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McMaster study reveals secrets of cystic fibrosis in baby sweat

New secrets have been revealed about how cystic fibrosis can manifest in young patients and how to treat it — and the answer lies in baby sweat.
McMaster study reveals secrets of cystic fibrosis in baby sweat

Photo : iStock

Cystic fibrosis (CF), a genetic disease which affects children and young adults, comes with lifelong health complications including digestive problems and persistent lung infections.

A new McMaster University study, which was published in the journal ACS Central Science on Monday, sheds new light on how CF works and, researchers say, could lead to an improved prognosis and better therapies.

 

Read the story here, and in French here.

New technique may better detect cystic fibrosis in newborns

New technique may better detect cystic fibrosis in newborns

Dr. Phil Britz-McKibbin

Researchers have identified new biological markers of cystic fibrosis (CF), a genetic disease which affects children and young adults, leaving them with lifelong health complications including digestive problems and persistent lung infections.

The findings, published in the journal ACS Central Science, shed new light on the underlying mechanisms of CF and could lead to improved prognosis and better therapies for a disease which is quite variable, affecting different children in different ways, say researchers.

“There are chemical signatures in sweat that tell us an infant has CF even when they do not exhibit any symptoms,” says Philip Britz-McKibbin, lead author of the study and a professor in the Department of Chemistry and Chemical Biology at McMaster University. “We set out to discover whether there were chemical indicators detected in sweat that could complement the gold standard for CF diagnosis: the sweat chloride test.”

Read the full story here.

Toward a better sweat test for babies with cystic fibrosis

Cystic fibrosis (CF) is an incurable genetic disease in which patients have chronic lung infections. The sooner CF is diagnosed, the better the symptoms can be managed. But current tests can give ambiguous results that do not reflect disease progression. Today, in ACS Central Science, researchers reveal a new type of sweat test that can overcome this challenge.

Patients with CF have a genetic mutation that promotes mucus buildup and enables biofilms to form in their lungs, leading to frequent lung infections and breathing difficulty. In addition, chloride ions accumulate in these patients, and they excrete this as a “salty” sweat. Physicians have used this interesting effect to develop a sweat test for CF diagnosis. However, the test does not provide any staging or prognostic information and often fails in borderline cases. Most people with the gene (more than 70 percent) are “carriers” who don’t develop the disease, so a genetic test alone is also not sufficient to diagnose CF. Philip Britz-McKibbin and colleagues hypothesized that there could be other molecules found in sweat that would provide the basis for a better test.

The researchers profiled the chemical composition of sweat from screen-positive infants including both unaffected carriers and confirmed CF cases. They identified several unknown chemicals in sweat that were consistently associated in babies who had CF, in addition to chloride. The researchers suggest that testing for these alternative molecules could be done for cases in which the chloride sweat test is too close to call. They also intend to track the progression of CF and monitor treatment responses to therapy in children using these and other sweat molecules.

The authors acknowledge funding from Cystic Fibrosis Canada, the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation and McMaster University.

The American Chemical Society, the world’s largest scientific society, is a not-for-profit organization chartered by the U.S. Congress. ACS is a global leader in providing access to chemistry-related information and research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

https://www.acs.org/content/acs/en/pressroom/newsreleases/2017/august/toward-a-better-sweat-test-for-babies-with-cystic-fibrosis.html

Scientists Discover Biological Markers Which Could Lead to Better Treatments for Cystic Fibrosis Patients

Newswise — Researchers have identified two new biological markers of cystic fibrosis (CF), a genetic disease which affects children and young adults, leaving them with lifelong health complications including digestive problems and persistent lung infections.

The findings, published in the journal ACS Central Science, shed new light on the underlying mechanisms of CF and could lead to improved prognosis and better therapies for a disease which is quite variable, affecting different children in different ways, say researchers.

“There are chemical signatures in sweat that tell us an infant has CF even when they do not exhibit any symptoms,” says Philip Britz-McKibbin, lead author of the study and a professor in the Department of Chemistry and Chemical Biology at McMaster University. “We set out to discover whether there were chemical indicators detected in sweat that could complement the gold standard for CF diagnosis: the sweat chloride test.”

The test is commonly used in universal newborn disease-screening programs and measures the concentrations of salt.  Elevated sweat chloride confirms that an infant actually has CF.  

But there are some obstacles that complicate clinical decision-making, explains Britz-McKibbin, because sweat chloride can result in ambiguous diagnoses in some borderline cases and does not reveal how the disease might progress for individual patients. 

“Sweat contains lots of information related to human health that researchers have not fully analyzed and we found some unexpected chemicals associated with CF,” he says.

Using a specialized technique developed at McMaster, scientists collected and analyzed sweat samples from infants in CF clinics at the McMaster Children’s Hospital and the Hospital for Sick Children in Toronto.

They identified several unknown chemicals beyond chloride that were consistently associated with babies who had CF, including two different drug and environmental compounds the infants secreted in sweat at much lower concentration levels.  

Testing for these biomarkers could be done in cases in which the chloride sweat test result is unclear, say researchers. The biomarkers also point to other underlying mechanisms that contribute to the progression of CF and could lead to better therapeutic interventions earlier in life.

“The easier it is to detect CF, the earlier it can be diagnosed, and the better people’s chances are at living a longer, healthier life”, says Joanna Valsamis, Chief Healthcare, Research and Advocacy Officer at Cystic Fibrosis Canada. “CF Canada invests heavily in research that aims to improve the lives of people living with CF, and findings such as those from Dr. Britz-McKibbin are crucial to our understanding of the disease.”

In Canada, one in every 3,600 children are diagnosed with CF.  But life expectancy rates have risen dramatically in recent decades with the median age of survival now over 50 years, due to better treatments to improve lung function, better nutrition and lung transplants.  Further benefits are expected with the advent of newborn screening programs that have resulted in early detection.

The research was funded in part by Cystic Fibrosis Canada. Since 1960, CF Canada has invested more than $244 million in leading CF research and care.  

http://www.newswise.com/articles/scientists-discover-biological-markers-which-could-lead-to-better-treatments-for-cystic-fibrosis-patients

Researchers announce new drug screening method

Canadian researchers have developed a new drug screening technique that could enable the rapid and accurate identification of fentanyl, along with many other illicit drugs which have been difficult to detect by urinalysis. 

