Vietnamese version of the coronary artery disease education questionnaire-Short version: Translation, adaptation and validation.

Abstract:
WHAT IS KNOWN AND OBJECTIVE
Coronary artery disease (CAD) is the leading cause of mortality worldwide. Patient education is an essential part of cardiac patients' care targeting self-management behaviour to reduce risk factors and subsequent events. There has been no Vietnamese questionnaire to assess patient's knowledge about CAD; therefore, the purpose of this study was to translate, cross-culturally adapt and validate the Coronary Artery Disease Education Questionnaire-Short Version (CADE-Q SV) for use in Vietnam.

METHODS
Translation and cross-cultural adaption of the tool were carried out in five stages: (a) two independent translations from English into Vietnamese were produced; (b) these two translations were then synthesized; (c) two translators blinded to the outcome measurements independently created separate back translations into English; (d) nine experts reached consensus on all items of the Vietnamese version of the CADE-Q SV; and (e) a pilot study was conducted on 35 patients with acute coronary syndrome (ACS). The validity and reliability of the questionnaires were then evaluated in 117 Vietnamese patients with ACS. The internal consistency and test-retest reliability were assessed by Cronbach's alpha and Cohen's kappa coefficient, respectively. Construct validity was determined by examining the relationship between knowledge scores and patient characteristics.

RESULTS
The Vietnamese version of CADE-Q SV was created, including 20 items divided into two domains: medical and psychological condition, and nutrition and exercise. There was good equivalence between the original and the Vietnamese versions in all four areas: semantic, idiomatic, experiential and conceptual equivalence. Cronbach's alpha coefficients were acceptable for the questionnaire as a whole (0.78) and for the two domains: medical and psychological condition (0.71) and nutrition and exercise (0.52). All Cohen's kappa coefficients confirmed test-retest reliability (Kappa > 0.600; P < .001). Construct validity was confirmed by a significant correlation of knowledge scores with education level (P = .004).

WHAT IS NEW AND CONCLUSION
The Vietnamese version of CADE-Q SV can be considered a valid and reliable questionnaire to evaluate patient's knowledge of CAD. Further studies could investigate the influence of knowledge scores on adherence to medications and clinical outcomes of patients with CAD.

Vietnamese
coronary artery disease
translation
adaptation
questionnaire


Associations between maternal plasma measurements of inflammatory markers and urinary levels of phenols and parabens during pregnancy: A repeated measures study.

Abstract:
BACKGROUND
Maternal immune system regulation is critical for maintenance of a healthy pregnancy and fetal development. Exposure to phenols and parabens is widespread, and may be linked to systemic inflammation and alteration of circulating immunological biomarkers.

OBJECTIVE
We sought to characterize associations between repeated measures of individual urinary phenols, parabens and plasma inflammatory markers across pregnancy.

METHODS
In the LIFECODES prospective birth cohort, we conducted a nested preterm birth case-control study, including 130 cases and 352 controls. In urine samples collected from each participant at up to four study visits during pregnancy, we measured concentrations of six phenols and four parabens, as well as five plasma inflammatory markers. We used multivariable linear mixed models to analyze repeated measures of exposures on inflammatory markers. We created and applied inverse probability weights to account for the sampling approach.

RESULTS
We observed bidirectional associations between select phenols and parabens and inflammatory markers. An interquartile range increase in triclosan (55.2 ng/mL) was associated with a 12.5% (95% CI: 3.67, 22.0) increase in C-reactive protein, a 7.95% (95% CI: 1.95, 14.3) increase in interleukin 10, and a 7.93% (95% CI: 3.82, 12,2) increase in tumor necrosis factor-α. Additionally, an interquartile range increase in 2,5-dichlorophenol (11.0 ng/mL) was associated with a 10% increase in C-reactive protein (95% CI: 1.92, 18.7). Conversely, an interquartile range increase in ethyl paraben (10.4 ng/mL) was associated with a 7.7% decrease in interleukin‑1β (95% CI: -14.1, -0.86).

CONCLUSIONS
Our findings can be organized into two thematic frameworks, one where concentrations of urinary phenols and parabens during pregnancy reflected a pro-inflammatory relationship with immunological biomarkers, and the other contrary theme - an anti-inflammatory relationship. These findings have implications for fetal development and reproductive outcomes, and emphasize the need for further research on immunological mechanisms of phenol and paraben action during pregnancy.

Aung|Max T|MT|
Ferguson|Kelly K|KK|
Cantonwine|David E|DE|
Bakulski|Kelly M|KM|
Mukherjee|Bhramar|B|
Loch-Caruso|Rita|R|
McElrath|Thomas F|TF|
Meeker|John D|JD|

Chlorinated phenols
Cytokines
Reproductive immunology


Combined Anterior Approach with Transcorporeal Herniotomy for a Huge Migrated Cervical Disc Herniation.

Abstract: The report describes the herniation of a huge migrated cervical disc, which was treated by a combined anterior approach. A 50-year-old man presented with radiculopathy and myelopathy. Radiological images revealed the herniation of a huge disc which had migrated superiorly from the C6-7 disc to the C5-6 disc. We tried to combine an anterior cervical discectomy and fusion (ACDF) and transcorporeal herniotomy to avoid corpectomy. Postoperatively, successful clinical and radiological results were obtained. It is therefore possible to remove a huge migrated herniated cervical disc completely by a combined ACDF and trancorporeal approach without corpectomy.

Choi|Kyung-Chul|KC|
Ahn|Yong|Y|
Lee|Choon Dae|CD|
Lee|Sang-Ho|SH|

Migration
Cervical disc herniation
Epidural


Urine Drug Screen Trends from 1998 through 2011 Among Emergency Department Patients Treated in a University Teaching Hospital.

Abstract: The emergency department (ED) at Louisiana State University-Health Science Center in Shreveport (LSUHSC-S) serves an urban population with a large rural catchment area. This study focuses on demographic variables in substance abuse trends in this region based on urine drug screen (UDS) results. A database of de-identified UDSs ordered in the ED at LSUHSC-S between 1998 and 2011 was analyzed. Samples were tested for the presence of amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, 3,4-methylenedioxymethamphetamine (MDMA), methadone, methamphetamine, opiates, phencyclidine, and propoxyphene. The patient population was categorized by age group, gender, and race. The majority of tests were performed on African-American and Caucasian patients ages 18 to 54 followed by the 0 to 11-year-old group. Of the drugs tested, cannabinoids represented the highest percentage of positive results in both the African-American and Caucasian populations. Opiates returned the highest percent of positive results among all prescription drugs. The Caucasian population predominated in positive tests for prescription drugs (opiates and benzodiazepines), while the African-American population predominated in results positive for illicit drugs (cannabinoids and cocaine). The increasing presence of opiates and cannabinoids, particularly in very young patients, should prompt policy makers and healthcare providers to develop intervention strategies to protect the most vulnerable populations.

Korneeva|Nadejda|N|
Cvek|Urska|U|
Leskova|Anna|A|
Hutchinson|Kimberley|K|
Callahan|Avery|A|
Patek|Gregory|G|
Trutschl|Marjan|M|
Kilgore|Phillip C S R|PCSR|
McGauly|Patrick|P|
Goeders|Nicolas|N|
Arnold|Thomas|T|

urine drug screening
emergency department
administrative database


Effect of exercise on key pharmacokinetic parameters related to metformin absorption in healthy humans: A pilot study.

Abstract: Exercise is widely accepted as having therapeutic effects; thus, it is important to know whether it interacts with medications. The aim of the present pilot study was to examine the effect of high-intensity interval exercise (known to have antidiabetic action) on key pharmacokinetic parameters related to absorption of metformin (the first-line medication against type 2 diabetes). Ten healthy men participated in two sessions, spaced one to two weeks apart in random, counterbalanced order. In both sessions, participants received 1000 mg of metformin orally, 1-1.5 hours after breakfast. Then, they either ran for 60 minutes at alternating intensity, starting at 40 minutes after metformin administration, and rested without food consumption over the next 3 hours or they rested without food consumption during the entire testing period. Venous blood samples were collected before and at 0.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after metformin administration for metformin determination by liquid chromatography-mass spectrometry. Capillary blood samples were also collected for lactate and glucose measurements. Data from the two sessions were compared through Wilcoxon or Student's t test, as appropriate. Maximum plasma concentration of metformin (Cmax ) was higher at exercise compared to rest (P = .059). Time to reach Cmax (Tmax ) decreased with exercise (P = .009), and the area under the metformin concentration vs time curve was higher at exercise (P = .047). The addition of exercise to metformin administration did not cause hypoglycemia or lactic acidosis. In conclusion, our results provide the first evidence that pharmacokinetic values related to metformin absorption are affected by exercise.

pharmacokinetics
metformin
absorption
high-intensity interval exercise
type 2 diabetes
bioavailability
liquid chromatography
mass spectrometry


Utility of multi-channel surface electromyography in assessment of focal hand dystonia.

Abstract:
INTRODUCTION
Surface electromyography (SEMG) allows objective assessment and guides selection of appropriate treatment in focal hand dystonia (FHD).

METHODS
Sixteen-channel SEMG obtained during different phases of a writing task was used to study timing, activation patterns, and spread of muscle contractions in FHD compared with normal controls. Customized software was developed to acquire and analyze EMG signals.

RESULTS
SEMG of FHD subjects (20) showed "early onset" during motor imagery, rapid proximal muscle recruitment, agonist-antagonist co-contraction involving proximal muscle groups, "delayed offset" after stopping writing, higher rectified mean amplitudes, and mirror activity in contralateral limb compared with controls (16). Muscle activation latencies were heterogenous in FHD.

CONCLUSIONS
Anticipation, delayed relaxation, and mirror EMG activation were noted in FHD. A clear pattern of muscle activation cannot be ascertained. Multi-channel SEMG can aid in objective assessment of temporal-spatial distribution of activity and can refine targeted therapies like chemodenervation and biofeedback.

Sivadasan|Ajith|A|
Sanjay|M|M|
Alexander|Mathew|M|
Devasahayam|Suresh R|SR|
Srinivasa|Babu K|BK|

focal hand dystonia (FHD)
early onset
delayed offset
mirror activity
surface electromyogram (SEMG)


Influence of cholesterol on cancer progression and therapy.

