Incidence and risk factors for cardiac implantable electronic device infection in current clinical settings in a Japanese population: A 20-year single-center observational study.

Abstract:
BACKGROUND
The incidence of cardiac implantable electronic device (CIED) infection is increasing worldwide. However, data regarding this phenomenon in Japan and information on factors associated with developing CIED infection are limited. Our aim was to compare the incidence of CIED infection between pre-current (past 10-20 years) and current (past 10 years) clinical settings and to investigate risk factors for CIED infection in current clinical settings in a Japanese population.

METHODS
This observational study included 1749 patients (age 77 ± 12 years, 824 males) who underwent a CIED-related procedure between August 1999 and July 2019 at our institution. We defined the pre-current and current clinical setting periods as August 1999-July 2009 (period I) and August 2009-July 2019 (period II), respectively. We compared the incidence rate of CIED infection between periods and evaluated the risk factors for CIED infection in period II by multivariate analysis.

RESULTS
A CIED infection was identified in 0.7% (5/709 patients) and 1.7% (17/1040) of patients in periods I and II, respectively. Notably, the rate of late (>6 months since last procedure) CIED infection was significantly increased in period II (1.3% vs. 0.1%, p < 0.01), despite the rate of early infection (≤6 months) being comparable (0.4% vs. 0.6%, p = 0.58). On multiple logistic regression, revision [odds ratio (95% confidence interval): 5.2 (1.6-16.3), p = 0.005] and age [0.96, (0.93-0.99), p = 0.007] were identified as independent risk factors for CIED infection in period II.

CONCLUSIONS
Our findings suggest that the increasing incidence of CIED infection in current clinical settings was due to an increase in late CIED infection. Furthermore, revision and younger age were identified as independent risk factors for CIED infection in current clinical settings. Our data indicate that clinicians should consider whether the merit of a procedure can overcome the risk of infection when planning revision or implantation in younger patients.

Ishiguchi|Hironori|H| Ishikura|Masahiro|M| Yoshida|Masaaki|M| Imoto|Koji|K| Sonoyama|Kazuhiko|K| Kawabata|Tetsuya|T| Ishihara|Yusuke|Y| Yoshiga|Yasuhiro|Y| Shimizu|Akihiko|A| Oda|Tsuyoshi|T|

Cardiac implantable electronic device
Infection
Pacemaker


Factors affecting test results and standardized method in quiet standing balance evaluation.

Abstract:
OBJECTIVE
To identify factors affecting test results of the quiet standing balance evaluation conducted by posturography and to investigate the standardized method by comparing results according to feet width.

METHOD
The study cohort consisted of 100 healthy individuals. We assessed the quiet standing balance of subjects by using 3 different methods: standing on a force plate with feet width the same as shoulder width (test 1); with feet width the same as half the shoulder width (test 2); with feet width determined by the subject's comfort (test 3). Subjects underwent each test with their eyes open and closed for 30 seconds each time. Parameters for measuring standing balance included the mean mediolateral and anteroposterior extent, speed, and the velocity moment of center of pressure (COP) movement.

RESULTS
All parameters showed better results when the subject's eyes were open rather than closed, and the mean AP extent and speed increased as the age of the subjects increased (p<0.01). However, there was no significant correlation between height and the study parameters, and no differences between men and women. Mean mediolateral extent and speed were significantly longer and faster in test 1 compared with tests 2 and 3 (p<0.01). The results of test 2 were better than the results of test 3, but the difference was not statistically significant.

CONCLUSION
COP movements increased with age and when subjects closed their eyes in an evaluation of quiet standing balance conducted by posturography. Gender and height did not affect results of the test. We suggest that an appropriate method for conducting posturography is to have the subject stand on a force plate with their feet width the same as half the shoulder width, because this posture provided relatively accurate balance capacity.

Yoon|Jung Joong|JJ|
Yoon|Tae Sik|TS|
Shin|Bo Mi|BM|
Na|Eun Hye|EH|


Revisiting the Applied Model for the Use of Observation: A Review of Articles Spanning 2011-2018.

Abstract: Purpose: To provide a review of current articles that have used observation interventions to enhance motor skill acquisition or performance of applied tasks, and to situate the research within the Applied Model for the Use of Observation (AMUO) with the goal of forming a basis for evidence-based guidelines for practitioners. Method: Key words (e.g., observation/modeling) were searched in varied data bases (e.g., Google Scholar/PubMed), along with a citation search of the relevant AMUO article, to generate a pool of articles for possible review. Selection criteria included publication between 2011 and 2018, and that the research focus was on the effects of an observation intervention on the acquisition or performance of an applied motor task. Results: Forty-eight articles were reviewed, with 21 of these targeting the basic question of whether observation is effective, and the remaining pertaining to the What, When, Who, and How features of the AMUO. The effectiveness of observation interventions was not only affirmed, but also extended to a wider scope of populations and settings. Greater insight into the necessary information with respect to the demonstration (what) and whether it should be before, after, or during physical practice (when) was obtained. As well, advantages of combining model types (who) and providing control to the learner (how) were reported. Conclusions: While more clarity was brought to certain features of the AMUO that could be used to provide evidence-based guidelines, more research is needed to fully inform practitioners for the effective use of observation interventions.

modeling
skill acquisition
Observational learning
performance enhancement


Current Understanding of Circulating Tumor Cells - Potential Value in Malignancies of the Central Nervous System.

Abstract: Detection of circulating tumor cells (CTCs) in the blood via so-called "liquid biopsies" carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date, studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies, one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems, such as the widely used Cell Search system, are reliant on markers, such as the epithelial cell adhesion molecule, which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors.

Adamczyk|Lukasz A|LA|
Williams|Hannah|H|
Frankow|Aleksandra|A|
Ellis|Hayley Patricia|HP|
Haynes|Harry R|HR|
Perks|Claire|C|
Holly|Jeff M P|JM|
Kurian|Kathreena M|KM|

circulating tumor cells
liquid biopsy
epithelial–mesenchymal transition
glioblastoma multiforme
glioma


Non-toxic doses of modified titanium dioxide nanoparticles (m-TiO2NPs) in albino CFW mice.

Abstract: Modified titanium dioxide (m-TiO2NPs) is a novel photocatalytic nanomaterial. Its level of toxicity was evaluated to be used in photodynamic treatment for cervical cancer. In the toxicity studies (Irwin test, acute and repeated doses (10 days)), female albino Swiss Webster (CFW) mice, 28 days old were used; the m-TiO2NPs was administered in single 300, 600 and 5,000 mg/kg of body weight (b.w) doses injected in the peritoneal zone. No adverse events or mortality were produced. Daily intraperitoneal doses of 300 and 600 mg/kg b.w every 24 h for 10 days did not produce adverse effects or mortality. There were no abnormal clinical signs or behavioral changes (neurological or physiological) in any of the mice. All organs exhibited normal architecture, and histological studies determined that m-TiO2NPs does not produce changes in the cells or tissues. Based on the test results, it is concluded that the m-TiO2NPs has not a toxic effect in doses equal to or less than 5,000 mg/kg b.w.

Basante-Romo|Mónica|M|
Gutiérrez-M|Jose Oscar|JO|
Camargo-Amado|Rubén|R|

Modified titanium dioxide
Acute toxicity
Murine biomodels
Repeated dose toxicity


Identification of a circulating microvesicle protein network involved in ST-elevation myocardial infarction.

Abstract: Membrane microvesicles (MVs) are released from activated cells, most notably platelets, into the circulation. They represent an important mode of intercellular communication, and their number is increased in patients with acute coronary syndromes. We present here a differential proteomic analysis of plasma MVs from ST-elevation myocardial infarction (STEMI) patients and stable coronary artery disease (SCAD) controls. The objective was the identification of MVs biomarkers/drug targets that could be relevant for the pathogenesis of the acute event. Proteome analysis was based on 2D-DIGE, and mass spectrometry. Validations were by western blotting in an independent cohort of patients and healthy individuals. A systems biology approach was used to predict protein-protein interactions and their relation with disease. Following gel image analysis, we detected 117 protein features that varied between STEMI and SCAD groups (fold change cut-off ≥2; p<0.01). From those, 102 were successfully identified, corresponding to 25 open-reading frames (ORFs). Most of the proteins identified are involved in inflammatory response and cardiovascular disease, with 11 ORFs related to infarction. Among others, we report an up-regulation of α2-macroglobulin isoforms, fibrinogen, and viperin in MVs from STEMI patients. Interestingly, several of the proteins identified are involved in thrombogenesis (e.g. α2-macroglobulin, and fibrinogen). In conclusion, we provide a unique panel of proteins that vary between plasma MVs from STEMI and SCAD patients and that might constitute a promising source of biomarkers/drug targets for myocardial infarction.

Vélez|Paula|P|
Parguiña|Andrés F|AF|
Ocaranza-Sánchez|Raymundo|R|
Grigorian-Shamagian|Lilian|L|
Rosa|Isaac|I|
Alonso-Orgaz|Sergio|S|
de la Cuesta|Fernando|F|
Guitián|Esteban|E|
Moreu|José|J|
Barderas|María G|MG|
González-Juanatey|José Ramón|JR|
García|Ángel|Á|

D044925:Oxidoreductases Acting on CH-CH Group Donors

Microvesicles
ST-elevation myocardial infarction
proteomics


Impacts of benzo(a)pyrene exposure on scallop (Chlamys farreri) gut health and gut microbiota composition.

Abstract: The gut tissue interacts with nutrients and pollutants which can impact gut health. Gut microbiota is essential to the host health, but is also easily affected by external environment. However, little is known about the toxicological assessment of environmental contaminants on gut health and microbiota, especially in marine invertebrates. In this study, we first explored the effect of benzo(a)pyrene (BaP) on the gut health and gut microbiota of scallops (Chlamys farreri). The scallops were exposed to different concentrations (0, 0.4, 2 and 10 μg/L) of BaP for 21 days. The histological morphology, immune- and oxidative enzyme-related gene expression, and lipid peroxidation of the scallops were analyzed at 7, 14 and 21 days. The results revealed that BaP could impair intestinal barrier function, increasing the intestinal permeability of scallops. Moreover, immune and antioxidant responses were induced in the gut tissue. After a 21-day exposure to different concentrations of BaP, the intestinal microbial community was analyzed based on 16S rRNA sequencing. Our results suggested that BaP exposure altered the gut microbial diversity and composition in scallops. Many beneficial genera declined after BaP treatment, while the potential pathogens were increased, such as Mycoplasma and Tenacibaculum. A series of hydrocarbon-degrading bacteria were recognized in BaP-treated groups, such as Pseudomonas, Polaribacter, Amphritea and Kordiimonas. Interestingly, the degrading bacteria present varied after exposure to different concentrations of BaP. Overall, this study provides new insights into gut health and gut microbiota in marine invertebrates following exposure to persistent organic pollutants.

