif only appear stable. In the cases of the GAU and UAG motifs "tug of war" situation between positive and negative Shears of A:A w:wC basepair induces conformational plasticity.

GENERAL SIGNIFICANCE
We have projected comprehensive reason behind the promiscuous nature of A:A w:wC basepair which brings occasional structural plasticity.

Maiti|Satyabrata|S| Mukherjee|Debasish|D| Roy|Parthajit|P| Chakrabarti|Jaydeb|J| Bhattacharyya|Dhananjay|D|

D000225:Adenine
D020029:Base Pairing
D019295:Computational Biology
D000080486:Computational Chemistry
D018360:Crystallography, X-Ray
D015226:Dinucleoside Phosphates
D006860:Hydrogen Bonding
D056004:Molecular Dynamics Simulation
D015394:Molecular Structure
D009690:Nucleic Acid Conformation
D012313:RNA

RNA double helices
Basepair stacking
Molecular dynamics simulation
Conformational plasticity
Density functional theory
Flanking basepair effect


Intrathecal SRT1720, a SIRT1 agonist, exerts anti-hyperalgesic and anti-inflammatory effects on chronic constriction injury-induced neuropathic pain in rats.

Abstract: Neuropathic pain is caused by lesion or inflammation of the nervous system and characterized by the symptoms of allodynia, hyperalgesia and spontaneous pain. SIRT1 (Sir2) is a NAD-dependent deacetylase and is reported to regulate a wide variety of cellular processes including inflammation, aging and lifespan extension. Nevertheless, the role of SIRT1 in neuropathic pain is not fully understood. The present study was intended to detect the effect of intrathecal SRT1720, a SIRT1 agonist, using quantitative real-time PCR and western blot analysis over time in rats following chronic constriction injury (CCI) or sham surgery. In addition, the effect of intrathecal injection of SRT1720 on thermal hyperalgesia and mechanical allodynia was evaluated in CCI rats. It was found that daily intrathecal injection of SRT1720 before and 1, 3, 5, 7 days after CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI rats. In addition, an intrathecal injection of STR1-siRNA before SRT1720 administration reversed the anti-nociceptive effect of SRT1720. Furthermore, intrathecal injection of SRT1720 significantly down-regulated the expression of mammalian target of rapamycin (mROT), NF-κB and inflammatory cytokines, such as IL-6, TNF-α and iNOS mRNA. These data indicate that intrathecal SRT1720 may be an alternative strategy for the treatment of neuropathic pain. Our findings suggest that intrathecal SRT1720, a SIRT1 agonist, exerts antihyperalgesic and antiinflammatory effects on CCI-induced neuropathic pain in rats.

Lv|Chen|C| Hu|Hong-Yi|HY| Zhao|Li|L| Zheng|Hui|H| Luo|Xian-Zhe|XZ| Zhang|Juan|J|

SRT1720
SIRT1
neuropathic pain
chronic constriction injury
antihyperalgesic
antiinflammatory


Effective Dose in Nuclear Medicine Studies and SPECT/CT: Dosimetry Survey Across Quebec Province.

Abstract: The aims of the current study were to draw a portrait of the delivered dose in selected nuclear medicine studies in Québec province and to assess the degree of change between an earlier survey performed in 2010 and a later survey performed in 2014. Methods: Each surveyed nuclear medicine department had to complete 2 forms: the first, about the administered activity in selected nuclear medicine studies, and the second, about the CT parameters used in SPECT/CT imaging, if available. The administered activities were converted into effective doses using the most recent conversion factors. Diagnostic reference levels were computed for each imaging procedure to obtain a benchmark for comparison. Results: The distributions of administered activity in various nuclear medicine studies, along with the corresponding distribution of the effective doses, were determined. Excluding 131I for thyroid studies, 67Ga-citrate for infectious workups, and combined stress and rest myocardial perfusion studies, the remainder of the 99mTc-based studies delivered average effective doses clustered below 10 mSv. Between the 2010 survey and the 2014 survey, there was a statistically significant decrease in delivered dose from 18.3 to 14.5 mSv. 67Ga-citrate studies for infectious workups also showed a significant decrease in delivered dose from 31.0 to 26.2 mSv. The standardized CT portion of SPECT/CT studies yielded a mean effective dose 14 times lower than the radiopharmaceutical portion of the study. Conclusion: Between 2010 and 2014, there was a significant decrease in the delivered effective dose in myocardial perfusion and 67Ga-citrate studies. The CT portions of the surveyed SPECT/CT studies contributed a relatively small fraction of the total delivered effective dose.

