Predictors of successful long-term weight loss maintenance: a two-year follow-up

Background

Weight regain is a common problem following weight loss intervention, with most people who seek treatment for obesity able to lose weight, but few able to sustain the changes in behavior required to prevent subsequent weight regain. The identification of factors that predict which patients will successfully maintain weight loss or who are at risk of weight regain after weight loss intervention is necessary to improve the current weight maintenance strategies. The aim of the present study is identify factors associated with successful weight loss maintenance by women with overweight or obesity who completed group cognitive behavioral treatment (CBT) for weight loss.

Methods

Ninety women with overweight or obesity completed a 7-month weight loss intervention. The data of 86 who completed follow-up surveys 12 and 24 months after the end of the treatment was analyzed. Depression, anxiety, binge eating, food addiction, and eating behaviors were assessed before and after the weight loss intervention. Participants who lost at least 10% of their initial weight during the weight loss intervention and had maintained the loss at the month 24 follow-up were defined as successful.

Results

The intervention was successful for 27 participants (31.3%) and unsuccessful for 59 (68.6%). Multiple logistic regression analysis extracted larger weight reduction during the weight loss intervention, a lower disinhibition score, and a low food addiction score at the end of the weight loss intervention as associated with successful weight loss maintenance.

Conclusion

The results suggest that larger weight reduction during the weight loss intervention and lower levels of disinhibition and food addiction at the end of the weight loss intervention predicted successful weight loss maintenance.

Trial registration

Trial registry name: Development and validation of effective treatments of weight loss and weight-loss maintenance using cognitive behavioral therapy for obese patients.Registration ID: UMIN000006803Registered 1 January 2012.URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000008052

     

Buprenorphine differentially affects M1- and M2-polarized macrophages from human umbilical cord blood

Background

As a partial μ-opioid receptor agonist with long half-life time, buprenorphine has been widely used to relieve chronic cancer and nonmalignant pain. The maintenance of chronic pain involves inflammation; however whether buprenorphine has anti-inflammation property remains unclear.

Methods

Macrophages, the immune cells that initiate and maintain inflammation, were isolated from human umbilical cord blood, and were polarized into M1 or M2 macrophages with IFN-γ in the presence of lipopolysaccharide (LPS) or IL-4, respectively. Quantitative PCR, ELISA,Western blotting analysis, and chromatin immunoprecipitation assays were employed to characterize M1 and M2 macrophages.

Results

1) Buprenorphine did not change not only the apoptosis, survival, andmorphology of resting macrophages, but also the antigen-presenting function of macrophages. 2) Buprenorphine inhibited the levels of mRNA and protein of several cytokines in M1 macrophages, and enhanced the expression of Ym1 and Fizz1 in M2 macrophages. 3) Buprenorphine did not affect the modulation of NF-κB and MAPK cascades by LPS in M1 macrophages. 4) Buprenorphine inhibited the expression of IRF5 and reduced binding of DNA to IRF5.

Conclusion

Buprenorphine may downregulate IRF5 pathway and limit M1 macrophage phenotype. These effects may contribute to its therapeutic benefit for chronic neuropathic pain.

     

Metabolic response of porcine colon explants to in vitro infection by <Emphasis Type="Italic">Brachyspira hyodysenteriae</Emphasis>: a leap into disease pathophysiology

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.

     

Synthesis and physicochemical characterization of the one-carbon carrier 10-formyltetrahydrofolate; a reference standard for metabolomics

Introduction

Metabolomics analysis depends on the identification and validation of specific metabolites. This task is significantly hampered by the absence of well-characterized reference standards. The one-carbon carrier 10-formyltetrahydrofolate acts as a donor of formyl groups in anabolism, where it is a substrate in formyltransferase reactions in purine biosynthesis. It has been reported as an unstable substance and is currently unavailable as a reference standard for metabolomics analysis.