Li|Dongyu|D| Miao|Jingjing|J| Pan|Luqing|L| Zhou|Yueyao|Y| Gao|Zhongyuan|Z| Yang|Yingying|Y| Xu|Ruiyi|R| Zhang|Xin|X|

Benzo(a)pyrene
Gut microbiota
Bivalve
Gut immunity


Prevalence of metallo-β-lactamase acquired genes among carbapenems susceptible and resistant Gram-negative clinical isolates using multiplex PCR, Khartoum hospitals, Khartoum Sudan.

Abstract:
BACKGROUND
The increased prevalence of carbapenem-resistant Gram-negative isolates caused by Metallo-β-lactamase (MBL) is worrisome in clinical settings worldwide. The mortality rate associated with infections caused by MBLs producing organisms ranging from 18 to 67%. This study aimed to determine the prevalence of Metallo-β-lactamase genes among some Gram-negative clinical isolates (Carbapenems susceptible and resistant).

METHODS
This paper describes a descriptive cross-sectional study carried out to detect MBL genes such as (blaVIM, blaIMP and blaNDM) by multiplex PCR mixture reaction among 200 Gram-negative clinical isolates (Citrobacter spp, Escherichia coli, Enterobacter spp, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Proteus valgaris). Khartoum hospitals during 2015 to 2016.

LIMITATION
The study organisms were not evaluated for non-MBL carbapenemases, such as KPC and OXA-48.

RESULTS
The prevalence of MBL genes by multiplex PCR assays among 200 Gram-negative clinical isolates was 72(36.1%). MBL positive genes among 100 carbapenems sensitive and 100 resistant isolates were 27(27%) and 45(45%) respectively. There was a statistically, significant association between the antimicrobial susceptibility and the presences of MBL genes (P.value = 0.008). E.coli was the predominant species possessing MBL genes 26(36.1%), with 22(30.7%) species having a combination of MBL genes. Verona integron Metallo beta-lactamase (VIM) was the most frequent genes 28(38.9%) out of 72 MBL detected genes, followed by imipenemase (IMP) was 19(26.4%), and consequently, New Delhi Metallo beta lactamase was 3(4.2%).

CONCLUSION
This study revealed a high prevalence of MBL genes in some Gram-negative isolates from Khartoum State Hospitals which were not previously established in these hospitals.

Adam|Mudathir Abdallah|MA|
Elhag|Wafa I|WI|

D060885:Multiplex Polymerase Chain Reaction

Carbapenem
PCR
Khartoum
VIM
IMP
Gram-negative bacteria
Metallo β-lactamase
NDM


Dose-intensive chemotherapy including rituximab is highly effective but toxic in human immunodeficiency virus-infected patients with Burkitt lymphoma/leukemia: parallel study of 81 patients.

Abstract: The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission. Four-year overall survival (OS) and progression-free survival (PFS) probabilities were 72% (95% confidence interval [CI]: 62-82%) and 71% (95% CI: 61-81%). CD4 T-cell count < 200/μL and bone marrow involvement were associated with poor OS (hazard ratio [HR] 3.2 [1.2-8.3] and HR 2.7 [1.1-6.6]) and PFS (HR 3.5 [1.3-9.1] and HR 2.4 [1-5.7]), bone marrow involvement with poor disease-free survival (DFS) (HR 14.4 [1.7-119.7] and Eastern Cooperative Oncology Group (ECOG) score > 2 (odds ratio [OR] 11.9 [1.4-99.9]) with induction death. In HIV-related BLL, intensive immunochemotherapy was feasible and effective, but toxic. Prognostic factors were performance status, CD4 T-cell count and bone marrow involvement.

Xicoy|Blanca|B|
Ribera|Josep-Maria|JM|
Müller|Markus|M|
García|Olga|O|
Hoffmann|Christian|C|
Oriol|Albert|A|
Hentrich|Marcus|M|
Grande|Carlos|C|
Wasmuth|Jan-Christian|JC|
Esteve|Jordi|J|
van Lunzen|Jan|J|
Del Potro|Eloy|E|
Knechten|Heribert|H|
Brunet|Salut|S|
Mayr|Christoph|C|
Escoda|Lourdes|L|
Schommers|Philipp|P|
Alonso|Natalia|N|
Vall-Llovera|Ferran|F|
Pérez|Montserrat|M|
Morgades|Mireia|M|
González|José|J|
Fernández|Angeles|A|
Thoden|Jan|J|
Gökbuget|Nicola|N|
Hoelzer|Dieter|D|
Fätkenheuer|Gerd|G|
Wyen|Christoph|C|
|||

D000971:Antineoplastic Combined Chemotherapy Protocols

prognostic factors
Burkitt lymphoma or leukemia
HIV infection
Specific chemotherapy


Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan in Castleman's Disease.

Abstract: Castleman's disease (CD) is a rare benign lymphoproliferative disorder. We are presenting three cases of CD of which one is unicentric CD, and the other two are an idiopathic multicentric CD. One of the two multicentric cases is associated with POEMS syndrome. The whole body 18F-Fluorodeoxyglucose positron-emission tomography-computed tomography scan plays a significant role in identifying the centricity, distribution of disease, response to therapy, and in early detection of remission.

Reddy Akepati|Naveen Kumar|NK|
Abubakar|Zakir Ali|ZA|
Bikkina|Prathyusha|P|


Association of the Single Nucleotide Polymorphisms in RUNX1, DYRK1A, and KCNJ15 with Blood Related Traits in Pigs.

Abstract: The aim of this study was to detect positional candidate genes located within the support interval (SI) regions based on the results of red blood cell, mean corpuscular volume (MCV), and mean corpuscular hemoglobin quantitative trait locus (QTL) in Sus scrofa chromosome 13, and to verify the correlation between specific single-nucleotide polymorphisms (SNPs) located in the exonic region of the positional candidate gene and the three genetic traits. The flanking markers of the three QTL SI regions are SW38 and S0215. Within the QTL SI regions, 44 genes were located, and runt-related transcription factor 1, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), and potassium inwardly-rectifying channel, subfamily J, member 15 KCNJ15-which are reported to be related to the hematological traits and clinical features of Down syndrome-were selected as positional candidate genes. The ten SNPs located in the exonic region of the three genes were detected by next generation sequencing. A total of 1,232 pigs of an F2 resource population between Landrace and Korean native pigs were genotyped. To investigate the effects of the three genes on each genotype, a mixed-effect model which is the considering family structure model was used to evaluate the associations between the SNPs and three genetic traits in the F2 intercross population. Among them, the MCV level was highly significant (nominal p = 9.8×10-9) in association with the DYRK1A-SNP1 (c.2989 G<A), and explained 4.9% of the phenotypic variance. However, since linkage disequilibrium is quite extensive in an F2 intercross, our approach has limited power to distinguish one particular positional candidate gene from a QTL region.

Lee|Jae-Bong|JB| Yoo|Chae-Kyoung|CK| Park|Hee-Bok|HB| Cho|In-Cheol|IC| Lim|Hyun-Tae|HT|

Blood Related Traits
Positional Candidate Gene
Landrace
Korean Native Pigs
Association Test


Physiological and molecular mechanisms underlying photoperiodism in the spider mite: comparisons with insects.

Abstract: Photoperiodism is an adaptive, seasonal timing system that enables organisms to coordinate their development and physiology to annual changes in the environment using day length (photoperiod) as a cue. This review summarizes our knowledge of the physiological mechanisms underlying photoperiodism in spider mites. In particular, the two-spotted spider mite Tetranychus urticae is focussed, which has long been used as a model species for studying photoperiodism. Photoperiodism is established by several physiological modules, such as the photoreceptor, photoperiodic time measurement system, counter system, and endocrine effector. It is now clear that retinal photoreception through the ocelli is indispensable for the function of photoperiodism, at least in T. urticae. Visual pigment, which comprised opsin protein and a vitamin A-based pigment, is involved in photoreception. The physiological basis of the photoperiodic time measurement system is still under debate, and we have controversial evidence for the hourglass-based time measurement and the oscillator-based time measurement. Less attention has been centred on the counter system in insects and mites. Mite reproduction is possibly regulated by the ecdysteroid, ponasterone A. Prior physiological knowledge has laid the foundation for the next steps essential for the elucidation of the molecular mechanisms driving photoperiodism.

Photoperiodism
Spider mite
Tetranychus urticae
Diapause
Photoperiodic response


Is Enhanced One-Stage Hepatectomy a Safe and Feasible Alternative to the Two-Stage Hepatectomy in the Setting of Multiple Bilobar Colorectal Liver Metastases? A Comparative Analysis between Two Pioneering Centers.

Abstract:
BACKGROUND
Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal metastases (CLM). As alternative, ultrasound-guided one-stage hepatectomy (E-OSH) has been proposed even for deep-located nodules to compare TSH and E-OSH.

METHODS
All consecutive TSH at the Paul Brousse Hospital and E-OSH at the Humanitas Research Hospital were considered. The inclusion criteria were ≥6 CLM, ≥3 CLM in the left liver, and ≥1 lesion with vascular contact. A total of 74 TSH and 35 E-OSH were compared.

RESULTS
The 2 groups had similar characteristics. Drop-out rate of TSH was 40.5%. In comparison with the cumulated hepatectomies of TSH, E-OSH had lower blood loss (500 vs. 1,100 mL, p = 0.009), overall morbidity (37.1 vs. 70.5%, p = 0.003), severe morbidity (14.3 vs. 36.4%, p = 0.04), and liver-specific morbidity (22.9 vs. 40.9%, p = 0.02). R0 resection rate was similar between groups. E-OSH and completed TSH had similar overall survival (5-year 38.2 vs. 31.8%), recurrence-free survival (3-year 17.6 vs. 17.7%), and recurrence sites.

CONCLUSIONS
E-OSH is a safe alternative to TSH for multiple bilobar deep-located CLM. Whenever feasible, E-OSH should even be considered the preferred option because it has excellent safety and oncological outcomes equivalent to completed TSH, without the drop-out risk.

Torzilli|Guido|G| Viganò|Luca|L| Cimino|Matteo|M| Imai|Katsunori|K| Vibert|Eric|E| Donadon|Matteo|M| Mansour|Doaa|D| Castaing|Denis|D| Adam|Ren|R|

Liver surgery for colorectal liver metastases


Transforming youth mental health services in a large urban centre: ACCESS Open Minds Edmonton.

Abstract:
AIM
This paper outlines the transformation of youth mental health services in Edmonton, Alberta, a large city in Western Canada. We describe the processes and challenges involved in restructuring how services and care are delivered to youth (11-25 years old) with mental health needs based on the objectives of the pan-Canadian ACCESS Open Minds network.

METHODS
We provide a narrative review of how youth mental health services have developed since our engagement with the ACCESS Open Minds initiative, based on its five central objectives of early identification, rapid access, appropriate care, continuity of care, and youth and family engagement.

