Fathers' Worries During Pregnancy: A Qualitative Content Analysis of Reddit.

Abstract: Qualitative investigations into the emotional needs of expectant fathers have been limited by difficulties with recruitment. This study aimed to unobtrusively obtain insights into fathers' worries during pregnancy by analyzing the content of posts on the Internet forum Reddit. The majority of worries related to infant well-being (50.8%), particularly the potential for perinatal loss (23.0%). Concerns relating to partner well-being and the couple relationship were also common, comprising 17.0% of posts. Several posts related to individual factors, such as apprehension about the father role (16.3%). Finally, situational factors such as work-family conflict accounted for 15.9% of posts. These findings contribute to the growing literature on fathers' experiences of pregnancy and can inform the development of father-inclusive perinatal education.

fathers
antenatal education
anxiety
fears
perinatal mental health


Cyclolinear Oligo- and Poly(iminoborane)s: The Missing Link in Inorganic Main-Group Macromolecular Chemistry.

Abstract: The reaction of n-C8 H17 B[N(Me)SiMe3 ]2 (1) with n-C8 H17 BCl2 (2 a) yielded, instead of a linear poly(iminoborane), the aminoborane n-C8 H17 B(Cl)N(Me)SiMe3 (4) and after cyclotrimerization the borazine cyclo-(n-C8 H17 BNMe)3 (6). Side reactions that result in borazine formation were effectively suppressed if 1,3-bis(trimethylsilyl)-1,3,2-diazaborolidines 7 were employed as co-monomers in combination with dichloro- or dibromoboranes 2 or 8, respectively. Silicon/boron exchange polycondensation led to oligo(iminoborane)s 11 a,b,ac,d. Alternative synthetic routes to such species involve Sn/B exchange of 1,3-bis(trimethylstannyl)-2-n-octyl-1,3,2-diazaborolidine (16) and n-C8 H17 BBr2 (8 a), and the initiated polycondensation of the dormant monomer 14 in the presence of a Brønsted acid (HCl, HOTf, or HNTf2 ; Tf=trifluoromethylsulfonyl). Although an attempt to obtain an oligo-/poly(iminoborane) with phenyl side groups yielded only insoluble material, the incorporation of aryl groups was proven for a derivative with both phenyl and n-octyl boron substituents (11 ac), as well as for a derivative with 4-n-butylphenyl side groups (11 d). The highest-molecular-weight sample obtained was 11 ac. Featuring about 18 catenated BN units, on average, this is the closest approach to a poly(iminoborane) known.

boron
main group elements
organic-inorganic hybrid materials
polymers
synthesis design


Intrabody against prolyl hydroxylase 2 ameliorates acetaminophen-induced acute liver injury in mice via concomitant promotion of angiogenesis and redox homeostasis.

Abstract: Acetaminophen (APAP) overdose has become the most common cause of drug-induced acute liver failure. Angiogenesis and redox homeostasis play an important role in liver protection and repair of APAP-induced acute liver injury (AILI). Hypoxia inducible factor-1 (HIF-1) is a transcription factor that plays a crucial role in regulating the expression of genes associated with angiogenesis, redox homeostasis and energy balance. Prolyl hydroxylase 2 (PHD2) predominantly hydroxylates proline residues in HIF-1α to promote its degradation. In our previous study, we reported an intrabody against PHD2 (ER-INP) that enhances angiogenesis by blocking PHD2 activity to increase HIF-1α abundance and activity. The present study was designed to explore the role and possible mechanisms of ER-INP in AILI in mice. Mice were pretreated intravenously with ER-INP before intraperitoneal injection of APAP to induce AILI. The results showed that pretreatment with ER-INP dramatically decreased the high ALT and AST activities and significantly ameliorated the centrilobular necrosis induced by APAP administration. ER-INP expression promoted angiogenesis in vivo by upregulating the mRNA and protein levels of HIF-1α target genes. Meanwhile, ER-INP pretreatment restored redox homeostasis, verified by reinforcement of PRDX4 activity and suppression of GSH depletion. This study demonstrated that ER-INP protects against AILI in part by increasing angiogenesis and maintaining redox homeostasis. These results indicate that ER-INP may provide a potential liver protection strategy against AILI in the future.

Zhao|Liangzhong|L| Zhao|Jialiang|J| Gao|Ruijuan|R| Tian|Yuan|Y| Zhang|Ying|Y| Tang|Weiwei|W| Jiang|Yu|Y| Li|Chengjuan|C| Wang|Manning|M| Yang|Fang|F| Li|Guiying|G|

D056486:Chemical and Drug Induced Liver Injury

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

Acetaminophen-induced acute liver injury


Excessive gestational weight gain prior to glucose screening and the risk of gestational diabetes: a meta-analysis.

Abstract:
AIMS/HYPOTHESIS
Excessive gestational weight gain (GWG) may be a risk factor for gestational diabetes mellitus (GDM). We aimed to study the association between excessive GWG (defined according to Institute of Medicine recommendations) prior to GDM screening, and GDM.

METHODS
We systematically searched four electronic databases from 1990 until September 2014 for observational studies published in English or German that reported an association between excessive GWG and GDM as the outcome. Random effects meta-analyses were performed to provide a pooled estimate of the OR comparing the risk of GDM in women with and without excessive GWG.

RESULTS
A total of eight studies involving 13,748 participants were included. The pooled analysis of unadjusted OR yielded a summary OR of 1.40 (95% CI 1.21, 1.61; p < 0.001) with low between-study heterogeneity (I(2) = 16.7%). A sensitivity analysis based on four studies reporting adjusted effect estimates revealed similar results (OR 1.42; 95% CI 1.20, 1.68; p < 0.001; I(2) = 0%). No evidence was found that the effect of GWG on GDM differs depending on maternal pre-pregnancy BMI category. A funnel plot did not indicate substantial publication bias.

CONCLUSIONS/INTERPRETATION
Avoiding excessive weight gain in pregnancy prior to the GDM screening test may be a potential strategy to reduce GDM risk. META-ANALYSIS REGISTRATION: www.crd.york.ac.uk/PROSPERO CRD42014008802.

Brunner|Stefanie|S|
Stecher|Lynne|L|
Ziebarth|Stephanie|S|
Nehring|Ina|I|
Rifas-Shiman|Sheryl L|SL|
Sommer|Christine|C|
Hauner|Hans|H|
von Kries|Rüdiger|R|

Gestational weight gain
Gestational diabetes
Meta-analysis
GDM
Pregnancy
IOM recommendations
Systematic review


The Role of Chromoendoscopy in Evaluating Colorectal Dysplasia.

Abstract: Chromoendoscopy pertains to image-enhanced endoscopic techniques such as dye-based chromoendoscopy and electronic chromoendoscopy using narrow-band imaging, flexible spectral imaging color enhancement, and i-scan. Dye-based chromoendoscopy has been demonstrated to improve colorectal dysplasia detection in high-risk patients with long-term inflammatory bowel disease, and electronic chromoendoscopy techniques have been shown to improve characterization of diminutive colorectal lesions, allowing for optical diagnosis during a colonoscopy examination. This article reviews endoscopic imaging using chromoendoscopy techniques for colorectal dysplasia evaluation.

Chromoendoscopy
colorectal dysplasia
dye-based chromoendoscopy
electronic chromoendoscopy
colorectal neoplasia


Battered Child Syndrome; a Case Study.

Abstract: One of the important and usual missed causes of pediatric traumas is child abuse. This ominous phenomenon, which can be presented physically, psychologically, sexually, and emotionally has grown significantly in recent years. Many children are not diagnosed in the early stages of evaluation. Battered Child Syndrome is used to describe the clinical condition of the child serious physical abuse by parents or caregivers. Medical staff should always keep the syndrome in their mind for those brought to the emergency department with trauma. In this report, we described a patient complained of dysphagia following a falling from a height and multiple epidural hematomas and final diagnosis of battered child syndrome.

Pezeshki|Arastoo|A|
Rahmani|Farzad|F|
Ebrahimi Bakhtavar|Hanieh|H|
Fekri|Sanaz|S|

Battered Child Syndrome
Child Abuse
Hematoma
brain edema
cerebral palsy


Predictors of survival, functional survival, and hospital readmission in octogenarians after surgical aortic valve replacement.

Abstract:
OBJECTIVE
To analyze outcomes and predictors of functional survival (personal care home admission and mortality) and hospital readmission in patients aged ≥80 years who underwent surgical aortic valve replacement (SAVR) in a Manitoba hospital.

METHODS
This was a retrospective cohort study of patients aged ≥80 years who underwent SAVR with or without coronary artery bypass grafting in Manitoba between 1995 and 2014. Data from the Manitoba Adult Cardiac Surgery database and the Manitoba Centre for Health Policy were used. Kaplan-Meier estimates of outcomes and Cox multivariate regression analysis of risk factors were performed. Survival was compared with that of age- and sex-matched life expectancy.

RESULTS
A total of 1872 patients were aged ≥50 years and 378 were aged ≥80 years, 55% of whom (n = 208) underwent concurrent coronary artery bypass grafting. Compared with younger patients, octogenarians had higher in-hospital mortality (8.5%; P <.001), longer median intensive care unit stay (47.2 hours; P <.001), and longer median in-hospital stay (13 days; P <.001). The median follow-up was 5.2 years. Functional survival was 82.4% at 1 year and 56.5% at 5 years, and freedom from hospital readmission was 61.5% at 1 year and 28.4% at 5 years. Survival approximated the age- and sex-matched life expectancy at 1 year (83.8%) and 5 years (60.8%). Preoperative atrial fibrillation, peripheral vascular disease, female sex, postoperative acute kidney injury, and blood transfusion were associated with adverse outcomes.

CONCLUSIONS
In eligible octogenarians, SAVR has acceptable 1- and 5-year functional survival and hospital readmission rates, but significant perioperative mortality and morbidity.

Kuo|Kendra|K|
Shah|Pallav|P|
Hiebert|Brett|B|
Love|Karin|K|
Menkis|Alan H|AH|
Manji|Rizwan A|RA|
Arora|Rakesh C|RC|

D019918:Heart Valve Prosthesis Implantation

readmission
octogenarian
cardiac surgery
aortic valve surgery
long-term survival


Dietary Fatty-Acid Compositions Are more Strongly Reflected in Fatty than Lean Dorsal Fillets of Common Carp (Cyprinus carpio L.).

Abstract: In this fish-feeding study, we tested similarity patterns between fatty acids (FA) in diets and common carp (Cyprinus carpio) of fish ponds used for semi-intensive aquaculture, containing naturally occurring pond zooplankton and different feeds (marine or terrestrial feeds) until carp reached market size. We evaluated if and how total lipid contents in dorsal fillets can reflect dietary FA compositions in farm-raised common carp and hypothesized that increasing total lipid contents in dorsal fillets significantly increase the similarity between dietary and dorsal fillets' FA compositions. Results of this study showed that carps had higher total lipids when supplied with marine feeds and dietary FA compositions were indeed more strongly reflected in fatty (i.e. high total lipid contents) than in leaner dorsal fillets (low total lipid contents). Increasing total lipid contents in dorsal fillets significantly increased the similarity between the dietary and dorsal fillets' FA compositions. In contrast, leaner dorsal fillets had FA patterns that were more distinct from dietary FA. Total lipid contents higher than ~60 mg/g dry weight in dorsal fillets had only limited effects on increasing the similarity between FA compositions of diets and dorsal fillets, and were independent of feed sources. It is thus suggested that higher total lipid contents in dorsal fillets can be used as a proxy to predict dietary FA profiles in common carps, or perhaps even in farm-raised fish in general.