Objectives

The current study was undertaken to provide the metabolomics community thoroughly characterized 10-formyltetrahydrofolate along with analytical methodology and guidelines for its storage and handling.

Methods

Anaerobic base treatment of 5,10-methenyltetrahydrofolate chloride in the presence of antioxidant was utilized to prepare 10-formyltetrahydrofolate.

Results

Pure 10-formyltetrahydrofolate has been prepared and physicochemically characterized. Conditions toward maintaining the stability of a solution of the dipotassium salt of 10-formyltetrahydrofolate have been determined.

Conclusion

This study describes the facile preparation of pure (>90%) 10-formyltetrahydrofolate, its qualitative physicochemical characterization, as well as conditions to enable its use as a reference standard in physiologic samples.

     

Effects of specific allergen immunotherapy on biological markers and clinical parameters in asthmatic children: a controlled-real life study

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.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

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.

     

Vasospasm is a significant factor in cyclosporine-induced neurotoxicity: Case report

Background

The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial.

Case presentation

We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment.Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved.

Conclusions

This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.

     

Identification of a urine metabolite constellation characteristic for kidney allograft rejection

Introduction

Allograft rejection is still an important complication after kidney transplantation. Currently, monitoring of these patients mostly relies on the measurement of serum creatinine and clinical evaluation. The gold standard for diagnosing allograft rejection, i.e. performing a renal biopsy is invasive and expensive. So far no adequate biomarkers are available for routine use.

Objectives

We aimed to develop a urine metabolite constellation that is characteristic for acute renal allograft rejection.

Methods

NMR-Spectroscopy was applied to a training cohort of transplant recipients with and without acute rejection.

Results

We obtained a metabolite constellation of four metabolites that shows promising performance to detect renal allograft rejection in the cohorts used (AUC of 0.72 and 0.74, respectively).

Conclusion

A metabolite constellation was defined with the potential for further development of an in-vitro diagnostic test that can support physicians in their clinical assessment of a kidney transplant patient.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

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.

     

Untargeted metabolomics suffers from incomplete raw data processing

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.

     

Advancing theory development: exploring the leadership–climate relationship as a mechanism of the implementation of cultural competence

Background

Leadership style and specific organizational climates have emerged as critical mechanisms to implement targeted practices in organizations. Drawing from relevant theories, we propose that climate for implementation of cultural competence reflects how transformational leadership may enhance the organizational implementation of culturally responsive practices in health care organizations.

Methods

Using multilevel data from 427 employees embedded in 112 addiction treatment programs collected in 2013, confirmatory factor analysis showed adequate fit statistics for our measure of climate for implementation of cultural competence (Cronbach’s alpha?=?.88) and three outcomes: knowledge (Cronbach’s alpha?=?.88), services (Cronbach’s alpha?=?.86), and personnel (Cronbach’s alpha?=?.86) practices.

Results

Results from multilevel path analyses indicate a positive relationship between employee perceptions of transformational leadership and climate for implementation of cultural competence (standardized indirect effect?=?.057, bootstrap p?<?.001). We also found a positive indirect effect between transformational leadership and each of the culturally competent practices: knowledge (standardized indirect effect?=?.006, bootstrap p?=?.004), services (standardized indirect effect?=?.019, bootstrap p?<?.001), and personnel (standardized indirect effect?=?.014, bootstrap p?=?.005).

Conclusions

Findings contribute to implementation science. They build on leadership theory and offer evidence of the mediating role of climate in the implementation of cultural competence in addiction health service organizations.

     

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

Context

Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

Objective

To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

Design

Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

Setting

Referral practice and research center.

Participants

60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

Main outcome measures

Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

Results

CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

Conclusion

A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

     

Identification of cancer subtypes from single-cell RNA-seq data using a consensus clustering method

Background

Human cancers are complex ecosystems composed of cells with distinct molecular signatures. Such intratumoral heterogeneity poses a major challenge to cancer diagnosis and treatment. Recent advancements of single-cell techniques such as scRNA-seq have brought unprecedented insights into cellular heterogeneity. Subsequently, a challenging computational problem is to cluster high dimensional noisy datasets with substantially fewer cells than the number of genes.

