Epidemiology of Histoplasmosis

Purpose of Review

Histoplasma capsulatum is an environmental fungus that contributes significant morbidity and mortality throughout the globe, especially in immunocompromised hosts. This review presents current data on the understanding of histoplasmosis epidemiology, including changing incidence among geographic regions and patient populations with increased risk.

Recent Findings

Global cases are more frequently identified due to the HIV epidemic, an increasing number of immunocompromised patients, and improved diagnostic capabilities. The global distribution of histoplasmosis extends to several countries in Central and South America and the Caribbean, as well as southern and sub-Saharan Africa, India, China, and Southeast Asia. Cases are also seen throughout Europe and non-endemic regions of the USA often due to migration and travelers.

Summary

The changing epidemiology of histoplasmosis underlines the importance of continued surveillance and reporting to better understand the regions which place patients at a higher risk for infection.

     

The Management of Chronic Pulmonary Aspergillosis: The UK National Aspergillosis Centre Approach

Purpose of Review

Chronic pulmonary aspergillosis (CPA) is a serious long-term fungal disease of the lung with a worldwide prevalence. Treatment of CPA is not straightforward given the often-multiple associated co-morbidities, complex clinical picture, drug interactions, toxicities and intolerances.

Recent Findings

First line treatment is oral itraconazole or voriconazole. In the event of intolerance or toxicity, patients may be swapped from itraconazole to voriconazole or vice versa. In the event of resistance or further intolerance, third line treatment with posaconazole could be initiated. In those with pan-azole resistance, short-term courses of intravenous liposomal amphotericin B or micafungin are fourth line therapy, keeping in mind the nephrotoxic effects of amphotericin B.

Summary

The available evidence for current treatments in CPA is limited and based mostly on retrospective cohort studies. There is a real need to raise awareness of this devastating disease to enable early treatment as well as prospective drug trials and studies to identify potential patient factors that correlate with progression, severity and overall outcomes in order to target future therapies.

     

Zygomycete Fungi Infection in Colombia: Literature Review

Purpose of Review

This review summarizes the reports of Zygomycete fungi infection in Colombia, as well as include the geographical distribution, species identification, and treatment of those clinical cases.

Recent Findings

Zygomycosis is not a new disease. However, the use of molecular tools has allowed the identification of some recently described species as their causal agents.

Summary

In Colombia, the prevalence of zygomycosis is unclear because reporting is not mandatory and because in many cases the etiological agent was not identified. It is important to establish the mandatory reporting of cases, to know the circulating fungal species, the treatment used, and the outcome of the patients. Regarding the treatment, amphotericin B remains as the best alternative. To our knowledge, this is the first compilation of the published cases of zygomicosis in the country.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

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.

     

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.

     

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.

     

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.

     

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.

     

Iridoid and phenylethanoid/phenylpropanoid metabolite profiles of <Emphasis Type="Italic">Scrophularia</Emphasis> and <Emphasis Type="Italic">Verbascum</Emphasis> species used medicinally in North America

Introduction

Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.

Objectives

We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.

Methods

Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.

Results

Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.

Conclusions

Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.

     

rDolphin: a GUI R package for proficient automatic profiling of 1D <Superscript>1</Superscript>H-NMR spectra of study datasets

Introduction

Adoption of automatic profiling tools for ¹H-NMR-based metabolomic studies still lags behind other approaches in the absence of the flexibility and interactivity necessary to adapt to the properties of study data sets of complex matrices.

Objectives

To provide an open source tool that fully integrates these needs and enables the reproducibility of the profiling process.

Methods

rDolphin incorporates novel techniques to optimize exploratory analysis, metabolite identification, and validation of profiling output quality.

Results

The information and quality achieved in two public datasets of complex matrices are maximized.

Conclusion

rDolphin is an open-source R package (http://github.com/danielcanueto/rDolphin) able to provide the best balance between accuracy, reproducibility and ease of use.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

From correlation to causation: analysis of metabolomics data using systems biology approaches

Introduction

Metabolomics is a well-established tool in systems biology, especially in the top–down approach. Metabolomics experiments often results in discovery studies that provide intriguing biological hypotheses but rarely offer mechanistic explanation of such findings. In this light, the interpretation of metabolomics data can be boosted by deploying systems biology approaches.

