Modeling development of frontal electroencephalogram (EEG) asymmetry: Sex differences and links with temperament.

Abstract: Asymmetric patterns of frontal brain electrical activity reflect approach and avoidance tendencies, with stability of relative right activation associated with withdrawal emotions/motivation and left hemisphere activation linked with approach and positive affect. However, considerable shifts in approach/avoidance-related lateralization have been reported for children not targeted because of extreme temperament. In this study, dynamic effects of frontal electroencephalogram (EEG) power within and across hemispheres were examined throughout early childhood. Specifically, EEG indicators at 5, 10, 24, 36, 48, and 72 months-of-age (n = 410) were analyzed via a hybrid of difference score and panel design models, with baseline measures and subsequent time-to-time differences modeled as potentially influencing all subsequent amounts of time-to-time change (i.e., predictively saturated). Infant sex was considered as a moderator of dynamic developmental effects, with temperament attributes measured at 5 months examined as predictors of EEG hemisphere development. Overall, change in left and right frontal EEG power predicted declining subsequent change in the same hemisphere, with effects on the opposing neurobehavioral system enhancing later growth. Infant sex moderated the pattern of within and across-hemisphere effects, wherein for girls more prominent left hemisphere influences on the right hemisphere EEG changes were noted and right hemisphere effects were more salient for boys. Largely similar patterns of temperament prediction were observed for the left and the right EEG power changes, with limited sex differences in links between temperament and growth parameters. Results were interpreted in the context of comparable analyses using parietal power values, which provided evidence for unique frontal effects.

Gartstein|Maria A|MA|
Hancock|Gregory R|GR|
Potapova|Natalia V|NV|
Calkins|Susan D|SD|
Bell|Martha Ann|MA|

sex differences
temperament
EEG asymmetry
developmental processes
latent change scores
panel models


First assessment of diffusion coefficients in model cheese by fluorescence recovery after photobleaching (FRAP).

Abstract: Mass transfer of solutes like salt, moisture and metabolites, is very important for the final quality of cheese, through the control of the brining and ripening processes. Numerous studies have reported salt and water transfer properties in cheese, but few have dealt with other solutes. Moreover, most diffusion coefficients have been obtained by macroscopic and destructive methods. We developed the fluorescence recovery after photobleaching (FRAP) technique on a confocal microscope to measure in situ and at the microscopic scale diffusion properties inside cheese. A model matrix based on ultrafiltrated milk was used. FITC-dextran molecules were chosen as models of migrant solutes. Diffusion coefficients were estimated with a modelling approach which takes into account diffusion during the bleach phase. The FITC-dextrans (4 and 20 kDa) were able to migrate in the proteinic network, but their mobility was 2.2-3 times lower than in water, depending on their size.

Floury|J|J| Madec|M-N|MN| Waharte|F|F| Jeanson|S|S| Lortal|S|S|

D036681:Fluorescence Recovery After Photobleaching

Diffusion
Cheese
FRAP
Confocal microscopy


Berberine ameliorates intrahippocampal kainate-induced status epilepticus and consequent epileptogenic process in the rat: Underlying mechanisms.

Abstract: Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms. BBR was daily administered at doses of 25 or 50mg/kg. Results showed that BBR treatment of kainate-microinjected rats at a dose of 50mg/kg lowered the incidence of SE and SRS. It also significantly restored hippocampal level of reactive oxygen species (ROS), glutathione (GSH), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), activity of catalase and caspase 3, nuclear factor-<kappa>B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), neural cell adhesion molecule (NCAM), glial fibrillary acidic protein (GFAP), cathepsin D, and heme oxygenase 1 (HO-1). Additionally, BBR protected against hippocampal CA3 neuronal loss and prevented development of aberrant mossy fiber sprouting (MFS) as an essential element of chronic epileptogenic circuit. These data suggest that BBR could mitigate SE and SRS in intrahippocampal kainate model of epilepsy and exert neuroprotective effect and its influence is mainly mediated via suppression of oxidative stress, neuroinflammation, and possibly apoptosis.

Sedaghat|Reza|R| Taab|Yosra|Y| Kiasalari|Zahra|Z| Afshin-Majd|Siamak|S| Baluchnejadmojarad|Tourandokht|T| Roghani|Mehrdad|M|

Berberine
Status epilepticus
Temporal lobe epilepsy
Oxidative stress
Neuroinflammation
Kainic acid


Chronic inflammation, cardiometabolic diseases and effects of treatment: Psoriasis as a human model.

Abstract: Chronic inflammation in humans is associated with accelerated development of cardiometabolic diseases such as myocardial infarction, stroke, and diabetes. Strong evidence from animal models and human interventional trials including CANTOS (The Canakinumab Anti-inflammatory Thrombosis Outcome Study) suggests that targeting residual systemic inflammation in humans may impart a benefit in reducing cardiometabolic diseases. Diseases associated with heightened immune-activation and systemic inflammation including psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus infection are associated with upwards of two to seven-fold risk of future adverse cardiac events even when adjusted for traditional risk factors. Over the past decade, psoriasis has been utilized as a human model to study inflammatory-induced cardiometabolic dysfunction and to better understand residual risk due to inflammation. The high prevalence and early onset of cardiovascular disease in psoriasis enhances the likelihood of discovering novel pathways in vascular disease progression when followed over time. Furthermore, the United States Food and Drug Administration approved treatments for psoriasis include cytokine inhibitors (anti-tumor necrosis factor, anti-interleukin 17, anti-interleukin 12/23) which while treating the skin disease provide a unique opportunity to characterize how treating the inflammatory pathways may impact atherosclerosis. Herein, we provide a review of chronic inflammation, cardiometabolic disease associations, and treatment effects with a focus on psoriasis as a human model of study.

Aksentijevich|Milena|M|
Lateef|Sundus S|SS|
Anzenberg|Paula|P|
Dey|Amit K|AK|
Mehta|Nehal N|NN|

Inflammation
Cardiometabolic disease
Psoriasis
Adipose dysfunction
Immune activation
Lipoprotein dysfunction


Ursolic Acid Protected Lung of Rats From Damage Induced by Cigarette Smoke Extract.

Abstract: Background: We found previously that ursolic acid (UA) administration could alleviate cigarette smoke-induced emphysema in rats partly through the unfolded protein response (UPR) PERK-CHOP and Nrf2 pathways, thus alleviating endoplasmic reticulum stress (ERS)-associated oxidative stress and cell apoptosis. We hypothesized that other UPR pathways may play similar roles in cigarette smoke extract (CSE)-induced emphysema. So, we sought to investigate the dynamic changes and effects of UPR and the downstream apoptotic pathways. Further, we investigated whether UA could alleviate CSE-induced emphysema and airway remodelling in rats, whether and when it exerts its effects through UPR pathways as well as Smads pathways. Methods: One hundred eight Sprague Dawley (SD) rats were randomly divided into three groups: Sham group, CSE group, and UA group, and each group was further divided into three subgroups, administered CSE (vehicle) for 2, 3, or 4 weeks; each subgroup had 12 rats. We examined pathological changes, analyzed the three UPR signaling pathways and subsequent ERS, intrinsic and extrinsic apoptotic pathway indicators, as well as activation of Smad2,3 molecules in rat lungs. Results: Exposure to CSE for 3 or 4 weeks could apparently induce emphysema and airway remodeling in rats, including gross and microscopic changes, alteration of mean alveolar number (MAN), mean linear intercept (MLI), and mean airway thickness in lung tissue sections. UA intervention could significantly alleviate CSE-induced emphysema and airway remodeling in rats. UA exerted its effects through ameliorating apoptosis by down regulating UPR signalling pathways and subsequent apoptosis pathways, as well as, downregulating p-Smad2 and p-Smad3 molecules. Conclusions: UA attenuated CSE-induced emphysema and airway remodeling, exerting its effects partly through regulation of three UPR pathways, amelioration downstream apoptotic pathways, and alleviating activation of Smad2 and Smad3.

Lin|Li|L| Hou|Gang|G| Han|Dan|D| Kang|Jian|J| Wang|Qiuyue|Q|

ursolic acid
cigarette smoke extract
endoplasmic reticulum stress
airway remodeling
chronic obstructive pulmonary disease


Effects of zinc and magnesium supplements on postpartum depression and anxiety: A randomized controlled clinical trial.

Abstract: Postpartum anxiety and depression are prevalent disorders. The authors of this study aimed to determine the effects of zinc and magnesium supplements on depressive symptoms and anxiety in postpartum women referred to three governmental, educational hospitals in Tabriz, Iran during 2014-2015. In this triple-blind, randomized, controlled clinical trial, the participants were randomly assigned to the zinc sulfate, magnesium sulfate, and placebo groups (n = 33 per group). The intervention groups received a 27-mg zinc sulfate tablet or 320-mg magnesium sulfate tablet per day for 8 weeks, whereas the control group received a placebo tablet each day during the same period. The Edinburgh Postnatal Depression Scale and the Spielberger State-Trait Anxiety Inventory were completed before and 8 weeks after the intervention. Blood samples were drawn from each participant to determine serum levels of zinc and magnesium before intervention at 48 hours after delivery. Also, a 24-hour dietary questionnaire was used during the first and last 3 days of the intervention. Adjusting for baseline scores as well as zinc and magnesium serum levels, no significant difference was observed between groups 8 weeks after delivery in mean scores of depressive symptoms (p = .553), state anxiety (p = .995), and trait anxiety (p = .234). This study concluded magnesium and zinc did not reduce postpartum anxiety and depressive symptoms.

Fard|Fatemeh Edalati|FE|
Mirghafourvand|Mojgan|M|
Mohammad-Alizadeh Charandabi|Sakineh|S|
Farshbaf-Khalili|Azizeh|A|
Javadzadeh|Yousef|Y|
Asgharian|Hanieh|H|

D011569:Psychiatric Status Rating Scales

zinc
magnesium
postpartum
Anxiety
depressive symptoms


The antitumor activity of umbelliferone in human renal cell carcinoma via regulation of the p110γ catalytic subunit of PI3Kγ.

Abstract: Umbelliferone exhibits extensive pharmacological activity, including anti-immunomodulatory, anti-inflammatory and antigenotoxicity activities. However, its antitumor properties still remain unclear in human renal cell carcinoma (RCC) cells. Our results have revealed that treatment of human RCC cells (786-O, OS-RC-2, and ACHN) with umbelliferone reduced cell proliferation in a concentration-dependent manner and induced dose-dependent apoptotic events. In addition, cell cycle analysis determined that umbelliferone treatment induced cell cycle arrest in the G1 phase in a dose-dependent manner. Furthermore, western blotting analysis showed a dose-dependent decrease in Ki67, MCM2, Bcl-2, CDK2, CyclinE1, CDK4, and CyclinD1 and a dose-dependent increase in Bax in RCC cells cultured with umbelliferone. Similarly, umbelliferone exhibited a dose-dependent reduction of p110γ when using western blotting analyses. Taken together, these results provide an insight into the pharmacology regarding the potential application of umbelliferone, which contributes to cell death by decreasing p110γ protein expression.