D000072098:Single Photon Emission Computed Tomography Computed Tomography

effective dose
SPECT
SPECT/CT
dosimetry
activity
conversion factor


Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome.

Abstract:
PURPOSE
Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features.

METHODS
Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individuals either by exome sequencing or LSS Sanger sequencing. Splicing defects were assessed by transcript analysis and minigene assay.

RESULTS
We reported ten APMR individuals from six unrelated families with biallelic variants in LSS. We additionally identified one affected individual with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. Quantification of cholesterol and its precursors did not reveal noticeable imbalance.

CONCLUSION
In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome.

Besnard|Thomas|T|
Sloboda|Natacha|N|
Goldenberg|Alice|A|
Küry|Sébastien|S|
Cogné|Benjamin|B|
Breheret|Flora|F|
Trochu|Eva|E|
Conrad|Solène|S|
Vincent|Marie|M|
Deb|Wallid|W|
Balguerie|Xavier|X|
Barbarot|Sébastien|S|
Baujat|Geneviève|G|
Ben-Omran|Tawfeg|T|
Bursztejn|Anne-Claire|AC|
Carmignac|Virginie|V|
Datta|Alexandre N|AN|
Delignières|Aline|A|
Faivre|Laurence|L|
Gardie|Betty|B|
Guéant|Jean-Louis|JL|
Kuentz|Paul|P|
Lenglet|Marion|M|
Nassogne|Marie-Cécile|MC|
Ramaekers|Vincent|V|
Schnur|Rhonda E|RE|
Si|Yue|Y|
Torti|Erin|E|
Thevenon|Julien|J|
Vabres|Pierre|P|
Van Maldergem|Lionel|L|
Wand|Dorothea|D|
Wiedemann|Arnaud|A|
Cariou|Bertrand|B|
Redon|Richard|R|
Lamazière|Antonin|A|
Bézieau|Stéphane|S|
Feillet|Francois|F|
Isidor|Bertrand|B|

LSS
alopecia
intellectual disability
cholesterol pathway
early-onset epileptic encephalopathy


How to share data for collaboration.

Abstract: Within the statistics community, a number of guiding principles for sharing data have emerged; however, these principles are not always made clear to collaborators generating the data. To bridge this divide, we have established a set of guidelines for sharing data. In these, we highlight the need to provide raw data to the statistician, the importance of consistent formatting, and the necessity of including all essential experimental information and pre-processing steps carried out to the statistician. With these guidelines we hope to avoid errors and delays in data analysis.

guidelines
statistician
analysis
data sharing
tidy data


Adherence to a procalcitonin-guided antibiotic treatment protocol in patients with severe sepsis and septic shock.

Abstract:
BACKGROUND
In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed.

METHODS
From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT < 0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes.

RESULTS
Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p = 0.001) and peak PCT levels (p < 0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p = 0.002). No differences were seen in terms of other clinical outcomes.

CONCLUSION
In patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing.

Sepsis
Procalcitonin
Protocol adherence
Antibiotic consumption


Extension Block Pinning Versus Hook Plate Fixation for Treatment of Mallet Fractures.

Abstract:
PURPOSE
To compare the outcomes and associated costs of the treatment of mallet fractures with either extension block pinning or open reduction and hook plate fixation.

METHODS
We treated 22 patients for a mallet fracture that involved at least 25% of the distal phalanx articular surface. Three joints demonstrated concomitant volar subluxation. Extension block pinning was used to treat 16 fractures (group 1) and 6 were treated with open reduction and hook plate fixation (group 2). All patients were evaluated at the second, fourth, and sixth weeks after surgery. Collected data included range of motion, extensor lag, and pain status. Patients were asked to grade preoperative and postoperative pain levels on a visual analog scale. Functional outcomes were determined by Crawford criteria. We retrospectively performed a cost analysis using our institutional records.

RESULTS
Mean follow-up was 12.7 months. Visual analog scale pain scores improved by a similar amount for both groups. Preoperative pain scores were 7.0 for group 1 and 7.5 for group 2. Postoperative levels were 2.0 and 2.0, respectively. Mean extensor lag was identical for both groups, 5°. Mean flexion was 70° for group 1 and 80° for group 2. Based on the Crawford criteria, group 1 had 5 patients rated as excellent, 6 as good, 3 as fair, and 2 as poor. Group 2 outcomes were 2 excellent, 2 good, and 2 fair. Five complications occurred in group 1, and 1 in group 2. Differences noted between groups were not statistically significant. Extension block pinning was more cost-effective than hook plate fixation.

