Lentiviral MGMT(P140K)-mediated in vivo selection employing a ubiquitous chromatin opening element (A2UCOE) linked to a cellular promoter.

Abstract: Notwithstanding recent successes, insertional mutagenesis as well as silencing and variegation of transgene expression still represent considerable obstacles to hematopoietic gene therapy. This also applies to O(6)-methylguanine DNA methyltransferase (MGMT)-mediated myeloprotection, a concept recently proven clinically effective in the context of glioblastoma therapy. To improve on this situation we here evaluate a SIN-lentiviral vector expressing the MGMT(P140K)-cDNA from a combined A2UCOE/PGK-promoter. In a murine in vivo chemoselection model the A2UCOE.PGK.MGMT construct allowed for significant myeloprotection as well as robust and stable selection of transgenic hematopoietic cells. In contrast, only transient enrichment and severe myelotoxicity was observed for a PGK.MGMT control vector. Selection of A2UCOE.PGK.MGMT-transduced myeloid and lymphoid mature and progenitor cells was demonstrated in the peripheral blood, bone marrow, spleen, and thymus. Unlike the PGK and SFFV promoters used as controls, the A2UCOE.PGK promoter allowed for sustained vector copy number-related transgene expression throughout the experiment indicating an increased resistance to silencing, which was further confirmed by CpG methylation studies of the PGK promoter. Thus, our data support a potential role of the A2UCOE.PGK.MGMT-vector in future MGMT-based myeloprotection and chemoselection strategies, and underlines the suitability of the A2UCOE element to stabilize lentiviral transgene expression in hematopoietic gene therapy.

Phaltane|Ruhi|R| Lachmann|Nico|N| Brennig|Sebastian|S| Ackermann|Mania|M| Modlich|Ute|U| Moritz|Thomas|T|

Gene therapy
In vivo selection
Lentiviral vector
MGMT
UCOE


Effect of Sterilization on Cyclic Fatigue Resistance of Proflexendo Endodontic Rotary Files.

Abstract:
Background
Proflexendo file (Nexen, Houston, TX, USA) is a recently developed, novel nickel-titanium rotary file. However, several physical properties of the Proflexendo system remain to be investigated.

Objectives
The aim of this study was to determine the effect of sterilization on cyclic resistance of Proflexendo files.

Material and Methods
A total of 120 unused Proflexendo rotary files (40 each of file sizes 40/0.04, 30/0.04 and 20/0.06) were used in this study. Each set of files was subdivided into four groups of ten files. Group 1 did not undergo any sterilization (control), Group 2 underwent two rounds (2×) of sterilization, Group 3 five rounds (5×) and Group 4 ten rounds (10×). Cyclic fatigue resistance was tested using an artificial canal with a 5-mm radius curve.

Results
The nonsterilized size 30/0.04 files had the highest cycles to failure, followed by the nonsterilized size 40/0.04 and 20/0.06 files (P < 0.001). With increasing rounds of sterilization, cycles to failure reduced for sizes 40 (2×, 5× and 10×) and 30 (2×) files compared with nonsterilized sizes 40 (P < 0.05) and 30 files (P < 0.001), respectively.

Conclusion
Under the conditions of the current study, the results provide preliminary evidence that autoclave sterilization of Proflexendo rotary files reduced their cyclic fatigue resistance, except for size 20 (2× and 5×) and 30 (10×) files, in which resistance increased. Single use of this file is recommended to reduce the risk of separation.

sterilization
Cyclic fatigue
Proflexendo
endodontic rotary file
nickel-titanium


Remarkable Impact of Acidic Ginsenosides and Organic Acids on Ginsenoside Transformation from Fresh Ginseng to Red Ginseng.

Abstract: Panax ginseng contains many chemical components, including acidic ginsenosides and organic acids. However, whether these acidic substances play a role in ginsenoside transformation during steaming treatment has not yet been explored. In this paper, the content of neutral ginsenosides, acidic ginsenosides, and their degradation products in unsteamed and steamed P. ginseng were simultaneously quantified by high-performance liquid chromatography. We observed that neutral ginsenosides were converted to rare ginsenosides during the root steaming but not during the individual ginsenoside steaming. In contrast, acidic malonyl ginsenosides released malonic acid and acetic acid through demalonylation, decarboxylation, deacetylation reactions during the steaming at 120 °C. These malonyl ginsenosides not only were converted to rare ginsenosides but also promoted the degradation of neutral ginsenosides. Further studies indicated that a low concentration of organic acid was the determining factor for the ginsenoside conversion. The related mechanisms were deduced to be mainly acidic hydrolysis and dehydration. In summary, acidic ginsenosides and organic acids remarkably affected ginsenoside transformation during the steaming process. Our results provide useful information for precisely understanding the ginsenoside conversion pathways and mechanisms underlying the steaming process.

Liu|Zhi|Z| Xia|Juan|J| Wang|Chong-Zhi|CZ| Zhang|Jin-Qiu|JQ| Ruan|Chang-Chun|CC| Sun|Guang-Zhi|GZ| Yuan|Chun-Su|CS|

D004339:Drug Compounding
D036145:Ginsenosides
D006358:Hot Temperature
D015394:Molecular Structure
D009930:Organic Chemicals
D005894:Panax
D010936:Plant Extracts

acidic ginsenosides
organic acids
ginsenoside transformation
red ginseng
steaming treatment


The atrazine metabolite diaminochlorotriazine suppresses LH release from murine LβT2 cells by suppressing GnRH-induced intracellular calcium transients.

Abstract: The primary metabolite of the herbicide atrazine (ATRA), diaminochlorotriazine (DACT), has been suggested to cause disruption in the hypothalamic-pituitary-gonadal axis leading to inhibition of luteinizing hormone (LH) release. DACT is a reactive electrophile known to form covalent protein adducts both in vitro and in vivo following ATRA exposure and maybe targeting proteins involved in GnRH-induced calcium signaling and subsequent LH release. To test this hypothesis, LβT2 pituitary cells were exposed to 300 μM DACT for 24 hrs and examined by fluorescence microscopy for GnRH-induced changes in intracellular calcium and LH release. LβT2 cells exposed to DACT had markedly diminished GnRH-induced intracellular calcium transients and a significant decreased LH release in response to GnRH. DACT appeared to cause a selective decrease in caffeine-sensitive ryanodine receptor-operated calcium stores in LβT2 cells, rather than in thapsigargin-sensitive ER calcium stores. This sensitivity correlated with the formation of covalent protein adducts by DACT, as determined by mass spectrometry. ERp57 was identified by mass spectrometry as a target of DACT adduction in the ER that could potentially mediate the effects of DACT on inhibition of GnRH-induced calcium signaling and inhibition of LH release. Intracellular calcium responses to GnRH and release of LH were restored in DACT-treated cells with the addition of a calcium ionophore (A23187). These data suggest that DACT forms adducts on proteins involved in calcium handling within the ER and that dysfunction in this critical signaling system is associated with loss of normal sensitivity to GnRH and subsequent decreased release of LH.

Dooley|Gregory P|GP|
Tjalkens|Ronald B|RB|
Hanneman|William H|WH|

atrazine
DACT
protein adducts
brain
chlorotriazines


The Road to the Alcohol Act 2018 in Finland: A conflict between public health objectives and neoliberal goals.

Abstract: Finnish alcohol policy has aimed for decades years to mitigate alcohol-related harm by using high taxation and restrictions on the physical availability of alcohol. The state monopoly on the retail of alcohol has played a central role in reducing the availability of alcohol. In 2011, preparations began for a comprehensive reform of the Alcohol Act 1994. Over time, the issue became highly politicised, lobbied and divisive. It took intense work of two consecutive governments to finalise the reform. The new Alcohol Act came into force in 2018. It expanded the rights of grocery stores to sell alcohol and reduced the administrative burden for on-premise sales. As a result, the state monopoly on the retail of alcohol was weakened, but it still has an important impact on the physical availability of alcohol. The Finnish public health community expected an increase in alcohol sales following the reform because of greater alcohol availability and expected price reductions related to greater competition of sales in grocery stores. However, prices decreased less than expected in 2018, partly due to a simultaneous increase in alcohol taxes. It is difficult to evaluate the impact of the reform at this early stage. However, after the reform, the 10-year (2008-2017) downward trend in the total per capita alcohol consumption was discontinued despite the tax increase. According to preliminary analyses, the change in the law may have slightly increased recorded alcohol sales but the effect was not statistically significant.

Karlsson|Thomas|T| Mäkelä|Pia|P| Tigerstedt|Christoffer|C| Keskimäki|Ilmo|I|

Finland
Public health
Harm
Alchol policy
Alchol related
Alcohol control
Policy reform


Maternal occupational exposure to endocrine-disrupting chemicals and urogenital anomalies in the offspring.

Abstract:
STUDY QUESTION
Is there an association between maternal occupational exposure to endocrine-disrupting chemicals (EDCs) early in pregnancy and subgroups of congenital anomalies of kidney and urinary tract (CAKUT), and hypospadias?

SUMMARY ANSWER
Exposure to specific EDCs can increase the risk of CAKUT and no association with hypospadias was observed.

WHAT IS KNOWN ALREADY
Previous studies showed an association between maternal occupational exposure to EDCs and hypospadias. However, little is known about the effect of these chemicals on the development of CAKUT, especially subgroups of urinary tract anomalies.

STUDY DESIGN, SIZE, DURATION
For this case-control study, cases with urogenital anomalies from the European Concerted Action on Congenital Anomalies and Twins Northern Netherlands (Eurocat NNL) registry and non-malformed controls from the Lifelines children cohort (living in the same catchment region as Eurocat NNL) born between 1997 and 2013 were selected. This study included 530 cases with CAKUT, 364 cases with hypospadias, 7 cases with both a urinary tract anomaly and hypospadias and 5602 non-malformed controls. Cases with a genetic or chromosomal anomaly were excluded, and to avoid genetic correlation, we also excluded cases in which a sibling with the same defect was included.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Information on maternal occupation held early in pregnancy was collected via self-administered questionnaires. Job titles were translated into occupational exposure to EDCs using a job-exposure matrix (JEM). Adjusted odds ratios (aORs) and 95% CIs were estimated to assess the association between maternal occupational exposure to EDCs (and to specific types of EDCs) and CAKUT and hypospadias.

MAIN RESULTS AND THE ROLE OF CHANCE
For CAKUT and hypospadias, 23.1% and 22.9% of the cases were exposed to EDCs, respectively, whereas 19.8% of the controls were exposed. We found an association between maternal occupational exposure to organic solvents/alkylphenolic compounds and CAKUT (aOR 1.41, 95% CI 1.01-1.97) that became stronger when combinations of urinary tract anomalies co-occurred with other defects (aOR 7.51, 95% CI 2.41-23.43). An association was also observed for exposure to phthalates/benzophenones/parabens/siloxanes and CAKUT (aOR 1.56, 95% CI 1.06-2.29), specifically urinary collecting system anomalies (aOR 1.62, 95% CI 1.03-2.54) and combinations of urinary tract anomalies (aOR 2.90, 95% CI 1.09-7.71). We observed no association between EDC exposure and hypospadias.