Schultz|Sebastian|S|
Koussoroplis|Apostolos-Manuel|AM|
Kainz|Martin J|MJ|

Fatty-acid composition
Common carp
Aquaculture
Total lipids
Fatty-acid retention
Polyunsaturated fatty acids
Stable isotopes


Cell-free DNA in blood and urine as a diagnostic tool for bladder cancer: a meta-analysis.

Abstract:
OBJECTIVE
To assess the diagnostic performance of cell-free DNA assays in the detection of bladder cancer.

PATIENTS AND METHODS
The quality of the studies included in this meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Statistical analyses were performed using the software RevMan 5.3 and Stata 14.0. We assessed the pooled sensitivity and specificity, positive/negative likelihood ratios (PLRs/NLRs), diagnostic odds ratios (DORs), and corresponding 95% confidence intervals (95% CIs). Summary receiver operating characteristic curve (ROC curve) and area under the curve (AUC) were used to summarize the overall test performance. Heterogeneity and publication bias were also examined.

RESULTS
Eleven studies included 802 bladder cancer patients and 668 controls met the eligibility criteria. The overall diagnostic accuracy was measured as follows: sensitivity 0.71 (95% CI = 0.64-0.77), specificity 0.78 (95% CI = 0.70-0.85), PLR 3.3 (95% CI = 2.4-54.5), NLR 0.37 (95% CI = 0.30-0.46), DOR 9 (95% CI = 6-14), and AUC 0.80 (95% CI = 0.77-0.83). Subgroup analysis suggested that ethnicity significantly accounted for the heterogeneity of specificity. The Deeks' funnel plot asymmetry test (P = 0.97) suggested no potential publication bias.

CONCLUSIONS
Cell-free DNA has a high diagnostic value in bladder cancer.

Wang|Xin-Shuai|XS| Zhao|Meng-Qi|MQ| Zhang|Li|L| Kong|De-Jiu|DJ| Ding|Xue-Zhen|XZ| Hu|Xiao-Chen|XC| Yang|Jun-Qiang|JQ| Gao|She-Gan|SG|

Cell-free DNA
bladder cancer
biomarker
diagnosis


Bone drilling methodology and tool based on position measurements.

Abstract: Bone drilling, despite being a very common procedure in hospitals around the world, becomes very challenging when performed close to organs such as the cochlea or when depth control is critical for avoiding damage to surrounding tissue. To date, several mechatronic prototypes have been proposed to assist surgeons by automatically detecting bone layer transitions and breakthroughs. However, none of them is currently accurate enough to be part of the surgeon's standard equipment. The present paper shows a test bench specially designed to evaluate prior methodologies and analyze their drawbacks. Afterward, a new layer detection methodology with improved performance is described and tested. Finally, the prototype of a portable mechatronic bone drill that takes advantage of the proposed detection algorithm is presented.

Díaz|Iñaki|I|
Gil|Jorge Juan|JJ|
Louredo|Marcos|M|

Bone drilling
Layer detection
Assisted surgery


High-efficiency c-Myc-mediated induction of functional hepatoblasts from the human umbilical cord mesenchymal stem cells.

Abstract:
BACKGROUND
Direct reprogramming of human fibroblasts to hepatocyte-like cells was proposed to generate large-scale functional hepatocytes demanded by liver tissue engineering. However, the difficulty in obtaining large quantities of human fibroblasts greatly restricted the extensive implementation of this approach. Meanwhile, human umbilical cord mesenchymal stem cells (HUMSCs) are the preferred cell source for HLCs with the advantages of limited ethical concerns, easy accessibility, and propagation in vitro. However, no direct reprogramming protocol for converting HUMSCs to hepatoblast-like cells (HLCs) has been reported.

METHODS
HLCs were successfully generated from HUMSCs by forced expression of FOXA3, HNF1A, and HNF4A (collectively as 3TFs) and c-Myc. In vitro and in vivo functional experiments were conducted to demonstrate the hepatic phenotype, characterization, and function of HUMSC-derived HLCs (HUMSC-iHeps). ChIP-seq and RNA-seq were integrated to reveal the potential molecular mechanisms underlying c-Myc-mediated reprogramming.

RESULTS
We showed that c-Myc greatly improved the trans-differentiation efficiency for HLCs from HUMSCs, which remained highly efficient in reprogramming fibroblasts into HLCs, suggesting c-Myc could promote direct reprogramming and its potentially widespread applicability for generating large amounts of HLCs in vitro. Mice transplantation experiments further confirmed the therapeutic potential of HUMSC-iHeps by liver function restoration and survival prolongation. Besides, in vivo safety assessment demonstrated the low risk of the tumorigenic potential of HUMSC-iHeps. We found that c-Myc functioned predominantly at an early phase of reprogramming, and we further unraveled the regulatory network altered by c-Myc.

CONCLUSIONS
c-Myc enhanced reprogramming efficiency of HLCs from HUMSCs. A large scale of functional HLCs generated more conveniently from HUMSCs could benefit biomedical studies and applications of liver diseases.

Deng|Jie|J| Luo|Kai|K| Xu|Pengchao|P| Jiang|Qingyuan|Q| Wang|Yuan|Y| Yao|Yunqi|Y| Chen|Xiaolei|X| Cheng|Fuyi|F| Xie|Dan|D| Deng|Hongxin|H|0000-0002-8875-4493

D045164:Mesenchymal Stem Cell Transplantation

Human umbilical cord mesenchymal stem cells


De novo mutation in X-linked hearing loss-associated POU3F4 in a sporadic case of congenital hearing loss.

Abstract:
OBJECTIVES
In this report, we present a male patient with no family history of hearing loss, in whom we identified a novel de novo mutation in the POU3F4 gene.

METHODS
One hundred ninety-four (194) Japanese subjects from unrelated and nonconsanguineous families were enrolled in this study. We used targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes for identifying the genetic causes of hearing loss.

RESULTS
A novel de novo frameshift mutation of POU3F4 to c.727_728insA (p.N244KfsX26) was identified. The patient was a 7-year-old male with congenital progressive hearing loss and inner ear deformity. Although the patient had received a cochlear implant, auditory skills were still limited. The patient also exhibited developmental delays similar to those previously associated with POU3F4 mutation.

CONCLUSION
This is the first report of a mutation in POU3F4 causing hearing loss in a Japanese patient without a family history of hearing loss. This study underscores the importance of comprehensive genetic testing of patients with hearing loss for providing accurate prognostic information and guiding the optimal management of patient rehabilitation.

Moteki|Hideaki|H|
Shearer|A Eliot|AE|
Izumi|Shuji|S|
Kubota|Yamato|Y|
Azaiez|Hela|H|
Booth|Kevin T|KT|
Sloan|Christina M|CM|
Kolbe|Diana L|DL|
Smith|Richard J H|RJ|
Usami|Shin-Ichi|S|

D016057:Evoked Potentials, Auditory, Brain Stem

POU3F4
hearing loss
massively parallel sequencing
genetics
cochlear implant


One-year clinical outcomes in invasive treatment strategies for acute ST-elevation myocardial infarction complicated by cardiogenic shock in elderly patients.

Abstract:
OBJECTIVE
To investigate the clinical outcomes of an invasive strategy for elderly (aged ≥ 75 years) patients with acute ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS).

METHODS
Data on 366 of 409 elderly CS patients from a total of 6,132 acute STEMI cases enrolled in the Korea Acute Myocardial Infarction Registry between January 2008 and June 2011, were collected and analyzed. In-hospital deaths and the 1-month and 1-year survival rates free from major adverse cardiac events (MACE; defined as all cause death, myocardial infarction, and target vessel revascularization) were reported for the patients who had undergone invasive (n = 310) and conservative (n = 56) treatment strategies.

RESULTS
The baseline clinical characteristics were not significantly different between the two groups. There were fewer in-hospital deaths in the invasive treatment strategy group (23.5% vs. 46.4%, P < 0.001). In addition, the 1-year MACE-free survival rate after invasive treatment was significantly lower compared with the conservative treatment (51% vs. 66%, P = 0.001).

CONCLUSIONS
In elderly patients with acute STEMI complicated by CS, the outcomes of invasive strategy are similar to those in younger patients at the 1-year follow-up.

Yoo|Yeon Pyo|YP|
Kang|Ki-Woon|KW|
Yoon|Hyeon Soo|HS|
Myung|Jin Cheol|JC|
Choi|Yu Jeong|YJ|
Kim|Won Ho|WH|
Park|Sang Hyun|SH|
Jung|Kyung Tae|KT|
Jeong|Myung Ho|MH|
|||

Cardiogenic shock
Elderly patients
Acute myocardial infarction


Fabrication of multilayered vascular tissues using microfluidic agarose hydrogel platforms.

Abstract: Vascular tissues fabricated in vitro are useful tools for studying blood vessel-related cellular physiologies and for constructing relatively large 3D tissues. An efficient strategy for fabricating vascular tissue models with multilayered, branched, and thick structures through the in situ hydrogel formation in fluidic channels is proposed. First, an aqueous solution of RGD-alginate containing smooth muscle cells (SMCs) is introduced into channel structures made of agarose hydrogel, forming a cell-embedding Ca-alginate hydrogel layer with a thickness of several hundred micrometers on the channel surface because of the Ca2+ ions diffused from the agarose hydrogel matrix. Next, endothelial cells (ECs) are introduced and cultured for up to seven days to form hierarchically organized, multilayered vascular tissues. The factors affecting the thickness of the Ca-alginate hydrogel layer, and prepared several types of microchannels with different morphologies are examined. The fabricated vascular tissue models are easily recovered from the channel by simply detaching the agarose hydrogel plates. In addition, the effect of O2 tension (20 or 80%) on the viability and elastin production of SMCs during the perfusion culture is evaluated. This technique would pave a new way for vascular tissue engineering because it enables the facile production of morphologically in vivo vascular tissue-like structures that can be employed for various biomedical applications.

Kinoshita|Keita|K| Iwase|Masaki|M| Yamada|Masumi|M| Yajima|Yuya|Y| Seki|Minoru|M|

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

Hydrogel
Tissue engineering
Biomedical engineering
Lab-on-chip
Organs-on-chip


Synergistic control of herpes simplex virus pathogenesis by IRF-3, and IRF-7 revealed through non-invasive bioluminescence imaging.

Abstract: Interferon regulatory factors IRF-3 and IRF-7 are central to the establishment of the innate antiviral response. This study examines HSV-1 pathogenesis in IRF-3(-/-), IRF-7(-/-) and double-deleted IRF3/7(-/-) (DKO) mice. Bioluminescence imaging of infection revealed that DKO mice developed visceral infection following corneal inoculation, along with increased viral burdens in all tissues relative to single knockout mice. While all DKO mice synchronously reached endpoint criteria 5 days post infection, the IRF-7(-/-) mice survived longer, indicating that although IRF-7 is dominant, IRF-3 also plays a role in controlling disease. Higher levels of systemic pro-inflammatory cytokines were found in IRF7(-/-) and DKO mice relative to wild-type and IRF-3(-/-) mice, and IL-6 and G-CSF, indicative of sepsis, were increased in the DKO mice relative to wild-type or single-knockout mice. In addition to controlling viral replication, IRF-3 and -7 therefore play coordinating roles in modulation of inflammation during HSV infection.

Murphy|Aisling A|AA|
Rosato|Pamela C|PC|
Parker|Zachary M|ZM|
Khalenkov|Alexey|A|
Leib|David A|DA|

D000818:Animals
D004195:Disease Models, Animal
D006561:Herpes Simplex
D018259:Herpesvirus 1, Human
D050838:Interferon Regulatory Factor-3
D050839:Interferon Regulatory Factor-7
D049449:Luminescence
D051379:Mice
D008810:Mice, Inbred C57BL
D018345:Mice, Knockout
D018805:Sepsis
D016019:Survival Analysis
D013997:Time Factors
D051598:Whole Body Imaging


Are computed tomography-based measures of specific abdominal muscle groups predictive of adverse outcomes in older cancer patients?

Abstract:
Purpose
It is unknown whether computed tomography (CT)-based total abdominal muscle measures are representative of specific abdominal muscle groups and whether analysis of specific abdominal muscle groups are predictive of the risk of adverse outcomes in older cancer patients.

Methods
Retrospective single-center cohort study in elective colon cancer patients aged ≥65 years. CT-based skeletal muscle (SM) surface area, muscle density and intermuscular adipose tissue (IMAT) surface area were determined for rectus abdominis; external- and internal oblique and transversus abdominis (lateral muscles); psoas; and erector spinae and quadratus lumborum (back muscles). Outcomes were defined as severe postoperative complications (Clavien-Dindo score >2) and long-term survival (median follow-up 5.2 years).

Results
254 older colon cancer patients were included (median 73.6 years, 62.2% males). Rectus abdominis showed the lowest SM surface area and muscle density and the back muscles showed the highest IMAT surface area. Psoas muscle density, and lateral muscle density and percentage IMAT were associated with severe postoperative complications independent of gender, age and cancer stage.

Conclusions
CT-based total abdominal muscle quantity and quality do not represent the heterogeneity that exists between specific muscle groups. The potential added value of analysis of specific muscle groups in predicting adverse outcomes in older (colon) cancer patients should be further addressed in prospective studies.

Looijaard|S M L M|SMLM|
Maier|A B|AB|
Voskuilen|A F|AF|
Van Zanten|T|T|
Bouman|D E|DE|
Klaase|J M|JM|
Meskers|C G M|CGM|

Computed tomography
Aged
Abdominal surgery
Body composition
Cancer surgery
Digestive system
Gastrointestinal system
Internal medicine
Medical imaging
Musculoskeletal system
Neoplasms
Oncology
Sarcopenia
Surgery


Confounding dynamic risk taking propensity with a momentum prognostic strategy: the case of the Columbia Card Task (CCT).

Abstract: Figner et al. (2009) developed the Columbia Card Task (CCT) to measure risk-taking attitudes. This tool consists of two versions: in the COLD version the decision maker needs to state in advance how many cards (out of 32) they want to turn over (so called static risk taking), in the HOT version they have the possibility of turning over all 32 cards one-by-one until they decide to finish (dynamic risk taking). We argue that the HOT version confounds an individual's willingness to accept risk with their beliefs in trend continuation vs. trend reversal in a prognostic task. In two experimental studies we show that people believing in trend continuation (momentum subjects) turn over more cards than those believing in trend reversal (contrarians) in the HOT version of the task. However, this is not the case in the COLD version. Thus, we provide evidence that, when considered as a dynamic risk propensity measure, the number of turned over cards in the HOT version of the CCT is a contaminated measure and reflects two phenomena: (1) risk preference and (2) the decision-maker's belief in trend continuation. We speculate that other dynamic risk taking measures can also be biased by a momentum strategy.

dynamic risk taking
prognostic strategies
Columbia Card Task (CCT)
positive and negative recency
streaks perception


Induction Effects of Bacteroides fragilis Derived Outer Membrane Vesicles on Toll Like Receptor 2, Toll Like Receptor 4 Genes Expression and Cytokines Concentration in Human Intestinal Epithelial Cells.

Abstract:
Objective
Gastrointestinal (GI) tract, like other mucosal surface, is colonized with a microbial population known as gut microbiota. Outer membrane vesicles (OMVs) which are produced by gram negative bacteria could be sensed by Toll like receptors (TLRs). The interaction between gut microbiota and TLRs affects homeostasis and immune responses. In this study, we evaluated TLR2, TLR4 genes expression and cytokines concentration in Caco-2 cell line treated with Bacteroides fragilis (B. fragilis) and its OMVs.

Materials and Methods
In this experimental study, OMVs were extracted using sequential centrifugation and their physicochemical properties were evaluated as part of quality control assessment. Caco-2 cells were treated with B. fragilis and its OMVs (180 and 350 μg/ml). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to assess TLR2 and TLR4 mRNA expression levels. Pro-inflammatory (IFNᵧ) and anti-inflammatory (IL- 4 and IL-10) cytokines were evaluated by ELISA.

Results
B. fragilis significantly decreased TLR2 and slightly increased TLR4 mRNA levels in Caco-2 cell line. The TLR2 mRNA level was slightly increased at 180 and 350 μg/ml of OMVs. Conversely, the TLR4 mRNA level was decreased at 180 μg/ml of OMVs, while it was significantly increased at 350 μg/ml of OMVs. Furthermore, B. fragilis and its OMVs significantly increased and decreased IFNᵧ concentration, respectively. Anti-inflammatory cytokines were increased by B. fragilis and its OMVs.

Conclusion
B. fragilis and its OMVs have pivotal role in the cross talk between gut microbiota and the host especially in the modulation of the immune system. Based on the last studies on immunomodulatory effect of B. fragilis derived OMVs on immune cells and our results, we postulate that B. fragilis derived OMVs could be possible candidates for the reduction of immune responses.

Ahmadi Badi|Sara|S|
Khatami|S Hohreh|SH|
Irani|S Hiva|SH|
Siadat|Seyed Davar|SD|

Bacteroides fragilis
Membrane Vesicles
Toll Like Receptors
Gut Microbiota


Synthesis of Benzo[b]azocin-2-ones by Aryl Amination and Ring-Expansion of α-(Iodophenyl)-β-oxoesters.

Abstract: Transformation of β-oxoesters with PhI(OCOCF3 )2 leads to α-(ortho-iodophenyl)-β-oxoesters. These materials are the starting point for the synthesis of 6-carboxybenzo[b]azocin-2-ones by a sequence of aryl amination and ring transformation. This reaction sequence starts with copper-catalyzed formation of N-alkyl anilines from the iodoarenes and primary amines in the presence of K3 PO4 as stoichiometric base. The intermediate products underwent ring transformation by addition of the nitrogen into the carbonyl group of the cycloalkanone, furnishing benzo-annulated eight-membered ring lactams. Under the same reaction conditions, the cyclohexanone and cycloheptanone derivatives gave no aminated products, but ring-transformed to benzofuran derivatives. The title compounds of this investigation contain two points for further diversification (the lactam nitrogen and the carboxylate function), thus, the suitability of this compound class as a scaffold was proven by appropriate functionalizations. The first series of derivatizations of the scaffold was initiated by hydrogenolytic debenzylation of N-benzyl derivative to provide the NH-congener, which could be deprotonated with LDA and alkylated at nitrogen to give further examples of this compound class. Secondly, the ester function was submitted to saponification and the resulting carboxylic acid could be amidated using HATU as coupling reagent to furnish different amides.

aryl amination
lactams
scaffolds
medium sized rings
ring expansion


PqqE from Methylobacterium extorquens AM1: a radical S-adenosyl-l-methionine enzyme with an unusual tolerance to oxygen.

Abstract: Methylobacterium extorquens AM1 is an aerobic facultative methylotroph known to secrete pyrroloquinoline quinone (PQQ), a cofactor of a number of bacterial dehydrogenases, into the culture medium. To elucidate the molecular mechanism of PQQ biosynthesis, we are focusing on PqqE which is believed to be the enzyme catalysing the first reaction of the pathway. PqqE belongs to the radical S-adenosyl-l-methionine (SAM) superfamily, in which most, if not all, enzymes are very sensitive to dissolved oxygen and rapidly inactivated under aerobic conditions. We here report that PqqE from M. extorquens AM1 is markedly oxygen-tolerant; it was efficiently expressed in Escherichia coli cells grown aerobically and affinity-purified to near homogeneity. The purified and reconstituted PqqE contained multiple (likely three) iron-sulphur clusters and showed the reductive SAM cleavage activity that was ascribed to the consensus [4Fe-4S](2+) cluster bound at the N-terminus region. Mössbauer spectrometric analyses of the as-purified and reconstituted enzymes revealed the presence of [4Fe-4S](2+) and [2Fe-2S](2+) clusters as the major forms with the former being predominant in the reconstituted enzyme. PqqE from M.extorquens AM1 may serve as a convenient tool for studying the molecular mechanism of PQQ biosynthesis, avoiding the necessity of establishing strictly anaerobic conditions.

Saichana|Natsaran|N| Tanizawa|Katsuyuki|K| Pechoušek|Jiří|J| Novák|Petr|P| Yakushi|Toshiharu|T| Toyama|Hirohide|H| Frébortová|Jitka|J|

D000595:Amino Acid Sequence
D001426:Bacterial Proteins
D010450:Endopeptidases
D020601:Methylobacterium extorquens
D008969:Molecular Sequence Data
D010100:Oxygen
D045542:PQQ Cofactor
D012436:S-Adenosylmethionine
D017386:Sequence Homology, Amino Acid
D015204:Spectroscopy, Mossbauer

PqqE
Methylobacterium extorquens AM1
PQQ
radical SAM enzyme


Women's attitudes, experiences and compliance concerning the use of Mindfetalness- a method for systematic observation of fetal movements in late pregnancy.

Abstract:
BACKGROUND
Maternal perception of decreased fetal movements and low awareness of fetal movements are associated with a negative birth outcome. Mindfetalness is a method developed for women to facilitate systematic observations of the intensity, character and frequency of fetal movements in late pregnancy. We sought to explore women's attitudes, experiences and compliance in using Mindfetalness.

METHODS
We enrolled 104 pregnant women treated at three maternity clinics in Stockholm, Sweden, from February to July of 2016. We educated 104 women in gestational week 28-32 by providing information about fetal movements and how to practice Mindfetalness. Each was instructed to perform the assessment daily for 15 min. At each subsequent follow-up, the midwife collected information regarding their perceptions of Mindfetalness, and their compliance. Content analyses, descriptive and analytic statistics were used in the analysis of data.

RESULTS
Of the women, 93 (89%) were positive towards Mindfetalness and compliance was high 78 (75%). Subjective responses could be binned into one of five categories: Decreased worry, relaxing, creating a relationship, more knowledge about the unborn baby and awareness of the unborn baby. Eleven (11%) women had negative perceptions of Mindfetalness, citing time, and the lack of need for a method to observe fetal movements as the most common reasons.

