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1.

Objective

The visceral sensitivity index (VSI) is a useful self-report measure of the gastrointestinal symptom-specific anxiety (GSA) of patients with irritable bowel syndrome (IBS). Previous research has shown that worsening GSA in IBS patients is related to the severity of GI symptoms, suggesting that GSA is an important endpoint for intervention. However, there is currently no Japanese version of the VSI. We therefore translated the VSI into Japanese (VSI-J) and verified its reliability and validity.

Material and methods

Participants were 349 university students aged 18 and 19 years and recruited from an academic class. We analyzed data from the VSI-J, Anxiety Sensitivity Index (ASI), Hospital Anxiety and Depression scale (HAD), and Irritable Bowel Syndrome Severity Index (IBS-SI). The internal consistency, stability, and factor structure of the VSI-J and its associations with anxiety, depression and severity measures were investigated.

Results

The factor structure of the VSI-J is unidimensional and similar to that of the original VSI (Cronbach’s α?=?0.93). Construct validity was demonstrated by significant correlations with ASI (r?=?0.43, p?<?0.0001), HAD-ANX (r?=?0.19, p?=?0.0003), and IBS-SI scores (r?=?0.45, p?<?0.0001). Furthermore, the VSI-J was a significant predictor of severity scores on the IBS-SI and demonstrated good discriminant (p?<?0.0001) and incremental (p?<?0.0001) validity.

Conclusion

These findings suggest that the VSI-J is a reliable and valid measure of visceral sensitivity.
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2.

Background

The onset and course of irritable bowel syndrome (IBS) are strongly influenced by psychological factors, and treatment often includes cognitive-behavioral therapy. We conducted a study of the relationships between cognitive appraisal of IBS symptoms and negative mood for the subtypes of IBS.

Method

The participants were 1087 college students who completed a set of questionnaires that included the Rome II Modular Questionnaire, Self-reported IBS Questionnaire, Cognitive Appraisal Rating Scale, and the Hospital Anxiety and Depression Scale.

Results

The participants included 206 individuals with IBS; 61 had diarrhea-predominant IBS (IBSD) and 45 had constipation-predominant IBS (IBSC). The overall IBS group scored higher on anxiety and depression than the control group. The IBSD and IBSC groups each had significantly higher scores for anxiety but did not significantly differ from the control group in scores for depression. There were no significant differences between the IBSD and IBSC groups in their cognitive appraisal of IBS symptoms. For the IBSD group, anxiety was significantly, positively correlated with commitment, effect, and threat, and depression was significantly, negatively correlated with controllability. In contrast, there were no significant correlations between mood and cognitive appraisal for the IBSC group. Multiple regression analyses with abdominal symptoms as dependent variables and cognitive appraisals as independent variables showed that for the IBSD group, abdominal pain was significantly, positively correlated with commitment, and abdominal discomfort was significantly, positively correlated with appraisal of effect and threat. For the IBSC group, abdominal pain and hard stool were significantly, positively correlated with commitment, and abdominal discomfort was significantly, positively correlated with appraisal of effect and threat.

Conclusion

IBS patients as a general group report high levels of anxiety and depression. However, IBSD and IBSC were both associated only with high anxiety, but not depression, when compared to the non-IBS control group. For the IBSD group, anxiety was associated with cognitive appraisals, but this association was not found for the IBSC group. These groups did not differ in their associated cognitive appraisals, and are similar in terms of the positive relationship between abdominal pain and discomfort and the cognitive appraisals of coping.
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3.

Background

Rome III was revised to Rome IV in May 2016. One important change in the Rome IV criteria is that abdominal pain must be present for a diagnosis of irritable bowel syndrome (IBS). Under Rome III, in contrast, patients with abdominal discomfort only could be diagnosed with IBS, but these cases under Rome IV are now classified as unspecified functional bowel disorder (FBD). In a simple comparison of Rome III and Rome IV, it is unclear whether this difference reflects the influence of symptomatic frequency or the presence of abdominal pain. In particular, the influence of abdominal pain restriction on the diagnosis of IBS with predominant constipation (IBS-C) in the Rome IV criteria is largely unknown.