Abstract: Cholesterol is a fundamental molecule necessary for the maintenance of cell structure and is vital to various normal biological functions. It is a key factor in lifestyle-related diseases including obesity, diabetes, cardiovascular disease, and cancer. Owing to its altered serum chemistry status under pathological states, it is now being investigated to unravel the mechanism by which it triggers various health complications. Numerous clinical studies in cancer patients indicate an alteration in blood cholesterol level (either decreased or increased) in comparison to normal healthy individuals. This article elaborates on our understanding as to how cholesterol is being hijacked in the malignancy for the development, survival, stemness, progression, and metastasis of cancerous cells. Also, it provides a glimpse of how cholesterol derived entities, alters the signaling pathway towards their advantage. Moreover, deregulation of the cholesterol metabolism pathway has been often reported to hamper various treatment strategies in different cancer. In this context, attempts have been made to bring forth its relevance in being targeted, in pre-clinical and clinical studies for various treatment modalities. Thus, understanding the role of cholesterol and deciphering associated molecular mechanisms in cancer progression and therapy are of relevance towards improvement in the management of various cancers.

Mayengbam|Shyamananda Singh|SS|
Singh|Abhijeet|A|
Pillai|Ajay D|AD|
Bhat|Manoj Kumar|MK|

Cholesterol Cancer Chemoresistance LDLR LDLc


Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome.

Abstract: Autocatalytic activation of an initiator caspase triggers the onset of apoptosis. In dying cells, caspase-9 activation is mediated by a multimeric adaptor complex known as the Apaf-1 apoptosome. The molecular mechanism by which caspase-9 is activated by the Apaf-1 apoptosome remains largely unknown. Here we demonstrate that the previously reported 1:1 interaction between Apaf-1 caspase recruitment domain (CARD) and caspase-9 CARD is insufficient for the activation of caspase-9. Rather, formation of a multimeric CARD:CARD assembly between Apaf-1 and caspase-9, which requires three types of distinct interfaces, underlies caspase-9 activation. Importantly, an additional surface area on the multimeric CARD assembly is essential for caspase-9 activation. Together, these findings reveal mechanistic insights into the activation of caspase-9 by the Apaf-1 apoptosome and support the induced conformation model for initiator caspase activation by adaptor complexes.

Hu|Qi|Q| Wu|Di|D| Chen|Wen|W| Yan|Zhen|Z| Yan|Chuangye|C| He|Tianxi|T| Liang|Qionglin|Q| Shi|Yigong|Y|

D051017:Apoptosis Regulatory Proteins
D053478:Apoptosomes
D053453:Caspase 9
D002384:Catalysis
D004789:Enzyme Activation
D006801:Humans
D006860:Hydrogen Bonding
D066298:In Vitro Techniques
D008239:Lysine
D008956:Models, Chemical
D008958:Models, Molecular
D016297:Mutagenesis, Site-Directed
D011487:Protein Conformation
D025941:Protein Interaction Mapping
D017433:Protein Structure, Secondary
D017434:Protein Structure, Tertiary
D011993:Recombinant Fusion Proteins

apoptosis
mechanism
CARD
caspase activation
induced proximity


Environmental (in)dependence of a hybrid zone: Insights from molecular markers and ecological niche modeling in a hybrid zone of Origanum (Lamiaceae) on the island of Crete.

Abstract: The role of environment and the relative significance of endogenous versus exogenous selection in shaping hybrid zones have been crucial issues in the studies of hybridization. Recent advances in ecological niche modeling (ENM) offer new methodological tools, especially in combination with the genotyping of individuals in the hybrid zone. Here, we study the hybrid zone between the widely known spices Origanum onites and Origanum vulgare ssp. hirtum in Crete. We analyze the genetic structure of both parental taxa and their hybrid Origanum × intercendens using AFLP markers on 15 sympatric and 12 allopatric populations and employ ecological niche modeling and niche similarity tests to study their niche patterns. We complement these analyses with seed viability measurements. Our study revealed that the hybridizing taxa O. onites and O. vulgare ssp. hirtum and the resulting genotypic classes showed geographical and environmental niche similarities based on the predictions of ENMs and the subsequent similarity tests. The occurrence of the hybrid zone is not directly dependent on environmental factors which favor the fitness of the hybrid compared to the parental taxa, but rather on aspects such as historical factors and management practices, which may contribute to the localization and maintenance of the contact zone between parental species. Our results suggest that if a minimum required niche differentiation between genotypic classes is not achieved, environmental dependence might not have a prominent role on the outcome of the hybridization.

Bariotakis|Michael|M|
Koutroumpa|Konstantina|K|
Karousou|Regina|R|
Pirintsos|Stergios A|SA|

hybridization
niche modeling
Origanum
spices
genotypic classes
management practices
contact zone


H5N1 influenza virulence, pathogenicity and transmissibility: what do we know?

Abstract: Highly pathogenic influenza viruses of the H5N1 subtype have infected more than 600 people since 1997, resulting in the deaths of approximately 60% of those infected. Multiple studies have established the viral hemagglutinin (HA) surface glycoprotein as the major determinant of H5N1 virulence. HA mediates host-specific virus binding to cells, and mutations that allow efficient binding to viral receptors on mammalian cells are critical (although not sufficient) for H5N1 transmissibility among mammals. The viral polymerase PB2 protein is also a critical virulence determinant, and adaptive mutations in this protein are crucial for efficient H5N1 virus replication in mammals. Additionally, viral proteins (such as NS1 and PB1-F2) with roles in innate immune responses also affect the virulence of highly pathogenic H5N1 viruses.


Association of day of the week with mortality after elective right hemicolectomy for colon cancer: Case analysis from the National Clinical Database.

Abstract:
Aim
We aimed to investigate whether later weekdays are related to worse short-term outcomes after elective right hemicolectomy for colon cancer.

Methods
We retrospectively analyzed adult patients who underwent elective right hemicolectomy for colon cancer between 2012 and 2017. Records lacking details about surgical mortality were excluded, and multiple imputation was performed for other missing data (variables). The primary endpoint was surgical mortality, defined as the sum of 30-day mortality and in-hospital deaths within 90 days postoperatively. Using 22 clinical variables, hierarchal logistic regression modeling with clustering of patients from the same institutes was performed.

Results
Of the 112 658 patients undergoing elective right hemicolectomy for colon cancer, the 30-day mortality and surgical mortality were 0.6% and 1.1%, respectively. Surgery on Friday was less frequent, accounting for 17.1% of all cases. The occurrence of severe postoperative complications, anastomotic leakage, or unadjusted odds ratio for surgical mortality did not show significant differences between weekdays. A hierarchal logistic regression model identified 19 independent factors for surgical mortality. Adjusted odds ratios for surgical mortality were 1.01 (95% confidence interval: 0.83-1.22, P = .915), 0.86 (95% confidence interval: 0.71-1.05, P = .144), 0.86 (95% confidence interval: 0.71-1.05, P = .408), and 0.83 (95% confidence interval: 0.68-1.03, P = .176) for Tuesday, Wednesday, Thursday, and Friday, respectively, showing no significant differences.

Conclusion
This study did not identify an evident difference in surgical mortality between weekdays; a safe elective right hemicolectomy for colon cancer is being offered throughout the week in Japan.

colectomy
colonic neoplasms
elective surgical procedures
hospital mortality
treatment outcome


Novel 1,3,4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2 mediated JAK2/STAT3 signals as evidenced through data-based mathematical modeling.

Abstract: We attempted a preclinical study using DMH-induced CRC rat model to evaluate the antitumor potential of our recently synthesized 1,3,4-thiadiazoles. The molecular insights were confirmed through ELISA, qRT-PCR and western blot analyses. The CRC condition was produced in response to COX-2 and IL-6 induced activation of JAK2/STAT3 which, in turn, was due to the enhanced phosphorylation of JAK2 and STAT3. The treatment with 1,3,4-thiadiazole derivatives (VR24 and VR27) caused the significant blockade of this signaling pathway. The behavior of STAT3 populations in response to IL-6 and COX-2 stimulations was further confirmed through data-based mathematical modeling using the quantitative western blot data. Finally, VR24 and VR27 restored the perturbed metabolites associated to DMH-induced CRC as evidenced through 1H NMR based serum metabolomics. The tumor protecting ability of VR24 and VR27 was found comparable or to some degree better than the marketed chemotherapeutics, 5-flurouracil.

Raj|Vinit|V|
Bhadauria|Archana S|AS|
Singh|Ashok K|AK|
Kumar|Umesh|U|
Rai|Amit|A|
Keshari|Amit K|AK|
Kumar|Pranesh|P|
Kumar|Dinesh|D|
Maity|Biswanath|B|
Nath|Sneha|S|
Prakash|Anand|A|
Ansari|Kausar M|KM|
Jat|Jawahar L|JL|
Saha|Sudipta|S|

Colorectal cancer
IL-6/COX-2 mediated JAK2/STAT3
Mathematical modeling
1,3,4-Thiadiazole derivatives
(1)H NMR-based metabolomics


Biochemical effects and safety of Gum arabic (Acacia Senegal) supplementation in patients with sickle cell anemia.

Abstract:
Background
Sickle cell anemia (SCA) is a hereditary chronic hemolytic anemia with several clinical consequences. Intravascular sickling of red blood cells leads to multi-organ dysfunction. Moreover, several biochemical abnormalities have been associated with SCA. Gum arabic (GA) is an edible dried gummy exudate obtained from Acacia Senegal tree. GA showed antioxidant and cytoprotective activities and demonstrated protection against hepatic, renal, and cardiac toxicities in experimental rats. We hypothesized that regular intake of GA improves renal and liver functions in patients with SCA.

Methods
Forty-seven patients (5-42 yr) carrying hemoglobin SS were recruited. The patients received 30 g/day GA for 12 weeks. Blood samples were collected before administering GA and then after 4, 8, and 12 weeks. Liver enzymes, total protein, albumin, electrolytes, urea, creatinine, and uric acid were determined in the serum. The study was approved by the Al Neelain University Institutional Review Board and Research Ethics Committee Ministry of Health. The trial was registered at ClinicalTrials.gov (identifier: NCT02467257).

Results
GA significantly decreased direct bilirubin level [statistical significance (P-value)=0.04]. It also significantly decreased serum alanine transaminase level after 4 weeks, which was sustained till the 8th week. GA, however, had no effect on serum aspartate transaminase level. In terms of renal function, GA decreased serum urea level but the effect was not sustained after the first month.

Conclusion
GA may alter the disease severity in SCA as demonstrated by its ability to decrease direct bilirubin and urea levels in the serum.

Kaddam|Lamis AbdelGadir|LA|
Fdl-Elmula|Imad|I|
Eisawi|Omer Ali|OA|
Abdelrazig|Haydar Awad|HA|
Elnimeiri|Mustafa Khidir|MK|
Saeed|Amal Mahmoud|AM|

Gum arabic
Sickle cell anemia
Liver enzyme
Urea
Bilirubin


Development of a novel 99m Tc-labeled small molecular antagonist for CXCR4 positive tumor imaging.

