Robotic arm probes chemistry of 3-D objects by mass spectrometry

When life on Earth was first getting started, simple molecules bonded together into the precursors of modern genetic material. A catalyst would have been needed, but enzymes had not yet evolved. One theory is that the catalytic minerals on a meteorite's surface could have jump-started life's first chemical reactions. But scientists need a way to directly analyze these rough, irregularly shaped surfaces. A new robotic system at Georgia Tech's Center for Chemical Evolution could soon let scientists better simulate and analyze the chemical reactions of early Earth on the surface of real rocks to further test this theory.

In a proof-of-concept study, scientists selected a region for analysis on round or irregularly-shaped objects using a 3-D camera on a robotic arm, which mapped the 3-dimentional coordinates of the sample's surface. The scientists programmed the robotic arm to poke the sample with an acupuncture needle. The needle collected a small amount of material that the robot deposited in a nearby mass spectrometer, which is a powerful tool for determining a substance's chemical composition.

"You see the object on a monitor and then you can point and click and take a sample from a particular spot and the robot will go there," said Facundo Fernandez, a professor in the School of Chemistry and Biochemistry, whose lab led the study. "We're using an acupuncture needle that will touch very carefully on the surface of the object and then the robot will turn around and put the material inside of a high resolution mass spectrometer."

The research was published online February 28 in the journal Analyst, a publication of the Royal Society of Chemistry. The work was supported by a National Science Foundation (NSF) Major Research Instrumentation Program (MRI) grant and by the National Science Foundation (NSF) and NASA Astrobiology Program, under the NSF Center for Chemical Evolution.

Mass spectrometry is a powerful tool for analyzing surface chemistry or for identifying biological samples. It's widely used in research labs across many disciplines, but samples for analysis typically have to be cleaned, carefully prepared, and in the case of rocks, cut into thin, flat samples. The new robotic system is the first report of a 3-D mass spectrometry native surface imaging experiment.

"Other people have used an acupuncture needle to poke a sample and then put that in mass spec, but nobody has tried to do a systematic, three-dimensional surface experiment," Fernandez said. "We are trying to push the limits."

To show that the system was capable of probing a three-dimensional object, the researchers imprinted ink patterns on the surfaces of polystyrene spheres. The team then used the robotic arm to model the surfaces, probe specific regions, and see if samples collected were sufficient for mass spectrometry analysis. The researchers were able to detect inks of different colors and create a 3-D image of the object with sufficient sensitivity for their proof-of-principle setup, Fernandez said.

The research was the result of collaboration between Fernandez's group, which specializes in mass spectrometry, and Henrik Christensen's robotics group in the College of Computing. Christensen is the KUKA Chair of Robotics and a Distinguished Professor of Computing. He is also the executive director of the Institute for Robotics and Intelligent Machines (IRIM) at Georgia Tech.

"The initial findings of this study mark a significant step toward using robots for three-dimensional surface experiments on geological material," Christensen said. "We are using the repeatability and accuracy of robots to achieve new capabilities that have numerous applications in biomedical areas such as dermatology."

"It doesn't happen very often that a group in mass spectrometry will have a very talented robotics group next to them," Fernandez said. "If we tried to learn the robotics on our own it could take us a decade, but for them it's something that's not that difficult."

Christensen's team loaned a Kuka KR5 sixx R650 robot to Fernandez's lab for the study. Afterwards, Fernandez's lab purchased their own robot from Universal Robots. They have also upgraded to a new mass spectrometer capable of resolution nearly eight times higher than the one used in the study. They will soon begin replicating early Earth chemistry on rocks and analyzing the reaction products with their robotic sampling system.

"We really want to look at rocks," Fernandez said. "We want to do reactions on rocks and granites and meteorites and then see what can be produced on the surface."

The technology could also be applied to other research fields, Fernandez said. For example, the robot-mass spec combo might be useful to dermatologists who often probe lesions on the skin, which have distinct molecular signatures depending on if the lesion is a tumor or normal skin tissue.

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Cancer treatment revolution potential with new drug

A revolution in cancer treatment could soon be underway following a breakthrough that may lead to a dramatic improvement in cancer survival rates.

A new study at the University of Warwick, published today in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body's natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.

Called ZL105, the drug is a compound based on the precious metal iridium. The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.

Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said "The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell 'power-house'. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects."

Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.

Study co-author Professor Peter J. Sadler said "Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments."

"Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.

"In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by patients" argues Professor Sadler.

This research could also lead to substantial improvements in cancer survival rates. "Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells" said Dr Romero-Canelon.