The method developed at McMaster University in Hamilton, Ont., would also expedite results by enabling technicians to run many more tests simultaneously, eliminating the two-stage process currently used in testing, with improved accuracy. 

The new method, reported in the current edition of the journal Analytical Chemistry, would address one of the primary causes of the opioid epidemic by better enabling public health and law enforcement agencies to monitor the constant flow of new, synthetic drugs entering the illegal market. 

Current drug testing methods rely on immunoassays. An immunoassay is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody or an antigen. Scientists say immunoassays are ineffective in testing many new, synthetic drugs, including synthetic opioids, tranquilizers, stimulants and anti-anxiety drugs. 

As a result, conventional testing methods produce a high number of false positives and false negatives, which requires additional tests to confirm findings. 

“Drug testing is always behind the times since screening relies on antibody reagents that target only known drugs and they are prone to error, which contributes to higher health care costs and delays to clinical decision making,” says Phillip Britz-McKibbin, a professor in the Department of Chemistry and Chemical Biology at McMaster and lead author of the study.

“Current technologies are not specific, accurate nor comprehensive enough, which impairs a physician’s ability to properly care for patients, such as monitoring for drug compliance, potential substitution or polydrug usage,” he says. Only accurate urine tests can show whether or not the patient is following a doctor’s prescription or taking other harmful substances that can hamper treatment efficacy and patient safety, Britz-McKibbin adds.

Researchers plan to further validate the new method by comparing it to conventional screening tests for a wide range of drugs of abuse on a group of hospital inpatients.

Earlier this year, the U.S. Food and Drug Administration FDA granted 510(k) clearance to the Sefria fentanyl urine enzyme immunoassay – the first immunoassay of its kind to receive clearance. The FDA action makes it available for use by certified reference laboratories, hospitals, physician offices and other healthcare settings that perform testing. Previously, fentanyl immunoassay tests were only available for forensic testing.

The Sefria technology was developed and is being marketed by Pomona, Calif.-based Immunalysis Corp., a division of Alere Inc. (NYSE: ALR).

The availability of an FDA-cleared fentanyl immunoassay enables more reference and hospital laboratories to conduct precise qualitative screening, which is a key strategy in stemming the alarming increase in misuse and abuse of fentanyl,” says Kathy Miller, vice president of sales and marketing at Immunalysis Corp. 

According to the Centers for Disease Control and Prevention, death rates from synthetic opioids such as fentanyl increased by 72.2 percent from 2014 to 2015, partly due to their low cost and high potency, which can be up to 50 times greater than heroin and 100 times greater than morphine. 

Fentanyl-related drug overdoses are often caused by unintentional ingestion when it is combined with street market heroin or cocaine, according to scientists, making it much more dangerous.

 

Link: http://theinfluence.org/researchers-announce-new-drug-screening-method/

Science grad: “I like knowing that I’m doing something that may have an impact on people’s lives”

Adriana Nori de Macedo first came to McMaster from Brazil in 2012 as a PhD student seeking to study abroad.

In the five years she spent at McMaster, she left an indelible mark, making important research contributions to help improve screening for preventable and genetic diseases – improvements that could one day transform the lives of people around the world.

“I like knowing that I’m doing something that may have an impact on people’s lives,” says Macedo, who graduates this week with a PhD from the Chemical Biology graduate program. “It’s a big motivation for me to do the best research that I can.”

Macedo came to McMaster from São Paulo, Brazil, where she went to university, completing her Master’s degree in analytical chemistry. When the time came to start working on her PhD, she set her sights on studying abroad.

“I decided that I wanted to have an international experience, to learn about university education in another country and improve my English,” she says. “I thought I would be a professor in the future, so I also felt like it would be a good opportunity for me to make more connections and learn more about research and education in a developed country.”

Looking for the right opportunity to pursue her research interests, Macedo sought advice from one of her professors, and was ultimately put in touch with Philip Britz-McKibbin, a professor in McMaster’s Department of Chemistry and Chemical Biology.

“Dr. Britz-McKibbon was coming to Brazil a few months later for a conference,” she recalls. “We had the chance to meet in person – he was very friendly and very welcoming. That’s when I decided I wanted to come to McMaster with him as my supervisor.”

Before long, she arrived in Hamilton and was working with Britz-McKibbin and his research group, applying her expertise in bioanalytical chemistry to multiple interdisciplinary research projects with potentially far-reaching implications for global public health.

Collaborating with epidemiologists at the Population Health Research Institute (PHRI), Macedo played a pivotal role in helping to develop a simpler, and more cost-effective method of analyzing iodine levels in urine to screen for iodine deficiency, the most common cause of preventable intellectual disabilities in children and which can also lead to hypothyroidism, increased risk of cardiovascular disease, depression, as well as some types of cancers.

She also worked with a multidisciplinary team that included clinicians at McMaster and Sick Kids, identifying compounds in infants’ sweat that could help improve the test used to screen for Cystic Fibrosis in newborns. Though her research results are preliminary, her findings could help improve the test and lead to earlier diagnosis of the disease.

“Usually babies who are diagnosed earlier in life have fewer hospitalizations and infections, especially during childhood, so they have better outcomes in general,” she says. “For parents, and the anxiety that comes with not knowing whether their child has a disease or not, I think this would be a great step.”

In addition to her research contributions, Macedo also honed her skills as a teaching assistant, a role she says she enjoyed. She designed a new experiment for an undergraduate chemistry lab course that tied in with her research on iodine nutrition. The experiment demonstrated the importance of continuously monitoring iodine levels in populations and helped students understand how analytical chemistry can impact public health decisions.

Macedo recently returned to Brazil.  She a now postdoctoral scholar at the University of São Paulo, and is continuing to conduct health-related research and work toward her goal of becoming a university professor.

She has taken what she learned at McMaster home with her and says that her time here helped her grow both personally and professionally.

“I’m grateful that I went to Canada, that I went to McMaster,” she says. “I had a great experience.”