Methods

We reclassified subjects from a Japanese internet survey experiencing abdominal pain or discomfort at least one day each week as surrogate Rome III IBS-C subjects. Among them, we then reclassified subjects experiencing abdominal pain as surrogate Rome IV IBS-C subjects and subjects not experiencing abdominal pain as surrogate Rome IV FBD subjects. Symptoms were quantified and compared between the two groups.

Results

The surrogate Rome IV IBS-C subjects felt a significantly higher degree of anxiety in their daily lives (p?<?0.001) compared with the surrogate Rome IV FBD subjects. The combined female and 20–49?years surrogate Rome IV IBS-C subjects felt a higher degree of anxiety in their daily lives (p?<?0.05) than the respective Rome IV FBD subjects.

Conclusions

These results suggest that female IBS-C patients aged 20–49?years with abdominal pain in Rome IV have more anxiety than those without abdominal pain in Rome III. Changes in the diagnostic criteria from Rome III to Rome IV will better identify candidates for the biopsychosocial approach.

Trial registration

Although this survey was an anonymous internet survey, we obtained informed consent for the study as an online response. The disclosure of this study was approved by the Ethics Committee of Tohoku University Graduate School of Medicine (approval number: 2015–1-405).
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4.

Background

The ubiquitous use of mobile phones in sending and receiving text messages has become a norm for young people. Undeniably, text messaging has become a new and important communication medium not only in the social realm but in education as well. The aim of this study is to evaluate the effectiveness of using text messaging as a means to collect data for a medical research project.A cross sectional study was carried out during a double blind, randomized controlled trial to assess the efficacy and safety of a probiotic in the management of Irritable Bowel Syndrome (IBS). The study aim was to assess the response rate of weekly symptom reports via Short Message Service (SMS). The subjects were undergraduates in a private medical university in Malaysia. They were identified through a previous university wide study as suffering from IBS based on Rome III criteria. The subjects were randomly assigned to either the treatment arm receiving a daily probiotic, or the placebo arm. They were required to score their symptoms using eight-item-questionnaires at baseline, and thereafter weekly, for a total of 8 weeks. All subjects were given the choice to communicate their symptom scores by text messaging via mobile phones or by email. SMS text messages were sent to remind trial subjects to attend face-to-face visits and to complete a paper based 34-item-questionnaires on IBS quality of life assessment at baseline and at end of 8 weeks.

Findings

The response rate of weekly symptom scores via Short Message Service (SMS) from a total of 38 subjects was 100%. Through the study, 342 reports were submitted: 33.3% of these were received on the due date without reminder, 60.0% one day after the deadline, after a single reminder, 6.1% 2-3 days after the deadline, after 2-3 reminders and 0.6% 5 days after the deadline, after SMS, phone reminder and face-to-face encounter. All SMS symptom reports, whether on time or late, were complete. With the help of SMS reminder, all trial subjects completed the paper based IBS quality of life assessment at baseline and at end of study.

Conclusions

This study found using text messaging via mobile phone an excellent instrument for collecting weekly symptom reports in response to trial medication, reminding trial subjects to attend face to face visits and completing more complex paper based evaluation. The 100% response rate of weekly symptom reports was facilitated by using simple number codes for SMS submission.

Trial Registration

Not appropriate.
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5.

Background

Severity gradation of missense mutations is a big challenge for exome annotation. Predictors of deleteriousness that are most frequently used to filter variants found by next generation sequencing, produce qualitative predictions, but also numerical scores. It has never been tested if these scores correlate with disease severity.

Results

wANNOVAR, a popular tool that can generate several different types of deleteriousness-prediction scores, was tested on Fabry disease. This pathology, which is caused by a deficit of lysosomal alpha-galactosidase, has a very large genotypic and phenotypic spectrum and offers the possibility of associating a quantitative measure of the damage caused by mutations to the functioning of the enzyme in the cells. Some predictors, and in particular VEST3 and PolyPhen2 provide scores that correlate with the severity of lysosomal alpha-galactosidase mutations in a statistically significant way.

Conclusions

Sorting disease mutations by severity is possible and offers advantages over binary classification. Dataset for testing and training in silico predictors can be obtained by transient transfection and evaluation of residual activity of mutants in cell extracts. This approach consents to quantitative data for severe, mild and non pathological variants.
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6.

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.
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7.