Wang|Xue|X| Huang|Shuaishuai|S| Xin|Xia|X| Ren|Yu|Y| Weng|Guobin|G| Wang|Ping|P|

D058544:Class Ib Phosphatidylinositol 3-Kinase

umbelliferone
renal cell carcinoma
p110γ
anti-cancer activity


Clinical and Radiographical Measurements of Supraeruption and Occlusal Interferences in Unopposed Posterior Teeth.

Abstract:
AIMS AND OBJECTIVES
This study compared the supraeruption of teeth for study casts (SCs) and panoramic radiographs (PRs) and its relation to tooth type, arch, facial sides, presence of occlusal interferences, and type of tooth movements.

MATERIALS AND METHODS
A total of 65 patients with their SCs and PRs were recruited. Supraerupted tooth type, arches, sides involved, and the presence of occlusal interferences were recorded. The SCs for supraerupted teeth were photographed, and supraeruption from PRs was recorded from the patients' files. The values were transferred to a software program and assessed.

RESULTS
The highest frequency was observed among the younger-age group and molars in both arches. Working side (WS) and retruded cuspal position (RCP) interferences were recorded the highest. Supraeruption values of 0.7-1.2 mm accounted for 47.5% (38) of the total. Tilting and tipping of teeth were the highest, followed by buccolingual displacement. Kappa tests showed good intraexaminer reliability and Bland-Altman plot showed 95% confidence interval band.

CONCLUSIONS
No significant differences were observed in the supraeruption values between the type of tooth among different subgroups of SCs and PRs. Significant differences were recorded between the types and sites of teeth, with a higher ratio observed in molar teeth, mandibular arch, and young age group. RCP and WS were the most recorded occlusal interferences and buccolingual displacement, and tilting and tipping were the most noticeable occlusal tooth movements.

CLINICAL SIGNIFICANCE
Diagnosis and measurements of supraeruption are essential, useful, and significant steps before treatments for replacement of missing tooth/teeth as well as corrections of occlusal interferences during different mandibular movements.

Al Moaleem|Mohammed M|MM|
Porwal|Amit|A|
Qahhar|Mohammed A|MA|
Al Qatarneh|Feras A|FA|
Areeshi|Seham A|SA|
Aldossary|Mohammad Bf|MB|

Occlusal interferences
Panoramic radiograph
Overeruption
Study casts Supraeruption..


An Analysis of Health Science Students' Preparedness and Perception of Interactive Virtual Laboratory Simulation.

Abstract: The achievement of learning goals via laboratory practical depends on both extrinsic and intrinsic factors. They could be limited by laboratory time, incurred cost, safety, self-efficacy, inadequate prior preparation by learners, and different learning styles. Hence, virtual laboratory simulation (vLAB) may be an appropriate e-learning tool to overcome these restrictions. In this study, student's perception of the usefulness of vLAB was determined by using deoxyribonucleic acid (DNA) gel electrophoresis and polymerase chain reaction (PCR) as case examples. The perception of Year 2 and 3 health science undergraduate students' (N = 87) was studied using a questionnaire consisting of 12 items, rated on a 5-point Likert-scale. The attainment of learning outcomes was assessed using pre-and post-tests containing multiple-choice questions (MCQs). In addition, student's experience and learning from the vLAB were further explored using qualitative analysis. Although there was no significant difference between the mean scores of the pre-and post-tests, results showed that all participants perceived vLAB well, with a median score of 4 (Agree) for all items in the questionnaire. It provides a meaningful learning experience and an authentic environment where students feel safe to practice what they have learnt in lectures. Moreover, vLAB facilitates individualised learning and enhances self-efficacy among students. In conclusion, vLAB prepares students for physical laboratory sessions by activating the prehension dimension of Kolb's learning cycle, therefore complementing and strengthening the attainments of health sciences laboratory learning goals and outcomes.

Virtual laboratory simulation
Individualised learning
Constructivism
Experiential learning


Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells.

Abstract: Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C)-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC) significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity.

Jiang|Chunwa|C| Masood|Muqaddas|M| Rasul|Azhar|A| Wei|Wei|W| Wang|Ya|Y| Ali|Muhammad|M| Mustaqeem|Muhammad|M| Li|Jiang|J| Li|Xiaomeng|X|

D004354:Drug Screening Assays, Antitumor

altholactone
NF-κB
STAT3
prostate cancer
natural compound


Posterior reversible leukoencephalopathy syndrome with spinal cord involvement in a 9-year-old girl.

Abstract: We report the youngest pediatric case of posterior reversible leukoencephalopathy syndrome confined to brainstem and spinal cord. At presentation bicytopenia, renal derangement, visual disturbances, magnetic resonance imaging findings, increased protein content, IgG index and cell count in the cerebrospinal fluid led us to extensive search for myelitis. She received a short course of steroid treatment. The final diagnosis was hypertension due to reflux nephropathy. Severe hypertension that exceeds the range of autoregulation in anterior spinal territory may result in spinal posterior reversible leukoencephalopathy syndrome. Clinicians should be aware of spinal posterior reversible leukoencephalopathy syndrome when cases have extensive lesions in the brainstem and spinal cord with none or minimal clinical findings, so called "clinical radiologic dissociation".

Yiş|Uluç|U|
Karaoğlu|Pakize|P|
Kurul|Semra Hız|SH|
Soylu|Alper|A|
Çakmakçi|Handan|H|
Kavukçu|Salih|S|


Anatomy and surgical approach of rat's vestibular sensors and nerves.

Abstract:
BACKGROUND
The rat is one of the most used species in the neurosciences, but how to selectively reach each of its 5 vestibular sensors has never been described. Besides, new functions of the vestibular system have been recently discovered in the rat involving vegetative, circadian and cognitive functions. But the central pathways sustaining these functions and the role of each of the vestibular sensors are not clear.

NEW METHODS
Here we want to describe the anatomy and look for a direct surgical approach to the 5 vestibular sensors in rats, as an indispensable technique to further study the central vestibular pathways. To do so we studied 10 rats either by microtomography with osmium tetroxide staining, histology with hematoxilyn-eosine staining or microsurgical dissection.

RESULTS
The microtomography allows a 3D representation of the 5 vestibular sensors and their nerves, with precise landmarks confirmed by the histological analysis. Each of the landmarks are illustrated and a selective surgical approach to each sensor and their nerves, is described step by step.

COMPARISON WITH EXISTING METHOD
Selective approaches to the vestibular sensors have been used in other species such as cats, monkeys and recently humans but the current study is the first allowing this technique in rats.

CONCLUSION
Each vestibular sensor of the rat can be reached by a selective surgical approach. This allows further techniques such as electrophysiology or neurotracing of the central vestibular pathways. This also indicates the rat as a potential model for vestibular prostheses.

Hitier|Martin|M|
Sato|Go|G|
Zhang|Yan-Feng|YF|
Zheng|Yiwen|Y|
Besnard|Stephane|S|
Smith|Paul F|PF|
Curthoys|Ian S|IS|

Anatomy
Rat
Microtomography
Ampulla
Macula
Vestibular organ


Multiple signal amplification strategies for ultrasensitive label-free electrochemical immunoassay for carbohydrate antigen 24-2 based on redox hydrogel.

Abstract: In this work, multiple signal amplification strategies for ultrasensitive label-free electrochemical immunoassay for carbohydrate antigen 24-2 (CA242) were developed using redox sodium alginate-Pb2+-graphene oxide (SA-Pb2+-GO) hydrogel. The SA-Pb2+-GO hydrogel was synthesised by simply mixing SA, GO, and Pb2+ and then implemented as a novel redox species with a strong current signal at -0.46V (vs. Ag/AgCl). After the three-dimensional and porous SA-Pb2+-GO hydrogel was in situ generated on a glassy carbon electrode (GCE), chitosan was adsorbed on the obtained electrode to further enrich Pb2+. When chitosan-Pb2+/SA-Pb2+-GO/GCE was incubated with anti-CA242 using glutaraldehyde and blocked by bovine serum albumin, the immunoassay platform for CA242 was obtained. Owing to the addition of GO, the obtained conductive SA-GO/GCE was beneficial for signal amplification. After incubating SA-GO/GCE with excessive amounts of Pb2+, the resistance of SA-Pb2+-GO/GCE further decreased and a strong redox signal was obtained. The chitosan fixed by electrostatic adsorption resulted in further adsorption of Pb2+, behaving as further amplifying the signal and improving conductivity. In this case, multiple signal amplification strategies were involved in the proposed immunosensor for the ultrasensitive detection of CA242. Under the optimal conditions, the proposed immunosensor exhibited a wide linear range from 0.005UmL-1 to 500UmL-1 with an ultralow detection limit of 0.067mUmL-1. In comparison to previous works, the sensitivity of this method was 32.98μA (log10CCA242)-1, which was a five-fold increase from the previous works.

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

Electrochemical immunoassay
Carbohydrate antigen 24-2
Hydrogel
Chitosan
Sodium alginate
Sodium alginate-Pb(2+)-graphene oxide


Brain circuits involved in understanding our own and other's internal states in the context of romantic relationships.

Abstract: Social interactions require the capacity to understand both our and other's internal states. These semi-independent skills, the ability to understand oneself and others, seem to rely on the same type of representations and recruit similar brain areas. In this study, we looked at the neural basis of self and other processing in the context of an interaction with a significant other. Fourty-two participants in a monogamous relationship completed an fMRI task in which they watched a set of video-vignettes of his/her romantic partner expressing emotional contents. Participants were asked to elaborate on his/her spouse´s experience (other condition) and on his/her own experience when watching the video-vignettes (self-condition). The results showed a significant overlap in the brain activation for both conditions (e.g. anterior insula, posterior cingulate/precuneus, inferior frontal gyrus, inferior parietal lobule). In addition, the self-condition recruited brain areas associated with interoceptive processing and affect sharing (e.g., posterior insula), whereas the other-condition engaged brain areas involved in the cognitive representation of another's internal states and self-other distinction (e.g., fusiform, supramarginal gyrus, angular gyrus and temporoparietal junction).

Esménio|Sofia|S|0000-0002-8155-1300
Soares|José Miguel|JM|
Oliveira-Silva|P|P|
Gonçalves|Óscar F|ÓF|
Decety|Jean|J|
Coutinho|Joana|J|

romantic relationships
Social cognition
self/other processing
theory of mind


Nitrite-reducing ability is related to growth inhibition by nitrite in Rhodobacter sphaeroides f. sp. denitrificans.

