Pancreatic cancer-associated inflammation drives dynamic regulation of p35 and Ebi3.

Abstract: B cells are important modulators of immune responses both in autoimmunity and cancer. We have previously shown that B regulatory (Breg) cells promote pancreatic cancer via production of IL35, a heterodimeric cytokine comprised of the subunits p35 (Il12a) and Ebi3. However, it is not known how production of IL35 is regulated in vivo in the context of cancer-associated inflammation. To begin addressing this question, we have generated a knock-in mouse model, Il12aGFP, where an IRES-emGFP gene was inserted within the 3' UTR of the Il12a locus. EmGFP signal in B cells from the Il12aGFP mice correlated with expression of p35 mRNA and protein. Using this model, we observed that in addition to Bregs, expression of GFP (p35) is upregulated in several other B cell subtypes in response to cancer. We assessed the expression of the other IL35 subunit, Ebi3, using a published tdTomato reporter model. We determined that Ebi3 expression was more tightly regulated in vivo and in vitro, suggesting that stimuli affecting Ebi3 upregulation are more likely to result in production of full IL35 heterodimer. We were also able to detect GFP and Tomato signal in myeloid & T cell lineages suggesting that these reporter models could also be used for tracking IL12-, IL27- and IL35-producing cells. Furthermore, using primary B cells isolated from reporter mice, we identified BCR, CD40 and TLR pathways as potential drivers of IL35 expression. These findings highlight the importance of pancreatic cancer-associated inflammatory processes as drivers of cytokine expression and provide a tool to dissect both disease-associated regulation of IL12- and IL35-competent lineage cells as well as establish assays for pharmacological targeting of individual subunits of heterodimeric IL12 family cytokines.

Michaud|Daniel|D|
Mirlekar|Bhalchandra|B|
Bischoff|Steven|S|
Cowley|Dale O|DO|
Vignali|Dario A A|DAA|
Pylayeva-Gupta|Yuliya|Y|

D015972:Gene Expression Regulation, Neoplastic

Pancreatic cancer
Reporter model
IL35 cytokine
Regulatory B cell


Experimental design of Al2O3/MWCNT/HDPE hybrid nanocomposites for hip joint replacement.

Abstract: Fracture in the hip joint is a major and quite common health issue, particularly for the elderly. The loads exploited by the lower limbs are very acute and severe; in the femur, they can be several folds higher than the whole weight of the body. Nanotechnology and nanocomposites offer great potential in biomedical applications. The organic materials are more biocompatible. Mechanical properties like strength and hardness are challenging parameters which control the selection of a joint. HDPE in its pure form has been successfully used as a prosthetic foot (external) but failed as an implant material due to limited mechanical properties. High-density polyethylene thermoplastic polymer (HDPE) and multi-walled carbon nanotubes (MWCNT)/Nano-Alumina is selected as a potential material for a biomedical implant and its mechanical properties and biocompatibility have been discussed. HDPE/MWCNT/Alumina (Al2O3) nanocomposites have not been explored yet for prosthetic implants. These nanocomposites were prepared in this investigation in different compositions. Prepared material has been physiochemically characterized to check the morphology and the structure. MWCNTs enhanced hardness and elastic modulus of the HDPE. Optimization of the material composition revealed that hybrid composite with structure (2.4% Al2O3 and 0.6% MWCNT) exhibits better mechanical properties compared to other ratios with 3% MWCNTs and 5% MWCNTs. Thermal gravimetric analysis (TGA) dedicates that the percentage of crystallization has been increased to 6% after adding MWCNT to HDPE. The moisture absorption decreased to 90% with 5% MWCNT. Experimental results of Colorimetric assay (MTT) of a normal human epithelial cell line (1- BJ1) over Al2O3/MWCNT@HDPE showed <20% cytotoxic activity, proving its acceptance for medical use. HDPE/MWCNT/Al2O3 nanocomposites emerged as a candidate material for artificial joints.

Dabees|Sameh|S|
Kamel|Bahaa M|BM|0000-0003-2850-6882
Tirth|Vineet|V|
Elshalakny|Abou Bakr|AB|

Al2o3
MWCNTs
HDPE
nanocomposites
Hip joint replacement
TGA
biomaterials


Network science approach to modelling the topology and robustness of supply chain networks: a review and perspective.

Abstract: Due to the increasingly complex and interconnected nature of global supply chain networks (SCNs), a recent strand of research has applied network science methods to model SCN growth and subsequently analyse various topological features, such as robustness. This paper provides: (1) a comprehensive review of the methodologies adopted in literature for modelling the topology and robustness of SCNs; (2) a summary of topological features of the real world SCNs, as reported in various data driven studies; and (3) a discussion on the limitations of existing network growth models to realistically represent the observed topological characteristics of SCNs. Finally, a novel perspective is proposed to mimic the SCN topologies reported in empirical studies, through fitness based generative network models.

Perera|Supun|S|
Bell|Michael G H|MGH|
Bliemer|Michiel C J|MCJ|

Network science
Fitness based attachment
Supply chain network modelling
Supply network topology and robustness


Disgust proneness and associated neural substrates in obesity.

Abstract: Defects in experiencing disgust may contribute to obesity by allowing for the overconsumption of food. However, the relationship of disgust proneness and its associated neural locus has yet to be explored in the context of obesity. Thirty-three participants (17 obese, 16 lean) completed the Disgust Propensity and Sensitivity Scale-Revised and a functional magnetic resonance imaging paradigm where images from 4 categories (food, contaminates, contaminated food or fixation) were randomly presented. Independent two-sample t-tests revealed significantly lower levels of Disgust Sensitivity for the obese group (mean score = 14.7) compared with the lean group (mean score = 17.6, P = 0.026). The obese group had less activation in the right insula than the lean group when viewing contaminated food images. Multiple regression with interaction analysis revealed one left insula region where the association of Disgust Sensitivity scores with activation differed by group when viewing contaminated food images. These interaction effects were driven by the negative correlation of Disgust Sensitivity scores with beta values extracted from the left insula in the obese group (r = -0.59) compared with a positive correlation in the lean group (r = 0.65). Given these body mass index-dependent differences in Disgust Sensitivity and neural responsiveness to disgusting food images, it is likely that altered Disgust Sensitivity may contribute to obesity.

Watkins|Tristan J|TJ|
Di Iorio|Christina R|CR|
Olatunji|Bunmi O|BO|
Benningfield|Margaret M|MM|
Blackford|Jennifer U|JU|
Dietrich|Mary S|MS|
Bhatia|Monisha|M|
Theiss|Justin D|JD|
Salomon|Ronald M|RM|
Niswender|Kevin|K|
Cowan|Ronald L|RL|


Systematic review and meta-analysis identify significant relationships between clinical anxiety and lower urinary tract symptoms.

Abstract:
BACKGROUND
Lower urinary tract symptoms (LUTS), such as voiding symptoms, overactive bladder, and interstitial cystitis, and anxiety disorders are often comorbid conditions in patients. However, the existing evidence regarding the rates and nature of the co-occurrence of these conditions has not been systematically evaluated. The aim of this study was to examine these relationships.

METHODS
We conducted a systematic review and meta-analysis to examine the relationship between LUTS and anxiety. We searched for articles published from January 1990 to July 2019 in PubMed, CENTRAL, PsycINFO, and Google Scholar. Outcomes were anxiety-related disorders and symptoms (clinically significant anxiety) and LUTS. We performed random-effects meta-analyses, inspected funnel plots, and applied the Egger's test to evaluate publication bias. We followed PRISMA guidelines and recorded our protocol on PROSPERO (ID = CRD42019118607).

RESULTS
We identified 814 articles, of which 94 fulfilled inclusion criteria, and 23 had sufficient data for meta-analysis. The odds ratio (OR) for clinically significant anxiety among individuals with LUTS was 2.87 (95% CI: 2.38,3.46, p < .001). The OR for LUTS among individuals with clinically significant anxiety was 2.87 (95% CI: 1.07,7.74, p < .001), although very few studies examined this relationship. A large value of I2 index suggests high heterogeneity between studies.

CONCLUSION
The results demonstrate a significant association between clinically significant anxiety and LUTS in both females and males. There were limited studies on younger individuals and on individuals ascertained for clinically significant anxiety, which should motivate further study in these areas. Understanding the co-occurrence of these conditions will lead to better prevention and interventions to ameliorate the progression of the symptoms and improve the quality of life. A thorough assessment of anxiety may provide more optimal care for LUTS patients.

Mahjani|Behrang|B|0000-0001-6087-9537
Koskela|Lotta Renström|LR|
Batuure|Anita|A|
Gustavsson Mahjani|Christina|C|
Janecka|Magdalena|M|
Hultman|Christina M|CM|
Reichenberg|Abraham|A|
Buxbaum|Joseph D|JD|
Akre|Olof|O|
Grice|Dorothy E|DE|

lower urinary tract symptoms
overactive bladder
interstitial cystitis
anxiety disorders
obsessive-compulsive disorder


Impact of Arterial Procedures on Coagulation and Fibrinolysis - A Pilot Study.

Abstract:
OBJECTIVE
The main goal of our study was to assess the impact of vascular procedures on the activity of hemostatic and fibrinolytic pathways.

METHODS
We enrolled 38 patients with ≥ 45 years old undergoing surgery for abdominal aortic aneurysm or peripheral artery disease under general or regional anesthesia and who were hospitalized at least one night after the procedure. Patients undergoing carotid artery surgery and those who had acute bypass graft thrombosis, cancer, renal failure defined as estimated glomerular filtration rate < 30 ml/min/1.73m2, venous thromboembolism three months prior to surgery, or acute infection were excluded from the study. We measured levels of markers of hemostasis (factor VIII, von Willebrand factor:ristocetin cofactor [vWF:CoR], antithrombin), fibrinolysis (D-dimer, tissue plasminogen activator [tPA], plasmin-antiplasmin complexes), and soluble cluster of differentiation 40 ligand (sCD40L) before and 6-12h after vascular procedure.

RESULTS
Significant differences between preoperative and postoperative levels of factor VIII (158.0 vs. 103.3, P<0.001), antithrombin (92.1 vs. 74.8, P<0.001), D-dimer (938.0 vs. 2406.0, P=0.005), tPA (10.1 vs. 12.8, P=0.002), and sCD40L (9092.9 vs. 1249.6, P<0.001) were observed. There were no significant differences between pre- and postoperative levels of vWF:CoR (140.6 vs. 162.8, P=0.17) and plasmin-antiplasmin complexes (749.6 vs. 863.7, P=0.21).