Abstract: The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of 99m Tc-labeled AMD3465, a small molecule antagonist of CXCR4. 99m Tc-AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF-7 (breast cancer), and CHO-CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF-7 and CHO xenografts showed that the uptakes of the radiotracer in MCF-7 tumors were significantly higher than those in the CXCR4-negative CHO tumors (P < 0.05), and the MCF-7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that 99m Tc-AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging.

Zhang|Xuran|X| You|Linyi|L| Chen|Shuting|S| Gao|Mengna|M| Guo|Zhide|Z| Du|Jin|J| Lu|Jie|J|0000-0001-6351-0508 Zhang|Xianzhong|X|

D000072098:Single Photon Emission Computed Tomography Computed Tomography


Gender ratios of administrative prevalence and incidence of attention-deficit/hyperactivity disorder (ADHD) across the lifespan: A nationwide population-based study in Taiwan.

Abstract: To verify the hypothesis that there is different gender ratio of attention-deficit/hyperactivity disorder (ADHD) among adults compared to children and adolescents in the clinical setting among Asian population. The nationwide population-based database containing data on enrollees in the National Health Insurance program in Taiwan during 2000-2007 was used in this study, and we investigated the lifetime gender ratios of administrative prevalence and incidence in healthcare-seeking ADHD patients (n=228,029). The male-to-female ratios of diagnosed incidence and prevalence of child/adolescent ADHD (age <20 years) ranged from 3.39 to 4.07 and 3.87-4.31, respectively. The male-to-female ratios of diagnosed incidence and prevalence of ADHD in the adult group (age 20-65 years) ranged from 0.24 to 0.76 and 0.35-0.98, respectively. In conclusion, there was substantially increased female-to-male ratio in adults ADHD compared to children and adolescents in the clinical setting. Further researches on the management and mechanism are needed.

Huang|Charles Lung-Cheng|CL|
Weng|Shih-Feng|SF|
Ho|Chung-Han|CH|

D001289:Attention Deficit Disorder with Hyperactivity


Sex differences in the acquisition and maintenance of cocaine and nicotine self-administration in rats.

Abstract:
RATIONALE
Consistent sex differences are observed in human drug addiction, with females often exceeding males on drug intake. However, there is still a need for animal models for some aspects of addiction such as acquisition of drug self-administration and the subsequent development of drug-seeking.

OBJECTIVES
The present study examined sex differences in the acquisition and maintenance of self-administration of two widely used stimulants, cocaine and nicotine.

METHODS
Male and female rats self-administered cocaine (0.4 mg/kg/infusion) or nicotine (0.03 mg/kg/infusion) daily under a fixed-ratio 1 (FR 1) schedule until acquisition criteria were met (maximum of 30 sessions). The self-administration criterion for cocaine was ≥20 infusions in a 2-h session and ≥5 infusions in a 1-h session for nicotine. Sex differences were assessed by examining the percentage of rats that met acquisition criteria, the number of sessions to meet criteria, and the number of infusions earned during the maintenance phase.

RESULTS
A significantly higher percentage of male rats acquired both cocaine and nicotine self-administration than females, and males met acquisition criteria in fewer sessions. However, after criteria were met, females self-administered more cocaine than males during the first 5 days of maintenance. There were no sex differences in nicotine infusions post-acquisition.

CONCLUSIONS
Differences in acquisition amongst sexes can reveal factors that are integral to initiation of drug use, an often overlooked phase of drug addiction.

Swalve|Natashia|N|
Smethells|John R|JR|
Carroll|Marilyn E|ME|

D000697:Central Nervous System Stimulants

Sex differences
Acquisition
Maintenance
Cocaine
Nicotine
Self-administration


Management guidelines for low anterior resection syndrome - the MANUEL project.

Abstract:
AIM
Little is known about the pathophysiology of low anterior resection syndrome (LARS), and evidence concerning the management of patients diagnosed with this condition is scarce. The aim of the LARS Expert Advisory Panel was to develop practical guidance for healthcare professionals dealing with LARS.

METHOD
The 'Management guidelines for low anterior resection syndrome' (MANUEL) project was promoted by a team of eight experts in the assessment and management of patients with LARS. After a face-to-face meeting, a strategy was agreed to create a comprehensive, practical guide covering all aspects that were felt to be clinically relevant. Eight themes were decided upon and working groups established. Each working group generated a draft; these were collated by another collaborator into a manuscript, after a conference call. This was circulated among the collaborators, and it was revised following the comments received. A lay patient revised the manuscript, and contributed to a section containing a patient's perspective. The manuscript was again circulated and finalized. A final teleconference was held at the end of the project.

RESULTS
The guidance covers all aspects of LARS management, from pathophysiology, to assessment and management. Given the lack of sound evidence and the often poor quality of the studies, most of the recommendations and conclusions are based on the opinions of the experts.

CONCLUSIONS
The MANUEL project provides an up-to-date practical summary of the available evidence concerning LARS, with useful directions for healthcare professional and patients suffering from this debilitating condition.

low anterior resection syndrome
LARS
guidance
colorectal surgery
complications
consensus
rectal surgery


Audiological findings in professionals exposed to music and their relation with tinnitus.

Abstract: Professional musicians are at high risk of developing tinnitus due to their over-exposure to music at both occupational and recreational level. This is a 5-year long prospective case series study performed in the Musicians/Performing Arts Medicine Clinic of the 1st Otorhinolaryngology Department of the National and Kapodistrian University of Athens. A total of 274 professional musicians underwent thorough medical history, history of music exposure, assessment of the impact their hearing status has on their professional life (Musicians Hearing Handicap Index), behavioral (Pure Tone Audiometry, standard and extended high frequency) and objective audiometric tests (TEOAE and DPOAE). Standard pure tone audiometry thresholds were correlated with the presence of tinnitus only at high frequencies. Musicians with tinnitus had a clinical and significant higher MHHI score and the incidence of tinnitus was significantly higher in participants suffering from musculoskeletal disease and those with abnormal PTA. Participants' hours of practice were similar in those with tinnitus and those without. The tinnitus group (and in order of descending effect size) had significantly worse thresholds in high frequency audiometry (≥3000Hz) as well as lower signal to noise ratios in DPOAE at almost all frequencies and in TEOAE at high frequencies (2.8 and 4kHz). A subgroup analysis of the musicians with normal PTA, showed that those with tinnitus showed elevated thresholds in the extended high frequency. In conclusion, tinnitus occurrence in musicians with normal audiogram is potentially correlated with high frequency hearing loss and impaired otoacoustic emissions and these two examinations should be considered in this group.

Vardonikolaki|Aikaterini|A| Kikidis|Dimitris|D| Iliadou|Eleftheria|E| Markatos|Nikolaos|N| Pastiadis|Kostas|K| Bibas|Athanasios|A|

Music
Tinnitus
Musician
Hearing
Audiometry
Otoacoustic emissions
Noise-induced hearing loss


Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model.

Abstract:
BACKGROUND
Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear.

OBJECTIVES
This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model.

METHODS
Murine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed.

RESULTS
Human microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP-1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals.

CONCLUSIONS
Whereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model.

Hinkel|Rabea|R|
Lange|Philipp|P|
Petersen|Björn|B|
Gottlieb|Elena|E|
Ng|Judy King Man|JK|
Finger|Stefanie|S|
Horstkotte|Jan|J|
Lee|Seungmin|S|
Thormann|Michael|M|
Knorr|Maike|M|
El-Aouni|Chiraz|C|
Boekstegers|Peter|P|
Reichart|Bruno|B|
Wenzel|Philip|P|
Niemann|Heiner|H|
Kupatt|Christian|C|

adenoassociated virus
reperfusion
endothelial
transgenic
cardiomyocyte


Determination the Levels of Subjective and Observer Rating of Drowsiness and Their Associations with Facial Dynamic Changes.

Abstract:
BACKGROUND
We determined the levels of subjective and observer drowsiness and facial dynamics changes.

METHODS
This experimental study was done in the virtual reality laboratory of Khaje-Nasir Toosi University of Technology in 2015. Facial dynamics changes like changes in eyes, mouth and eyebrows were surveyed on twenty-five drivers in 2015byKSS (Karolinska Sleepiness Scale) and ORD (Observer Rating of Drowsiness). ANOVA Repeated Measure and MANOVA Repeated Measure tests were used for data analysis. Also, neural network and Viola-Jones were used to detect facial characteristics. PERCLOS (Percentage of Eye Closure), blink frequency and blink duration were inspected for eyes parameters. The size of open mouth during drowsiness was inspected for mouth parameter. During the inspection of eyebrow, the number 50 denoted eyebrow in normal position. For eyebrows above the normal position, a range of 50 to 55 was specified; in addition, 45-50 was found as the specified range for eyebrows under normal position.

RESULTS
Descriptive statistics of the dynamic changes in mouth and eyes illustrated that during the driving process, the level of sleepiness increased as well as changes of eyes and mouth. However, statistical findings during car driving revealed that dynamic changes in eyebrows had clear expression with a constant trend. Similar studies on data obtained from KSS and ORD showed that both of these parameters simultaneously increased as well as the level of drowsiness. In addition, a significant relationship existed between facial expression and drowsiness.

CONCLUSION
This research would be an effective and efficient tool for timely alarming and detecting the drowsiness quickly and precisely.

Poursadeghiyan|Mohsen|M|
Mazloumi|Adel|A|
Saraji|Gebraeil Nasl|GN|
Niknezhad|Ali|A|
Akbarzadeh|Arash|A|
Ebrahimi|Mohammad Hossein|MH|

Facial dynamic changes
ORD
KSS
Driver drowsiness


New concepts in the surgical treatment of actual and impending pathological fractures in metastatic disease.

Abstract:
INTRODUCTION
Long bone metastases are a disease of high social importance. The goals of surgical treatment are to relieve pain, maintain or restore joint function, and prevent or treat pathological fractures. "Oligometastases" is a disease with a limited number (3-5) of metastatic lesions in the same body district, where an aggressive treatment can be carried out with "curative" intent. This study aimed to evaluate patients with bone metastases surgically treated to determine how surgical treatment can influence prognosis and quality of life, comparing solitary metastasis, oligometastases, and multiple metastases.

PATIENTS AND METHODS
This is a retrospective analysis of 130 patients with long bone metastases surgically treated between October 2015 and August 2019: 40 patients had solitary metastasis; 38 had less than three metastases (oligometastases), and 52 had multiple metastases. Surgery was resection and reconstruction with a cemented prosthesis (95) or nailing (35).

RESULTS
Overall survival was significantly better in patients with solitary metastasis or oligometastases than in those with multiple metastases (p <0.0001). Patients treated with resection and prosthesis had significantly better survival than those treated with nailing (p <0.0001). Implant complications requiring surgical revision occurred in 20 patients treated with prostheses, while no complications occurred in patients treated with nailing.