Background

Intraoral disease is a common occurrence in patients with eating disorders, particularly dental erosion, which frequently becomes severe and may hinder daily life. The severity varies from patient to patient. Understanding the underlying mechanisms may help prevent dental erosion in these patients. Accordingly, we investigated the relationship between the severity of erosion and the behavior of patients with eating disorders, with a focus on daily diet and vomiting behavior.

Methods

A total 71 female eating disorder outpatients from the Clinical Center of Psychosomatic Dentistry of Nippon Dental University Hospital and the Psychosomatic Internal Medicine Department of Kudanzaka Hospital or who were hospitalized at Hasegawa Hospital were enrolled. Dental erosion severity and location were determined by oral examination. Patients who induced vomiting were queried on their behavior during vomiting and on routine diet habits. Patients with dental erosion were further divided into mild and severe groups based on the lesion severity and the groups compared.

Results

Dental erosion was observed in 43 of 50 subjects who induced vomiting. Dental erosion was most frequent on the palatal side of the anterior maxillary teeth, occurring in 81.3% of the subjects. There were significant differences observed between the mild and severe groups according to post-vomiting oral hygiene. Significantly more subjects in the mild group consumed large amounts of water before vomiting, and significantly more subjects in the severe group routinely consumed carbonated beverages or sweetened food.

Conclusions

While self-induced vomiting is the main cause of dental erosion in eating disorder patients, the erosion severity may be affected by behavior when inducing vomiting or by routine consumption of certain foods and beverages. Addressing these factors may help prevent severe dental erosion in patients who chronically induce vomiting.
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8.

BACKGROUND

Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.

OBJECTIVE

The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.

METHODS

A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.

RESULTS

Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.

CONCLUSION

These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.
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9.

Background

Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Fascin is an evolutionarily highly conserved cytoskeletal protein of 55 kDa containing two actin binding domains that cross-link filamentous actin to hexagonal bundles.

Methods

Here we have studied by immunohistochemistry the spatiotemporal accumulation of Fascin?+?cells in sciatic nerves of EAN rats.

Results

A robust accumulation of Fascin?+?cell was observed in the peripheral nervous system of EAN which was correlated with the severity of neurological signs in EAN.

Conclusion

Our results suggest a pathological role of Fascin in EAN.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticphatology.diagnomx.eu/vs/6734593451114811
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10.

Background

Allergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy).

Methods

7–18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up.

Results

There was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation.

Conclusions

Our data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.
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11.

Introduction

Periodontitis is a chronic, non-reversible inflammatory disease of the oral cavity leading to destruction of periodontal tissues. Thus, the estimation of bacterial metabolite, tissue damage and secretory metabolites of the triggered inflammatory cells likely to yield results. It may be of value for understanding the pathophysiology of the disease by metabolic profiling of saliva samples using high-resolution NMR spectroscopy.

Objective

The study will evaluate the difference in salivary metabolites in healthy and periodontal condition along with fetching of possible biomarkers in case of chronic periodontitis.

Methods

1H- NMR spectroscopy has been employed in 114 saliva samples in search of distinctive differences and spectral data were further subjected to multivariate analysis.

Result

One-hundred metabolites were characterised and assigned in the 1H NMR spectra of saliva. The statistical analysis of control (Healthy subjects) and diseased (Periodontal subjects) using PLS-DA model resulted in R2 of 0.84 and Q2 of 0.79. There was an elevation in the concentration of statistically discriminant metabolites. The twenty newly identified metabolites in saliva indicates bacterial population shift along with change in homeostasis. These disturbs the biofilm, a real protector against any possible bio-damage on tooth surface. These newly identified metabolites could define better geographically diversified periodontal condition.

Conclusion

Analysis clearly differentiates healthy subjects from the diseased ones. Few newly identified metabolites along with the pool of metabolites may serve as biomarkers for distinguishing the severity and complexity of periodontitis.
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12.

Background

Psychophysiological processing has been reported to play a crucial role in irritable bowel syndrome (IBS) but there has been no report on modulation of the stress marker chromogranin A (CgA) resulting from muscle stretching. We hypothesized that abdominal muscle stretching as a passive operation would have a beneficial effect on a biochemical index of the activity of the sympathetic/adrenomedullary system (salivary CgA) and anxiety.