RESULTS
Building on an initial community mapping exercise, a service network has been developed; teams that were previously age-oriented have been integrated together to seamlessly cover the age 11 to 25 range; early identification has thus far focused on high-school populations; and an actual drop-in space facilitates rapid access and linkages to appropriate care within the 30-day benchmark.

CONCLUSIONS
Initial aspects of the transformation have relied on restructuring and partnerships that have generated early successes. However, further transformation over the longer term will depend on data demonstrating how this has impacted clinical outcomes and service utilization. Ultimately, sustainability in a large urban centre will likely involve scaling up to a network of similar services to cover the entire population of the city.

Abba-Aji|Adam|A|0000-0003-0369-4768
Hay|Katherine|K|
Kelland|Jill|J|
Mummery|Christine|C|
Urichuk|Liana|L|
Gerdes|Cindy|C|
Snaterse|Mark|M|
Chue|Pierre|P|
Lal|Shalini|S|0000-0002-7501-5018
Joober|Ridha|R|
Boksa|Patricia|P|
Malla|Ashok|A|
N Iyer|Srividya|S|0000-0001-5367-9086
Shah|Jai L|JL|0000-0002-7549-6990

youth mental health
access
Canada
case identification
service transformation


High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial.

Abstract:
PURPOSE
This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock.

METHODS
Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care.

RESULTS
Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010).

CONCLUSION
The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

D000327:Adsorption
D017052:Hospital Mortality
D006801:Humans
D007362:Intensive Care Units
D017582:Renal Replacement Therapy
D012772:Shock, Septic

Continuous renal replacement therapy (CRRT)

Extracorporeal blood purification techniques


Cross-linked electrospun cartilage acellular matrix/poly(caprolactone-co-lactide-co-glycolide) nanofiber as an antiadhesive barrier.

Abstract:
In this work, we chose cartilage acellular matrix (CAM) as a promising antiadhesive material because CAM effectively inhibits the formation of blood vessels, and we used electrospinning to prepare antiadhesive barriers. Additionally, we synthesized N-hydroxysuccinimide (NHS)-poly(caprolactone-co-lactide-co-glycolide)-NHS (MP) copolymers (to tune degradation) as a cross-linking agent for CAM. This is the first report on the development of electrospun cross-linked (Cx) CAM/MP (CA/P) nanofiber (NF) (Cx-CA/P-NF) with a tunable degradation period as an antiadhesive barrier. Compared with the CA/P-NF before cross-linking, the electrospun Cx-CA/P-NF after cross-linking showed different biodegradation. Cx-CA/P-NF significantly inhibited the in vitro attachment and proliferation of human umbilical vein endothelial cells (HUVECs), as confirmed by an MTT assay and scanning electron microscopy images. Cx-CA/P-NFs implanted between a surgically damaged peritoneal wall and cecum gradually degraded in 7 days; this process was monitored by NIR imaging. The in vivo evaluation of the anti-tissue adhesive effect of Cx-CA/P-NFs revealed little adhesion, few blood vessels, and negligible inflammation at 7 days determined by hematoxylin and eosin staining. ED1 staining of Cx-CA/P-NFs showed infiltration of few macrophages because of the inflammatory response to the Cx-CA/P-NF as compared with an untreated injury model. Additionally, Cx-CA/P-NFs significantly suppressed the formation of blood vessels between the peritoneal wall and cecum, according to CD31 staining. Overall, Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Thus, it is reasonable to conclude that the Cx-CA/P-NF designed herein successfully works as an antiadhesive barrier with a tunable degradation period.

STATEMENT OF SIGNIFICANCE
The cartilage acellular matrix (CAM) can inhibit the formation of fibrous tissue bridges and blood vessels between the tissue at an injured site and the surrounding healthy tissues. However, CAM has not been rigorously investigated as an antiadhesive barrier. In this manuscript, the cross-linked CAM nanofiber (Cx-CA/P-NF) designed herein successfully works as an antiadhesive barrier. Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Moreover, we demonstrated the suitable properties of Cx-CA/P-NF such as easy cross-linking by maintaining the antiadhesive properties, controllable biodegradation, and in vivo antiadhesive effect of Cx-CA/P-NF.

Lee|Jin Woo|JW|
Park|Joon Yeong|JY|
Park|Seung Hun|SH|
Kim|Min Ju|MJ|
Song|Bo Ram|BR|
Yun|Hee-Woong|HW|
Kang|Tae Woong|TW|
Choi|Hak Soo|HS|
Kim|Young Jick|YJ|
Min|Byoung Hyun|BH|
Kim|Moon Suk|MS|

D061307:Human Umbilical Vein Endothelial Cells

Cross-linking
Cartilage acellular matrix
Antiadhesive barrier
Degradation
Polyester


Techniques and survival incidence for revascularization of degloved fingers.

Abstract:
We report techniques and survival incidence of three subtotally and nine completely degloved fingers in seven patients. We performed end-to-end arterial repairs in seven fingers, vein graft repairs for arteries in two fingers, arteriovenous anastomoses in three fingers. End-to-end vein anastomosis was performed in all fingers. One finger requred re-exploration. Soft tissues in the eight degloved fingers survived completely, two failed completely, and two were partially necrotic. We conclude from our results that following revascularization, the skin from a completely degloved finger skin will survive in approximately two cases out of three.

LEVEL OF EVIDENCE
IV.

Kayalar|Murat|M|
Güntürk|Özgün Barış|ÖB|
Kaplan|İbrahim|İ|
Sügün|Tahir Sadık|TS|
Ademoğlu|Yalçın|Y|

revascularization Degloving amputation avulsion replantation


DAZL is a master translational regulator of murine spermatogenesis.

Abstract: Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells, and is essential for embryonic germ cell development and differentiation, yet the gametogenic function of DAZL has not been fully characterized and most of its in vivo direct targets remain unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells, meiotic arrest and spermatid arrest. Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at the 3'-untranslated region and interacted with translation proteins including poly(A) binding protein. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts, were significantly decreased, resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.

Li|Haixin|H|
Liang|Zhuqing|Z|
Yang|Jian|J|
Wang|Dan|D|
Wang|Hanben|H|
Zhu|Mengyi|M|
Geng|Baobao|B|
Xu|Eugene Yujun|EY|

translational regulation
CLIPs
DAZ
RNA binding proteins
infertility


The care center influences the management of lymphoma patients in a universal health care system: an observational cohort study.

Abstract:
BACKGROUND
Healthcare providers-related disparities in adherence to the treatment plan among lymphoma patients are found even in a universal healthcare system, but the mechanism remains unclear. We investigated the association between the type of care center and the relative dose intensity and determined whether it persists after adjustment for patients' recruitment differences.

METHODS
Prospective observational cohort study of 294 patients treated with standard protocols for diffuse large B-cell lymphoma (DLBCL) in teaching or community public hospitals or in private centers in the French Midi-Pyrénées region from 2006-2013. To test our assumptions, we used multinomial and mixed-effect logistic models progressively adjusted for patients' biomedical characteristics, socio-spatial characteristics and treatment-related toxicity events.

RESULTS
Patients treated using standard protocols in the teaching hospital had more advanced stage and poorer initial prognosis without limitation regarding the distance from the residence to the care center. Patients' recruitment profile across the different types of care center failed to explain the difference in relative dose intensity. Low relative dose intensity was less often observed in teaching hospital than elsewhere.

CONCLUSION
We showed that even in a universal healthcare system, disparities in the management of DLBCL patients' do exist according to the types of care center. A main issue may be to find and diffuse the reasons of this benefit in cancer management in the teaching hospital to the other centers.

Lamy|S|S|
Bettiol|C|C|
Grosclaude|P|P|
Compaci|G|G|
Albertus|G|G|
Récher|C|C|
Nogaro|J C|JC|
Despas|F|F|
Laurent|G|G|
Delpierre|C|C|

Lymphoma
Observational cohort
Relative dose intensity
Center-related management disparity
French current practice


Is there any intron sliding in mammals?

Abstract:
BACKGROUND
Eukaryotic protein-coding genes consist of exons and introns. Exon-intron borders are conserved between species and thus their changes might be observed only on quite long evolutionary distances. One of the rarest types of change, in which intron relocates over a short distance, is called "intron sliding", but the reality of this event has been debated for a long time. The main idea of a search for intron sliding is to use the most accurate genome annotation and genome sequence, as well as high-quality transcriptome data. We applied them in a search for sliding introns in mammals in order to widen knowledge about the presence or absence of such phenomena in this group.

RESULTS
We didn't find any significant evidence of intron sliding in the primate group (human, chimpanzee, rhesus macaque, crab-eating macaque, green monkey, marmoset). Only one possible intron sliding event supported by a set of high quality transcriptomes was observed between EIF1AX human and sheep gene orthologs. Also, we checked a list of previously observed intron sliding events in mammals and showed that most likely they are artifacts of genome annotations and are not shown in subsequent annotation versions as well as are not supported by transcriptomic data.

CONCLUSIONS
We assume that intron sliding is indeed a very rare evolutionary event if it exists at all. Every case of intron sliding needs a lot of supportive data for detection and confirmation.

Intron sliding
Introns
Transcriptome
Gene annotation
Intron evolution


Generating a Core Set of Outcomes for Hospital-Based Violence Intervention Programs.

Abstract: Hospital-based violence intervention programs (HVIPs) engage individuals who have experienced violent victimization in postmedical care programming, with the goal of reducing the incidence and impact of future injuries. Although there is some empirical support for HVIPs' impact on violence and crime-related outcomes, proper impact assessment is limited by a lack of systematized research on outcomes that relate to the proximal goals and activities of the programs themselves. To address this critical gap, we conducted a two-stage Delphi method to elicit and prioritize these outcomes using the wisdom and experience of those who are engaged in service delivery (i.e., HVIP community-based practitioners, program coordinators, and embedded researchers; N = 79). Through this process, respondents prioritized outcomes related to posttraumatic stress symptoms, beliefs about aggression, coping strategies, and emotional regulation, which have not been consistently measured using validated or standardized tools. Results suggest that, rather than limiting program outcomes to those related to repeat violent injury or criminality, hospital- and community-based violence prevention programs seek to improve and measure mental health and socioemotional outcomes as a benchmark for healing and recovery after a violent injury. Prioritization of these outcomes broadens the definition of recovery to include psychosocial health and well-being. In addition, inclusion of these outcomes in effectiveness studies will serve to bolster the relevance of findings, and provide support for continued development and refinement of HVIP practice.

Monopoli|W John|WJ|0000-0002-8634-5602
Myers|Rachel K|RK|
Paskewich|Brooke S|BS|
Bevans|Katherine B|KB|
Fein|Joel A|JA|

Delphi method
violence prevention
program evaluation


Non-targeted profiling of circulating microRNAs in women with polycystic ovary syndrome (PCOS): effects of obesity and sex hormones.