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'Glue' holding together skin cells, other epithelial tissue more active than realized

The strong mechanical attachments -- the "glue" -- that hold together the cells of the skin and the other epithelial tissues of the body are the adherens junctions.

These junctions are responsible for maintaining the shape and integrity of the sheets of epithelial cells that line such body cavities as the digestive tract, as well as the surfaces of structures such as the heart. Defects in the proteins of these attachments have been implicated as potential contributors to the development and spread of cancer.

Recent research on Drosophila flies, combined with previous studies in cell cultures, are challenging the traditional view that adherens junctions maintain tissue integrity by passively resisting disruptive forces.

In studies with Drosophila embryos, the Princeton University lab of Nobel laureate Eric Wieschaus, Ph.D., has uncovered the first evidence in living organisms that adherens junctions actively respond to mechanical cues by remodeling their own position and intensity, which in turn restructures the cells.

Mo Weng, Ph.D., postdoctoral fellow in the lab, used live imaging and quantitative image analysis of fixed and live embryos to determine that these changes depend on mechanical force mediated by the motor protein myosin and precede the changes in the distribution of cell polarity proteins, such as Bazooka, that are responsible for spatial organization of the cells.

Understanding the regulation and functioning of adherens junctions sheds light on the organization of multi-cellularity -- from cell-cell contacts to the remodeling of tissues and organs during life.

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Fewer children at risk for deficient vitamin D

Under new guidelines from the Institute of Medicine, the estimated number of children who are at risk of having insufficient or deficient levels of vitamin D is drastically reduced from previous estimates, according to a Loyola University Chicago Stritch School of Medicine study.

The study, led by Holly Kramer, MD, MPH, and Ramon Durazo-Arvizu, PhD, is published online ahead of print in the Journal of Pediatric Endocrinology and Metabolism.

New Institute of Medicine guidelines say most people get sufficient vitamin D when their blood levels are at or above 20 nanograms per milliliter (ng/mL). The Pediatric Endocrine Society has a similar guideline. However, other guidelines recommend vitamin D levels above 30 ng/mL.

Loyola researchers studied vitamin D data from a nationally representative sample of 2,877 U.S. children and adolescents ages 6 to 18 who participated in the National Health and Nutrition Examination Survey.

The study found that under the Institute of Medicine guidelines, 10.3 percent of children ages 6 to 18 are at risk of inadequate or deficient vitamin D levels. (This translates to an estimated 5.5 million children.)

By comparison, a 2009 study in the journal Pediatrics, which defined sufficient vitamin D levels as greater than 30 ng/mL, found that an estimated 70 percent of people ages 1 to 21 had deficient or insufficient vitamin D levels.

Under previous guidelines, millions of children who had vitamin D levels between 20 and 30 ng/mL would have needed supplementation. Under the Institute of Medicine guidelines, children in this range no longer need to take vitamin D supplements.

The new study found that children at risk of vitamin D deficiency under the Institute of Medicine guidelines are more likely to be overweight, female, non-white and between the ages of 14 and 18.

The Institute of Medicine's new vitamin D guidelines are based on nearly 1,000 published studies and testimony from scientists and other experts. The IOM found that vitamin D is essential to avoid poor bone health, such as rickets. But there have been conflicting and mixed results in studies on whether vitamin D can also protect against cancer, heart disease, autoimmune diseases and diabetes. Moreover, excessive vitamin D can damage the kidneys and heart, the IOM found.

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Twenty-five percent of breast cancer survivors report financial decline due to treatment

Four years after being treated for breast cancer, a quarter of survivors say they are worse off financially, at least partly because of their treatment, according to a new study led by University of Michigan Comprehensive Cancer Center researchers. In addition, 12 percent reported that they still have medical debt from their treatment.

Financial decline varied significantly by race, with Spanish-speaking Latinas most likely to be impacted. Debt was reported more frequently in English-speaking Latinas and Blacks, the study found. Results appear in the Journal of Clinical Oncology.

"As oncologists, we are proud of the advances in our ability to cure an increasing proportion of patients diagnosed with breast cancer. But as treatments improve, we must ensure that we do not leave these patients in financial ruin because of our efforts," says study author Reshma Jagsi, M.D., D.Phil., associate professor of radiation oncology at the University of Michigan Medical School.

The researchers surveyed women in Detroit and Los Angeles who had been diagnosed with early stage breast cancer, based on data obtained from the National Cancer Institute's Surveillance, Epidemiology and End Results population-based registry. Women were surveyed about nine months after diagnosis and again about four years later, with 1,502 women responding to both surveys.