CONCLUSION
Vascular surgery leads to significant alterations in hemostatic and fibrinolytic systems. However, the direction of these changes in both pathways remains unclear and seems to be different depending on the type of surgery. A study utilizing dynamic methods of coagulation and fibrinolysis assessment performed on a larger population is warranted.

Polok|Kamil Jurand|KJ|
Górka|Jacek|J|
Fronczek|Jakub|J|
Górka|Karolina|K|
Kaczmarek|Bogusz|B|
Iwaniec|Teresa|T|
Iwaszczuk|Paweł|P|
Musiał|Jacek|J|
Szczeklik|Wojciech|W|

Blood
Coagulation/Anticoagulation
Fibrin/Fibrosis/Fibrinolysis
Vascular Surgical Procedures


The Epigenetic Consequences of Paternal Exposure to Environmental Contaminants and Reproductive Toxicants.

Abstract: Human populations are exposed to a wide spectrum of environmental contaminants, some of which are considered reproductive toxins. The influence of such toxins on the male reproductive system has been investigated extensively in animal models, while epidemiological studies seek to understand the effect of human exposures. The basic tenant of epidemiological studies in male human reproduction is to infer how one or more substances alter the hormonal profile, seminal characteristics, or both. Determining if a substance alters semen quality may not always provide the underlying mechanism. The mechanisms by which toxins may alter human sperm and semen quality are typically examined as a function of hormonal changes and cellular damage. The possibility that more subtle epigenetic alterations underlie some of the reproductive changes has, until recently, received little attention. In this review, we discuss the roles of epigenetics in human spermatogenesis, while considering the impact of reproductive toxicants on the epigenome.

Estill|Molly S|MS|
Krawetz|Stephen A|SA|

Epigenetics
Sperm
Spermatogenesis
In utero
RNA
Testis


Methods and Measures Used to Evaluate Patient-Operated Mobile Health Interventions: Scoping Literature Review.

Abstract:
BACKGROUND
Despite the prevalence of mobile health (mHealth) technologies and observations of their impacts on patients' health, there is still no consensus on how best to evaluate these tools for patient self-management of chronic conditions. Researchers currently do not have guidelines on which qualitative or quantitative factors to measure or how to gather these reliable data.

OBJECTIVE
This study aimed to document the methods and both qualitative and quantitative measures used to assess mHealth apps and systems intended for use by patients for the self-management of chronic noncommunicable diseases.

METHODS
A scoping review was performed, and PubMed, MEDLINE, Google Scholar, and ProQuest Research Library were searched for literature published in English between January 1, 2015, and January 18, 2019. Search terms included combinations of the description of the intention of the intervention (eg, self-efficacy and self-management) and description of the intervention platform (eg, mobile app and sensor). Article selection was based on whether the intervention described a patient with a chronic noncommunicable disease as the primary user of a tool or system that would always be available for self-management. The extracted data included study design, health conditions, participants, intervention type (app or system), methods used, and measured qualitative and quantitative data.

RESULTS
A total of 31 studies met the eligibility criteria. Studies were classified as either those that evaluated mHealth apps (ie, single devices; n=15) or mHealth systems (ie, more than one tool; n=17), and one study evaluated both apps and systems. App interventions mainly targeted mental health conditions (including Post-Traumatic Stress Disorder), followed by diabetes and cardiovascular and heart diseases; among the 17 studies that described mHealth systems, most involved patients diagnosed with cardiovascular and heart disease, followed by diabetes, respiratory disease, mental health conditions, cancer, and multiple illnesses. The most common evaluation method was collection of usage logs (n=21), followed by standardized questionnaires (n=18) and ad-hoc questionnaires (n=13). The most common measure was app interaction (n=19), followed by usability/feasibility (n=17) and patient-reported health data via the app (n=15).

CONCLUSIONS
This review demonstrates that health intervention studies are taking advantage of the additional resources that mHealth technologies provide. As mHealth technologies become more prevalent, the call for evidence includes the impacts on patients' self-efficacy and engagement, in addition to traditional measures. However, considering the unstructured data forms, diverse use, and various platforms of mHealth, it can be challenging to select the right methods and measures to evaluate mHealth technologies. The inclusion of app usage logs, patient-involved methods, and other approaches to determine the impact of mHealth is an important step forward in health intervention research. We hope that this overview will become a catalogue of the possible ways in which mHealth has been and can be integrated into research practice.

D020811:Biomedical Technology
D002908:Chronic Disease
D003920:Diabetes Mellitus
D006801:Humans
D063731:Mobile Applications
D017216:Telemedicine

mobile health
interventions
self-management
apps
noncommunicable diseases
chronic disease
patient-centered approach
patient-operated intervention


Linkage analysis in a Dutch population isolate shows no major gene for left-handedness or atypical language lateralization.

Abstract: Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits.

linkage analysis
left-handedness
language lateralization
genetics
asymmetry
hand-preference


Attentional and executive functions are differentially affected by post-traumatic stress disorder and trauma.

Abstract:
BACKGROUND
Among the neurocognitive impairments observed in patients with Post-traumatic Stress Disorder (PTSD), attentional and executive dysfunctions appear to correlate with negative effects on education, work, daily life activities, and social relations, as well as the re-experiencing, avoidance, and hyperarousal symptoms of PTSD. However, there is no consensus regarding which aspects of attentional and executive functions are impaired in PTSD patients.

METHODS
Attentional and executive functions were assessed using the digit span (WAIS-III) and spatial span (WMS-III) tests under forward and backward recall conditions, the Stroop Test, and the Wisconsin Card Sorting Test (WCST). Our sample was composed of victims of urban violence who developed PTSD (PTSD+) (n = 81), victims of urban violence who did not develop PTSD (PTSD-) (n = 70), and healthy controls not exposed to trauma (HC) (n = 50).

RESULTS
The PTSD+ group had poorer performance on the spatial span forward subtest (p = 0.023; eta(2) = 0.038) and poorer execution time (p = 0.023; eta(2) = 0.042) and accuracy (p = 0.019; eta(2) = 0.044) on the Stroop Test compared to HC.

CONCLUSIONS
These data suggest that there are few differences between the PTSD+ and HC groups, which are restricted to less complex measures of attentional and executive functional processes (short term capacity, selective attention, processing speed, and inhibitory control) and are related to visual stimuli. Therefore, cognitive impairments directly correlated with the manifestation of PTSD.

Flaks|Mariana K|MK|
Malta|Stella M|SM|
Almeida|Priscila P|PP|
Bueno|Orlando F A|OF|
Pupo|Mariana C|MC|
Andreoli|Sérgio B|SB|
Mello|Marcelo F|MF|
Lacerda|Acioly L T|AL|
Mari|Jair J|JJ|
Bressan|Rodrigo A|RA|

D001289:Attention Deficit Disorder with Hyperactivity

D011569:Psychiatric Status Rating Scales

Executive functions
Post-traumatic stress disorder
Trauma
Cognition
Neuropsychology


Supramolecular gels of cholesterol-modified gellan gum with disc-like and worm-like micelles.

Abstract: The association between a hydrophobically modified polysaccharide, gellan gum, with micelles based on a surfactant bearing the same hydrophobic tail as pendant groups was investigated by rheology and small-angle neutron scattering (SANS). Gellan gum grafted with cholesterol groups (20% mol/mol tetrasaccharide unit), GeCh, was mixed with polyoxyethylene cholesteryl ether (ChEO10), which comprises a cholesterol group as the tail linked to a small polyoxyethylene headgroup, and self-assembles into micelles with an unusual disc-like morphology. The addition of 0.5% polymer to solutions of ChEO10 induced a remarkable transition from a Newtonian fluid to a predominantly solid-like viscoelastic behaviour, leading to a ×105 increase in zero-shear viscosity (with 5% ChEO10). Increasing surfactant concentration led to an enhancement of the viscoelasticity, but the elastic modulus G' reached a plateau around 15% surfactant, attributed to a saturation of the sticker groups. The effect of micellar morphology on the network was studied by adding a small headgroup co-surfactant, triethylene glycol monododecyl ether, to ChEO10 micelles, which drives their elongation into wormlike micelles. Networks obtained with the long, flexible micelles displayed enhanced solid-like behaviour, with no cross-over between G' and G″ over the measured range of frequencies, reflecting relaxation times of the order of minutes or hours. The morphology of the gels studied by SANS revealed a scattering dominated by strongly interacting micelles (described by discs of 140 Å diameter and a hydrated ∼38 Å PEO corona) and the presence of micellar clusters induced by the presence of the polymer. The scattering data therefore confirm that the onset of gelation is due to surfactant micelles acting as junction points for the network.

Zoratto|Nicole|N|
Grillo|Isabelle|I|
Matricardi|Pietro|P|
Dreiss|Cécile A|CA|

Supramolecular gels
Small-angle neutron scattering
Polyoxyethylene cholesteryl ether
Wormlike micelles
Associative networks
Hydrophobically modified polymers
Oscillatory rheology


Long-term outcomes of ocular adnexal lesions in IgG4-related ophthalmic disease.

Abstract:
AIMS
To determine the long-term outcomes of ocular adnexal lesions in immunoglobulin G4-related ophthalmic disease (IgG4-ROD).

METHODS
This retrospective, non-randomised exploratory study included 82 patients with ocular adnexal lesions. We evaluated the long-term outcomes in 71 patients during the median follow-up period of 30 months, who underwent either watchful waiting (n=20; range 12-90 months) or systemic corticosteroid treatment, delivered according to consensus guidelines (n=51; range 9- 115 months). We also analysed factors that might contribute to recalcitrance to treatment.

RESULTS
Of 82 patients, 40 (49%) were male, and the median patient age was 60 years old. Twenty-one (26%) patients with extraocular muscle (EOM) and/or trigeminal nerve branch (CN V) enlargements had a significantly high frequency of multiple ocular adnexal lesions (p<0.0001, Fisher's exact test). In addition, two patients developed EOM and/or CN V enlargements de novo over time. Twenty patients with solitary lacrimal gland enlargements preferred watchful waiting, due to mild symptoms. Of these, 18 (90%) lesions remained dormant throughout a median follow-up of 27 months. Among 51 patients treated with corticosteroids, 31 (61%) experienced relapses after treatment and required systemic low-dose maintenance treatment. A multivariate analysis indicated that EOM and/or CN V enlargements comprised a risk factor for relapse (HR 2.7; 95% CI 1.1 to 6.7).