LIMITATIONS, REASONS FOR CAUTION
The different study designs of Eurocat NNL and Lifelines could have introduced differential information bias. Also, exposure misclassification could be an issue: it is possible that the actual exposure differed from the exposure estimated by the JEM. In addition, women could also have been exposed to other exposures not included in the analysis, which could have resulted in residual confounding by co-exposures.

WIDER IMPLICATIONS OF THE FINDINGS
Women, their healthcare providers, and their employers need to be aware that occupational exposure to specific EDCs early in pregnancy may be associated with CAKUT in their offspring. An occupational hygienist should be consulted in order to take exposure to those specific EDCs into consideration when risk assessments are carried out at the workplace.

STUDY FUNDING/COMPETING INTEREST(S)
N.S. was paid by the Graduate School of Medical Sciences (MD/PhD programme), University Medical Center Groningen (UMCG), Groningen, the Netherlands. Eurocat Northern Netherlands is funded by the Dutch Ministry of Health, Welfare and Sports. The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), University Groningen and the Northern Provinces of the Netherlands. The authors report no conflict of interest.

TRIAL REGISTRATION NO
N/A.

Spinder|N|N|0000-0002-7841-8007
Bergman|J E H|JEH|
van Tongeren|M|M|
Boezen|H M|HM|
Kromhout|H|H|
de Walle|H E K|HEK|


Management of Cardiac Toxicity Induced by Chemotherapy.

Abstract: Cardiotoxicity encompasses a spectrum of adverse cardiological effects experienced by cancer patients during and after receiving antineoplastic treatments. The intersection of cancer care with the management of the multiple comorbid non-communicable diseases carried by patients or related to cancer treatments motivates the need for an integrated and multidisciplinary approach to therapeutic clinical decision-making. This present review aimed to provide a perspective and an update of the current pharmacotherapy approaches for the prevention and management of cardiotoxicity from antiblastic chemotherapy; as such, it addresses myocardial, vascular, and arrhythmic disorders associated to chemotherapy, by navigating the current knowledge and clinical indications in support of the medical interventions. Clinical scenarios of pharmacological interventions take place with patients receiving anthracycline and, by extrapolation, other agents with cardiotoxic potentials and non-chemotherapy agents, including various small molecules and immunotherapy agents. Analysis of these scenarios aims to provide practical evidence-based guidance for the management of drug-induced cardiac dysfunctions. The possible role of new biomarkers for the early recognition of cardiotoxicity is mentioned across the clinical studies, with reference to the pharmacological biomarker-driven interventions delivered. To best inform survivorship care, the management and context of cardio-oncology services are discussed within the broader network of providers and settings of care.

Trapani|Dario|D| Zagami|Paola|P| Nicolò|Eleonora|E| Pravettoni|Gabriella|G| Curigliano|Giuseppe|G|

chemotherapy
cardiotoxicity
pharmacotherapy
cardio-oncology
treatment-related adverse events


The Weight of Emotions in Decision-Making: How Fearful and Happy Facial Stimuli Modulate Action Readiness of Goal-Directed Actions.

Abstract: Modern theories of behavioral control converge with the idea that goal-directed/voluntary behaviors are intimately tied to the evaluation of resources. Of key relevance in the decision-making processes that underlie action selection are those stimuli that bear emotional content. However, even though it is acknowledged that emotional information affects behavioral control, the exact way in which emotions impact on action planning is largely unknown. To clarify this issue, I gave an emotional version of a go/no-go task to healthy participants, in which they had to perform the same arm reaching movement when pictures of fearful or happy faces were presented, and to withhold it when pictures of faces with neutral expressions were presented. This task allows for the investigation of the effects of emotional stimuli when they are task-relevant without conflating movement planning with target detection and task switching. It was found that both the reaction times (RTs) and the percentages of errors increased when the go-signal was the image of a fearful looking face, as opposed to when the go-signal was a happy looking face. Importantly, to control for the role of the features of the stimuli, I ran a control task in which the same pictures were shown; however, participants had to move/withhold the commanded movement according to gender, disregarding the emotional valence. In this context, the differences between RTs and error percentages between the fearful and happy faces disappeared. On the one hand, these results suggest that fearful facial stimuli are likely to capture and hold attention more strongly than faces that express happiness, which could serve to increase vigilance for detecting a potential threat in an observer's environment. On the other hand, they also suggest that the influence of fearful facial stimuli is not automatic, but it depends on the task requirements.

emotion
go/no-go task
decision making
motor control
reaching arm movements


Phase II study of cetuximab plus S-1/cisplatin therapy in Japanese patients with advanced gastric cancer.

Abstract:
OBJECTIVE
We evaluated the efficacy and safety of first-line S-1 plus cisplatin in combination with cetuximab for Japanese patients with advanced gastric cancer, including gastroesophageal junction adenocarcinoma.

METHODS
This open-label, single arm, multicenter, phase 2 trial was conducted to assess first-line cetuximab plus S-1 plus cisplatin for advanced gastric cancer. A total of 40 patients from 10 centers were enrolled. Cetuximab was administered weekly, with the initial infusion at 400 mg/m2 and then 250 mg/m2 each subsequent week. S-1 plus cisplatin chemotherapy was concomitantly conducted in a 5-week cycle: S-1 (40-60 mg, adjusted for body surface area) was given twice daily for 3 consecutive weeks, followed by a 2-week rest period, and cisplatin (60 mg/m2) was given on day 8 of each cycle for a maximum of 8 cycles. Treatment continued until the occurrence of radiographically confirmed progressive disease, unacceptable toxicity or withdrawal of consent. The primary endpoint was the best overall response. Secondary endpoints included progression-free survival and safety.

RESULTS
A total of 40 patients were evaluable. One patient (2.5%) had a complete response; 15 patients (37.5%) had a partial response. The observed overall response rate according to the independent review committee was 40.0% (95% confidence interval, 24.9-56.7; P = 0.7043 [one-sided null hypothesis: overall response rate ≤ 43%]); median PFS was 5.6 months (95% confidence intervals, 4.2-8.3). No adverse events leading to death were reported during the study, and no specific safety concerns were observed.

CONCLUSIONS
Overall, the addition of cetuximab to S-1 plus cisplatin was well tolerated in patients with advanced gastric cancer but provided no additional clinical benefit in this study. ClinicalTrials.gov identifier: NCT01388790.

Yamaguchi|Kensei|K|0000-0001-6887-5709 Fuse|Nozomu|N| Komatsu|Yoshito|Y| Fujii|Hirofumi|H| Hironaka|Shuichi|S| Omuro|Yasushi|Y| Muro|Kei|K| Yasui|Hirofumi|H| Ueda|Shinya|S| Nishina|Tomohiro|T| Watanabe|Morihiro|M| Ohtsu|Atsushi|A|

D000971:Antineoplastic Combined Chemotherapy Protocols

cetuximab
S-1
cisplatin
stomach neoplasms
tegafur-gimeracil-oteracil


Receipt of pharmacotherapy for opioid use disorder by justice-involved U.S. Veterans Health Administration patients.

Abstract:
BACKGROUND
Pharmacotherapy - methadone, buprenorphine, or naltrexone - is an evidence-based treatment for opioid use disorder, but little is known about receipt of these medications among veterans involved in the justice system. The current study examines receipt of pharmacotherapy for opioid use disorder among veterans with a history of justice involvement at U.S. Veterans Health Administration (VHA) facilities compared to veterans with no justice involvement.

METHODS
Using national VHA clinical and pharmacy records, we conducted a retrospective cohort study of veterans with an opioid use disorder diagnosis in fiscal year 2012. Using a mixed-effects logistic regression model, we examined receipt of pharmacotherapy in the 1-year period following diagnosis as a function of justice involvement, adjusting for patient and facility characteristics.

RESULTS
The 1-year rate of receipt for pharmacotherapy for opioid use disorder was 27% for prison-involved veterans, 34% for jail/court-involved veterans, and 33% for veterans not justice-involved. Compared to veterans not justice-involved, those prison-involved had 0.75 lower adjusted odds (95% confidence interval [CI]: 0.65-0.87) of receiving pharmacotherapy whereas jail/court-involved veterans did not have significantly different adjusted odds.

CONCLUSIONS
Targeted efforts to improve receipt of pharmacotherapy for opioid use disorder among veterans exiting prison is needed as they have lower odds of receiving these medications.

Finlay|Andrea K|AK|
Harris|Alex H S|AH|
Rosenthal|Joel|J|
Blue-Howells|Jessica|J|
Clark|Sean|S|
McGuire|Jim|J|
Timko|Christine|C|
Frayne|Susan M|SM|
Smelson|David|D|
Oliva|Elizabeth|E|
Binswanger|Ingrid|I|

D014493:United States Department of Veterans Affairs


Suspected Gentamicin-Induced Retinal Vascular Occlusion after Vitrectomy.

Abstract: Retinal vascular occlusion after ocular surgery is a rare but serious complication. A history of cardiovascular diseases, retrobulbar anesthesia injection, high intraocular pressure during the perioperative period, and drug toxicity have been reported as possible causative factors. We report here two cases of multiple retinal vascular occlusions after the subconjunctival injection of gentamicin at the end of uncomplicated 25-gauge vitrectomy. Case 1 was a 61-year-old man who developed a macular hole in the right eye. Phacovitrectomy with gas tamponade was performed. On postoperative day (POD) 1, dot hemorrhage was observed on the temporal side of the optic disk. On POD10, macular whitening, retinal hemorrhage, and multiple occlusion of retinal arteries and veins were observed. Case 2 was a 51-year-old woman who was diagnosed with rhegmatogenous retinal detachment in the right eye and underwent phacovitrectomy with gas tamponade. On POD3, macular whitening with cotton wool spots and retinal hemorrhage were observed with macular ischemia owing to occlusion of retinal arteries and veins. In both cases, subconjunctival injection of gentamicin given at the end of surgery was the most suspected cause of retinal vascular occlusion.

Murao|Fumiko|F| Kinoshita|Takamasa|T| Katome|Takashi|T| Sano|Hiroki|H| Niki|Masanori|M| Mitamura|Yoshinori|Y|

Retinal vascular occlusion
Vitrectomy
Gentamicin
Macular ischemia


Obesity May Not Be a Risk of Non-Target Lesion Revascularization in the Elderly Patients.

Abstract: Obesity is assumed to be one of the robust risk factors for coronary artery disease. However, the effects of obesity on the progression of atherosclerosis in patients in different age groups after percutaneous coronary intervention (PCI) remain unclear. This study aimed to examine the effect of obesity on prognosis in different age groups.Consecutive patients who underwent urgent or elective PCI were surveyed for this study and were then divided into the elderly group and middle-aged group with a cut-off age of 70 years. All patients underwent coronary angiography or coronary computed tomography angiography 1 year after PCI to examine the progression of atherosclerosis. The primary endpoint was revascularization for a new lesion within 2 years after PCI. In addition, the main effects and correlations between obesity and age were examined. Multivariate logistic regression analysis was conducted to identify independent predictors of non-target lesion revascularization (non-TLR).Of the 711 patients who met the criteria and were available for follow-up analysis, the incidence of non-TLR within 2 years was 97/711 (13.6%). The higher incidence of non-TLR in patients with obesity was observed only in the middle-aged group. Furthermore, in the multivariate analysis, obesity was independently associated with non-TLR only in the middle-aged group.The findings of the present study would enable us to construct the hypothesis that obesity in elderly patients may not be an independent predictor of the incidence of non-TLR, indicating that the management to prevent non-TLR may vary depending on the age of the patient.