Abstract: Growth inhibition of Rhodobacter sphaeroides f. sp. denitrificans IL106 by nitrite under anaerobic-light conditions became less pronounced when the gene encoding nitrite reductase was deleted. Growth of another deletion mutant of the genes encoding nitric oxide reductase was severely suppressed by nitrite. Our results suggest that nitrite reductase increases the sensitivity to nitrite through the production of nitric oxide.

Shimizu|Takayuki|T| Horiguchi|Kouhei|K| Hatanaka|Yui|Y| Masuda|Shinji|S| Shimada|Keizo|K| Matsuura|Katsumi|K| Haruta|Shin|S|

Rhodobacter
nitrite reductase
Denitrification
nitrite toxicity
photosynthetic bacteria


Field trial of insect-resistant and herbicide-tolerant genetically modified cotton (Gossypium hirsutum L.) for environmental risk assessment in Japan.

Abstract: Japan imports cottonseed mainly from Australia and the USA where more than 96% of all cotton varieties grown are genetically modified (GM). GM crops undergo an environmental risk assessment (ERA) under the Law Concerning the Conservation and Sustainable Use of Biological Diversity before import into Japan. Potential adverse effects on biodiversity are comprehensively assessed based on competitiveness, production of harmful substances and outcrossing ability. Even though imported cottonseed is intended for food and feed uses and not for cultivation, the potential risks from seed spillage during transport must be evaluated. In most cases, the ERA requires data collected from in-country field trials to demonstrate how the GM crop behaves in Japan's environment. Confined field trials in Japan were conducted for the ERA of Lepidoptera-resistant and glufosinate-tolerant GM cotton (Gossypium hirsutum L.) lines GHB119 and T304-40. These lines were compared with conventional varieties for growth habit, morphological characteristics, seed dormancy, and allelopathic activity associated with competitiveness and production of harmful substances. Outcrossing ability was not a concern due to the absence of sexually compatible wild relatives in Japan. Although slight statistical differences were observed between the GM line and its conventional comparator for some morphological characteristics, transgenes or transformation were not considered to be responsible for these differences. The trial demonstrated that competitiveness and production of harmful substances by these GM cotton lines were equivalent to conventional cotton varieties that have a long history of safe use, and no potential adverse effects to biosafety in Japan were observed.

Asanuma|Yoko|Y| Gondo|Takahiro|T| Ishigaki|Genki|G| Inoue|Koichi|K| Zaita|Norihiro|N| Muguerza|Melody|M| Akashi|Ryo|R|

field trial
Gossypium hirsutum L.
environmental risk assessment (ERA)
biological diversity
genetically modified (GM) cotton


Investigation of the nutritional, functional and technological effects of the sourdough fermentation of sprouted flours.

Abstract: In recent years, recommendations on whole grains consumption have been added to the overall dietary guidelines of many countries around the world. Despite the many benefits on human health, whole grains contain several anti-nutritional factors which decrease their nutritional quality leading to a poor use in human diet. Here, an integrate biotechnological approach, combining germination and sourdough fermentation with selected lactic acid bacteria, was set-up in order to improve the functional and nutritional quality of wheat, barley, chickpea, lentil and quinoa grains. Sourdough fermentation with Lactobacillus rossiae LB5, Lactobacillus plantarum 1A7 and Lactobacillus sanfranciscensis DE9 further enhanced the nutritional and functional features of sprouted flours by means of increased peptides, free amino acids and γ‑aminobutyric acid concentrations, and decreased phytic acid, condensed tannins, raffinose and trypsin inhibitory activity. Sensory appreciable wheat breads fortified with the fermented sprouted flours were manufactured and characterized, showing high protein digestibility and low starch availability.

Montemurro|Marco|M|
Pontonio|Erica|E|
Gobbetti|Marco|M|
Rizzello|Carlo Giuseppe|CG|

Sourdough
Sprouted flours
Germination
Lactic acid bacteria
Bread
Antinutritional factors


Large sternal exostoses presenting as stridor: A surgical and anesthetic challenge.

Abstract:
BACKGROUND AND AIMS
Large osteochondroma arising from chest wall and sternum is uncommon and presentation with airway compression is further uncommon.

METHODS
Here we present a case of large chest wall osteochondroma as a part of hereditary multiple exostoses in a 9-year-old boy presented with a history of stridor and shortness of breath. The bony mass of the right chest wall was extending up to a suprasternal notch and compressing the trachea.

RESULTS
The case was successfully managed by initial femoro-femoral cardiopulmonary bypass under local anesthesia before the induction of anesthesia to prevent respiratory collapse, followed by debulking surgery was done.

exostoses
osteochondroma
airway obstruction
femoro-femoral bypass


Forecasting the milk yield of cows on farms equipped with automatic milking system with the use of decision trees.

Abstract: The purpose of this paper was to utilize the decision trees technique to determine the factors responsible for high monthly milk yield in Polish Holstein-Friesian cows from 27 herds equipped with milking robots. The applied statistical method-the decision tree technique-showed that the most important factors responsible for monthly milk yield of dairy cows using robots were, in descending order of importance: milking frequency, lactation number, month of milking, and type of lying stall. At the same time, it has been ascertained that the highest monthly milk yield (47.24 kg) can be expected from multiparous cows kept in barns with a deep bedding that were milked more frequently than three times per day. On the other hand, the lowest milk production (13.56 kg) was observed among dairy cows milked less frequently than two times a day, with an average number of milked quarters lower than 3.97. The application of the decision trees technique allows a breeder to select appropriate levels of environmental factors and parameters that will help to ensure maximized milk production.

Piwczyński|Dariusz|D|
Sitkowska|Beata|B|
Kolenda|Magdalena|M|0000-0002-9260-4391
Brzozowski|Marcin|M|
Aerts|Joanna|J|
Schork|Pamela M|PM|

milk yield
cows
automatic milking system
decision trees


Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle.

Abstract: Skeletal muscle adapts to external stimuli such as increased work. Muscle progenitors (MPs) control muscle repair due to severe damage, but the role of MP fusion and associated myonuclear accretion during exercise are unclear. While we previously demonstrated that MP fusion is required for growth using a supra-physiological model (Goh and Millay, 2017), questions remained about the need for myonuclear accrual during muscle adaptation in a physiological setting. Here, we developed an 8 week high-intensity interval training (HIIT) protocol and assessed the importance of MP fusion. In 8 month-old mice, HIIT led to progressive myonuclear accretion throughout the protocol, and functional muscle hypertrophy. Abrogation of MP fusion at the onset of HIIT resulted in exercise intolerance and fibrosis. In contrast, ablation of MP fusion 4 weeks into HIIT, preserved exercise tolerance but attenuated hypertrophy. We conclude that myonuclear accretion is required for different facets of exercise-induced adaptive responses, impacting both muscle repair and hypertrophic growth.

Goh|Qingnian|Q|
Song|Taejeong|T|
Petrany|Michael J|MJ|
Cramer|Alyssa Aw|AA|0000-0003-2997-5066
Sun|Chengyi|C|0000-0001-8500-1878
Sadayappan|Sakthivel|S|
Lee|Se-Jin|SJ|
Millay|Douglas P|DP|0000-0001-5188-0720

D032496:Satellite Cells, Skeletal Muscle

myonuclear accretion
exercise
muscle hypertrophy
cell fusion
developmental biology
mouse
myomaker
regenerative medicine
stem cells


Linkages between soil carbon, soil fertility and nitrogen fixation in Acacia senegal plantations of varying age in Sudan.

Abstract:
Background
Over the last decades sub-Saharan Africa has experienced severe land degradation and food security challenges linked to loss of soil fertility and soil organic matter (SOM), recurrent drought and increasing population. Although primary production in drylands is strictly limited by water availability, nutrient deficiencies, particularly of nitrogen (N) and phosphorus (P), are also considered limiting factors for plant growth. It is known that SOM (often measured as soil organic carbon (SOC)) is a key indicator of soil fertility, therefore, management practices that increase SOM contents, such as increasing tree cover, can be expected to improve soil fertility. The objectives of this study were to investigate the effect of Acacia senegal (Senegalia senegal) trees on soil nitrogen, phosphorus and potassium (K) in relation to SOC, the potential of A. senegal for N2 fixation, and to identify possible N and P ecosystem limitations.

Methods
Soil nutrient (total N, P, K and available P and exchangeable K) concentrations and stocks were determined for the 0-10, 10-20,20-30 and 30-50 cm layers of A. senegal plantations of varying age (ranging from 7 to 24-years-old) and adjacent grasslands (reference) at two sites in semi-arid areas of Sudan. At both sites, three plots were established in each grassland and plantation. The potential of A. senegal for N2 fixation in relation to plantations age was assessed using δ15N isotopic abundances and nutrient limitations assessed using C:N:P stoichiometry.

Results
Soil concentrations of all studied nutrients were relatively low but were significantly and directly correlated to SOC concentrations. SOC and nutrient concentrations were the highest in the topsoil (0-10 cm) and increased with plantations age. Acacia foliage δ15N values were >6‰ and varied little with plantations age. Soil C:N and C:P ratios did not differ between grassland and plantations and only 0-10 cm layer N:P ratios showed significant differences between grassland and plantations.

Discussion
The results indicated that soil fertility in the Sahel region is strongly related to SOM contents and therefore highlighting the importance of trees in the landscape. The higher mineral nutrient concentrations in the topsoil of the plantations may be an indication of 'nutrient uplift' by the deeper roots. The high foliar δ15N values indicated that N2 fixation was not an important contributor to soil N contents in the plantations. The accretion of soil N cannot be explained by deposition but may be related to inputs of excreted N brought into the area annually by grazing and browsing animals. The soil C:N:P stoichiometry indicated that the plantations may be limited by P and the grasslands limited by N.

Drylands
Senegalia senegal
Soil nutrients
Sahel
Nitrogen isotopes
Woodland savanna


An aberrant right hepatic artery arising from the gastroduodenal artery: a pitfall encountered during pancreaticoduodenectomy.

Abstract:
PURPOSE
Among the variations of the right hepatic artery (RHA), the identification of an aberrant RHA arising from the gastroduodenal artery (GDA) is vital for avoiding damage to the RHA during surgery, since ligation of the GDA is necessary during pancreaticoduodenectomy (PD). However, this variation is not frequently reported. The purpose of this study was to focus on an aberrant RHA arising from the GDA, which was not noted in the classifications reported by Michels and Hiatt.