CONCLUSIONS
This exploratory study showed that different types of ocular adnexal lesions in IgG4-ROD displayed distinct proliferative activities. Our results suggested that EOM and/or CN V enlargements might be secondary lesions that confer refractoriness to systemic corticosteroid treatment recommended by consensus guidelines.

Kubota|Toshinobu|T|0000-0003-0653-0267 Katayama|Masao|M| Nishimura|Reiko|R| Moritani|Suzuko|S|


Ammonium application mitigates the effects of elevated carbon dioxide on the carbon/nitrogen balance of Phoebe bournei seedlings.

Abstract: The study of plant responses to increases in atmospheric carbon dioxide (CO2) concentration is crucial to understand and to predict the effect of future global climate change on plant adaptation and evolution. Increasing amount of nitrogen (N) can promote the positive effect of CO2, while how N forms would modify the degree of CO2 effect is rarely studied. The aim of this study was to determine whether the amount and form of nitrogen (N) could mitigate the effects of elevated CO2 (eCO2) on enzyme activities related to carbon (C) and N metabolism, the C/N ratio, and growth of Phoebe bournei (Hemsl.) Y.C. Yang. One-year-old P. bournei seedlings were grown in an open-top air chamber under either an ambient CO2 (aCO2) (350 ± 70 μmol•mol-1) or an eCO2 (700 ± 10 μmol•mol-1) concentration and cultivated in soil treated with either moderate (0.8 g per seedling) or high applications (1.2 g per seedling) of nitrate or ammonium. In seedlings treated with a moderate level of nitrate, the activities of key enzymes involved in C and N metabolism (i.e., Rubisco, Rubisco activase and glutamine synthetase) were lower under eCO2 than under aCO2. By contrast, key enzyme activities (except GS) in seedlings treated with high nitrate or ammonium were not significantly different between aCO2 and eCO2 or higher under eCO2 than under aCO2. The C/N ratio of seedlings treated with moderate or high nitrate under eCO2was significantly changed compared with the seedlings grown under aCO2, whereas the C/N ratio of seedlings treated with ammonium was not significantly different between aCO2 and eCO2. Therefore, under eCO2, application of ammonium can be beneficial C and N metabolism and mitigate effects on the C/N ratio.

Wang|Xiao|X|0000-0002-5127-0794 Wei|Xiaoli|X| Wu|Gaoyin|G| Chen|Shengqun|S|

nitrogen
Phoebe bournei
elevated CO2
enzyme activity
carbon and metabolism


An interaction between NDE1 and high birth weight increases schizophrenia susceptibility.

Abstract: Pre- and perinatal environmental factors have been shown to increase schizophrenia risk particularly when combined with genetic liability. The investigation of specific gene environment interactions in the etiology of psychiatric disorders has gained momentum. We used multivariate GEE regression modeling to investigate the interaction between genes of the DISC1 pathway and birth weight, in relation to schizophrenia susceptibility in a Finnish schizophrenia family cohort. The study sample consisted of 457 subjects with both genotype and birth weight information. Gender and place of birth were adjusted for in the models. We found a significant interaction between birth weight and two NDE1 markers in relation to increased schizophrenia risk: a four SNP haplotype spanning NDE1 (b=1.26, SE=0.5, p=0.012) and one of its constituent SNPs rs4781678 (b=1.33, SE=0.51, p=0.010). Specifically, high birth weight (>4000g) was associated with increased schizophrenia risk among subjects homozygous for the previously identified risk alleles. The study was based on a family study sample with high genetic loading for schizophrenia and thus our findings cannot directly be generalized as representing the general population. Our results suggest that the functions mediated by NDE1 during the early stages of neurodevelopment are susceptible to the additional disruptive effects of pre- and perinatal environmental factors associated with high birth weight, augmenting schizophrenia susceptibility.

Wegelius|Asko|A| Pankakoski|Maiju|M| Tomppo|Liisa|L| Lehto|Ulriika|U| Lönnqvist|Jouko|J| Suvisaari|Jaana|J| Paunio|Tiina|T| Hennah|William|W|

NDE1
Birth weight
Schizophrenia
Gene
Environment
DISC1
Neurodevelopment


LPS-stimulated inflammation inhibits BMP-9-induced osteoblastic differentiation through crosstalk between BMP/MAPK and Smad signaling.

Abstract: Inflammation is a common situation during bone healing and is recognized to inhibit osteogenic differentiation and bone formation. However, the effect of inflammation on BMP-9-induced osteoblastic differentiation remains unclear. In the present study, we found that an inflammatory environment triggered by lipopolysaccharide (LPS) in vitro suppressed BMP-9-induced osteogenic differentiation. In addition, LPS decreased BMP-9-induced phosphorylation of Smad1/5/8 and showed obvious inhibitory effects on BMP-9-induced Smad signaling. We then confirmed that LPS and BMP-9 can activate p38MAPK and ERK1/2 signaling, and that LPS stimulation reduces BMP-9-induced Runx2 expression through the activation of p38MAPK and ERK1/2 signaling. Finally, we determined that blockade of MAPK signaling by specific inhibitors reverses the inhibitory effect of LPS on BMP-9-induced osteogenic differentiation, and that MAPK acts as a mediator of the negative regulatory role of LPS in BMP-9-induced activation of Smad signaling. Based on these results, we conclude that the LPS-mediated inflammatory environment inhibits BMP-9-induced osteogenic differentiation, via crosstalk between BMP/MAPK and Smad signaling. The elucidation of these mechanisms may hasten the development of new strategies and improve the osteoinductive efficacy of BMP-9 in the clinic, resulting in enhanced osteoblastic differentiation and bone formation.

Daigang|Lu|L| Jining|Qu|Q| Jinlai|Lei|L| Pengfei|Wang|W| Chuan|Sun|S| Liangku|Huang|H| Ding|Tian|T| Zhe|Song|S| Wei|Wei|W| Zhong|Li|L| Kun|Zhang|Z|

D048051:p38 Mitogen-Activated Protein Kinases


Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model--a functional multineuron calcium imaging study.

Abstract: Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure-like events (SLEs) at single-cell resolution. Using functional multineuron Ca(2+) imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg(2+) -free conditions. Bicuculline induced recurrent synchronous Ca(2+) influx, and the events were correlated with SLEs. Other proconvulsants, such as 4-aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca(2+) influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline-induced synchronous Ca(2+) influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca(2+) influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca(2+) influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca(2+) influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs.

Hongo|Yoshie|Y| Takasu|Keiko|K| Ikegaya|Yuji|Y| Hasegawa|Minoru|M| Sakaguchi|Gaku|G| Ogawa|Koichi|K|

antiepileptic drugs
seizure-like events
hippocampus
synchronous Ca2+ influx


Pressure-Sensitive Tissue Adhesion and Biodegradation of Viscoelastic Polymer Blends.

Abstract: Viscoelastic blends of biodegradable polyesters with low and high molecular weight distributions have remarkably strong adhesion (significantly greater than 1 N/cm2) to soft, wet tissue. Those that transition from viscous flow to elastic, solidlike behavior at approximately 1 Hz demonstrate pressure-sensitivity yet also have sufficient elasticity for durable bonding to soft, wet tissue. The pressure-sensitive tissue adhesive (PSTA) blends produce increasingly stronger pull-apart adhesion in response to compressive pressure application, from 10 to 300 s. By incorporating a stiffer high molecular weight component, the PSTA exhibits dramatically improved burst pressure (greater than 100 kPa) when used as a tissue sealant. The PSTA's biodegradation mechanism can be switched from erosion (occurring primarily over the first 10 days) to bulk chemical degradation (and minimal erosion) depending on the chemistry of the high molecular weight component. Interestingly, fibrosis toward the PSTA is reduced when fast-occurring erosion is the dominant biodegradation mechanism.

tissue adhesion
viscoelasticity
biodegradable polymer
rheology
wound dressing


Where's the Advantage? Mutual Exclusivity Promotes Children's Initial Mapping, but Not Long-Term Memory, for Words Compared to Other Strategies.

Abstract: Children frequently apply a novel label to a novel object, a behavior known as the mutual exclusivity bias (MEB). This study examined how MEB affects children's retention for word mappings. In Experiment 1, preschoolers (N = 39; M  = 46.62 months) and adults (N = 24; M  = 21.63 years) completed an immediate word mapping task and a delayed retention test. Both samples used MEB during referent selection, but neither group displayed higher retention for words mapped via MEB than words mapped via other referent selection strategies at test. Experiment 2 replicated Experiment 1 with preschoolers (N = 85; M  = 47.78 months) and provided evidence against the possibility that interference from multiple words contributed to children's faster forgetting of word mappings when using MEB. Experiment 3 presented children (N = 30; M  = 51.13 months) with an abbreviated version of the task, providing evidence against the alternative hypothesis that cognitive load during learning caused the forgetting observed in Experiments 1 and 2. Taken together, these experiments suggest that MEB supports initial word mapping but may not provide an advantage for long-term retention.

Bredemann|Catherine A|CA|
Vlach|Haley A|HA|

mutual exclusivity
long-term memory
cognitive development
language acquisition
word learning


The Influence of Skill Development Training Program for Spiritual Care of Elderly Individual on Elderly Care Technician Students' Perception of Spiritual Support.

Abstract: Spiritual care means helping an individual protect, maintain and gain all the dimensions of his/her existence. Elderly care technicians face numerous cases or crisis situations in which elderly individuals from different backgrounds question the meaning and value of life. Elderly care technicians must acknowledge that the spirituality is an important element in the way an elderly individual receives healthcare and they must be equipped for this matter. This study was conducted in order to examine the influence of "Skill Development Training Program for Spiritual Care of Elderly Individual," which was carried out with students from elderly care program, on the perception of spirituality support in a pretest-posttest quasi-experimental study design with control group. As the data collection form, "Spiritual Support Perception" (SSP) scale was used. The mean scores of the intervention group after the training and after one month are 50.39 ± 5.34 and 51.13 ± 4.98, respectively, and those of the control group are 43.16 ± 4.83 and 42.72 ± 4.48. A statistically significant difference was found between the mean scores of the intervention group from the pretest and the posttests immediately after the training and one month after the training (f = 94.247, p = 0.001). In the control group, however, there was no significant change in the SSP mean scores (f = 0.269, p = 0.77). As a result, this study pointed out the necessity of such training programs for healthcare professionals to make a distinction between their professional duties and their own personalities in order to offer spiritual care to the elderly individual.