Shibata|Kenichi|K| Kameshima|Masataka|M| Fujiyama|Hiroaki|H| Ehara|Mariko|M| Suzuki|Yoriyasu|Y| Yamada|Sumio|S|

Age
Percutaneous coronary intervention
Clinical outcomes
Coronary risk factors
Japanese


Anatomic suitability for "off-the-shelf" thoracic single side-branched endograft in patients with type B aortic dissection.

Abstract:
OBJECTIVE
Treatment of type B aortic dissections with thoracic endovascular aortic repair (TEVAR) has been adopted in many centers with the goal of covering the proximal entry tear. Coverage of the left subclavian artery (LSCA) is commonly required to achieve a dissection-free proximal seal zone. A novel thoracic single side-branched (TSSB) endograft device offers a potential off-the-shelf option to achieve total endovascular incorporation of LSCA during zone 2 TEVAR. The aim of this study was to determine what percentage of patients with type B aortic dissection who require zone 2 TEVAR meet the anatomical requirements for this device.

METHODS
All consecutive patients undergoing TEVAR for type B aortic dissections at a single institution from 2006 to 2016 were evaluated. Three-dimensional centerline reconstruction of preoperative computed tomography angiography was performed to identify the diameter of the aorta, distances between branch vessels, diameter of the target branch vessel, and location of the primary entry tear. Only patients who met criteria for zone 2 TEVAR were included in the analysis. The primary outcome was percentage of patients that meet all anatomical requirements for TSSB. Individual criteria were evaluated independently, and results were stratified by dissection chronicity.

RESULTS
Eighty-seven patients who underwent TEVAR for Stanford type B aortic dissections were reviewed. Fifty-seven (66%) would have required zone 2 TEVAR. Indications for TEVAR were malperfusion (12), aneurysm (15), persistent pain (22), rupture (3), uncontrolled hypertension (5), and other (3). Mean follow-up was 19 months (range, 1-72 months). Only 16 of the 57 patients (28%) met all the requirements for anatomic suitability. The primary contributor was that only 49% of patients had sufficient length between arch branches to prevent coverage of a proximal branch.

CONCLUSIONS
Although the new TSSB device can allow for a more proximal seal zone and eliminate the need for open aortic arch debranching, only 28% of patients with type B dissection who required zone 2 TEVAR met all the anatomic requirements for this device. Future devices will need to account for the short distance between the left carotid and LSCA to be more broadly applicable.

Magee|Gregory A|GA|
Veranyan|Narek|N|
Kuo|Eric C|EC|
Ham|Sung Wan|SW|
Ziegler|Kenneth R|KR|
Weaver|Fred A|FA|
Fleischman|Fernando|F|
Bowdish|Michael E|ME|
Han|Sukgu M|SM|

D000368:Aged
D000784:Aneurysm, Dissecting
D001013:Aorta, Thoracic
D017545:Aortic Aneurysm, Thoracic
D001807:Blood Vessel Prosthesis
D057510:Endovascular Procedures
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D011474:Prosthesis Design
D012189:Retrospective Studies

Aortic dissection
TEVAR
Arch anatomy
Branched endograft


An online investigation into the impact of adding epidemiological information to imaging reports for low back pain.

Abstract: Degenerative changes commonly feature on spinal images and are often identified in the imaging reports of pain-free individuals. Many of these findings relate to "normal" age-related characteristics, however are frequently interpreted as implying abnormality and may adversely influence patient outcomes. The aim of this study was to investigate the impact of adding epidemiological information to lumbar imaging reports in a general adult population. This study was an online, scenario-based, randomised experiment. Participants were presented with a "virtual patient" scenario via an online survey and then randomly allocated to either receive a standard imaging report or a standard report with additional epidemiological information. The primary outcome was a composite "back-related perceptions" (BRP) score. Data from 247 participants (72% female) were included in the analysis. There was a small effect of group on BRP [F(12,444) = 6.75, p = 0.010] with participants who received the additional epidemiological information demonstrating more positive perceptions. Including epidemiological information in spinal imaging reports positively impacted "virtual-patient" perceptions in an online scenario-based study. This finding suggests that implementing a simple imaging reporting strategy may be reassuring and should be further considered for its potential to positively impact patient outcomes. Further research is warranted in clinical populations.

Medalian|Yasmin|Y|
Moseley|G Lorimer|GL|
Karran|Emma L|EL|

reporting
low back pain
spinal imaging
reassurance
communication


Women's representation in French Internal Medicine meetings: gender distribution among speakers, moderators and organisers, 2013-2018.

Abstract: Medical meetings are a time for increasing scientific visibility and leadership. We aimed to examine women's representation in French National Internal Medicine meetings (2013-2018). Women represented 25% of congress presidents, 22% of plenary session speakers, 19% of plenary session moderators and 25% oral session moderators, but 45% of anonymously selected oral communication speakers. Women are under-represented among invited speakers in French Internal Medicine meetings.

internal medicine
gender
speakers
congress
invitation


The Prevalence of Atrial Fibrillation and Conduction Abnormalities in Chagas' Disease: A Meta-Analysis.

Abstract:
BACKGROUND/OBJECTIVES
Chagas' disease (CD) has been associated with atrial fibrillation (AF) and electrocardiographic (ECG) conduction defects. However, prior studies have shown conflicting results. We performed a meta-analysis comparing the prevalence of AF and conduction abnormalities between CD and non-CD patients.

METHODS
PubMed, EMBASE, Cochrane Central, and Latin American databases were searched for studies that directly compared the prevalence of AF and conduction defects in CD and non-CD patients. Odds ratios (OR) were computed using random-effects model due to anticipated heterogeneity. We further performed subanalyses limited to studies that included only patients with cardiomyopathy.

RESULTS
A total of 17,238 patients from 30 studies were included, of whom 6,840 (40%) had a positive serology for CD. In the pooled data, AF was significantly more prevalent in the CD group (OR 1.62; 95%CI 1.21-2.15; P = 0.001). However, no significant difference was observed between groups when the analysis included only patients with cardiomyopathy (OR 1.21; 95%CI 0.97-1.50; P = 0.08) or heart failure (OR 1.09; 95%CI 0.81-1.47; P = 0.55). The combination of right bundle branch block (RBBB) and left anterior fascicular block (LAFB) had the highest OR for increased prevalence in patients with Chagas' cardiomyopathy compared to non-CD etiologies (OR 5.31; 95%CI 1.23-22.86; P = 0.03).

CONCLUSIONS
Our meta-analysis suggests that the prevalence of AF in patients with Chagas' cardiomyopathy is not significantly different from non-CD cardiomyopathies. The pattern of RBBB and LAFB in patients with cardiomyopathy of unknown etiology and epidemiologic risk factors should raise the possibility of CD and prompt specific diagnostic testing.

Cardoso|Rhanderson|R|
Garcia|Daniel|D|
Fernandes|Gilson|G|
He|L I|LI|
Lichtenberger|Paola|P|
Viles-Gonzalez|Juan|J|
Coffey|James O|JO|
Mitrani|Raul D|RD|

D000200:Action Potentials
D001281:Atrial Fibrillation
D002598:Chagas Cardiomyopathy
D016009:Chi-Square Distribution
D004562:Electrocardiography
D006329:Heart Conduction System
D006339:Heart Rate
D006801:Humans
D016017:Odds Ratio
D015995:Prevalence
D011379:Prognosis
D012307:Risk Factors

atrial fibrillation
right bundle branch block
left anterior fascicular block
Chagas’ disease
electrocardiogram
left bundle branch block


An unusual case of carcinoma erysipelatoides originating from gastric adenocarcinoma.

Abstract: Carcinoma erysipelatoides, also known as inflammatory metastatic carcinoma, is a rare form of cutaneous metastasis. It is most commonly caused by breast carcinoma, but rarely associated with gastric adenocarcinoma. Herein, we report an unusual case of carcinoma erysipelatoides in a 55 year-old female who had been diagnosed with signet ring cell carcinoma of the stomach metastasizing to ovaries.

Choi|Won Jun|WJ|
Jue|Mihn Sook|MS|
Ko|Joo Yeon|JY|
Ro|Young Suck|YS|

Carcinoma erysipelatoides
Signet ring cell carcinoma
Stomach neoplasm


Primary central nervous system lymphoma in neuropsychiatric systemic lupus erythematosus: case-based review.

Abstract: Primary central nervous system lymphoma (PCNSL) sometimes occurs in immune-compromised hosts or patients with autoimmune diseases. Some cohort studies have previously reported an increased risk of non-Hodgkin's lymphoma in systemic lupus erythematosus (SLE), while some cases of PCNSL in patients with SLE were reported. We present the case of PCNSL which developed in a patient with the active phase of neuropsychiatric SLE (NPSLE). Furthermore, we reviewed published English articles to confirm the characteristics of PCNSL related to SLE. To our knowledge, this is the first report of PCNSL occurring in NPSLE. Histology demonstrated B-cell lymphoma with a positive Epstein-Barr virus-encoded RNA. This patient recovered following surgical resection of the lymphoma, whole brain radiation therapy, intravenous infusion of rituximab (RTX), and administration of belimumab after RTX. Given the series of reviews, our report suggests that the persistence of damage in the central nervous system (CNS) and long-term exposure to immunosuppressants may impact oncogenic immune responses within the CNS, leading to PCNSL development.

D020945:Lupus Vasculitis, Central Nervous System

Neuropsychiatric systemic lupus erythematosus


High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial.

Abstract:
BACKGROUND
There is a high prevalence of vitamin D deficiency in the critically ill patient population. Several intensive care unit studies have demonstrated an association between vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) < 20 ng/mL] and increased hospital length of stay (LOS), readmission rate, sepsis and mortality.

MATERIAL AND METHODS
Pilot, double blind randomized control trial conducted on mechanically ventilated adult ICU patients. Subjects were administered either placebo, 50,000 IU vitamin D3 or 100,000 IU vitamin D3 daily for 5 consecutive days enterally (total vitamin D3 dose = 250,000 IU or 500,000 IU, respectively). The primary outcome was plasma 25(OH)D concentration 7 days after oral administration of study drug. Secondary outcomes were plasma levels of the antimicrobial peptide cathelicidin (LL37), hospital LOS, SOFA score, duration of mechanical ventilation, hospital mortality, mortality at 12 weeks, and hospital acquired infection.