Abstract:
PURPOSE
Circulating micro-ribonucleic acids (miRNAs) are small noncoding RNA molecules that influence gene transcription. We conducted the present profiling study to characterize the expression of circulating miRNAs in lean and obese patients with polycystic ovary syndrome (PCOS), the most common endocrine and metabolic disorder in premenopausal women.

BASIC PROCEDURES
We selected 11 control women, 12 patients with PCOS and 12 men so that they were similar in terms of body mass index. Five control women, 6 men and 6 patients with PCOS had normal weight whereas 6 subjects per group were obese. We used miRCURY LNA™ Universal RT microRNA PCR for miRNA profiling.

MAIN FINDINGS
The expression of 38 miRNAs and was different between subjects with PCOS and male and female controls. The differences in 15 miRNAs followed a pattern suggestive of androgenization characterized by expression levels that were similar in patients with PCOS and men but were different compared with those of control women. The expression of 13 miRNAs in women with PCOS was similar to that of control women and different compared with the expression observed in men, suggesting sexual dimorphism and, lastly, we observed 5 miRNAs that were expressed differently in women with PCOS compared with both men and control women, suggesting a specific abnormality in expression associated with the syndrome. Obesity interacted with the differences in several of these miRNAs, and the expression levels of many of them correlated with the hirsutism score, sex hormones and/or indexes of obesity, adiposity and metabolic dysfunction.

PRINCIPAL CONCLUSIONS
The present results suggest that several serum miRNAs are influenced by PCOS, sex hormones and obesity. Our findings may guide the targeted search of miRNAs as clinically relevant markers for PCOS and its association with obesity and metabolic dysfunction in future studies.

Murri|Mora|M|
Insenser|María|M|
Fernández-Durán|Elena|E|
San-Millán|José L|JL|
Luque-Ramírez|Manuel|M|
Escobar-Morreale|Héctor F|HF|

microRNA
Polycystic ovary syndrome
Obesity
Sex
Androgens
Estrogens


Medicinal Plant Compounds for Combating the Multi-drug Resistant Pathogenic Bacteria: A Review.

Abstract:
BACKGROUND
Globally, people utilize plants as the main source of remedy to heal various ailments. Medicinal plants have been utilized to treat ailments since the invention of modern scientific systems of medicine. The common remedy of infectious diseases mainly depends on the inhibition capacity of compounds or killing potential. The issue may give a clue for the development of a novel antimicrobial agent.

METHODS
Currently, microorganisms which are resistant towards antibiotics are probably a matter of serious concern for the overall well-being of health. At the moment, new therapeutic targets aside from the microorganism wall-based activities are in progress. For instance, the autoinducer molecules produced by the quorum sensing system are used to control antibiotic resistance and biofilm formation.

RESULTS
This therapeutic target is well-studied worldwide, however, the scientific data are not updated and only current studies started to gain insight into its perspective as a target to struggle against infectious diseases. Microbial resistance against antimicrobial compounds is a topic of serious concern in recent time.

CONCLUSION
Hence, this paper aims to confer a current overview of the novel compounds, quorum sensing, quorum quenching, biofilm formation in the development of antibiotic resistance and an update on their importance as a potential target for natural substances.

D024901:Drug Resistance, Multiple, Bacterial

medicinal plant
pathogenic bacteria
Antibiotics
antibiotic resistance
biofilm
quorum sensing.


Anodal transcranial direct current stimulation of the motor cortex induces opposite modulation of reciprocal inhibition in wrist extensor and flexor.

Abstract: Transcranial direct current stimulation (tDCS) is used as a noninvasive tool to modulate brain excitability in humans. Recently, several studies have demonstrated that tDCS applied over the motor cortex also modulates spinal neural network excitability and therefore can be used to explore the corticospinal control acting on spinal neurons. Previously, we showed that reciprocal inhibition directed to wrist flexor motoneurons is enhanced during contralateral anodal tDCS, but it is likely that the corticospinal control acting on spinal networks controlling wrist flexors and extensors is not similar. The primary aim of the study was to explore the effects of anodal tDCS on reciprocal inhibition directed to wrist extensor motoneurons. To further examine the supraspinal control acting on the reciprocal inhibition between wrist flexors and extensors, we also explored the effects of the tDCS applied to the ipsilateral hand motor area. In healthy volunteers, we tested the effects induced by sham and anodal tDCS on reciprocal inhibition pathways innervating wrist muscles. Reciprocal inhibition directed from flexor to extensor muscles and the reverse situation, i.e., reciprocal inhibition, directed from extensors to flexors were studied in parallel with the H reflex technique. Our main finding was that contralateral anodal tDCS induces opposing effects on reciprocal inhibition: it decreases reciprocal inhibition directed from flexors to extensors, but it increases reciprocal inhibition directed from extensors to flexors. The functional result of these opposite effects on reciprocal inhibition seems to favor wrist extension excitability, suggesting an asymmetric descending control onto the interneurons that mediate reciprocal inhibition.

Lackmy-Vallée|Alexandra|A| Klomjai|Wanalee|W| Bussel|Bernard|B| Katz|Rose|R| Roche|Nicolas|N|

D065908:Transcranial Direct Current Stimulation


Amelioration of salt induced toxicity in pearl millet by seed priming with silver nanoparticles (AgNPs): The oxidative damage, antioxidant enzymes and ions uptake are major determinants of salt tolerant capacity.

Abstract: Abiotic stresses in plants reduce crop growth and productivity. Nanoparticles (NPs) are effectively involved in the physiochemical processes of crop plants, especially under the abiotic stresses; whereas, less information is available regarding the role of AgNPs in salt-stressed plants. Therefore, in the current study, we investigated the effects of seed priming with commercially available silver nanoparticles (AgNPs) (size range between 50 and 100 nm) on plant morphology, physiology, and antioxidant defence system of pearl millet (Pennisetum glaucum L.) under different concentrations of salt stress (0, 120 and 150 mM NaCl). The seed priming with AgNPs at different levels (0, 10, 20 and 30 mM) mitigated the adverse impacts of salt stress and improved plant growth and defence system. The results demonstrated that salt-stressed plants had restricted growth and a noticeable decline in fresh and dry weight. Salt stress enhanced the oxidative damage by excessive production of hydrogen peroxide (H2O2), malondialdehyde (MDA) contents in pearl millet leaves. However, seed priming with AgNPs significantly improved the plant height growth related attributes, relative water content, proline contents and ultimately fresh and dry weight at 20 mM AgNPs alone or with salt stress. The AgNPs reduced the oxidative damage by improving antioxidant enzyme activities in the pearl millet leaves under salt stress. Furthermore, sodium (Na+) and Na+/K+ ratio was decreased and potassium (K+) increased by NPs, and the interactive effects between salt and AgNPs significantly impacted the total phenolic and flavonoid content in pearl millet. It was concluded that seed priming with AgNPs could enhance salinity tolerance in crop plants by enhancing physiological and biochemical responses. This might boost global crop production in salt-degraded lands.

Khan|Imran|I|
Raza|Muhammad Ali|MA|
Awan|Samrah Afzal|SA|
Shah|Ghulam Abbas|GA|
Rizwan|Muhammad|M|
Ali|Basharat|B|
Tariq|Rezwan|R|
Hassan|Muhammad Jawad|MJ|
Alyemeni|Mohammed Nasser|MN|
Brestic|Marian|M|
Zhang|Xinquan|X|
Ali|Shafaqat|S|
Huang|Linkai|L|

Seed priming
Silver nanoparticles
Antioxidants
Plant growth
Salinity


A combined small-angle X-ray and neutron scattering study of the structure of purified soluble gastrointestinal mucins.

Abstract: The structures of purified soluble porcine gastric (Muc5ac) and duodenal (Muc2) mucin solutions at neutral and acidic pH were examined using small-angle X-ray scattering and small-angle neutron scattering experiments. We provide evidence for the morphology of the network above the semidilute overlap concentration and above the entanglement concentration. Furthermore, we investigated the gelation of both types of mucin solutions in response to a reduction in pH, where we observed the formation of large-scale heterogeneities within the polymer solutions, typical of microphase-separated gels. The concentration dependence of the inhomogeneity length scale (Ξ) and the amplitude of the excess scattering intensity [I(ex) (0)] are consistent with previously studied gelled synthetic polymeric systems. The persistence lengths of the chains were found to be similar for both Muc5ac and Muc2 from Kratky plots of the neutron data (8 ± 2 nm).

Georgiades|Pantelis|P|
di Cola|Emanuela|E|
Heenan|Richard K|RK|
Pudney|Paul D A|PD|
Thornton|David J|DJ|
Waigh|Thomas A|TA|

D000818:Animals
D041981:Gastrointestinal Tract
D006863:Hydrogen-Ion Concentration
D055271:Mucin 5AC
D055262:Mucin-2
D033363:Neutron Diffraction
D053838:Scattering, Small Angle
D012995:Solubility
D034421:Sus scrofa
D014961:X-Ray Diffraction


Activity-Centred Analysis and Design (ACAD): Core purposes, distinctive qualities and current developments.

Abstract: This paper provides a summary account of Activity-Centred Analysis and Design (ACAD). ACAD offers a practical approach to analysing complex learning situations, in a way that can generate knowledge that is reusable in subsequent (re)design work. ACAD has been developed over the last two decades. It has been tested and refined through collaborative analyses of a large number of complex learning situations and through research studies involving experienced and inexperienced design teams. The paper offers a definition and high level description of ACAD and goes on to explain the underlying motivation. The paper also provides an overview of two current areas of development in ACAD: the creation of explicit design rationales and the ACAD toolkit for collaborative design meetings. As well as providing some ideas that can help teachers, design teams and others discuss and agree on their working methods, ACAD has implications for some broader issues in educational technology research and development. It questions some deep assumptions about the framing of research and design thinking, in the hope that fresh ideas may be useful to people involved in leadership and advocacy roles in the field.

Design rationale
Analytical frameworks
Design for learning
Design tools
Educational design
Learning activity
Teaching-as-design


Spiritual and Sexual Identity: Exploring Lesbian, Gay, and Bisexual Clients' Perspectives of Counseling.

Abstract: Although religious and spiritual issues have emerged as areas of focus in counseling, very few scholars have explored the meaning and experiences of lesbian, gay, and bisexual (LGB) clients who addressed their sexual and religious/spiritual identities in counseling. Using consensual qualitative research (CQR; Hill, 2012), the current study explores the perspectives of 12 LGB persons who sought counseling that involved religious/spiritual concerns. Four themes in participant interviews are identified, including (a) self-acceptance, (b) goals of counseling, (c) identification with counselor, and (d) counseling environment and relationship. Implications of findings for the counseling field are discussed.