CONCLUSIONS
We find extension block pinning to be an equally effective but more cost-efficient treatment than open reduction and hook plate fixation.

TYPE OF STUDY/LEVEL OF EVIDENCE
Therapeutic III.

Toker|Serdar|S| Türkmen|Faik|F| Pekince|Oğuzhan|O| Korucu|İsmail|İ| Karalezli|Nazım|N|

D000293:Adolescent
D000328:Adult
D001860:Bone Plates
D005260:Female
D050278:Finger Phalanges
D005500:Follow-Up Studies
D005593:Fracture Fixation, Internal
D050723:Fractures, Bone
D006801:Humans
D057072:Intra-Articular Fractures
D008297:Male
D008875:Middle Aged
D016059:Range of Motion, Articular
D012189:Retrospective Studies
D016896:Treatment Outcome
D055815:Young Adult

Extension block pinning
hook plate
mallet fracture


Role of Periarticular Liposomal Bupivacaine Infiltration in Patients Undergoing Total Knee Arthroplasty-A Meta-analysis of Comparative Trials.

Abstract:
BACKGROUND
Over last 2 years, many trials have evaluated newly approved liposomal bupivacaine for periarticular infiltration in total knee arthroplasty (TKA) with mixed results. Our meta-analysis attempts to consolidate the results and make evidence-based conclusions.

METHODS
Trails comparing periarticular infiltration of liposomal bupivacaine to conventional analgesic regimens for total knee arthroplasty published till June 2016 were searched in medical database. Comparisons were made for length of stay (LOS), postoperative pain scores, range of motion, and opioid consumption. Meta-regression was performed for LOS to evaluate various analgesic control subgroups.

RESULTS
Sixteen trials were included in the final analysis. Liposomal bupivacaine group showed a shorter LOS (reported in 13 subgroups) than control group by 0.17 ± 0.04 days (random effects, P < .001, I2 = 84.66%). Meta-regression for various types of control showed a predictability (R2) of 73%, τ2 = 0.013 (random effects, P < .001, I2 = 45.16). Only femoral block subgroup attained statistically significant shorter LOS on splitting the control group. Numeric pain scores were lower for pooled control group and local anesthetic infiltration subgroup in immediate postoperative phase. Second postoperative day analgesia was statistically superior to overall clubbed controls and femoral block subgroup. Superiority and/or inferiority of liposomal bupivacaine could not be proven for opioid consumption and range of motion because of a small pooled sample size. Publication bias is likely for LOS (Egger test, X intercept = 2.42, P < .001).

CONCLUSION
Liposomal bupivacaine infiltration has questionable clinical advantage, as it marginally shortens patient's hospital stay especially in comparison with patients receiving analgesic femoral nerve block. Compared with conventional regimens, it can provide slightly superior yet sustained (till second postoperative day) perioperative analgesia. High heterogeneity suggests need for standardization of infiltration techniques for better predictability of results.

Singh|Preet Mohinder|PM|
Borle|Anuradha|A|
Trikha|Anjan|A|
Michos|Lia|L|
Sinha|Ashish|A|
Goudra|Basavana|B|

D000701:Analgesics, Opioid
D000772:Anesthesia, Local
D000779:Anesthetics, Local
D019645:Arthroplasty, Replacement, Knee
D002045:Bupivacaine
D006801:Humans
D007902:Length of Stay
D008081:Liposomes
D009407:Nerve Block
D010149:Pain, Postoperative
D011184:Postoperative Period
D016059:Range of Motion, Articular

liposomal bupivacaine
total knee arthroplasty
analgesia arthroplasty
arthroplasty analgesia
liposomal bupivacaine infilteration
meta-analysis knee


Misinterpretation of the Borg's Rating of Perceived Exertion Scale by patients with panic disorder during ergospirometry challenge.

Abstract:
INTRODUCTION
The most widely used instrument to measure perceived exertion or exercise intensity is the Borg's Rating of Perceived Exertion (RPE) Scale. Panic attacks are aversive experiences that may be triggered by bodily sensations such as palpitations, breathlessness or dizziness due to increasing autonomic distress, prior sensitisation to panic and fear conditioning. The consequence is catastrophic interpretation of bodily sensations of arousal in general, which can lead to misinterpretation of exertion or exercise intensity.