The surveys asked about patients' perceptions of whether they were worse off financially since their diagnosis, and whether that has caused long-term challenges. For example, patients were asked if they had altered their medical care because of financial concerns, by skipping medication or by missing a doctor's appointment or a mammogram. Other questions looked at broader hardships, such as going without health insurance, having utilities turned off or moving out of their home.

Blacks and English-speaking Latinas were more likely than Whites to have experienced one of these issues. Other factors that made a woman more likely to experience these hardships include age under 65, household income under $50,000, part-time work at diagnosis, reduced work hours after diagnosis, lack of substantial prescription drug coverage, breast cancer recurrence, and undergoing chemotherapy.

"These patients are particularly vulnerable to financial distress," Jagsi says. "We need to ensure appropriate communication between patients and their doctors regarding the financial implications of a cancer diagnosis and treatment decisions to help reduce this long-term burden."

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State-of-the-state on genetic-based testing, treatment for breast cancer revealed

Dartmouth researchers at its Norris Cotton Cancer Center have compiled a review of the role that information gathered through genetic testing plays in the diagnosis and treatment of breast cancer. The paper entitled "Personalized Therapy for Breast Cancer" was accepted on March 17, 2014, for publication in Clinical Genetics. The paper discusses targeted therapies, new biomarkers, and the quality of commercially available testing methods.

Genomic testing is changing the way breast cancer is diagnosed and treated. By examining a woman's genes to look for specific mutations or biomarkers, treatment can be personalized to the tumor cell's biology and a woman's genetics.

"A personalized approach increases the precision and success of breast cancer treatment," said Gregory Tsongalis, PhD, director of Molecular Pathology at Norris Cotton Cancer Center and lead author of the paper. "Molecular profiling exposes a tumor's Achilles' heel. We can see what messages the tumor cells are receiving and sending. It is a biological intelligence gathering mission in an attempt to interrupt the disease.

According to Tsongalis large scale genetic testing of breast cancer is not yet part of routine clinical care as it is with lung and colon cancers, even though he and his team run a genetics laboratory for routine cancer care. Genetic testing according to Tsongalis is a powerful weapon in the diagnosis and treatment of breast cancer.

With results from the genetic testing of a tumor cell's biology, clinicians categorize breast cancer in ways that allow them to select the most effective treatments. Based on genetic biomarkers, there are three categories of breast cancer:

1. ER-positive breast cancer needs hormones, such as estrogen to grow. Estrogen fuels cancer cell growth, stops cancer cells from dying, and helps the cells lay down roots to maintain blood supply for tumors. ER-positive cancers are less aggressive and often treated with drugs that are selective estrogen receptor modulators (SERM), such as Tamoxifen, Raloxifene, Toremifene and aromatese inhibitors (AIs) such as Letrozole, Anastrozole and Exemestane. SERM drugs block estrogen from telling cancer cells to divide and grow; they have been shown successful in treating as well as preventing ER positive breast cancer. AIs block intake of estrogen in the system and reduce estrogen levels in serum, tissue, and tumor cells. AIs are commonly used in post-menopausal women.
2. HER2 -positive breast cancer cells contain large amounts of protein that help them grow and multiply. Medications turn off the production of protein to stop tumor growth and kill cancer cells. HER2 treatments include Trastuzumab, Laptinib, Pertuzumab, and Trastuzumab Emtansine.
3. Triple negative (ER-negative/PR-negative/HER2-negative) breast cancer is the most aggressive type and has the poorest clinical outcome. There is no approved personalized therapy for triple negative, but research has identified six subtypes of tumors. This is the first step in identifying biomarkers that can lead to the development of personalized treatments.

"Genomic testing of breast cancer has expanded our understanding of the disease process and has proven more effective than traditional laboratory tests," said Tsongalis. "At NCCC all of our breast cancer patients are tested for abnormal copies of the HER2 gene using specially designed DNA probes. New biomarkers and the reclassification of cancers based on these biomarkers has led to the development of new, effective treatments that can be personalized to an individual breast cancer patient."

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Plasma tool for destroying cancer cells

Plasma medicine is a new and rapidly developing area of medical technology. Specifically, understanding the interaction of so-called atmospheric pressure plasma jets with biological tissues could help to use them in medical practice.