METHODS
A total of 574 patients undergoing a PD between Jan 2001 and Dec 2015 at a tertiary care hospital in Switzerland (n = 366) and between Jan 2009 and May 2015 at a hospital in Japan (n = 208) were included in the analysis. Of these, preoperative CT angiography or/and MRI angiography findings were available for 532 patients. We retrospectively analyzed the hepatic artery variations, patient demographics, and surgical outcomes.

RESULTS
Among the 532 patients who received a PD, an RHA originating from the GDA was observed in 19 cases (3.5%). Eleven patients (2.1%) had both an aberrant RHA and an aberrant left hepatic artery (LHA) (Hiatt Type 4). Six patients (1.2%) had a replaced CHA arising from the SMA (Hiatt Type 5). We could, therefore, correctly identify the aberration in all cases.

CONCLUSIONS
We observed rarely reported but important aberrant RHA variations arising from the GDA. To prevent injury during PD in patients with this type of aberrant RHA, intensive preparations using CT and/or MRI imaging before surgery and intraoperative liver Doppler ultrasonography are considered to be essential.

Aberrant right hepatic artery
Pancreaticoduodenectomy
Pancreas


The proto-oncogene Myc drives expression of the NK cell-activating NKp30 ligand B7-H6 in tumor cells.

Abstract: Natural Killer (NK) cells are innate effector cells that are able to recognize and eliminate tumor cells through engagement of their surface receptors. NKp30 is a potent activating NK cell receptor that elicits efficient NK cell-mediated target cell killing. Recently, B7-H6 was identified as tumor cell surface expressed ligand for NKp30. Enhanced B7-H6 mRNA levels are frequently detected in tumor compared to healthy tissues. To gain insight in the regulation of expression of B7-H6 in tumors, we investigated transcriptional mechanisms driving B7-H6 expression by promoter analyses. Using luciferase reporter assays and chromatin immunoprecipitation we mapped a functional binding site for Myc, a proto-oncogene overexpressed in certain tumors, in the B7-H6 promoter. Pharmacological inhibition or siRNA/shRNA-mediated knock-down of c-Myc or N-Myc significantly decreased B7-H6 expression on a variety of tumor cells including melanoma, pancreatic carcinoma and neuroblastoma cell lines. In tumor cell lines from different origin and primary tumor tissues of hepatocellular carcinoma (HCC), lymphoma and neuroblastoma, mRNA levels of c-Myc positively correlated with B7-H6 expression. Most importantly, upon inhibition or knock-down of c-Myc in tumor cells impaired NKp30-mediated degranulation of NK cells was observed. Thus, our data imply that Myc driven tumors could be targets for cancer immunotherapy exploiting the NKp30/B7-H6 axis.

Textor|Sonja|S| Bossler|Felicitas|F| Henrich|Kai-Oliver|KO| Gartlgruber|Moritz|M| Pollmann|Julia|J| Fiegler|Nathalie|N| Arnold|Annette|A| Westermann|Frank|F| Waldburger|Nina|N| Breuhahn|Kai|K| Golfier|Sven|S| Witzens-Harig|Mathias|M| Cerwenka|Adelheid|A|


Comparison of the Effects of Hand Reflexology versus Acupressure on Anxiety and Vital Signs in Female Patients with Coronary Artery Diseases.

Abstract: Hospitalization in the cardiac care unit can increase anxiety in patients. This study aimed to compare hand reflexology versus acupressure on anxiety and vital signs in female patients with coronary artery diseases. This double-blinded randomized placebo-controlled trial with a pre- and post-intervention design was conducted on 135 female patients with coronary artery diseases. Female patients hospitalized in a cardiac care unit were randomly divided into three groups of hand reflexology, acupressure and placebo (n = 45 patients in each group) using blocking and a table of random numbers. Data was collected using the Spielberger anxiety inventory. Also, their vital signs were measured before, immediately after and half an hour after the intervention. Data analysis was performed using descriptive and analytical statistics. Before the intervention, there was no statistically significant difference in anxiety levels between the groups (p > 0.05). Also, the effects of hand reflexology and acupressure immediately and half an hour later on the reduction of anxiety and vital signs were equal (p < 0.05). Implementation of hand reflexology and acupressure can have positive effects on anxiety and vital signs in patients with coronary artery diseases. They can reduce patients' anxiety with an equal effectiveness.

Rahmani Vasokolaei|Zohre|Z|
Rejeh|Nahid|N|
Heravi-Karimooi|Majideh|M|
Tadrisi|Seyed Davood|SD|
Saatchi|Kiarash|K|
Poshtchaman|Zahra|Z|
Sieloff|Christina|C|
Vaismoradi|Mojtaba|M|

hand reflexology
acupressure
anxiety
vital sign
coronary artery disease
complementary therapies


Mesoscale eddies and Trichodesmium spp. distributions in the southwestern North Atlantic.

Abstract: Trichodesmium abundance was elevated in certain cyclonic and anticyclonic eddiesEnhancement in cyclonic eddies could be driven by Ekman convergenceAnticyclonic eddies with elevated abundance were anomalously fresh.

Olson|Elise M|EM|
McGillicuddy|Dennis J|DJ|
Flierl|Glenn R|GR|
Davis|Cabell S|CS|
Dyhrman|Sonya T|ST|
Waterbury|John B|JB|

Amazon plume
eddy‐wind interaction
video plankton recorder


The Neurovascular Unit: Focus on the Regulation of Arterial Smooth Muscle Cells.

Abstract: The neurovascular unit is a physiological unit present in the brain, which is constituted by elements of the nervous system (neurons and astrocytes) and the vascular system (endothelial and mural cells). This unit is responsible for the homeostasis and regulation of cerebral blood flow. There are two major types of mural cells in the brain, pericytes and smooth muscle cells. At the arterial level, smooth muscle cells are the main components that wrap around the outside of cerebral blood vessels and the major contributors to basal tone maintenance, blood pressure and blood flow distribution. They present several mechanisms by which they regulate both vasodilation and vasoconstriction of cerebral blood vessels and their regulation becomes even more important in situations of injury or pathology. In this review, we discuss the main regulatory mechanisms of brain smooth muscle cells and their contributions to the correct brain homeostasis.

Neurovascular unit
smooth muscle cells
cerebral blood flow
vasoconstriction
vasodilatation.


Measuring emotion socialization in families affected by pediatric cancer: Refinement and reduction of the Parents' Beliefs about Children's Emotions questionnaire.

Abstract: The aim of this study is to conduct a multimethod psychometric reduction in the Parents' Beliefs about Children's Emotions (PBCE) questionnaire using an item response theory framework with a pediatric oncology sample. Participants were 216 pediatric oncology caregivers who completed the PBCE. The PBCE contains 105 items (11 subscales) rated on a 6-point Likert-type scale. We evaluated the PBCE subscale performance by applying a partial credit model in WINSTEPS. Sixty-six statistically weak items were removed, creating a 44-item PBCE questionnaire with 10 subscales and 3 response options per item. The refined scale displayed good psychometric properties and correlated .910 with the original PBCE. Additional analyses examined dimensionality, item-level (e.g. difficulty), and person-level (e.g. ethnicity) characteristics. The refined PBCE questionnaire provides better test information, improves instrument reliability, and reduces burden on families, providers, and researchers. With this improved measure, providers can more easily identify families who may benefit from psychosocial interventions targeting emotion socialization. The results of the multistep approach presented should be considered preliminary, given the limited sample size.

Beitra|Danette|D|
El-Behadli|Ana F|AF|
Faith|Melissa A|MA|

Parents’ Beliefs about Children’s Emotions


Redox-Dependent Chromatin Remodeling: A New Function of Nitric Oxide as Architect of Chromatin Structure in Plants.

Abstract: Nitric oxide (NO) is a key signaling molecule in all kingdoms. In plants, NO is involved in the regulation of various processes of growth and development as well as biotic and abiotic stress response. It mainly acts by modifying protein cysteine or tyrosine residues or by interacting with protein bound transition metals. Thereby, the modification of cysteine residues known as protein S-nitrosation is the predominant mechanism for transduction of NO bioactivity. Histone acetylation on N-terminal lysine residues is a very important epigenetic regulatory mechanism. The transfer of acetyl groups from acetyl-coenzyme A on histone lysine residues is catalyzed by histone acetyltransferases. This modification neutralizes the positive charge of the lysine residue and results in a loose structure of the chromatin accessible for the transcriptional machinery. Histone deacetylases, in contrast, remove the acetyl group of histone tails resulting in condensed chromatin with reduced gene expression activity. In plants, the histone acetylation level is regulated by S-nitrosation. NO inhibits HDA complexes resulting in enhanced histone acetylation and promoting a supportive chromatin state for expression of genes. Moreover, methylation of histone tails and DNA are important epigenetic modifications, too. Interestingly, methyltransferases and demethylases are described as targets for redox molecules in several biological systems suggesting that these types of chromatin modifications are also regulated by NO. In this review article, we will focus on redox-regulation of histone acetylation/methylation and DNA methylation in plants, discuss the consequences on the structural level and give an overview where NO can act to modulate chromatin structure.

Ageeva-Kieferle|Alexandra|A|
Rudolf|Eva Esther|EE|
Lindermayr|Christian|C|

nitric oxide
S-nitrosation
acetylation
methylation
chromatin modulation
redox-modification


Sodium Monoiodoacetate Dose-Dependent Changes in Matrix Metalloproteinases and Inflammatory Components as Prognostic Factors for the Progression of Osteoarthritis.

Abstract: Osteoarthritis (OA) is a degenerative joint disease that primarily affects people over 65 years old. During OA progression irreversible cartilage, synovial membrane and subchondral bone degradation is observed, which results in the development of difficult-to-treat chronic pain. One of the most important factors in OA progression is joint inflammation. Both proinflammatory and anti-inflammatory factors, as well as extracellular matrix degradation enzymes (matrix metalloproteinases (MMPs), play an important role in disease development. One of the most widely used animal OA models involves an intra-articular injection of sodium monoiodoacetate (MIA) directly into the joint capsule, which results in glycolysis inhibition in chondrocytes and cartilage degeneration. This model mimics the degenerative changes observed in OA patients. However, the dose of MIA varies in the literature, ranging from 0.5 to 4.8 mg. The aim of our study was to characterize grading changes after injection of 1, 2 or 3 mg of MIA at the behavioral and molecular levels over a 28-day period. In the behavioral studies, MIA injection at all doses resulted in a gradual increase in tactile allodynia and resulted in abnormal weight bearing during free walking sequences. At several days post-OA induction, cartilage, synovial membrane and synovial fluid samples were collected, and qPCR and Western blot analyses were performed. We observed significant dose- and time-dependent changes in both gene expression and protein secretion levels. Inflammatory factors (CCL2, CXCL1, IL-1β, COMP) increased at the beginning of the experiment, indicating a transient inflammatory state connected to the MIA injection and, in more severe OA, also in the advanced stages of the disease. Overall, the results in the 1 mg MIA group were not consistently clear, indicating that the lowest tested dose may not be sufficient to induce long-lasting OA-like changes at the molecular level. In the 2 mg MIA group, significant alterations in the measured factors were observed. In the 3 mg MIA group, MMP-2, MMP-3, MMP-9, and MMP-13 levels showed very strong upregulation, which may cause overly strong reactions in animals. Therefore, a dose of 2 mg appears optimal, as it induces significant but not excessive OA-like changes in a rat model.

