New research points the way toward a potential vaccine against Zika, and may explain why the formerly mild virus exploded with such fury when it arrived in Brazil.

A pair of studies published Thursday focus on Zika's complex relationship with a related virus called dengue, a common illness in Latin America and the Caribbean that causes flu-like symptoms. Dengue is spread by the same mosquito species as Zika, and the two viruses are so similar that blood tests sometimes can't tell the two apart.

When people are infected with dengue, or any virus, the immune system releases key proteins called antibodies to neutralize the invaders. Authors of a study published Thursday in Nature found that two of the antibodies the body makes to fight dengue also prevent Zika infections.

That finding could help scientists develop vaccines against Zika and dengue, said study coauthor Juthathip Mongkolsapaya, a researcher at Imperial College London. Scientists also might be able to use these antibodies to treat Zika, she said.

Several groups are already working on Zika vaccines.

Inovio Pharmaceuticals announced this week that it has received Food and Drug Administration permission for a small, early clinical trial of a Zika vaccine it's developing with GeneOne Life Science. The National Institute of Allergy and Infectious Diseases is pursuing four types of Zika vaccines; officials there say they expect to begin clinical trials in August.

Yet the close relationship between dengue and Zika has a dark side.

There are four varieties of dengue virus. While people infected with the virus one time may develop relatively mild symptoms, those are infected a second time, with a different variety of of dengue virus, can develop severe, life-threatening complications, said Amesh Adalja, a senior associate at the Center for Health Security at the University of Pittsburgh Medical Center.

In a second paper, published in Nature Immunology, researchers found that the vast majority of dengue antibodies do nothing to stop Zika infection. In fact, a lab experiment showed that most dengue antibodies actually helped Zika viruses proliferate and invade cells. That suggests that people previously infected with dengue, whose antibodies against dengue remain in their blood, might have a more severe reaction to Zika, said Gavin Screaton, chair of medicine at Imperial College London.

These results lend support to similar findings from Florida Gulf Coast University and the University of Pittsburgh Center for Vaccine Research.

Mother Jusikelly da Silva holds her 7-month-old daughter Luhandra, who was born with microcephaly, as she wears her new glasses while waiting for a bus on June 2, 2016 in Recife, Brazil. (Photo: Mario Tama, Getty Images)

Not everyone is convinced that past dengue infections can make Zika cases more severe.

While dengue antibodies may exacerbate Zika infections in the lab, there's no evidence that this happens in the real world, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Scientists first discovered Zika in 1947, but it was never known to cause birth defects until Brazil experienced an alarming increase last year in microcephaly, a condition in which babies are born with abnormally small heads and incomplete brain development.

Brazil has reported 1,660 cases of microcephaly, about 10 times more than usual, according to the World Health Organization. Microcephaly linked to Zika has been reported in 11 other countries or territories, including Puerto Rico, Panama, El Salvador, Colombia, Martinique, the Marshall Islands, French Polynesia and Cape Verde.

These locations have different varieties of dengue viruses, Adalja said. It's possible that some varieties of the virus are more likely to be associated with Zika complications than others.

Researchers have looked at a number of possible explanations for Zika's explosive growth, said Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston. It's possible Zika's spread has been aided by environmental factors, such as climate change, poverty and urbanization. It's also possible the virus has mutated.

To really understand whether dengue antibodies exacerbate Zika infections, researchers will need to study pregnant women, said Ernesto Marques, scientific director of Cura Zika, an international alliance between the University of Pittsburgh and Brazil's Oswaldo Cruz Foundation, known as Fiocruz.

The National Institutes of Health announced this week that it will partner with Fiocruz in a study of up to 10,000 pregnant women in areas with Zika outbreaks, beginning with Puerto Rico and expanding to Brazil and Colombia.

Leaders of the new study will study whether a past dengue infection increases the risk of complications on pregnant women and their babies. Researchers also will compare the health of babies born to mothers infected with Zika virus and those who were not, recording rates of miscarriage, premature birth, microcephaly, malformations of the nervous system and other complications.

Researchers will study whether these problems are more common in women who had symptoms of Zika compared to those with no symptoms. Only about 20% of Zika patients develop symptoms, which include rash, fever, joint pain and pink eye. Researchers also will study whether complications are more common in women infected early in pregnancy compared to those infected later. Doctors will follow women throughout pregnancy and for six weeks after delivery.

An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery. The discovery would allow health care providers to identify women at greatest risk and help motivate women to make early lifestyle changes and follow other strategies that could prevent them from developing the disease later in life.

Gestational diabetes is defined as glucose intolerance that is first identified during pregnancy. It occurs in three to 13 percent of all pregnant women, and increases a woman's risk of developing type 2 diabetes by 20 to 50 percent within five years after pregnancy.

The joint efforts of the University of Toronto's Michael Wheeler, a professor in the Department of Physiology, and Erica Gunderson, Senior Research Scientist with the Kaiser Permanente Northern California Division of Research, led to development of a technique called targeted metabolomics to better predict the development of type 2 diabetes in women with recent gestational diabetes. Typically, diabetes is diagnosed by measuring blood sugar levels in the form of glucose, an important fuel used by cells in the body. The researchers identified several other metabolites that indicate early changes that signify future diabetes risk long before changes in glucose levels occur.

The team tested fasting blood samples collected from women with gestational diabetes within two months after delivery -- predicting with 83 percent accuracy which women would develop the disease later on. These results were significantly better at predicting the development of type 2 diabetes than conventional methods, a fasting blood test followed by the time-consuming and inconvenient oral glucose tolerance test.

"After delivering a baby, many women may find it very difficult to schedule two hours for another glucose test," says Wheeler, who is also a Senior Scientist at the Toronto General Research Institute. "What if we could create a much more effective test that could be given to women while they're still in the hospital? Once diabetes has developed, it's very difficult to reverse."

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"Early prevention is the key to minimizing the devastating effects of diabetes on health outcomes," says Dr. Gunderson. "By identifying women soon after delivery, we can focus our resources on those at greatest risk who may benefit most from concerted early prevention efforts."

The fasting blood samples used for this study were obtained from 1,035 women diagnosed with gestational diabetes and enrolled in the Kaiser Permanente's Study of Women, Infant Feeding and Type 2 Diabetes after GDM Pregnancy, also known as the SWIFT Study, which was funded by the U.S. National Institutes of Health (R01 HD050625). The SWIFT study screened women with oral glucose tolerance tests at 2 months after delivery and then annually thereafter to evaluate the impact of breastfeeding and other characteristics on the development of type 2 diabetes after a pregnancy complicated by gestational diabetes.

The American Diabetes Association recommends type 2 diabetes screening at six to 12 weeks after delivery in women with gestational diabetes, and every one to three years afterwards for life. The time-consuming nature of the two-hour oral glucose test is believed to be one reason for low compliance rates of less than 40 percent in some settings.

The new method may also be able to predict individuals who may develop type 2 diabetes in the general population - a major advance at a time when more than 300 million people suffer from the preventable form of this disease. A next-generation blood test that's more simple and accurate than the current options could help to identify individuals who would benefit most from more timely and effective interventions to prevent type 2 diabetes.

Wheeler and Gunderson are now hoping to conduct additional tests in women with gestational diabetes to evaluate racial and ethnic differences in prediction, and investigate high risk groups with prediabetes to learn if metabolomics will predict type 2 diabetes in the general population.

Source:

University of Toronto

July 31 is the deadline to submit your CME presentation and workshop proposals for AAPA 2017 in Las Vegas! Questions? Contact conferencecme@aapa.org.

The itchy, red welts that appear after being bitten by a mosquito may help any viruses the insect is carrying pass on to a new host. A mouse study published June 21 in Immunity suggests that the swelling and irritation that make mosquito bites so unpleasant may provide a mechanism by which viruses like Zika are able to replicate and spread. "Before we did this study, little was known about the events and processes that occur at mosquito bite sites," says Clive McKimmie, a Research Fellow at the University of Leeds and the paper's senior author. 

"Our findings suggest that the inflammatory response at these sites helps viruses to replicate, enhancing their ability to cause disease." In the new research, the investigators used mouse models to study the bites of the Aedes aegypti mosquito, the species that spreads infections such as Zika, dengue, and chikungunya. When a mosquito bites, it injects saliva into the skin. The saliva triggers an immune response, in which white blood cells called neutrophils and myeloid cells rush to the site. In this study, the team injected mice with viruses into the skin with or without the presence of a mosquito bite at the injection site and compared the reaction. 

They found that instead of helping, some of these immune cells get infected and inadvertently replicate virus. In the absence of mosquito bites and their accompanying inflammation, the viruses failed to replicate well. But the presence of mosquito bites at the infection site resulted in an order of magnitude higher levels of virus. Further studies showed that the influx of white blood cells was required for enhanced replication of the viruses. According to McKimmie, previous studies that have used in vivo models to study the course of mosquito­borne infections 6/22/2016 Inflammation from mosquito bites may enhance viral infection haven't looked at the bite as a necessary component. 

"We think the bite itself is affecting the systemic course and clinical outcome of the infection," he says. "If you want an in vivo model that replicates the most relevant parts of infection, you should include this inflammatory aspect." "This was a big surprise we didn't expect," he adds. "These viruses are not known for infecting immune cells. And sure enough, when we stopped these immune cells from coming in, the bite did not enhance the infection anymore." Although this research is still early work done in mice, McKimmie says the finding suggests new approaches for combating viruses that lead to health problems in humans.

 "We're quite keen to see if using topical creams to suppress bite inflammation will enable you to stop a virus from making someone as sick as it otherwise would do," he says. He notes that if it's proven effective, this approach could work against future virus outbreaks that we don't know about yet. "Nobody expected Zika, and before that nobody expected chikungunya," he says.

 "There are estimated to be hundreds of other mosquito­borne viruses out there and it's hard to predict what's going to start the next outbreak." More information: Immunity, Pingen et al: "Host inflammatory response to mosquito bites enhances severity of arbovirus infection."

 http://www.cell.com/immunity/fulltext/S1074­7613(16)30205­9 , DOI: 10.1016/j.immuni.2016.06.002 Provided by Cell Press "Inflammation from mosquito bites may enhance viral infection" June 21, 2016 http://medicalxpress.com/news/2016­06­inflammation­mosquito­viralinfection.html

Written by Honor Whiteman

Published: Tuesday 21 June 2016

Researchers have identified an existing drug that they say has the potential to prevent or delay breast cancer for women at high risk of developing the disease.

Researchers found the drug denosumab stopped the growth of cells that are a precursor to breast cancer in women with a BRCA1 gene mutation.

In a study published the journal Nature Medicine, researchers reveal how the drug denosumab halted the growth of pre-cancerous cells in breast tissue of women with a faulty BRCA1 gene.

Women with a BRCA1 gene mutation are at significantly greater risk for breast and ovarian cancers; around 55-65 percent of women with such a mutation will develop the disease by the age of 70, according to the National Cancer Institute, compared with 12 percent of those in the general population.

At present, the only way for women with a BRCA1 mutation to significantly reduce their risk of breast and ovarian cancers is to opt for a mastectomy - the surgical removal of one or both breasts - or an oophorectomy - the removal of the ovaries.

But in this latest study, Prof. Geoff Lindeman, of the Walter and Eliza Hall Institute of Medical Research (WEHI), Australia, and colleagues show promise for a non-surgical alternative.

Uncovering the 'holy grail' of cancer research

To reach their findings, the team analyzed a number of breast tissue samples from women with and without a BRCA1 mutation.

Fast facts about breast cancer

• This year, around 246,660 new cases of invasive breast cancerwill be diagnosed in the U.S.
• Around 40,450 women will die from breast cancer in 2016
• There are currently more than 2.8 million breast cancer survivors in the U.S.

Learn more about breast cancer

From this, they identified cells in the breast tissue from women with a BRCA1 mutation that act as a precursor to breast cancer.

"These cells proliferated rapidly, and were susceptible to damage to their DNA - both factors that help them transition towards cancer," explains study co-author Prof. Emma Nolan, of the Department of Medical Biology at The University of Melbourne, Australia.

What is more, the researchers found that a protein called RANK acted as a marker for these pre-cancerous cells - a finding that excited the team, given that there are already drugs in clinical use that target and block the RANK pathways.

As such, the researchers decided to investigate how one of these drugs - known as RANK ligand inhibitors - would affect the progression of pre-cancerous breast cells.

They focused on a medication called denosumab, which is currently used to treatosteoporosis and bone cancers, including breast cancers that have spread to the bone.

On applying denosumab to BRCA1-mutated breast tissue, they found itdeactivated the growth activity of pre-cancerous cells. What is more, the drug halted breast cancer development in a BRCA1-deficient mouse model.

Overall, the researchers say their findings indicate that targeting the RANK pathway may be an effective strategy to reduce breast cancer risk in women with a BRCA1 mutation.

"By thoroughly dissecting how normal breast tissue develops, we have been able to pinpoint the precise cells that are the culprits in cancer formation.

It is very exciting to think that we may be on the path to the 'holy grail' of cancer research, devising a way to prevent this type of breast cancer in women at high genetic risk."

Study co-author Prof. Jane Visvader, WEHI

The authors say that a clinical trial is already underway to further investigate the breast cancer-preventing potential of RANK-inhibiting drugs.

Learn how even light alcohol consumption may increase breast cancer risk.

Written by Honor Whiteman

The Centers for Disease Control and Prevention (CDC) has recently launched the U.S. Zika Pregnancy Registry to understand more about pregnancy and infant outcomes following Zika virus infection during pregnancy. The Wisconsin Department of Health Services (DHS) intends to collaborate with CDC on this registry. Health care providers are asked to identify any cases of pregnant women with laboratory evidence of Zika virus or any infants with suspected congenital Zika virus exposure. If you have identified a woman or infant meeting these criteria, please call DHS at 608-267-9003 or the CDC Zika Pregnancy Registry at 770-488-7100.

Additional information regarding the U.S. Zika Pregnancy Registry can be found at http://www.cdc.gov/zika/hc-providers/registry.html. Registry fact sheets designed specifically for obstetric health care providers, pediatric health care providers, pregnant women, and parents can be accessed using the links below and are also available in Spanish.

For the latest updates regarding Zika virus, please visit http://www.cdc.gov/zika/ and https://www.dhs.wisconsin.gov/arboviral/zika.htm. 

Zika Pregnancy Registry Fact Sheet for obstetric providers (PDF)

Pika Pregnancy Registry Fact Sheet for pregnant women (PDF)

Australian researchers have discovered that an existing medication could have promise in preventing breast cancer in women carrying a faulty BRCA1 gene. People who carry a faulty BRCA1 gene are at high risk of developing aggressive breast cancer. Currently many women with a gene mutation choose surgical removal of their breast tissue and ovaries to reduce their chance of developing breast and ovarian cancer. 

By pinpointing the cells that give rise to breast cancers in women who have inherited a faulty version of the BRCA1 gene, Walter and Eliza Hall Institute researchers have identified that the drug denosumab may have potential to prevent breast cancer from developing. If confirmed in clinical studies, this would provide a non­surgical option to prevent breast cancer in women with elevated genetic risk. Using samples of breast tissue donated by women carrying a faulty BRCA1 gene, Ms Emma Nolan, Professor Jane Visvader and Professor Geoff Lindeman were able to pinpoint the cells that give rise to breast cancer. 

The research, which also involved researchers at the Australian familial cancer consortium kConFab and US biotechnology company Amgen was published today in Nature Medicine. Cancer precursor cells in BRCA1­mutant breast tissue had many similarities to aggressive forms of breast cancer, said Ms Nolan, who is a PhD student at the institute enrolled through The University of Melbourne's Department of Medical Biology. 

"These cells proliferated rapidly, and were susceptible to damage to their DNA ­ both factors that help them transition towards cancer," she said. "We were excited to discover that these pre­cancerous cells could be identified by a marker protein called RANK." Professor Lindeman, who is also a medical oncologist at The Royal Melbourne Hospital, said the discovery of RANK as a marker of cancer precursors was an important breakthrough, because inhibitors of the RANK signalling pathway were already in clinical use. "An inhibitor called denosumab is already used in the clinic to treat osteoporosis and breast cancer that has spread to the bone," he said. "We therefore investigated what effect RANK inhibition had on the cancer precursor cells in BRCA1­mutant breast tissue." 

The research team showed that RANK inhibition switched off cell growth in breast tissue from women with a faulty BRCA1 gene and curtailed breast cancer development in laboratory models. "We think this strategy could delay or prevent breast cancer in women with an inherited BRCA1 gene mutation," Professor Lindeman said. "A clinical trial has already begun to investigate this further." "This is potentially a very important discovery for women who carry a faulty BRCA1 gene, who have few other options. Current cancer prevention strategies for these women include surgical removal of the breasts and/or ovaries, which can have serious impacts on people's lives. 

To progress this work, denosumab would need to be formally tested in clinical trials in this setting as it is not approved for breast cancer prevention," Professor Lindeman said. Professor Visvader said the discovery had its basis in more than a decade of investigations of breast stem cell function. 

"By thoroughly dissecting how normal breast tissue develops, we have been able to pinpoint the precise cells that are the culprits in cancer formation," she said. "It is very exciting to think that we may be on the path to the 'holy grail' of cancer research, devising a way to prevent this type of breast cancer in women at high genetic risk." 

The research team worked closely with Mrs Avis Macphee, a patient advocate, through the Walter and Eliza Hall Institute's consumer­researcher buddy system. The research was supported by The National Breast Cancer Foundation, The Qualtrough Cancer Research Fund, The Joan Marshall Breast Cancer Research Fund, the Australian Cancer Research Foundation, Cancer Council Victoria, the Cancer Therapeutics Cooperative Research Centre, an Amgen Preclinical Research Program Grant, the National Health and Medical Research Council, the Victorian Cancer Agency, and the Victorian Government Operational Infrastructure Support Scheme. 

More information: RANK ligand as a potential target for breast cancer prevention in BRCA1­mutation carriers, Nature Medicine, DOI: 10.1038/nm.4118 Provided by Walter and Eliza Hall Institute "'Holy grail' of breast cancer prevention in high­risk women may be in sight" 

June 20, 2016 http://medicalxpress.com/news/2016­06­holy­grail­breastcancer­high­risk.htm

Women with lupus are at significantly greater risk for cervical cancer than those in the general population, concludes a new study led by the Karolinska Institutet in Sweden.

Researchers say SLE may double women's risk of cervical dysplasia or invasive cervical cancer.

Lead researcher Dr. Hjalmar Wadström, of the Department of Medicine Solna at Karolinska, and colleaguesrecently presented their findings at the European League Against Rheumatism Annual Congress (EULAR 2016), held this week in London, United Kingdom.

When talking about lupus, the majority of people are referring to systemic lupus erythematosus (SLE), which is the most common form of the condition. 

SLE is an autoimmune disease where the immune system attacks the body's tissues and organs, including the skin, joints, brain, kidneys, and blood vessels.

According to the Lupus Research Institute, SLE is estimated to affect more than 1.5 million people in the United States, of whom more than 90 percent are women aged 15­44.

While symptoms of SLE vary, they may include pain or swelling in the joints, skin rashes or sores, sun
sensitivity, muscle pain, fever, fatigue, and mouth ulcers. Among young women, SLE is known to increase the risk of cardiovascular disease, kidney disease, and stroke.

Previous studies have also suggested the autoimmune disease may increase women's risk of cervical cancer, though Dr. Wadström and colleagues note that such evidence has been conflicting.
 
Cervical dysplasia, cancer risk doubled for women with SLE
To find out more about the potential link between SLE and cervical cancer, the team analyzed data from Sweden's National Patient Register, the Swedish National Cervical Screening Registry, and the Swedish Cancer

Fast facts about cervical cancer

• This year, around 12,990 new cases of cervical cancer will be diagnosed in the U.S.
• Around 4,120 women will die from the disease in 2016
• Most cases occur in women under the age of 50.
• Using this data, the team calculated the rates of invasive cervical cancer and cervical dysplasia between 2006­
• 2012 among the general female population and those with SLE.

Cervical dysplasia is abnormal cell growth on the lining of the cervix ­ most commonly caused by infection with human papillomavirus (HPV). If untreated, the condition may lead to cervical cancer.
The researchers found that women with SLE were at twice the risk of developing cervical dysplasia or
invasive cervical cancer, compared with the general female population.

Women with SLE who were treated with immunosuppressant medication were found to be at the highest risk of cervical dysplasia or invasive cervical cancer, the team reports.

These findings remained after accounting for age, sex, education, utilization of healthcare, number of children,marital status, family history of cervical cancer, and cervical cancer screening in the past 5 years. The researchers say their findings emphasize the importance of regular cervical cancer screening for women with SLE, even if they are not being treated with immunosuppressant drugs. 

"Previous evidence that SLE or its treatment might increase the risk of cervical neoplasia has been
inconclusive.

Our findings have confirmed that SLE is a risk factor for cervical malignancies, even after adjusting for important risk determinants such as previous cervical screening."

Dr. Hjalmar Wadström

June is LGBT Pride Month!

Save the date for APAOG's next webinar on September 27th, 2016. The webinar will focus on LGBT Reproductive Health.

(Reuters Health) - Obesity rates for U.S. women and teens are on the rise, according to two new studies from the U.S. Centers for Disease Control and Prevention (CDC) published in JAMA.

About 41 percent of women and 35 percent of men are obese, according to survey data collected as recently as 2014 and reported in one of the studies.

A decade earlier, about 38 percent of women and 34 percent of men were obese, the study found. Only the increase for women was large enough to be sure it wasn’t due to chance.

Over this same period, obesity rates for teens rose from about 17 percent to 21 percent, CDC researchers report in the second study.

“The most recent data before this point showed no increases overall in youth, men or women over the previous decade,” said Cynthia Ogden, a CDC researcher who worked on both studies.

“These trends are not explained by changes in age or educational levels in the population or by changes in the distribution of race-ethnic groups in the population or changes in smoking status,” Ogden added by email.

Globally, 1.9 billion adults are overweight or obese, according to the World Health Organization. