bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting Independence in Dementia (PRIDE): protocol for a feasibility randomised controlled trial
Authors: Shafayat Aisha , Csipke Emese , Bradshaw Lucy , Charlesworth Georgina , Day Florence , Leung Phuong , Moniz-Cook Esme , Montgomery Alan A. , Morris Steve , Mountain Gail , Ogollah Reuben , Sprange Kirsty , Yates Lauren , Orrell Martin
Published: December 2019

Background

Memory services often see people with early stage dementia who are largely independent and able to participate in community activities but who run the risk of reducing activities and social networks. PRIDE is a self-management intervention designed to promote living well and enhance independence for people with mild dementia.

This study aims to examine the feasibility of conducting a definitive randomised trial comparing the clinical and cost-effectiveness of the PRIDE intervention offered in addition to usual care or with usual care alone.

Methods/design

PRIDE is a parallel, two-arm, multicentre, feasibility, randomised controlled trial (RCT). Eligible participants aged 18 or over who have mild dementia (defined as a score of 0.5 or 1 on the Clinical Dementia Rating Scale) who can participate in the intervention and provide informed consent will be randomised (1:1) to treatment with the PRIDE intervention delivered in addition to usual care, or usual care only. Participants will be followed-up at 3 and 6 month’s post-randomisation. There will be an option for a supporter to join each participant. Each supporter will be provided with questionnaires at baseline and follow-ups at 3 to 6 months. Embedded qualitative research with both participants and supporters will explore their perspectives on the intervention investigating a range of themes including acceptability and barriers and facilitators to delivery and participation. The feasibility of conducting a full RCT associated with participant recruitment and follow-up of both conditions, intervention delivery including the recruitment, training, retention of PRIDE trained facilitators, clinical outcomes, intervention and resource use costs and the acceptability of the intervention and study related procedures will be examined.

Discussion

This study will assess whether a definitive randomised trial comparing the clinical and cost-effectiveness of whether the PRIDE intervention offered in addition to usual care is feasible in comparison to usual care alone, and if so, will provide data to inform the design and conduct of a future trial.

Trial registration

ISRCTN, ISRCTN11288961, registered on 23 October 2019, http://www.isrctn.com/ISRCTN12345678 Protocol V2.1 dated 19 June 2019.
Electronic health record nested pragmatic randomized controlled trial of a reminder system for serum lithium level monitoring in patients with mood disorder: KONOTORI study protocol
Authors: Seki Tomotsugu , Aki Morio , Kawashima Hirotsugu , Miki Tomotaka , Tanaka Shiro , Kawakami Koji , Furukawa Toshi A.
Published: December 2019

Background

The weaknesses of classical explanatory randomized controlled trials (RCTs) include limited generalizability, high cost, and time burden. Pragmatic RCTs nested within electronic health records (EHRs) can be useful to overcome such limitations. Serum lithium monitoring has often been underutilized in real-world practice in Japan. This trial aims to evaluate the effectiveness of the EHR-nested reminder system for serum lithium level monitoring in the maintenance of therapeutic lithium concentration and in the improvement of the quality of care for patients on lithium maintenance therapy.

Methods

The Kyoto Toyooka nested controlled trial of reminders (KONOTORI trial) is an EHR-nested, parallel-group, superiority, stratified, permuted block-randomized controlled trial. Screening, random allocation, reminder output, and outcome collection will be conducted automatically by the EHR-nested trial program. Patients with a mood disorder taking lithium carbonate for maintenance therapy will be randomly allocated to the two-step reminder system for serum lithium monitoring or to usual care. The primary outcome is the achievement of therapeutic serum lithium concentration between 0.4 and 1.0 mEq/L at 18 months after informed consent.

Discussion

The KONOTORI trial uses EHRs to enable the efficient conduct of a pragmatic trial of the reminder system for lithium monitoring. This may contribute to improved quality of care for patients on lithium maintenance therapy.

Trial registration

University Hospital Medical Information Network (UMIN) Clinical Trials Registry,UMIN000033633. Registered on 3 July 2018.
Effectiveness of an online self-management tool, OPERAS (an On-demand Program to EmpoweR Active Self-management), for people with rheumatoid arthritis: a research protocol
Authors: Tam Johnathan , Lacaille Diane , Liu-Ambrose Teresa , Shaw Chris , Xie Hui , Backman Catherine L. , Esdaile John M. , Miller Kimberly , Petrella Robert , Li Linda C.
Published: December 2019

Background

Active self-management is a process where patients are fully engaged in managing their health in daily life by having access to contextualized health data and tailored guidance to support a healthy lifestyle. This study aims to determine whether an e-health intervention that incorporates symptom/disease activity monitoring and physical activity counselling can improve self-management ability in patients with rheumatoid arthritis (RA).