DISCUSSION
Survival of cancer patients has improved in the last two decades, leading to an increase of diagnosed metastases. Patients with oligometastases have a survival similar to those with a single metastasis. Optimal implants survival curves should stay above the curves of patients survival.

CONCLUSIONS
Since there are no differences in survival, patients with oligometastases should be treated as patients with a solitary lesion, with more aggressive surgery (wide resection and reconstruction with prosthesis). Intramedullary nailing is still indicated in metaphyseal or diaphyseal metastases in patients with advanced disease or poor prognosis when the life expectancy does not overcome the expected survival of the nail, avoiding the need for further surgery.

Cappellari|Alessandro|A| Trovarelli|Giulia|G| Crimì|Alberto|A| Pala|Elisa|E| Angelini|Andrea|A| Berizzi|Antonio|A| Ruggieri|Pietro|P|

Oligometastases
Intramedullary nailing
Bone metastasis
Modular prosthesis


Laccase immobilized polyaniline/magnetic graphene composite electrode for detecting hydroquinone.

Abstract: Magnetic graphene nanocomposites were prepared by hydrothermal synthesis, and aniline polymerization was initiated by magnetic graphene. These polyaniline/magnetic graphene (PANI/MG) composites were used to immobilize laccase to construct biosensors. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and infrared spectroscopy (IR) were used to characterize these composites. Cyclic voltammetry and chronoamperometry technique were used to test the electrical properties of the constructed polyaniline/magnetic graphene laccase modified electrode. The results show that the polyaniline/magnetic graphene immobilizing laccase modified electrode exhibited superior electrical properties, including high sensitivity, detection limit and linear range. The hydroquinone was used as an analytical and detection probe. The selectivity was 0.03639 A/(mol/L), the linear range was 0.4-337.2 μmol/L, and the detection limit was 2.94 μM (signal/noise = 3, minimum identification value of effective signal). The biosensor can reach the conditions for detecting the actual water sample.

Lou|Congqiang|C| Jing|Tao|T| Zhou|Juying|J| Tian|Jingzhi|J| Zheng|Yongjie|Y| Wang|Chao|C| Zhao|Zhiyuan|Z| Lin|Jing|J| Liu|Hu|H| Zhao|Chunqi|C| Guo|Zhanhu|Z|

D017550:Spectroscopy, Fourier Transform Infrared


The impact of lifetime PTSD on the seven-year course and clinical characteristics of OCD.

Abstract: Research has suggested that the co-occurrence of PTSD in individuals with OCD is associated with more severe symptoms and less responsivity to empirically supported treatment as compared to individuals with OCD and no history of PTSD. However, much of this work has been limited by non-empirical case report design, cross-sectional and retrospective analyses, or small sample sizes. The current study extended this research by comparing the clinical characteristics of individuals with OCD with and without a lifetime PTSD diagnosis in a large, naturalistic, longitudinal sample over the course of seven years. At baseline, individuals with comorbid lifetime PTSD reported significantly more severe symptoms of OCD (including symptom levels and insight), lower quality of life, and higher rates of comorbid lifetime mood and substance use disorders than participants without lifetime PTSD. Further, individuals with comorbid OCD and lifetime PTSD reported significantly more severe OCD symptoms over the course of seven years than those without lifetime PTSD. These results are largely consistent with the existing literature and support the need to consider PTSD symptoms in the assessment and treatment of OCD.

Ojserkis|Rachel|R|
Boisseau|Christina L|CL|
Reddy|Madhavi K|MK|
Mancebo|Maria C|MC|
Eisen|Jane L|JL|
Rasmussen|Steven A|SA|

Obsessive-compulsive disorder
Posttraumatic stress disorder
Trauma


Tuberculosis vaccine research in China.

Abstract: It is now privately acknowledged that there may be little if any perceptible impact of the national Bacille Calmette-Guerin (BCG) vaccination program on disease prevalence, despite the extensive coverage of the newborn infant population and likely benefit in the early years of life. A better preventive vaccine than BCG is now being sought by Chinese researchers. Urgency has been added to the control problem by the emergence of multidrug-resistant tuberculosis (TB). Furthermore, expensive second-line drugs seem unlikely to be made available by the government to treat drug-resistant cases, so attention in addition has turned to the potential of immunotherapy as an adjunct to chemotherapy. Research trends are summarized here.


Hemodynamic instability during anesthesia in an adolescent with Loeys-Dietz syndrome: a case report.

Abstract: We present a case of a 12-year-old male with Loeys-Dietz syndrome (LDS), a rare life-threatening genetic disorder. Multiple manifestations of LDS were present, including easy bruising, aortic root dilatation, multiple areas of vessel tortuosity, and joint laxity. The patient's medications included a beta-blocker and an angiotensin II receptor antagonist for prophylaxis against further aortic root dilatation due to his LDS. He experienced intraoperative hemodynamic instability and became pulseless during an orthopedic procedure, which had to be abandoned. Anesthesia was reattempted 2 days after cessation of the patient's antihypertensive medications and was successful with only minor postoperative hypertension.

Bunting|Alexandra C|AC|
Bould|M Dylan|MD|

angiotensin receptor antagonists/adverse effects


Association between serum level of ubiquinol and NT-proBNP, a marker for chronic heart failure, in healthy elderly subjects.

Abstract: Ubiquinone and ubiquinol represent the oxidized and reduced forms of Coenzyme Q10 (CoQ10). CoQ10 is present in membranes of almost all human tissues and organs, with highest concentration in the heart. In patients with heart failure, serum levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP) are an indicator of disease severity. Here, we investigated the relationship between serum levels of CoQ10 and NT-proBNP in healthy volunteers of an elderly study population (mean age 52 years, n = 871). We found a negative association between serum levels of ubiquinol and NT-proBNP (P < 0.001). Accordingly, the CoQ10 redox state (% oxidized form of CoQ10) is positively associated with serum NT-proBNP level (P < 0.001). Compared to patients who survived a myocardial infarction (n = 21), healthy subjects have lower NT-proBNP level (500.39 ± 631.28 pg/ml vs. 76.90 ± 120.27 pg/ml, P < 0.001), higher ubiquinol serum level (0.43 ± 0.19 µmol/L vs. 0.71 ± 0.32 µmol/L; P < 0.001), and a lower CoQ10 redox state (27.6 ± 13.8% vs. 17.6 ± 10.1%; P < 0.001). Interestingly, ubiquinol supplementation (150 mg/day; 14 day; n = 53) slightly reduces the expression of CLCN6, a gene related to NT-proBNP level. In summary, higher serum levels of ubiquinol are associated with lower serum NT-proBNP levels in healthy elderly subjects. However, to what extent a high serum level of ubiquinol is a protective factor for heart failure remains to be elucidated in prospective studies.

Onur|Simone|S| Niklowitz|Petra|P| Jacobs|Gunnar|G| Lieb|Wolfgang|W| Menke|Thomas|T| Döring|Frank|F|

NT-proBNP
heart failure
CoQ10 redox state
antioxidants
oxidative stress


Microsurgical Resection of a Left Supramarginal Gyrus AVM Causing Radionecrosis.

Abstract: Late radiation necrosis is a rare entity presenting in 2.2% to 9% of radiation-treated arteriovenous malformations (AVMs). It occurs by a mean of 3 years following treatment. There are few reports in the literature of radionecrosis and solid lesions treated with surgery.1-4 To the authors' knowledge, this case has the longest interval between radiosurgery and the presentation of cerebral necrosis. In this surgical video, we present the case of a 51-year-old female with a left supramarginal gyrus AVM that received radiosurgery with gamma knife; after 20 years, she began having seizures and aphasia. The magnetic resonance imaging scan revealed a lesion simulating an intra-axial tumor causing important edema and mass effect. Medical treatment was given including high-dose steroids without success, therefore microsurgery was performed. The surgery was presented in a step-by-step basis and correlation was performed with the involved adjacent anatomy, to illustrate the anatomy of the approach and surgical landmarks. The patient's symptoms resolved completely, and the postoperative magnetic resonance imaging scan showed complete resection and resolution of the edema. The histopathological findings were consistent with a radionecrosis and AVM. The patient signed the Institutional Consent Form, which states that she accepts the procedure and allows the use of her images and videos for any type of medical publications in conferences and/or scientific articles.

Serrato-Avila|Juan Leonardo|JL|
da Costa|Marcos Devanir Silva|MDS|
Stávale|Joao Norberto|JN|
Lima|Joao Vitor Fernandes|JVF|
Carrasco-Hernandez|Juan Pablo|JP|
Alejandro|Sebastián Aníbal|SA|
Chaddad-Neto|Feres|F|

Microsurgical resection
Supramarginal gyrus AVM
Radionecrosis


Gold nanoprobes for multi loci assessment of multi-drug resistant tuberculosis.

Abstract: Tuberculosis, still one of the leading human infectious diseases, reported 8.7 million new cases in 2011 alone. Also, the increasing rate of multidrug-resistant tuberculosis (MDRTB) and its treatment difficulties pose a serious public health threat especially in developing countries. Resistance to isoniazid and rifampicin, first line antibiotics, is commonly associated with point mutations in katG, inhA and rpoB genes of Mycobacterium tuberculosis complex (MTBC). Therefore, the development of cheap, fast and simple molecular methods to assess susceptibility profiles would have a huge impact in the capacity of early diagnosis and treatment of MDRTB. Gold nanoparticles functionalized with thiol-modified oligonucleotides (Au-nanoprobes) have shown the potential to provide a rapid and sensitive detection method for MTBC and single base mutations associated with antibiotic resistance, namely the characterization of the three most relevant codons in rpoB gene associated to rifampicin resistance. Here we extend the Au-nanoprobe approach towards discriminating specific mutations within inhA and rpoB genes in PCR amplified DNA from isolates. Using a multiplex PCR reaction for these two genes, it is possible to assess both loci in parallel, and extend the potential of the Au-nanoprobe method to MDRTB molecular characterization with special application in the most frequent Portuguese genotypes.

Pedrosa|Pedro|P|
Veigas|Bruno|B|
Machado|Diana|D|
Couto|Isabel|I|
Viveiros|Miguel|M|
Baptista|Pedro V|PV|

D060885:Multiplex Polymerase Chain Reaction

Tuberculosis
MDRTB
inhA
rpoB
Gold nanoparticles
Nanodiagnostics


Nest-departure behaviour of gynes and drones in the invasive yellowjacket Vespula germanica (Hymenoptera: Vespidae).