Goodrich|Kristopher M|KM|
Buser|Juleen K|JK|
Luke|Melissa|M|
Buser|Trevor J|TJ|

LGB
Consensual qualitative research
identification
real relationship
religious counseling
spiritual counseling
working relationship


Functionalization of single-walled carbon nanotubes and their binding to cancer cells.

Abstract:
BACKGROUND
Single-walled carbon nanotubes (SWCNTs) have novel properties including their nanoscale size and ease of cellular uptake. This makes them useful for drug delivery, and their photo-thermal effects make them potentially useful in a wide range of applications, particularly the treatment of solid tumors. The poor solubility of SWCNTs has, however, been an issue that may potentially limit the utility of SWCNTs for cancer treatment. Functionalization of the surface of the tubes may be an approach to overcome this problem.

METHODS
SWCNTs were refluxed in HNO₃/H₂SO₄ (1:3) at 120°C for 120 minutes. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements, and near infrared (NIR) light exposure were used to assess the functionalization process. The attachment of a carbohydrate-binding protein (lectin) labeled with fluorescein isothiocyanate to the functionalized SWCNTs enabled evaluation of the functionalization step via confocal microscopy. The lectin from Helix pomatia, (Helix pomatia agglutinin [HPA]), can detect changes in protein glycosylation associated with aggressive metastatic cancer. The interaction between the lectin HPA alone and HPA conjugated to the functionalized SWCNTs with human breast cancer cells (MCF-7) was measured using a quartz crystal microbalance biosensor.

RESULTS
Following the functionalization process, TEM images showed a layer had formed on the surface of the SWCNTs. In the FTIR experiment, results illustrated the presence of the -COOH group on the functionalized SWCNTs. Contact angle measurements showed that upon functionalization the hydrophilicity of the SWCNTs increased. The temperature increase in the liquid (supernatant) surrounding the functionalized SWCNTs following exposure to light in the NIR (808 nm) was greater than for non-functionalized SWCNTs. The biosensor work showed that HPA binds with high affinity (nanomolar range) to human breast cancer cells; HPA-binding properties to MCF-7 cells were retained following conjugation to the functionalized SWCNTs.

CONCLUSION
Treating pure SWCNTs with HNO₃/H₂SO₄ (1:3) at 120°C for 120 minutes is an effective method for functionalization of SWCNTs. HPA linked to SWCNTs is a suitable candidate for the delivery of the functionalized SWCNTs to cancer cells.

Madani|Seyed Yazdan|SY|
Tan|Aaron|A|
Dwek|Miriam|M|
Seifalian|Alexander M|AM|

D017550:Spectroscopy, Fourier Transform Infrared

SWCNT
human breast cancer cells
HPA lectin


Blockade of tumour necrosis factor-α in experimental autoimmune encephalomyelitis reveals differential effects on the antigen-specific immune response and central nervous system histopathology.

Abstract: In various autoimmune diseases, anti-tumour necrosis factor (TNF)-α treatment has been shown to reduce both clinical disease severity and T helper type 1 (Th1)1/Th17 responses. In experimental autoimmune encephalomyelitis (EAE), however, the role of TNF-α has remained unclear. Here, C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 and treated with anti-TNF-α, control antibody or vehicle. The clinical disease course, incidence and severity were assessed. On day 20 after immunization the antigen-specific Th1/Th17 response was evaluated by enzyme-linked immunospot (ELISPOT) in spleen and central nervous system (CNS). Also, the extent of spinal cord histopathology was analysed on semi- and ultrathin sections. Our results demonstrate that anti-TNF-α treatment reduced the incidence and delayed the onset of EAE, but had no effect on disease severity once EAE had been established. Whereas anti-TNF-α treatment induced an increase in splenic Th1/Th17 responses, there was no effect on the number of antigen-specific Th1/Th17 cells in the spinal cord. Accordingly, the degree of CNS histopathology was comparable in control and anti-TNF-α-treated mice. In conclusion, while the anti-TNF-α treatment had neither immunosuppressive effects on the Th1/Th17 response in the CNS nor histoprotective properties in EAE, it enhanced the myelin-specific T cell response in the immune periphery.

Batoulis|H|H|
Recks|M S|MS|
Holland|F O|FO|
Thomalla|F|F|
Williams|R O|RO|
Kuerten|S|S|

T cells
EAE/MS
inflammation
monocytes/macrophages
neuroimmunology


Prediction of Residual Curing Capacity of Melamine-Formaldehyde Resins at an Early Stage of Synthesis by In-Line FTIR Spectroscopy.

Abstract: Melamine-formaldehyde (MF) resins are widely used as surface finishes for engineered wood-based panels in decorative laminates. Since no additional glue is applied in lamination, the overall residual curing capacity of MF resins is of great technological importance. Residual curing capacity is measured by differential scanning calorimetry (DSC) as the exothermic curing enthalpy integral of the liquid resin. After resin synthesis is completed, the resulting pre-polymer has a defined chemical structure with a corresponding residual curing capacity. Predicting the residual curing capacity of a resin batch already at an early stage during synthesis would enable corrective measures to be taken by making adjustments while synthesis is still in progress. Thereby, discarding faulty batches could be avoided. Here, by using a batch modelling approach, it is demonstrated how quantitative predictions of MF residual curing capacity can be derived from inline Fourier Transform infrared (FTIR) spectra recorded during resin synthesis using partial least squares regression. Not only is there a strong correlation (R2 = 0.89) between the infrared spectra measured at the end of MF resin synthesis and the residual curing capacity. The inline reaction spectra obtained already at the point of complete dissolution of melamine upon methylolation during the initial stage of resin synthesis are also well suited for predicting final curing performance of the resin. Based on these IR spectra, a valid regression model (R2 = 0.85) can be established using information obtained at a very early stage of MF resin synthesis.

decorative laminates
batch modelling
inline spectroscopy
melamine formaldehyde (MF)
process analytics


A glucose anode for enzymatic fuel cells optimized for current production under physiological conditions using a design of experiment approach.

Abstract: This study reports a design of experiment methodology to investigate and improve the performance of glucose oxidizing enzyme electrodes. Enzyme electrodes were constructed by co-immobilization of amine-containing osmium redox complexes, multiwalled carbon nanotubes and glucose oxidase in a carboxymethyldextran matrix at graphite electrode surfaces to provide a 3-dimensional matrix for electrocatalytic oxidation of glucose. Optimization of the amount of the enzyme electrode components to produce the highest current density under pseudo-physiological conditions of 5 mM glucose in saline buffer at 37 °C was performed using response surface methodology. A statistical analysis showed that the proposed model had a good fit with the experimental results. From the validated model, the addition of multiwalled carbon nanotubes and carboxymethyldextran components was identified as major contributing factors to the improved performance. Based on the optimized amount of components, enzyme electrodes display current densities of 1.2±0.1 mA cm(-2) and 5.2±0.2 mA cm(-2) at 0.2 V vs. Ag/AgCl in buffer containing 5 mM and 100 mM glucose, respectively, largely consistent with the predicted values. This demonstrates that use of a design of experiment approach can be applied effectively and efficiently to improve the performance of enzyme electrodes as anodes for biofuel cell device development.

Design of experiment
Glucose oxidation
Biofuel cell
Osmium mediator


Effect of Process Orientation on the Mechanical Behavior and Piezoelectricity of Electroactive Paper.

Abstract: This paper reports the effect of process orientation on the mechanical behavior and piezoelectricity of electroactive paper (EAPap) made from natural cotton pulp. EAPap is fabricated by a casting and wet drawing of cellulose film after dissolving cotton with LiCl and DMAc solvent. During the fabrication, permanent wrinkles, a possible factor for performance deterioration, were found in the films. Finite element method was introduced to identify the formation mechanism behind the wrinkles. The simulation results show that the wrinkles were caused by buckling and are inevitable under any conditions. The tensile and piezoelectric tests show that the orientation dependency of the stretched EAPap gives the anisotropic characteristics on both mechanical and piezoelectric properties. In this research, the anisotropic elastic moduli and Poisson's ratios are reported. The piezoelectric charge constant of EAPap in the linear elastic is calculated. The piezoelectric charge constants of EAPap are associated with the alignment angle in the order of 45° > 0° > 90° due to the strong shear effect. The higher stretching ratio gives the higher piezoelectricity due to the alignment of the molecular chains and the microstructure in EAPap. The highest piezoelectric charge constant is found to be 12 pC/N at a stretching ratio of 1.6 and aligning angle of 45°.

Yoon|Sean|S|
Kim|Jung Woong|JW|
Kim|Hyun Chan|HC|
Kim|Jaehwan|J|0000-0002-6152-2924

piezoelectricity
electroactive paper
wet drawing
cellulose
finite element method


A rare case of primary lymphoma of the caecum presenting as intussusception.

Abstract: Mucosa associated lymphoid tissue (MALT) lymphomas are rare neoplasms. They are most common in the stomach followed by small intestine and colon. The symptoms are nonspecific and generally do not present with intussusception. Here we report a rare clinical entity in which a 35-year-old female presented to the emergency with severe abdominal pain which was sudden in onset. History revealed that she had been having vague mild abdominal pain for 2 years. Ultrasonography showed ileocolic intussusception with hypoechoic lesion of 54 × 46 mm seen at the lead point. Emergency laparotomy with the right hemi-colectomy was done. The specimen was sent for histopathological examination which revealed a diagnosis of MALT lymphoma. Awareness of the varied clinical presentation helps in formulating the appropriate therapeutic strategy.

Jayabackthan|Leena|L|
Murgi|Sandeep Babukumar|SB|
Graham|Shane|S|
Kini|Reshma G|RG|


Observing the self, avoiding the experience? The role of the observer perspective in autobiographical recall and its relationship to depression in adolescence.

Abstract: The tendency to adopt an observer perspective (OP) when recalling autobiographical memories has been shown to be related to both avoidance and depression in adults. Very little research has examined this relationship in adolescents, however, and none of this work has adopted a longitudinal paradigm. This is an important gap in light of the marked escalation in rates of depression across the adolescent period. The current study therefore examined the concurrent and longitudinal (one year) relationships between observer perspective in the Minimal Instruction Autobiographical Memory Test (Mi-AMT; Debeer, E., Hermans, D., & Raes, F. (2009). Associations between components of rumination and autobiographical memory specificity as measured by a minimal instructions autobiographical memory test. Memory, 17(8), 892-903. https://doi.org/10.1080/09658210903376243), avoidance, and depression in a large, longitudinal sample of adolescents (mean age = 15.03 at T1). Consistent with predictions we found a significant but small cross-sectional correlation between OP and higher levels of depressive symptoms, however the relationship with avoidance was not significant. Contrary to predictions, the longitudinal relationships of OP with avoidance and depression were not significant. These findings raise the possibility that OP may be negligibly related to avoidance or depression during adolescence.

avoidance
observer perspective
depression
adolescents
autobiographical memory


Preparation and evaluation of gellan gum hydrogel reinforced with silk fibers with enhanced mechanical and biological properties for cartilage tissue engineering.