CONCLUSION
Women in late pregnancy are generally positive about Mindfetalness and their compliance with daily use is high. The technique helped them to be more aware of, and create a relationship with, their unborn baby. Mindfetalness can be a useful tool in antenatal care. However, further study is necessary in order to determine whether the technique is able to reduce the incidence of negative birth outcome.

D007722:Health Knowledge, Attitudes, Practice

Attitude
Compliance
Fetal movements
Mindfetalness
Relationship


The Sequential Indirect Effect of Negative Urgency on Drinking Consequences Through Distress Intolerance and Drinking Motives: Initial Examination in College Students Reporting Past Month Alcohol Use.

Abstract: Identification of cognitive and affective vulnerabilities among college drinkers may aid in developing focused interventions that promote a reduction in the prevalence of alcohol use. Negative urgency (NU) and distress intolerance (DI) evidence concurrent, unique, and synergistic relations with drinking motives and negative consequences of alcohol use. Utilizing a sequential multiple mediation framework to investigate a comprehensive model of these variables, we examined NU as a behavioral risk factor that potentiates the development of DI, thereby contributing to drinking motives that increase the risk of problematic use in young adults. A diverse sample of undergraduate students (N = 616; M age= 19.1, SD=1.4, range=18-25; 50.6% female; 60.6% Caucasian; recruited between September 2015 and Spring 2017) reporting past month alcohol use completed an online questionnaire battery. The results suggested that NU may contribute to negative alcohol use outcomes via its relation to DI and the motivation to drink in order to cope with negative emotional states and conform to social pressure. These findings suggest that NU may be a primary intervention target in young adults.

Yang|Min-Jeong|MJ|
Borges|Allison|A|
Leyro|Teresa M|TM|

Negative urgency
Distress intolerance
Alcohol
Conformity motives
Coping motives


Mesenchymal Stem Cell-Conditioned Medium Improves Mitochondrial Dysfunction and Suppresses Apoptosis in Okadaic Acid-Treated SH-SY5Y Cells by Extracellular Vesicle Mitochondrial Transfer.

Abstract:
BACKGROUND
Mesenchymal stem cells-conditioned medium (MSC-CM) provides a promising cell-free therapy for Alzheimer's disease (AD) mainly due to the paracrine of MSCs, but the precise mechanisms remain unclear. Studies suggests that mitochondrial dysfunction precedes the accumulation of amyloid-β plaques and neurofibrillary tangles, and involves in the onset and development of AD.

OBJECTIVE
In the present study, we evaluated the protective effects and explored the related-mitochondrial mechanisms of human umbilical cord derived MSC-CM (hucMSC-CM) in an AD model in vitro.

METHODS
To this end, an AD cellular model was firstly established by okadaic acid (OA)-treated SH-SY5Y cells, and then treated by hucMSC-CM to assess the oxidative stress, mitochondrial function, apoptosis, AD-related genes, and signaling pathways.

RESULTS
hucMSC-CM significantly deceased tau phosphorylated at Thr181 (p181-tau) level, which was increased in AD. hucMSC-CM also alleviated intracellular and mitochondrial oxidative stress in OA-treated SH-SY5Y cells. In addition, hucMSC-CM suppressed apoptosis and improved mitochondrial function in OA-treated SH-SY5Y cells. Flow cytometric analysis indicated that hucMSC-CM exerted the protective effects relying on or partly extracellular vesicle (EV) mitochondrial transfer from hucMSCs to OA-treated SH-SY5Y cells. Moreover, RNA sequencing data further demonstrated that hucMSC-CM regulated many AD-related genes, signaling pathways and mitochondrial function.

CONCLUSION
These results indicated that MSC-CM or MSC-EVs containing abundant mitochondria may provide a novel potential therapeutic approach for AD.

Zhang|Zhihua|Z| Sheng|Hongxia|H| Liao|Li|L| Xu|Chen|C| Zhang|Ang|A| Yang|Yang|Y| Zhao|Long|L| Duan|Lian|L| Chen|Hu|H| Zhang|Bin|B|

mesenchymal stem cell-conditioned medium


What human blood-brain barrier models can tell us about BBB function and drug discovery?

Abstract: Introduction: Human in vitro blood-brain barrier (BBB) models could be important tools for studying BBB development, maintenance and regulation. However, our capacity to obtain information from these models is still limited in part because only in recent years have (i) these models been derived from non-brain cell sources (e.g. stem cells), (ii) microfluidic systems been developed to recapitulate aspects of BBB physiology and (iii) new insights into the molecular and cellular mechanisms of BBB diseases (e.g. Huntington´s, Allan-Herndon-Dudley Syndrome) been described. Area covered: This article reviews the technological advances in the derivation of human cells from the neurovascular unit using stem cells and the creation of personalized BBB models generated from patients with neurodegenerative diseases. It also reviews the scientific advances generated from in vitro BBB models. Expert opinion: The recent technological advances in the derivation of human cells from the neurovascular unit from stem cells as well as in the generation of BBB-on-a-chip that recapitulate in vitro part of the BBB physiology are significant to generate more robust BBB models; however, a considerable effort is still needed to validate the potential of these models to recapitulate the in vivo cellular and molecular mechanisms, in particular regarding BBB function in health and disease.

D000818:Animals
D001812:Blood-Brain Barrier
D001927:Brain Diseases
D055808:Drug Discovery
D006801:Humans
D056656:Lab-On-A-Chip Devices
D008954:Models, Biological
D019636:Neurodegenerative Diseases
D013234:Stem Cells

BBB function
drug discovery
Blood-brain barrier (BBB)
stem cells
human  models


Buffering effects of safe, supportive, and nurturing relationships among women with childhood histories of maltreatment.

Abstract:
BACKGROUND
Adults who were victims of childhood maltreatment tend to have poorer health compared with adults who did not experience abuse. However, many are in good health. We tested whether safe, supportive, and nurturing relationships buffer women with a history of childhood maltreatment from poor health outcomes in later life.

METHODS
Participants included women from the Environmental Risk (E-Risk) Longitudinal Twin Study who were involved in an intimate relationship at some point by the time their twin children were 10 years old. Women were initially interviewed in 1999-2000 (mean age = 33 years) and 2, 5, and 7 years later. They reported on their physical and mental health, and their health-risk behaviours.

RESULTS
Compared with women who did not experience abuse in childhood, women with histories of maltreatment were at elevated risk for mental, physical, and health-risk behaviours, including major depressive disorder, sleep, and substance use problems. Cumulatively, safe, supportive, and nurturing relationships characterized by a lack of violence, emotional intimacy, and social support buffered women with a history of maltreatment from poor health outcomes.

CONCLUSIONS
Our findings emphasize that negative social determinants of health - such as a childhood history of maltreatment - confer risk for psychopathology and other physical health problems. If, however, a woman's current social circumstances are sufficiently positive, they can promote good health, particularly in the face of past adversity.

Jaffee|S R|SR|
Takizawa|R|R|
Arseneault|L|L|

D000328:Adult
D054523:Adult Survivors of Child Abuse
D001008:Anxiety Disorders
D003865:Depressive Disorder, Major
D004739:England
D005260:Female
D006304:Health Status
D006801:Humans
D007398:Interpersonal Relations
D008137:Longitudinal Studies
D011203:Poverty
D065840:Protective Factors
D012307:Risk Factors
D012747:Sexual Partners
D012893:Sleep Wake Disorders
D012944:Social Support
D019966:Substance-Related Disorders
D014852:Wales

buffering effect
relationships
Maltreatment
health outcomes
longitudinal


Molecular insights into the formation of drug-monoacyl phosphatidylcholine solid dispersions for oral delivery.

Abstract: Phospholipid-based formulations provide a key technology to formulate poorly water-soluble drugs. A recent interest has been in using phospholipids with a high content of monoacyl phosphatidylcholine (monoacyl PC) due to its ability to form mixed micelles of mono- and di-acylphospholipids upon aqueous dispersion. The present work focused on binary drug- monoacyl PC systems (at about equimolar ratio) with respect to screening of solid dispersion feasibility. It was tested whether or not a molecular rule of thumb can predict the desirable absence of drug crystallinity in the products. Subsequently, molecular simulations were performed to gain a better understanding of molecular association between drugs and monoacyl PC. Finally, the glass-forming ability (GFA) of pure drugs was considered with respect to solid dispersion formation. All products were obtained from a solvent-evaporation process and subsequent analysis of potential drug crystallinity was measured with X-ray powder diffraction and differential scanning calorimetry. Molecular simulations were making use of a Monte Carlo algorithm and molecular properties relevant for GFA were calculated. As a result, the dataset of 28 drugs confirmed an earlier proposed empirical rule that enthalpy of fusion and logP were important for solid dispersion formation, while some relevance was also evidenced for drug energies of frontal orbitals. Interestingly, the Monte Carlo simulations revealed several likely associations between drug and phospholipid rather than a well-defined single complex formation. However, drug-excipient interactions were still pivotal, since GFA of pure drug could not predict solid dispersion formation. These findings led to important molecular insights into binary solid dispersions of drug and monoacyl PC, which can guide formulators in early drug product development.

Gautschi|Nicolas|N|
Van Hoogevest|Peter|P|
Kuentz|Martin|M|

Poorly water-soluble drugs
Phospholipid
Monoacyl phosphatidylcholine
Monte Carlo simulation
Glass formation


Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis.

Abstract:
OBJECTIVES
Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with cyclophosphamide have an increased malignancy risk compared with the general population. We investigated whether treatment with rituximab instead of cyclophosphamide has decreased the malignancy risk in patients with AAV.

METHODS
The study included patients with AAV treated at a tertiary vasculitis referral centre between 2000 and 2014. The malignancy incidence in these patients was compared with the incidence in the general population by calculating standardised incidence ratios (SIRs), adjusted for sex, age and calendar year. Malignancy incidence was compared between rituximab-treated and cyclophosphamide-treated patients.

RESULTS
Of the 323 included patients, 33 developed a total of 45 malignancies during a mean follow-up of 5.6 years. This represented a 1.89-fold increased (95% CI 1.38 to 2.53) malignancy risk, and a non-significantly increased risk if non-melanoma skin cancer was excluded (SIR, 1.09; 95% CI 0.67 to 1.69). The risk of non-melanoma skin cancer was 4.58-fold increased (95% CI 2.96 to 6.76). Cyclophosphamide-treated patients had an increased malignancy risk compared with the general population (SIR, 3.10; 95% CI 2.06 to 4.48). In contrast, rituximab-treated patients had a malignancy risk similar to the general population (SIR, 0.67; 95% CI 0.08 to 2.43). The malignancy risk in cyclophosphamide-treated patients was 4.61-fold higher (95% CI 1.16 to 39.98) than in rituximab-treated patients.

CONCLUSIONS
The malignancy risk in patients with AAV was lower in rituximab-treated patients than in cyclophosphamide-treated patients. Notably, rituximab treatment was not associated with an increased malignancy risk compared with the general population. Rituximab could therefore be a safe alternative to cyclophosphamide in the treatment of AAV.

van Daalen|Emma E|EE|
Rizzo|Raffaella|R|
Kronbichler|Andreas|A|
Wolterbeek|Ron|R|
Bruijn|Jan A|JA|
Jayne|David R|DR|
Bajema|Ingeborg M|IM|
Rahmattulla|Chinar|C|

D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Cyclophosphamide
DMARDs (biologic)
Outcomes research
Systemic vasculitis


In Vitro Assay for Measuring Receptor-Kinase Activity in the Bacillus subtilis Chemotaxis Pathway.