Methods

Fifteen control and eighteen untreated IBS subjects underwent experimental abdominal muscle stretching for 4 min. Subjects relaxed in a supine position with their knees fully flexed while their pelvic and trunk rotation was passively and slowly moved from 0 degrees of abdominal rotation to about 90 degrees or the point where the subject reported feeling discomfort.Changes in the Gastrointestinal Symptoms Rating Scale (GSRS), State Trait Anxiety Inventory (STAI), Self-rating Depression Scale (SDS), ordinate scale and salivary CgA levels were compared between controls and IBS subjects before and after stretching. A three-factor analysis of variance (ANOVA) with period (before vs. after) as the within-subject factor and group (IBS vs. Control), and sex (men vs. female) as the between-subject factors was carried out on salivary CgA.

Results

CgA showed significant interactions between period and groups (F[1, 31] = 4.89, p = 0.03), and between groups and sex (F[1, 31] = 4.73, p = 0.03). Interactions between period and sex of CgA secretion were not shown (F[1, 3] = 2.60, p = 0.12). At the baseline, salivary CgA in IBS subjects (36.7 ± 5.9 pmol/mg) was significantly higher than in controls (19.9 ± 5.5 pmol/mg, p < 0.05). After the stretching, salivary CgA significantly decreased in the IBS group (25.5 ± 4.5 pmol/mg), and this value did not differ from that in controls (18.6 ± 3.9 pmol/mg).

Conclusion

Our results suggest the possibility of improving IBS pathophysiology by passive abdominal muscle stretching as indicated by CgA, a biochemical index of the activity of the sympathetic/adrenomedullary system.
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13.

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.
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14.

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.
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15.

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.
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16.

Background

Spontaneous urticaria is a common allergic skin condition affecting 0.5–1% of individuals and may burden on health care expenditure or may be associated with remarkable morbidity.

Aim

In this study, we measured the effect of vitamin D supplementation in patients with a diagnosis of CSU. Furthermore, quality of life and cytokine changes were evaluated.

Methods

The clinical trial was conducted on 20 patients with idiopathic chronic urticaria. Vitamin D was administered orally for 8 weeks and disease activity was measured pre- and post-treatment using USS and DLQI. On the other hand expressions of IL-17, IL-10, Foxp3, and TGF-β by Real-time RT-PCR were assessed.

Results

USS questionnaire showed that severity of idiopathic urticaria after the intervention, which compared with the first day reached a significant 55% reduction. The DLQI quality of life questionnaire 2 months after treatment showed 55% improvement. Along with the significant improvement of clinical symptoms, use of vitamin D increase FOXP3 gene expression and downregulation of IL-10, TGF-B, and FOXP3, IL-17, but these changes were not statistically significant.

Limitation

These might happen due to lack of enrolled population in the investigation.

Conclusion

Vitamin D can be used along with standard medical care and it’s a safe and cost-effective method for the treatment of chronic urticaria with deficiency of vitamin D.
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17.

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.
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18.

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.
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19.

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.
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20.

Background

Breast arterial calcification is a frequently benign finding on mammography that usually is not reported. An increasing attention has been formed to determine the association between breast arterial calcification (BAC) and Coronary artery disease. In the current study we have aimed to evaluate the relationship between BAC on mammography with coronary CT angiography findings.

Methods

The case control study was carried out on 60 women; 30 CAD and 30 healthy subjects as control, admitted to Golestan hospital radiology department. The mammography was performed in two views; Craniocaudal (CC) view and mediolateral oblique (MLO) and BAC was graded based on the severity and extent of calcifications. Coronary Arterial Calcification (CAC) were scored by Agatston criteria.

Results

Overly, 36 patients (60%) were positive for BAC. Twenty six out of them (72%) were CAD. There was a positive significant correlation between BAC and CAD. The sensitivity and specificity of BAC for CAD were 69% and 47%, respectively. Moreover, the severe BAC scores were significantly higher in CAD patients than non-CAD.

Conclusion

Our findings in line with several previous studies indicated the positive significant association between BAC and CAD occurrence. While the sensitivity and specificity of BAC in diagnosis of CAD is low, suggested the using of BAC just as a CAD risk factor. The relatively low sample size is the major limitation of the study.
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