Methods

In this paper, we introduced a consensus clustering framework conCluster, for cancer subtype identification from single-cell RNA-seq data. Using an ensemble strategy, conCluster fuses multiple basic partitions to consensus clusters.

Results

Applied to real cancer scRNA-seq datasets, conCluster can more accurately detect cancer subtypes than the widely used scRNA-seq clustering methods. Further, we conducted co-expression network analysis for the identified melanoma subtypes.

Conclusions

Our analysis demonstrates that these subtypes exhibit distinct gene co-expression networks and significant gene sets with different functional enrichment.

     

Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

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.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

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.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

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.

     

Pharmacokinetic profile of a 24-hour controlled-release OROS<Superscript>®</Superscript> formulation of hydromorphone in the presence and absence of food

Background

The objective of this study was to compare the pharmacokinetic profile of a novel, once-daily, controlled-release formulation of hydromorphone (OROS^® hydromorphone) under fasting conditions with that immediately after a high-fat breakfast in healthy volunteers. The effect of the opioid antagonist naltrexone on fasting hydromorphone pharmacokinetics also was evaluated.

Methods

In an open-label, three-way, crossover study, 30 healthy volunteers were randomized to receive a single dose of 16 mg OROS^® hydromorphone under fasting conditions, 16 mg OROS^® hydromorphone under fed conditions, or 16 mg OROS^® hydromorphone under fasting conditions with a naltrexone 50-mg block. Plasma samples taken pre-dose and at regular intervals up to 48 hours post-dose were assayed for hydromorphone concentrations. Analysis of variance was performed on log-transformed data; for mean ratios of 0.8 to 1.2 (20%), differences were considered minimal. Bioequivalence was reached if 90% confidence intervals (CI) of treatment mean ratios were between 80% and 125%.

Results

The mean geometric ratios of the fed and fasting treatment groups for maximum plasma concentration (C_max) and area under the concentration-time curve (AUC_0-t; AUC_0-∞) were within 20%. Confidence intervals were within 80% to 125% for AUC_0-t and AUC_0-∞ but were slightly higher for C_max (105.9% and 133.3%, respectively). With naltrexone block, the hydromorphone C_max increased by 39% and the terminal half-life decreased by 4.5 hours. There was no significant change in T_max, AUC_0-t or AUC_0-∞.

Conclusion

Standard bioavailability measures show minimal effect of food on the bioavailability of hydromorphone from OROS^® hydromorphone. Naltrexone co-administration results in a slight increase in the rate of absorption but not the extent of absorption.

Trial Registration

Clinical Trials.gov NCT00399295

     

TarMet: a reactive GUI tool for efficient and confident quantification of MS based targeted metabolic and stable isotope tracer analysis

Introduction

Untargeted and targeted analyses are two classes of metabolic study. Both strategies have been advanced by high resolution mass spectrometers coupled with chromatography, which have the advantages of high mass sensitivity and accuracy. State-of-art methods for mass spectrometric data sets do not always quantify metabolites of interest in a targeted assay efficiently and accurately.

Objectives

TarMet can quantify targeted metabolites as well as their isotopologues through a reactive and user-friendly graphical user interface.

Methods

TarMet accepts vendor-neutral data files (NetCDF, mzXML and mzML) as inputs. Then it extracts ion chromatograms, detects peak position and bounds and confirms the metabolites via the isotope patterns. It can integrate peak areas for all isotopologues automatically.

Results

TarMet detects more isotopologues and quantify them better than state-of-art methods, and it can process isotope tracer assay well.

Conclusion

TarMet is a better tool for targeted metabolic and stable isotope tracer analyses.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

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.