Abstract: The sensing apparatus of the Bacillus subtilis chemotaxis pathway involves a complex consisting of chemoreceptors, the CheA histidine kinase, and the CheV and CheW adaptor proteins. Attractants and repellents alter the rate of CheA autophosphorylation, either by directly binding the receptors or by indirectly interacting with them through intermediate binding proteins. We describe an in vitro assay for measuring receptor-kinase activity in B. subtilis. This assay has been used to investigate the mechanism of signal transduction in B. subtilis chemotaxis and the disparate mechanisms employed by this bacterium for sensory adaptation and gradient sensing.

Walukiewicz|Hanna E|HE|
Ordal|George W|GW|
Rao|Christopher V|CV|

D001412:Bacillus subtilis
D001426:Bacterial Proteins
D001681:Biological Assay
D002630:Chemotactic Factors
D002633:Chemotaxis
D008565:Membrane Proteins
D010766:Phosphorylation
D015398:Signal Transduction

Bacillus subtilis
Chemotaxis
Chemoreceptors
CheA
Kinase assay


Optical coherence tomography evaluation of late strut coverage patterns between first-generation drug-eluting stents and everolimus-eluting stent.

Abstract:
OBJECTIVES
To compare strut coverage patterns between everolimus-eluting stent (EES) and first-generation drug-eluting stents (DES) at more than 12 months after successful implantation, using optical coherence tomography (OCT).

BACKGROUND
No sufficient OCT data has been reported comparing late strut coverage patterns between EES and first-generation DES. The favorable late results after EES implantation could be related to lower rates of uncovered and malapposed struts.

METHODS
A total of 66 DES (21 EES, 23 SES, and 22 PES) that were implanted at least 1 year in advance in 40 patients and met good late angiographic results were evaluated by OCT. The percentage of uncovered and malapposed struts, calculated as the ratio of uncovered or malapposed struts to total struts in all cross-sectional images per stent, was compared among the three groups.

RESULTS
A total of 35,061 struts were analyzed: 11,967 from EES, 11,855 from SES, and 11m239 from PES. The average tissue coverage thickness of the struts per stent was greater in EES than in SES and PES (109 ± 40 µm vs. 72 ± 27 µm and 83 ± 26 µm, respectively; P = 0.001). The percentage of uncovered struts (1.9 ± 4.1% in EES vs. 11.6 ± 12.7% in SES, P = 0.01 and vs. 7.1 ± 5.2% in PES, P < 0.001) and malapposed struts (0.1 ± 0.3% in EES vs. 1.8 ± 3.5% in SES, P = 0.01 and vs. 3.5 ± 5.1% in PES, P = 0.02) was much lower in EES than in first-generation DES, with no significant differences between SES and PES.

CONCLUSIONS
Late strut coverage patterns are not similar between EES and first-generation DES. EES showed a lower percentage of uncovered and malapposed struts.

de Lezo Herrerosde Tejada|Javier Suárez|JS|

optical coherence tomography
malapposed struts
uncovered struts
drug delivery
neointimal coverage
stent structure


Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer.

Abstract:
BACKGROUND
Companion animals are also affected by IgE-mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles.

METHODS
Custom-designed allergen microarray was produced on the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or were clinically asymptomatic.

RESULTS
Horses showed individual IgE-binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S-albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet.

CONCLUSION
In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen-specific preventive and therapeutic concepts.

molecular
allergen
horse
microarray
IgE
ISAC
component-resolved diagnosis


The Relationship between Coaches' and Athletes' Competitive Anxiety,and their Performance.

Abstract:
OBJECTIVE
This study was performed to survey the relationship between coaches' and athletes' competitive anxiety, and their performance.

METHODS
This is a descriptive correlational study performed using a demographic questionnaire, an athletic performance checklist, and sport competition anxiety test designed by Martens consisting of 15 questions. The study population consisted of 540 players and 60 coaches from 60 futsal teams (5 main players, 4 reserves, and 1 coach for each team). All of the players and the coaches were surveyed in a census method and no sampling was done. The data were analyzed by SPSS software, using chi-square, and Pearson correlation coefficient test.

RESULTS
The results showed a positive significant relationship between the coaches' anxiety level and sport competition anxiety level in the athletes (p = 0.019, r = 0.56). It also showed that there was a negative significant relationship between the coaches' anxiety level and performance level of the athletes (p = 0.012, r = -0.80). A negative significant relationship was also demonstrated between the athletes' competitive anxiety level, and their athletic experiences (p < 0.001, r = -0.45) and age (p = 0.001, r = -0.37).

CONCLUSIONS
Coaches and officials should consider sport competition anxiety among athletes before and during competitions. Formal and planned competitions, training sessions, and preparation practices can be a major factor assisting to decrease athletes' anxiety.

DECLARATION OF INTEREST
None.

Coach
Competitive Anxiety
Performance
Player
Futsal


Anesthetic effect of propofol combined with remifentanil or sevoflurane anesthesia on patients undergoing radical gastrectomy.

Abstract: Anesthetic effect of propofol combined with remifentanil or sevoflurane intravenous anesthesia on patients undergoing radical gastrectomy was evaluated. The clinical data of 516 cancer patients who received radical gastrectomy in the First Bethune Hospital of Jilin University between January 2011 and December 2017 were retrospectively analyzed. In total 203 patients with propofol combined with remifentanil anesthesia were used as group A, and 313 patients with propofol combined with sevoflurane anesthesia as group B. The changes of respiration and circulation were analyzed at the time of entering the operating room (t0), the beginning of the operation (t1), 10 min after the beginning of the operation (t2) and 10 min after operation (t3). The onset time of anesthesia, the total time of operation, the time of waking up after operation and the time of leaving the operating room were analyzed. The effects of sedation and amnesia were evaluated, and the occurrence of adverse reactions were recorded. The inhibition of circulation and respiration was more obvious at t1 and t2 in group A when compared to group B (P<0.05), and the respiration and circulation in group B was more stable than that in group A (P<0.001). Patients' sedation scores in group A were lower than those in group B, and the difference was statistically significant (P<0.05); there were 56 (27.59%) patients and 30 (9.58%) patients with postoperative pain in group A and group B, respectively (P<0.001). The application of propofol combined with sevoflurane in the anesthesia of patients undergoing radical gastrectomy can make the respiration and circulation more stable, and reduce the incidence of postoperative pain and adverse reactions.

Feng|Yazhen|Y| Li|Ji|J| Wang|Hushan|H| Duan|Zongsheng|Z|

anesthetic effect
propofol
sevoflurane
cancer patient


Dopamine D1-like receptors in prelimbic, but not infralimbic, medial prefrontal cortex contribute to chronic stress-induced increases in cue-induced relapse to palatable food seeking during forced abstinence.

Abstract: Chronic stress exposure causes increased vulnerability to future relapse-like behavior in male, but not female, rats with a history of palatable food self-administration. These effects are mediated by dopamine D1-like receptors, but the anatomical location of chronic stress' dopaminergic mechanism is not known. Thus, male rats were trained to respond for palatable food pellets in daily sessions. During subsequent forced abstinence from food self-administration, stress was manipulated (0 or 3 h restraint/day for 7 days). Rats also received bilateral microinjections of the D1-like receptor antagonist SCH-23390 (0.25 μg/0.5 μl/side) or vehicle (0.5 μl/side) delivered to either prelimbic or infralimbic medial prefrontal cortex prior to daily treatments. Relapse tests in the presence of food-associated cues were conducted 7 days after the last treatment. Stress caused an increase and a decrease in responding during relapse tests in rats that received prelimbic vehicle and SCH-23390 infusions, respectively, relative to unstressed rats. In rats receiving IL infusions, however, stress caused an increase in responding regardless of whether the infusion was vehicle or SCH-23390. These results establish a specific role for prelimbic D1-like receptors in chronic stress-potentiated relapse.

Ball|Kevin T|KT|
Bennardo|Guy M|GM|
Roe|Jonathan|J|
Wunderlich|Kyle J|KJ|

Dopamine
Prelimbic
Infralimbic
Relapse
Food seeking
Chronic stress


More evidence against the Spinozan model: Cognitive load diminishes memory for "true" feedback.

Abstract: We tested two competing models on the memory representation of truth-value information: the Spinozan model and the Cartesian model. Both models assume that truth-value information is represented with memory "tags," but the models differ in their coding scheme. According to the Cartesian model, true information is stored with a "true" tag, and false information is stored with a "false" tag. In contrast, the Spinozan model proposes that only false information receives "false" tags. All other (i.e., untagged) information is considered as true by default. Hence, in case of cognitive load during feedback encoding, the latter model predicts a load effect on memory for "false" feedback, but not on memory for "true" feedback. To test this prediction, participants studied trivia statements (Experiment 1) or nonsense statements that allegedly represented foreign-language translations (Experiment 2). After each statement, participants received feedback on the (alleged) truth value of the statement. Importantly, half of the participants experienced cognitive load during feedback processing. For the trivia statements of Experiment 1, we observed a load effect on memory for both "false" and "true" feedback. In contrast, for the nonsense statements of Experiment 2, we found a load effect on memory for "true" feedback only. Both findings clearly contradict the Spinozan model. However, our results are also only partially in line with the predictions of the Cartesian model. For this reason, we suggest a more flexible model that allows for an optional and context-dependent encoding of "true" tags and "false" tags.

Descartes
Feedback memory
Multinomial model
Spinoza
Truth bias


Interpersonal difficulties in obesity: A systematic review and meta-analysis to inform a rejection sensitivity-based model.

Abstract: Obesity is associated with difficulties due to stigma and loneliness. These impact negatively on individuals' quality of life and behaviour change efforts. Increased sensitivity to others' negative feedback might play a role in the maintenance of these difficulties and could be addressed in psychological interventions. We conducted a systematic review of interpersonal difficulties in individuals with obesity, across the lifespan. We investigated early interpersonal adversity (i.e. frequency of teasing/bullying), perceived interpersonal stress and quality of social life, based on a rejection sensitivity model. The databases PubMed, Web of Knowledge and AGRIS, Embase, Medline and PsychINFO were searched for published peer-reviewed journal articles (1980-June 2018). Thirty-two studies met inclusion criteria. Results from the meta-analyses (n = 16 studies) indicated that overweight/obese individuals reported more frequent experiences of teasing/bullying, greater interpersonal stress and poorer quality of social life than healthy weight individuals. Findings in the systematic review aligned to this evidence. Psychological interventions targeting increased sensitivity to negative interpersonal feedback could improve interpersonal functioning and, in turn, eating behaviours in individuals with obesity.

Albano|Gaia|G|
Rowlands|Katie|K|
Baciadonna|Luigi|L|
Coco|Gianluca Lo|GL|
Cardi|Valentina|V|

Overweight
Binge eating disorder
Interactions
Isolation


A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients with EGFR-mutated, MET-amplified advanced non-small-cell lung cancer.