PURPOSE
To verify the effectiveness of the Borg's RPE Scale as a measure of perceived effort in panic disorder subjects.

METHODS
The study enrolled 72 subjects: the control group (C, healthy sedentary subjects, n=30) and patients with panic disorder (PD, n=42). All subjects were submitted to an ergospirometry challenge. Perceived exertion RPE scores and heart rate at 90% VO2max were compared between groups.

RESULTS
Patients with PD showed lower levels of maximal oxygen consumption, when compared with C group [VO2max (mL/kg/min): PD=29.42±6.50xC=34.51±5.35; Student's t-test=-3.51; p <0.05]. Furthermore, among PD subjects, the maximum heart rate during ergospirometry challenge was lower than expected [predict max HR (bpm)=200.85±6.33xheart rate test (bpm)=178.86±7.28; Z=-5.64; p<0.05]. Perceived exertion, as measured by RPE, was also overestimated in relation to heart rate at 90% of maximum oxygen consumption compared with controls (RPE90%VO2max: PD=18.93±0.55xC=16.67±0.60; U=8.00; Z=7.42; p<0.05).

CONCLUSIONS
The present study findings suggest that the Borg's RPE Scale may not be an appropriate measure of subjective exertion among subjects with panic disorder performing a cardiopulmonary exercise test.

Muotri|Ricardo William|RW|
Bernik|Marcio Antonini|MA|
Neto|Francisco Lotufo|FL|

Misinterpretation
Panic Disorder
Ergospirometry
Anxiety Disorders
Borg´s Scale


Factors associated with the number and size of renal angiomyolipomas in sporadic angiomyolipoma (sAML): a study of adult patients with sAML managed in a Dutch tertiary referral center.

Abstract:
PURPOSE
To describe the patient characteristics, treatments, disease monitoring, and kidney function of patients with sporadic angiomyolipoma (sAML), stratified by the number and size of renal angiomyolipomas (AMLs).

METHODS
Single-center retrospective analysis of patients with sAML treated from 1990 to 2015 in a dedicated clinic for inheritable tumor syndromes in a tertiary referral center from the Netherlands. Patients' first AML assessment at the clinic was defined as the index date. Patient characteristics were measured at the index date. Treatments, disease monitoring, and kidney function were measured post-index date.

RESULTS
The study sample included 53 patients followed for a total of 184.6 patient-years. At the index date, the largest AML was ≥ 3.5 cm for 26 patients and < 3.5 cm for 27 patients (including six patients with five or more AMLs of < 3.5 cm). As compared to patients with AMLs < 3.5 cm, patients with largest AML ≥ 3.5 cm had higher frequency of pre-index bleeding episodes (31 vs. 4%), pre-index hypertension (35 vs. 15%), post-index nephrectomy (19 vs. 4%), post-index embolization (8 vs. 0%), and post-index renal scans (1.14 vs. 0.74 scans/year). Kidney impairment was especially pronounced in young adults with AML ≥ 3.5 cm. On average, patients with sAML developed chronic kidney disease stage two earlier than the general Dutch population (age 42 vs. 55 years), but later than the patients with tuberous sclerosis complex (35 years).

CONCLUSIONS
Patients with sAML, especially those with larger AMLs, have high disease burden.

Angiomyolipoma
Treatment
Disease monitoring
Kidney function


Polymorphs, co-crystal structure and pharmacodynamics study of MBRI-001, a deuterium-substituted plinabulin derivative as a tubulin polymerization inhibitor.

Abstract: MBRI-001, a deuterium-substituted plinabulin derivative, has been reported to have better pharmacokinetic and similar antitumor effects in comparison with plinabulin. In this approach, we further carried out its polymorphs, co-crystal structure of MBRI-001-tubulin and tubulin inhibition study. Among the different polymorphs, Form F (MBRI-001/H2O) was prepared and evaluated, which had better physical stability and suitable process for scale-up production. Co-crystal structure of MBRI-001-tubulin (PDB:5XI5) was prepared and analyzed. The result of tubulin polymerization assay demonstrated that MBRI-001 could inhibit tubulin polymerization which was similar as plinabulin. Subsequently, the anti-proliferative activities of plinabulin and MBRI-001 were evaluated against two different human lung cancer cell lines. In vivo study, MBRI-001 revealed similar antitumor inhibition in comparison with plinabulin in A549 xenograft tumor model. Therefore, we suggested that MBRI-001 could be developed as a promising anti-cancer agent in near future.