RESULTS
A total of 31 subjects were enrolled with 13 (43%) being vitamin D deficient at entry (25(OH)D levels < 20 ng/mL). The 250,000 IU and 500,000 IU vitamin D3 regimens each resulted in a significant increase in mean plasma 25(OH)D concentrations from baseline to day 7; values rose to 45.7±19.6 ng/mL and 55.2 ± 14.4 ng/mL, respectively, compared to essentially no change in the placebo group (21±11.2 ng/mL), p<0.001. There was a significant decrease in hospital length of stay over time in the 250,000 IU and the 500,000 IU vitamin D3 group, compared to the placebo group (25 ± 14 and 18 ± 11 days compared to 36 ± 19 days, respectively; p=0.03). There was no statically significant change in plasma LL-37 concentrations or other clinical outcomes by group over time.

CONCLUSIONS
In this pilot study, high-dose vitamin D3 safely increased plasma 25(OH)D concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes.

CLINICAL TRIAL REGISTRATION
www.clinicaltrials.gov (NCT01372995).

Han|Jenny E|JE|
Jones|Jennifer L|JL|
Tangpricha|Vin|V|
Brown|Mona A|MA|
Brown|Lou Ann S|LAS|
Hao|Li|L|
Hebbar|Gautam|G|
Lee|Moon Jeong|MJ|
Liu|Shuling|S|
Ziegler|Thomas R|TR|
Martin|Greg S|GS|

vitamin D
antimicrobial peptides
LL-37
critical care
lung failure


Menu label accuracy at a university's foodservices. An exploratory recipe nutrition analysis.

Abstract: The increase in the weight of American adults and children has been positively associated with the prevalence of the consumption of food-away-from-home. The objective was to assess the accuracy of claimed nutritional information of foods purchased in contracted foodservices located on the campus of an institution of higher education. Fifty popular food items were randomly collected from five main dining outlets located on a selected campus in the northeastern United States. The sampling was repeated three times on separate occasions for an aggregate total of 150 food samples. The samples were then weighed and assessed for nutrient composition (protein, cholesterol, fiber, carbohydrates, total fat, calories, sugar, and sodium) using nutrient analysis software. Results were compared with foodservices' published nutrition information. Two group comparisons, claimed and measured, were performed using the paired-sample t-test. Descriptive statistics were used as well. Among the nine nutritional values, six nutrients (total fat, sodium, protein, fiber, cholesterol, and weight) had more than 10% positive average discrepancies between measured and claimed values. Statistical significance of the variance was obtained in four of the eight categories of nutrient content: total fat, sodium, protein, and cholesterol (P < .05). Significance was also reached in the variance of actual portion weight compared to the published claims (P < .001). Significant differences of portion size (weight), total fat, sodium, protein, and cholesterol were found among the sampled values and the foodservices' published claims. The findings from this study raise the concern that if the actual nutritional information does not accurately reflect the declared values on menus, conclusions, decisions and actions based on posted information may not be valid.

Feldman|Charles|C| Murray|Douglas|D| Chavarria|Stephanie|S| Zhao|Hang|H|

D002791:Cholesterol, Dietary
D004040:Dietary Carbohydrates
D004041:Dietary Fats
D004043:Dietary Fiber
D004044:Dietary Proteins
D019422:Dietary Sucrose
D002149:Energy Intake
D005504:Food Analysis
D005515:Food Labeling
D005522:Food Services
D006801:Humans
D009753:Nutritive Value
D012982:Sodium, Dietary
D014481:United States
D014495:Universities

Menu labeling
Foodservice
Nutrition
Portion size


Could local surgery improve survival in de novo stage IV breast cancer?

Abstract:
BACKGROUND
Resection of the primary tumor is recommended for symptom relief in de novo stage IV breast cancer. We explored whether local surgery could provide a survival benefit in these patients and attempted to characterize the population that could benefit from surgery.

METHODS
Metastatic Breast cancer patients (N = 313) with intact primary tumor between January 2006 and April 2013 were separated into two groups according to whether or not they had undergone surgery. The difference in characteristics between the two groups was analyzed using chi-square test, Fisher's exact test and Mann-Whitney test. Univariable and multivariable Cox regression and stratified survival analysis were used to assess the effect of surgery on survival.

RESULTS
Of the 313 patients, 188 (60.1%) underwent local surgery. Patients with local surgery had a 47% reduction in mortality risk vs. those with no surgery (median survival 78 months vs. 37 months; HR = 0.53; 95% CI, 0.36-0.78) after adjustment for clinical and tumor characteristics. Stratified survival analysis showed that patients with bone metastasis alone (and primary tumor ≤5 cm), soft tissue metastasis, or ≤ 3 metastasis sites benefit from surgery.

CONCLUSION
Surgical resection of the primary tumor can improve survival in selected de novo stage IV breast cancer patients.

Local surgery
De novo stage IV
Bone metastasis
Soft tissue metastasis
Primary tumor size


The Perception of Religious Leaders on HIV and Their Role in HIV Prevention: A Case Study of African, Caribbean, and Black (ACB) Communities in Windsor, Ontario.

Abstract: This paper explores the perception of African, Caribbean, and Black (ACB) religious leaders on HIV vulnerability and their role in HIV prevention among ACB communities in Windsor, Ontario. We conducted one semi-structured focus group discussion with nine Black religious leaders, most of whose congregants are members of the ACB community. Most religious leaders in the focus group had a negative perception of the transmission of HIV, but they acknowledged their own important role in HIV prevention strategies. This role is collaborative in nature, from the stage of designing HIV prevention strategies to implementing prevention messages. The religious leaders noted, however, that some challenges, such as church doctrine and congregational culture, are likely to impede their HIV prevention efforts.

Religious leaders
HIV
HIV prevention
ACB communities


A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects.

Abstract: We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main drawback of the former model was its restriction on the route of glucose entrance to the body which was limited to the intravenous glucose injection. To handle the oral glucose intake, we have added a model of glucose absorption in the gastrointestinal tract to the former model to address the resultant variations of blood glucose concentrations following an oral glucose intake. Another model representing the incretins production in the gastrointestinal tract along with their hormonal effects on boosting pancreatic insulin production is also added to the former model. We have used two sets of clinical data obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization problem. The results show acceptable precision of the estimated model parameters and demonstrate the capability of the model in accurate prediction of the body response during the clinical studies.

Vahidi|O|O|
Kwok|K E|KE|
Gopaluni|R B|RB|
Knop|F K|FK|

Compartmental model
Incretins
Oral glucose tolerance test
Nonlinear optimization
Parameter estimation
Type 2 diabetes mellitus


Complete mitogenome of the foxface rabbitfish Siganus vulpinus (Perciformes, Siganidae): indication of potential interbreeding in rabbitfishes.

Abstract: In the present study, the complete mitochondrial genome of the foxface rabbitfish Siganus vulpinus (Perciformes, Siganidae) is determined. The entire sequence is 16,505 bp in length, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 control region. The genome organization is similar to those found in other rabbitfishes. Apart from ND6 and 8 tRNA genes, all other mitochondrial genes are encoded on the heavy strand. Overall base compositions of mitogenome are 29.3% of A, 29.3% of C, 25.7% of T, and 15.7% of G, showing an obvious anti-G bias which is commonly found in fishes. The high similarity of mitochondrial genome between S. vulpinus and S. unimaculatus indicate that natural interbreeding might exist in breeding season.

D000818:Animals
D001482:Base Composition
D020029:Base Pairing
D001483:Base Sequence
D004272:DNA, Mitochondrial
D050259:Genes, Mitochondrial
D054629:Genome, Mitochondrial
D007178:Inbreeding
D010473:Perciformes
D012343:RNA, Transfer

Siganus vulpinus
Siganidae
Mitochondrial genome


Gemcitabine, paclitaxel, and oxaliplatin (GEMPOX) in the treatment of relapsed/refractory intracranial nongerminomatous germ cell tumors.

Abstract: Intracranial germ cell tumors (GCT) account for less than 5% of all central nervous system tumors in children in Western countries. Approximately 40% are nongerminomatous GCT (NGGCT). Despite correct treatment, 16% to 47% of the patients will relapse. There are no standard approaches in case of recurrence, and treatment in this situation remains a challenge. We report three patients diagnosed with relapsed intracranial NGGCT treated with gemcitabine, paclitaxel, and oxaliplatin, in whom the tumor showed a remarkable response with normalization of tumor markers.

Perez-Somarriba|Marta|M|
Moreno-Tejero|Maria Luisa|ML|
Rozas|Maria Isabel|MI|
Pelaez|Irene|I|
Madero|Luis|L|
Lassaletta|Alvaro|A|0000-0003-2881-1473

D009373:Neoplasms, Germ Cell and Embryonal

relapsed intracranial nongerminomatous germ cell tumors


Ultrasound guided peritubal infiltration of 0.25% Bupivacaine versus 0.25% Ropivacaine for postoperative pain relief after percutaneous nephrolithotomy: A prospective double blind randomized study.

Abstract:
BACKGROUND AND AIM
Percutaneous nephrolithotomy (PCNL) is a common for managing renal calculi. Pain in the initial post operatie period is relieved by infiltration of local anaesthetic around the nephrostomy tract. We aimed to compare the analgesic efficacy of bupivacaine and ropivacaine.

METHODS
A total of 100 adult patients undergoing elective PCNL-under balanced general anaesthesia were randomly divided into bupivacaine group (Group B) and ropivacaine group (Group R). After completion of procedure, 23G spinal needle was inserted at 6 and 12 O'clock position under ultrasonic guidance up to renal capsule along the nephrostomy tube. A volume of 10 ml of either 0.25% bupivacaine or 0.25% ropivacaine solution was infiltrated in each tract while withdrawing the needle. Post-operative pain was assessed using visual analogue scale (VAS) and dynamic visual analogue scale (D-VAS) for initial 24 h. Intravenous tramadol was given as rescue analgesia when VAS >4. Time to first rescue analgesic, number of doses and total amount of tramadol required in initial 24 h and side-effects were noted.

RESULTS
Visual analogue scale and D-VAS at 6 h and 8 h in Group B was significantly higher than Group R. Mean time to first rescue analgesia in Group R was significantly longer than Group B. Mean number of doses of tramadol and total consumption of tramadol in 24 h was less in Group R, though not statistically significant.

CONCLUSION
Peritubal infiltration of 0.25% ropivacaine infiltration along the nephrostomy tract is more effective than 0.25% bupivacaine in alleviating initial post-operative pain after PCNL.

Parikh|Geeta P|GP|
Shah|Veena R|VR|
Vora|Kalpana S|KS|
Parikh|Beena K|BK|
Modi|Manisha P|MP|
Kumari|Pratibha|P|

ultrasound
Bupivacaine
ropivacaine
percutaneous nephrolithotomy
post-operative pain


Diversity of the Bosmina (Cladocera: Bosminidae) in China, revealed by analysis of two genetic markers (mtDNA 16S and a nuclear ITS).

