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Archive for the ‘Biomarkers & Medical Diagnostics’ Category


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Scientists at the Stanford University School of Medicine have completed the first-ever characterization of the meticulously timed immune system changes in women that occur during pregnancy. The findings were published in Science Immunology revealed that there is an immune clock of pregnancy and suggest it may help doctors predict preterm birth.

 

The timing of immune system changes follows a precise and predictable pattern in normal pregnancy. Although physicians have long known that the expectant mother’s immune system adjusts to prevent her body from rejecting the fetus, no one had investigated the full scope of these changes, nor asked if their timing was tightly controlled.

 

Nearly 10 percent of U.S. infants are born prematurely, arriving three or more weeks early, but physicians lack a reliable way to predict premature deliveries. Previous research at Stanford and other places suggested that inflammatory immune responses may help in triggering early labor. It suggested that if scientists identify an immune signature of impending preterm birth, they should be able to design a blood test to detect it.

 

The researchers used mass cytometry, a technique developed at Stanford, to simultaneously measure up to 50 properties of each immune cell in the blood samples. They counted the types of immune cells, assessed what signaling pathways were most active in each cell, and determined how the cells reacted to being stimulated with compounds that mimic infection with viruses and bacteria.

 

The researchers developed an algorithm that captures the immunological timeline during pregnancy that both validates previous findings and sheds new light on immune cell interaction during gestation. By defining this immunological chronology during normal term pregnancy, they can now begin to determine which alterations associate with pregnancy-related pathologies.

 

With an advanced statistical modeling technique, introduced for the first time in this study, the scientists then described in detail how the immune system changes throughout pregnancy. Instead of grouping the women’s blood samples by trimester for analysis, the model treated gestational age as a continuous variable, allowing the researchers to account for the exact time during pregnancy at which each sample was taken. The mathematical model also incorporated knowledge from the existing scientific literature of how immune cells behave in nonpregnant individuals to help determine which findings were most likely to be important.

 

The study confirmed immune features of pregnancy that were already known. Such as the scientists saw that natural killer cells and neutrophils have enhanced action during pregnancy. The researchers also uncovered several previously unappreciated features of how the immune system changes, such as the finding that activity of the STAT5 signaling pathway in CD4+T cells progressively increases throughout pregnancy on a precise schedule, ultimately reaching levels much higher than in nonpregnant individuals. The STAT5 pathway is involved in helping another group of immune cells, regulatory T cells, to differentiate. Interestingly, prior research in animals has indicated that regulatory T cells are important for maintaining pregnancy.

 

The next step will be to conduct similar research using blood samples from women who deliver their babies prematurely to see where their trajectories of immune function differ from normal.

 

This study revealed a precisely timed chronology of immune adaptations in peripheral blood over the course of a term pregnancy. This finding was enabled by high-content, single-cell mass cytometry coupled with a csEN algorithm accounting for the modular structure of the immune system and previous knowledge. The study provided the conceptual backbone and the analytical framework to examine whether disruption of this chronology is a diagnostically useful characteristic of preterm birth and other pregnancy-related pathologies.

 

References:

 

http://immunology.sciencemag.org/content/2/15/eaan2946.full

 

http://med.stanford.edu/news/all-news/2017/09/immune-system-changes-during-pregnancy-are-precisely-timed.html

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078586/

 

http://www.nature.com/nm/journal/v19/n5/full/nm.3160.html?foxtrotcallback=true

 

https://www.ncbi.nlm.nih.gov/pubmed/14758358

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SNP-based Study on high BMI exposure confirms CVD and DM Risks – no associations with Stroke

Reporter: Aviva Lev-Ari, PhD, RN

Genes Affirm: High BMI Carries Weighty Heart, Diabetes Risk – Mendelian randomization study adds to ‘burgeoning evidence’

by Crystal Phend, Senior Associate Editor, MedPage Today, July 05, 2017

 

The “genetically instrumented” measure of high BMI exposure — calculated based on 93 single-nucleotide polymorphisms associated with BMI in prior genome-wide association studies — was associated with the following risks (odds ratios given per standard deviation higher BMI):

  • Hypertension (OR 1.64, 95% CI 1.48-1.83)
  • Coronary heart disease (CHD; OR 1.35, 95% CI 1.09-1.69)
  • Type 2 diabetes (OR 2.53, 95% CI 2.04-3.13)
  • Systolic blood pressure (β 1.65 mm Hg, 95% CI 0.78-2.52 mm Hg)
  • Diastolic blood pressure (β 1.37 mm Hg, 95% CI 0.88-1.85 mm Hg)

However, there were no associations with stroke, Donald Lyall, PhD, of the University of Glasgow, and colleagues reported online in JAMA Cardiology.