Spiritual care
Elderly care technicians
Spiritual care support perception


Comparative effect of Citrus sinensis and carbimazole on serum T4, T3 and TSH levels.

Abstract:
BACKGROUND
There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T4, T3 and thyroid stimulating hormone (TSH) levels.

OBJECTIVE
To compare the effect of Citrus sinensis and carbimazole (CARB) on blood levels of thyroid hormones (T4 and T3) and TSH.

MATERIALS AND METHODS
Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ), 0.1 μg/g of levothyroxine (LVT) and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T4 and T3 were assayed with the serum using ARIA II automated radioimmunoassay instrument.

RESULTS
The results showed that TSH level was significantly (P < 0.05) decreased in LVT treated group compared with the FOJ group. T4 was significantly (P < 0.05) decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T4 when compared with FOJ group. T3 was significantly (P < 0.05) decreased in the CARB group compared with the control.

CONCLUSION
These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB.

Uduak|Okon Akpan|OA|
Ani|Elemi John|EJ|
Etoh|Emmauel Columba Inyang|EC|
Macstephen|Adienbo Ologbagno|AO|

Citrus sinensis
carbimazole
thyroid stimulating hormone
thyroid hormones


Cortico-Cerebellar Structural Connectivity Is Related to Residual Motor Output in Chronic Stroke.

Abstract: Functional imaging studies have argued that interactions between cortical motor areas and the cerebellum are relevant for motor output and recovery processes after stroke. However, the impact of the underlying structural connections is poorly understood. To investigate this, diffusion-weighted brain imaging was conducted in 26 well-characterized chronic stroke patients (aged 63 ± 1.9 years, 18 males) with supratentorial ischemic lesions and 26 healthy participants. Probabilistic tractography was used to reconstruct reciprocal cortico-cerebellar tracts and to relate their microstructural integrity to residual motor functioning applying linear regression modeling. The main finding was a significant association between cortico-cerebellar structural connectivity and residual motor function, independent from the level of damage to the cortico-spinal tract. Specifically, white matter integrity of the cerebellar outflow tract, the dentato-thalamo-cortical tract, was positively related to both general motor output and fine motor skills. Additionally, the integrity of the descending cortico-ponto-cerebellar tract contributed to rather fine motor skills. A comparable structure-function relationship was not evident in the controls. The present study provides first tract-related structural data demonstrating a critical importance of distinct cortico-cerebellar connections for motor output after stroke.

Schulz|Robert|R|
Frey|Benedikt M|BM|
Koch|Philipp|P|
Zimerman|Maximo|M|
Bönstrup|Marlene|M|
Feldheim|Jan|J|
Timmermann|Jan E|JE|
Schön|Gerhard|G|
Cheng|Bastian|B|
Thomalla|Götz|G|
Gerloff|Christian|C|
Hummel|Friedhelm C|FC|

D038524:Diffusion Magnetic Resonance Imaging

cerebellum
recovery
dentato-thalamo-cortical
cortico-ponto-cerebellar
motor cortex


Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction.

Abstract: The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment.

Kong|Qingxia|Q| Min|Xia|X| Sun|Ran|R| Gao|Jianying|J| Liang|Ruqing|R| Li|Lei|L| Chu|Xu|X|


Detection and characterization of polioviruses originating from urban sewage in Yaounde and Douala, Cameroon 2016-2017.

Abstract:
OBJECTIVE
Transmission of wild polioviruses (WPVs) and vaccine-derived polioviruses (VDPVs) have been interrupted in Cameroon since July 2014. Subsequently, Cameroon withdrew Sabin type 2 from routine immunization in April 2016. This study aimed to investigate the detection rates and overtime distribution of the types of PVs recovered from urban sewage in Cameroon.

RESULTS
From January 2016 to December 2017, 517 sewage specimens originating from Yaounde (325 specimens) and Douala (192 specimens) were analyzed. No WPVs and VDPVs were isolated in this study. In contrast, vaccine strains of poliovirus were detected throughout the study period. Isolates Sabin types 1 and 3 were sporadically detected whereas Sabin 2 was found only from January to May 2016 both in Yaounde and Douala. The absence of Sabin 2 in sewage specimens since June 2016 indicates its rapid disappearance after withdrawal from routine immunization in April 2016. This study provides substantial support to the observation that WPV and VDPVs have been successfully eliminated in Cameroon. However, it remains essential to maintain and extend high quality environmental surveillance as long as WPV reservoirs and VDPV outbreaks are detected in Africa.

Sewage Cameroon Vaccine Poliovirus Surveillance Eradication


Hyperandrogenism and phenotypes of polycystic ovary syndrome are not associated with differences in obstetric outcomes.

Abstract:
OBJECTIVES
To investigate obstetric outcomes in Danish women with different phenotypes of polycystic ovary syndrome (PCOS) and isolated hyperandrogenism (HA) and describe the risk of adverse obstetric outcomes in women with PCOS and HA compared to controls.

DESIGN
Cohort study.

SETTING
Odense University Hospital, Denmark.

POPULATION
Women with PCOS were identified prospectively starting in 1997. Singleton pregnancies in women with PCOS and HA during 2003-2011 were included (n = 199). A control group was matched to the patient cohort according to date of childbirth (n = 995).

METHODS
Data on clinical characteristics and obstetric outcomes were collected in patients with PCOS and HA and controls. In PCOS and HA, total and free testosterone, sex hormone binding globulin, and hemoglobin A1c were measured outside pregnancy. During pregnancy, oral glucose tolerance tests were performed in 39 patients and 123 controls according to Danish national guidelines. PCOS phenotypes were based on the Rotterdam criteria.

MAIN OUTCOME MEASURES
Gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, delivery by emergency cesarean section, preterm delivery and anthropometric measures in the newborn.

RESULTS
The incidence of adverse obstetric outcomes and anthropometric measures among the newborns were comparable between different phenotypes of PCOS and patients with HA. In the oral glucose tolerance test, patients had a higher risk of gestational diabetes mellitus compared with controls; the odds ratio (95% confidence interval) was 3.3 (1.5-6.9) after adjustment for age, parity, and body mass index (p = 0.002). The incidence of other adverse obstetric outcomes was similar in patients and controls.

CONCLUSIONS
Obstetric outcomes were comparable in women with different PCOS phenotypes.

Mumm|Hanne|H|
Jensen|Dorte Møller|DM|
Sørensen|Jens Aage|JA|
Andersen|Lise Lotte Torvin|LL|
Ravn|Pernille|P|
Andersen|Marianne|M|
Glintborg|Dorte|D|

hyperandrogenism
Polycystic ovary syndrome
obstetric outcomes
testosterone
hemoglobin A1c
gestational diabetes mellitus
polycystic ovary syndrome phenotypes


Hepatitis E Virus Infection: Circulation, Molecular Epidemiology, and Impact on Global Health.

Abstract: Infection with hepatitis E virus (HEV) represents the most common source of viral hepatitis globally. Although infecting over 20 million people annually in endemic regions, with major outbreaks described since the 1950s, hepatitis E remains an underestimated disease. This review gives a current view of the global circulation and epidemiology of this emerging virus. The history of HEV, from the first reported enteric non-A non-B hepatitis outbreaks, to the discovery of the viral agent and the molecular characterization of the different human pathogenic genotypes, is discussed. Furthermore, the current state of research regarding the virology of HEV is critically assessed, and the challenges towards prevention and diagnosis, as well as clinical risks of the disease described. Together, these points aim to underline the significant impact of hepatitis E on global health and the need for further in-depth research to better understand the pathophysiology and its role in the complex disease manifestations of HEV infection.

hepatitis E
infection
epidemiology
global health
outbreak


Observing prioritization effects on cognition and gait: The effect of increased cognitive load on cognitively healthy older adults' dual-task performance.

Abstract: Previous studies exploring the effects of attention-prioritization on cognitively healthy older adults' gait and cognitive dual task (DT) performance have shown DT cost in gait outcomes but inconsistent effects on cognitive performance, which may reflect task difficulty (the cognitive load). This study aimed to identify whether changing the cognitive load during a walking and counting DT improved the challenge/sensitivity of the cognitive task to observe prioritization effects on concurrent gait and cognitive performance outcomes. Seventy-two cognitively healthy older adults (Mean=73years) walked 15m, counted backwards in 3s and 7s as single tasks (ST), and concurrently walked and counted backwards as DTs. Attention-prioritization was examined in Prioritizing Walking (PW) and Prioritizing Counting (PC) DT conditions. Dual-task performance costs (DTC) were calculated for number of correct cognitive responses (CCR) in the counting tasks, and step-time variability and velocity in the gait task. All DT conditions showed a benefit (DTB) for cognitive outcomes with trade-off cost to gait. In the Serial 3s task, the cognitive DTBs increased in PC over the PW condition (p<0.05), with a greater cost to walking velocity (p<0.05). DT effects were more pronounced in the Serial 7s with a lower cognitive DTB when PC than when PW, (p<0.05) with no trade-off increase in cost to gait outcomes (p<0.05). The findings suggest that increased cognitive load during a gait and cognitive DT produces more pronounced gait measures of attention-prioritization in cognitively healthy older adults. A cognitive load effect was also observed in the cognitive outcomes, with unexpected results.

Maclean|Linda M|LM|
Brown|Laura J E|LJE|
Khadra|H|H|
Astell|Arlene J|AJ|

Cognitive load
Older adults
Dual-task
Attention-prioritization


A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties.

Abstract:
Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications.

STATEMENT OF SIGNIFICANCE
In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials.

Mastrogiacomo|S|S|
Güvener|N|N|
Dou|W|W|
Alghamdi|H S|HS|
Camargo|W A|WA|
Cremers|J G O|JGO|
Borm|P J A|PJA|
Heerschap|A|A|
Oosterwijk|E|E|
Jansen|J A|JA|
Walboomers|X F|XF|

D057872:Pulp Capping and Pulpectomy Agents

Direct pulp capping
BMP-2 (bone morphogenetic protein-2)
CPC (calcium phosphate cement)
DCA (dual contrast agent)
MRI (magnetic resonance imaging)


A prospective, longitudinal study to evaluate the clinical utility of a predictive algorithm that detects risk of opioid use disorder.