Abstract:
BACKGROUND
China is an important biogeographical zone in which the genetic legacies of the Tertiary and Quaternary periods are abundant, and the contemporary geography environment plays an important role in species distribution. Therefore, many biogeographical studies have focused on the organisms of the region, especially zooplankton, which is essential in the formation of biogeographical principles. Moreover, the generality of endemism also reinforces the need for detailed regional studies of zooplankton. Bosmina, a group of cosmopolitan zooplankton, is difficult to identify by morphology, and no genetic data are available to date to assess this species complex in China. In this study, 48 waterbodies were sampled covering a large geographical and ecological range in China, the goal of this research is to explore the species distribution of Bosmina across China and to reveal the genetic information of this species complex, based on two genetic markers (a mtDNA 16S and a nuclear ITS). The diversity of taxa in the Bosmina across China was investigated using molecular tools for the first time.

RESULTS
Two main species were detected in 35 waterbodies: an endemic east Asia B. fatalis, and the B. longirostris that has a Holarctic distribution. B. fatalis had lower genetic polymorphism and population differentiation than B. longirostris. B. fatalis was preponderant in central and eastern China, whereas B. longirostris was dominated in western China. The third lineage (B. hagmanni) was only detected in a reservoir (CJR) of eastern China (Guangdong province). Bosmina had limited distribution on the Tibetan plateau.

CONCLUSIONS
This study revealed that the biogeography of Bosmina appear to be affected by historical events (Pleistocene glaciations) and contemporary environment (such as altitude, eutrophication and isolated habitat).

Wang|Liufu|L| Zhuang|Hang|H| Zhang|Yingying|Y| Wei|Wenzhi|W|

Bosmina
China
Distribution
Genetic investigation


Clinical features and management of antrochoanal polyps in children: Cues from a clinical series of 58 patients.

Abstract:
OBJECTIVE
To review the clinical features of pediatric patients affected by antrochoanal polyps (ACPs) and surgically treated at three University settings.

METHODS
Retrospective study. The present research includes the clinical data of subjects affected by ACPs, aged <18 years and referred to three ENT Departments, between January 1st 2003 and September 30th 2016. All patients underwent nasal endoscopy and sinonasal imaging; all subjects have been treated surgically.

RESULTS
Fifty-eight patients underwent functional endoscopic sinus surgery (FESS) for ACPs removal, under general anesthesia. There were no major intraoperative complications. Recurrence occurred in 12 cases (20.5%).

CONCLUSIONS
FESS was the first-choice treatment for APCs in the present series; our recurrence rate was similar to that of other reports available in literature. Recurrences of ACPs in children still represent a clinical challenge; it is likely that an improved comprehension of ACPs biology could help in better understanding the pathophysiology of this disease.

Pagella|Fabio|F| Emanuelli|Enzo|E| Pusateri|Alessandro|A| Borsetto|Daniele|D| Cazzador|Diego|D| Marangoni|Roberta|R| Maiorano|Eugenia|E| Zanon|Alessia|A| Cogliandolo|Cristina|C| Ciorba|Andrea|A| Pelucchi|Stefano|S|

Antrochoanal polyps
Children
Surgery
FESS
Recurrence


The impact of nurse staffing levels on nursing-sensitive patient outcomes: a multilevel regression approach.

Abstract: The goal of this study is to provide empirical evidence of the impact of nurse staffing levels on seven nursing-sensitive patient outcomes (NSPOs) at the hospital unit level. Combining a very large set of claims data from a German health insurer with mandatory quality reports published by every hospital in Germany, our data set comprises approximately 3.2 million hospital stays in more than 900 hospitals over a period of 5 years. Accounting for the grouping structure of our data (i.e., patients grouped in unit types), we estimate cross-sectional, two-level generalized linear mixed models (GLMMs) with inpatient cases at level 1 and units types (e.g., internal medicine, geriatrics) at level 2. Our regressions yield 32 significant results in the expected direction. We find that differentiating between unit types using a multilevel regression approach and including postdischarge NSPOs adds important insights to our understanding of the relationship between nurse staffing levels and NSPOs. Extending our main model by categorizing inpatient cases according to their clinical complexity, we are able to rule out hidden effects beyond the level of unit types.

D010561:Personnel Staffing and Scheduling

Nurse staffing
Nursing-sensitive patient outcomes
Acute care
Multilevel models
Quality of care


Effect of Torula Yeast (Candida utilis)-Derived Glucosylceramide on Skin Dryness and Other Skin Conditions in Winter.

Abstract: Glucosylceramide (GlcCer) is present in foods such as barley, corn, and wheat flour. GlcCer derived from different foods has differences in its physiological effects, depending on the sphingoid backbone and constituent fatty acids. In this study, we investigated the moisturizing and skin conditioning effects of GlcCer derived from torula yeast (Candida utilis) in healthy human subjects. The participants were randomly distributed in a crossover, double-blind comparative manner. Seventeen volunteers were orally administered both 1.8 mg/d of GlcCer derived from torula yeast and a placebo for 4 wk. Before and after oral administration, transepidermal water loss (TEWL) was measured and the objective skin condition observation and a questionnaire on skin condition were conducted. The primary endpoint was TEWL; secondary endpoints included the objective and subjective skin conditions. The change in TEWL over the study period on the forearm was -0.97±0.48 and -1.26±0.46 g/m2•h in the placebo and GlcCer groups, respectively, with significantly lower (p=0.01) TEWL observed in the GlcCer group. Brown spots increased in the placebo group but significantly decreased in the GlcCer group (p=0.04). Although chapped skin worsened in the placebo group, it significantly improved in the GlcCer group (p=0.04). The use of torula yeast-derived GlcCer as a functional cosmeceutical food is a viable option to ameliorate skin conditions, including improvement in skin barrier function, reduction of brown spots, and fixation of chapped skin.

Fukunaga|Shoko|S| Wada|Sayori|S| Sato|Toshiya|T| Hamaguchi|Masahide|M| Aoi|Wataru|W| Higashi|Akane|A|

torula yeast
skin dryness
skin condition
GlcCer
TEWL


Enhanced Recovery After Surgery (ERAS) multimodal programme as experienced by pancreatic surgery patients: Findings from an Italian qualitative study.

Abstract:
BACKGROUND
ERAS has recently been implemented in pancreatic surgery settings, but there is little evidence regarding the effects as perceived by patients. Given the lack of the knowledge in the field, the aim of this study was to capture the experience of patients undergoing pancreatic surgery who received perioperative care based on the ERAS programme.

METHODS
We designed a qualitative study undertaken in the pancreatic surgery unit of San Raffaele Hospital in Milan, Italy. Twenty-two consecutive patients were invited to participate in the study and 13 patients were interviewed. Data was collected between March and December 2012 either through face-to-face or semi-structured telephone follow-up from three to six weeks after discharge. Data was analysed using the interpretative phenomenological approach.

RESULTS
Patients who underwent surgical pancreatic procedures and treated with ERAS programme reported experiences based on four themes: (1) Feeling prepared to face surgery, (2) Being actively "inside" or "outside" the programme, (3) Healing at home: the best setting, and (4) "Perceiving the ordinary as extraordinary": reaching independence, once at home.

CONCLUSION
According to the findings, uncomplicated pancreatic surgery patients may benefit from the ERAS programme. Preadmission counselling should help patients to assume an active role. Once the patient returns home, the availability of a caregiver should be thoroughly assessed to guarantee the support needed by patients to successfully complete the ERAS(programme. Surgery and nursing staff should carefully monitor patients and suggest whether they continue, interrupt, or individualise the scheduled ERAS interventions in accordance with a patient's clinical condition and preferred personal timing.

Galli|Emanuele|E| Fagnani|Cristina|C| Laurora|Ilaria|I| Marchese|Carmen|C| Capretti|Giovanni|G| Pecorelli|Nicolò|N| Marzo|Elisabetta|E| Palese|Alvisa|A| Zannini|Lucia|L|

Enhanced Recovery After Surgery
ERAS
Pancreatic surgery
Italian
Qualitative study
Latin culture
Patient' experience


Diminished CCl4 -induced hepatocellular carcinoma, oxidative stress, and apoptosis by co-administration of curcumin or selenium in mice.

Abstract: Hepatocellular carcinoma (HCC) is a lethal disease, and in HCC advanced stages, there is limited therapeutic efficacy. HCC results in a complication of fibrosis or cirrhosis. In this study, the protective effect of curcumin and selenium versus hepatocellular carcinoma caused by CCl4 in experimental animals was investigated. In all, 70 mice were divided into seven groups to study the effect of curcumin and selenium on CCl4 -induced hepatocellular carcinoma. After treatment time, different animal groups were sacrificed, serum and liver samples were collected and processed for assay of biochemical and molecular parameters. Our results showed that CCl4 administration induced various alterations such as significant elevation in the serum levels of ALT, AST, and hepatic contents of malondialdehyde (MDA), and depletion in the levels of antioxidant parameters. CCl4 induced apoptosis in the hepatic cells indicated by an increased level of p53, CD4, CD8, Bax, and Annexin V/PI in addition to significant decrease in the level of Bcl-2. Administration of curcumin and selenium restored this abnormal variation in these biochemical parameters to normal values. Our study addressed that curcumin or selenium may be helpful in the protection against liver damage induced by CCl4 . The hepatoprotective impact of curcumin or selenium might be mediated primarily by its potent antioxidant activity. PRACTICAL APPLICATIONS: Hepatocellular carcinoma (HCC) ranked third common cause of death, primary liver cancer. Exposure to CCl4 was found to induce significant hepatotoxicity, characterized by fibrosis, bile duct proliferation, cirrhosis, and reduced hepatic function The work was prepared to investigate the protecting capacity of curcumin, selenium alone, and in combination against HCC induced by CCl4 in the experimental animal model. This study proved the protective effect of curcumin and selenium, alone and in combination with each other, where curcumin showed multiple pharmacological activities, including anti-inflammation and antioxidant, and have an essential role in inhibiting the progression of HCC.

oxidative stress
apoptosis
mice
liver
aminotransferase


Engineering of methionine chain elongation part of glucoraphanin pathway in E. coli.

Abstract: The methionine-derived glucosinolate glucoraphanin is associated with the health-promoting properties of broccoli. This has developed a strong interest in producing this compound in high amounts from a microbial source. Glucoraphanin synthesis starts with a five-gene chain elongation pathway that converts methionine to dihomo-methionine, which is subsequently converted to glucoraphanin by the seven-gene glucosinolate core structure pathway. As dihomo-methionine is the precursor amino acid for glucoraphanin production, a first challenge is to establish an expression system for production of dihomo-methionine. In planta, the methionine chain elongation enzymes are physically separated within the cell with the first enzyme in the cytosol while the rest are located in the chloroplast. A de-compartmentalization approach was applied to produce dihomo-methionine by expression of the respective plant genes in Escherichia coli cytosol. Introduction of two plasmids encoding the methionine chain elongation pathway into E. coli resulted in production of 25mgL(-1) of dihomo-methionine. In addition to chain-elongated methionine products, side-products from chain elongation of leucine were produced. Methionine supplementation enhanced dihomo-methionine production to 57mgL(-1), while keeping a steady level of the chain-elongated leucine products. Engineering of the de-compartmentalized pathway of dihomo-methionine in E. coli cytosol provides an important first step for microbial production of the health-promoting glucoraphanin.