Abstract: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended first-line treatments in EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC). However, acquired resistance (e.g. MET amplification) is frequently observed. Savolitinib (volitinib, HMPL-504, AZD6094) is an oral, potent, and highly selective MET-TKI. In this phase Ib, open-label, multicenter study, we enrolled Chinese patients with EGFRm advanced NSCLC, whose disease progressed following prior EGFR-TKI treatment. In the safety run-in, patients received savolitinib 600 or 800 mg plus gefitinib 250 mg orally once daily, and dose-limiting toxicities were recorded. In the expansion phase, patients with MET amplification received savolitinib plus gefitinib. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity. Thirteen patients were enrolled in the safety phase (median age 52 years, 46% female) and 51 enrolled in the expansion phase (median age 61 years, 67% female). No dose-limiting toxicities were reported in either dose group during the safety run-in. Adverse events of grade ≥ 3 in the safety run-in and expansion phases (n = 57) were reported in 21 (37%) patients. The most frequently reported adverse events (all grades) were: vomiting (n = 26, 46%), nausea (n = 23, 40%), increased aspartate aminotransferase (n = 22, 39%). Of four deaths, none were treatment-related. The objective response rates in EGFR T790M-negative, -positive, and -unknown patients were 52% (12/23), 9% (2/23), and 40% (2/5), respectively. Savolitinib 600 mg plus gefitinib 250 mg once daily had an acceptable safety profile and demonstrated promising antitumor activity in EGFRm, MET-amplified advanced NSCLC patients who had disease progression on EGFR-TKIs. NCT02374645, Date of registration: March 2nd 2015.

Savolitinib Gefitinib EGFR-TKI EGFRm NSCLC MET


Breast oedema following free flap breast reconstruction.

Abstract:
OBJECTIVES
Breast oedema causes significant morbidity and is historically difficult to quantify. The aim of this study was to identify changes in breast tissue water content from pre-operative levels in the native breast to post-operative levels in mastectomy skin flaps and free flaps in the reconstructed breast.

MATERIALS AND METHODS
One hundred patients undergoing unilateral mastectomy and immediate free flap breast reconstruction were examined pre-operatively and at three post-operative appointments. A validated moisture meter was used to record dermal water percentages of each breast quadrant and areola in both breasts pre-operatively, then four quadrants of both breasts plus the unaffected areola and free flap at each post-operative review.

RESULTS AND CONCLUSION
Native skin of the reconstructed breast showed significant, persistent increase in MWC from 45.6% ± 0.5% to 72.8% ± 0.9% at 1st follow up (p < 0.001), decreasing only to 67.6% ± 0.8% by 3rd follow up. There was a marked difference (p < 0.001) in the mean water content (MWC) of the initial free flap (39.7% ± 0.6%) compared to 61.8% ± 1.7% at 1st follow up, then 55.1% ± 1.4% at 2nd and 53.7% ± 1.3% at 3rd follow ups. The unaffected breast showed a small but significant increase in MWC of all quadrants at subsequent follow up (greatest difference 3.1% at 1st follow up). This patient group demonstrates significant, persistent oedema of the reconstructed breast, which can be monitored using a non-invasive moisture meter.

Greenhowe|Jennifer|J|
Stephen|Christopher|C|
McClymont|Liusaidh|L|
Munnoch|D Alex|DA|

Breast oedema
Moisture meter
Flap reconstruction


Environmentally persistent free radicals: Occurrence, formation mechanisms and implications.

Abstract: Environmentally persistent free radicals (EPFRs) are defined as organic free radicals stabilized on or inside particles. They are persistent because of the protection by the particles and show significant toxicity to organisms. Increasing research interests have been attracted to study the potential environmental implications of EPFRs. Because of their different physical forms from conventional contaminants, it is not applicable to use the commonly used technique and strategy to predict and assess the behavior and risks of EPFRs. Current studies on EPFRs are scattered and not systematic enough to draw clear conclusions. Therefore, this review is organized to critically discuss the current research progress on EPFRs, highlighting their occurrence and transport, generation mechanisms, as well as their environmental implications (including both toxicity and reactivity). EPFR formation and stabilization as affected by the precursors and environmental factors are useful breakthrough to understand their formation mechanisms. To better understand the major differences between EPFRs and common contaminants, we identified the unique processes and/or mechanisms related to EPFRs. The knowledge gaps will be also addressed to highlight the future research while summarizing the research progress. Quantitative analysis of the interactions between organic contaminants and EPFRs will greatly improve the predictive accuracy of the multimedia environmental fate models. In addition, the health risks will be better evaluated when considering the toxicity contributed by EFPRs.

Pan|Bo|B| Li|Hao|H| Lang|Di|D| Xing|Baoshan|B|

D004784:Environmental Monitoring
D004785:Environmental Pollutants
D005609:Free Radicals
D006801:Humans

Organic contaminants
Degradation
Humic substances
Stabilized free radicals
Transition metals


Functional profiling of microtumors to identify cancer associated fibroblast-derived drug targets.

Abstract: Recent advances in chemotherapeutics highlight the importance of molecularly-targeted perturbagens. Although these therapies typically address dysregulated cancer cell proteins, there are increasing therapeutic modalities that take into consideration cancer cell-extrinsic factors. Targeting components of tumor stroma such as vascular or immune cells has been shown to represent an efficacious approach in cancer treatment. Cancer-associated fibroblasts (CAFs) exemplify an important stromal component that can be exploited in targeted therapeutics, though their employment in drug discovery campaigns has been relatively minimal due to technical logistics in assaying for CAF-tumor interactions. Here we report a 3-dimensional multi-culture tumor:CAF spheroid phenotypic screening platform that can be applied to high-content drug discovery initiatives. Using a functional genomics approach we systematically profiled 1,024 candidate genes for CAF-intrinsic anti-spheroid activity; identifying several CAF genes important for development and maintenance of tumor:CAF co-culture spheroids. Along with previously reported genes such as WNT, we identify CAF-derived targets such as ARAF and COL3A1 upon which the tumor compartment depends for spheroid development. Specifically, we highlight the G-protein-coupled receptor OGR1 as a unique CAF-specific protein that may represent an attractive drug target for treating colorectal cancer. In vivo, murine colon tumor implants in OGR1 knockout mice displayed delayed tumor growth compared to tumors implanted in wild type littermate controls. These findings demonstrate a robust microphysiological screening approach for identifying new CAF targets that may be applied to drug discovery efforts.

Horman|Shane R|SR|
To|Jeremy|J|
Lamb|John|J|
Zoll|Jocelyn H|JH|
Leonetti|Nicole|N|
Tu|Buu|B|
Moran|Rita|R|
Newlin|Robbin|R|
Walker|John R|JR|
Orth|Anthony P|AP|


BORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer.

Abstract: Cancer germline (CG) genes are normally expressed in germ cells and aberrantly expressed in a variety of cancers; their immunogenicity has led to the widespread development of cancer vaccines targeting these antigens. BORIS/CTCFL is an autosomal CG antigen and promising cancer vaccine target. BORIS is the only known paralog of CTCF, a gene intimately involved in genomic imprinting, chromatin insulation, and nuclear regulation. We have previously shown that BORIS is expressed in epithelial ovarian cancer (EOC) and that its expression coincides with promoter and global DNA hypomethylation. Recently, 23 different BORIS mRNA variants have been described, and have been functionally grouped into six BORIS isoform families (sf1-sf6). In the present study, we have characterized the expression of BORIS isoform families in normal ovary (NO) and EOC, the latter of which were selected to include two groups with widely varying global DNA methylation status. We find selective expression of BORIS isoform families in NO, which becomes altered in EOC, primarily by the activation of BORIS sf1 in EOC. When comparing EOC samples based on methylation status, we find that BORIS sf1 and sf2 isoform families are selectively activated in globally hypomethylated tumors. In contrast, CTCF is downregulated in EOC, and the ratio of BORIS sf1, sf2, and sf6 isoform families as a function of CTCF is elevated in hypomethylated tumors. Finally, the expression of all BORIS isoform families was induced to varying extents by epigenetic modulatory drugs in EOC cell lines, particularly when DNMT and HDAC inhibitors were used in combination.

Link|Petra A|PA|
Zhang|Wa|W|
Odunsi|Kunle|K|
Karpf|Adam R|AR|

D015972:Gene Expression Regulation, Neoplastic

D020084:Long Interspersed Nucleotide Elements

D009375:Neoplasms, Glandular and Epithelial

BORIS
epigenetics
ovarian cancer
CTCF
DNA methylation


A Comparison of Inductive Sensors in the Characterization of Partial Discharges and Electrical Noise Using the Chromatic Technique.

Abstract: Partial discharges (PDs) are one of the most important classes of ageing processes that occur within electrical insulation. PD detection is a standardized technique to qualify the state of the insulation in electric assets such as machines and power cables. Generally, the classical phase-resolved partial discharge (PRPD) patterns are used to perform the identification of the type of PD source when they are related to a specific degradation process and when the electrical noise level is low compared to the magnitudes of the PD signals. However, in practical applications such as measurements carried out in the field or in industrial environments, several PD sources and large noise signals are usually present simultaneously. In this study, three different inductive sensors have been used to evaluate and compare their performance in the detection and separation of multiple PD sources by applying the chromatic technique to each of the measured signals.

inductive sensors
chromatic technique
partial discharges (PDs)
condition monitoring
electrical insulation condition


Seizure modulation by sleep and sleep state.

Abstract: Sleep is a dynamic process, during which the electrical rhythms of the brain orchestrate a complicated progression of changing frequencies, patterns and connectivity. Each stage of sleep is different electrophysiologically from wakefulness, and from other sleep stages. It should be no surprise, then, that the various sleep states influence the origin, suppression, and spread of seizures, and that different seizure types are affected in individual (and sometimes contradictory) ways. While much of the electrical symphony that occurs in both normal and epileptic brains is incompletely understood, at the basic level some interesting and often clinically important influences of the various sleep states have been identified. While interictal epileptiform activity is not a seizure, these markers of epilepsy are affected by sleep. Both initiation and propagation of various seizure types are affected by sleep, and these are discussed separately. Finally, the relationship between sleep and epilepsy is clearly reciprocal, and the final sections will explore the changes in sleep that seizures and antiepileptic drugs can induce.

Sleep
Epilepsy
Anticonvulsant drug
Sleep disorder


Integrating docking and molecular dynamics approaches for a series of proline-based 2,5-diketopiperazines as novel αβ-tubulin inhibitors.

Abstract: In this work, docking tools were utilized in order to study the binding properties of more than five hundred of proline-based 2,5-diketopiperazine in the binding site of αβ-tubulin. Results revealed that 20 compounds among them showed lower binding energies in comparison with Tryprostatin-A, a well known tubulin inhibitor and therefore could be potential inhibitors of tubulin. However, the precise evaluation of binding poses represents the similar binding modes for all of these compounds and Tryprostatin-A. Finally, the best docked complex was subjected to a 25 ns molecular dynamics simulation to further validate the proposed binding mode of this compound.