Abstract:
Purpose
The purpose of this study was to determine the clinical utility of an algorithm-based decision tool designed to assess risk associated with opioid use. Specifically, we sought to assess how physicians were using the profile in patient care and how its use affected patient outcomes.

Patients and methods
A prospective, longitudinal study was conducted to assess the utility of precision medicine testing in 5,397 patients across 100 clinics in the USA. Using a patent-protected, validated algorithm combining specific genetic risk factors with phenotypic traits, patients were categorized into low-, moderate-, and high-risk patients for opioid abuse. Physicians who ordered precision medicine testing were asked to complete patient evaluations and document their actions, decisions, and perceptions regarding the utility of the precision medicine tests. The patient outcomes associated with each treatment action were carefully documented.

Results
Physicians used the profile to guide treatment decisions for over half of the patients. Of those, guided treatment decisions for 24.5% of the patients were opioid related, including changing the opioid prescribed, starting an opioid, or titrating a patient off the opioid. Treatment guidance was strongly influenced by profile-predicted opioid use disorder (OUD) risk. Most importantly, patients whose physicians used the profile to guide opioid-related treatment decisions had improved clinical outcomes, including better pain management by medication adjustments, with an average pain decrease of 3.4 points on a scale of 1-10.

Conclusion
Patients whose physicians used the profile to guide opioid-related treatment decisions had improved clinical outcomes, as measured by decreased pain levels resulting from better pain management with prescribed medications. The clinical utility of the profile is twofold. It provides clinically actionable recommendations that can be used to 1) prevent OUD through limiting initial opioid prescriptions and 2) reduce pain in patients at low risk of developing OUD.

Brenton|Ashley|A|
Lee|Chee|C|
Lewis|Katrina|K|
Sharma|Maneesh|M|
Kantorovich|Svetlana|S|
Smith|Gregory A|GA|
Meshkin|Brian|B|

clinical utility
opioid
opioid use disorder
patient outcomes
precision medicine
pain management
personalized medicine


Extraction and preconcentration of trace Al and Cr from vegetable samples by vortex-assisted ionic liquid-based dispersive liquid-liquid microextraction prior to atomic absorption spectrometric determination.

Abstract: In the study, a simple, and efficient microextraction approach, which is termed as vortex-assisted ionic liquid-based dispersive liquid-liquid microextraction (VA-IL-DLLME), was developed for flame atomic absorption spectrometric analysis of aluminum (Al) and chromium (Cr) in vegetables. The method is based on the formation of anionic chelate complexes of Al(III) and Cr(VI) with o-hydroxy azo dye, at pH 6.5, and then extraction of the hydrophobic ternary complexes formed in presence of cetyltrimethylammonium bromide (CTAB) into a 125 μL volume of 1-butyl-3-methylimidazolium bis(trifluorosulfonyl)imide [C4mim][Tf2N]) as extraction solvent. Under optimum conditions, the detection limits were 0.02 µg L-1 in linear working range of 0.07-100 µg L-1 for Al(III), and 0.05 µg L-1 in linear working range of 0.2-80 µg L-1 for Cr(VI). After the validation by analysis of a certified reference material (CRM), the method was successfully applied to the determination of Al and Cr in vegetables using standard addition method.

Vegetables
Microextraction
Aluminum
Chromium
Flame atomic absorption spectrometry
Ionic liquid


Perspectives of Primary Care Providers Toward Palliative Care for Their Patients.

Abstract:
PURPOSE
The need for all providers to deliver basic palliative care has emerged as patients' needs outstrip the capacity of specialty palliative care. Many patients with complex illnesses have unmet needs and are seen in primary care more than other settings. We explore primary care providers' willingness and perceived capacity to provide basic palliative care, and their concerns and perceived barriers.

METHODS
We performed semistructured telephone interviews with 20 primary care providers about their perceptions of palliative care, including needs, practices, experiences, access, and what would be helpful for their practices to systematically provide basic palliative care.

RESULTS
We identified 3 major themes: (1) Participants recognize palliative needs in patients with complex problems. (2) They reactively respond to those needs using practice and community resources, believing that meeting those needs at a basic level is within the scope of primary care. (3) They can identify opportunities to improve the delivery of a basic palliative approach in primary care through practice change and redesign strategies used in enhanced primary care environments.

CONCLUSIONS
Systematic attention along the multidimensional domains of basic palliative care might allow practices to address unmet needs in patients with complex illnesses by using existing practice improvement models, strategies, and prioritization.

Nowels|David|D|
Jones|Jacqueline|J|
Nowels|Carolyn T|CT|
Matlock|Daniel|D|

D006301:Health Services Needs and Demand

Palliative Care
Telephone
Perception
Health Resources
Primary Health Care
Qualitative Research
Residence Characteristics


Toxicometallomics of Cadmium, Manganese and Arsenic with Special Reference to the Roles of Metal Transporters.

Abstract: The transport systems for metals play crucial roles in both the physiological functions of essential metals and the toxic effects of hazardous metals in mammals and plants. In mammalian cells, Zn transporters such as ZIP8 and ZIP14 have been found to function as the transporters for Mn(II) and Cd(II), contributing to the maintenance of Mn homeostasis and metallothionein-independent transports of Cd, respectively. In rice, the Mn transporter OsNramp5 expressed in the root is used for the uptake of Cd from the soil. Japan began to cultivate OsNramp5 mutant rice, which was found to accumulate little Cd, to prevent Cd accumulation. Inorganic trivalent arsenic (As(III)) is absorbed into mammalian cells via aquaglyceroporin, a water and glycerol channel. The ortholog of aquaporin in rice, OsLsi1, was found to be an Si transporter expressed in rice root, and is responsible for the absorption of soil As(III) into the root. Since rice is a hyperaccumulator of Si, higher amounts of As(III) are incorporated into rice compared to other plants. Thus, the transporters of essential metals are also utilized to incorporate toxic metals in both mammals and plants, and understanding the mechanisms of metal transports is important for the development of mitigation strategies against food contamination.

Cadmium Manganese Arsenic Transporter Silicon Zinc


Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders.

Abstract: The prefrontal cortex shows structural and functional alterations in mood disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its receptor TrkB are reported to be involved in depression. Here, we found that mRNA levels of key elements of retinoid signaling were significantly reduced in the postmortem dorsolateral prefrontal cortex/anterior cingulate cortex (ACC) from elderly depressed patients who did not die from suicide. Decreased mRNA levels of BDNF and TrkB isoforms were also found. Similar alterations were observed in rats subjected to chronic unpredictable mild stress. Along with neurons immunopositive for both retinoic acid receptor-α (RARα) and TrkB, a positive correlation between mRNA levels of the 2 receptors was found in the ACC of control subjects but not of depressed patients. In vitro studies showed that RARα was able to bind to and transactivate the TrkB promoter via a putative RA response element within the TrkB promoter. In conclusion, the retinoid and BDNF-TrkB signaling in the prefrontal cortex are compromised in mood disorders, and the transcriptional upregulation of TrkB by RARα provide a possible mechanism for their interaction. The retinoid signaling pathway that may activate TrkB expression will be an alternative novel target for BDNF-based antidepressant treatment.

Qi|Xin-Rui|XR|
Zhao|Jun|J|
Liu|Ji|J|
Fang|Hui|H|
Swaab|Dick F|DF|
Zhou|Jiang-Ning|JN|

D000080924:Aldehyde Dehydrogenase 1 Family

mood disorder
brain-derived neurotrophic factor
dorsolateral prefrontal cortex
anterior cingulate cortex
retinoic acid receptor-α


Comparison of new monofocal innovative and standard monofocal intraocular lens after phacoemulsification.

Abstract:
PURPOSE
To evaluate the early findings of new monofocal intraocular lens (Tecnis® Eyhance) in comparison with standard monofocal intraocular lens (Tecnis® 1-piece) in patients who underwent cataract surgery.

METHODS
Sixty-four eyes of thirty-two patients (each intraocular lens model was implanted bilaterally in 16 patients) were included in this retrospective study. Preoperative and postoperative (at one month) manifest refraction, spherical equivalent (SE) values, monocular and binocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UCIVA), distance-corrected intermediate visual acuity (DCIVA), distance-corrected near visual acuity (DCNVA), binocular defocus curve, photopic contrast-sensitivity, spectacle independence, photic phenomena, tolerance to residual refractive errors and complications were recorded.

RESULTS
The mean monocular postoperative UDVA, CDVA, DCNVA, spherical equivalent and cylinder values were comparable between each group (p > 0.05). Monocular and binocular DCIVA and UCIVA were significantly higher in Tecnis® Eyhance group than Tecnis® 1-piece group (p = 0.033, p = 0.038, respectively). No statistically significant difference was detected between groups regarding the photopic contrast sensitivities for any spatial frequency (p > 0.05). Spectacle independence was significantly higher in Tecnis® Eyhance group than Tecnis® 1-piece group. Tecnis® Eyhance IOL revealed a good tolerance to unexpected residual refractive errors than Tecnis® 1-piece IOL.

CONCLUSION
Tecnis® Eyhance appears to be an effective option for both patients and surgeons regarding better intermediate visual acuities and more forgiving for residual refractive errors relative to the standard monofocal intraocular lenses. However, longer follow-up studies with larger group of patients are needed to evaluate the effectiveness of Tecnis® Eyhance intraocular lens.

Monofocal intraocular lens
Cataract surgery
Residual refractive error
Contrast sensitivity
Intermediate vision


Dynamics of HCV RNA levels during acute hepatitis C virus infection.

Abstract: Understanding viral dynamics during acute hepatitis C virus (HCV) infection can provide important insights into immunopathogenesis and guide early treatment. The aim of this study was to investigate the dynamics of HCV RNA and alanine transaminase (ALT) levels during recent HCV infection in the Australian Trial in Acute Hepatitis C (ATAHC). ATAHC was a prospective study of the natural history of recently acquired HCV infection. Longitudinal HCV RNA and ALT levels were compared among individuals with persistent infection and spontaneous clearance. Among those with HCV persistence (n = 104) and HCV clearance (n = 30), median HCV RNA (5.2 vs. 4.1 log IU/ml, respectively) and ALT levels (779 vs. 1,765 IU/L, respectively) were high during month two following infection, and then declined during months three and four in both groups. Among those with HCV persistence, median HCV RNA was 2.9 log IU/ml during months four, increased to 5.5 log IU/ml during month five, and remained subsequently relatively stable. Among those with HCV clearance, median HCV RNA was undetectable by month five. Median HCV RNA levels were comparable between individuals with HCV persistence and HCV clearance during month three following infection (3.2 vs. 3.5 log IU/ml, respectively; P = 0.935), but markedly different during month five (5.5 vs. 1.0 log IU/ml, respectively; P < 0.001). In conclusion, dynamics of HCV RNA levels in those with HCV clearance and HCV persistence diverged between months three and five following infection, with the latter time-point being potentially useful for commencing early treatment.