Bryk|Marta|M| Chwastek|Jakub|J| Mlost|Jakub|J| Kostrzewa|Magdalena|M| Starowicz|Katarzyna|K|

matrix metalloproteinases
osteoarthritis
cartilage
synovial membrane
chronic pain
pain
inflammation
synovial fluid


Transcription Factor IRF4 Promotes CD8+ T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection.

Abstract: During chronic stimulation, CD8+ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected with lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1. These regulators promoted expression of inhibitory receptors, including PD-1, and mediated impaired cellular metabolism. Furthermore, they repressed the expression of TCF1, a transcription factor required for memory T cell differentiation. Reducing IRF4 expression restored the functional and metabolic properties of antigen-specific T cells and promoted memory-like T cell development. These findings indicate that IRF4 functions as a central node in a TCR-responsive transcriptional circuit that establishes and sustains T cell exhaustion during chronic infection.

Man|Kevin|K|
Gabriel|Sarah S|SS|
Liao|Yang|Y|
Gloury|Renee|R|
Preston|Simon|S|
Henstridge|Darren C|DC|
Pellegrini|Marc|M|
Zehn|Dietmar|D|
Berberich-Siebelt|Friederike|F|
Febbraio|Mark A|MA|
Shi|Wei|W|
Kallies|Axel|A|

D050976:Basic-Leucine Zipper Transcription Factors

D051538:Hepatocyte Nuclear Factor 1-alpha

D061026:Programmed Cell Death 1 Receptor

transcription
IRF4
exhaustion
chronic infection
BATF
TCF1
memory
differentiation
CD8(+)
NAICE
NFAT
NFAT_AP-1_IRF4 composite element
metabolic function


Association of Epstein-Barr virus with invasive breast carcinoma and its impact on well-known clinicopathologic parameters in Iranian women.

Abstract:
BACKGROUND
The association between Epstein-Barr virus (EBV) and breast carcinoma in Iranian women is uncertain. We examined EBV latent membrane protein-1 (LMP-1) antigen expression in breast carcinoma and its relationship with clinicopathologic parameters among a population of Iranian patients.

MATERIALS AND METHODS
This study was performed on formalin fixed and paraffin embedded tissue specimens with a diagnosis of invasive breast carcinoma archived at one university hospital in Isfahan city, Iran. We used immunohistochemistry to detect LMP-1 of EBV in carcinoma and its adjacent normal tissue. The frequency of LMP-1 expression in breast carcinoma and its relationship with age, tumor size, tumor type, tumor grade and lymph node status were then determined.

RESULTS
A total of 80 cases were evaluated including 77 (96.3%) ductal, 1 (1.3%) lobular, 1 (1.3%) medullary and 1 (1.3%) mucinous carcinoma. LMP-1 expression was seen in 6 cases (7.5%) of breast carcinoma whereas normal breast tissue adjacent to carcinoma was negative for LMP-1 in all of the cases. A statistically significant association was seen between EBV and invasive breast carcinoma (P = 0.03). No significant relationship was observed between LMP-1 expression on one hand and age, tumor size, tumor type, tumor grade and lymph node status on the other.

CONCLUSION
EBV may play an etiological role in some of the cases of breast carcinoma in Iranian women. EBV expression does not seem to have a significant impact on the major clinicopathologic prognostic determinants of breast carcinoma.

Epstein-Barr virus
Breast carcinoma
latent membrane protein-1 antigen


Our bodies are our own: resistance to ABC-based HIV-prevention programmes in northern Tanzanian conservation organisations.

Abstract: ABC-based HIV-prevention programmes have been widely employed in northern Tanzanian wildlife conservation settings in an attempt to (re)shape the sexual behaviours of conservation actors. Utilising findings from 66 semi-structured interviews conducted in 2009-2010, this paper examines ABC prevention as a form of Foucauldian governmentality--circulating technologies of power that mobilise disciplinary technologies and attempt to transform such efforts into technologies of the self--and explores how individuals understand and respond to attempts to govern their behaviour. ABC regimes attempt to rework subjectivity, positioning HIV-related behaviours within a risk-based neoliberal rationality. However, efforts to use ABC as a technology to govern populations and individual bodies are largely incommensurate with existing Tanzanian sociocultural formations, including economic and gendered inequalities, and local understandings of sexuality. The language research participants used to talk about ABC and the justifications they offered for non-compliance illuminate this discrepancy. Data reveal that the recipients of ABC campaigns are active producers of understandings that work for them in their lives, but may not produce the behavioural shifts envisioned by programme goals. These findings corroborate previous research, which questions the continued plausibility of ABC as a stand-alone HIV- prevention framework.

D003247:Conservation of Natural Resources

ABC approach
HIV prevention
Tanzania
governmentality
risk


COVID-19 Infection: Concise Review Based on the Immunological Perspective.

Abstract: The outbreak of coronavirus disease 2019 (COVID-19) has posed a serious threat to public health. There is an urgent need for discovery methods for the prevention and treatment of COVID-19 infection. Understanding immunogenicity together with immune responses are expected to provide further information about this virus. We hope that this narrative review article may create new insights for researchers to take great strides toward designing vaccines and novel therapies in the near future. The functional properties of the immune system in COVID-19 infection is not exactly clarified yet. This is compounded by the many gaps in our understanding of the SARS-CoV-2 immunogenicity properties. Possible immune responses according to current literature are discussed as the first line of defense and acquired immunity. Here, we focus on proposed modern preventive immunotherapy methods in COVID-19 infection.

COVID-19
Coronavirus
2019 novel coronavirus
host immune response
vaccine development


Adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging: a pilot study.

Abstract:
PURPOSE
This pilot study evaluated adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging.

METHODS
This was a single-arm prospective investigational pilot study that enrolled 86 patients between August 2012 and April 2014. Descriptive statistics for patient age, race, insurance, stage, duration of treatment, and comorbidities were computed. All patients received routine prescriptions in a "bubble" pack or daily blister pack dispensed by one pharmacy. Participants were considered adherent if they had taken ≥ 80% of the dispensed drug. Disease-free survival (DFS) and overall survival (OS) data were obtained at 78 months.

RESULTS
Fifty patients were included in the analysis. The overall adherence rate was 97%. None of the variables examined (race, age, insurance status, and stage) had an impact on adherence rate. Only duration of endocrine therapy had a marginal effect on adherence (p value = 0.06). The late cohort (duration of therapy 37-60 months) was least likely to be compliant at 89.53%. Our 5-year DFS was 94% and 5-year OS was 96%. There was no statistically significant difference in DFS and OS between patients with adherence rate > 90% and < 90%.

CONCLUSION
Adherence rate to bubble packaging was higher than that in historical studies. Although this is a single-arm pilot study, these data suggest bubble packaging of anti-estrogen may be a reasonable option to improve adherence in hormone receptor-positive breast cancer patients.

D000971:Antineoplastic Combined Chemotherapy Protocols

Adherence
Anti-estrogen therapy
Breast cancer
Bubble packaging


Increasing Incidence of Anaplasmosis in the United States, 2012 Through 2016.

Abstract: Anaplasmosis is a tick-borne disease that is primarily caused by the rickettsial bacterium Anaplasma phagocytophilum. Anaplasmosis is a febrile disease with common symptoms, including headaches, fever, and lethargy, but it can cause serious organ failure and even death if left untreated. Human infections are reported annually to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Diseases Surveillance System (NNDSS). This report analyzed the cases of anaplasmosis reported by the NNDSS from 2012 to 2016. In total, there were 15,778 reported A. phagocytophilum infections, and the incidence rate was 7.27 cases per million persons per year, with the number of reported cases increasing each year. The demographic group most affected was middle-aged and elderly white males. Infections were most abundant in the coastal northeast and northern midwest regions. Our study provides useful results for a basic understanding of incidence, distribution, and severity of A. phagocytophilum infections.

Baker|Adam|A|
Wang|Hsiao-Hsuan|HH|
Mogg|Michael|M|
Derouen|Zakary|Z|
Borski|Jennifer|J|
Grant|William E|WE|


Distribution of HPV Genotypes and Involvement of Risk Factors in Cervical Lesions and Invasive Cervical Cancer: A Study in an Indian Population.

Abstract: Human papilloma virus (HPV) is considered as the main sexually transmitted etiological agent for the cause and progression of preneoplastic cervical lesions to cervical cancer. This study is discussing the prevalence of HPV and its genotypes in cervical lesions and invasive cervical cancer tissues and their association with various risk factors in women from Varanasi and its adjoining areas in India. A total of 122 cervical biopsy samples were collected from SS Hospital and Indian Railways Cancer Institute and Research Centre, Varanasi and were screened for HPV infection by PCR using primers from L1 consensus region of the viral genome. HPV positive samples were genotyped by type-specific PCR and sequencing. The association of different risk factors with HPV infection in various grades of cervical lesion was evaluated by chi-square test. A total of 10 different HPV genotypes were observed in women with cervicitis, CIN, invasive squamous cell cervical carcinoma and adenocarcinoma. Increased frequency of HPV infection with increasing lesion grade (p=0.002) was observed. HPV16 being the predominant type was found significantly associated with severity of the disease (p=0.03). Various socio- demographic factors other than HPV including high parity (p<0.0001), rural residential area (p<0.0001), elder age (p<0.0001), low socio-economic status (p<0.0001) and women in postmenopausal group (p<0.0001) were also observed to be associated with cervical cancer.These findings show HPV as a direct cause of cervical cancer suggesting urgent need of screening programs and HPV vaccination in women with low socio-economic status and those residing in rural areas.

Srivastava|Shikha|S|
Shahi|U P|UP|
Dibya|Arti|A|
Gupta|Sadhana|S|
Roy|Jagat K|JK|

genotypes
Cervical cancer
rural area
clinical- pathological parameters
human papillomavirus
socio-demographic factors


Are low doses of non-vitamin K antagonists effective in Chinese patients with atrial fibrillation? A report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry.