Abstract: Inbreeding costs can be high in haplodiploid hymenopterans due to their particular mechanism of sex determination (i.e., single-locus complementary sex-determination system, sl-CSD), as it can lead to the production of sterile males. Therefore, mechanisms contributing to reduced inbred matings can be beneficial. In this sense, asynchronous nest departure of sibling drones and gynes could reduce kin encounters in social hymenopterans. Using six observation colonies, we determined under field conditions the nest departure behaviour of sibling reproductives of the social wasp Vespula germanica (Hymenoptera: Vespidae). We determined that sexuals leave the nests definitively and detected asynchronous departure not fixed to a particular caste at a seasonal scale in some colonies, as gynes or drones delayed their departure as a function of the departure of the opposite sex, depending on the colony. At a higher temporal resolution (i.e., within a day), we discovered that drones consistently began to leave nests 1 h before gynes and this difference was driven by those individuals that left on the same day as did the opposite-sex kin. Even though other mechanisms such as polyandry and differential dispersal could also be important at reducing inbred matings in the species, the observed departure patterns (i.e., in some colonies actually leave together with the opposite caste, while in others temporal segregation seems to occur) from nests could be complementary to the former and be important at reducing the negative effects of inbreeding in this invasive species.

gynes
Drones
social wasp
temporal segregation
inbreeding avoidance
mating behaviour
outbreeding


Validation of Korean Version of the London Chest Activity of Daily Living Scale in Patients With Chronic Obstructive Pulmonary Disease.

Abstract:
Objective
To translate the English version of the London Chest Activity of Daily Living scale (LCADL) into a Korean version and to determine the reliability and validity of the Korean version in patients with chronic obstructive pulmonary disease (COPD).

Methods
The English version of LCADL was translated into Korean and back-translated into English. Subsequently, the back-translated version was reviewed and compared with the original, and thus the final K-LCADL was obtained. To evaluate the validation of the K-LCADL, patients simultaneously completed a pulmonary function test, a 6-Minute Walk Test (6MWT), and questionnaires, including the modified Medical Research Council (mMRC) dyspnea scale, the Korean version of the St. George's Respiratory Questionnaire (K-SGRQ), the Korean version of the COPD Assessment Test (K-CAT), and the Korean version of the EuroQoL-5 Dimensions (K-EQ-5D). To assess test-retest reliability, the K-LCADL was again administered to the same patients within 2 weeks from initial assessment.

Results
A total of 94 patients participated in the present study. The total K-LCADL score was positively correlated with the K-SGRQ (r=0.802, p<0.001), the mMRC dyspnea scale (r=0.603, p<0.001), and the K-CAT score (r=0.714, p<0.001), and negatively correlated with the K-EQ-5D (r=-0.764, p<0.001), 6MWT (r=-0.635, p<0.001), forced expiratory volume in one second 1 (r=-0.416, p=0.002), and forced vital capacity (r=-0.397, p=0.023). Intraclass correlation coefficient of the K-LCADL was 0.951 (p<0.001).

Conclusion
The K-LCADL is a reliable and valid questionnaire for evaluating limitation of activities of daily living in patients with COPD.

Validation
Activities of daily living
Chronic obstructive pulmonary disease
Dyspnea


Medicolegal Issues in Expedition and Wilderness Medicine.

Abstract: There is increased participation in wilderness expeditions to remote and austere environments, which increases the likelihood of an accident and/or medical emergency and the professional liability risks for trip organizers. Trip organizers, outfitters, tour guides, and health care providers must understand the medicolegal liabilities involved in and the legal protection and immunity available when rendering care in austere and challenging settings to mitigate risks and prepare for the level of medical care that may be required. There is a great deal of variability in the legal protections provided by Good Samaritan laws and interpretations may differ among jurisdictions.

Professional liability
Good Samaritan laws
Duty to rescue
Medical clearance
Medical malpractice
Waiver of liability


Reversible Thermochromism and Strong Ferromagnetism in Two-Dimensional Hybrid Perovskites.

Abstract: Two-dimensional (2D) hybrid perovskites have shown many attractive properties associated with their soft lattices and multiple quantum well structure. Herein, we report the synthesis and characterization of two new multifunctional 2D hybrid perovskites, (PED)CuCl4 and (BED)2 CuCl6 , which show reversible thermochromic behavior, dramatic temperature-dependent conductivity change, and strong ferromagnetism. Upon temperature change, the (PED)CuCl4 and (BED)2 CuCl6 crystals exhibit a reversible color change between yellow and red-brown. The associated structural changes were monitored by in situ temperature-dependent powder X-ray diffraction (PXRD). The (BED)2 CuCl6 exhibits superior thermal stability, with a thermochromic working temperature up to 443 K. The conductivity of (BED)2 CuCl6 changes over six orders of magnitude upon temperature change. The 2D perovskites exhibit ferromagnetic properties with Curie temperatures around 13 K.

thermochromism
ferromagnetism
conductivity
2D perovskites
copper


Novel synthetic bis-indolic derivatives with antistaphylococcal activity, including against MRSA and VISA strains.

Abstract:
OBJECTIVES
We report the synthesis, antibacterial activity and toxicity of 24 bis-indolic derivatives obtained during the development of new ways of synthesis of marine bis-indole alkaloids from the spongotine, topsentin and hamacanthin classes.

METHODS
Innovative ways of synthesis and further structural optimizations led to bis-indoles presenting either the 1-(1H-indol-3'-yl)-1,2-diaminoethane unit or the 1-(1H-indol-3-yl)ethanamine unit. MIC determination was performed for reference and clinical strains of Staphylococcus aureus and CoNS species. MBC, time-kill kinetics, solubility, hydrophobicity index, plasma protein-binding and cytotoxicity assays were performed for lead compounds. Inhibition of the S. aureus NorA efflux pump was also tested for bis-indoles with no antistaphylococcal activity.

RESULTS
Lead compounds were active against both S. aureus and CoNS species, with MICs between 1 and 4 mg/L. Importantly, the same MICs were found for MRSA and vancomycin-intermediate S. aureus strains. Early concentration-dependent bactericidal activity was observed for lead derivatives. Compounds with no intrinsic antibacterial activity could inhibit the S. aureus NorA efflux pump, which is involved in resistance to fluoroquinolones. At 0.5 mg/L, the most effective compound led to an 8-fold reduction of the ciprofloxacin MIC for the SA-1199B S. aureus strain, which overexpresses NorA. However, the bis-indole compounds displayed a high hydrophobicity index and high plasma protein binding, which significantly reduced antibacterial activity.

CONCLUSIONS
We have synthesized and characterized novel bis-indole derivatives as promising candidates for the development of new antistaphylococcal treatments, with preserved activity against MDR S. aureus strains.

Caspar|Yvan|Y|
Jeanty|Matthieu|M|
Blu|Jérôme|J|
Burchak|Olga|O|
Le Pihive|Emmanuelle|E|
Maigre|Laure|L|
Schneider|Dominique|D|
Jolivalt|Claude|C|
Paris|Jean-Marc|JM|
Hequet|Arnaud|A|
Minassian|Frédéric|F|
Denis|Jean-Noël|JN|
Maurin|Max|M|

bis-indoles
efflux pumps
antibiotics
drug development
drug susceptibility testing
staphylococci


Tollip is a critical mediator of cerebral ischaemia-reperfusion injury.

Abstract: Toll-like receptor (TLR) signalling plays an important role in regulating cerebral ischaemia-reperfusion (I/R) injury. Toll-interacting protein (Tollip) is an endogenous negative modulator of TLR signalling that is involved in several inflammatory diseases. Our previous study showed that Tollip inhibits overload-induced cardiac remodelling. However, the role of Tollip in neurological disease remains unknown. In the present study, we proposed that Tollip might contribute to the progression of stroke and confirmed this hypothesis. We found that Tollip expression was significantly increased in I/R-challenged brain tissue of humans, mice and rats in vivo and in primary neurons subjected to oxygen and glucose deprivation in vitro, indicating the involvement of Tollip in I/R injury. Next, using genetic approaches, we revealed that Tollip deficiency protects mice against I/R injury by attenuating neuronal apoptosis and inflammation, as demonstrated by the decreased expression of pro-apoptotic and pro-inflammatory genes and the increased expression of anti-apoptotic genes. By contrast, neuron-specific Tollip over-expression exerted the opposite effect. Mechanistically, the detrimental effects of Tollip on neuronal apoptosis and inflammation following I/R injury were largely mediated by the suppression of Akt signalling. Additionally, to further support our findings, a Tollip knockout rat strain was generated via CRISPR-Cas9-mediated gene inactivation. The Tollip-deficient rats were also protected from I/R injury, based on dramatic decreases in neuronal apoptosis and ischaemic inflammation through Akt activation. Taken together, our findings demonstrate that Tollip acts as a novel modulator of I/R injury by promoting neuronal apoptosis and ischaemic inflammation, which are largely mediated by suppression of Akt signalling.

Li|Mingchang|M| Feng|Bin|B| Wang|Lang|L| Guo|Sen|S| Zhang|Peng|P| Gong|Jun|J| Zhang|Yan|Y| Zheng|Ankang|A| Li|Hongliang|H|

D047908:Intracellular Signaling Peptides and Proteins

Tollip
stroke
apoptosis
Akt
knockout rat


Identification and expression of a unique neonatal variant of the GABAA receptor α3 subunit.

Abstract: The GABAA receptor provides the majority of inhibitory neurotransmission in the adult central nervous system but in immature brain is responsible for much of the excitatory drive, a requirement for normal brain development. It is well established that GABAA receptor subunit expression changes across the course of brain development. In the present study, we have identified a splice variant of the GABAA receptor α3 subunit which appears unique to the developing brain, referred to here as the GABAA receptor α3 subunit neonatal variant (GABAA receptor α3N). RT-PCR and sequence analysis revealed splicing of exon 8 of the α3 subunit. Western blot analysis showed expression of GABAA receptor α3N in the cortex of several neonatal species and significantly reduced expression of this splice variant in the corresponding adult brains. Expression was evident in multiple brain regions and decreased across development in the pig. Fractionation revealed differential cellular localisation in the parietal cortex, hippocampus and thalamus of the full-length GABAA receptor α3 and GABAA receptor α3N. Immunoprecipitation showed direct interaction with the GABAA receptor subunits α1 and γ2 but not with gephyrin.


Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma.

Abstract: The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

liquid biopsy
monocarboxylate transporter 1
extracellular vesicles
synovial sarcoma
non-invasive biomarker


Detection of bacterial contamination and DNA quantification in stored blood units in 2 veterinary hospital blood banks.