Hajarizadeh|Behzad|B|
Grebely|Jason|J|
Applegate|Tanya|T|
Matthews|Gail V|GV|
Amin|Janaki|J|
Petoumenos|Kathy|K|
Hellard|Margaret|M|
Rawlinson|William|W|
Lloyd|Andrew|A|
Kaldor|John|J|
Dore|Gregory J|GJ|
|||

alanine transaminase
persistent infection
spontaneous clearance
chronic
viral load


Tribulus terrestris versus placebo in the treatment of erectile dysfunction: A prospective, randomized, double blind study.

Abstract:
OBJECTIVES
To evaluate the possible effects of Tribulus terrestris herbal medicine in the erectile dysfunction treatment and to quantify its potential impact on serum testosterone levels.

DESIGN AND METHODS
Prospective, randomized, double-blind and placebo-controlled study including thirty healthy men selected from 100 patients who presented themselves spontaneously complaining of erectile dysfunction, ≥ 40 years of age, nonsmokers, not undergoing treatment for prostate cancer or erectile dysfunction, no dyslipidemia, no phosphodiesterase inhibitor use, no hormonal manipulation and, if present hypertension and/or diabetes mellitus should be controlled. International Index of Erectile Function (IIEF-5) and serum testosterone were obtained before randomization and after 30 days of study. Patients were randomized into two groups of fifteen subjects each. The study group received 800 mg of Tribulus terrestris, divided into two doses per day for thirty days and the control group received placebo administered in the same way.

RESULTS
The groups were statistically equivalent in all aspects evaluated. The mean (SD) age was 60 (9.4) and 62.9 (7.9), P = .36 for intervention and placebo groups, respectively. Before treatment, the intervention group showed mean IIEF-5 of 13.2 (5-21) and mean total testosterone 417.1 ng/dl (270.7-548.4 ng/dl); the placebo group showed mean IIEF-5 of 11.6 (6-21) and mean total testosterone 442.7 ng/dl (301-609.1 ng/dl). After treatment, the intervention group showed mean IIEF-5 of 15.3 (5-21) and mean total testosterone 409.3 ng/dl (216.9-760.8 ng/dl); the placebo group showed mean IIEF-5 of 13.7 (6-21) and mean total testosterone 466.3 ng/dl (264.3-934.3 ng/dl). The time factor caused statistically significant changes in both groups for IIEF-5 only (P = .0004), however, there was no difference between the two groups (P = .7914).

CONCLUSIONS
At the dose and interval studied, Tribulus terrestris was not more effective than placebo on improving symptoms of erectile dysfunction or serum total testosterone.

Santos|C A|CA|
Reis|L O|LO|
Destro-Saade|R|R|
Luiza-Reis|A|A|
Fregonesi|A|A|

Herbal medicine
Testosterone
Alternative medicine
Disfunción sexual
Fitoterapia
Impotence
Impotencia
Libido
Medicina alternativa
Placebo and Chinese medicine
Placebo y medicina china
Sexual dysfunction
Testosterona


Surgical aspects of thoracic aortic aneurysms: A case series from a real-world setting.

Abstract:
Background
The objective of the present study is to review different surgical features and treatment modalities of thoracic aortic aneurysms.

Methods
This was a retrospective study of 17 patients operated on for thoracic aortic aneurysm in the Department of Cardiovascular Surgery of the Military Hospital of Rabat (Morocco) over a 10-year period, from January 2007 to December 2016. All patients with aneurysms located in the thoracic aorta or extended to the abdominal aorta were included in the study.

Results
The mean age of the patients was 49 ± 6 years. 58% of the patients were symptomatic. 10 patients (62%) had an aneurysm of the ascending thoracic aorta and 2 patients had an aneurysm of the ascending aorta extended to the arch. In 2 patients, the aneurysm was located in the descending thoracic aorta. Three patients (18%) had a post-traumatic false aneurysm of the aortic isthmus. Six patients underwent a Bentall procedure. One patient underwent the Yacoub technique. Two patients underwent ascending aorta replacement using the Wheat technique. In addition, two patients underwent ascending aorta and arch replacement and five patients (29%) underwent descending thoracic aorta replacement. In-hospital mortality was 12%. Two patients (12%) developed paraplegia and two developed renal failure (12%).

Conclusion
Thoracic aortic aneurysms are a serious pathology requiring surgical treatment before complications arise. Replacement of the arch and the descending thoracic aorta still remain a challenge for cardiovascular surgeons because of neurological complications.

Seghrouchni|Aniss|A|
Atmani|Noureddine|N|
Moutakiallah|Younes|Y|
El Bekkali|Youssef|Y|
Ait Houssa|Mahdi|M|

Aneurysm
Morocco
Thoracic aorta
Circulatory arrest
Extracorporeal circulation
PROCESS


Amphipathic helical peptides hamper protein-protein interactions of the intrinsically disordered chromatin nuclear protein 1 (NUPR1).

Abstract:
BACKGROUND
NUPR1 is a multifunctional intrinsically disordered protein (IDP) involved, among other functions, in chromatin remodelling, and development of pancreatic ductal adenocarcinoma (PDAC). It interacts with several biomolecules through hydrophobic patches around residues Ala33 and Thr68. The drug trifluoperazine (TFP), which hampers PDAC development in xenografted mice, also binds to those regions. Because of the large size of the hot-spot interface of NUPR1, small molecules could not be adequate to modulate its functions.

METHODS
We explored how amphipathic helical-designed peptides were capable of interacting with wild-type NUPR1 and the Thr68Gln mutant, inhibiting the interaction with NUPR1 protein partners. We used in vitro biophysical techniques (fluorescence, circular dichroism (CD), nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC)), in silico studies (docking and molecular dynamics (MD)), and in cellulo protein ligation assays (PLAs) to study the interaction.

RESULTS
Peptide dissociation constants towards wild-type NUPR1 were ~ 3 μM, whereas no interaction was observed with the Thr68Gln mutant. Peptides interacted with wild-type NUPR1 residues around Ala33 and residues at the C terminus, as shown by NMR. The computational results clarified the main determinants of the interactions, providing a mechanism for the ligand-capture that explains why peptide binding was not observed for Thr68Gln mutant. Finally, the in cellulo assays indicated that two out of four peptides inhibited the interaction of NUPR1 with the C-terminal region of the Polycomb RING protein 1 (C-RING1B).

CONCLUSIONS
Designed peptides can be used as lead compounds to inhibit NUPR1 interactions.

GENERAL SIGNIFICANCE
Peptides may be exploited as drugs to target IDPs.

Santofimia-Castaño|Patricia|P|
Rizzuti|Bruno|B|
Abián|Olga|O|
Velázquez-Campoy|Adrián|A|
Iovanna|Juan L|JL|
Neira|José L|JL|

D051792:Basic Helix-Loop-Helix Transcription Factors

D057927:Hydrophobic and Hydrophilic Interactions

D054730:Protein Interaction Domains and Motifs

Peptides
NMR
Calorimetry
Molecular dynamics
Cancer
Drug design


Polyvictimization and mental health consequences of female genital mutilation/circumcision (FGM/C) among Somali refugees in Kenya.

Abstract: Female genital mutilation or circumcision (FGM/C) is a perilous social and cultural practice that affects the physical, mental, and psychological health of affected women. It is widespread around the world, affecting 200 million women and girls. This study aimed to explore the relation of FGM/C to mental and physical conditions in Somali refugees displaced in a low-resource setting, applying the concept of poly-victimization to reveal multifaceted trauma sequelae. Data for this cross-sectional study with 143 female Somali youth living in Eastleigh, Kenya were collected between April and May in 2013. FGM/C was strongly associated with negative physical and mental health outcomes, including post-traumatic stress disorder and depressive, anxiety, and somatic symptoms. Logistic regression analysis revealed that separation from a parent and poly-victimization experiences were significantly associated with FGM/C experience. The results also showed that FGM/C and other traumas did not occur singly but were indicative of cumulative adversities, especially for women who were socially vulnerable and marginalized. The results of this study highlight the practice of FGM/C in the context of other adverse living conditions of refugees and the importance of attending to other co-occurring risk factors that prevail with FGM/C practice in the ecological system of refugee forced migration.

Im|Hyojin|H|
Swan|Laura E T|LET|
Heaton|Lindsay|L|

Female genital mutilation/cutting (FGM/C)


25 years of African trypanosome research: From description to molecular dissection and new drug discovery.

Abstract: The Molecular Parasitology conference was first held at the Marine Biological laboratory, Woods Hole, USA 25 years ago. Since that first meeting, the conference has evolved and expanded but has remained the showcase for the latest research developments in molecular parasitology. In this perspective, I reflect on the scientific discoveries focussed on African trypanosomes (Trypanosoma brucei spp.) that have occurred since the inaugural MPM meeting and discuss the current and future status of research on these parasites.

D000818:Animals
D000981:Antiprotozoal Agents
D055808:Drug Discovery
D049673:History, 20th Century
D049674:History, 21st Century
D006801:Humans
D014346:Trypanosoma brucei brucei
D014353:Trypanosomiasis, African

Trypanosome
Molecular parasitology
Trypanosoma brucei


Structural basis for cooperative binding of azoles to CYP2E1 as interpreted through guided molecular dynamics simulations.