 

By Erica Balch

 

Link: https://brighterworld.mcmaster.ca/articles/science-grad-i-like-knowing-that-im-doing-something-that-may-have-an-impact-on-peoples-lives/

Designing a New Drug Test - CJMLS

Read our recent cover story/interview, "Designing a New Drug Test" by Jane Langille in the Fall 2018 edition of the Canadian Journal for Medical Laboratory Sciences.

 

Read here: https://csmls.org/csmls/media/documents/publications/journals/CJMLS_Fall2018_Proof4.pdf

Congrats to Mai for a successful PhD Defense

Congrats to Mai for a successful PhD defense yesterday morning!

 

Mai-phd-defense-3

Attend the Canadian Metabolomics Conference in Canmore Alberta

The Second Annual Canadian Metabolomics Conference will be held from May 1st to 2nd in Canmore, Alberta. The conference will highlight work by leading researchers, including new technologies and approaches for metabolomics research, and applications in various fields. The conference will feature networking opportunities and a poster session designed for trainees to present their work. The Alberta Epigenetics Network will be offering trainee travel awards. Our goal is to highlight the exceptional metabolomics science that is being done in Canada and abroad, and foster Canada’s leadership role in the global research community.

https://www.canmetcon.ca/

Congrats Alicia on your journal cover page publication

We are always excited when we can make it on the cover! A big congratulations to Alicia for her work on metabolic signatures of Cystic Fibrosis for Newborn Screening that is featured as the cover article in the Journal of Proteome Research.

Metabolic Signatures of Cystic Fibrosis Identified in Dried Blood Spots For Newborn Screening Without Carrier Identification

Thanks McMaster for featuring our Cystic Fibrosis work

Take a look at the exciting research going on in the Britz-McKibbin lab.

https://www.youtube.com/watch?v=OUajUH3oQ8Y

Congratulations Sabrina

Congrats Sabrina on your successful thesis presentation today. We can't wait to continue our cannabis assay research and development this summer. 

Undergraduate Thesis Day

A big congratulations to all of our undergraduate thesis students, Rebecca, Richel, Holly, Tiffany and Lucas, on their presentations today. We wish you nothing but the best for the future and have enjoyed participating in your research this past semester. 

Very excited to present our JoVE publication

We are so excited to share our JoVE article and video. Thanks for all the hard work Meera, Zach, Sabrina and Clara! Take a minute and check it out for yourself (link below).

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-capillary Electrophoresis Mass Spectrometry

 

Welcome to our new undergraduate students

A warm welcome to Sean, Rochelle and Nicolas our new undergraduate students. We are looking forward to a productive summer and can't wait to see the progress you all make on your projects.

Congratulations Ritchie on receiving the 2019 Impact Award

The Impact Award is given to students in Chemistry who have published a high impact article or communication. Check out the article below. Also shout-out to Sandi for her contributions as well.

Robust Method for High-Throughput Screening of Fatty Acids by Multisegment Injection-Nonaqueous Capillary Electrophoresis-Mass Spectrometry with Stringent Quality Control

We are excited to be attending the 102nd CCCE Conference in June

Check our Ritchie's, Erick's and Stellena's posters at the event being held in Quebec City from June 3rd to June 7th 2019.

Congratulations Sandi on your Program Excellence Award

Help us congratulate Sandi on her Program Excellence Award! The Britz Group couldn't be prouder to see your success and be apart of your research opportunities.

Great Poster Sabrina

We had a great time at the 2nd annual Michael G. DeGroote Centre for Medicinal Cannabis Research Conference on Friday and Saturday. Sabrina presented a great poster on using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry, a method developed in the Britz Group, for detecting cannabis metabolites in urine.

We really enjoyed our time at CSC

Great presentations Stellena and Ritchie at CSC last week. Also great poster Erick! Looking forward to the productive summer ahead continuing our research.

Convocation: Spring 2019

A big congratulations to Mai on her convocation after successfully defending her PhD last winter. Also a congratulations to our undergraduate students, Zach, Sabrina, Tiffany, Holly, Richel, Lucas, and Rebecca on graduating from the Bachelor of Science program here at McMaster. From Mai to the undergrads, we know each one of you are going to go on to do wonderful things and we can't wait to hear all about it. 

Wonderful seminar Michelle!

What a great afternoon in the Britz-McKibbin lab getting to support Michelle Saoi at her departmental seminar. We love being able to support one another and hear about the research we have all been up to. Michelle has provided very meaningful advancements in tissue metabolomics using capillary electrophoresis-mass spectrometry. From research on the effects of sarcopenia in older adults to observing the metabolomic effects of ingesting bicarbonate during strenuous exercise, Michelle is definitely on the cutting edge of a lot of interesting research. Come on out this Tuesday June 18th to Michelle's PhD defence at 9am if you want to hear more.

Another successful PhD defence!!!

A massive congratulations to Michelle Saoi on her successful PhD defence this morning. Although we are sad to see you go we couldn't be happier on your success. Best of luck in New York during your Post Doc!!

Metabolomics 2019

We had a great time attending Metabolomics 2019 in the Netherlands. Hopefully you had the chance to visit Sandi and Dr. Britz's posters during the conference to hear about Sandi's research on reliable fatty acid biomarkers of maternal dietary fat intake and the group's research (presented by Dr. Britz) in collaboration with the DIGEST study. It was also great catching up with former members of the Britz-McKibbin group: Adriana and Mai.

Metabolomics Publication

Take a look at Mai's recent publication in Metabolomics where elevated urinary levels of collagen degradation and epithelial cell turnover products were discovered in irritable bowel syndrome (IBS) patients. Hopefully this novel discovery can help with the accurate diagnosis of IBS pateints which is currently the most commonly diagnosed functional gastrointestinal disorder in developed countries.

Metabolomics reveals elevated urinary excretion of collagen degradation and epithelial cell turnover products in irritable bowel syndrome patients

In the news...

Thanks McMaster University for featuring Mai's recent research into finding a possible urine biomarker for the accurate diagnosis of IBD (irritable bowel syndrome). Considering the prevalence of IBD, we hope this is only the beginning of it's diagnostic testing. Take a looks at the article published on McMaster's website.