Abstract: Various research about cartilage regeneration using biomaterials has been done recently. Particularly, gellan gum hydrogel (GG) is reported to be suitable as a biomaterial for cartilage tissue engineering (TE) for its water uptaking ability, producibility, and environmental resemblance of native cartilage. Despite these advantages, mechanical and cell adhesion properties are still difficult to modulate. Reinforcement is essential to overcome these problems. Herein, GG was modified by physically blending with different lengths of silk fiber (SF). As SF is expected to improve such disadvantages of GG, mechanical and biological properties were characterized to confirm its reinforcement ability. Mechanical properties such as degradation rate, swelling rate, compression strength, and viscosity were studied and it was confirmed that SF significantly reinforces the mechanical properties of GG. Furthermore, in vitro study was carried out to confirm morphology, biocompatibility, proliferation, and chondrogenesis of chondrocytes encapsulated in the hydrogels. Overall, chondrocytes in the GG blended with SF (SF/GG) showed enhanced cell viability and growth. According to this study, SF/GG can be a promising biomaterial for cartilage TE biomaterial.

gellan gum
hydrogel
silk fiber
tissue engineering
chondrogenesis


Ultrasonic activation of irrigants increases growth factor release from human dentine.

Abstract:
OBJECTIVES
Bioactive proteins are sequestered in human dentine and play a decisive role in dental pulp regeneration and repair. They can be released and exposed on the dentine surface by acids, but also chelators, such as ethylenediaminetetraacetic acid (EDTA). The objectives of this study were (i) to evaluate whether ultrasonic activation of irrigants in the root canal will promote growth factor release from dentine and (ii) to collect bioactive proteins in a physiological solution.

MATERIALS AND METHODS
Human dentine disks underwent irrigation with and without ultrasonic activation. The protocols included treatment by either a single or two consecutive steps with 10 % EDTA and phosphate-buffered saline (PBS), where each sample was treated three times. To mimic clinical conditions, selected irrigation regimens were applied to root canals of extracted human teeth after preparation. Amounts of transforming growth factor β1 (TGF-β1) in solution were quantified using enzyme-linked immunosorbent assays. Nonparametric statistical analysis was performed to compare different groups as well as repetitions within a group (Mann-Whitney U test, α = 0.05). Additionally, morphological changes of dentine surfaces were visualized by scanning electron microscopy (SEM).

RESULTS
TGF-β1 was not detectable after irrigation of dentine with PBS, neither with nor without ultrasonic activation. Irrigation with EDTA released TGF-β1, and ultrasonic activation of EDTA enhanced this effect. However, preceding EDTA conditioning enabled the release of bioactive proteins into PBS solution. Similar results were observed in dentine disks and root canals. Visualization of dentine surfaces after different treatment revealed superficial erosion after ultrasonic activation irrespective of the irrigant solution, but different degrees of exposure of organic substance.

CONCLUSIONS
Ultrasonic activation enhances growth factor release from human dentine. Bioactive proteins can be isolated in physiological solvents and may act as autologous supplements for regenerative endodontic treatment or pulp tissue engineering.

CLINICAL RELEVANCE
Autologous growth factors from human dentine can advance treatment strategies in dental pulp tissue engineering.

Widbiller|M|M|
Eidt|A|A|
Hiller|K-A|KA|
Buchalla|W|W|
Schmalz|G|G|
Galler|K M|KM|

D053773:Transforming Growth Factor beta1

Ultrasonic activation
Dentine
Ethylenediaminetetraacetic acid
Tissue engineering
Regenerative endodontic procedure
Transforming growth factor beta1


Insight into the primary mode of action of TiO2 nanoparticles on Escherichia coli in the dark.

Abstract: Large-scale production and incorporation of titanium dioxide nanoparticles (NP-TiO2 ) in consumer products leads to their potential release into the environment and raises the question of their toxicity. The bactericidal mechanism of NP-TiO2 under UV light is known to involve oxidative stress due to the generation of reactive oxygen species. In the dark, several studies revealed that NP-TiO2 can exert toxicological effects. However, the mode of action of these nanoparticles is still controversial. In the present study, we used a combination of fluorescent probes to show that NP-TiO2 causes Escherichia coli membrane depolarization and loss of integrity, leading to higher cell permeability. Using both transcriptomic and proteomic global approaches we showed that this phenomenon translates into a cellular response to osmotic stress, metabolism of cell envelope components and uptake/metabolism of endogenous and exogenous compounds. This primary mechanism of bacterial NP-TiO2 toxicity is supported by the observed massive cell leakage of K(+) /Mg(2+) concomitant with the entrance of extracellular Na(+), and by the depletion of intracellular ATP level.

Sohm|Bénédicte|B| Immel|Françoise|F| Bauda|Pascale|P| Pagnout|Christophe|C|

Escherichia coli
Titanium dioxide nanoparticles
Toxicity
Transcriptomics
Osmotic stress
Microbiology


From tumor hypoxia to cancer progression: the implications of hypoxia-inducible factor-1 expression in cancers.

Abstract: Hypoxia, defined as a decrease of tissue oxygen levels, represents a fundamental pathophysiological condition in the microenvironment of solid tumors. Tumor hypoxia is known to be associated with radio/chemo-resistance and metastasis that eventually lead to cancer progression contributing to poor prognosis in cancer patients. Among transcription factors that accumulated under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that has received the most intense attention in this field of research due to its capacity to modulate several hundred genes. With a clearer understanding of the HIF-1 pathway, efforts are directed at manipulation of this complex genetic process in order to ultimately decrease cellular HIF-1 levels. Some novel agents have been shown to have HIF-1 inhibition activity through a variety of molecular mechanisms and have provided promising results in the preclinical setting.

Nurwidya|Fariz|F| Takahashi|Fumiyuki|F| Minakata|Kunihiko|K| Murakami|Akiko|A| Takahashi|Kazuhisa|K|

Tumor hypoxia
Cancer progression
Hypoxia-inducible factor-1


Current Approaches to the Pharmacologic Treatment of Core Symptoms Across the Lifespan of Autism Spectrum Disorder.

Abstract: There are no approved medications for autism spectrum disorder (ASD) core symptoms. However, given the significant clinical need, children and adults with ASD are prescribed medication off label for core or associated conditions, sometimes based on limited evidence for effectiveness. Recent developments in the understanding of biologic basis of ASD have led to novel targets with potential to impact core symptoms, and several clinical trials are underway. Heterogeneity in course of development, co-occurring conditions, and age-related treatment response variability hampers study outcomes. Novel measures and approaches to ASD clinical trial design will help in development of effective pharmacologic treatments.

Pandina|Gahan|G|
Ring|Robert H|RH|
Bangerter|Abigail|A|
Ness|Seth|S|

Autism
ASD
Clinical trials
Drug development
Therapeutics


Doctors' and nurses' views and experience of transferring patients from critical care home to die: a qualitative exploratory study.

Abstract:
BACKGROUND
Dying patients would prefer to die at home, and therefore a goal of end-of-life care is to offer choice regarding where patients die. However, whether it is feasible to offer this option to patients within critical care units and whether teams are willing to consider this option has gained limited exploration internationally.

AIM
To examine current experiences of, practices in and views towards transferring patients in critical care settings home to die.

DESIGN
Exploratory two-stage qualitative study

SETTING/PARTICIPANTS
Six focus groups were held with doctors and nurses from four intensive care units across two large hospital sites in England, general practitioners and community nurses from one community service in the south of England and members of a Patient and Public Forum. A further 15 nurses and 6 consultants from critical care units across the United Kingdom participated in follow-on telephone interviews.

FINDINGS
The practice of transferring critically ill patients home to die is a rare event in the United Kingdom, despite the positive view of health care professionals. Challenges to service provision include patient care needs, uncertain time to death and the view that transfer to community services is a complex, highly time-dependent undertaking.

CONCLUSION
There are evidenced individual and policy drivers promoting high-quality care for all adults approaching the end of life encompassing preferred place of death. While there is evidence of this choice being honoured and delivered for some of the critical care population, it remains debatable whether this will become a conventional practice in end of life in this setting.

Coombs|Maureen|M| Long-Sutehall|Tracy|T| Darlington|Anne-Sophie|AS| Richardson|Alison|A|

D000328:Adult
D001291:Attitude of Health Personnel
D003422:Critical Care
D005260:Female
D017144:Focus Groups
D006699:Home Care Services
D006801:Humans
D008297:Male
D008875:Middle Aged
D010360:Patient Transfer
D036301:Qualitative Research
D013727:Terminal Care
D006113:United Kingdom

Critical care
end-of-life care
doctors and nurses
transfer home


Effects of phentolamine infusion during selective cerebral perfusion in neonatal piglets.

Abstract:
BACKGROUND
An optimal selective cerebral perfusion protocol in pediatric cardiac surgery is unknown. Phentolamine is frequently used in pediatric cardiopulmonary bypass. We sought to determine the effects of continuous phentolamine infusion during selective cerebral perfusion.

METHODS
Twenty-seven neonatal piglets (3.38 ± 0.32 kg) were randomly assigned to 3 groups; sham (n = 7, anesthesia alone, no surgery or bypass), control (n = 10, saline infusion), or experimental (n = 10, phentolamine infusion 0.1 mg/kg per hour). Animals underwent 90 minutes of selective cerebral perfusion. Cerebral vascular resistance index (CVRI) and metabolic rate of oxygen (CMRO2) were determined every 15 minutes. Standardized sections of hippocampus, basal ganglia, and neo-cortex were obtained. Tissue samples were stained for caspase-3 and analyzed for positive apoptotic cell count. Data were analyzed with repeated measures and one-way analysis of variance.

RESULTS
The CVRI tended to increase over time in the control group and decrease over time in the experimental group, but difference was not statically significant (0.46 ± 0.24 vs 0.39 ± 0.10 mm Hg × min × kg(2/3)/mL, p = 0.15). Mean CMRO2 was higher in the control group compared with the experimental group (0.90 ± 0.27 vs 0.59 ± 0.12 mLO2/min × kg(2/3), p = 0.005) and decreased over time in both groups. The percentage of caspase-3 positive cells was significantly different among regions (hippocampus = 16.9 ± 8.8; basal ganglia = 14.6 ± 7.5; neocortex = 10.8 ± 6.3; p < 0.0001) but not significantly different among sham (11.8% ± 2.68%), control (14.4% ± 2.24%), and experimental (15.5% ± 2.24%) groups.

CONCLUSIONS
A continuous infusion of phentolamine during selective cerebral perfusion significantly decreases CMRO2 and tends to decrease CVRI when compared with control. At the dose studied and at the time of tissue sampling, phentolamine does not appear to decrease apoptosis during or early after selective cerebral perfusion.