Under the supervision of Sylwia Ptasinska from the University of Notre Dame, in Indiana, USA, Xu Han and colleagues conducted a quantitative and qualitative study of the different types of DNA damage induced by atmospheric pressure plasma exposure, the paper is published inThe European Physical Journal D, as part of a special issue on nanoscale insights into Ion Beam Cancer Therapy. This approach, they hope, could ultimately lead to devising alternative tools for cancer therapy as well as applications in hospital hygiene, dental care, skin diseases, antifungal care, chronic wounds and cosmetics treatments.

To investigate the DNA damage from the so-called non-thermal Atmospheric Pressure Plasma Jet (APPJ), the team adopted a common technique used in biochemistry, called agarose gel electrophoresis. They studied the nature and level of DNA damage by plasma species, so-called reactive radicals, under two different conditions of the helium plasma source with different parameters of electric pulses.

They also identified the effect of water on DNA damage. To do so, they examined the role of reactive radicals involved in DNA damage processes occurring in an aqueous environment. They then compared them to previous results obtained in dry DNA samples.

The next step would involve investigating plasma made from helium mixtures with different molecular ratios of other gases, such as oxygen, nitrous oxide, carbon dioxide and steam, under different plasma source conditions. The addition of another gas is expected to increase the level of radical species, such as reactive oxygen species and reactive nitrogen species, known to produce severe DNA damage. These could, ultimately, help to destroy cancerous tumour cells.

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WHO opens public consultation on draft sugars guideline

5 March 2014 | GENEVA - WHO is launching a public consultation on its draft guideline on sugars intake. When finalized, the guideline will provide countries with recommendations on limiting the consumption of sugars to reduce public health problems like obesity and dental caries (commonly referred to as tooth decay).

Comments on the draft guideline will be accepted via the WHO web site from 5 through 31 March 2014. Anyone who wishes to comment must submit a declaration of interests. An expert peer-review process will happen over the same period. Once the peer-review and public consultation are completed, all comments will be reviewed, the draft guidelines will be revised if necessary and cleared by WHO’s Guidelines Review Committee before being finalized.

New draft guideline proposals

WHO’s current recommendation, from 2002, is that sugars should make up less than 10% of total energy intake per day. The new draft guideline also proposes that sugars should be less than 10% of total energy intake per day. It further suggests that a reduction to below 5% of total energy intake per day would have additional benefits. Five per cent of total energy intake is equivalent to around 25 grams (around 6 teaspoons) of sugar per day for an adult of normal Body Mass Index (BMI).

The suggested limits on intake of sugars in the draft guideline apply to all monosaccharides (such as glucose, fructose) and disaccharides (such as sucrose or table sugar) that are added to food by the manufacturer, the cook or the consumer, as well as sugars that are naturally present in honey, syrups, fruit juices and fruit concentrates.

Much of the sugars consumed today are “hidden” in processed foods that are not usually seen as sweets. For example, 1 tablespoon of ketchup contains around 4 grams (around 1 teaspoon) of sugars. A single can of sugar-sweetened soda contains up to 40 grams (around 10 teaspoons) of sugar.

The draft guideline was formulated based on analyses of all published scientific studies on the consumption of sugars and how that relates to excess weight gain and tooth decay in adults and children.

• Read the draft guideline and submit your comments

Note to editors

Papers published with findings of two systematic reviews (analyses of published scientific studies) commissioned by WHO that informed the development of the draft guidelines:

• Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies
  Conducted by the University of Otago, New Zealand) published in the BMJ
• Effect on caries of restricting sugars intake: Systematic review to inform WHO guidelines
  Conducted by Newcastle University, UK) published in the Journal of Dental Research

For more information please contact:

Tarik Jasarevic
WHO, Geneva
Communications Officer
Telephone: +41 22 791 5099
Mobile: +41 79367 6214
E-mail:jasarevict@who.int

Glenn Thomas
WHO, Geneva
WHO Communications Officer
Telephone: +41 22 791 3983
Mobile: +41 79 509 0677
E-mail:thomasg@who.int

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Message from WHO Director-General on International Women’s Day

On this day, WHO joins others in celebrating women’s achievements. These achievements are inspiring, and they can inspire change. In health development, as in many other areas, women are agents of change. They are the driving force that creates better lives for families, communities and, increasingly, the countries they have been elected to govern.

As I have learned from my discussions with parliaments in several countries, women are increasingly winning top leadership roles, in rich and poor countries alike, and this helps shape entire societies in broadly beneficial ways. Every time a women excels in a high-profile position, her achievement lifts the social status of women everywhere.

To inspire change, all women need to be free to achieve their full potential. This means freedom from all forms of discrimination, freedom to pursue all opportunities, including education, freedom to earn and spend their own income, and freedom to follow the career paths they decide they want.