Abstract: Blood transfusions in veterinary medicine have become increasingly more common and are now an integral part of lifesaving and advanced treatment in small and large animals. Important risks associated with transfusion of blood products include the transmission of various infectious diseases. Several guidelines suggest what infectious agents to screen for in canine and feline transfusion medicine. However, while the risk of bacterial contamination of blood products during storage and administration has not been documented in veterinary medicine, it has emerged as a cause of morbidity and mortality in human transfusion medicine. Clinical experience shows that the majority of blood component bacterial contaminations are caused by only a few species. Unlike other types of bacteria, psychrotolerant species like Pseudomonas spp. and Serratia spp. can proliferate during the storage of blood units at 4°C from a very low titer at the time of blood collection to a clinically significant level (> 10(5) CFU/mL) causing clinical sepsis resulting from red blood cell concentrate transfusions in human medicine. The purpose of this report was to describe the detection and quantification procedures applied in 4 cases of bacterial contamination of canine and feline blood units, which suggest the need for further investigations to optimize patients' safety in veterinary transfusion medicine.

Bacterial contamination
blood transfusion
blood products
Pseudomonas spp.
Serratia spp.


A comparison of clinical outcomes following atrial fibrillation ablation for heart failure patients with preserved or reduced left ventricular function: A systematic review and meta-analysis.

Abstract:
BACKGROUND
This review aims to determine if patients who undergo atrial fibrillation (AF) ablation with heart failure with preserved ejection fraction (HFpEF) do better, or worse or the same compared to patients with heart failure with reduced ejection fraction (HFrEF).

METHODS
A search of MEDLINE and EMBASE was performed using the search terms: "atrial fibrillation", "ablation" and terms related to HFpEF and HFrEF in order to identify studies that evaluated one or more of i) AF recurrence, ii) periprocedural complications and iii) adverse outcomes at follow up for patients with HFpEF and HFrEF who underwent AF ablation. Data was extracted from included studies and statistically pooled to evaluate adverse events and AF recurrence.

RESULTS
5 studies were included in this review and the sample size of the studies ranged from 91 to 521 patients with heart failure. There was no significant difference in the pooled rate for no AF or symptom recurrence after AF ablation comparing patients with HFpEF vs HFrEF (RR 1.07 95%CI 0.86-1.33, p = 0.15). The most common complications were access site complications/haematoma/bleeding which occurred in similar proportion in each group; HFpEF (3.1%) and HFrEF (3.1%). In terms of repeat ablations, two studies were pooled to yield a rate of 78/455 (17.1%) for HFpEF vs 24/279 (8.6%) for HFrEF (p = 0.001.

CONCLUSIONS
Heart failure patients with preserved or reduced ejection fraction have similar risk of AF or symptom recurrence after AF ablation but two studies suggest that patients with HFpEF are more likely to have repeat ablations.

Panchal|Gaurav|G|
Kwok|Chun Shing|CS|
Morley-Davies|Adrian|A|
Zachariah|Donah|D|
Phan|Thanh|T|

Heart failure with preserved ejection fraction

Heart failure with reduced ejection fraction


Pharmacogenetics and nutritional supplementation in age-related macular degeneration.

Abstract: The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available.

Hampton|Blake M|BM|
Kovach|Jaclyn L|JL|
Schwartz|Stephen G|SG|

age-related maculopathy susceptibility 2 (ARMS2)


STAT3 hyperactivation due to SOCS3 deletion in murine osteocytes accentuates responses to exercise- and load-induced bone formation.

Abstract: Cortical bone develops and changes in response to mechanical load, which is sensed by bone-embedded osteocytes. The bone formation response to load depends on STAT3 intracellular signals, which are upregulated after loading, and are subject to negative feedback from Suppressor of Cytokine Signaling 3 (Socs3). Mice with Dmp1Cre-targeted knockout of Socs3 have elevated STAT3 signaling in osteocytes and display delayed cortical bone maturation characterized by impaired accrual of high-density lamellar bone. This study aimed to determine whether these mice exhibit an altered response to mechanical load. The approach used was to test both treadmill running and tibial compression in female Dmp1Cre.Socs3f/f mice. Treadmill running for 5 days per week from 6 to 11 weeks of age did not change cortical bone mass in control mice, but further delayed cortical bone maturation in Dmp1Cre.Socs3f/f mice. Accrual of high-density bone was further suppressed, and cortical thickness was less than in genetically matched sedentary controls. When strain-matched anabolic tibial loading was tested, both control and Dmp1Cre.Socs3f/f mice exhibited a significant increase in cortical thickness and periosteal perimeter in loaded tibia compared to the contralateral non-loaded bone. At the site of greatest compressive strain, the loaded Dmp1Cre.Socs3f/f tibiae showed a significantly greater response than controls, indicated by a greater increase in cortical thickness. This was due to a greater bone formation response on both periosteal and endocortical surfaces, including formation of abundant woven bone on the periosteum. This suggests a greater sensitivity to mechanical load in Dmp1Cre.Socs3f/f bone. In summary, mice with targeted SOCS3 deletion and immature cortical bone have an exaggerated response to both physiological and experimental mechanical loads. We conclude that there is an optimal level of osteocytic response to mechanical load required for cortical bone maturation and that load-induced bone formation may be increased by augmenting STAT3 signaling within osteocytes.


The dynamic eggs of the Phasmatodea and their apparent convergence with plants.

Abstract: The egg stages of animal life cycles are underappreciated in terms of their capacity for dispersal, protection, and biotic and abiotic interactions. Some of the most intriguing egg morphologies are seen in stick and leaf insects (Phasmatodea). Phasmids are charismatic insects, particularly due to their incredible camouflage, though a lesser-known fact is that their eggs are incredibly diverse in shape and structure, reflecting varying ecological niches. Perhaps most remarkable are those eggs which appear to resemble plant seeds in both their appearance and means of dispersal, such as via water and animal vectors. Numerous hypotheses surrounding the function of these egg morphologies and their apparent convergence with seeds have been proposed; however, empirical evidence remains lacking. Here, we present an initial synthesis of available evidence surrounding the ecology and dispersal strategies of phasmid eggs and weigh up the evidence for convergent evolution between phasmid eggs and seeds. In doing so, we highlight areas where further research is needed and discuss how the ecology of phasmid eggs may interplay with other aspects of phasmid ecology, distribution, and evolution.

Egg
Dispersal
Seeds
Myrmecochory
Phoresy
Stick insects


Improved non-destructive method for 90Sr activity determination in aqueous solutions using Monte Carlo simulation.

Abstract: The development of new methods and improvements of existing methods for the specific activity determination of 90Sr and other distinct beta emitters has been of considerable interest. The reason for this interest is that the notably small number of methods that are able to meet all the set criteria, such as reliability of the results, measurement uncertainty and time, and minimum production of radioactive waste, as well as applicability to various samples with reference to their nature, geometry and composition. In this paper, two methods for rapid 90Sr activity determination based on Monte Carlo simulations are used, one for a Si semiconductor detector for beta spectrometric measurements and the other for the Geiger-Muller (GM) ionization probe. To improve the reliability of the measurement results, samples with high and low strontium activity solutions were prepared in the form of dry residues. The results of the proposed methodology were verified with a standard method using a liquid scintillation counter, and notably good agreements are achieved.

Samardžić|Selena|S| Milošević|Miodrag|M| Todorović|Nataša|N| Lakatoš|Robert|R|

D001610:Beta Particles
D003198:Computer Simulation
D006801:Humans
D009010:Monte Carlo Method
D055848:Nuclear Power Plants
D011834:Radiation Monitoring
D011848:Radioactive Pollutants
D011874:Radiometry
D015203:Reproducibility of Results
D012588:Scintillation Counting
D012666:Semiconductors
D012825:Silicon
D013326:Strontium Radioisotopes
D014875:Water Pollutants, Radioactive

Si semiconductor detector
GM probe
MCNP-5 simulation
Sr activity


Outcomes of Patients With Hypothyroidism and COVID-19: A Retrospective Cohort Study.

Abstract: Coronavirus diseases (COVID-19) is associated with high rates of morbidity and mortality and worse outcomes have been reported for various morbidities. The impact of pre-existing hypothyroidism on COVID-19 outcomes remains unknown. The aim of the present study was to identify a possible association between hypothyroidism and outcomes related to COVID-19 including hospitalization, need for mechanical ventilation, and all-cause mortality. All patients with a laboratory confirmed COVID-19 diagnosis in March 2020 in a large New York City health system were reviewed. Of the 3703 COVID-19 positive patients included in present study, 251 patients (6.8%) had pre-existing hypothyroidism and received thyroid hormone therapy. Hypothyroidism was not associated with increased risk of hospitalization [Adjusted Odds Ratio (ORadj): 1.23 (95% Confidence Interval (CI): 0.88- 1.70)], mechanical ventilation [ORadj: 1.17 (95% CI: 0.81-1.69)] nor death [ORadj: 1.07 (95% CI: 0.75-1.54)]. This study provides insight into the role of hypothyroidism on the outcomes of COVID-19 positive patients, indicating that no additional precautions or consultations are needed. However, future research into the potential complications of COVID-19 on the thyroid gland and function is warranted.

van Gerwen|Maaike|M|
Alsen|Mathilda|M|
Little|Christine|C|
Barlow|Joshua|J|
Naymagon|Leonard|L|
Tremblay|Douglas|D|
Sinclair|Catherine F|CF|
Genden|Eric|E|

outcomes hypothyroidism COVID-19 cohort epidemiology survival


Hydroxytyrosol regulates the autophagy of vascular adventitial fibroblasts through the SIRT1-mediated signaling pathway.

Abstract: Hydroxytyrosol (HT), a phenolic compound in olive oil, exerts an anti-inflammatory effect in cardiovascular diseases. Recent studies found that autophagy was a therapeutic target of diseases. However, the effect of HT on autophagy in vascular adventitial fibroblasts (VAFs) remains unknown. Thus, in this study, we aimed to determine the effect of HT on cell autophagy and related signaling pathway and whether HT regulates the inflammatory response through autophagy in VAFs. Our results showed that HT promoted cell autophagy by increasing the conversion of LC3 and Beclin1 expression and the autophagic flux in VAFs stimulated with tumor necrosis factor-α (TNF-α). HT also upregulated the expression of the deacetylase sirtuin 1 (SIRT1) protein and mRNA compared with the TNF-α group. The molecular docking studies showed the good compatibility between HT and SIRT1, indicating that HT might act through SIRT1. Further study found that HT regulated autophagy through SIRT1-mediated Akt/mTOR suppression in VAFs. In addition, HT inhibited TNF-α-induced inflammatory response in VAFs through SIRT1. Furthermore, the study showed that HT inhibited the inflammatory response of VAFs through autophagy. These findings indicate that HT regulates the autophagy of VAFs through SIRT1-mediated Akt/mTOR suppression and then inhibits the inflammatory response of VAFs.