Mirza|Nadia|N|
Crocoll|Christoph|C|
Erik Olsen|Carl|C|
Ann Halkier|Barbara|B|

Glucoraphanin
Chain elongation pathway
Dihomo-methionine
Aliphatic glucosinolates


Interprofessional Education Within a Pilot HIV-Care Elective Course.

Abstract: Objective. To create an IPE course that improved knowledge related to HIV history, prevention, and therapy, in health professions students and improved their interest and confidence in becoming interprofessional collaborative clinicians, specifically involved in the care of people living with HIV. Methods. A motivational design framework was used to create an interprofessional course that incorporated whole-task complex scenarios, team-based application, and experiential components. Multiple sources of quantitative and qualitative data, including the AIDS Education and Training Center evaluation tool and Interprofessional Collaborative Competency Attainment Scale instrument, as well as assignments and course evaluations, were collected and analyzed. Results. Fifteen students from medicine, nursing, and pharmacy participated in 2017, and 21 students from medicine, nursing, pharmacy, and social work participated in 2018. In both offerings, students rated the course experience positively and self-reported increases in confidence related to interprofessional competencies. Ninety-three percent and 68% of the students in 2017 and 2018, respectively, stated they planned to be involved in HIV care to some degree in the future. Students demonstrated high levels of knowledge of the AIDS Training & Education Center National HIV Curriculum at the end of the 2018 course offering. Conclusion. This educational course design provided an effective interprofessional learning experience and establishes a sustainable interprofessional format for teaching health professions students about HIV.

Pittenger|Amy L|AL|
Goodroad|Brian|B|
Nicol|Melanie|M|
Durgin|Elise N|EN|
Eveland|Lindsay|L|
Kaiser|Robyn|R|
Benbenek|Mary|M|
Benson|Nicole|N|
Rybicki|Sarah|S|

Interprofessional
motivational design
HIV/AIDS


The structures and phase transitions in 4-aminopyridinium tetraaquabis(sulfato)iron(III), (C5H7N2)[FeIII(H2O)4(SO4)2].

Abstract: The organic-inorganic hybrid compound 4-aminopyridinium tetraaquabis(sulfato)iron(III), (C5H7N2)[FeIII(H2O)4(SO4)2] (4apFeS), was obtained by slow evaporation of the solvent at room temperature and characterized by single-crystal X-ray diffraction in the temperature range from 290 to 80 K. Differential scanning calorimetry revealed that the title compound undergoes a sequence of three reversible phase transitions, which has been verified by variable-temperature X-ray diffraction analysis during cooling-heating cycles over the temperature ranges 290-100-290 K. In the room-temperature phase (I), space group C2/c, oxygen atoms from the closest Fe-atom environment (octahedral) were disordered over two equivalent positions around a twofold axis. Two intermediate phases (II), (III) were solved and refined as incommensurately modulated structures, employing the superspace formalism applied to single-crystal X-ray diffraction data. Both structures can be described in the (3+1)-dimensional monoclinic X2/c(α,0,γ)0s superspace group (where X is ½, ½, 0, ½) with modulation wavevectors q = (0.2943, 0, 0.5640) and q = (0.3366, 0, 0.5544) for phases (II) and (III), respectively. The completely ordered low-temperature phase (IV) was refined with the twinning model in the triclinic P{\overline 1} space group, revealing the existence of two domains. The dynamics of the disordered anionic substructure in the 4apFeS crystal seems to play an essential role in the phase transition mechanisms. The discrete organic moieties were found to be fully ordered even at room temperature.

phase transitions
incommensurately modulated structures
organic template materials
sulfate


Abbreviated assessment of bisphenol A toxicology literature.

Abstract: Bisphenol A (BPA), synthesized in 1891, is produced in quantities of >2 million metric tons annually for polycarbonate plastics, epoxy resins and food contact applications. BPA can be a weak estrogen mimic, and is ubiquitous in humans (in 93% US population; in 96% US pregnant women). European/US food/drug agencies conclude that current BPA levels present no risk to the general population (some include infants/children); basic endocrine disruption (ED) researchers state that entire populations are at risk from these levels. The US Food and Drug Administration banned BPA in baby bottles in 2012 'not based on safety concerns'; the US Environmental Protection Agency and its UK counterpart concurred. Basic ED researchers report reproductive/developmental effects from perinatal BPA exposure in mice at very low doses, e.g. 2 ng/g body weight (0.002 mg/kg body weight), with non-monotonic dose-response (NMDR) curves, using few animals per group and few groups; contract research organizations, in good laboratory practice- and guideline-compliant large studies in rats and mice, report no low-dose effects or NMDR curves. The argument rages!

D014486:United States Food and Drug Administration

Non-monotonic dose–response (NMDR) curves


One new piperazinedione isolated from a mangrove-derived fungus Aspergillus niger JX-5.

Abstract: One new piperazinedione derivative, nigerpiperazine A (1), along with six known compounds (2-7) were isolated from the fungus Aspergillus niger JX-5 from mangrove Ceriops tagal. Nigerpiperazine A (1) was elucidated by spectroscopic analyses and 13C NMR chemical shift calculations, compounds 4 and 5 were determined by X-ray and the CD spectra. The absolute configuration of 4 was identified by X-ray for the first time. Compounds 1 and 4 showed inhibitory activities against Helicoverpa armigera Hubner with the IC50 values of 200 and 100 µg/mL, respectively.

Bai|Meng|M| Wang|Yue|Y| Liu|Ting|T| Lian|Yu-Xing|YX| Bai|Qi-Qi|QQ| Song|Xiao-Ping|XP| Han|Chang-Ri|CR| Zheng|Cai-Juan|CJ| Chen|Guang-Ying|GY|

piperazinedione
Aspergillus niger
insecticidal activity
pyrone derivatives


Time delay and associated mortality from negative smear to positive Xpert MTB/RIF test among TB/HIV patients: a retrospective study.

Abstract:
BACKGROUND
The GeneXpert MTB/RIF Assay (Xpert®) is known to be a feasible, effective and a hopeful tool for rapid tuberculosis (TB) diagnosis and treatment. However, little is known about the time delay caused by initial negative sputum smear microscopy (NSSM), but consecutive positive Xpert TB test (PXTBt) and its association with TB mortality in resource-constrained settings. We aimed to estimate the median time delay between initial NSSM but consecutive PXTBt and TB treatment initiation and its association with TB mortality among TB/HIV co-infected patients in Beira, Mozambique.

METHODS
we used data from a retrospective cohort study of TB/HIV co-infected patients in six TB services in Beira city. The study included all patients that tested NSSM, followed by a PXTBt in the six health centers with TB services during the year 2015. Data were extracted from the laboratory and TB treatment registers. To assess the difference in median time delays between groups, Mann-Whitney and Kruskal-Wallis tests were computed. To analyze the associations between the time delays and TB mortality, logistic regression model was used.

RESULTS
Among the 283 patients included in the study, median (IQR) age was 31 (17) years, 59.0% were males, 57.6% in the WHO clinical fourth stage of HIV. The median (IQR) values for diagnostic delay, treatment delay and total time delay was 10 (9) days, 13 (12) days and 28 (20) days, respectively. For TB/HIV co-infected patients who tested negative for smear microscopy initially, a total time delay of one month or longer was associated with high mortality (aOR = 12.40, 95% CI: 5.70-22.10).

CONCLUSION
Our study indicates that delays in TB diagnosis and treatment resulting from initial NSSM, but consecutive PXTBt are common in Beira city and are one of the main factors associated with TB mortality among TB/HIV co-infected patients. Applying GeneXpert assay as gold standard for HIV-positive patients with suspected pulmonary TB or replacing the sputum smear microscopy by Xpert assay and its availability within 24 h is urgently needed to ensure early diagnosis and treatment, and to maximize the impact of the few resources available in the country.

GeneXpert MTB/RIF
TB mortality
TB/HIV co-infection
Beira-Mozambique
Delay TB diagnosis & treatment
Negative smear microscopy


SNP-Density Crossover Maps of Polymorphic Transposable Elements and HLA Genes Within MHC Class I Haplotype Blocks and Junction.

Abstract: The genomic region (~4 Mb) of the human major histocompatibility complex (MHC) on chromosome 6p21 is a prime model for the study and understanding of conserved polymorphic sequences (CPSs) and structural diversity of ancestral haplotypes (AHs)/conserved extended haplotypes (CEHs). The aim of this study was to use a set of 95 MHC genomic sequences downloaded from a publicly available BioProject database at NCBI to identify and characterise polymorphic human leukocyte antigen (HLA) class I genes and pseudogenes, MICA and MICB, and retroelement indels as haplotypic lineage markers, and single-nucleotide polymorphism (SNP) crossover loci in DNA sequence alignments of different haplotypes across the Olfactory Receptor (OR) gene region (~1.2 Mb) and the MHC class I region (~1.8 Mb) from the GPX5 to the MICB gene. Our comparative sequence analyses confirmed the identity of 12 haplotypic retroelement markers and revealed that they partitioned the HLA-A/B/C haplotypes into distinct evolutionary lineages. Crossovers between SNP-poor and SNP-rich regions defined the sequence range of haplotype blocks, and many of these crossover junctions occurred within particular transposable elements, lncRNA, OR12D2, MUC21, MUC22, PSORS1A3, HLA-C, HLA-B, and MICA. In a comparison of more than 250 paired sequence alignments, at least 38 SNP-density crossover sites were mapped across various regions from GPX5 to MICB. In a homology comparison of 16 different haplotypes, seven CEH/AH (7.1, 8.1, 18.2, 51.x, 57.1, 62.x, and 62.1) had no detectable SNP-density crossover junctions and were SNP poor across the entire ~2.8 Mb of sequence alignments. Of the analyses between different recombinant haplotypes, more than half of them had SNP crossovers within 10 kb of LTR16B/ERV3-16A3_I, MLT1, Charlie, and/or THE1 sequences and were in close vicinity to structurally polymorphic Alu and SVA insertion sites. These studies demonstrate that (1) SNP-density crossovers are associated with putative ancestral recombination sites that are widely spread across the MHC class I genomic region from at least the telomeric OR12D2 gene to the centromeric MICB gene and (2) the genomic sequences of MHC homozygous cell lines are useful for analysing haplotype blocks, ancestral haplotypic landscapes and markers, CPSs, and SNP-density crossover junctions.

Kulski|Jerzy K|JK|
Suzuki|Shingo|S|
Shiina|Takashi|T|

crossovers polymorphisms MHC haplotypes retroelements indels snps


Beyond intersubjectivity in olfactory psychophysics I: Troubles with the Subject.

Abstract: This article provides an experience-oriented relational account that goes beyond a human control of the world. Rather than working with the notion of intersubjectivity (commonly evoked in sensory STS, and still conserving the subject/object opposition), the article reports on how the sense of smell affords a rethinking of our relationship with the world. It does so by challenging the assumption of olfactory ineffability as it turns to a place whose inhabitants speak about smell as a part of their everyday affairs: a laboratory of olfactory psychophysics. There, we attend to a multimodal, embodied language that participates in preparing, running and analyzing scientific experiments. While Western languages are short on specialized vocabulary for expressing olfactory qualities and it feels difficult to talk about smell, laboratory events manifest smell language in its enmeshing with the sensory realm and the world. Noticing these ties destabilizes the idea of agential subject, highlighting instead our pre-intentional sensibility, in its connection with the world. A sister article on 'troubles with the Object' (Alač, 2020) continues to argue that the notion of intersubjectivity is overly narrow, highlighting our immersion in the world (rather than assuming our dominance of it).

subjectivity
ethnomethodology
olfaction
sensory ethnography


Renal artery responses to trace amines: Multiple and differential mechanisms of action.