Argueta-Morales|Ivan Ricardo|IR|
Munro|Hamish M|HM|
Olsen|Monica|M|
Ionan|Constantine|C|
Nguyen|Moui|M|
Amin|Sarina|S|
Danker|Sara|S|
Meador|Lauren C|LC|
Decampli|William M|WM|


A randomized, placebo-controlled trial investigating the acute and chronic benefits of American Ginseng (Cereboost®) on mood and cognition in healthy young adults, including in vitro investigation of gut microbiota changes as a possible mechanism of action.

Abstract:
PURPOSE
Cereboost®, an American ginseng extract, has shown improved short-term memory and attention/alertness in healthy young and middle-aged individuals, potentially via modulation of the gut microbiome and upregulation of neurotransmitters such as acetylcholine. Here, we explored the effects of Cereboost® on cognition and mood in the first 6 h post intervention (acute), after 2 weeks daily supplementation (chronic), and whether 2 weeks daily supplementation altered the response to a single acute dose (acute-on-chronic). A concurrent in vitro study evaluated effects of repeated Cereboost® administration on human gut microbiota.

METHODS
Cognitive effects of Cereboost® were assessed using a double-blind, randomized, placebo-controlled clinical trial, with 61 healthy young adults. Modulation of the gut microbiome was concurrently modelled using the Simulator of the Human Microbial Ecosystem (SHIME®), using a young adult donor.

RESULTS
Consistent with previous findings, Cereboost® improved working memory and attention during the immediate postprandial period; effects that were amplified following two weeks' treatment (acute-on-chronic) compared to acute testing alone. Chronic supplementation improved cognition on an acetylcholine-sensitive attention task and improved mental fatigue and self-assurance aspects of mood. The parallel in vitro study revealed significantly increased acetate, propionate, and butyrate levels in simulated proximal and distal colon regions, linked with observed increases in Akkermansia muciniphila and Lactobacillus.

CONCLUSION
This study confirmed the promising effects of Cereboost® on cognitive function and mood, while suggesting a possible link to alterations of the gut microbiome and modulation of acetylcholine. Further studies will be required to unravel the underlying mechanisms that are involved.

REGISTRATION
The study was pre-registered at ClinicalTrials.gov on 6th July 2018 (Identifier: NCT03579095).

American ginseng
Mood
Cognition
Gut microbiome
SCFA


A significant proportion of patients with primary central nervous system lymphoma harbor clonal bone marrow B-cells.

Abstract: Clonal bone marrow (BM) B-cell populations are a common finding in patients with suspected primary central nervous system lymphoma (PCNSL). To assess their clinical significance, benign monoclonal B-cell lymphocytosis (MBL) needs to be differentiated from concomitant BM involvement, since patients with secondary central nervous system lymphoma (SCNSL) generally require more intensive treatment directed also at the component outside the central nervous system (CNS). Here, we retrospectively analyzed BM samplings in 51 patients with suspected PCNSL. We found clonal B cell populations in 8 of 51 cases (16%) by flow cytometry. None of these eight cases had BM involvement by high-grade lymphoma. No lymphoma relapses outside the CNS were recorded. Together, our data points at a significant percentage of patients with suspected PCNSL harboring clonal BM B-cells, which in this patient group always represented benign MBL. Failure to differentiate these populations from systemic lymphoma involvement may result in overtreatment of patients.

Brandt|Anna|A|0000-0002-3059-6146
Matschke|Jakob|J|
Fehrle|Wilfried|W|
von Wenserski|Lisa|L|
Bokemeyer|Carsten|C|
Illerhaus|Gerald|G|0000-0002-0009-8138
Binder|Mascha|M|

D016543:Central Nervous System Neoplasms

Primary central nervous system lymphoma
clonal bone marrow B-cells
flow cytometry


Evaluation of the diagnostic role of transvaginal ultrasound measurements of endometrial thickness to detect endometrial malignancy in asymptomatic postmenopausal women.

Abstract:
PURPOSE
To assess the diagnostic accuracy of endometrial thickness measurements of transvaginal ultrasound (TVUS) in asymptomatic postmenopausal women in the detection of endometrial malignancy.

METHODS
A retrospective cohort study in a university hospital was undertaken with 276 consecutive asymptomatic postmenopausal women undergoing dilatation and curettage (D&C) and hysteroscopy for an incidental finding of thickened endometrium (≥4 mm) between 2003 and 2012. Different endometrial thickness cutoff values were tested on the basis of a pathologic report with carcinoma conditions (endometrial hyperplasia with atypia and endometrial carcinoma).

RESULTS
The mean age of patients was 59.8 ± 9.0 years. The mean duration of menopause was 11.2 ± 8.9 years. The final pathology diagnoses included 107 (38.8 %) patients with polyps, 42 (15.2 %) with atrophic endometrium, 39 (14.1 %) with estrogen exposure, and 19 (6.9 %) with normal endometrium. With regard to carcinoma conditions, nine patients (3.3 %) had endometrial hyperplasia with atypia and eight patients (2.9 %) had endometrial carcinoma. The area under the ROC curve was 0.52 (95 % CI 0.44-0.57), which indicated a poor accuracy of endometrial thickness of TVUS for carcinoma conditions.

CONCLUSIONS
Routine use of endometrial thickness measurement with TVUS does not seem to be an effective diagnostic tool for endometrial cancer because it has a low diagnostic performance in asymptomatic postmenopausal women. Further prospective studies are required to assess the endometrial thickness measurement with TVUS as a screening method in these women.

Yasa|Cenk|C|
Dural|Ozlem|O|
Bastu|Ercan|E|
Ugurlucan|Funda Gungor|FG|
Nehir|Aslı|A|
İyibozkurt|Ahmet Cem|AC|

Endometrial thickness
Asymptomatic postmenopausal women
Endometrial hyperplasia with atypia
Endometrial cancer
Transvaginal ultrasonography


Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway.

Abstract: Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the bioactive component of Zedoary oil, whose potential anti-tumor effect has attracted considerable attention in recent years. Though many researchers have reported curcumol and its bioactivity, the potential molecular mechanism for its anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the present study, we found that curcumol showed growth inhibition and induced apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of its proliferation inhibition and apoptosis came with suppression of IGF-1R expression, and then increased the phosphorylation of p38 mitogen activated protein kinase (MAPK), which might result in a cascade response by inhibiting the CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose) polymerase 1 (PARP-1) apoptosis signals. Moreover, curcumol inhibited colorectal cancer in xenograft models of nude mice. Immunohistochemical and Western blot analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as well as CREB1, and increase the expression of Bax and the phosphorylation of p38, which were consistent with our in vitro study. Overall, our in vitro and in vivo data confirmed the anti-cancer activity of curcumol, which was related to a significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy.

Wang|Juan|J| Huang|Fengxiang|F| Bai|Zhun|Z| Chi|Bixia|B| Wu|Jiacai|J| Chen|Xu|X|

D023041:Xenograft Model Antitumor Assays

D048051:p38 Mitogen-Activated Protein Kinases

curcumol
colorectal cancer
IGF-1R
p38 MAPK
anti-tumor


Impact of sonolytic ozonation (O3/US) on degradation of pesticide residues in fresh vegetables and fruits: Case study of Faisalabad, Pakistan.

Abstract: High pesticide residues in fresh produce is a serious food safety issue. This study was aimed at assessing the pesticides residues in some important vegetables and fruits marketed in Faisalabad, Pakistan and the impact of sonolytic ozonation (O3/US) treatment in removing these contaminants. From a short grower's survey, five registered and mostly used pesticides (acetamiprid, carbendazim, imidacloprid, thiacloprid and thiamethoxam) were identified. A time optimization trial of O3/US application (05, 10 and 15 min) on okra, showed that 10 min treatment significantly reduced three identified chemicals (thiamethoxam 100 %, imidacloprid and thiacloprid 97.17 %), without any adverse effect on its quality. In follow up trial, five fresh vegetables (cauliflower, chillies, cucumber, spinach and tomato) three fresh fruits (grapes, guava and peach) collected from three markets of Faisalabad, were pooled together to have uniform samples. Vegetables and fruits were treated with O3/US for 10 and 6 min, respectively, along with control (simple tap wash) for determining the impacts on pesticides degradation. Samples were processed for extraction, clean up and analysis using HPLC-UV-Vis in isocratic mode. The data revealed the presence of five mentioned chemicals, with an accumulative mean residue of 9.006 and 1.921 µg/g in tested vegetables and fruits, respectively. After subjecting to O3/US, the accumulative chemical residues were reduced to 3.214 µg/g (64.313 %) and 1.064 (44.6 %) in treated vegetables and fruits respectively. Irrespective of fresh produce, the mean residues of thiamethoxam, imidachloprid, acetamiprid and thiachloprid and carbendazim were reduced by 99.3 %, 52.6 %, 65.2 %, 87.3 % and 72% respectively. It was concluded that sonolytic ozonation treatment was effective in significant reduction of pesticide residues from vegetables and fruits and thus can be employed as a good food safety practice at culinary level to reduce the associated health hazardous risks.

Siddique|Zarghona|Z|
Malik|Aman Ullah|AU|
Asi|Muhammad Rafique|MR|
Inam-Ur-Raheem|Muhammad|M|
Iqbal|Muhammad|M|
Abdullah|Muhammad|M|

Sonolytic ozonation
Pesticides degradation
Fruits and vegetables


Russulaceae in American Samoa: new species and further support for an Australasian origin for Samoan ectomycorrhizal fungi.

Abstract: Two new species from the Russulaceae, Lactifluus aurantiotinctus and Russula pallidirosea, are described from American Samoa. Based on analyses of nuc rDNA internal transcribed spacer region barcodes (ITS), L. aurantiotinctus has an affinity to subgenus Lactariopsis and strong phylogeographic ties to Papua New Guinea. The ITS data indicate that Russula pallidirosea has an affinity to subgenus Heterophyllidia and suggest that it also has phylogeographic ties to Australasia. Both species were associated with the ectomycorrhizal tree Intsia bijuga.

Lactifluus Russula Polynesia biogeography ectomycorrhizae


Assessing global range expansion in a cryptic species complex: insights from the red seaweed genus Asparagopsis (Florideophyceae).

Abstract: The mitochondrial genetic diversity, distribution and invasive potential of multiple cryptic operational taxonomic units (OTUs) of the red invasive seaweed Asparagopsis were assessed by studying introduced Mediterranean and Hawaiian populations. Invasive behavior of each Asparagopsis OTU was inferred from phylogeographic reconstructions, past historical demographic dynamics, recent range expansion assessments and future distributional predictions obtained from demographic models. Genealogical networks resolved Asparagopsis gametophytes and tetrasporophytes into four A. taxiformis and one A. armata cryptic OTUs. Falkenbergia isolates of A. taxiformis L3 were recovered for the first time in the western Mediterranean Sea and represent a new introduction for this area. Neutrality statistics supported past range expansion for A. taxiformis L1 and L2 in Hawaii. On the other hand, extreme geographic expansion and an increase in effective population size were found only for A. taxiformis L2 in the western Mediterranean Sea. Distribution models predicted shifts of the climatically suitable areas and population expansion for A. armata L1 and A. taxiformis L1 and L2. Our integrated study confirms a high invasive risk for A. taxiformis L1 and L2 in temperate and tropical areas. Despite the differences in predictions among modelling approaches, a number of regions were identified as zones with high invasion risk for A. taxiformis L2. Since range shifts are likely climate-driven phenomena, future invasive behavior cannot be excluded for the rest of the lineages.

Zanolla|Marianela|M|0000-0001-9585-5906
Altamirano|María|M|
Carmona|Raquel|R|
De la Rosa|Julio|J|
Souza-Egipsy|Virginia|V|
Sherwood|Alison|A|
Tsiamis|Konstantinos|K|
Barbosa|Ana Márcia|AM|
Muñoz|Antonio Román|AR|
Andreakis|Nikos|N|

cryptic
Asparagopsis
Mediterranean Sea
distribution models
invasion risk
Hawaiian Archipelago
Phylogeography


The Emerging Role of Nutraceuticals and Phytochemicals in the Prevention and Treatment of Alzheimer's Disease.

Abstract: One of the major challenges of medical sciences has been finding a reliable compound for the pharmacological treatment of Alzheimer's disease (AD). As most of the drugs directed to a variety of targets have failed in finding a medical solution, natural products from Ayurvedic medicine or nutraceutical compounds emerge as a viable preventive therapeutics' pathway. Considering that AD is a multifactorial disease, nutraceutical compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs used for AD treatment. We review in-depth important medicinal plants that have been already investigated for therapeutic uses against AD, focusing on a diversity of pharmacological actions. These targets include inhibition of acetylcholinesterase, β-amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc., and pharmacological actions so diverse as anti-inflammatory, memory enhancement, nootropic effects, glutamate excitotoxicity, anti-depressants, and antioxidants. In addition, we also discuss the activity of nutraceutical compounds and phytopharmaceuticals formulae, mainly directed to tau protein aggregates mechanisms of action. These include compounds such as curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, oleocanthal, and meganatural-az and other phytochemicals such as huperzine A, limonoids, azaphilones, and aged garlic extract. Finally, we revise the nutraceutical formulae BrainUp-10 composed of Andean shilajit and B-complex vitamins, with memory enhancement activity and the control of neuropsychiatric distress in AD patients. This integrated view on nutraceutical opens a new pathway for future investigations and clinical trials that are likely to render some results based on medical evidence.

Calfio|Camila|C|
Gonzalez|Andrea|A|
Singh|Sandeep Kumar|SK|
Rojo|Leonel E|LE|
Maccioni|Ricardo B|RB|

nutraceutical compounds
multitarget approaches
mechanisms
Alzheimer’s disease
anti-tau molecules
disease prevention and treatment


Practice variation in total hip arthroplasty versus hemiarthroplasty for treatment of fractured neck of femur in Australia.

Abstract:
AIMS
Displaced femoral neck fractures (FNF) may be treated with partial (hemiarthroplasty, HA) or total hip arthroplasty (THA), with recent recommendations advising that THA be used in community-ambulant patients. This study aims to determine the association between the proportion of FNF treated with THA and year of surgery, day of the week, surgeon practice, and private versus public hospitals, adjusting for known confounders.

PATIENTS AND METHODS
Data from 67 620 patients in the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from 1999 to 2016 inclusive were used to generate unadjusted and adjusted analyses of the associations between patient, time, surgeon and institution factors, and the proportion of FNF treated with THA.

RESULTS
Overall, THA was used in 23.7% of patients. THA was more frequently used over time, in younger patients, in healthier patients, in cases performed on weekdays (adjusted odds ratio (OR) 1.27; 95% confidence interval (CI) 1.14 to 1.41), in private hospitals (adjusted OR 4.34; 95% CI 3.94 to 4.79) and by surgeons whose hip arthroplasty practice has a relatively higher proportion of elective patients (adjusted OR 1.65; 95% CI 1.49 to 1.83).

CONCLUSION
Practice variation exists in the proportion of FNF patients treated with THA due to variables other than patient factors. This may reflect variation in resources available and surgeon preference, and uncertainty regarding the relative indication.

Harris|I A|IA|
Cuthbert|A|A|
de Steiger|R|R|
Lewis|P|P|
Graves|S E|SE|

D000078337:Procedures and Techniques Utilization

Total hip arthroplasty
Hemiarthroplasty
Femoral neck fractures


Antimicrobial agent prescription: a prospective cohort study in patients with sepsis and septic shock.

Abstract:
OBJECTIVE
To assess the true association between appropriate prescription of antibiotics and prognosis in patients with sepsis, a key issue in health care and quality improvement strategies.

METHODS
Prospective cohort study in three university hospitals to determine whether the empirical prescription of antibiotics was adequate or inadequate, and to compare hospital death rates and length of stay according to different classifications of antibiotics prescription. Logistic regression models for risk estimation were fitted.

RESULTS
A total of 705 patients with severe sepsis were included. No differences were found in positive-culture patients (n = 545) regarding the risk of death with insufficient spectrum antibiotics, compared to patients who received adequate spectrum antibiotics (OR = 0.90; 95% CI = 0.55-1.48). Delay in initiating antibiotics was not associated with the risk of death in patients with adequate spectrum of antibiotics, either with positive (OR = 1.04; 95% CI = 0.99-1.08) or negative cultures (OR = 0.98; 95% CI = 0.92-1.04). There were no differences in the length of hospital stay, according to the antibiotic prescription (median 11 days, IQR = 7-18 days for the whole cohort).

CONCLUSIONS
No associations were found between inadequate antibiotic prescription or delay to initiate therapy and mortality or length of stay.

Castaño|Pablo|P| Plaza|Maribel|M| Molina|Fernando|F| Hincapié|Carolina|C| Maya|Wilmar|W| Cataño|Juan|J| González|Javier|J| León|Alba|A| Jaimes|Fabián|F|

sepsis
shock
length of stay
agents antibactériens
antibacterial agents
durée de séjour
hospital mortality
mortalité hospitalière
état de choc


Post-intubation acute laryngeal injuries in infants and children: A new classification system.

Abstract:
OBJECTIVE
To compare the Classification of Acute Laryngeal Injuries (CALI) with other classifications to determine which of these offers the greatest sensitivity and specificity in predicting the development of subglottic stenosis.

METHODS
All children intubated for the first time in the pediatric intensive care unit were included and subjected to flexible fiber-optic laryngoscopy (FFL) within 8 h of extubation. Their injuries were categorized using the CALI, as well as adapted classifications from Lindholm, Colice and Benjamin. The children were followed up to determine who developed subglottic stenosis.

RESULTS
This study included 194 children, with a median age of 2.67 months. The sensitivity and specificity of the CALI were 90% and 73%, respectively. The CALI showed greater specificity than the adapted classifications from Colice and Benjamin (p < 0.001 for both), and greater sensitivity than the adapted classification from Lindholm (p < 0.001).

CONCLUSIONS
Based on the CALI, 90% of children who developed subglottic stenosis had moderate to severe injuries on the initial FFL. The CALI includes all injury types described by Benjamin, as well as a proposed severity scale for these lesions, and was predictive of the development of chronic laryngeal injury.

Schweiger|Cláudia|C|
Manica|Denise|D|
Kuhl|Gabriel|G|
Sekine|Leo|L|
Marostica|Paulo José Cauduro|PJ|

Infants
Subglottic stenosis
Granulation tissue
Larynx
Ulceration


Global patterns of protection of elevational gradients in mountain ranges.

Abstract: Protected areas (PAs) that span elevational gradients enhance protection for taxonomic and phylogenetic diversity and facilitate species range shifts under climate change. We quantified the global protection of elevational gradients by analyzing the elevational distributions of 44,155 PAs in 1,010 mountain ranges using the highest resolution digital elevation models available. We show that, on average, mountain ranges in Africa and Asia have the lowest elevational protection, ranges in Europe and South America have intermediate elevational protection, and ranges in North America and Oceania have the highest elevational protection. We use the Convention on Biological Diversity's Aichi Target 11 to assess the proportion of elevational gradients meeting the 17% suggested minimum target and examine how different protection categories contribute to elevational protection. When considering only strict PAs [International Union for Conservation of Nature (IUCN) categories I-IV, n = 24,706], nearly 40% of ranges do not contain any PAs, roughly half fail to meet the 17% target at any elevation, and ∼75% fail to meet the target throughout ≥50% of the elevational gradient. Observed elevational protection is well below optimal, and frequently below a null model of elevational protection. Including less stringent PAs (IUCN categories V-VI and nondesignated PAs, n = 19,449) significantly enhances elevational protection for most continents, but several highly biodiverse ranges require new or expanded PAs to increase elevational protection. Ensuring conservation outcomes for PAs with lower IUCN designations as well as strategically placing PAs to better represent and connect elevational gradients will enhance ecological representation and facilitate species range shifts under climate change.

Elsen|Paul R|PR|0000-0002-9953-7961
Monahan|William B|WB|
Merenlender|Adina M|AM|

protected areas
climate change
Aichi Target 11
biodiversity
conservation planning


On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson's Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine.

Abstract: Recent research shows that energy metabolism can strongly influence proteostasis and thereby affect onset of aging and related disease such as Parkinson's disease (PD). Changes in glycolytic and proteolytic activities (influenced by diet and development) are suggested to synergistically create a self-reinforcing deleterious cycle via enhanced formation of triose phosphates (dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate) and their decomposition product methylglyoxal (MG). It is proposed that triose phosphates and/or MG contribute to the development of PD and its attendant pathophysiological symptoms. MG can induce many of the macromolecular modifications (e.g. protein glycation) which characterise the aged-phenotype. MG can also react with dopamine to generate a salsolinol-like product, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinaline (ADTIQ), which accumulates in the Parkinson's disease (PD) brain and whose effects on mitochondria, analogous to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), closely resemble changes associated with PD. MG can directly damage the intracellular proteolytic apparatus and modify proteins into non-degradable (cross-linked) forms. It is suggested that increased endogenous MG formation may result from either, or both, enhanced glycolytic activity and decreased proteolytic activity and contribute to the macromolecular changes associated with PD. Carnosine, a naturally-occurring dipeptide, may ameliorate MG-induced effects due, in part, to its carbonyl-scavenging activity. The possibility that ingestion of highly glycated proteins could also contribute to age-related brain dysfunction is briefly discussed.

aging methylglyoxal carnosine glycation mitochondria Parkinson’s glycolysis homeostasis proteolysis