Wang|Weirong|W| Jing|Ting|T| Yang|Xiaofeng|X| He|Yanhao|Y| Wang|Bo|B| Xiao|Yunfang|Y| Shang|Chenxu|C| Zhang|Jiye|J| Lin|Rong|R|

hydroxytyrosol
autophagie
autophagie
vascular adventitial fibroblasts
SIRT1
Akt/mTOR
autophagy
fibroblastes de l’adventice vasculaire
inflammation


Prevalence of Internalized HIV-Related Stigma Among HIV-Infected Adults in Care, United States, 2011-2013.

Abstract: HIV-infected U.S. adults have reported internalized HIV-related stigma; however, the national prevalence of stigma is unknown. We sought to determine HIV-related stigma prevalence among adults in care, describe which socio-demographic groups bear the greatest stigma burden, and assess the association between stigma and sustained HIV viral suppression. The Medical Monitoring Project measures characteristics of U.S. HIV-infected adults receiving care using a national probability sample. We used weighted data collected from June 2011 to May 2014 and assessed self-reported internalized stigma based on agreement with six statements. Overall, 79.1% endorsed ≥1 HIV-related stigma statements (n = 13,841). The average stigma score was 2.4 (out of a possible high score of six). White males had the lowest stigma scores while Hispanic/Latina females and transgender persons who were multiracial or other race had the highest. Although stigma was associated with viral suppression, it was no longer associated after adjusting for age. Stigma was common among HIV-infected adults in care. Results suggest individual and community stigma interventions may be needed, particularly among those who are <50 years old or Hispanic/Latino. Stigma was not independently associated with viral suppression; however, this sample was limited to adults in care. Examining HIV-infected persons not in care may elucidate stigma's association with viral suppression.

Baugher|Amy R|AR|
Beer|Linda|L|
Fagan|Jennifer L|JL|
Mattson|Christine L|CL|
Freedman|Mark|M|
Skarbinski|Jacek|J|
Shouse|R Luke|RL|
|||

Stigma
United States
HIV
Viral suppression
Age


Comparison of photon volumetric modulated arc therapy, intensity-modulated proton therapy, and intensity-modulated carbon ion therapy for delivery of hypo-fractionated thoracic radiotherapy.

Abstract:
PURPOSE
The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy.

METHODS AND MATERIALS
Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared.

RESULTS
There were no significant differences in target volume dose coverage or dose conformity, except improved D95 was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D1cc and D5cc for major blood vessels, as compared with IMPT (p = 0.01).

CONCLUSION
Although it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion.

Chi|Alexander|A| Lin|Lien-Chun|LC| Wen|Sijin|S| Yan|Haijuan|H| Hsi|Wen-Chien|WC|


Diagnosis and surgical repair of congenital double aortic arch in infants.

Abstract:
OBJECTIVES
Double aortic arch (DAA) is a rare congenital vascular malformation. This study aims to summarize the experience of diagnosis and surgical treatment for congenital double aortic arch.

METHODS
The clinical data of 24 cases with double aortic arch (DAA) from January 2008 to January 2018 in our hospital was reviewed retrospectively.

RESULTS
A total of 24 cases, including 12 patients with isolated DAA and 12 patients with DAA and associated intracardiac defects were identified. There were 14 males and 10 females, with an average age of 11 months. The associated intracardiac malformations included ventricular septal defect (VSD), atrial septal defect (ASD), patent ductus arteriosus (PDA), tetralogy of Fallot (TOF), transposition of the great arteries (TGA), pulmonary stenosis (PS), and patent foramen ovale (PFO). Of the 12 patients with DAA and intracardiac malformations, 7 patients underwent intracardiac repair simultaneously, however, 3 patients underwent isolated double aortic arch correction. One patient with DAA and TGA underwent surgical correction of congenital vascular ring at the first stage, and the arterial switch operation was performed at the second stage. The clinical outcomes of 23 patients were promising, however, in one patient, parents decided not to do the surgery due to personal reasons. The average follow-up time was 35 months.

CONCLUSIONS
Tracheal and esophageal compression are commonly seen in patients with DAA, however could be relieved significantly after surgery. In particular cases, the simultaneous intracardiac defects repair could be performed. Misdiagnosis was easily established with isolated echocardiography. Fortunately, the correct diagnosis of DAA and associated intracardiac defects could be established with the use of combined chest computed tomography.

Yang|Yiting|Y| Jin|Xin|X| Pan|Zhengxia|Z| Li|Yonggang|Y| Wu|Chun|C|

Double aortic arch
Cardiac malformation
Cardiac surgery
Esophagus stenosis
Tracheal stenosis
Tracheal stenosis index


Comparison between recent and long-term physical activity levels as predictors of cardiometabolic risk: a cohort study.

Abstract:
OBJECTIVE
To compare recent and long-term physical activity levels as predictors of cardiometabolic risk in a risk factor-free adult population.

DESIGN
A 12-year prospective cohort study.

SETTING
The Finnish Public Sector study with surveys conducted in four waves at 4-year intervals.

PARTICIPANTS
19 230 participants (mean age 50.2 (SD 9.1) years, 84% women) with no prevalent cardiometabolic risk factors at wave 3 were included. Physical activity was assessed at waves 1, 2 and 3. The long-term physical activity level was determined as the mean of activity from wave 1 to 3 (over 8 years).

OUTCOME MEASURE
4-year incidence of cardiometabolic risk factors (obesity, hypertension, dyslipidaemia and diabetes) after wave 3, measured individually and as a sum (accumulation of two or more risk factors vs none). Logistic and multinomial logistic regression analyses were used for the analysis.

RESULTS
Graded associations between higher physical activity levels and lower odds of all risk factors were observed (p for trend <0.01). In comparison with the persistently vigorously active participants (≥60 metabolic equivalent (MET)-hours/week), those who were persistently inactive (<7 MET-hours/week) were about four times more likely to develop obesity (OR=4.24, 95% CI=2.83 to 6.36), two times more likely to develop hypertension (OR=2.02, 95% CI=1.45 to 2.82) and dyslipidaemia (OR=1.82, 95% CI=1.03 to 3.22) and eight times more likely to develop diabetes (OR=7.84, 95% CI=1.78 to 34.6). The corresponding OR for accumulating two or more risk factors was 5.24-fold (95% CI=2.39 to 11.47). For recently inactive versus recently vigorously active, the estimates were weaker (OR=2.36, 95% CI=1.71 to 3.25 for obesity; 1.78, 95% CI=1.35 to 2.35 for hypertension; 1.71, 95% CI=1.04 to 2.82 for dyslipidaemia; 3.56, 95% CI=1.06 to 11.96 for diabetes and 2.66, 95% CI=1.48 to 4.78 for ≥2 risk factors).

CONCLUSION
Cardiometabolic risk associated with physical inactivity is better captured by repeated measurements of physical activity than by a single measurement of the most recent activity level.

physical activity
obesity
hypertension
dyslipidaemia
diabetes


A Side Door to Meckel's Cave: Anatomic Feasibility Study for the Lateral Transorbital Approach.

Abstract:
BACKGROUND
In the last decade, endoscopic skull base surgery has significantly developed and generated a plethora of techniques and approaches for access to the cranial ventral floor. However, the exploration for the least-aggressive, maximally efficient approach continues.

OBJECTIVE
To describe in detail an anatomical study, along with the technical nuances of a novel endoscopic approach to Meckel's Cave (MC) using a lateral transorbital (LTO) route.

METHODS
Eighteen orbits of injected cadaveric specimens were operated on, using an endoscopic LTO approach to MC, middle cranial fossa, and paramedian skull base preserving the orbital rim. Surgical navigation and an after-the-fact infratemporal craniectomy were utilized to identify the limits of the approach.

RESULTS
Following a transorbital approach opening a trapezoid window at the superolateral aspect (average 166.7 mm 2 ), a middle fossa "peeling" and full visualization of MC was accomplished with no difficulties in all specimens. The entire approach was performed extradurally without the need to expose the temporal lobe.

CONCLUSION
In a cadaveric model, the endoscopic LTO approach affords a direct route to access MC. Its main advantage is that it is minimally disruptive in nature, less brain retraction is required, and it reaches the middle fossa in an anterolateral perspective. It also requires no manipulation of the temporalis muscle, limited cosmetic incision, and rapid recovery. It seems a viable alternative to traditional approaches for lesions lateral to the cranial nerves at the cavernous sinus and MC, that is, schwannomas. Clinical utilization of this approach will challenge its efficacy and identify limitations.

Priddy|Blake Harrison|BH|
Nunes|Cristian Ferrareze|CF|
Beer-Furlan|Andre|A|
Carrau|Ricardo|R|
Dallan|Iacopo|I|
Prevedello|Daniel Monte-Serrat|DM|

Meckel's Cave
Transorbital
Schwannoma
Endoscopy
Gasserian
Trigeminal


Antihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: In vivo, functional ex vivo and in silico studies.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Achillea millefolium L. (Asteraceae), known as yarrow (milenrama), is a plant used in Mexican traditional medicine for the treatment of hypertension, diabetes, and related diseases.

AIM
To determine the vasorelaxant and antihypertensive effect of A. millefollium and to isolate the main bioactive antihypertensive agents.

MATERIALS AND METHODS
Organic (hexane, dichloromethane and methanol) and hydro-alcohol (Ethanol-H2O: 70:30) extracts obtained from flowers, leaves and stems were evaluated on isolated aorta rat rings with and without endothelium to determine their vasorelaxant effect. Hexane extract from flowers (HEAmF) was studied to evaluate its antihypertensive effect on spontaneously hypertensive rats (SHR). From HEAmF, bioactive compounds were obtained by bio-guided phytochemical separation through chromatography.

RESULTS
Organic extracts showed the best vasorelaxant activity. Hexane extract from flowers was the most potent and efficient ex vivo vasorelaxant agent, showing significant decrease of systolic and diastolic blood pressure in SHR (p < 0.05). Phytochemical separation of HEAmF yielded two epimeric sesquiterpene lactones: leucodin (1) and achillin (2), the major components of the extract. Both 1 and 2 showed similar vasorelaxant action ex vivo (p < 0.05), and their effects where modified by L-NAME (10 μM, nitric oxide synthase inhibitor), by ODQ (1 μM, soluble guanylyl cyclase inhibitor), and also relaxed the contraction induced by KCl (80 mM). Finally, 1 and 2 intragastric administration (50 mg/kg) decreased systolic and diastolic blood pressure in SHR.

CONCLUSIONS
Achillea millefolium showed antihypertensive and vasorelaxant effects, due mainly to leucodin and achillin (epimers). Both compounds showed antihypertensive activity by vasorelaxation putatively by endothelium-dependent NO release and cGMP increase, as well as by calcium channels blockade.