Abstract:
BACKGROUND
Suboptimal low dosages of non-vitamin K antagonist oral anticoagulants (NOACs) are often inappropriately used due to a fear of bleeding, particularly among elderly patients. Such practice is common in Asia, and we aimed to evaluate the use of low-dose NOACs and their impact on clinical outcomes among Chinese patients with atrial fibrillation.

METHODS
The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry was a prospective, multicenter study conducted in China from October 2014 to December 2018. For this report, we included NOAC-treated patients with available data on NOAC dosage and one-year follow-up. Logistic regression analysis assessed the association (adjusted for age, sex, prior ischemic stroke, prior major bleeding, heart failure, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, liver disease, current anemia) between the low doses and study outcomes among NOAC-treated patients, as well as comparisons with non-anticoagulated patients.

RESULTS
The eligible cohort included 1310 NOAC-treated patients (mean age of 72.1 ± 10.9; 38.9% female), of whom 341 (26.0%) received a low "off-label" dose. The use of low-dose NOACs was independently associated with higher odds of the composite outcome (OR: 2.51; 95% CI: 1.11-5.71) and thromboembolism (OR: 4.73; 95% CI: 1.11-20.01). Compared with non-anticoagulated patients, lower rates of the composite outcome (7.3% vs. 11.3%; p = 0.025) and all-cause death (5.3% vs. 9.7%; p = 0.007) were seen in the low-dose group (ORs 0.50; 95% CI: 0.32-0.78, and 0.42; 95% CI: 0.26-0.70, respectively).

CONCLUSIONS
Low doses of NOACs should not be recommended as a part of standard therapy among Chinese patients with atrial fibrillation as their use was associated with a higher odds ratio of the composite outcome and thromboembolic events compared with standard dose NOAC regimens. Compared to non-treatment, the use of low-dose NOAC may result in a survival benefit (but not thromboembolic reduction) among high-risk patients.

non-vitamin K antagonists
Atrial fibrillation
oral anticoagulation
Asia
stroke
prevention


Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes.

Abstract:
INTRODUCTION
The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT).

METHODS
This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated.

RESULTS
Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37 months). At a median follow-up of 102 months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD) ± chemotherapy. The worst outcomes were in patients who developed metastases after BF (302 pts; 26.5%) and in cases with a Gleason > 7.

CONCLUSIONS
In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

Biochemical failure
Prostate cancer
Radiotherapy
Salvage therapy
Survival rate


The effect of the Iranian health transformation plan on hospitalization rate: insights from an interrupted time series analysis.

Abstract:
BACKGROUND
Healthcare policy- and decision-makers make efforts to build and maintain high-performing and effective health systems, implementing effectiveness programs and health reforms. In May 2014, the Iranian Ministry of Health and Medical Education has launched a series of ambitious reforms, known as the Health Transformation Plan (HTP). This study aimed to determine the effect of the HTP on hospitalization rate in Iranian public hospitals affiliated to the Ministry of Health and Medical Education.

METHODS
This study was designed as a quasi-experimental, counterfactual study utilizing the interrupted time series analysis (ITSA), comparing the trend of hospitalization rate before and after the HTP implementation in 16 hospitals in the Lorestan province. Data was collected from March 2012 to February 2019.

RESULTS
In the first month of the HTP implementation, an increase of 2.627 [95% CI: 1.62-3.63] was noted (P < 0.001). Hospitalization rate increased by 0.68 [95% CI: 0.32-0.85] after the HTP implementation compared to the first month after the launch of the HTP (P < 0.001). After the HTP implementation, monthly hospitalization rate per 1000 persons significantly increased by 0.049 [95% CI: 0.023-0.076] (P < 0.001).

CONCLUSIONS
The HTP implementation has resulted in an increased hospitalization rate. Health planners should continue to further improve this service. ITSA can play a role in evaluating the impact of a given health policy.

Beiranvand|Siavash|S|
Saki|Mandana|M|
Behzadifar|Meysam|M|
Bakhtiari|Ahad|A|
Behzadifar|Masoud|M|
Keshvari|Mohammad|M|
Bragazzi|Nicola Luigi|NL|

D065186:Interrupted Time Series Analysis

Health transformation plan
Hospitalization rate
Interrupted time series analysis
Health policy
Iran


Whole exome sequencing analyses reveal gene-microbiota interactions in the context of IBD.

Abstract:
OBJECTIVE
Both the gut microbiome and host genetics are known to play significant roles in the pathogenesis of IBD. However, the interaction between these two factors and its implications in the aetiology of IBD remain underexplored. Here, we report on the influence of host genetics on the gut microbiome in IBD.

DESIGN
To evaluate the impact of host genetics on the gut microbiota of patients with IBD, we combined whole exome sequencing of the host genome and whole genome shotgun sequencing of 1464 faecal samples from 525 patients with IBD and 939 population-based controls. We followed a four-step analysis: (1) exome-wide microbial quantitative trait loci (mbQTL) analyses, (2) a targeted approach focusing on IBD-associated genomic regions and protein truncating variants (PTVs, minor allele frequency (MAF) >5%), (3) gene-based burden tests on PTVs with MAF <5% and exome copy number variations (CNVs) with site frequency <1%, (4) joint analysis of both cohorts to identify the interactions between disease and host genetics.

RESULTS
We identified 12 mbQTLs, including variants in the IBD-associated genes IL17REL, MYRF, SEC16A and WDR78. For example, the decrease of the pathway acetyl-coenzyme A biosynthesis, which is involved in short chain fatty acids production, was associated with variants in the gene MYRF (false discovery rate <0.05). Changes in functional pathways involved in the metabolic potential were also observed in participants carrying rare PTVs or CNVs in CYP2D6, GPR151 and CD160 genes. These genes are known for their function in the immune system. Moreover, interaction analyses confirmed previously known IBD disease-specific mbQTLs in TNFSF15.

CONCLUSION
This study highlights that both common and rare genetic variants affecting the immune system are key factors in shaping the gut microbiota in the context of IBD and pinpoints towards potential mechanisms for disease treatment.

Hu|Shixian|S|0000-0002-1190-0325
Vich Vila|Arnau|A|0000-0003-4691-5583
Gacesa|Ranko|R|
Collij|Valerie|V|
Stevens|Christine|C|
Fu|Jack M|JM|
Wong|Isaac|I|
Talkowski|Michael E|ME|
Rivas|Manuel A|MA|
Imhann|Floris|F|
Bolte|Laura|L|
van Dullemen|Hendrik|H|
Dijkstra|Gerard|G|0000-0003-4563-7462
Visschedijk|Marijn C|MC|
Festen|Eleonora A|EA|
Xavier|Ramnik J|RJ|
Fu|Jingyuan|J|
Daly|Mark J|MJ|
Wijmenga|Cisca|C|
Zhernakova|Alexandra|A|
Kurilshikov|Alexander|A|
Weersma|Rinse K|RK|0000-0001-7928-7371

D048868:Adaptor Proteins, Signal Transducing

D020022:Genetic Predisposition to Disease

genetics
inflammatory bowel disease
intestinal microbiology


Outcomes, risk factors and health burden of contrast-induced acute kidney injury: an observational study of one million hospitalizations with image-guided cardiovascular procedures.

Abstract:
BACKGROUND
Despite the use of low-osmolar contrast media that have significantly reduced the occurrence of severe adverse reactions, contrast-induced (CI) acute kidney injury (AKI) remains the third cause of AKI in hospitals. We sought to estimate the frequency of CI-AKI among hospitalized patients undergoing image-guided cardiovascular procedures, to quantify the effect of risk factors on the development of this complication and to assess relative organizational and economic burden in healthcare.

METHODS
A retrospective cross-sectional population-based study using the extensive French hospital discharge database (PMSI) was carried out. Hospitalizations with image-guided cardiovascular procedures using a contrast media were identified in adults over a 2-year period (2012-2013). Suspected CI-AKI was defined as the presence, during hospitalization, of a diagnostic code of AKI (International Classification of Diseases, 10th revision [ICD-10] codes: N141, 142, N144, N990, N17, N19 or R392) or a code of renal replacement therapy procedure (Classification Commune des Actes Médicaux [CCAM] codes: JVJB001, JVJF002-005 and JVJF008) as creatinine criteria were not available.

RESULTS
During 1,047,329 hospitalizations studied, 32,308 suspected CI-AKI were observed, yielding a frequency of 3.1 %. By multivariate analysis, factors that significantly increased the risk of suspected CI-AKI included cardiogenic shock (odds ratio [OR] = 20.5, 95 % confidence interval [95 % CI] [18.7; 22.5]), acute heart failure (OR = 2.5, 95 % CI [2.4; 2.6]) and chronic kidney disease (OR = 2.3, 95 % CI [2.2; 2.3]. Renal replacement therapy was initiated during 6,335 (0.6 %) hospitalizations. The mean length of stay and cost of hospitalizations associated with suspected CI-AKI was higher than in hospitalizations without suspected CI-AKI (20.5 vs 4.7 days, p < 0.00001 and €15,765 vs €3,352, p < 0.0001, respectively).

CONCLUSIONS
This is the first large-scale population-based study to estimate frequency and health burden of suspected CI-AKI occurring after image-guided cardiovascular procedures, and the first available data in a French population. We showed that this iatrogenic complication remains of high concern despite prevention efforts and contrast media product improvement. From our results, suspected CI-AKI is associated with particularly high mortality, significantly extends hospitalizations, and leads to additional costs reaching a total of €200M per year.

Aubry|Pierre|P| Brillet|Georges|G| Catella|Laura|L| Schmidt|Aurélie|A| Bénard|Stève|S|

Acute kidney injury
Cardiovascular procedure
Contrast media
Cost analysis
Epidemiology


Incorporating Low-dose Epidemiology Data in a Chlorpyrifos Risk Assessment.

Abstract: USEPA assessed whether epidemiology data suggest that fetal or early-life chlorpyrifos exposure causes neurodevelopmental effects and, if so, whether they occur at exposures below those causing the current most sensitive endpoint, 10% inhibition of blood acetylcholinesterase (AChE). We previously conducted a hypothesis-based weight-of-evidence analysis and found that a proposed causal association between chlorpyrifos exposure and neurodevelopmental effects in the absence of AChE inhibition does not have a substantial basis in existing animal or in vitro studies, and there is no plausible basis for invoking such effects in humans at their far lower exposure levels. The epidemiology studies fail to show consistent patterns; the few associations are likely attributable to alternative explanations. Human data are inappropriate for a dose-response assessment because biomarkers were only measured at one time point, may reflect exposure to other pesticides, and many values are at or below limits of quantification. When considered with pharmacokinetic data, however, these biomarkers provide information on exposure levels relative to those in experimental studies and indicate a margin of exposure of at least 1,000. Because animal data take into account the most sensitive lifestages, the use of AChE inhibition as a regulatory endpoint is protective of adverse effects in sensitive populations.