Scientists find simple urine test could offer a non-invasive approach for diagnosis of IBS patients

More research coming out

They say in academia summer is the time you are most productive and that is definitely the case this summer in the Britz group with another publication coming out today. Congratulations to Michelle (first author) and Alice (second author), both from our group, on your publication in Metabolites. Take a look at their findings on how metabolomics was used to study step reduction in older adults and their potential increased risk of developing sarcopenia.

Metabolic Perturbations from Step Reduction in Older Persons at Risk for Sarcopenia: Plasma Biomarkers of Abrupt Changes in Physical Activity

Great Seminar Nadine

It is always a pleasure to hear all about a members research and the contributions they have made in their field of study. Great seminar today Nadine, best of luck at your defense on Thursday. Come on out if your free - Thursday August 1st at 9:30am in the Grad Studies Office.

PhD: Nadine

A very big congratulations to Nadine who successfully defended her PhD (Targeted and Non-Targeted Metabolite Analysis for Disease Risk Assessment) today. Welcome to the PhD club! We can't wait to hear all about your future endeavors, we know you'll make a significant impact no matter where you end up. We hope you enjoyed your sip out of the chalice at the Phoenix this afternoon.

Welcome Gustavo

A very warm welcome to Gustavo from Brazil who is here to shadow us for a few weeks before translating CE-MS to his research group. We can't wait to share all our wisdom and can't wait to learn from you as well! As a lab group we headed to an escape room this afternoon. Of course we escaped, nobody can keep the Britz-McKibbin group locked up!!!

Goodbye to the undergrads

A big thank-you to Sabrina, Sean, Rochelle, and Nick for a great summer in the Brtiz-McKibbin group. We really enjoyed mentoring you this summer and can't wait to hear all about your future endeavours. We hope you truly enjoyed your summer with us, we sure did!!!

Looking forward to September when Nick will be re-joining us as a CHEM 3RP3 student along with our other undergraduate thesis students. Best of luck to all our out-going and in-coming undergrads during your Fall semester.

Check out our lastest collaboration

We are so happy to promote our latest collaboration with McMaster's Health Science Department. Congratulations Nadine on getting your DIGEST (Diet & Gene Interaction Study) work published, great work. Take a look at her paper below, some really interesting research on being able to metabolically differentiate patient diets. This could revolutionize the use to food frequency questionaires.

Metabolic Trajectories Following Contrasting Prudent and Western Diets from Food Provisions: Robust Biomarkers of Short-Term Changes in Habitual Diet

Listen to Dr. Britz in the latest CSMLS podcast

We always love getting the opportunity to try new things. Check out what Dr. Britz had to say about the ongoing opioid crisis in North America.

The opioid epidemic is a complex and multi-layered problem. In the episode Dr. Britz contributed to, they explore how various factors are contributing to this crisis. They also delve into how one novel drug testing methodology might just be one piece of the puzzle to combat the epidemic.

Episode 28 – A Piece of the Puzzle

Check out our most recent article

We very excited to have been able to contribute to the latest GIT Laboratory & Biotechnology issue. Check out our article by Meera, Zach, Sabrina, and Dr. Britz titled Comprehensive Surveillance of Drugs of Abuse: A Method for Rapid and Accurate Urine Drug Testing in an Opioid Crisis.

The opioid crisis is an emerging public health emergency as reflected by the alarming increase in opioid-related deaths and addictions across North America. This is largely attributed to their widespread use as analgesics for the treatment of chronic pain. This problem is further compounded by the concurrent use of by other medications prone to abuse and poisoning, which are increasingly used without a prescription (e.g. benzodiazepenes). The adulteration of illicit drugs has also contributed to a rise in accidental drug overdose fatalities due to access to highly potent yet inexpensive synthetic opioids on the illegal drug market, such as fentanyl. In this context, methadone maintenance programs offer a harm reduction strategy to treat opioid addiction as methadone acts as a long-acting opioid agonist that inhibits pain while attenuating opioid withdrawal symptoms without generating euphoric-like sensations. However, optimum dose regimes are critical for successful treatment outcomes given

Toronto Post-ASMS Symposium - Oct 21

19th Toronto Post-ASMS Mass Spec Symposium, a Free-to-Attend Mass Spec Users' Meeting will take place on Oct. 21 at Crowne Plaza Toronto Airport.

List of Talks (in speaker name alphabetical order):

  • Prof. Nicolas BissonLaval University/CHU Research Center of Quebec, Quebec, QC
    "Functional proteomics insights into receptor tyrosine kinase biology"
  • Dr. Eric BonneilUniversity of Montreal, Montreal, QC
    "Segmented Ion Fractionation and High Field Asymmetric Waveform Ion Mobility Spectrometry expands proteome coverage to uncover sequence variants"
  • Prof. Christoph BorchersMcGill University/University of Victoria, Montreal, QC
    "Structure determination of neurodegenerative disease-related misfolded protein aggregates by short-distance crosslinking constraint-guided discrete molecular dynamics (CL-DMD)"
  • Prof. Christine Des RosiersUniversity of Montreal/Montreal Heart Institute, Montreal, QC
    "Comprehensive lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarker in a monogenic form of mitochondrial disorder"
  • Prof. Jennifer Geddes-McAlisterUniversity of Guelph, Guelph, ON
    "Dynamic proteomic profiling of the Salmonella-host interplay reveals new modes of action for known and novel virulence factors"
  • Dr. Kaveh KahenSigma Analytical Services, Toronto, ON
    "The use of mass spectrometry for quality control and understanding the complex chemistry of cannabis and its therapeutic effects"
  • Dr. Yuyong KeEndoCeutics, Quebec City, QC
    "Application of LC-MS in the investigation of recovery loss, degradation and storage stability of finished products"
  • Dr. John KellyNational Research Council Canada, Ottawa, ON
    "A comparative study of N-glycosylation assays for the characterization of Fc and Fab N-glycans on monoclonal antibodies"
  • Dr. Lili MatsAgriculture and Agri-Food Canada, Guelph, ON
    "Effects of purple potato rich diet on fecal metabolome profiles of mice as determined by untargeted LC-MS/MS screening"
  • Mr. Kevork MekhssianAltasciences, Laval, QC
    "A sensitive LC-HRMS method for the quantitation of dystrophin protein in human muscle tissue"
  • Dr. Adrien MusukuPharmascience, Montreal, QC
    "Matrix Effect, Recovery and Stability Issues in Regulated Cannabis Testing: Should Proficiency Testing Be Mandatory to Ensure Reliable Pesticides Analysis by LC-MS/MS?"
  • Prof. Hannes RostUniversity of Toronto, Toronto, ON
    "Ion Mobility Separation improves MS sensitivity and duty cycle for data-independent acquisition on the timsTOF Pro"
  • Dr. Audrey Roy-LachapelleEnvironment Canada, Montreal, QC
    "High-throughput determination of seventeen cyanotoxins and suspect screening of other cyanopeptides by SPE-UHPLC-HRMS in Canadian lakes"
  • Dr. Varoon SinghUniversity of Waterloo, Waterloo, ON
    "Direct Coupling of Magnetic Nanoparticles and Enhancement of Blade Spray Ionization Mass Spectrometry for Quantitation of Analytes in Complex Matrices"
  • Prof. Jeff SmithCarleton University, Ottawa, ON
    "iTrEnDi on biomolecules and beyond: enhancing MS-based quantitative analyses using new in situ diazoalkane chemistry"
  • Dr. Jonathan St-GermainPrincess Margaret Hospital, Toronto, ON
    "FBXO11 Network Identifies Novel Disease-Relevant Interaction with the Ubiquitin-Specific Protease USP28"
  • Prof. Bingyun SunSimon Fraser University, Vancouver, BC
    "Body-wide proteome dynamics in the understanding and assessment of multiorgan drug response"
  • Dr. Difei SunLifelabs Medical Laboratories, Toronto, ON - TBC
    "Method development and validation of LC-MS/MS based assay for detection of carfentanil and norcarfentanil in human urine"
  • Prof. Derek WilsonYork University, Toronto, ON
    "Illuminating the 'Dark Stage' of Amyloidogenesis in Neurodegenerative Disease Drug Development"
  • Prof. Arash Zarrine-AfsarUniversity of Toronto, Toronto, ON
    "Metabolic discrepancies within histologically equivalent tissues may limit the relevance of tumour bearing mice for mass spectrometry research"

Fun Part of the Meeting:

  • Good Food and Good Science as always!
  • Raffle Time - 3 Winners will be Drawn, and Each Winner will Receive a VISA Gift Card of $100

Many thanks to our 2019 Post-ASMS Sponsors:

  • Peak Scientific
  • Agilent Technologies
  • Waters
  • Phytronix
  • Parker Hannifin
  • Sciex
  • Mandel Shimadzu
  • Bruker
  • EVOSEP
  • Thermo Scientific
  • Hamilton
  • Canadian Life Science
  • LECO
  • Zef Scientific
  • PerkinElmer
  • DIKMA
  • IonBench

Detailed information of this meeting is available at http://www.cfabs.org/ms_2019_toronto_PostASMS.php

This meeting is Free-to-Attend for Mass Spec users, but pre-registration to attend is required.

We look forward to seeing you on Oct. 21.

New Students

After a very productive summer here in the Britz group, and after saying good-bye to our summer undergrads we are really excited to welcome our new undergrads and a grad student to our research group. A warm welcome to our new MSc candidate (Chemistry) Megan Magee who recently completed her undergrad at Guelph University in Chemistry. After taking a year off she's excited to be back and participating in some exciting, novel research in the Britz-McKibbin group. Also we welcome, our new undergraduate research and co-op students, Eric, Hani, Paula, Nicole, and Sena, we look forward to an exciting year ahead and can't wait to hear about all of you progress on your respective projects.

Why not participate in one of our studies?

Study Summary: In collaboration with Spark Medical Cannabis Clinic and PureSinse, a licensed producer of medicinal cannabis, the Britz-McKibbin research group at McMaster University is currently studying how the metabolism of cannabis differs in humans when ingested orally as an oil extract or vaped/smoked as a dried leaf.

This work is especially relevant for patients taking other medications concurrently, and who suffer from chronic pain, anxiety, or insomnia. Several factors impact patient treatment responses to prescribed medicinal cannabis, which remain poorly understood, and highly variable between subjects.

This study aims to better identify and characterize various metabolites of cannabis, known as cannabinoids, that are excreted in urine reflecting how quickly and in what manner the body eliminates medicinal cannabis.

Knowledge gained from this study will help us better understand how medicinal cannabis can be optimally prescribed to individual patients as a way to maximize its therapeutic benefits safely without any adverse drug interactions.

Investigating medical cannabis metabolism: Each person metabolizes cannabis differently depending on lifestyle, genes, mode if intake, and other factors that remain poorly understand. By studying small molecules found in your urine known as metabolites, we can better understand your individual metabolism. This information may help doctors better prescribe medicinal cannabis for optimized therapeutic benefits.

Participation: You are free to leave the study at any time ever after enrolment. Your decision will not affect the level of care you receive at SPARK. Participants of this study will receive a $10 Starbucks gift card upon their second visit to SPARK clinic.

 

Congrats Michelle on your most recent publication

Check out Michelle Saoi's recent publication in the Journal of Proteomics Research titled High Throughput Screening of Serum γ-Glutamyl Dipeptides for Risk Assessment of Nonalcoholic Steatohepatitis with Impaired Glutathione Salvage Pathway. Considering the exact mechanisms of non-alcoholic fatty liver disease (NAFLD) pathophysiology remain poorly understood, including its progression to the more severe nonalcoholic steatohepatitis (NASH), Michelle's research highlights a targeted analysis of a panel of 16 serum γ-glutamyl dipeptides from a cohort of NASH adult patients from Japan. SPOILER ALERT! Her findings highlight the key role of defects in the γ-glutamyl cycle for differentiation of NASH patients, which may enable better risk assessment of long-term survivorship as a complement to standard liver enzyme screens and histopathology.

More accepted papers

We are excited to announce two more papers from the Britz-McKibbin group have been accepted!

Jen Wild's work on improved monitoring of PKU paitents titled "Metabolomics for Improved Treatment Monitoring of Phenylketonuria: Urinary Biomarkers for Non-invasive Assessment of Dietary Adherence and Nutritional Deficiencies" was recently accepted in Analyst.

As well as Nadine Wellington's work titled "Elucidating the Anomalous Binding Enhancement of Isoquinoline Boronic Acid in Acidic Conditions for Sialic Acid: Biorecognition Beyond Vicinal Diols" was recently accepted in Chemistry - A European Journal.

Congrats to both of these former students! Stay tuned for more information when both papers are published.

Take a look at our DIGEST paper

We are very excited for another recent publication out of the Britz-McKibbin group. To date this is one of our largest collaborations involving Health Science here at McMaster. Why not take a look at Nadine's results where she metabolically phenotyped 42 healthy participants after being assigned either a "prudent" or "western" diet using single spot urine and fasting plasma samples to provide a complete list of biomarkers for changes in habitual diet of participants. Targeted and nontargeted metabolite profiling was conducted using three complementary analytical platforms, where 80 plasma metabolites and 84 creatinine-normalized urinary metabolites were reliably measured in the majority of participants. Check it out...

Metabolic Trajectories Following Contrasting Prudent and Western Diets from Food Provisions: Identifying Robust Biomarkers of Short-Term Changes in Habitual Diet

Jen's PKU Work

Congratulations to one of our former group members, Jen Wild, on her paper outlining potential urinary biomarkers for the dietary assessment of phenylketonuria (PKU). Considering the management of PKU requires lifelong restriction of phenylalanine (Phe) intake, typically specialized medical foods are used to prevent neurocognitive impairment in affected patients, and thus a need for a non-invasive assessment of dietary adherence is important. Plasma metabolomic studies demonstrated that non-adherent PKU patients had lower circulating concentrations of Tyr, arginine, 2-aminobutyric acid, and propionylcarnitine that were inversely correlated to Phe. Nontargeted metabolite profiling also revealed urinary biomarkers associated with poor dietary adherence among PKU patients, including elevated concentrations of catabolites indicative of Phe intoxication (e.g., phenylpyruvic acid, phenylacetylglutamine, hydroxyphenylacetic acid). Take a look at her manuscript below:

Metabolomics for improved treatment monitoring of phenylketonuria: urinary biomarkers for non-invasive assessment of dietary adherence and nutritional deficiencies

Diet Detectives

Researchers at McMaster have identified several chemical signatures, detectable in blood and urine, that can accurately measure dietary intake, potentially offering a new tool for physicians, dietitians and researchers to assess eating habits, measure the value of fad diets and develop health policies.

The research, published in the journal Nutrients, addresses a major challenge in assessing diets: studies in nutrition largely rely on participants to record their own food intake, which is subject to human error, forgetfulness or omission.

“This has been a major issue in nutritional research and may be one of the main reasons for the lack of real progress in nutritional sciences and chronic disease prevention,” says Philip Britz-McKibbin, a professor in the Department of Chemistry and Chemical Biology at McMaster University and lead author of the study, which was a collaboration with Dr. Sonia Anand and colleagues from the Departments of Medicine, and Health Research, Evidence, and Impact.

Scientists set out to determine if they could identify chemical signatures, or metabolites, that reflect changes in dietary intake, measure those markers and then compare the data with the foods study participants were provided and then reported they had eaten. The specimens analyzed were from healthy individuals who participated in the Diet and Gene Intervention Study (DIGEST).

Over a two-week period, researchers studied two contrasting diets: the Prudent diet,  rich in fruits, vegetables, lean meats, and whole grains, and a contemporary Western diet, rich in trans fats, processed foods, red meat and sweetened beverages.

Researchers were able to validate a panel of metabolites in urine and plasma that correlated with the participants’ consumption of fruits, vegetables, protein and/or fiber.

“We were able to detect short-term changes in dietary patterns which could be  measured objectively,” says Britz-McKibbin. “And it didn’t take long for these significant changes to become apparent.”

Britz-McKibbin cautions that food chemistry is highly complex. Our diets are composed of thousands of different kinds of chemicals, he says, and researchers don’t know what role they all may play in overall health.

In future, he hopes to broaden this work by examining a larger cohort of participants over a longer period of time. His team is also exploring several ways to assess maternal nutrition during crucial stages of fetal development and its impact on obesity and metabolic syndrome risk in children.

The study was funded by the Natural Sciences and Engineering Research Council of Canada, Genome Canada, Labarge Optimal Aging Initiative Opportunities Fund, and the Faculty of Science at McMaster.

DIGEST work also featured in Toronto Star

We are very excited to hear that Metro news (owned by the Toronto Star) also picked up our DIGEST work on dietary markers. Take a look at the link below if you haven't had the chance to read it yet.

MANA 2019

We had a great time at the inaugural MANA (Metabolomics Association of North America) conference this year in Atlanta, USA. Biban, one of our PhD candidate students was able to present her research involving new advances in biomonitoring of smoke exposure. Her talk was well received, great work Biban!

MetaboNews Spotlight Article

It's always a pleasure to be featured in spotlight articles. The Metabolomics Innovation Centre (TMIC) releases a monthly newsletter to keep metabolomic researchers and other professionals informed about new technologies, software, databases, events, job postings, conferences, training opportunities, interviews, publications, awards, and other newsworthy items concerning metabolomics. Take a look at the article highlighting the metabolomic approach we take when it comes to Drugs of Abuse testing and surveillance.

Comprehensive Drug Surveillance in an Era of Polypharmacy by Multisegment-Injection-Capillary Electrophoresis-Mass Spectrometry

Wishing our new co-ops a warm welcome

Here at the Britz-McKibbin group we are very excited to welcome Hani and Sriprada. We know both of them will be great additions as co-op students. Both Hani and Sriprada are joining us as Level 3 Chemical Biology students from here at McMaster. We can't wait to show them all metabolomics has to offer.

But with new co-ops starting we also had to say good-bye to our previous co-op Nicole. As she finishes up her undergrad this semester we wish her nothing but the best. Thanks for all your hard work and we are excited to hear all about your future experiences.

Congrats Hani on your NSERC

Congrats Hani on getting NSERC for the Winter 2020 term, we are so happy to have you as apart of our team.

Ritchie Ly: McMaster Student Union's TA of the Year

A very big congratulations to Ritchie on winning the TA of the Year award presented by the McMaster Student Union. Your dedication not only to your ongoing research in the Britz-McKibbin group, but to also to the students that you TA is a great reminder for all of us not only within our research group, but within the Chemistry and Chemical Biology department here at McMaster. We can't wait for you to pick up your award on March 27th 2020. Very much deserved and keep up the great work!

!!!New Paper Alert!!!

Check out Sandi's recently published paper in the Journal of Lipid Research titled "Serum non-esterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil and dairy in women". See abstract and link below!

https://www.jlr.org/content/early/2020/03/31/jlr.D120000630.abstract

Abstract

Nutritional studies rely on various biological specimens for fatty acid (FA) determination, yet it is unclear how levels of serum non-esterified FA (NEFAs) correlate with other circulating lipid pools. Here, we used a high throughput method (< 4 min/sample) based on multisegment injection-non-aqueous-capillary electrophoresis–mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first  identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n=50). Acute changes in serum NEFA trajectories were also studied in non-pregnant women (n=18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum omega-3 (ω-3) FA correlated with self-reported total ω-3 daily intake, notably eicosapentaenoic acid (EPA) as its NEFA (r=0.46; p=0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r=0.43; p=0.002), outcomes consistent with results from  total FA serum hydrolysates. In the intervention cohort, serum ω-3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (p=0.0004). Unlike for docosahexaenoic acid, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r=0.66; p=4.6 × 10-10), and was better suited to detect dietary non-adherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to diet records or food frequency questionnaires.

Recent research featured on McMaster's Website

We are very excited that McMaster recently featured Sandi Azab's work on a reliable and accurate blood test to track individual fat intake, a tool that could guide public health policy on healthy eating in the future. Great work Sandi! Check out the article below!!

McMaster chemists develop foolproof new test to track the fats we eat

New Manuscript Alert

The Britz-McKibbin group is very excited to announce the recently publication of some of Michelle Saoi's PhD research assessing sex-specific differences in fetal development during gestation in placental tissue. This work was done in collaboration with Deb Sloboda's group and we can't wait for you to check out the paper published in Scientific Reports. Michelle recently graduated from McMaster and is currently a Metabolomics Specialist at the Memorial Sloan Kettering Cancer Centre in NYC!

PAD and CLTI Discoveries

The Britz-McKibbin group is very excited to announce another new publication in the Journal of Clinical Medicine. Sandi performed serum metabolomics to reveal the mechanisms of peripheral artery disease (PAD) pathophysiology that may improve its diagnosis and prognosis to chronic limb-threatening ischemia (CLTI) complementary to the ankle–brachial index (ABI) and clinical presentations. This was a very interesting study that was done in collaboration with Dr. Qadura at St. Michael's Hospital in Toronto. Not only did they discover lower serum concentrations of creatine, histidine, lysine, oxoproline, monomethylarginine, as well as higher circulating phenylacetylglutamine levles in PAD patients, they also discovered higher serum concentrations of carnitine, creatinine, cystine and trimethylamine-N-oxide in CLTI cases. We hope this research into PAD and CLTI can help improve patient outcomes in the future. Take a look at their work!

Another publication

It's been another really productive week here in the Britz-McKibbin group with another publication from Sandi. For this work Sandi studied perfluoroalkyl substances (PFASs), a major contaminant class due to their ubiquitous prevalence, persistence, and endocrine disrupting activity that can contribute to chronic disease risk (most notably with exposures early in life). Sandi found that PFAS exposures in pregnant women was lower in this specific birth cohort (SouTh Asian birth cohoRT) relative to serum collected prior to 2009 likely due to subsequent phase out of their production. Overall, the method highlighted in this paper offers a convenient approach for large‐scale biomonitoring of environmental exposures to legacy PFASs and their emerging replacements. Take a look at the manuscript (link below)!

Rapid biomonitoring of perfluoroalkyl substance exposures in serum by multisegment injection‐nonaqueous capillary electrophoresis‐tandem mass spectrometry

 

 

MACData Graduate Fellowship: Ritchie Ly

A big congratulations to Ritchie for being awarded the MacDATA Graduate Fellowship. For those of you familiar with MSI-CE-MS, the platform used in the Britz-McKibbin group, although we have found ways to increase the throughput of data acquisition, data processing is still a bottleneck. We cannot wait to see what improvements Ritchie can make to help make data processing more efficient.

The aims of the MacDATA Graduate Fellowship Program are: (1) To provide trainees with an opportunity to acquire practical and theoretical skills in data science. (2) To facilitate exchange of expertise and knowledge in data science across faculties.

Congratulations to Dr. Sandi Azab on her successful PhD defense (Chemical Biology)!

Congratulations to Dr. Sandi Azab on her successful PhD defense (Chemical Biology) on Friday August 14, 2020. 

 

Check out some new work published in Anal Chem by Biban

Article link: https://pubs.acs.org/doi/10.1021/acs.analchem.0c03212

 

Urinary 1-hydroxypyrene (HP) is a widely used biomarker of polycyclic aromatic hydrocarbon exposure relevant for biomonitoring the deleterious health impacts from tobacco smoke and ambient air pollution, as well as the hazards of certain occupations. Conventional methods for urinary HP analysis based on liquid chromatography with native fluorescence detection or tandem mass spectrometry (MS/MS) and gas chromatography–mass spectrometry (GC–MS) are limited by low sample throughput and complicated sample workup protocols that are prone to bias. Herein, we introduce a high throughput method to directly analyze the intact glucuronide conjugate of HP (HP-G) in human urine after a simple acidified ether extraction procedure when using multisegment injection–capillary electrophoresis–tandem mass spectrometry (MSI–CE–MS/MS). Multiplexed analyses of 13 independent urine extracts are achieved in a single run (<3 min/sample) with stringent quality control while avoiding enzyme deconjugation and precolumn chemical derivatization. Method validation demonstrates good technical precision (CV = 7.7%, n = 45) and accuracy with a mean recovery of (93 ± 3%) for urinary HP-G at three concentration levels with adequate detection limits (7 ng/L, S/N = 3). An interlaboratory method comparison of urine samples collected from firefighters deployed in the 2016 Fort McMurray wildfire also confirms good mutual agreement with an acceptable negative bias (mean bias = 15%, n = 55) when measuring urinary HP-G by MSI–CE–MS/MS as compared to total hydrolyzed urinary HP by GC–MS due to the low residual levels of free HP and its sulfate conjugate. This multiplexed separation platform is optimal for large-scale biomonitoring studies of air pollution relevant to global health as well as occupational smoke exposures in firefighters susceptible to dermal PAH absorption when using personal protective equipment.

Recently accepted CE-MS ring trial our group participated in is out now!

Article link: https://pubs.acs.org/doi/abs/10.1021/acs.analchem.0c03129

 

Capillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison to other separation techniques remains underrepresented in metabolomics, as this analytical approach is still perceived as technically challenging and less reproducible, notably for migration time. The latter is key for a reliable comparison of metabolic profiles and for unknown biomarker identification that is complementary to high resolution MS/MS. In this work, we present the results of a Metabo-ring trial involving 16 CE-MS platforms among 13 different laboratories spanning two continents. The goal was to assess the reproducibility and identification capability of CE-MS by employing effective electrophoretic mobility (µeff) as the key parameter in comparison to the relative migration time (RMT) approach. For this purpose, a representative cationic metabolite mixture in water, pretreated human plasma and urine samples spiked with the same metabolite mixture, were used and distributed for analysis by all laboratories. The µeff was determined for all metabolites spiked into each sample. The background electrolyte (BGE) was prepared and employed by each participating lab following the same protocol. All other parameters (capillary, interface, injection volume, voltage ramp, temperature, capillary conditioning and rinsing procedure, etc.) were left to the discretion of the contributing labs. The results revealed that the reproducibility of the µeff for 20 out of the 21 model compounds was below 3.1% vs. 10.9% for RMT, regardless of the huge heterogeneity in experimental conditions and platforms across the thirteen labs. Overall, this Metabo-ring trial demonstrated that CE-MS is a viable and reproducible approach for metabolomics.

Check out our newest IBD paper

A big congratulations to Julie-Anne, a former undergrad in the Britz-McKibbin group currently in Medical School at McGill University for her recent publication in the Journal of Pharmaceutical and Biomedical Analysis. Therein she validated two methods for determination of 3 short chain fatty acids (SCFAs) and 5 electrolytes in lyophilized fecal extracts using CE-iUV. She was able to study how these SCFAs and electrolytes varied among Crohn's and ulcerative colitis patients who were treated with exclusive enteral nutrition or corticosteroid therapy. Check out her work!!

Lyophilized fecal short-chain fatty acid and electrolyte determination by capillary electrophoresis with indirect UV detection for assessment of pediatric inflammatory bowel disease

 

Welcome Na-Yung to the research group

It's a new semester and that means a new co-op student is starting in the Britz-McKibbin group. Welcome to the group Na-Yung, we are looking forward to your contributions this semester to our lab group's research particularly with the large-scale epidemiological PURE study. With it being the end of last semester too we also have to say good-bye to Eric. Thanks for all of your help as a co-op student. With that being said, we are happy to still have you in the research group as you finish your final semester at McMaster as a research student.

New publication alert!

Congratulations to Meera, Zach, Biban and everyone else who contributed to our most recent publication in Nature Protocols. Over 7 months, 4 cohorts or pregnant women from across Canada were profiled (n = 1004) using metabolomics. Stringent quality controls were used to ensure samples were analyzed both accurately and precisely using multisegment injection-capillary electrophoresis-mass spectrometry. We also report reference intervals for 53 serum metabolites from a diverse population of women in their second trimester of pregnancy. Take a look at the publication!

The maternal serum metabolome by multisegment injection-capillary electrophoresis-mass spectrometry: a high-throughput platform and standardized data workflow for large-scale epidemiological studies

Check out our newest publication

The Britz-McKibbin group would like to congratulate one of our former members, Mai Yamamoto, for her recent publication seeking to identify urinary metabolic signatures of pediatric IBD at diagnosis, and during induction treatment. We are always excited to see one of our current (or former) student's work get published. In Mai's work over 122 urinary metabolites were reliably measured from pediatric IBD patients and dynamic changes in sum-normalized urinary metabolites were also monitored following exclusive enteral nutrition (EEN) or corticosteroid therapy (CT) in repeat urine samples collected over 8 weeks. Take a look at her results!

Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease

Undergraduate Thesis Night

A big congratulations to all of our undergraduate thesis students who defended their theses tonight! A great job done by all. Everyone in the Britz-McKibbin group wishes each of you nothing but the best in your future endeavors. Also a HUGE congrats to Sriprada Thallpalli on winning the Analytical section's award for best presentation!

Welcoming Navneet to the group

The Britz group would also like to welcome Navneet Kang to our research group as an NSERC undergraduate summer student. Navneet comes to us from the Chemical Biology program here at McMaster. We can't wait to see what exciting research you are apart of this summer.

MSI-CE-MS versus 1H NMR

Check out our newest publication that features the first inter-method comparison of MSI-CE-MS with 1H NMR for serum metabolite quantification, as well as the identification of serum biomarkers associated with liver fibrosis progression in hepatitis C patients. Congratulations to Meera and Zach as well as our previous thesis students, Holly and Richel for this publication. Thanks to all of our collaborators as well including Dr. Sarfaraz and Dr. Wishart for your ongoing support and collaboration.

A Cross-Platform Metabolomics Comparison Identifies Serum Metabolite Signatures of Liver Fibrosis Progression in Chronic Hepatitis C Patients

Welcome new undergrad students

It's a new academic year in the Britz-McKibbin group and that means we have new undergrads to introduce. Welcome Vanessa, Claire, and Luxiga to our research group, we can't wait to see all your progress this year! Welcome back to Na-Yung, Navneet, Hani, and Michael as well who have all returned for further research opportunities. Glad to have all of you back!!

Ritchie's MSI-NACE-MS

Congratulations to Ritchie on your most recent publication in the Journal of Proteome Research featuring your breakthrough lipidomics MSI-NACE-MS work done in collaboration with Human Metabolome Technologies (HMT) in Japan!