Ma|Mingxu|M| Ding|Zhongpeng|Z| Wang|Shixiao|S| Ma|Lingling|L| Wang|Yuxi|Y| Zhong|Lili|L| Li|Zhongping|Z| Yang|Jinliang|J| Li|Wenbao|W|

Polymorphs
Co-crystal structure
MBRI-001
Tubulin inhibition
Anti-cancer agent


Transcatheter valve implantation for degenerated tricuspid bioprosthesis and failed tricuspid ring.

Abstract:
Background
Transcatheter tricuspid valve-in-valve (TViV) and valve in-ring (TViR) implantation have become a viable therapy for a failed tricuspid bioprosthesis. Here we report short (thirty days) and long (one-year) term clinical outcomes of ten patients who underwent TViV at our institution.

Methods
The electronic databases of New York Presbyterian Columbia Medical Center were retrospectively reviewed for cases of transcatheter tricuspid valve replacement (TViV or TViR). Between 2012 and 2019, data from ten patients who underwent TViV were collected. The primary safety outcome was procedure-related adverse events, including clinically evident cardiac perforation, new pericardial effusion and sustained ventricular arrhythmia. The primary efficacy endpoint was defined as successful valve deployment with total (paravalvular or intravalvular) tricuspid regurgitation (TR) estimated as mild or less. Results are descriptive in nature.

Results
A total of ten patients who underwent TViV were included in the study. Of them, 40% presented with isolated tricuspid bioprosthetic stenosis (TS), 20% with isolated TR and 40% with mixed TS and TR. All patients were treated with the SAPIEN valve (first generation, XT, or Sapien 3). The TViV procedure was successful in all patients, and no immediate post-replacement paravalvular leak (PVL) or intra-procedural complications were reported. The primary safety and efficacy endpoints were met in all patients. At thirty-days, all patients were alive and reported significant improvements in symptoms and functional status.

Conclusions
Transcatheter tricuspid valve implantation is a safe and effective therapy for degenerative tricuspid bioprosthesis.

Transcatheter tricuspid valve replacement


Circadian disruption in the pathogenesis of metabolic syndrome.

Abstract: Metabolic syndrome is a multifactorial process induced by a combination of genetic and environmental factors and recent evidence has highlighted that circadian disruption and sleep loss contribute to disease pathogenesis. Emerging work in experimental genetic models has provided insight into the mechanistic basis for clock disruption in disease. Indeed, disruption of the clock system perturbs both neuroendocrine pathways within the hypothalamus important in feeding and energetics, in addition to peripheral tissues involved in glucose and lipid metabolism. This review illustrates the impact of molecular clock disruptions at the level of both brain and behavior and peripheral tissues, with a focus on how such dysregulation in turn impacts lipid and glucose homeostasis, inflammation and cardiovascular function. New insight into circadian biology may ultimately lead to improved therapeutics for metabolic syndrome and cardiovascular disease in humans.

Metabolism
Cardiovascular disease
Circadian rhythm


Antioxidant farnesylated hydroquinones from Ganoderma capense.

Abstract: Phytochemical investigation of the fruiting bodies of Ganoderma capense led to isolation of eight aromatic meroterpenoids (1-8). Ganocapensins A and B (1, 2) possessed a thirteen-membered and a fourteen-membered ether rings, respectively. The structures of new isolates including absolute configuration were elucidated on the basis of extensive spectroscopic technologies and Mosher's method. All isolated compounds showed significant antioxidant effects with IC50 values ranging from 6.00±0.11 to 8.20±0.30μg/ml in the DPPH radical scavenging assay.

Peng|Xingrong|X| Li|Lei|L| Wang|Xia|X| Zhu|Guolei|G| Li|Zhongrong|Z| Qiu|Minghua|M|

Ganoderma capense
Aromatic meroterpenoid
Antioxidant activity
Macrocyclic aromatic meroterpenoid


Superior antihypertensive and cardioprotective effects of chlorthalidone compared with hydrochlorothiazide.