Goodman|Julie E|JE|
Prueitt|Robyn L|RL|
Rhomberg|Lorenz R|LR|

epidemiology
chlorpyrifos
risk assessment
acetylcholinesterase
neurodevelopment


The impact of endurance training and table soccer on brain metabolites in schizophrenia.

Abstract: Higher glutamate and glutamine (together: Glx) and lower N-acetyl-aspartate (NAA) levels were reported in schizophrenia. Endurance training normalizes NAA in the hippocampus, but its effects on other metabolites in the brain and the relationship of metabolites to clinical symptoms remain unknown. For 12 weeks, 20 schizophrenia inpatients (14 men, 6 women) and 23 healthy controls (16 men, 7 women) performed endurance training and a control group of 21 schizophrenia inpatients (15 men, 6 women) played table soccer. A computer-assisted cognitive performance training program was introduced after 6 weeks. We assessed cognitive performance, psychopathological symptoms, and everyday functioning at baseline and after 6 and 12 weeks and performed single voxel magnetic resonance spectroscopy of the hippocampus, left dorsolateral prefrontal cortex (DLPFC), and thalamus. We quantified NAA, Glx, total creatine (tCr), calculated NAA/tCr and Glx/tCr and correlated these ratios with physical fitness, clinical and neurocognitive scores, and everyday functioning. At baseline, in both schizophrenia groups NAA/tCr was lower in the left DLPFC and left hippocampus and Glx/tCr was lower in the hippocampus than in the healthy controls. After 6 weeks, NAA/tCr increased in the left DLPFC in both schizophrenia groups. Brain metabolites did not change significantly in the hippocampus or thalamus, but the correlation between NAA/tCr and Glx/tCr normalized in the left DLPFC. Global Assessment of Functioning improvements correlated with NAA/tCr changes in the left DLPFC. In our study, endurance training and table soccer induced normalization of brain metabolite ratios in the brain circuitry associated with neuronal and synaptic elements, including metabolites of the glutamatergic system.

Schizophrenia
Glx
NAA
Clinical symptoms
Aerobic exercise
MRS


Nanopurpurin-based photodynamic therapy destructs extracellular matrix against intractable tumor metastasis.

Abstract: Nanomaterials-based photodynamic therapy (PDT) has been used to treat malignant cells. However, the intrinsic impact of nanomaterials-based PDT on mechanical properties of intractable tumor cells is not well understood. Herein, we demonstrated that the mechanical forces of Taxol-resistant tumor cells were decreased by nanopurpurin-based PDT destructing extracellular matrix (ECM), increasing therapy sensitivity and repressing tumor metastasis. Combining FIRMS and general confocal microscope, we observed that the disruption of ECM by photodynamic reaction of P18-nanoconfined liposome (P18⊂L) induced a decrease of adhesion force and biomechanical properties of Taxol-resistant cells through the attenuation of actomyosin-based contractility thereby inhibiting cell migration and metastasis in vivo. Moreover, the destroyed ECM by P18⊂L PDT increased the therapy sensitivity. A clearer understanding of the effect of nanopurpurin-based PDT on mechanical properties and behaviors of intractable tumor cells will provide new and important basis for developing new therapeutic strategies.

Zhang|Di|D| Feng|Feng|F| Li|Qilong|Q| Wang|Xiuyu|X| Yao|Li|L|

Photodynamic therapy
Extracellular matrix
Tumor metastasis
Adhesion
Biomechanical forces


Fibrinogen Interaction with Astrocyte ICAM-1 and PrPC Results in the Generation of ROS and Neuronal Death.

Abstract: Many neuroinflammatory diseases, like traumatic brain injury (TBI), are associated with an elevated level of fibrinogen and short-term memory (STM) impairment. We found that during TBI, extravasated fibrinogen deposited in vasculo-astrocyte interfaces, which was associated with neurodegeneration and STM reduction. The mechanisms of this fibrinogen-astrocyte interaction and its functional role in neurodegeneration are still unclear. Cultured mouse brain astrocytes were treated with fibrinogen in the presence or absence of function-blocking antibody or peptide against its astrocyte receptors intercellular adhesion molecule-1 (ICAM-1) or cellular prion protein (PrPC), respectively. Fibrinogen interactions with astrocytic ICAM-1 and PrPC were characterized. The expression of pro-inflammatory markers, generations of reactive oxygen species (ROS) and nitric oxide (NO) in astrocytes, and neuronal death caused by astrocyte-conditioned medium were assessed. Data showed a strong association between fibrinogen and astrocytic ICAM-1 or PrPC, overexpression of pro-inflammatory cytokines and overproduction of ROS and NO, resulting in neuronal apoptosis and death. These effects were reduced by blocking the function of astrocytic ICAM-1 and PrPC, suggesting that fibrinogen association with its astrocytic receptors induce the release of pro-inflammatory cytokines, resulting in oxidative stress, and ultimately neuronal death. This can be a mechanism of neurodegeneration and the resultant STM reduction seen during TBI.

ROS
neuron
pro-inflammatory markers
NO
apoptosis
proximity ligation


Evaluating and Optimizing Online Advertising: Forget the Click, but There Are Good Proxies.

Abstract: Online systems promise to improve advertisement targeting via the massive and detailed data available. However, there often is too few data on exactly the outcome of interest, such as purchases, for accurate campaign evaluation and optimization (due to low conversion rates, cold start periods, lack of instrumentation of offline purchases, and long purchase cycles). This paper presents a detailed treatment of proxy modeling, which is based on the identification of a suitable alternative (proxy) target variable when data on the true objective is in short supply (or even completely nonexistent). The paper has a two-fold contribution. First, the potential of proxy modeling is demonstrated clearly, based on a massive-scale experiment across 58 real online advertising campaigns. Second, we assess the value of different specific proxies for evaluating and optimizing online display advertising, showing striking results. The results include bad news and good news. The most commonly cited and used proxy is a click on an ad. The bad news is that across a large number of campaigns, clicks are not good proxies for evaluation or for optimization: clickers do not resemble buyers. The good news is that an alternative sort of proxy performs remarkably well: observed visits to the brand's website. Specifically, predictive models built based on brand site visits-which are much more common than purchases-do a remarkably good job of predicting which browsers will make a purchase. The practical bottom line: evaluating and optimizing campaigns using clicks seems wrongheaded; however, there is an easy and attractive alternative-use a well-chosen site-visit proxy instead.

Dalessandro|Brian|B| Hook|Rod|R| Perlich|Claudia|C| Provost|Foster|F|

evaluation
online advertising
proxy modeling
CTR
data science


Current Knowledge and Practice of Pediatric Providers in Umbilical Cord Blood Banking.

Abstract: More than 35 000 umbilical cord blood (UCB) transplants have been performed worldwide, prompting the development of private and public banks to collect and store UCB cells. We hypothesized that pediatricians, who are uniquely poised to discuss UCB banking (UCBB) during prenatal or sibling visits, rarely do so. Through distribution of a 26-question electronic survey to general and subspecialty pediatric providers, we assessed baseline knowledge and conversations about UCBB. A total of 473 providers completed the survey; only 22% of physicians ever discussed UCBB with expectant parents. The majority responded that autologous UCB transplants were indicated in malignant (73%) and nonmalignant (61%) conditions; however, these are rare indications. Providers practicing >10 years were more likely to address UCBB ( P ≤ .001), whereas younger and female general pediatric providers were significantly less likely ( P < .001). Overall, pediatric providers rarely speak to families about UCBB, and we believe that they can be better informed to its current clinical utility.

Armstrong|Amy E|AE|
Fonstad|Rachel|R|
Spellman|Stephen|S|
Tullius|Zoe|Z|
Chaudhury|Sonali|S|

D007722:Health Knowledge, Attitudes, Practice

umbilical cord blood
autologous stem cell transplantation
private umbilical cord blood banking
public umbilical cord blood banking
umbilical cord blood transplantation


Thriving from Work: Conceptualization and Measurement.

Abstract: Work is a major contributor to our health and well-being. Workers' thriving is directly influenced by their job design, work environment and organization. The purpose of this report is to describe the qualitative methods used to develop the candidate items for a novel measure of Thriving from Work through a multi-step iterative process including: a literature review, workshop, interviews with experts, and cognitive testing of the candidate items. Through this process, we defined Thriving from Work as the state of positive mental, physical, and social functioning in which workers' experiences of their work and working conditions enable them to thrive in their overall lives, contributing to their ability to achieve their full potential in their work, home, and community. Thriving from Work was conceptualized into 37 attributes across seven dimensions: psychological, emotional, social, work-life integration, basic needs, experience of work, and health. We ultimately identified, developed and/or modified 87 candidate questionnaire items mapped to these attributes that performed well in cognitive testing in demographically and occupationally diverse workers. The Thriving from Work Questionnaire will be subjected to psychometric testing and item reduction in future studies. Individual items demonstrated face validity and good cognitive response properties and may be used independently from the questionnaire.

Peters|Susan E|SE|0000-0002-2705-643X
Sorensen|Glorian|G|
Katz|Jeffrey N|JN|
Gundersen|Daniel A|DA|
Wagner|Gregory R|GR|0000-0003-4165-7079

thriving
cognitive interviewing
flourishing
healthy work design and well-being
measurement of well-being
questionnaire design
survey design
total worker health
worker thriving
worker well-being


Laparoscopic versus open repair for perforated peptic ulcer: A meta analysis of randomized controlled trials.

Abstract:
INTRODUCTION
The role of laparoscopic surgery in the repair for peptic ulcer disease is unclear. The present study aimed to compare the safety and efficacy of laparoscopic versus open repair for peptic ulcer disease.

METHODS
Randomized controlled trials (RCTs) comparing laparoscopic versus open repair for peptic ulcer disease were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and references of identified articles and relevant reviews. Primary outcomes were postoperative complications, mortality, and reoperation. Secondary outcomes were operative time, postoperative pain, postoperative hospital stay, nasogastric tube duration, and time to resume diet. Statistical analysis was carried out by Review Manage software.

RESULTS
Five RCTs investigating a total of 549 patients, of whom, 279 received laparoscopic repair and 270 received open repair, were included in the final analysis. There were no significant differences between these two procedures in some primary outcomes including overal postoperative complication rate, mortality, and reoperation rate. Subcategory analysis of postoperative complications showed that laparoscopic repair had also similar rates of repair site leakage, intra-abdominal abscess, postoperative ileus, pneumonia, and urinary tract infection as open surgery, except of the lower surgical site infection rate (P < 0.05). In addition, there were also no significant differences between these two procedures in some second outcomes including operative time, postoperative hospital stay, and time to resume diet, but laparoscopic repair had shorter nasogastric tube duration (P < 0.05) and less postoperative pain (P < 0.05) than open surgery.