Methods

The ‘Empowering active self-management of arthritis: Raising the bar with OPERAS (an On-demand Program to EmpoweR Active Self-management)’ project is a randomized controlled trial that uses a delayed control design. One hundred thirty-four participants with RA will be randomly assigned to start the intervention either immediately (immediate group) or 6 months later (delayed group). The intervention involves (1) use of a Fitbit-compatible web app to record and monitor their RA disease activity, symptoms, and time spent on physical activity and a Fitbit; (2) group education and individual counselling by a physiotherapist (PT); and (3) six phone calls with a PT. The primary outcome measure is self-management ability measured by the Patient Activation Measure. Secondary outcome measures include disease status, fatigue, pain, depressive symptoms, and characteristics of habitual behavior and also time spent in physical activity and sedentary activity with a wearable multi-sensor device (SenseWear Mini). After the 6-month intervention, we will interview a sample of participants to examine their experiences with the intervention.

Discussion

The results of this study will help to determine whether this technology-enhanced self-management intervention improves self-management ability and health outcomes for people living with RA. A limitation of this study is that participants will need to self-report their symptoms, disease status, and treatment use through questionnaires on the OPERAS web app. The user-friendly interface, reminder emails from the research staff, and tailored guidance from PTs will encourage participants to actively engage with the app.

Trial registration

Date of last update in ClinicalTrials.gov: January 2, 2019. ClinicalTrials.gov Identifier: NCT03404245.
Vaccination of mice with a recombinant novel cathepsin B inhibits Trichinella spiralis development, reduces the fecundity and worm burden
Authors: Cui Jing , Han Yue , Yue Xin , Liu Fang , Song Yan Yan , Yan Shu Wei , Lei Jun Jun , Zhang Xi , Jiang Peng , Wang Zhong Quan
Published: December 2019

Background

Trichinella spiralis is a major zoonotic tissue-dwelling nematode, which is a public health concern and a serious hazard to animal food safety. It is necessary to exploit an anti-Trichinella vaccine to interrupt the transmission of Trichinella infection among animals and from animals to humans. The purpose of the present study was to characterize the novel T. spiralis cathepsin B (TsCB) and to evaluate the immune protection elicited by immunization with recombinant TsCB (rTsCB).

Methods

The complete cDNA sequences of the TsCB gene were cloned, expressed and purified. The antigenicity of rTsCB was investigated by western blot analysis and ELISA. Transcription and expression of TsCB at various T. spiralis life-cycle stages were analyzed by RT-PCR and indirect immunofluorescent assay (IIFA). The mice were subcutaneously immunized with rTsCB, and serum level of TsCB-specific IgG (IgG1 and IgG2a) and IgE antibodies were assayed by ELISA. Immune protection elicited by vaccination with rTsCB was investigated.

Results

The TsCB was transcribed and expressed in four T. spiralis life-cycle stages (adult worm, AW; newborn larvae, NBL; muscle larvae, ML; and intestinal infective L1 larvae), it was primarily located in the cuticle and stichosome of the parasitic nematode. Vaccination of mice with rTsCB produced a prominent antibody response (high level of specific IgG and IgE) and immune protection, as demonstrated by a 52.81% AW burden reduction of intestines at six days post-infection (dpi) and a 50.90% ML burden reduction of muscles at 35 dpi after oral larva challenge. The TsCB-specific antibody response elicited by immunization with rTsCB also impeded intestinal worm growth and decreased the female fecundity.

Conclusions

TsCB might be considered as a novel potential molecular target to develop vaccines against T. spiralis infection.
LNA-anti-miR-150 ameliorated kidney injury of lupus nephritis by inhibiting renal fibrosis and macrophage infiltration
Authors: Luan Junjun , Fu Jingqi , Chen Chengjie , Jiao Congcong , Kong Weiwei , Zhang Yixiao , Chang Qing , Wang Yanqiu , Li Detian , Illei Gabor G. , Kopp Jeffrey B. , Pi Jingbo , Zhou Hua
Published: December 2019

Background

The prevalence of lupus nephritis (LN) remains high despite various emerging monoclonal antibodies against with targeting systemic lupus erythematosus (SLE). Renal fibrosis is the main feature of late stage LN, and novel therapeutic agents are still needed. We previously reported that microRNA (miR)-150 increases in renal biopsies of American LN patients and that miR-150 agonist promotes fibrosis in cultured kidney cells. Presently, we aim to verify whether locked nucleic acid (LNA)-anti-miR-150 can ameliorate LN in mice and to investigate its corresponding mechanisms.

Methods

We first observed natural history and renal miR-150 expression in female Fcgr2b−/− mice of a spontaneously developed LN model. We then verified miR-150 renal absorption and determined the dose of the suppressed miR-150 by subcutaneous injection of LNA-anti-miR-150 (2 and 4 mg/kg). Thirdly, we investigated the therapeutic effects of LNA-anti-miR-150 (2 mg/kg for 8 weeks) on LN mice and the corresponding mechanisms by studying fibrosis-related genes, cytokines, and kidney resident macrophages. Lastly, we detected the expression of renal miR-150 and the mechanism-associated factors in renal biopsies from new onset untreated LN patients.

Results

Fcgr2b−/− mice developed SLE indicated by positive serum autoantibodies at age 19 weeks and LN demonstrated by proteinuria at age 32 weeks. Renal miR-150 was overexpressed in LN mice compared to wild type mice. FAM-labeled LNA-anti-miR-150 was absorbed by both glomeruli and renal tubules. LNA-anti-miR-150 suppressed the elevated renal miR-150 levels in LN mice compared to the scrambled LNA without systemic toxicity. Meanwhile, serum double strand-DNA antibody, proteinuria, and kidney injury were ameliorated. Importantly, the elevated renal pro-fibrotic genes (transforming growth factor-β1, α-smooth muscle antibody, and fibronectin) and decreased anti-fibrotic gene suppressor of cytokine signal 1 were both reversed. Renal pro-inflammatory cytokines (interferon-γ, interleukin-6, and tumor necrosis factor-α) and macrophages were also decreased. In addition, the changes of renal miR-150 and associated proteins shown in LN mice were also seen in human subjects.

Conclusions

LNA-anti-miR-150 may be a promising novel therapeutic agent for LN in addition to the current emerging monoclonal antibodies, and its renal protective mechanism may be mediated by anti-fibrosis and anti-inflammation as well as reduction of the infiltrated kidney resident macrophages.
Distinct DNA methylation targets by aging and chronic inflammation: a pilot study using gastric mucosa infected with Helicobacter pylori
Authors: Yamashita Satoshi , Nanjo Sohachi , Rehnberg Emil , Iida Naoko , Takeshima Hideyuki , Ando Takayuki , Maekita Takao , Sugiyama Toshiro , Ushijima Toshikazu
Published: December 2019

Background

Aberrant DNA methylation is induced by aging and chronic inflammation in normal tissues. The induction by inflammation is widely recognized as acceleration of age-related methylation. However, few studies addressed target genomic regions and the responsible factors in a genome-wide manner. Here, we analyzed methylation targets by aging and inflammation, taking advantage of the potent methylation induction in human gastric mucosa by Helicobacter pylori infection-triggered inflammation.

Results

DNA methylation microarray analysis of 482,421 CpG probes, grouped into 270,249 genomic blocks, revealed that high levels of methylation were induced in 44,461 (16.5%) genomic blocks by inflammation, even after correction of the influence of leukocyte infiltration. A total of 61.8% of the hypermethylation was acceleration of age-related methylation while 21.6% was specific to inflammation. Regions with H3K27me3 were frequently hypermethylated both by aging and inflammation. Basal methylation levels were essential for age-related hypermethylation while even regions with little basal methylation were hypermethylated by inflammation. When limited to promoter CpG islands, being a microRNA gene and high basal methylation levels strongly enhanced hypermethylation while H3K27me3 strongly enhanced inflammation-induced hypermethylation. Inflammation was capable of overriding active transcription. In young gastric mucosae, genes with high expression and frequent mutations in gastric cancers were more frequently methylated than in old ones.

Conclusions

Methylation by inflammation was not simple acceleration of age-related methylation. Targets of aberrant DNA methylation were different between young and old gastric mucosae, and driver genes were preferentially methylated in young gastric mucosa.
Reproductive stoppage in autism spectrum disorder in a population of 2.5 million individuals
Authors: Kuja-Halkola Ralf , Larsson Henrik , Lundström Sebastian , Sandin Sven , Chizarifard Azadeh , Bölte Sven , Lichtenstein Paul , Frans Emma
Published: December 2019

Background

It has been suggested that parents of children with autism spectrum disorder (ASD) curtail their reproduction, a phenomenon known as reproductive stoppage. To investigate the presence of reproductive stoppage, we followed the reproduction in mothers of children with or without an ASD diagnosis using Swedish population-based registries.

Methods

We followed all families with first child born in 1987 or later. In total 2,521,103 children, nested within 1,270,017 mothers, were included. Exposure was presence of ASD diagnosis in earlier born siblings, and outcome was considered as (1) inter-pregnancy interval and (2) number of subsequent children.

Results

Analyses of inter-pregnancy intervals showed that the association differed across birth orders, with a lower rate of second children when first child had ASD diagnosis, but an increased rate of third and higher birth orders in families where a previous child had an ASD diagnosis. When all birth orders were simultaneously considered, families with a child with an ASD diagnosis were less likely to have another child (hazard ratio (HR), 0.79; 95% confidence interval [95% CI], 0.78–0.80). However, when adjusted for birth order, the association was close to null (HR, 0.97; 95% CI, 0.96–0.99), and after additional adjustments (maternal age, birth period, sex, paternal age, and maternal education), the association disappeared (HR, 1.00; 95% CI, 0.99–1.02). In analyses of subsequent children, after adjustment for covariates, families with an ASD diagnosis had 4% more subsequent children (rate ratio, 1.04; 95% CI, 1.03–1.05).

Limitations

The study was undertaken in a country with largely tax-funded healthcare; results may not generalize to other societies. Following the current dominating umbrella concept of ASD, we did not differentiate between the ASD sub-diagnoses; it is possible that reproductive patterns can be dependent on ASD subtypes and the severity and composition of ASD phenotypes and comorbidities.

Conclusions

This study does not support a universal reproductive stoppage effect in ASD families, when birth order and other factors are considered. Therefore, proper attention to birth order and other factors may alleviate potential bias in familial aggregation studies of ASD.
The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
Authors: Warrington Junie P. , Fan Fan , Duncan Jeremy , Cunningham Mark W. , LaMarca Babette B. , Dechend Ralf , Wallukat Gerd , Roman Richard J. , Drummond Heather A. , Granger Joey P. , Ryan Michael J.
Published: December 2019

Background

Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure.

Methods

Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry.

Results

Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content.

Conclusions

These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia.
Multilinear fractional integral operators on central Morrey spaces with variable exponent
Authors: Wang Hongbin , Xu Jingshi
Published: December 2019

In this paper, we obtain the boundedness of the multilinear fractional integral operators and their commutators on central Morrey spaces with variable exponent.
Dynamical analysis of a giving up smoking model with time delay
Authors: Zhang Zizhen , Wei Ruibin , Xia Wanjun
Published: December 2019

In this paper, we are concerned with a delayed smoking model in which the population is divided into five classes. Sufficient conditions guaranteeing the local stability and existence of Hopf bifurcation for the model are established by taking the time delay as a bifurcation parameter and employing the Routh–Hurwitz criteria. Furthermore, direction and stability of the Hopf bifurcation are investigated by applying the center manifold theorem and normal form theory. Finally, computer simulations are implemented to support the analytic results and to analyze the effects of some parameters on the dynamical behavior of the model.
High negative predictive value of 68Ga PSMA PET-CT for local lymph node metastases in high risk primary prostate cancer with histopathological correlation
Authors: Rahman Labib Ataur , Rutagengwa Damacent , Lin Peter , Lin Michael , Yap June , Lai Ken , Mancuso Pascal , Rathore Prem , Haghighi Kayvan , Gassner Paul , Wong Lee Hao , Lalak Nestor
Published: December 2019

Background

Current guidelines highlight the importance of accurate staging in the management and prognostication of high risk primary prostate cancer. Conventional radiologic imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Despite promising results, there is limited published data on the diagnostic accuracy of PSMA PET-CT to assess local nodal metastases prior to radical prostatectomy.

This study aims to assess the diagnostic efficacy of 68Ga PSMA PET-CT in local lymph node staging of high risk primary prostate cancer when compared to histopathological findings following radical prostatectomy with pelvic lymph node dissection.

Methods

We retrospectively analysed consecutive patients with high risk primary prostate cancer referred by urologists for primary staging PSMA PET-CT using a 68Ga-labeled PSMA ligand, Glu-NH-CO-NHLys-(Ahx)-[HBEDD-CC], from October 2015 to October 2017. The scans of patients who underwent radical prostatectomy with pelvic lymph node dissection were interpreted by the consensus reading of two experienced nuclear medicine physicians blinded to clinical and histopathological data. The contemporaneous records of the referring urologists were retrospectively reviewed for noteworthy unexpected PET findings that altered their personal preference for surgical management.

Results

Seventy-one patients were recruited and analysed. PSMA PET-CT showed findings compatible with local disease in 47 patients (66.2%), lymph node metastases in 10 patients (14.1%) and distant metastases in 14 patients (19.7%). Twenty-eight patients (twenty-seven of whom had local disease only) underwent surgery yielding 214 lymph nodes, all of which were negative on histopathological analysis. On a node-based analysis, 213 of 214 lymph nodes were accurately identified as negative for disease with a negative predictive value of 100%. 11 patients had unexpected PET findings contemporaneously documented by urologists to alter their preference for surgical management.

Conclusions

PSMA PET-CT appears to have a high negative predictive value for local lymph node metastases in high risk primary prostate cancer when compared to histopathological findings following radical prostatectomy with pelvic lymph node dissection.
A case of Gerstmann-Straussler-Scheinker (GSS) disease with supranuclear gaze palsy
Authors: Ufkes Nicole A. , Woodard Craig , Dale Marian L.
Published: December 2019

Background

Gerstmann-Straussler-Scheinker disease (GSS), an autosomal dominant prion disorder, usually presents as a slowly progressive cerebellar ataxia followed by later cognitive decline. We present a member of the GSS Indiana Kindred with supranuclear palsy, a less common feature in GSS.

Case presentation

A 42-year-old man presented with 12 months of progressive gait and balance difficulty. Exam was notable for ataxia and cerebellar eye movement abnormalities. Genetic testing revealed a F198S variant in the prion protein (PRNP) gene, the pathological variant of GSS associated with his family, the Indiana kindred. Eighteen months after initial presentation supranuclear palsy developed.

Conclusions

GSS is a neurodegenerative prion disease with diverse clinical presentations, and exhibits greater variability in disease phenotype compared to other inherited spongiform encephalopathies. GSS should be on the differential for patients with ataxia and supranuclear palsy, and it is important to assess both horizontal and vertical saccades and optokinetic nystagmus in patients with ataxia.
Lymphangiography and focal pleurodesis treatment of chylothorax with an aberrant thoracic duct following oesophagectomy: a case report
Authors: Ishida Tomoyuki , Kanamori Jun , Daiko Hiroyuki
Published: December 2019

Background

Management of postoperative chylothorax usually consists of nutritional regimens, pharmacological therapies such as octreotide, and surgical therapies such as ligation of thoracic duct, but a clear consensus is yet to be reached. Further, the variation of the thoracic duct makes chylothorax difficult to treat. This report describes a rare case of chylothorax with an aberrant thoracic duct that was successfully treated using focal pleurodesis through interventional radiology (IVR).

Case presentation

The patient was a 52-year-old man with chylothorax after a thoracoscopic oesophagectomy for oesophageal cancer. With conventional therapy, such as thoracostomy tube, octreotide or fibrogammin, a decrease in the amount of chyle was not achieved. Therefore, we performed lymphangiography and pleurodesis through IVR. The patient appeared to have an aberrant thoracic duct, as revealed by magnetic resonance imaging (MRI); however, after focal pleurodesis, the leak of chyle was diminished, and the patient was discharged 66 days after admission.

Conclusions

Chylothorax remains a difficult complication. Focal pleurodesis through IVR can be one of the options to treat chylothorax.
Comparing the impacts of various inputs(I + 1 & I-1) on pre-intermediate EFL learners’ Reading comprehension and Reading motivation: the case of Ahvazi learners
Authors: Namaziandost Ehsan , Nasri Mehdi , Ziafar Meisam
Published: December 2019

Considering the vital role of comprehensible input, this study attempted to compare the effects of input with various difficulty levels on Iranian EFL learners’ reading comprehension and reading motivation. To fulfil this objective, 54 Iranian pre-intermediate EFL learners were selected from two intact classes (n = 27 each). The selected participants were randomly assigned to two equal groups, namely “i + 1″ (n = 27) and “i-1″ group (n = 27). Then, the groups were pretested by a researcher-made reading comprehension test. After carrying out the pre-test, the treatment (i.e., extensive reading at different levels of difficulty) was practiced on the both groups. The participants in “i + 1″ group received reading passages beyond the current level, on the other hand, the “i-1″ group received those reading passages which were below their current level. After the instruction ended, a modified version of pre-test was conducted as posttest to determine the impacts of the treatment on the students’ reading comprehension. The obtained results indicated that there was a significant difference between the post-tests of “i + 1″ and “i-1″ groups. The findings showed that the “i + 1″ group significantly outperformed the “i-1″ group (p < .05) on the post-test. Moreover, the findings indicated that “i + 1″ group’s motivation increased after the treatment. The implications of the study suggest that interactive type of input is beneficial to develop students’ language skills.
The impact of externalized migration governance on Turkey: technocratic migration governance and the production of differentiated legal status
Authors: Üstübici Ayşen
Published: December 2019

The article highlights international dimensions of the emergence and transformation of migration policies in Turkey from the early 2000s onwards, including the context of the Syrian displacement, which made Turkey the top refugee hosting country in the world. While the transformation of migration governance in Turkey has widely been discussed, the effects of externalization on Turkey have remained focused on foreign policy and Turkey-EU relations. Only recently has the research explored the socio-legal implications of migration governance in terms of the emergence of categorizations leading to differentiated inclusion of migrant groups. The article establishes the historical and conceptual link between technocratic responses to externalization dynamics and the emergence of differentiated legal status. The article argues that measures of externalization brought a technocratic approach to migration governance. As a result, the complex, controversial aspects of the externalization process, such as the production of differentiated legal statuses amongst migrant communities with protection needs, have so far been overshadowed.
Antimutagenic components in Spatholobus suberectus Dunn against N-methyl-N-nitrosourea
Authors: Inami Keiko , Asada Yoshihisa , Harada Takumi , Okayama Yuta , Usui Noriko , Mochizuki Masataka
Published: December 2019

Background

An extract from Spatholobus suberectus (S. suberectus) Dunn has been reported to show potent antimutagenic effects against N-alkyl-N-nitrosoureas in umu screening. The aim of this study was to identify the antimutagenic components from extracts of S. suberectus against N-methyl-N-nitrosourea (MNU) in the Ames assay with Salmonella typhimurium strain TA1535 and to elucidate the antimutagenic mechanism of the flavonoids.

Results

From the ethyl acetate fraction obtained from fractionation of the methanol extract of S. suberectus Dunn, medicarpin, formononetin and isoliquiritigenin were successfully isolated through a combination of normal- and reversed-phase chromatography. Genistein and naringenin, which were already reported to be contained in S. suberectus Dunn, were also tested for their antimutagenicity towards MNU, along with formononetin, isoliquiritigenin and medicarpin. Our results demonstrated that genistein, isoliquiritigenin, medicarpin and naringenin were antimutagenic against MNU without showing cytotoxicity. MNU is reported to cause not only DNA alkylation but also induce reactive oxygen species. The hydroxyl radical scavenging capacity of the flavonoids was correlated with the antimutagenic capacity, indicating that the hydroxyl radical scavenging activity was involved in their antimutagenicity towards MNU.

Conclusions

It is important to prevent DNA damage by N-nitrosamines for cancer chemoprevention. Genistein, isoliquiritigenin, medicarpin and naringenin were demonstrated to possess an antigenotoxic effects against carcinogenic MNU due to their radical scavenging activity.
Efficacy evaluation of a cordless ultrasonic unit in achieving reduction of bacterial load within a root canal system as compared to a conventional ultrasonic unit and negative pressure irrigation
Authors: Mikulik Randall , Naji Ali , van der Hoeven Ransome , Tsesis Igor , Rosen Eyal , Jaramillo David E.
Published: December 2019

Introduction

Increase in efficacy during root canal irrigation may contribute to better treatment outcomes. This study investigated the efficacy of ultrasonic and negative pressure irrigation systems using sodium hypochlorite (NaOCl) in the reduction of bacterial load in human teeth.

One hundred thirty-one single-rooted teeth were cleaned and shaped, autoclaved, and incubated with E. faecalis. Teeth were randomly assigned to three experimental groups (n = 40) and treated in the presence of 1% sodium hypochlorite using EndoUltra cordless ultrasonic, conventional ultrasonic, and Endovac negative pressure irrigation. Syringe irrigation controls were treated with 1% sodium hypochlorite and phosphate-buffered saline via side-vented needle irrigation. All groups with NaOCl received 5% sodium thiosulfate neutralization for 5 min after treatment. Samples of root canal fluid and dentin chips were acquired from canals before and after treatment, incubated on BHI agar, and colony forming units categorized according to quantity. Wilcoxon rank-sum and Bonferroni tests were used for statistical analysis. p values less than 0.05 were considered significant.

Results

Endovac group was significantly better in eliminating bacteria from the root canals than 1% NaOCl (p = 0.006) and PBS syringe irrigation (p = 0.015). However, it was not significantly different from the two ultrasonic groups (p > 0.05). Both ultrasonic groups showed better performance than 1% NaOCl and PBS syringe irrigation, however, not statistically significant (p < 0.03). There was no significant difference between the two ultrasonic devices (p > 0.05).

Conclusion

EndoVac may be an important tool for bacterial load reduction in oval canals.
The 6-item Female Sexual Function Index (FSFI-6): factor structure, reliability, and demographic correlates among infertile women in Iran
Authors: Maroufizadeh Saman , Riazi Hedyeh , Lotfollahi Hajar , Omani-Samani Reza , Amini Payam
Published: December 2019

Background

The 6-item Female Sexual Function Index (FSFI) is a short form of the original 19-item FSFI that measures sexual function in women. The aim of this study was to examine the factor structure and reliability of the FSFI-6 and to determine the demographic correlates of sexual dysfunction among infertile women in Iran.

Results

In total, 250 infertile women participated in this study. The mean total FSFI-6 score was 20.71 ± 5.09. Internal consistency of the FSFI-6 was high (Cronbach’s alpha = 0.856). All inter-item correlations and item-total correlations were in acceptable range. The results of confirmatory factor analysis provided support for a unidimensional model of the FSFI-6. Among demographic and infertility variables, higher women’s age, low education, unwanted marriage, short infertility duration, and low frequency of intercourse were associated with sexual dysfunction.

Conclusions

The FSFI-6 demonstrated sound reliability and validity in this study, supporting its continued use for measuring sexual disfunction among infertile women. Its brevity and comprehensiveness allow a quick assessment both in clinical and research settings.
An overview of the findings of dynamic upper limbs’ arterial and venous duplex in cases of vascular thoracic outlet syndrome
Authors: Baz Ahmed A.
Published: December 2019

Background

To describe the findings of the dynamic upper limb arterial and venous duplex in the assessment of vascular compression in cases of VTOS. This study was conducted on 58 patients with VTOS; they were evaluated by dynamic duplex examination.

Results

Vascular compression was subdivided into a venous compression that was detected in (84.4%,n = 49), arterial compression that was seen in (1.7%,n = 1), and combined arterial and venous compression that was present in (13.7%,n = 8); bilateral compression was existing in (94.4%,n = 55), compression at the scalene triangle was seen in (1.7%,n = 1), at the costo-clavicular space was seen in (91.3%,n = 53), and at the retro-pectoral space was depicted in (8.6%,n = 5).

Complicated arterial compression was detected in (1.7%,n = 1), whereas venous complications were seen in (6.8%,n = 4).

Conclusion

Dynamic duplex ultrasound offered a simple, noninvasive, and quick technique that can help in the evaluation of the vascular thoracic outlet syndrome without exposure to ionizing radiation or contrast media administration like that in CT; nevertheless, it is done with the patient in the upright position, thus avoiding the high false-negative results associated with the supine position that is used in the CT and MRI studies.
Diffraction velocity analysis in a single-channel seismic survey in the Joetsu Basin
Authors: Santos Luiz Alberto , Neves Eloise Helena Policarpo , Freire Antônio Fernando Menezes , Santos Marco Antônio Cetale , Matsumoto Ryo , Ajus Claudia M. I.
Published: December 2019

Historically, marine research has been using single-channel seismic (SCS) devices for scientific projects. Despite SCS’s abundant data availability and the contribution it has brought for subsurface comprehension, few efforts have been dedicated to improve the SCS processing flow to extract more information carried by seismic signals and for better imaging. Diffractions present the necessary means to estimate sediment acoustic properties useful for imaging, stability studies, and geohazard prevention. The root-mean-square (rms) velocity is estimated from diffractions using a diffraction velocity analysis workflow composed of the following main steps: separation of diffractions from specular events using stationary phase properties and plane-wave destruction filtering, determination of diffractor locations in time, velocity scanning using constant rms velocity time migration, automatic picking of rms velocity at the diffractor location in the scan volume, and quality control to avoid spurious rms velocity. The method circumvents the sparsity and nonuniform distribution of diffractions for smooth lateral velocity change conditions. Application in a SCS line acquired in the Joetsu Basin, Japan Sea, indicates improvement in the focusing of deeper events compared to the previous processing flow, and it adds consistent information about the acoustic properties of the subsurface.
Using highly accurate land gravity and 3D geologic modeling to discriminate potential geothermal areas: Application to the Upper Rhine Graben, France
Authors: Abdelfettah Yassine , Hinderer Jacques , Calvo Marta , Dalmais Eléonore , Maurer Vincent , Genter Albert
Published: December 2019

New land gravity data results acquired in northern Alsace were presented. Compared to the available old Bouguer anomaly, we recovered an accurate Bouguer anomaly field showing data uncertainties [Formula: see text]. A qualitative data analysis using pseudotomographies reveals several negative anomalies suggesting a decrease of the bulk density at the depth of geothermal interest. We have performed a quantitative study on the basis of the existing 3D geologic model derived from a reinterpretation of the vintage seismics. The theoretical gravity response indicates a great mismatch with the observed Bouguer anomaly. The stripping approach was applied, and the stripped Bouguer anomaly indicates that the density values of the Jurassic, but especially for the Triassic, the Buntsandstein, and the upper part of the basement, were overestimated even using the density values measured in the deep geothermal borehole. This suggests that the borehole density values do not reflect the density variations occurring at larger scale. To reduce the Bouguer anomaly during stripping, a negative density contrast should be affected to the Buntsandstein layer overlaying the basement, suggesting that the part located between the Buntsandstein and the upper part of the basement presents a low-density value compared to the reference density, which is not necessarily expected and is not observed in the densities measured in the borehole. Interestingly, a correlation is found between the gravity analyses and the thermal gradient boreholes in the northern part of the study area. For two boreholes, the gravity interpretation suggests a huge density decrease in the Buntsandstein, which may arise from a combination of high-density fracturing and the important quantity of geothermal fluid significantly affecting the bulk density. Analysis of the thermal borehole data suggests that these two boreholes indicate higher geothermal potential compared with the other boreholes.
Atrial Fibrillation and Stroke Risk in Patients With Cancer: A Primer for Oncologists
Authors: Sorigue Marc , Miljkovic Milos D.
Published: December 2019

Cancer and atrial fibrillation (AF) are common conditions, but for patients affected with both, there is a lack of data about management of anticoagulation and cerebrovascular outcomes. In the first section of this review, we summarize the most relevant studies on stroke risk and management of AF in patients with active cancer, attempting to answer questions of whether to anticoagulate, whom to anticoagulate, and what agents to use. In the second section of the review, we suggest a decision algorithm on the basis of the available evidence and provide practical recommendations for each of the anticoagulant options. In the third section, we discuss the limitations of the available evidence. On the basis of low-quality evidence, we find that patients with cancer and AF have a risk of stroke similar to that of the general population but a substantially higher risk of bleeding regardless of the anticoagulant agent used; this makes anticoagulation-related decisions complex and evidence from the general population not immediately applicable. In general, we suggest stopping anticoagulation in patients with high risk of bleeding and in those with a moderate bleeding risk without a high thromboembolic risk and recommend anticoagulation as in the general population for patients at a low risk for bleeding. However, regardless of initial therapy, we recommend reassessing whether anticoagulation should be given at each point in the clinical course of the disease. High-quality evidence to guide anticoagulation for AF in patients with cancer is needed.
Oncologic Implications of Chronic Hepatitis C Virus Infection
Authors: Hwang Jessica P. , LoConte Noelle K. , Rice John P. , Foxhall Lewis E. , Sturgis Erich M. , Merrill Janette K. , Torres Harrys A. , Bailey Howard H.
Published: December 2019

Chronic hepatitis C virus (HCV) infection increases the risk for several types of cancer, including hepatocellular carcinoma (HCC) and B-cell non-Hodgkin lymphoma, as primary and second primary malignancies. HCV-infected patients with cancer, particularly those undergoing anticancer therapy, are at risk for development of enhanced HCV replication, which can lead to hepatitis flare and progression of liver fibrosis or cirrhosis. Risk factors for HCV infection include injection drug use, blood transfusion, or solid organ transplantation before 1992, receipt of clotting factor concentrates before 1987, long-term hemodialysis, chronic liver disease, HIV positivity, and occupational exposure. Widely available direct-acting antivirals are highly effective against HCV and well tolerated. Identification of HCV-infected individuals is the essential first step in treatment and eradication of the infection. One-time screening is recommended for persons born from 1945 to 1965; screening is also recommended for persons with risk factors. Recently, a public health recommendation has been drafted to screen all adults age 18 to 79 years. Two oncology organizations recommend screening all patients with hematologic malignancies and hematopoietic cell transplant recipients, and a recently published multicenter prospective study supports universal HCV screening for all patients with cancer. HCV screening entails testing for anti-HCV antibodies in serum and, when results are positive, HCV RNA quantitation to confirm infection. Direct-acting antiviral therapy eradicates HCV in almost all cases. Virologic cure of HCV prevents chronic hepatitis and progression to liver fibrosis or cirrhosis. HCV eradication also decreases the risk of developing HCV-associated primary and second primary malignancies, and it may allow HCV-infected patients access to important cancer clinical trials. Patients with HCV-related cirrhosis require lifelong surveillance for HCC, even after viral eradication.
Precision Oncology and the Universal Health Coverage System in Japan
Authors: Ebi Hiromichi , Bando Hideaki
Published: December 2019

Although precision oncology is transforming clinical management of patients with cancer, many hospitals face challenges to effectively implement precision oncology. In addition, the cost and time exerted for genomic profiling needs to be balanced with expectations of benefit for each patient. This article summarizes the effort to implement precision oncology in Japan. The most promising development is that tests to profile the genomes of select cancers are now fully covered by the national health insurance system. In May 2019, two gene panels were approved with reimbursement: FoundationOne CDx Cancer Genomic Profile and OncoGuide NCC Oncopanel System, the latter of which was developed in Japan. To make better use of scarce resources, the reimbursement is restricted to patients with solid tumors that have progressed on standard chemotherapy, rare tumors, or tumors of unknown primary. To centralize Japanese precision oncology, the government designated approximately 170 hospitals and stratified them to three layers on the basis of their roles. In addition, Japan’s National Cancer Center launched a Center for Cancer Genomics and Advanced Therapeutics (C-CAT) that collects genomic information and clinical characteristics of patients who received genomic profiling tests. C-CAT is expected to be the central data repository, to match patients with clinical trials, and to assist translational research. The centralized system under the national health insurance system could be a double-edged sword. Although tight regulation may make it hard to keep up with the rapid development of precision oncology, a federated ecosystem for sharing clinical and genomic data will be a precious asset and allow for shared access to data. Access to unapproved drugs and administrative support from C-CAT will be keys for Japanese precision oncology to meet its full potential.
Postprandial Dyslipidemia, Hyperinsulinemia, and Impaired Gut Peptides/Bile Acids in Adolescents with Obesity
Authors: Higgins Victoria , Asgari Shervin , Hamilton Jill K , Wolska Anna , Remaley Alan T , Hartmann Bolette , Holst Jens J , Adeli Khosrow
Published: December 2019

Background

With increased rates of obesity and insulin resistance in youth, development of postprandial dyslipidemia, an important cardiovascular disease risk factor, is a concern. Glucagon-like peptides (ie, GLP-1 and GLP-2) and bile acids have been shown to regulate dietary fat absorption and postprandial lipids in animal models and humans. We hypothesize that the physiological response of GLPs and bile acids to dietary fat ingestion is impaired in adolescents with obesity and this associates with marked postprandial dyslipidemia and insulin resistance.

Methods

In this cross-sectional study, normal weight adolescents and adolescents with obesity underwent a 6-hour oral fat tolerance test. The postprandial lipoprotein phenotype profile was determined using various assays, including nuclear magnetic resonance spectroscopy, to characterize lipoprotein particle number, size, lipid content, and apolipoproteins. GLP-1 and GLP-2 were quantified by electrochemiluminescent immunoassays. Total bile acids were measured by an automated enzymatic cycling colorimetric method and the bile acid profile by mass spectrometry.

Results

Adolescents with obesity exhibited fasting and postprandial dyslipidemia, particularly augmented postprandial excursion of large triglyceride-rich lipoproteins. Postprandial GLPs were reduced and inversely correlated with postprandial dyslipidemia and insulin resistance. Postprandial bile acids were also diminished, particularly lithocholic acid, a potent stimulator of GLP-1 secretion.

Conclusion

Blunted postprandial GLP and bile acid response to dietary fat ingestion strongly associates with marked postprandial dyslipidemia. Further investigation is needed to assess their potential utility as early biomarkers for postprandial dyslipidemia in adolescents with obesity.
Cilia-driven asymmetric Hedgehog signalling determines the amphioxus left-right axis by controlling Dand5 expression
Authors: Zhu Xin , Shi Chenggang , Zhong Yanhong , Liu Xian , Yan Qiuning , Wu Xiaotong , Wang Yiquan , Li Guang
Published: December 2019

Cilia rotation-driven nodal flow is crucial for the left-right (L-R) break in symmetry in most vertebrates. However, the mechanism by which the flow signal is translated to asymmetric gene expression has been insufficiently addressed. Here, we show that Hedgehog (Hh) signalling is asymmetrically activated (L<R) in the region in which initial asymmetric Dand5 expression is detected. Upregulation of Hh signalling on the left side of wild-type embryos induces ectopic Dand5 expression on the left side, and the unilateral recovery of Hh signalling in Hh homozygous mutants induces Dand5 expression in the Hh signal recovery side. Immunofluorescence analysis results revealed that Hh fusion protein is asymmetrically enriched in the anterior-right paraxial mesoderm at the early neurula stage. Inhibiting embryonic cilia motility using methylcellulose (MC) blocks Hh protein enrichment on the right hand side and randomizes Dand5 expression and organ positioning along the L-R axis. These findings present a model showing that cilia movement is crucial for the symmetry breaks in amphioxus through asymmetric Hh protein transport. The resultant asymmetric Hh signalling provides a clue into the induction of asymmetric Dand5 expression.

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