The associations independent of age, sex, Townsend deprivation scores, alcohol intake, and smoking history were found in baseline data from 119,859 participants in the population-based U.K. Biobank who had complete medical, sociodemographic, and genetic data.

“The main advantage of an MR approach is that certain types of study bias can be minimized,” the team noted. “Because DNA is stable and randomly inherited, which helps to mitigate errors from reverse causality and confounding, genetic variation can be used as a proxy for lifetime BMI to overcome limitations such as reverse causality and confounding, a process that hampers observational analyses of obesity and its consequences.”

 

Other related articles published in this Open Access Online Scientific Journal include the following:

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    Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics

    Nov 28, 2015 | Kindle eBook

    by Justin D. Pearlman MD ME PhD MA FACC and Stephen J. Williams PhD
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    Perspectives on Nitric Oxide in Disease Mechanisms (Biomed e-Books Book 1)

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    Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery (Series C Book 2)

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    Metabolic Genomics & Pharmaceutics (BioMedicine – Metabolomics, Immunology, Infectious Diseases Book 1)

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    by Larry H. Bernstein MD FCAP and Prabodah Kandala PhD
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    Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics (Series E: Patient-Centered Medicine Book 3)

    Dec 26, 2015 | Kindle eBook

    by Larry H. Bernstein MD FACP and Aviva Lev-Ari PhD RN
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    Genomics Orientations for Personalized Medicine (Frontiers in Genomics Research Book 1)

    Nov 22, 2015 | Kindle eBook

    by Sudipta Saha PhD and Ritu Saxena PhD
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    Cancer Biology and Genomics for Disease Diagnosis (Series C: e-Books on Cancer & Oncology Book 1)

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    Regenerative and Translational Medicine: The Therapeutic Promise for Cardiovascular Diseases

    Dec 26, 2015 | Kindle eBook

    by Justin D. Pearlman MD ME PhD MA FACC and Stephen J. Williams
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    Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation: The Art of Scientific & Medical Curation

    Nov 29, 2015 | Kindle eBook

    by Larry H. Bernstein MD FCAP and Aviva Lev-Ari PhD RN
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Genomic Diagnostics: Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single Molecule DNA Sequencing

Curator: Aviva Lev-Ari, PhD, RN

 

This article presents Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single molecule DNA sequencing

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Reporter and Curator: Irina Robu, PhD

Monitoring cancer patients and evaluating their response to treatment can sometimes involve invasive procedures, including surgery.

The liquid biopsies have become something of a Holy Grail in cancer treatment among physicians, researchers and companies gambling big on the technology. Liquid biopsies, unlike traditional biopsies involving invasive surgery — rely on an ordinary blood draw. Developments in sequencing the human genome, permitting researchers to detect genetic mutations of cancers, have made the tests conceivable. Some 38 companies in the US alone are working on liquid biopsies by trying to analyze blood for fragments of DNA shed by dying tumor cells.

Premature research on the liquid biopsy has concentrated profoundly on patients with later-stage cancers who have suffered treatments, including chemotherapy, radiation, surgery, immunotherapy or drugs that target molecules involved in the growth, progression and spread of cancer. For cancer patients undergoing treatment, liquid biopsies could spare them some of the painful, expensive and risky tissue tumor biopsies and reduce reliance on CT scans. The tests can rapidly evaluate the efficacy of surgery or other treatment, while old-style biopsies and CT scans can still remain inconclusive as a result of scar tissue near the tumor site.

As recently as a few years ago, the liquid biopsies were hardly used except in research. At the moment, thousands of the tests are being used in clinical practices in the United States and abroad, including at the M.D. Anderson Cancer Center in Houston; the University of California, San Diego; the University of California, San Francisco; the Duke Cancer Institute and several other cancer centers.

With patients for whom physicians cannot get a tissue biopsy, the liquid biopsy could prove a safe and effective alternative that could help determine whether treatment is helping eradicate the cancer. A startup, Miroculus developed a cheap, open source device that can test blood for several types of cancer at once. The platform, called Miriam finds cancer by extracting RNA from blood and spreading it across plates that look at specific type of mRNA. The technology is then hooked up at a smartphone which sends the information to an online database and compares the microRNA found in the patient’s blood to known patterns indicating different type of cancers in the early stage and can reduce unnecessary cancer screenings.

Nevertheless, experts warn that more studies are essential to regulate the accuracy of the test, exactly which cancers it can detect, at what stages and whether it improves care or survival rates.