Abstract:
PURPOSE
The rise in consumption of dietary supplements containing the trace amines p-tyramine, p-synephrine and p-octopamine has been associated with cardiovascular side effects. Since renal blood flow plays an important role in blood pressure regulation, this study investigated the mechanisms of action of these trace amines on isolated porcine renal arteries.

MAIN METHODS
Contractile responses to amines were investigated in noradrenaline-depleted rings of porcine main renal arteries in the absence and presence of the α1-adrenoceptor antagonist, prazosin (1 μM), β-adrenoceptor antagonist, propranolol (1 μM), or the trace amine-associated receptor (TAAR-1) antagonist, EPPTB (RO-5212773; 100 nM or 100 μM).

KEY FINDINGS
All three amines induced constrictor responses of similar magnitude and potency. However, their mechanisms of action on the renal artery appeared to differ. Depleting endogenous noradrenaline stores significantly reduced maximum responses to tyramine and synephrine, but less for octopamine. When direct responses were examined after depleting tissues of noradrenaline, responses to synephrine and octopamine, but not tyramine, were reduced in the presence of prazosin(1 μM) and potentiated in the presence of propranolol (1 μM) or L-NNA (100 μM). Generally, vasoconstrictor responses remaining after noradrenaline-depletion and α-adrenoceptor blockade were not affected by the TAAR-1 antagonist EPPTB (0.1-100 μM), although responses to low concentration of synephrine and octopamine were enhanced by this antagonist.

SIGNIFICANCE
Tyramine appears to mediate constriction of the renal artery mainly via an indirect sympathomimetic mechanism, whereas synephrine and octopamine exert additional direct effects on α1-adrenoceptors and possibly contractile TAAR (not TAAR-1). The two amines also activate simultaneous inhibitory responses via β-adrenoceptors, TAAR-1 and nitric oxide release.

Koh|Andy Hsien Wei|AHW|
Chess-Williams|Russ|R|
Lohning|Anna Elizabeth|AE|

Renal artery
Trace amine-associated receptor
Tyramine
Octopamine
Vasoconstriction


To Determine the Surgical Outcome of Anterior Cervical Corpectomy and Fusion without Fixation for Ossification of Posterior Longitudinal Ligament.

Abstract:
Aims
The purpose of our study is to evaluate the surgical outcome in patients undergoing anterior cervical corpectomy without fixation with plates and screws for the treatment of ossification of posterior longitudinal ligament (OPLL).

Subjects and Methods
The type of study was case series and was conducted from January 2015 to December 2015 for 1-year duration at the Department of Neurosurgery at a Tertiary Care hospital in Karachi, Pakistan. A total of n = 20 patients (16 men and 4 women; mean age of 57.45 ± 6.4 years [range: 45-68 years]) were included after thorough clinical history and physical examination. Neurological evaluation was done using the Japanese Orthopedic Association (JOA) scoring system. The pre- and post-operative JOA scores were used to calculate recovery rate (RR) of the patients. Radiographic assessment was done using various modalities such as X-ray, computed tomography scan, and magnetic resonance imaging. Surgical outcome and complications were studied and the data were analyzed using SPSS 21.

Results
After the uniform follow-up period of 12 months, mean JOA scores improved from 9.1 ± 1.37 preoperatively to 14.3 ± 1.69 postoperatively and mean RR was 67.01 ± 15.5%. All the patients showed successful osseous fusion while one patient did not. Two patients developed cerebrospinal fluid leakage, one patient developed recurrent laryngeal nerve palsy, and one expired due to iatrogenic neurological deterioration.

Conclusion
Anterior cervical corpectomy without fixation with plates and screws is an effective surgical procedure for the treatment of OPLL (for up to three cervical levels of OPLL). It gives good neurological recovery with fewer postoperative complications.

Younus|Syed Muneeb|SM|
Imran|Muhammad|M|
Khan|Ateeq Ahmed|AA|
Basar|Saqib|S|
Sheikh|Daniya|D|


The performance of resurfacing implants for focal cartilage defects depends on the degenerative condition of the opposing cartilage.

Abstract:
BACKGROUND
Non-degradable resurfacing implants are being developed for treatment of focal cartilage defects. Performance of these implants has been investigated opposing intact cartilage. This study investigates whether implants would perform equally well when the opposing cartilage is fibrillated.

METHODS
Human osteochondral strips (~2x1x1 cm) with a smooth (n = 9) or fibrillated (n = 17) cartilage surface were obtained from human tibial plateaus excised during total knee arthroscopy. A custom-made pin-on-plate sliding indenter was used to apply simultaneous compression (0.75-3 MPa) and movement (4 mm/s over 6 mm). Either metal implants, polycarbonate-urethane or healthy porcine osteochondral plugs with a diameter of 6 mm were used as indenter.

FINDINGS
Cartilage roughness of the osteochondral strips was significantly higher for the fibrillated than the smooth group prior to sliding-indentation. Roughness of the indenters was not significantly altered by sliding indentation using either smooth or fibrillated cartilage. For all but one sample, sliding of smooth cartilage against any of the indenter surfaces did not cause damage. However, samples with fibrillated cartilage showed varied responses from seemingly unaffected to severe tissue wear as quantified by analysis of Indian ink staining and histology.

INTERPRETATION
This study demonstrates that the opposing cartilage quality is relevant for the clinical success of implanting an artificial implant in a focal cartilage defect. Therefore it is essential to test the efficacy of newly developed implants against arthritic joint surfaces, and care should be taken when interpreting in vivo studies in which implants are inserted in healthy joints.

Damen|A H A|AHA|
Nickien|M|M|
Ito|K|K|
van Donkelaar|C C|CC|

Resurfacing implant
Metal
Wear
Cartilage mechanics
Osteoarthritis
Polymer


Automated cryo-EM structure refinement using correlation-driven molecular dynamics.

Abstract: We present a correlation-driven molecular dynamics (CDMD) method for automated refinement of atomistic models into cryo-electron microscopy (cryo-EM) maps at resolutions ranging from near-atomic to subnanometer. It utilizes a chemically accurate force field and thermodynamic sampling to improve the real-space correlation between the modeled structure and the cryo-EM map. Our framework employs a gradual increase in resolution and map-model agreement as well as simulated annealing, and allows fully automated refinement without manual intervention or any additional rotamer- and backbone-specific restraints. Using multiple challenging systems covering a wide range of map resolutions, system sizes, starting model geometries and distances from the target state, we assess the quality of generated models in terms of both model accuracy and potential of overfitting. To provide an objective comparison, we apply several well-established methods across all examples and demonstrate that CDMD performs best in most cases.

D001331:Automation
D019295:Computational Biology
D020285:Cryoelectron Microscopy
D056004:Molecular Dynamics Simulation

cryo-EM
structure refinement
molecular dynamics
molecular biophysics
structural biology


Isolation and identification of anti-proliferative peptides from Spirulina platensis using three-step hydrolysis.

Abstract:
BACKGROUND
Spirulina platensis is an excellent source of proteins (>60%) that can be hydrolyzed into bioactive peptides.

RESULTS
In this study, whole proteins of Spirulina platensis were extracted and hydrolyzed using three gastrointestinal endopeptidases (pepsin, trypsin and chymotrypsin). Subsequently, gel filtration chromatography was employed to separate hydrolysates, and four fractions (Tr1-Tr4) were obtained. Among them, Tr2 showed the strongest anti-proliferation activities on three cancer cells (MCF-7, HepG-2 and SGC-7901), with IC50 values of <31.25, 36.42 and 48.25 µg mL-1 , respectively. Furthermore, a new peptide, HVLSRAPR, was identified from fraction Tr1. This peptide exhibited strong inhibition on HT-29 cancer cells with an IC50 value of 99.88 µg mL-1 .

CONCLUSION
Taken together, these peptides possessed anti-proliferation activities on cancer cells and low cytotoxicity on normal cells, suggesting that they might serve as a natural anticancer agent for nutraceutical and pharmaceutical industries. © 2016 Society of Chemical Industry.

Spirulina platensis
hydrolysis
gastrointestinal endopeptidases
anti-proliferation


Degradation of Monosaccharides, Disaccharides, and Fructans in the Stomach of Horses Adapted to a Prebiotic Dose of Fructooligosaccharides and Inulin.

Abstract: For a period of 20 days, 12 horses either received a prebiotic supplementation with fructooligosaccharides and inulin via Jerusalem artichoke meal (JAM) or corncob meal without grains (CMG) as placebo. The horses were euthanized 1 hour postprandial, gastric digesta was sampled from pars nonglandularis (PNG) and pars glandularis (PG), and concentrations of starch, mono- and disaccharides, fructans, d- and l-lactic acid, and short chain fatty acids were analyzed. Concentrations of starch and simple sugars were widely the same in JAM supplemented and not supplemented meals. However, fructans were less than half as much without supplementation as with supplementation of JAM. Glucose, fructose, sucrose, and fructans disappeared to a larger extent with prebiotic supplementation than without (106.6% vs. 86.7% glucose, 73.1% vs. 66.8% fructose, 91.5% vs. 14.7% sucrose, and 68.3% vs. 35.4% fructans remained in PNG; 81.9% vs. 38.3% glucose, 52.2% vs. 53.4% fructose, 47.1% vs. 0% sucrose, and 48.5% vs. 31.7% fructans remained in PG with CMG vs. JAM feeding). Disappearance of simple sugars and fructans was primarily associated with appearance of n-butyric acid (r = -0.21 - r = -0.33).

Bachmann|Martin|M|
Glatter|Maren|M|
Bochnia|Mandy|M|
Greef|Jörg M|JM|
Breves|Gerhard|G|
Zeyner|Annette|A|

Degradation
Stomach
Horses
Fructooligosaccharides
Inulin-type fructans


BCRP/ABCG2 inhibitors: a patent review (2009-present).

Abstract:
INTRODUCTION
BCRP/ABCG2 is a polyspecific ATP binding cassette transporter involved in multidrug resistance of tumors. Compared with P-glycoprotein/ABCB1 only a few inhibitors are known.

AREAS COVERED
Identification of ABCG2 inhibitors in compound libraries and efforts made to develop new ABCG2 inhibitors are discussed in the review. Additionally, development of new test systems for testing ABCG2 activity and medical applications of ABCG2 inhibitors and activators are reviewed.

EXPERT OPINION
ABCG2 is highly expressed in side-population cells, which possess stem cell properties and are resistant to chemotherapy and radiotherapy. These cells are thought to lead to a relapse after chemotherapy. Therefore, inhibition of ABCG2 could have an additional benefit besides counteracting multidrug resistance. Among the new chemical entities, the bivalent flavonoids seem promising, as selective and broad spectrum inhibitors were found within this class of compounds. However, the available pharmacological data are rather preliminary.