Abstract: Diuretics are the most commonly used drugs for the treatment of hypertension, either alone or in combination with other antihypertensive drugs. Of all diuretics, hydrochlorothiazide (HCTZ) and chlorthalidone (CTD) are the most commonly used, with HCTZ being the most widely prescribed diuretic. Recent studies have shown that CTD is a better diuretic with superior antihypertensive effectiveness and cardiovascular protection. Although these diuretics are chemically, pharmacokinetically and pharmacodynamically different, CTD continues to be called a "thiazide-like" diuretic. The only common features they both share are a sulfhydryl group in their molecules and their common mechanism and site of diuretic action. In order to get a better understanding of the true pharmacologic actions as well as the benefits and risks of these diuretics, a MEDLINE search of the English language literature between 1964 and January 2021 was conducted, using the terms "diuretics", "hydrochlorothiazide", "chlorthalidone", "hypertension", "cardiovascular disease" and "treatment". From this search, 28 pertinent papers were selected and they will be discussed in this review together with collateral literature. The analysis of results revealed that CTD is superior to HCTZ in antihypertensive effectiveness and cardioprotection and should be the preferred diuretic for the treatment of hypertension.

Chlorthalidone
Hydrochlorothiazide
Diuretics
Treatment of hypertension
Cardiovascular disease


Oral Teratoma with a Primitive Neuroectodermal Tumor Component: A Case Report.

Abstract: Teratomas are tumors of germ cell derivation consist of tissues derived from all the three germ cell layers. They comprise the most common extragonadal germ cell tumors (EGCT) in childhood. EGCTs of head and neck region account for only 5% of all benign and malignant germ cell tumors and for 6% of all teratomas. Primitive neuroectodermal tumor (PNET) arising from germ cell tumor is a distinct entity. It develops from the malignant transformation of teratomas along ectodermal lines. This paper presents a rare case of oral teratoma in a 6-year-old male who reported with pain and swelling in the right upper back teeth region of jaw. Under light microscopy, mature and immature structures representatives of trilineage derivatives were appreciated. Sheets of small round cells showing vague rosette and membranous positivity to CD-99 directed us to consider the above diagnosis.

Acharya|Swetha|S| Tayaar|Amsavardani|A| Adirajaiah|Sahana|S| Kulandswamy|Gopalkrishnan|G|

Oral teratoma
Primitive neuroectodermal tumor
Childhood.
Small round cell tumor


Comparing three-dimensional models of placenta accreta spectrum with surgical findings.

Abstract:
OBJECTIVE
Placenta accreta spectrum (PAS) is associated with significant maternal morbidity mainly related to blood loss. Pre-operative planning is aided by antenatal ultrasound and magnetic resonance imaging. We sought to assess whether three-dimensional (3D) models from MR images were accurate when compared with surgical and pathological findings.

METHODS
Digital Imaging and Communications in Medicine files containing MR images with varying severity of PAS (n = 4) were modeled using 3D Slicer. Placenta, bladder, and myometrial defects were modeled. Myometrial defects at three different uterine locations were included-anterior, lateral and inferior. 3D models were used to identify the relationship between the myometrial defect and the internal cervical os. Findings were validated in a larger series of PAS cases (n = 14) where patterns of invasion were compared with estimated blood loss and distance from defect to the internal os.

RESULTS
The defect illustrated in the four 3D models correlates to both surgical and pathological findings in terms of depth and pattern of invasion, location of defect, bladder involvement. Blood loss and topography of the defect from 3D modeling were examined in 14 further cases. Inferior defects were associated with increased blood loss compared with anterior defects. Increased distance from cervix was associated with reduced blood loss (R2  = 0.352, P = 0.01).

CONCLUSION
Three-dimensional models of PAS provide an accurate preoperative description of placental invasion and should be investigated as a tool for selecting patients for uterine-conserving surgery. Accurate 3D models of placenta accreta spectrum are achievable and may provide additional information, such as distance of the defect from the internal os.

placenta accreta spectrum
3D modeling
MRI-generated images
surgical planning


Acute traumatic coagulopathy: clinical characterization and mechanistic investigation.

Abstract: Trauma remains the leading cause of death and morbidity worldwide and bleeding is the primary reason for this mortality. Over the past 11 years there has been a paradigm shift in our understanding of coagulopathy after trauma. Specifically its incidence, biological drivers, clinical sequelae have been elucidated. From this understanding a concurrent change in resuscitation practices has occurred. This manuscript will review the history of resuscitation after injury, the discovery and clinical and biological characterization of acute traumatic coagulopathy and the changes in resuscitation practices aimed at combating coagulopathy and inflammatory perturbation after trauma. Finally it will discuss the ongoing state of the science and suggest topics for continued biological and clinical study.

Coagulopathy
Trauma
Bleeding
Resuscitation
Coagulation
Protein C