Abstract: CYP2E1 metabolizes a wide array of small, hydrophobic molecules, resulting in their detoxification or activation into carcinogens through Michaelis-Menten as well as cooperative mechanisms. Nevertheless, the molecular determinants for CYP2E1 specificity and metabolic efficiency toward these compounds are still unknown. Herein, we employed computational docking studies coupled to molecular dynamics simulations to provide a critical perspective for understanding a structural basis for cooperativity observed for an array of azoles from our previous binding and catalytic studies (Hartman et al., 2014). The resulting 28 CYP2E1 complexes in this study revealed a common passageway for azoles that included a hydrophobic steric barrier causing a pause in movement toward the active site. The entrance to the active site acted like a second sieve to restrict access to the inner chamber. Collectively, these interactions impacted the final orientation of azoles reaching the active site and hence could explain differences in their biochemical properties observed in our previous studies, such as the consequences of methylation at position 5 of the azole ring. The association of a second azole demonstrated significant differences in interactions stabilizing the bound complex than observed for the first binding event. Intermolecular interactions occurred between the two azoles as well as CYP2E1 residue side chains and backbone and involved both hydrophobic contacts and hydrogen bonds. The relative importance of these interactions depended on the structure of the respective azoles indicating the absence of specific defining criteria for binding unlike the well-characterized dominant role of hydrophobicity in active site binding. Consequently, the structure activity relationships described here and elsewhere are necessary to more accurately identify factors impacting the observation and significance of cooperativity in CYP2E1 binding and catalysis toward drugs, dietary compounds, and pollutants.

Levy|Joseph W|JW|
Hartman|Jessica H|JH|
Perry|Martin D|MD|
Miller|Grover P|GP|

D065607:Cytochrome P-450 Enzyme Inhibitors

Azole
Molecular dynamics
Docking
Structure activity relationships
Allostery
Cytochrome P450


The Association Between Autism Symptoms and Child Functioning in a Sample With ADHD Recruited From the Community.

Abstract: Objective: Although autism spectrum disorder (ASD) symptoms are associated with poorer functioning in children with attention-deficit/hyperactivity disorder (ADHD), it is unclear which ASD symptom domains are most impairing. This study investigated whether specific ASD symptom domains were associated with child functioning in children with ADHD. Method: Parents of 164 children with ADHD completed a diagnostic interview to assess ADHD and comorbidities. Parents reported on ASD symptoms (Social Communication Questionnaire) and child quality of life (Pediatric Quality of Life Inventory 4.0). Parents and teachers completed the Strengths and Difficulties Questionnaire (emotional, conduct, and peer problems). Results: Repetitive and stereotyped behaviors were independently associated with emotional (p = .02) and conduct (p = .03) problems, and poorer quality of life (p = .004). Reciprocal social interaction deficits were independently associated with peer problems (p = .03). Conclusion: Reciprocal social interaction deficits and repetitive and stereotyped behaviors are important areas that should be focused on in ADHD assessment and treatment.

Stephens|Kate|K|
O'Loughlin|Rachel|R|
Green|Jessica L|JL|
Anderson|Vicki|V|
Rinehart|Nicole|N|
Nicholson|Jan M|JM|
Hazell|Philip|P|
Silk|Timothy J|TJ|
Efron|Daryl|D|
Sciberras|Emma|E|0000-0003-2812-303X

ADHD
Autism Spectrum Disorders (ASD)
comorbidity


Clinical features of patients with hepatic portal venous gas.

Abstract:
BACKGROUND
Hepatic portal venous gas (HPVG) is a rare clinical condition that is caused by a variety of underlying diseases. However, the factors that would permit accurate identification of bowel ischemia, requiring surgery, in patients with HPVG have not been fully investigated.

METHODS
Thirty patients that had been diagnosed with HPVG using computed tomography between 2010 and 2019 were allocated to two groups on the basis of clinical and intraoperative findings: those with (Group 1; n = 12 [40%]) and without (Group 2; n = 18 [60%]) bowel ischemia. Eleven patients underwent emergency surgery, and bowel ischemia was identified in eight of these (73%). Four patients in Group 1 were diagnosed with bowel ischemia, but treated palliatively because of their general condition. We compared the characteristics and outcomes of Groups 1 and 2 and identified possible prognostic factors for bowel ischemia.

RESULTS
At admission, patients in Group 1 more commonly showed the peritoneal irritation sign, had lower base excess, higher lactate, and higher C-reactive protein, and more frequently had comorbid intestinal pneumatosis. Of the eight bowel ischemia surgery patients, four (50%) died, mainly because of anastomotic leak following bowel resection and primary anastomosis (3/4, 75%). All except one patient in Group 2, who presented with aspiration pneumonia, responded better to treatment.

CONCLUSIONS
Earlier identification and grading of bowel ischemia according to the findings at admission should benefit patients with HPVG by reducing the incidence of unnecessary surgery and increasing the use of safer procedures, such as prophylactic stoma placement.

Hepatic portal venous gas
Bowel ischemia
Predictive factors


Age differences in sarcoidosis patients with posterior ocular lesions.

Abstract:
PURPOSE
To determine if age- and gender-related differences are correlated with the clinical aspects of posterior ocular lesions in sarcoidosis patients.

METHODS
Age at disease onset, gender, and ocular findings were obtained from clinical records. Out of the 84 patients enrolled in the study, 22 were 45 years old or younger while 62 were older than 45. After division of the fundus field into three areas, lesion locations were investigated.

RESULTS
The mean age of disease onset in the male (44.5 ± 16.8 years) was lower than in the female (55.5 ± 16.8 years). The lesions at the posterior segment in the older patients were found to be located around the peripheral area. However, no statistically significant difference in the location of the lesions was found for gender.

CONCLUSIONS
There was a statistically significant difference between younger and older sarcoidosis patients for the disease lesions. Lesions were located around the peripheral area at the posterior segment in older patients.

Nagata|Kenji|K| Maruyama|Kazuichi|K| Sugita|Sunao|S| Fukuchi|Urara|U| Terada|Yukiko|Y| Ishizuka|Atsuko|A| Nakazawa|Toru|T| Mochizuki|Manabu|M| Kinoshita|Shigeru|S|

Age
sarcoidosis
gender
posterior segment
disease lesion area
uveitis


Effect of Supplementing Hydrolysable Tannins to a Grower-Finisher Diet Containing Divergent PUFA Levels on Growth Performance, Boar Taint Levels in Back Fat and Intestinal Microbiota of Entire Males.

Abstract: A retrospective data analysis suggested that the levels of boar taint compounds depend on the polyunsaturated fatty acid (PUFA) level of the adipose tissue (AT) being significantly greater in the unsaturated AT. In addition, we recently reported that hydrolysable tannins (HTs) offered to entire males (EMs) reduce skatole and, to a greater extent, indole levels in the AT. Thus, the objective of the study was to determine the impact of HTs and a high dietary level of PUFA on growth performance and board taint compounds in EMs. In addition, the interaction between PUFA and HTs on gut microbiota and its link to intestinal skatole and indole production was investigated. At 25 kg BW, 44 EM originating from 11 litters were randomly assigned within litter to four dietary treatments. Two basal grower (25-60 kg BW) and finisher (60-105 kg BW) diets containing either 2% soy oil (H = high PUFA level) or 2% tallow (L = low PUFA level) were formulated. The H and L diets were either supplemented (H+/L+) or not (H-/L-) with 3% chestnut extract containing 50% HTs. The pigs had ad libitum access to the diets and were slaughtered at 170 days of age. The microbiota composition was investigated through the 16S rRNA gene sequences obtained by next-generation sequencing (Illumia MiSeq platform, San Diego, CA, USA) and analyzed with a specific packages in R, version 3.5.0. Regardless of the PUFA content, the EMs fed the H+ diets were 2% (p < 0.01) less feed efficient overall. This was due to the slower (p = 0.01) growth in the finisher period despite similar feed intake. Carcass characteristics were not affected by the diets. Regardless of HT feeding, the PUFA level in the AT of the H pigs was 10% greater (p = 0.05) than in the L pigs. The indole level tended (p = 0.08) to be 50% lower in the H+ group. Surprisingly, the pigs that were fed diet H- had greater skatole levels than those fed diet L-, with intermediate skatole levels in the H+ and L+. Independent of the PUFA level, the HTs decreased bacteria abundance and qualitatively affected the microbiota composition. In conclusion, these data do not confirm that boar taint compound levels were related to PUFA levels in the AT. However, HTs can be considered to be a promising alternative to conventional antibacterial additives, with no detrimental effects on pig gut health and with appealing properties for reducing the synthesis of the main components of boar taint.

hydrolysable tannins
PUFA
boar taint
gut microbiota
gut health


Development of PCR-based markers and whole-genome selection model for anthracnose resistance in white lupin (Lupinus albus L.).

Abstract: White lupin (Lupinus albus L.) is a high-protein grain legume crop, grown since ancient Greece and Rome. Despite long domestication history, its cultivation remains limited, partly because of susceptibility to anthracnose. Only some late-flowering, bitter, low-yielding landraces from Ethiopian mountains displayed resistance to this devastating disease. The resistance is controlled by various genes, thereby complicating the breeding efforts. The objective of this study was developing tools for molecular tracking of Ethiopian resistance genes based on genotyping-by-sequencing (GBS) data, envisaging linkage mapping and genomic selection approaches. Twenty GBS markers from two major quantitative trait loci (QTLs), antr04_1/antr05_1 and antr04_2/antr05_2, were converted to PCR-based markers using assigned transcriptome sequences. Newly developed markers improved mapping resolution around both anthracnose resistance loci, providing more precise QTL estimation. PCR-based screening of diversified domesticated and primitive germplasm revealed the high specificity of two markers for the antr04_1/antr05_1 locus (TP222136 and TP47110) and one for the antr04_2/antr05_2 locus (TP338761), highlighted by simple matching coefficients of 0.96 and 0.89, respectively. Moreover, a genomic selection approach based on GBS data of a recombinant inbred line mapping population was assessed, providing an average predictive ability of 0.56. These tools can be used for preselection of candidate white lupin germplasm for anthracnose resistance assays.

D002874:Chromosome Mapping
D060467:Disease Resistance
D008040:Genetic Linkage
D005819:Genetic Markers
D018745:Genome, Plant
D031297:Lupinus
D010935:Plant Diseases
D040641:Quantitative Trait Loci

Anthracnose resistance
White lupin
Genomic selection
Quantitative trait
Marker-assisted selection


Pituitary tumour fibroblast-derived cytokines influence tumour aggressiveness.