The health sector can do much to free women by ensuring they have access to all the health services they need, including sexual and reproductive health services. Participants at last year’s London Summit on Family Planning achieved a breakthrough commitment to halve the number of girls and women in developing countries who want modern contraceptives but have no access. This commitment will give 120 million additional women the right to decide whether, when, and how many children they want to have. This, too, is freedom.

Throughout history, women have been associated with care and compassion. Worldwide, up to 80% of health care is provided in the home, almost always by women. This should inspire our admiration, but it should also underscore the need for change. Most of this work is unsupported, unrecognized, and unpaid.

Polio is on the verge of eradication largely thanks to the millions of women – from vaccinators to administrators to medical doctors and mothers – who have made the vaccination and protection of children their life’s mission. On this International Women’s Day, let me thank these women for a level of dedication that can improve the world in a permanent way.

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WHO issues new guidance on how to provide contraceptive information and service

6 March 2014 | GENEVA - In advance of International Women’s Day on 8 March 2014, WHO is launching new guidance to help countries ensure human rights are respected in providing more girls, women, and couples with the information and services they need to avoid unwanted pregnancies.

An estimated 222 million girls and women who do not want to get pregnant, or who want to delay their next pregnancy, are not using any method of contraception. Access to contraception information and services will allow better planning for families and improved health.

WHO guidance recommendations

“Ensuring availability and accessibility to the information and services they need is crucial, not only to protect their rights, but also their health.”

Dr Flavia Bustreo, WHO’s Assistant Director-General for Family, Women, and Children’s Health

The guidance recommends that everyone who wants contraception should be able to obtain detailed and accurate information, and a variety of services, such as counselling as well as contraceptive products. It also underlines the need for no discrimination, coercion or violence, with special attention given to assuring access to those who are disadvantaged and marginalized.

Other key measures are scientifically accurate sex education programmes for young people, including information on how to use and acquire contraceptives. The guidance states that adolescents should be able to seek contraceptive services without having to obtain permission from parents or guardians. It also recommends that women be able to request services without having to obtain authorization from their husbands. It emphasizes the importance of respecting the privacy of individuals, including confidentiality of medical and other personal information.

“A lack of contraception puts 6 out of 10 women in low-income countries at risk of unintended pregnancy,” says Dr Flavia Bustreo, WHO’s Assistant Director-General for Family, Women, and Children’s Health. “Ensuring availability and accessibility to the information and services they need is crucial, not only to protect their rights, but also their health. These unintended pregnancies can pose a major threat to their own and their children’s health and lives.”

Access to contraception

In low- and middle-income countries, complications of pregnancy and childbirth are among the leading cause of death in young women aged 15–19 years. Stillbirths and death in the first week of life are 50% higher among babies born to mothers younger than 20 years than among babies born to mothers 20–29 years old.

Access to contraception allows couples to space pregnancies and enables those who wish to limit the size of their families to do so. Evidence suggests that women who have more than four children are at increased risk of death from complications of pregnancy and childbirth.

Many people who cannot currently access contraception services are young, poor, and live in rural areas and urban slums. Efforts are under way to address this need. The 2012 London Summit on Family Planning committed to extend family planning services to at least 120 million more people by the year 2020.

“Global targets are stimulating much needed action to increase access to modern contraception,” says Dr Marleen Temmerman, Director of WHO’s Department of Reproductive Health and Research. “But we have to be careful that our efforts to meet those targets do not lead to human rights infringements. It is not just about increasing numbers, it’s also about increasing knowledge. It is vital for women—and men—to understand how contraception works, be offered a choice of methods, and be happy with the method they receive.”

The International Conference on Population and Development held in Cairo in 1994 highlighted the importance of a rights-based approach to family planning. The past 20 years have seen a large amount of work demanding and defining a rights-based approach to health services—including contraception. Yet there has been comparatively little practical advice how to do so. WHO’s new guidance aims to address that gap.

The guidance also suggests ways to improve supply chains and affordability, recommends additional training for health workers, and outlines a series of steps to improve access in crisis settings, in HIV clinics, and during pre-natal and post-natal care.

The new guidance complements existing WHO recommendations for sexual and reproductive health programmes, including guidance on maternal and newborn health, sexuality education, prevention of unsafe abortion, and core competencies for primary health care.

For more information, please contact:

Glenn Thomas
WHO Communications Officer
Telephone: +41 22 791 3983
Mobile: +41 79 509 0677
E-mail: thomasg@who.int

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