SOURCE

https://www.fastcompany.com/3037117/a-new-device-can-detect-multiple-types-of-cancer-with-a-single-blood-test

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/

Other related articles published in this Open Access Online Scientific Publishing Journal include the following:

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/28/liquid-biopsy-chip-detects-an-array-of-metastatic-cancer-cell-markers-in-blood-rd-worcester-polytechnic-institute-micro-and-nanotechnology-lab/

Liquid Biopsy Assay May Predict Drug Resistance

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/11/06/liquid-biopsy-assay-may-predict-drug-resistance/

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI

Curator: Marzan Khan, B.Sc

https://pharmaceuticalintelligence.com/2017/01/05/one-blood-sample-can-be-tested-for-a-comprehensive-array-of-cancer-cell-biomarkers-rd-wpi

 

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Low sperm count and motility are markers for male infertility, a condition that is actually a neglected health issue worldwide, according to the World Health Organization. Researchers at Harvard Medical School have developed a very low cost device that can attach to a cell phone and provides a quick and easy semen analysis. The device is still under development, but a study of the machine’s capabilities concludes that it is just as accurate as the elaborate high cost computer-assisted semen analysis machines costing tens of thousands of dollars in measuring sperm concentration, sperm motility, total sperm count and total motile cells.

 

The Harvard team isn’t the first to develop an at-home fertility test for men, but they are the first to be able to determine sperm concentration as well as motility. The scientists compared the smart phone sperm tracker to current lab equipment by analyzing the same semen samples side by side. They analyzed over 350 semen samples of both infertile and fertile men. The smart phone system was able to identify abnormal sperm samples with 98 percent accuracy. The results of the study were published in the journal named Science Translational Medicine.

 

The device uses an optical attachment for magnification and a disposable microchip for handling the semen sample. With two lenses that require no manual focusing and an inexpensive battery, it slides onto the smart phone’s camera. Total cost for manufacturing the equipment: $4.45, including $3.59 for the optical attachment and 86 cents for the disposable micro-fluidic chip that contains the semen sample.

 

The software of the app is designed with a simple interface that guides the user through the test with onscreen prompts. After the sample is inserted, the app can photograph it, create a video and report the results in less than five seconds. The test results are stored on the phone so that semen quality can be monitored over time. The device is under consideration for approval from the Food and Drug Administration within the next two years.

 

With this device at home, a man can avoid the embarrassment and stress of providing a sample in a doctor’s clinic. The device could also be useful for men who get vasectomies, who are supposed to return to the urologist for semen analysis twice in the six months after the procedure. Compliance is typically poor, but with this device, a man could perform his own semen analysis at home and email the result to the urologist. This will make sperm analysis available in the privacy of our home and as easy as a home pregnancy test or blood sugar test.

 

The device costs about $5 to make in the lab and can be made available in the market at lower than $50 initially. This low cost could help provide much-needed infertility care in developing or underdeveloped nations, which often lack the resources for currently available diagnostics.

 

References:

 

https://www.nytimes.com/2017/03/22/well/live/sperm-counts-via-your-cellphone.html?em_pos=small&emc=edit_hh_20170324&nl=well&nl_art=7&nlid=65713389&ref=headline&te=1&_r=1

 

http://www.npr.org/sections/health-shots/2017/03/22/520837557/a-smartphone-can-accurately-test-sperm-count

 

https://www.ncbi.nlm.nih.gov/pubmed/28330865

 

http://www.sciencealert.com/new-smartphone-microscope-lets-men-check-the-health-of-their-own-sperm

 

https://www.newscientist.com/article/2097618-are-your-sperm-up-to-scratch-phone-microscope-lets-you-check/

 

https://www.dezeen.com/2017/01/19/yo-fertility-kit-men-test-sperm-count-smartphone-design-technology-apps/

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

During pregnancy, the baby is mostly protected from harmful microorganisms by the amniotic sac, but recent research suggests the baby could be exposed to small quantities of microbes from the placenta, amniotic fluid, umbilical cord blood and fetal membranes. One theory is that any possible prenatal exposure could ‘pre-seed’ the infant microbiome. In other words, to set the right conditions for the ‘main seeding event’ for founding the infant microbiome.

When a mother gives birth vaginally and if she breastfeeds, she passes on colonies of essential microbes to her baby. This continues a chain of maternal heritage that stretches through female ancestry for thousands of generations, if all have been vaginally born and breastfed. This means a child’s microbiome, that is the trillions of microorganisms that live on and in him or her, will resemble the microbiome of his/her mother, the grandmother, the great-grandmother and so on, if all have been vaginally born and breastfed.

As soon as the mother’s waters break, suddenly the baby is exposed to a wave of the mother’s vaginal microbes that wash over the baby in the birth canal. They coat the baby’s skin, and enter the baby’s eyes, ears, nose and some are swallowed to be sent down into the gut. More microbes form of the mother’s gut microbes join the colonization through contact with the mother’s faecal matter. Many more microbes come from every breath, from every touch including skin-to-skin contact with the mother and of course, from breastfeeding.

With formula feeding, the baby won’t receive the 700 species of microbes found in breast milk. Inside breast milk, there are special sugars called human milk oligosaccharides (HMO’s) that are indigestible by the baby. These sugars are designed to feed the mother’s microbes newly arrived in the baby’s gut. By multiplying quickly, the ‘good’ bacteria crowd out any potentially harmful pathogens. These ‘good’ bacteria help train the baby’s naive immune system, teaching it to identify what is to be tolerated and what is pathogen to be attacked. This leads to the optimal training of the infant immune system resulting in a child’s best possible lifelong health.

With C-section birth and formula feeding, the baby is not likely to acquire the full complement of the mother’s vaginal, gut and breast milk microbes. Therefore, the baby’s microbiome is not likely to closely resemble the mother’s microbiome. A baby born by C-section is likely to have a different microbiome from its mother, its grandmother, its great-grandmother and so on. C-section breaks the chain of maternal heritage and this break can never be restored.

The long term effect of an altered microbiome for a child’s lifelong health is still to be proven, but many studies link C-section with a significantly increased risk for developing asthma, Type 1 diabetes, celiac disease and obesity. Scientists might not yet have all the answers, but the picture that is forming is that C-section and formula feeding could be significantly impacting the health of the next generation. Through the transgenerational aspect to birth, it could even be impacting the health of future generations.

References:

https://blogs.scientificamerican.com/guest-blog/shortchanging-a-babys-microbiome/

https://www.ncbi.nlm.nih.gov/pubmed/23926244

https://www.ncbi.nlm.nih.gov/pubmed/26412384

https://www.ncbi.nlm.nih.gov/pubmed/25290507

https://www.ncbi.nlm.nih.gov/pubmed/25974306

https://www.ncbi.nlm.nih.gov/pubmed/24637604

https://www.ncbi.nlm.nih.gov/pubmed/22911969

https://www.ncbi.nlm.nih.gov/pubmed/25650398

https://www.ncbi.nlm.nih.gov/pubmed/27362264

https://www.ncbi.nlm.nih.gov/pubmed/27306663

http://www.mdpi.com/1099-4300/14/11/2036

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464665/

https://www.ncbi.nlm.nih.gov/pubmed/24848255

https://www.ncbi.nlm.nih.gov/pubmed/26412384

https://www.ncbi.nlm.nih.gov/pubmed/28112736

http://ndnr.com/gastrointestinal/the-infant-microbiome-how-environmental-maternal-factors-influence-its-development/

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VOC – Biomarkers for Disease Diagnosis: Sniffing Out Cancer: Israeli Prof. Finds Diseases Like Cancer And Parkinson’s Can Be Detected On The Breath

Reporter: Aviva Lev-Ari, PhD, RN

 

VOC – Volatile Organic Compounds as BioMarkers.

voc

Image Source: http://nocamels.com/2017/01/disease-detection-smelling-breath/?utm_source=activetrail&utm_medium=email&utm_campaign=nc19/1/17

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http://nocamels.com/2017/01/disease-detection-smelling-breath/?utm_source=activetrail&utm_medium=email&utm_campaign=nc19/1/17

Sniffing Out Cancer: Israeli Prof. Finds Diseases Like Cancer And Parkinson’s Can Be Detected On The Breath

by Yonatan Sredni, NoCamels January 16, 2017 

What if detecting cancer was as easy as breathing in and out? According to the results of a recent study, it is.

An international team of 56 researchers in five countries has confirmed that different diseases are characterized by different “chemical signatures” identifiable in breath samples.

The findings by the team led by Israel’s Professor Hossam Haick of the Technion-Israel Institute of Technology were published recently in ACS Nano.

SEE ALSO: Revolutionary Device Detects Deadly Diseases, Cancer, On The Breath

Although diagnostic techniques based on breath samples have been demonstrated in the past, until now there has not been scientific proof that different and unrelated diseases are characterized by distinct chemical breath signatures. Also, technologies developed to date for this type of diagnosis have been limited to detecting a small number of diseases.

17 diseases, 13 shared chemical components

The study of more than 1,400 patients included 17 different and unrelated diseases: lung cancer, colorectal cancer, head and neck cancer, ovarian cancer, bladder cancer, prostate cancer, kidney cancer, stomach cancer, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, Parkinson’s disease (two types), multiple sclerosis, pulmonary hypertension, preeclampsia and chronic kidney disease. Samples were collected between January 2011 and June 2014 from 14 departments at nine medical centers in five countries: Israel, France, the USA, Latvia and China.

The researchers tested the chemical composition of the breath samples using an accepted analytical method (mass spectrometry). They discovered that all 17 of the diseases contained the same 13 chemical components, albeit in different compositions.

SOURCE

http://nocamels.com/2017/01/disease-detection-smelling-breath/?utm_source=activetrail&utm_medium=email&utm_campaign=nc19/1/17

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