Abstract: Tumour-associated fibroblasts (TAFs) are key elements of the tumour microenvironment, but their role in pituitary neuroendocrine tumours (PitNETs) has been little explored. We hypothesised that TAF-derived cytokines may play a role in tumour aggressiveness and that their release can be inhibited by somatostatin analogues. TAFs were isolated and cultured from 16 PitNETs (11 clinically non-functioning tumours and 5 somatotropinomas). The fibroblast secretome was assessed with a 42-plex cytokine array before and after multiligand somatostatin receptor agonist pasireotide treatment. Angiogenesis and epithelial-to-mesenchymal transition pathway assessment included CD31, E-cadherin and ZEB1 expression. GH3 cells treated with TAF- or skin fibroblast-conditioned medium were assessed for migration, invasion and cell morphology changes. PitNET TAFs secreted significant amounts of cytokines including CCL2, CCL11, VEGF-A, CCL22, IL-6, FGF-2 and IL-8. TAFs from PitNETs with cavernous sinus invasion secreted higher IL-6 levels compared to fibroblasts from non-invasive tumours (P = 0.027). Higher CCL2 release from TAFs correlated with more capillaries (r = 0.672, P = 0.004), and TAFs from PitNETs with a higher Ki-67 tended to secrete more CCL2 (P = 0.058). SST1 is the predominant somatostatin receptor in TAFs, and pasireotide decreased TAF-derived IL-6 by 80% (P < 0.001) and CCL2 by 35% (P = 0.038). GH3 cells treated with TAF-conditioned medium showed increased migration and invasion compared to cells treated with skin fibroblast-conditioned medium, with morphological and E-cadherin and ZEB1 expression changes suggesting epithelial-to-mesenchymal transition. TAF-derived cytokines may increase PitNET aggressiveness, alter angiogenesis and induce epithelial-to-mesenchymal transition changes. Pasireotide's inhibitory effect on TAF-derived cytokines suggest that this effect may play a role in its anti-tumour effects.

Marques|Pedro|P|
Barry|Sayka|S|
Carlsen|Eivind|E|
Collier|David|D|
Ronaldson|Amy|A|
Awad|Sherine|S|
Dorward|Neil|N|
Grieve|Joan|J|
Mendoza|Nigel|N|
Muquit|Samiul|S|
Grossman|Ashley B|AB|
Balkwill|Frances|F|
Korbonits|Márta|M|

cytokine
tumour-associated fibroblasts
tumour microenvironment
pituitary neuroendocrine tumour
pasireotide


Angiographic detection of cerebral cavernous malformations with C-arm cone beam CT imaging in three patients.

Abstract: Cerebral cavernous malformations (CMs) are typically not seen during conventional digital subtraction angiography (DSA) and are therefore classically referred to as angiographically occult malformations. We present three cases in which DSA with selective intra-arterial contrast injection in the common carotid artery and C-arm cone beam CT imaging was able to demonstrate a CM. In addition, an associated developmental venous anomaly (DVA) was present in all three cases, although detected by MRI in only one of them. In light of this finding, we suspect that the incidence of DVA associated with CM is probably higher than previously reported.

Radvany|Martin G|MG|
Rigamonti|Daniele|D|
Gailloud|Philippe|P|

D020786:Hemangioma, Cavernous, Central Nervous System


Ammonium nitrate regulated the color characteristic changes of pigments in Monascus purpureus M9.

Abstract: Monascus pigments (MPs) with different color characteristics, produced by submerged fermentation of Monascus purpureus M9, have potential application in food industry. In the present study, the effects and regulatory mechanisms of ammonium nitrate (AN) on the color characteristics of MPs were investigated. The concentration of intracellular pigments was significantly decreased when subjected to AN. The hue and lightness value indicated AN altered the total pigments appearance from original red to orange. The HPLC analysis for six major components of MPs showed that the production of rubropunctatin or monascorubrin, was significantly reduced to the undetectable level, whereas the yields of monascin, ankaflavin, rubropunctamine and monascorubramine, were apparently increased with AN supplement. To be noted, via real-time quantitative PCR strategy, the expression level of mppG, closely relative to orange pigments biosynthesis, was significantly down-regulated. However, the expression of mppE, involved in yellow pigments pathway, was up-regulated. Moreover, the broth pH value was dropped to 2.5-3.5 in the fermentation process resulted from AN treatment, along with the increased extracellular polysaccharide biosynthesis. Taken together, the change of MPs categories and amounts by AN might be the driving force for the color characteristics variation in M. purpureus M9. The present study provided useful data for producing MPs with different compositions and modified color characteristics.

Ammonium nitrate
Color characteristics
Monascus pigments
Gene expression
Pigments conversion


Benign myoepithelioma of the soft palate: an unusual clinical entity.

Abstract: Myoepitheliomas are rare benign tumours that affect the exocrine glands and are sporadically located in the salivary glands. The most common location of myoepithelioma in the oral cavity is the parotid gland and it is seldom encountered in the palate. The diagnosis of this entity is challenging since its clinical presentation may resemble those of more common neoplasms, rendering a complex histopathological diagnosis. The aim of the present case report is to describe an unusual case of myoepithelioma of the soft palate in a male patient, which developed as an asymptomatic, slowly growing mass. The tumour was assessed with histopathological examination and the diagnosis was verified via immunohistochemistry. Finally, the treatment included surgical resection of the tumour and no signs of recurrence were noted 2.5 years after the surgical procedure. Early diagnosis and treatment plays an important role in the prognosis of this pathological entity.


Multiple Ways of cfDNA Reception and Following ROS Production in Endothelial Cells.

Abstract: Oxidized cell-free DNA acts as a stress signal molecule and triggers an adaptive response in human cells. Various membrane DNA recognizing receptors are known as potential sensors for such DNA fragments. In order to clarify which of these sensors are able to interact with cfDNA fragments, circulating in human blood flow in heath and disease, we studied the influence of various cfDNA types on endothelial cells. We incubated these fragments at a physiologically optimal concentration with HUVEC cells for 3-24 h and detected the expression of either TLR9 or AIM2, RIG1 and STING receptors at mRNA and protein levels. We estimated that the activation of both TLR9 and other types of intracellular receptors initiates stress signaling in the endothelium independently. Signal transduction through these receptors activates NOX4 as the main source of ROS production in HUVECs.

Alekseeva|Anna Yu|AY|
Kameneva|Larisa V|LV|
Kostyuk|Svetlana V|SV|
Veiko|Natalia N|NN|

D061307:Human Umbilical Vein Endothelial Cells

D020133:Reverse Transcriptase Polymerase Chain Reaction

ROS
Cell-free DNA
HUVECs
Cardiovascular diseases
DNA sensors


Gloss and surface roughness of pre-polymerized composite materials designed for posterior CAD/CAM crown restorations corroded with acidulated phosphate fluoride application.

Abstract: This study assessed the gloss and surface roughness of computer-aided design/computer-aided manufacturing (CAD/CAM) resin composites corroded with acidulated phosphate fluoride (APF) application. One ceramic block, ten CAD/CAM resin composites for premolars, and four CAD/CAM resin composites for molars were assessed. The surface topography of the materials before and after APF application was observed using an electron microscope. The results were analyzed by Wilcoxon signed-rank test and Dunnett's many to one test (p<0.05). Gloss after APF application was significantly lower for all CAD/CAM resin composites except Artesano. Ra after APF application was significantly higher for all CAD/CAM resin composites except Artesano, Dentcraft HR Block, and Estelite P Block, and Sa was significantly higher for all CAD/CAM resin composites. Irregular surface topography was observed after APF application and the surface features differed among the materials. Therefore, APF application may be detrimental to the surface properties of CAD/CAM resin composites.

Mikami|Wataru|W| Koizumi|Hiroyasu|H| Kodaira|Akihisa|A| Hiraba|Haruto|H| Yoneyama|Takayuki|T| Matsumura|Hideo|H|

Gloss
Surface roughness
Composite
CAD/CAM
Acidulated phosphate fluoride


Cyto-Histo Correlation of a Very Rare Tumor: Superficial Angiomyxoma.

Abstract: Superficial angiomyxoma (SA) is one of the superficially located myxoid soft tissue tumor. Because of the rarity of this tumor, there is paucity of fine needle aspiration cytology (FNAC) findings. Here, we present a case of SA in a 14-year-old girl who presented with a left leg swelling. The cytology of the lesion along with the histopathologic correlation is presented.

Bembem|Khuraijam|K| Jaiswal|Ankita|A| Singh|Meeta|M| Verma|Nidhi|N| Jain|Shyama|S| Bhat|Anusha|A|

superficial angiomyxoma
Carney's complex
myxoid tumor


hMENA(11a), a hMENA isoform sending survival signals.

Abstract: Human MENA(11a) (hMENA(11a)), an epithelial-associated isoform of the actin binding protein enabled homolog (ENAH, also known as mammalian ENA [MENA]), is upregulated and phosphorylated following the activation of human epidermal growth factor receptor (HER) 1, HER2, and HER3. Here, we reveal a novel role of this isoform in sustaining cell survival and propose hMENA(11a) as a marker of HER3 activation and resistance to phosphatidylinositol-3-kinase inhibition therapies.

Trono|Paola|P|
Di Modugno|Francesca|F|
Nisticò|Paola|P|


Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel.

Abstract:
BACKGROUND
Poly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been demonstrated to be biocompatible and thermosensitive. In this study, its potential efficacy and mechanisms of preventing postsurgical abdominal adhesions were investigated.

RESULTS
PECE hydrogel was transformed into gel state from sol state in less than 20 seconds at 37°C. None of the animals treated with the hydrogel (n = 15) developed adhesions. In contrast, all untreated animals (n = 15) had adhesions that could only be separated by sharp dissection (P < 0.001). The hydrogel adhered to the peritoneal wounds, gradually disappeared from the wounds within 7 days, and transformed into viscous fluid, being completely absorbed within 12 days. The parietal and visceral peritoneum were remesothelialized in about 5 and 9 days, respectively. The hydrogel prevented the formation of fibrinous adhesion and the invasion of fibroblasts. Also, along with the hydrogel degradation, a temporary inflammatory cell barrier was formed which could effectively delay the invasion of fibroblasts during the critical period of mesothelial regeneration.

CONCLUSION
The results suggested that PECE hydrogel could effectively prevent postsurgical intra-abdominal adhesions, which possibly result from the prevention of the fibrinous adhesion formation and the fibroblast invasion, the promotion of the remesothelialization, and the hydroflotation effect.

Yang|Bing|B| Gong|ChangYang|C| Zhao|Xia|X| Zhou|ShengTao|S| Li|ZhengYu|Z| Qi|XiaoRong|X| Zhong|Qian|Q| Luo|Feng|F| Qian|ZhiYong|Z|

biocompatible thermosensitive barrier anti-adhesion