Arias-Durán|Luis|L|
Estrada-Soto|Samuel|S|
Hernández-Morales|Monserrat|M|
Millán-Pacheco|César|C|
Navarrete-Vázquez|Gabriel|G|
Villalobos-Molina|Rafael|R|
Ibarra-Barajas|Maximiliano|M|
Almanza-Pérez|Julio C|JC|

Antihypertensive
Vasorelaxation
Leucodin
Achillin
Calcium channel blockade
Aorta


Metabolic depression and the evolution of hypoxia tolerance in threespine stickleback, Gasterosteus aculeatus.

Abstract: Anthropogenic increases in global temperature and agricultural runoff are increasing the prevalence of aquatic hypoxia throughout the world. We investigated the potential for a relatively rapid evolution of hypoxia tolerance using two isolated (for less than 11 000 years) populations of threespine stickleback: one from a lake that experiences long-term hypoxia (Alta Lake, British Columbia) and one from a lake that does not (Trout Lake, British Columbia). Loss-of-equilibrium (LOE) experiments revealed that the Alta Lake stickleback were significantly more tolerant of hypoxia than the Trout Lake stickleback, and calorimetry experiments revealed that the enhanced tolerance of Alta Lake stickleback may be associated with their ability to depress metabolic rate (as indicated by metabolic heat production) by 33% in hypoxia. The two populations showed little variation in their capacities for O2 extraction and anaerobic metabolism. These results reveal that intraspecific variation in hypoxia tolerance can develop over relatively short geological timescales, as can metabolic rate depression, a complex biochemical response that may be favoured in long-term hypoxic environments.

metabolic depression
hypoxia tolerance
threespine stickleback
calorimetry
fish
oxygen consumption


Roseovarius nitratireducens sp. nov., a halotolerant bacterium isolated from a saline lake.

Abstract: A Gram-stain-negative, aerobic, non-motile and ovoid- to rod-shaped bacterial strain, designated TFZT, was isolated from a water sample of a saline lake in Xinjiang, China and subjected to polyphasic taxonomic investigation. Strain TFZT grew at 4-42 °C and pH 6.5-10.0 (optimum, 30 °C and pH 7.0) and with 0.5-18.0 % (w/v) NaCl (optimum, 1.5 %). According to phylogenetic analysis based on 16S rRNA gene sequences, strain TFZT was assigned to the genus Roseovarius with highest 16S rRNA gene sequence similarity of 97.5 % to Roseovarius tolerans EL-172T, followed by Roseovarius azorensis SSW084T (96.6 %) and Roseovarius mucosus DSM 17069T (95.5 %). Digital DNA-DNA hybridization (DDH) and average nucleotide identity (ANI) were determined to evaluate the genomic relationship between strain TFZT and R. tolerans EL-172T. Digital DDH estimation (22.80±2.35 %) as well as ANI (80.1 %) proved the dissimilarity of strain TFZT. Chemotaxonomic analysis showed that strain TFZT contained ubiquinone-10 as the predominant respiratory quinone and possessed summed feature 8 (comprising C18 : 1 ω7c and/or ω6c) and C16 : 0 as the predominant form of fatty acid. The polar lipids of strain TFZT consisted of phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and five unidentified lipids. The DNA G+C content was 65.4 mol% (by genome sequencing). Based on the polyphasic taxonomic characterization, strain TFZT is considered to represent a novel species of the genus Roseovarius, for which the name Roseovarius nitratireducens sp. nov. is proposed (type strain TFZT=MCCC 1K03339T=KCTC 52967T).

Shen|Xia|X| Zhao|Zhe|Z| Wu|Chen|C| Yu|Xiao-Yun|XY| Li|Yu|Y| Sun|Cong|C| Wu|Min|M|

Roseovarius nitratireducens
saline lake
taxonomy


Diagnosis of inflammatory peri-implant diseases using an immunochromatographic assay for calprotectin in peri-implant crevicular fluid.

Abstract:
BACKGROUND
The incidence rate of peri-implant diseases is increasing with implant placement. Early detection of peri-implant diseases is important to prevent and treat these diseases, and a simple and objective diagnostic method is expected. Immunochromatographic (IC) assays are used for rapid diagnostic methods for some diseases. The aim of this clinical study was to determine the amount of calprotectin, an inflammatory marker, in peri-implant crevicular fluid (PICF) using an IC chip, and estimate the possibility of this diagnostic system.

METHODS
Forty-six individuals with dental implants participated in a pilot study. PICF samples were collected from the peri-implant sites with or without inflammation after clinical examinations including probing depth (PD), bleeding on probing (BOP) and gingival index (GI). Calprotectin in PICF was determined by an IC chip and enzyme-linked immunosorbent assay (ELISA) for calprotectin. The density of calprotectin line on the IC chip was measured using an IC reader (IC reader value). The relationship between IC reader value and ELISA value or clinical parameters was investigated. A receiver operating characteristic (ROC) curve analysis of IC reader value of calprotectin was performed to predict inflammation in peri-implant diseases.

RESULTS
IC reader value of calprotectin was significantly correlated with its ELISA value and PD. IC reader values of calprotectin in PICF samples from periodontal sites with GI-1 and GI-2, and with BOP-positive sites were significantly higher than those of PICF samples from GI-0 sites, and BOP-negative sites, respectively. The IC reader value for calprotectin in PICF samples from inflammatory diseased sites was significantly higher than that of non-diseased sites. ROC analysis suggested that the IC reader value of PICF calprotectin was useful for predicting inflammatory peri-implant diseases.

CONCLUSION
IC assay for PICF calprotectin may be a possible system for diagnosing the inflammatory peri-implant diseases.

Kido|Rie|R| Kido|Jun-Ichi|JI|0000-0002-3949-5931 Nishikawa|Yasufumi|Y| Sakamoto|Eijiro|E| Tomotake|Yoritoki|Y| Yumoto|Hiromichi|H|

Diagnosis
Peri-implant diseases
Immunochromatographic assay
Calprotectin
Peri-implant crevicular fluid


Questions Regarding the Implementation of EU Mutagenesis Ruling in France.

Abstract: The European Commission has asked EU Member States for comments on a French law notification demanding plant varieties produced with the help of in vitro mutagenesis have to be eliminated from the national catalog of approved varieties because of missing legal authorization deemed required by genetic engineering law. Primary target are herbicide-tolerant Clearfield oilseed rape varieties. The scientific reasoning is questionable, traceability is illusive, and law enforcement is likely to be impossible.

Bartsch|Detlef|D| Ehlers|Ulrich|U| Hartung|Frank|F| Kahrmann|Jens|J| Leggewie|Georg|G| Sprink|Thorben|T| Wilhelm|Ralf|R|

Clearfield oilseed rape
European Commission (EC) decisions
mutagenesis techniques
plant breeding regulation
risk coherence


Association of MTHFR C677T and A1298C Polymorphisms with Susceptibility to Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis.

Abstract:
Background
The relation between methylenetetrahydrofolate reductase)MTHFR(polymorphisms and the risk of developing Chronic lymphocytic leukemia (CLL) is not still clear, while there are reports about the association of MTHFR C677T and A1298C polymorphisms with developing CLL, there are other reports that rolled out the association of MTHFR polymorphisms with developing CLL. Therefore herein we carried out this meta-analysis to clear the association of MTHFR polymorphisms with the risk of CLL.

Methods
A comprehensive search was performed through PubMed, Scopus and Embase from inception to Aug 2020. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was evaluated using the Cochran Q test and the I2 statistic.

Results
Totals of 1290 cases and 1887 controls for the C677T polymorphism and 1117 cases and 1256 controls for the A1298C polymorphism were included in our analysis. Analyzing the MTHFR C677T and A1298C polymorphisms genotypes showed an association between MTHFR polymorphism at A1298C under Allelic model and the risk of CLL (OR = 1.12, 95% CI = 1.01-1.25), however there was no association between MTHFR polymorphism at MTHFR C677T and risk of CLL.

Conclusion
The risk of developing CLL might be associated with MTHFR polymorphism at A1298C under allelic model and not associated with MTHFR polymorphisms at C677T, However, further studies considering other factors such as age, gender, ethnicity, gene-gene interaction and environmental condition are needed to clear the true association of MTHFR polymorphisms with CLL.

Raoufi|Atefeh|A|
Rahimi Kelarijani|Behdad|B|
Ahadi|Hamid Reza|HR|
Hassani Derakhshandeh|Bahareh|B|
Nooroollahzadeh|Zahra|Z|
Hajifathali|Abbas|A|


Influence of cleaning methods after 3D printing on two-body wear and fracture load of resin-based temporary crown and bridge material.

Abstract:
OBJECTIVES
To investigate the impact of different cleaning methods on the fracture load and two-body wear of additively manufactured three-unit fixed dental prostheses (FDP) for long-term temporary use, compared to the respective outcomes of milled provisional PMMA FDPs.

MATERIALS AND METHODS
Shape congruent three-unit FDPs were 3D printed using three different resin-based materials [FPT, GCT, NMF] or milled [TEL] (N = 48, n = 16 per group). After printing, the FDPs were cleaned using: Isopropanol (ISO), Yellow Magic 7 (YEL), or centrifugal force (CEN). Chewing simulation was carried out with a vertical load of 50 N (480,000 × 5 °C/55 °C). Two-body wear and fracture load were measured. Data were analyzed using global univariate ANOVA with partial eta squared, Kruskal-Wallis H, Mann-Whitney U, and Spearman's rho test (p < 0.05).

RESULTS
TEL showed less wear resistance than FPT (p = 0.001) for all cleaning methods tested. Concerning vertical material loss, NMF and GCT were in the same range of value (p = 0.419-0.997), except within FDPs cleaned in ISO (p = 0.021). FPT showed no impact of cleaning method on wear resistance (p = 0.219-0.692). TEL (p < 0.001) showed the highest and FPT (p < 0.001) the lowest fracture load. Regarding the cleaning methods, specimens treated with ISO showed lower fracture load than specimens cleaned with CEN (p = 0.044) or YEL (p = 0.036).

CONCLUSIONS
The material selection and the cleaning method can have an impact on two-body wear and fracture load results.

CLINICAL RELEVANCE
Printed restorations showed superior two-body wear resistance compared to milled FDPs but lower fracture load values. Regarding cleaning methods, ISO showed a negative effect on fracture load compared to the other methods tested.

D003442:Crowns
D003799:Dental Stress Analysis
D008422:Materials Testing
D066330:Printing, Three-Dimensional

Cleaning method
3D printing
Two-body wear
Fracture load
Additive manufacturing
Post-processing