Fani|Najmeh|N| Bordbar|Abdol-Khalegh|AK| Ghayeb|Yousef|Y| Sepehri|Saghi|S|

D020816:Amino Acid Motifs
D001665:Binding Sites
D054659:Diketopiperazines
D006801:Humans
D006860:Hydrogen Bonding
D026121:Indole Alkaloids
D062105:Molecular Docking Simulation
D056004:Molecular Dynamics Simulation
D008969:Molecular Sequence Data
D010879:Piperazines
D011392:Proline
D011485:Protein Binding
D017510:Protein Folding
D017433:Protein Structure, Secondary
D017434:Protein Structure, Tertiary
D021122:Protein Subunits
D055672:Static Electricity
D013816:Thermodynamics
D014404:Tubulin
D050257:Tubulin Modulators

αβ-tubulin
molecular dynamics simulation
Tryprostatin
diketopiperazine
molecular docking


Traditional Chinese medicine in cardiovascular drug discovery.

Abstract: In this virtual special issue entitled "Traditional Chinese Medicine in Cardiovascular Drug Discovery", a collection of 18 basic research, clinical research and review articles was published to highlight the therapeutic potential of traditional Chinese medicine (TCM) and their bioactive components in treating atherosclerosis, coronary artery disease, ischemic cardiomyopathy, heart failure and beyond.

D000818:Animals
D002317:Cardiovascular Agents
D055808:Drug Discovery
D004365:Drugs, Chinese Herbal
D006801:Humans
D008516:Medicine, Chinese Traditional

Traditional Chinese medicine
Drug discovery
Therapeutics
Cardiovascular disease


Mesenteric tissue oxygenation status on the development of necrotizing enterocolitis.

Abstract:
BACKGROUND
Necrotizing enterocolitis (NEC) is an important cause of morbidity and mortality in preterm infants. There is limited data about the role of mesenteric oxygenation status during the first enteral feeding. Therefore, the aim of this study was to determine the mesenteric tissue oxygen saturation values before, during and after the first enteral feeding and to evaluate the effect of these values on the development of NEC in preterm infants.

METHODS
A total of 105 preterm babies with ≤ 32 gestational weeks were included in this prospective study. The continuous monitoring of the mesenteric tissue oxygenation status was performed before, during and 3 hours after the first feeding by near-infrared spectroscopy (NIRS).

RESULTS
The mean gestational week and birth weight of the study group were 28.8±2.1 weeks, and 1215±387 g, respectively. The first enteral feeding was started at 2.4±1.4 days with breast milk in 85% of infants. A total of 12 infants (11.4%) developed NEC (66% stage II, 34% stage III). The mean mesenteric tissue oxygen saturation levels of the infants that developed NEC were significantly lower both before and one hour after feeding (56.1±3.4 vs. 34±8.8, and 47.4±3.3 vs 37.8±10.9, respectively) compared with infants that did not develop NEC.

CONCLUSIONS
Lower mesenteric tissue oxygenation values measured before, and one hour after enteral feeding was associated with NEC development. We suggest that lower mesenteric tissue oxygenation during continuous monitoring of first enteral feeding may be used to predict NEC development during follow-up.

Özkan|Hilal|H|
Çetinkaya|Merih|M|
Dorum|Bayram Ali|BA|
Köksal|Nilgün|N|

necrotizing enterocolitis
enteral feeding
near-infrared spectroscopy
NICU
premature


Factors influencing long-term heart failure mortality in patients with obstructive hypertrophic cardiomyopathy in Western Sweden: probable dose-related protection from beta-blocker therapy.

Abstract:
Objective
In order to avoid effects of referral bias, we assessed risk factors for disease-related mortality in a geographical cohort of patients with hypertrophic obstructive cardiomyopathy (HOCM), and any therapy effect on survival.

Methods
Diagnostic databases in 10 hospitals in the West Götaland Region yielded 251 adult patients with HOCM (128 male, 123 female). Case notes were reviewed for clinical data and ECG and ultrasound findings. Beta-blockers were used in 71.3% of patients from diagnosis (median metoprolol-equivalent dose of 125 mg/day), and at latest follow-up in 86.1%; 121 patients had medical therapy alone, 88 short atrioventricular delay pacing and 42 surgical myectomy. Mean follow-up was 14.4±8.9 (mean±SD) years. Primary endpoint was disease-related death, and secondary endpoint heart failure deaths.

Results
There were 65 primary endpoint events. Independent risk factors for disease-related death on multivariate Cox hazard regression were: female sex (p=0.005), age at diagnosis (p<0.001), outflow gradient ≥50 mm Hg at diagnosis (p=0.036) and at follow-up (p=0.001). Heart failure caused 62% of deaths, and sudden cardiac death 17%. Late independent predictors of heart failure death were: female sex (p=0.003), outflow gradient ≥50 mm Hg at latest follow-up (p=0.032), verapamil/diltiazem therapy (p=0.012) and coexisting hypertension (p=0.031), but not other comorbidities. Neither myectomy nor pacing modified survival, but early and maintained beta-blocker therapy was associated with dose-dependent reduction in disease-related mortality in the multivariate model (p=0.028), and final dose was also associated with reduced heart failure mortality (p=0.008). Kaplan-Meier survival curves analysed in initial dose bands of 0-74, 75-149 and ≥150 mg metoprolol/day showed 10-year freedom from disease-related deaths of 83.1%, 90.7% and 97.0%, respectively (ptrend=0.00008). Even after successful relief of outflow obstruction by intervention, there was survival benefit of metoprolol doses ≥100 mg/day (p=0.01).

Conclusions
In population-based HOCM cohorts heart failure is a dominant cause of death and on multivariate analysis beta-blocker therapy was associated with a dose-dependent cardioprotective effect on total, disease-related as well as heart failure-related mortality.

heart failure
mortality
beta-blockers
risk factors
hypertrophic obstructive cardiomyopathy
metoprolol


Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized, double-blind, placebo-controlled studies in Japanese patients with restless legs syndrome.

Abstract:
OBJECTIVE
Restless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.

METHODS
We combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.

RESULTS
The post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m2) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.

CONCLUSIONS
Our results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.

Inoue|Yuichi|Y| Hirata|Koichi|K| Hoshino|Yuya|Y| Yamaguchi|Yusuke|Y|

Gabapentin enacarbil
Japanese
Restless legs syndrome
Placebo response
Treatment response


Prospective audit of complications after ultrasonography-guided percutaneous nephrostomy for upper urinary tract obstruction using modified Clavien classification system.

Abstract:
Introduction
Percutaneous nephrostomy (PCN) is a commonly performed intervention in urology for various benign and malignant conditions causing upper urinary tract obstruction. We present a prospective audit of complications of ultrasonography (USG) guided PCN using modified Clavien classification system (mCCS).

Methods
The data were prospectively collected for 368 PCN performed in 344 patients from June 2015 to January 2017, for various benign and malignant diseases causing upper urinary tract obstruction. Patients were followed for 1 month, and complications arisen of PCN were noted.

Results
PCN was successful in 356 renal units. The 12 patients in which PCN failed was due to minimal pelvicalyceal dilatation and PCN was successfully performed after 48 h by a senior urologist. 207 patients had malignant disease and 161 patients had benign condition. Most common malignant disease was carcinoma cervix. 238 were noninfected while 130 had infected renal units. 62 (16.84%) patients had Grade I (self-limiting hematuria/cot/debris/fever). 37 (10.0%) patients had Grade II (7 - transfusion and 30 - urinary tract infection). 34 (9.2%) had Grade III a (repositioning/change/reinsertion of PCN tube under local anesthesia) and 4 (1.1%) had Grade III b (repositioning under anesthesia). 8 (2.2%) Grade IV a (Sepsis), 0 Grade IV b, and 0 Grade V complications were observed.

Conclusion
USG-guided PCN is a safe, minimally invasive, and effective procedure for upper urinary tract diversion with a low rate of morbidity. Individual complications are within the threshold limits set by the American College of Radiology, the Society of Interventional Radiology. mCCS is well applicable and easily reproducible tool for reporting the complications of PCN.

Kumar|Sunil|S|
Dutt|Uma Kant|UK|
Singh|Suresh|S|
Dorairajan|L N|LN|
Sreerag|K S|KS|
Zaphu|Tepukiel|T|
Manikandan|R|R|

complications
percutaneous nephrostomy
Clavien–Dindo classification
ultrasound guidance


Impact of letrozole versus clomiphene citrate on endometrial receptivity in Iraqi women with polycystic ovarian syndrome.

Abstract:
WHAT IS KNOWN AND OBJECTIVES
Letrozole is widely known for its use as an ovulation inductor. This study aims to investigate the effects of letrozole and clomiphene citrate in females with polycystic ovarian syndrome.

METHODS
This is a randomized non-blinded controlled trial study that included 80 infertile females with polycystic ovarian syndrome receiving a standard dose of either clomiphene citrate or letrozole on day 2 of the cycle. An ultrasound was done to examine growth of the follicle, endometrial thickness on days 12-13, and a Doppler study to measure resistance index (RI), pulsatility index and ratio of systolic/diastolic velocity.

RESULTS AND DISCUSSION
The mean levels of dominant follicle and oestradiol were significantly higher in the clomiphene citrate group than in the letrozole group. The letrozole group had a significantly greater endometrial thickness than the clomiphene citrate group. The resistance index and pulsatility index were lower in the letrozole group and in pregnant women than in the clomiphene citrate group and the non-pregnant group.

WHAT IS NEW AND CONCLUSION
The use of letrozole for ovulation induction in polycystic ovarian syndrome patients has a better effect on endometrial receptivity markers when compared to clomiphene citrate.

letrozole
clomiphene citrate
polycystic ovarian syndrome
resistance index
pulsatility index
vascular endothelium growth factor


Cathepsin D in a murine model of frontotemporal dementia with Parkinsonism-linked to chromosome 17.

Abstract: Tauopathies, such as Alzheimer's disease (AD) and Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), are characterized by tau accumulation. This accumulation could result from alterations in tau degradation by either the ubiquitin-proteasome system or the autophagy-lysosomal pathway. To analyze a possible alteration of the autophagy-lysosomal pathway in transgenic mice expressing human tau with three FTDP-17 missense mutations (TauVLW mice), we studied the lysosomal enzyme Cathepsin D. The hippocampi of TauVLW mice, where the human mutant tau accumulates, showed both increased Cathepsin D and partial colocalization of Cathepsin D with human mutant tau. At the ultrastructural level, some multivesicular bodies showed human mutant tau-immunopositive vesicles. This finding could provide insights into the molecular mechanisms of tau degradation in human tauopathies.

D015971:Gene Expression Regulation, Enzymologic

Cathepsin D
FTDP-17
lysosomal system
mutated tau


A single amino acid substitution in isozyme GST mu in Triclabendazole resistant Fasciola hepatica (Sligo strain) can substantially influence the manifestation of anthelmintic resistance.