Objectives

This review aims to provide an overview of systems biology approaches that are relevant to metabolomics and to discuss some successful applications of these methods.

Methods

We review the most recent applications of systems biology tools in the field of metabolomics, such as network inference and analysis, metabolic modelling and pathways analysis.

Results

We offer an ample overview of systems biology tools that can be applied to address metabolomics problems. The characteristics and application results of these tools are discussed also in a comparative manner.

Conclusions

Systems biology-enhanced analysis of metabolomics data can provide insights into the molecular mechanisms originating the observed metabolic profiles and enhance the scientific impact of metabolomics studies.

     

The altered human serum metabolome induced by a marathon

Introduction

Endurance races have been associated with a substantial amount of adverse effects which could lead to chronic disease and long-term performance impairment. However, little is known about the holistic metabolic changes occurring within the serum metabolome of athletes after the completion of a marathon.

Objectives

Considering this, the aim of this study was to better characterize the acute metabolic changes induced by a marathon.

Methods

Using an untargeted two dimensional gas chromatography time-of-flight mass spectrometry metabolomics approach, pre- and post-marathon serum samples of 31 athletes were analyzed and compared to identify those metabolites varying the most after the marathon perturbation.

Results

Principle component analysis of the comparative groups indicated natural differentiation due to variation in the total metabolite profiles. Elevated concentrations of carbohydrates, fatty acids, tricarboxylic acid cycle intermediates, ketones and reduced concentrations of amino acids indicated a metabolic shift between various fuel substrate systems. Additionally, elevated odd-chain fatty acids and α-hydroxy acids indicated the utilization of α-oxidation and autophagy as alternative energy-producing mechanisms. Adaptations in gut microbe-associated markers were also observed and correlated with the metabolic flexibility of the athlete.

Conclusion

From these results it is evident that a marathon places immense strain on the energy-producing pathways of the athlete, leading to extensive protein degradation, oxidative stress, mammalian target of rapamycin complex 1 inhibition and autophagy. A better understanding of this metabolic shift could provide new insights for optimizing athletic performance, developing more efficient nutrition regimens and identify strategies to improve recovery.

     

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.

     

Tinea Capitis: Current Review of the Literature

Purpose of Review

This review summarizes the fungal literature currently available for tinea capitis (TC), as well as providing data for clinical utility.

Recent Findings

Available studies in TC are scarce; however, they provide important information about efficacy and outcome in clinical practice.

Summary

Treatment of TC is effective; however, it requires a minimum of 1 month. Systemic treatment is often required to favor enhance drug penetration into the deep part of the hair follicle. The newest oral antifungal has higher efficacy rates than conventional therapy, as well as much shorter duration of treatment but at higher costs. We perform a review of the literature including treatment schemes.

     

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.

     

A systems biology approach to invasive behavior: comparing cancer metastasis and suburban sprawl development

Background

Despite constant progress, cancer remains the second leading cause of death in the United States. The ability of tumors to metastasize is central to this dilemma, as many studies demonstrate successful treatment correlating to diagnosis prior to cancer spread. Hence a better understanding of cancer invasiveness and metastasis could provide critical insight.

Presentation of the hypothesis

We hypothesize that a systems biology-based comparison of cancer invasiveness and suburban sprawl will reveal similarities that are instructive.

Testing the hypothesis

We compare the structure and behavior of invasive cancer to suburban sprawl development. While these two systems differ vastly in dimension, they appear to adhere to scale-invariant laws consistent with invasive behavior in general. We demonstrate that cancer and sprawl have striking similarities in their natural history, initiating factors, patterns of invasion, vessel distribution and even methods of causing death.

Implications of the hypothesis

We propose that metastatic cancer and suburban sprawl provide striking analogs in invasive behavior, to the extent that conclusions from one system could be predictive of behavior in the other. We suggest ways in which this model could be used to advance our understanding of cancer biology and treatment.

     

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.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.