D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2

ABCG2
inhibitor
ATP binding cassette transporter
breast cancer resistance protein


Using Video Game Telemetry Data to Research Motor Chunking, Action Latencies, and Complex Cognitive-Motor Skill Learning.

Abstract: Many theories of complex cognitive-motor skill learning are built on the notion that basic cognitive processes group actions into easy-to-perform sequences. The present work examines predictions derived from laboratory-based studies of motor chunking and motor preparation using data collected from the real-time strategy video game StarCraft 2. We examined 996,163 action sequences in the telemetry data of 3,317 players across seven levels of skill. As predicted, the latency to the first action (thought to be the beginning of a chunked sequence) is delayed relative to the other actions in the group. Other predictions, inspired by the memory drum theory of Henry and Rogers, received only weak support.

Thompson|Joseph J|JJ|
McColeman|C M|CM|
Stepanova|Ekaterina R|ER|
Blair|Mark R|MR|

Video games
Telemetry
Motor chunking
Skill learning
Big data
Expertise


Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy.

Abstract: Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness among young adults. In this study, we investigated the potential of four quinone analogues (CoQ1, CoQ10, decylubiquinone and idebenone) in compensating for the deleterious effect of the m.11778G>A mitochondrial DNA mutation. The LHON fibroblast cell lines tested exhibited reduced cell growth, impaired mitochondrial bioenergetics and elevated levels of reactive oxygen species (ROS). Idebenone increased ATP production and reduced ROS levels, but the effect was partial and cell-specific. The remaining quinone analogues had variable effects and a negative impact on certain mitochondrial parameters was observed in some cell lines.

Yu-Wai-Man|Patrick|P|
Soiferman|Devorah|D|
Moore|David G|DG|
Burté|Florence|F|
Saada|Ann|A|

D029242:Optic Atrophy, Hereditary, Leber

Idebenone
Quinone
Leber hereditary optic neuropathy
Coenzyme Q(10)
Mitochondrial disease
Optic atrophy


Prioritizing highway safety improvement projects: A Monte-Carlo based Data Envelopment Analysis approach.

Abstract: Road authorities have to prioritize safety improvement projects due to budget limitations. This process needs to estimate expected benefits (reduction in average crash frequency) and costs of projects. Due to variances of crash modification factor (CMF), crash frequency and cost of projects, prediction of costs and benefits would be accompanied by uncertainty and it can subsequently lead to a wrong decision making. To deal with the inherent uncertainty in the decision making process, this paper presents a ranking approach based on integration of Data Envelopment Analysis and Monte-Carlo simulation. A Monte-Carlo simulation is applied to generate stochastic values as input and outputs of the problem instead of running DEA model just for deterministic case. Data from an existing case study is used to evaluate the performance of the proposed methodology. Numerical results indicate that DEA results are very sensitive to data uncertainty and uncertainties can have great influence in ranking results of road safety improvement projects especially when both input and output data are uncertain. It also indicates that how the proposed methodology can be useful for detecting sensitive decision-making units and providing a more comprehensive view for decision makers to allocate a limit budget to the most efficient safety improvement projects.

D000063:Accidents, Traffic
D000076624:Built Environment
D003362:Cost-Benefit Analysis
D003657:Decision Making
D006801:Humans
D009010:Monte Carlo Method
D017751:Safety Management

Prioritizing
Safety improvement projects
Data Envelopment Analysis
Monte-Carlo simulation
Road safety


Modulation of brain insulin signaling in Alzheimer's disease: New insight on the protective role of green coffee bean extract.

Abstract: Objective: Alzheimer's disease (AD), a neurodegenerative disorder, involves brain insulin signaling cascades and insulin resistance (IR). Because of limited treatment options, new treatment strategies are mandatory. Green coffee bean extract (GCBE) was reported to attenuate IR and improve brain energy metabolism. We aimed to investigate the possible use of GCBE as a prophylactic strategy to delay the onset of AD or combined with pioglitazone (PIO) as a strategy to retard the progression of AD.Methods: Rats received 10% fructose in drinking water for 18 weeks to induce AD. GCBE-prophylactic group received GCBE for 22 weeks started 4 weeks prior to fructose administration. The PIO group treated with PIO for 6 weeks started on week 12 of fructose administration. The GCBE+PIO group received GCBE for 22 weeks started 4 weeks prior to fructose administration and treated with PIO for the last 6 weeks of fructose administration.Results: Pretreatment with GCBE, either alone or combined with PIO, alleviated IR-induced AD changes. GCBE improved cognition, decreased serine phosphorylation of insulin receptor substrate, increased phosphoinositol-3 kinase (PI3K) activity and protein kinase B (Akt) gene expression, decreased glycogen synthase kinase-3β (GS3Kβ) gene expression and Tau hyperphosphorylation.Discussion: GCBE exerted neuroprotective effects against IR-induced AD mediated by alleviating IR and modulating brain insulin signaling cascade.

Mohamed|Hoda E|HE|
Asker|Mervat E|ME|
Younis|Nahla N|NN|
Shaheen|Mohamed A|MA|
Eissa|Rana G|RG|

Insulin resistance
Pioglitazone
Fructose
Tau hyperphosphorylation
Neurofilament


Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

Abstract:
BACKGROUND
Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied.

OBJECTIVES
To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy.

METHODS
134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values.

RESULTS
Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25).

CONCLUSIONS
Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded.

Miceli Sopo|S|S|
Greco|M|M|
Monaco|S|S|
Varrasi|G|G|
Di Lorenzo|G|G|
Simeone|G|G|
|||

Honey
Acute cough
Children
Dextromethorphane
Levodropropizine


An updated animal model capturing both the cognitive and emotional features of post-traumatic stress disorder (PTSD).

Abstract: The new-released Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines post-traumatic stress disorder (PTSD) as a "trauma and stressor-related disorder". PTSD pathogenesis relies on paradoxical changes of emotional memory processing induced by the trauma exposure and associated with emotional dysfunction. Several animal models of PTSD have been validated and are currently used. Each one mimics a particular subset of the disorder with particular emphasis, mainly driven by the past classification of PTSD in the DSM-4, on the emotional features. In view of the recent update in the DSM-5, our aim was to develop, by using well-validated paradigms, a modified model of PTSD able to mimic at the same time both the cognitive and emotional features of the disease. We exposed male rats to either a piece of worn cat collar or to a series of inescapable footshocks paired with a PTSD risk factor, i.e., social isolation. Animals were subsequently re-exposed to the conditioned contexts at different time intervals in order to test memory retention for the stressors. In addition, footshock-exposed rats were tested in the elevated-plus-maze and social interaction tests. We found that rats exposed to a cat collar exhibited an acute fear response that did not lead to enduring memory retention. Conversely, footshock-exposed rats expressed a successful retention of the stressful experience at 1, 7, 14, 21 and 56 post-exposure days. Footshock-exposed rats displayed an anxious behavioral profile in the social interaction test and a significantly reduced locomotor activity in the elevated-plus-maze test. These dysfunctions were not observed when animals were socially housed, thus highlighting a social buffering effect in the development of the pathology. Our results underline the good validity of a footshock-based paradigm paired with social isolation as a PTSD animal model, able to mimic at the same time both some of the enduring cognitive and emotional facets of the pathology.

Berardi|Andrea|A| Trezza|Viviana|V| Palmery|Maura|M| Trabace|Luigia|L| Cuomo|Vincenzo|V| Campolongo|Patrizia|P|

stress
trauma
memory
animal models of PTSD
rats
footshock
predator odor
social behavior


TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial.

Abstract:
Background
Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy.

Methods
Patients with stage III/IV unresectable, squamous cell carcinoma of the head and neck received up to four cycles of TPF-E (cisplatin and docetaxel 75 mg/m2 on day 1 followed by 5-FU 750 mg/m2/day as a continuous infusion on days 1-5 plus cetuximab at a loading dose of 400 mg/m2 followed by a weekly dose of 250 mg/m2), with prophylactic antibiotics but no growth factors. Patients not progressing after four cycles of TPF-E were randomly assigned to radiotherapy (70 Gy over 7 weeks in 2 Gy fractions) and weekly cetuximab with either weekly cisplatin 40 mg/m2 or carboplatin, AUC of 1.5 mg/ml/min. Primary endpoint was feasibility.

Results
Forty-seven patients were recruited. One patient did not start TPF (hypersensitivity reaction during the cetuximab loading dose). Induction TPF-E was discontinued in 12 patients due to toxicity (6 patients), medical decision (2), death (1), patient refusal (1), protocol violation (1), co-morbidity (1). Three further patients were not randomized [progressive disease (1), protocol violation (1), toxicity and co-morbidity (1)]. Of particular interest are three patients who suffered from bowel perforation, one patient who died as results of pneumonia and septic shock, and a second patient who was found dead at home 12 days after starting TPF-E (cause of death unknown). Weekly cisplatin and carboplatin was stopped early in seven and four patients, respectively. Radiotherapy was stopped in two patients with cisplatin and interrupted in one patient with cisplatin and four patients with carboplatin.

Conclusions
The addition of cetuximab to full dose TPF induction chemotherapy led to unacceptable complications and premature closing of the study. Only 34 out of 46 patients completed four cycles of TPF-E and only 30 started biochemoradiation.

Specenier|P M|PM|
Remenar|E|E|
Buter|J|J|
Schrijvers|D L|DL|
Bergamini|C|C|
Licitra|L F|LF|
Awada|A|A|
Clement|P M|PM|
Fortpied|C|C|
Menis|J|J|
Vermorken|J B|JB|

D000077195:Squamous Cell Carcinoma of Head and Neck

TPF
cetuximab
induction chemotherapy
biochemoradiation
head and neck cancer
locoregionally advanced


A night float week in a surgical clerkship improves student team cohesion.

Abstract:
BACKGROUND
We hypothesize that night float rotations in the third-year surgical clerkship improve student learning and perceptions of team cohesion.

METHODS
A 1-week night float (NF) system was implemented during the 2013 to 2014 academic year for students. Each student completed 1 week of NF with the Trauma/Emergency General Surgery service. The Perceived Cohesion Scale survey was prospectively administered and National Board of Medical Examiners academic performance retrospectively reviewed.

RESULTS
We surveyed 70 medical students, 37 traditional call and 33 NF students, with 91% response rate. Perception of team cohesion increased significantly, without perceived loss of educational benefit. Examination scores increased significantly comparing pre- and postintervention groups, with this trend continuing in the following academic year.

CONCLUSIONS
A week-long student NF experience significantly improved perception of team cohesion and standardized examination results. A dedicated period of NF during the surgical clerkship may improve its overall educational value.

Connelly|Christopher R|CR|
Kemp Bohan|Phillip M|PM|
Cook|Mackenzie R|MR|
Moren|Alexis M|AM|
Schreiber|Martin A|MA|
Kiraly|Laszlo N|LN|

Night float
Surgical clerkship
Team cohesion
Medical education
Resident duty hours