Abstract: The helminth parasite Fasciola hepatica causes fascioliasis in human and domestic ruminants. Economic losses due to this infection are estimated in U$S 2000-3000 million yearly. The most common method of control is the use of anthelmintic drugs. However, there is an increased concern about the growing appearance of F. hepatica resistance to Triclabendazole (TCBZ), an anthelmintic with activity over adult and young flukes. F. hepatica has eight Glutathione S-Transferase (GST) isozymes, which are enzymes involved in the detoxification of a wide range of substrates through chemical conjugation with glutathione. In the present work we identified and characterized the GST mu gene isolated from the TCBZ-susceptible and TCBZ-resistant F. hepatica strains. Total RNA was transcribed into cDNA by reverse transcription and a 657 bp amplicon corresponding to the GST mu gene was obtained. The comparative genetic analysis of the GST mu gene of the TCBZ susceptible strain (Cullompton) and TCBZ resistant strain (Sligo) showed three nucleotide changes and one amino acid change at position 143 in the GST mu isozyme of the TCBZ-resistant strain. These results have potential relevance as they contribute better understand the mechanisms that generate resistance to anthelmintics.

Fernández|V|V| Estein|S|S| Ortiz|P|P| Luchessi|P|P| Solana|V|V| Solana|H|H|

D020133:Reverse Transcriptase Polymerase Chain Reaction

Isozyme
Triclabendazole
Fasciola hepatica
Glutathione S-Transferases mu


Engineering low phorbol ester Jatropha curcas seed by intercepting casbene biosynthesis.

Abstract: Casbene is a precursor to phorbol esters and down-regulating casbene synthase effectively reduces phorbol ester biosynthesis. Seed-specific reduction of phorbol ester (PE) helps develop Jatropha seed cake for animal nutrition. Phorbol esters (PEs) are diterpenoids present in some Euphorbiaceae family members like Jatropha curcas L. (Jatropha), a tropical shrub yielding high-quality oil suitable as feedstock for biodiesel and bio jet fuel. Jatropha seed contains up to 40 % of oil and can produce oil together with cake containing high-quality proteins. However, skin-irritating and cancer-promoting PEs make Jatropha cake meal unsuitable for animal nutrition and also raise some safety and environmental concerns on its planting and processing. Two casbene synthase gene (JcCASA163 and JcCASD168) homologues were cloned from Jatropha genome and both genes were highly expressed during seed development. In vitro functional analysis proved casbene synthase activity of JcCASA163 in converting geranylgeranyl diphosphate into casbene which has been speculated to be the precursor to PEs. A seed-specific promoter driving inverted repeats for RNAi interference targeting at either JcCASA163 or both genes could effectively down-regulate casbene synthase gene expression with concurrent marked reduction of PE level (by as much as 85 %) in seeds with no pleiotropic effects observed. Such engineered low PE in seed was heritable and co-segregated with the transgene. Our work implicated casbene synthase in Jatropha PE biosynthesis and provided evidence for casbene being the precursor for PEs. The success in reducing seed PE content through down-regulation of casbene synthase demonstrates the feasibility of intercepting PE biosynthesis in Jatropha seed to help address safety concerns on Jatropha plantation and seed processing and facilitate use of its seed protein for animal nutrition.

D018506:Gene Expression Regulation, Plant

Phorbol ester
Jatropha curcas
Casbene synthase
Animal nutrition
Detoxification
RNAi gene silencing


The Microstructure, Electric, Optical and Photovoltaic Properties of BiFeO3 Thin Films Prepared by Low Temperature Sol⁻Gel Method.

Abstract: Ferroelectrics have recently attracted attention as a candidate class of materials for use in photovoltaic devices due to their abnormal photovoltaic effect. However, the current reported efficiency is still low. Hence, it is urgent to develop narrow-band gap ferroelectric materials with strong ferroelectricity by low-temperature synthesis. In this paper, the perovskite bismuth ferrite BiFeO3 (BFO) thin films were fabricated on SnO2: F (FTO) substrates by the sol-gel method and they were rapidly annealed at 450, 500 and 550 °C, respectively. The microstructure and the chemical state's evolution with annealing temperature were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS), and the relationship between the microstructure and electric, optical and photovoltaic properties were studied. The XRD, SEM and Raman results show that a pure phase BFO film with good crystallinity is obtained at a low annealing temperature of 450 °C. As the annealing temperature increases, the film becomes more uniform and has an improved crystallinity. The XPS results show that the Fe3+/Fe2+ ratio increases and the ratio of oxygen vacancies/lattice oxygen decreases with increasing annealing temperature, which results in the leakage current gradually being reduced. The band gap is reduced from 2.68 to 2.51 eV due to better crystallinity. An enhanced photovoltaic effect is observed in a 550 °C annealed BFO film with a short circuit current of 4.58 mA/cm2 and an open circuit voltage of 0.15 V, respectively.

Wang|Jiaxi|J|0000-0002-2016-1747 Luo|Li|L|0000-0001-7975-0012 Han|Chunlong|C| Yun|Rui|R| Tang|Xingui|X|0000-0001-6429-2098 Zhu|Yanjuan|Y| Nie|Zhaogang|Z| Zhao|Weiren|W| Feng|Zhechuan|Z|

photovoltaic
bismuth ferrite
sol–gel method


The lncRNA VPS9D1-AS1 Promotes Hepatocellular Carcinoma Cell Cycle Progression by Regulating the HuR/CDK4 Axis.

Abstract: Long noncoding RNAs (lncRNAs) represent promising therapeutic targets associated with hepatocellular carcinoma (HCC). lncRNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) regulates colon and prostate cancer, but its relevance in HCC remains to be clarified. Using microarray data from the NCBI Gene Expression Omnibus (GEO) database (GSE65485) and The Cancer Genome Atlas (TCGA) database, VPS9D1-AS1 expression in HCC and normal liver tissue sample HCC were compared. Relative lncRNA expression was also measured through real-time quantitative PCR (qPCR) in 80 pairs of HCC tumor and paracancerous tissues and in human HCC cell lines. VPS9D1-AS1 knockdown was achieved by transfecting these HCC cells with a specific siRNA construct in vitro, and the proliferation of these cells was quantified through cell proliferation assays and colony formation assays, while flow cytometry was employed to assess their cell cycle progression. The role of the VPS9D1-AS1 lncRNA as a regulator of HCC tumorigenesis was also assessed in vivo by subcutaneously implanting BALB/c nude mice with HepG2 cells stably expressing either sh-VPS9D1-AS1 or a control shRNA construct. Mechanistic analyses were additionally conducted by examining in vitro CDK4 and HuR expression through western blotting and qPCR. VPS9D1-AS1 expression was significantly increased in HCC tissues in the analyzed databases and our independent tissue samples. Elevated VPS9D1-AS1 expression was related to larger tumor size and more advanced tumor, node, metastasis (TNM) stage, and HCC patients expressing higher levels of this lncRNA exhibited poorer survival outcomes. Knocking down VPS9D1-AS1 impaired the proliferative and colony formation activity of HepG2 cells while promoting their apoptotic death. Consistently, VPS9D1-AS1 silencing suppressed HCC tumor growth in vivo. Mechanistically, VPS9D1-AS1 was able to bind to the HuR protein and thereby influence the stability and expression of the CDK4 mRNA, thus impacting HCC cell proliferation. The VPS9D1-AS1/HuR/CDK4 signaling axis regulates HCC tumor cell oncogenic activity, highlighting this pathway as a promising therapeutic target.

Zhou|Ning|N| Li|Sheng|S| Wu|Deming|D| Zhang|Fan|F| Tang|Futian|F| Li|Yumin|Y|0000-0001-5571-6346


Tracking the Rules of Transmission and Introgression with Networks.

Abstract: Understanding how an animal organism and its gut microbes form an integrated biological organization, known as a holobiont, is becoming a central issue in biological studies. Such an organization inevitably involves a complex web of transmission processes that occur on different scales in time and space, across microbes and hosts. Network-based models are introduced in this chapter to tackle aspects of this complexity and to better take into account vertical and horizontal dimensions of transmission. Two types of network-based models are presented, sequence similarity networks and bipartite graphs. One interest of these networks is that they can consider a rich diversity of important players in microbial evolution that are usually excluded from evolutionary studies, like plasmids and viruses. These methods bring forward the notion of "gene externalization," which is defined as the presence of redundant copies of prokaryotic genes on mobile genetic elements (MGEs), and therefore emphasizes a related although distinct process from lateral gene transfer between microbial cells. This chapter introduces guidelines to the construction of these networks, reviews their analysis, and illustrates their possible biological interpretations and uses. The application to human gut microbiomes shows that sequences present in a higher diversity of MGEs have both biased functions and a broader microbial and human host range. These results suggest that an "externalized gut metagenome" is partly common to humans and benefits the gut microbial community. We conclude that testing relationships between microbial genes, microbes, and their animal hosts, using network-based methods, could help to unravel additional mechanisms of transmission in holobionts.

Vigliotti|Chloé|C| Bicep|Cédric|C| Bapteste|Eric|E| Lopez|Philippe|P| Corel|Eduardo|E|

networks
similarity networks
bipartite graphs
evolution
microbiome
metagenomes
graph theory


Preoperative botulinum toxin A injection in complex abdominal wall reconstruction- a propensity-scored matched study.

Abstract:
INTRODUCTION
Fascial closure during complex abdominal wall reconstruction (AWR) improves recurrence and wound infection rates. To facilitate fascial closure in massive ventral hernias preoperative Botulinum Toxin A (BTA) injection can be used.

METHODS
2:1 propensity-scored matching of patients undergoing AWR with and without BTA was performed based on BMI, defect width, and loss of domain using CT-volumetric analysis.

RESULTS
145 patients without BTA and 75 with BTA were comparable on hernia size (240vs251cm2, p = 0.589) and hernia volume (1405vs1672cm3, p = 0.243). Patients with BTA had higher wound class (CDC≥3 37%vs13%, p < 0.001). Patients with BTA had a higher fascial closure rate (92%vs81%, p = 0.036), received more components separation (61%vs47%, p = 0.042), lower wound infection rate (12%vs26%,p = 0.019) and comparable recurrence rates (9%vs12%, p = 0.589). Recurrences occurred more often without complete fascial closure compared to patients with (33%vs7%, p < 0.001).

CONCLUSION
In patients with massive ventral hernias and severe loss of domain, preoperative BTA-injection improves fascial closure rates during AWR.

Deerenberg|Eva Barbara|EB|
Shao|Jenny Meng|JM|
Elhage|Sharbel Adib|SA|
Lopez|Robert|R|
Ayuso|Sullivan Armando|SA|
Augenstein|Vedra Abdomerovic|VA|
Heniford|B Todd|BT|

D058107:Abdominal Wound Closure Techniques

Botulinum toxin a
Complex abdominal wall reconstruction
Recurrence
Ventral
Hernia
Incisional


A new system for classifying accessory canal morphology.

Abstract: Thorough knowledge of anatomical complexities of the root canal system has a direct impact on the effectiveness of canal preparation and filling, and is an essential prerequisite for successful root canal treatment. A wide range of complex variations in root canal anatomy exists, including root canal configuration type, developmental anomalies and minor canal morphology such as accessory canals and apical deltas. Accessory canals and apical deltas have been associated with pulp disease, primary canal infection, canal reinfection and post-treatment disease. The current definitions of accessory canal anatomy are not standardized and potentially confusing. Given their role in endodontic disease and their impact on treatment outcomes, there is a need to have a simple classification of their anatomy to provide an accurate description of their position and path from the canal to the external surface of the root. The purpose of this article is to introduce a new system for classifying accessory canal morphology for use in research, clinical practice and training.

accessory canal morphology
accessory canals
classification