CONCLUSIONS
Laparoscopic surgery is comparable with open surgery in the setting of repair for perforated peptic ulcer. The obvious advantages of laparoscopic surgery are the lower surgical site infection rate, shorter nasogastric tube duration and less postoperative pain. However, more higher quality studies should be undertaken to further assess the safety and efficacy of laparoscopic repair for peptic ulcer disease.

Tan|Shanjun|S| Wu|Guohao|G| Zhuang|Qiulin|Q| Xi|Qiulei|Q| Meng|Qingyang|Q| Jiang|Yi|Y| Han|Yusong|Y| Yu|Chao|C| Yu|Zhen|Z| Li|Ning|N|

D016032:Randomized Controlled Trials as Topic

Peptic ulcer
Laparoscopic repair
Meta-analysis


Clinical considerations for biosimilar antibodies.

Abstract: Biosimilar agents are approximate copies of branded biologic therapies. Since the first biosimilar was authorized in the European Union in 2006, fifteen additional agents have been approved by the European Medicines Agency, including two biosimilar monoclonal antibodies (mAbs). Biosimilar mAbs represent a distinct class given their large molecular size, complex protein structure, and post-translational modifications. While guidelines have been established for the development, approval, and use of biosimilars, further scrutiny and discussion is necessary to fully understand their potential impact on clinical outcomes. This review takes a critical look at the structural complexity of biosimilar mABs, the feasibility of indication extrapolation, the impact of product variability on immunogenicity, the importance of comprehensive pharmacovigilance, and the potential for ongoing pharmacoeconomic impact.

Biosimilar
Biologic
Monoclonal antibody
Extrapolation
Immunogenicity
Pharmacovigilance
Pharmacoeconomics


The anorexigenic effect of adrenomedullin in Japanese quail (Coturnix japonica) involves increased proopiomelanocortin and cocaine- and amphetamine-regulated transcript mRNAs in the arcuate nucleus of the hypothalamus.

Abstract: Central administration of adrenomedullin (AM), a 52-amino acid peptide, is associated with anorexigenic effects in some species, including rodents and chickens. However, the associated hypothalamic mechanisms remain unclear and it is unknown if this peptide exerts satiety-inducing effects in other avian species. The objective of this study was thus to investigate AM-induced anorexigenic effects in 7-day-old Japanese quail (Coturnix japonica). After intracerebroventricular injection of 0.3, 1.0, or 3.0 nmol of AM, quail injected with 3.0 nmol of AM ate and drank less than vehicle-injected quail at 180 min after injection. Except for the 1.0 nmol dose of AM exerting an anorexigenic effect at 90 min after injection, no other inhibitory effects on food or water intake were observed. At 60 min after injection, the AM-injected quail had more c-Fos immunoreactive cells in the arcuate nucleus (ARC) than vehicle-injected birds. In the ARC, AM injection was associated with increased proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNAs. In conclusion, the results suggest that the anorexigenic effect of AM is possibly influenced by the synergistic effect of POMC and CART in the ARC.

Wang|J|J|
Webster|A|A|
Sims|W|W|
Gilbert|E R|ER|
Cline|M A|MA|

Cocaine- and amphetamine-regulated transcript


Thermal expansion behavior of A- and B-type amylose crystals in the low-temperature region.

Abstract: The thermal expansion behaviors of A-type and B-type amylose crystals, which were prepared by recrystallization of short amylose chains synthesized by phosphorylase, were investigated using synchrotron X-ray powder diffraction between 100 and 300K. For both types of crystals, the room-temperature phase (RT phase), which is the usually observed phase, transitioned to a low-temperature phase (LT phase), on cooling. The phase transitions took place reversibly with rapid changes in the unit-cell parameters around 200-270K. The differences between the RT and LT phase were investigated using solid-state (13)C NMR spectroscopy, which revealed there were changes in molecular chain conformations. These results suggest that the phase transition of water molecules on the crystalline surfaces affects the thermal behavior and structure of polysaccharide crystals.

Kobayashi|Kayoko|K| Kimura|Satoshi|S| Naito|Philip-Kunio|PK| Togawa|Eiji|E| Wada|Masahisa|M|

D066241:Carbon-13 Magnetic Resonance Spectroscopy

Thermal expansion
Amylose
Synchrotron X-ray powder diffraction
Solid-state (13)C NMR


Social distancing in airplane seat assignments.

Abstract: This paper addresses the airplane passengers' seat assignment problem while practicing social distancing among passengers. We proposed a mixed integer programming model to assign passengers to seats on an airplane in a manner that will respect two types of social distancing. One type of social distancing refers to passengers being seated far enough away from each other. The metric for this type of social distancing is how many passengers are seated so close to each other as to increase the risk of infection. The other type of social distancing refers to the distance between seat assignments and the aisle. That distance influences the health risk involved in passengers and crew members walking down the aisle. Corresponding metrics for both health risks are included in the objective function. To conduct simulation experiments, we define different scenarios distinguishing between the relative level of significance of each type of social distancing. The results suggest the seating assignments that best serve the intention of the scenarios. We also reformulate the initial model to determine seat assignments that maximize the number of passengers boarding an airplane while practicing social distancing among passengers. In the last part of this study, we compare the proposed scenarios with the recommended middle-seat blocking policy presently used by some airlines to keep social distancing among passengers. The results show that the proposed scenarios can provide social distancing among seated passengers similar to the middle-seat blocking policy, while reducing the number of passengers seated close to the aisle of an airplane.

Salari|Mostafa|M|
Milne|R John|RJ|
Delcea|Camelia|C|
Kattan|Lina|L|
Cotfas|Liviu-Adrian|LA|

Social distancing
Airplane seat assignment
Mixed integer programming
Airplane boarding
COVID-19
SARS-CoV-2


Carotid artery dissection and stroke complicating treatment of postmandibular distraction ankylosis: a case report.

Abstract: Mandibular distraction osteogenesis is an increasingly accepted treatment option for severe upper airway obstruction in grade 3 Robin sequence. Complications are rarely reported but can include fracture, pin dislodgement, tooth bud damage, and temporomandibular joint ankylosis. Operative correction of these complications can carry inherent risks of their own. We present a patient who incurred carotid artery dissection and stroke after release of postdistraction coronoid-zygomatic ankylosis for the treatment of mandibular micrognathia.

Arnspiger|Sarah A|SA|
Felder|John M|JM|
Wood|Benjamin C|BC|
Rogers|Gary F|GF|
Oh|Albert K|AK|

D020215:Carotid Artery, Internal, Dissection

stroke
mandibular distraction
distraction osteogenesis
Robin sequence
micrognathia
Treacher Collins syndrome
mandibular pseudoankylosis
surgical complications


Managing arrhythmias in the intensive care unit.

Abstract: Patients admitted to the intensive care unit (ICU) are at increased risk for cardiac arrhythmias, the most common of which can be subdivided into tachyarrhythmias and bradyarrhythmias. These arrhythmias may be the primary reason for ICU admission or may occur in the critically ill patient. This article addresses the occurrence of arrhythmias in the critically ill patient, and discusses their pathophysiology, implications, recognition, and management.

Intensive care unit
Cardiac arrhythmia
Tachyarrhythmia
Bradyarrhythmia


Combination of polyethylene glycol impregnation and paraffin heat treatment to protect round bamboo from cracking.

Abstract: Round bamboo has drawn more and more attention in architecture, decoration and recreational products. Splitting brings some safety problems, which shorten the service life of round bamboo. In this paper, three schemes were adopted as follows to solve the problem: round bamboo was impregnated in polyethylene glycol (PEG)-1000 solution alone, heat treatment in paraffin alone or treated with the combination of PEG impregnation and paraffin heat treatment (PEG-PH). The treated bamboo was exposed outdoors for 26 weeks to evaluate the development of cracks. Results showed as follows: the initial split of PEG-PH-treated bamboo appeared after 22 weeks, while that of the controls after 2 weeks, the total length of cracks was 2271.31 and 873.5 mm for the control and PEG-PH-treated bamboo, respectively. To reveal the reasons for reduced cracks, scanning electron micrograph (SEM) was employed to observe the microstructure of bamboo; besides, hydrophobicity of bamboo was characterized by the water contact angle. PEG can swell the cell wall and the better hydrophobicity of round bamboo could be achieved after PEG-PH treatment. Therefore, the combination of PEG immersion and paraffin heating is an effective and practicable method in bamboo treatment, especially for round bamboo with high moisture content.

Rao|Jin|J|0000-0003-0680-9786
Jiang|Jun|J|
Prosper|Nayebare Kakwara|NK|
Yang|Xiushu|X|
Liu|Tingsong|T|
Cai|Wei|W|
Wang|Hui|H|
Sun|Fangli|F|0000-0003-3487-7399

paraffin heat treatment
round bamboo
cracking resistance
outdoor exposure
polyethylene glycol treatment


Equivalence of glatiramer acetate products: challenges in assessing pharmaceutical equivalence and critical clinical performance attributes.

Abstract:
INTRODUCTION
This review discusses the challenges to characterize and evaluate the peptide based drug glatiramer acetate (GA) and its follow-on products used for treatment of multiple sclerosis patients.

AREAS COVERED
GA is a highly complex mixture of peptides consisting of four amino acids. The various (physico)-chemical approaches and bioassays used for characterizing this complex drug product are described. It is not possible to link data from preclinical performance to outcomes observed in clinical trials as no critical attributes suitable for predicting the clinical performance in MS patients have been identified yet. The limited insight into the precise mechanism(s) of action of GA may explain why these critical clinical performance attributes still have not been identified.

EXPERT OPINION
The complexity of GA and lack of understanding of critical clinical performance attributes leads to a number of issues to be resolved as they hamper industry and regulatory bodies in designing and evaluating follow-on/generic applications of GA. The following questions are waiting to be addressed: Preclinical characterization vs clinical outcome: what is the relation? What are possible biomarkers? How to choose the right patient group? What is the experience with existing follow-on versions? Is there a place for GA 'betters'? How to evaluate existing and draft new guidance documents and pharmacopoeial monographs?

D016568:Drugs, Generic
D000068717:Glatiramer Acetate
D006801:Humans
D007166:Immunosuppressive Agents
D009103:Multiple Sclerosis
D013810:Therapeutic Equivalency

glatiramer acetate
multiple sclerosis
Copaxone
European medicines agency (EMA)
Food and Drug Administration (FDA)
Glatiramoids
Glatopa
follow-on versions/generics
genetic profiling
physico-chemical characterization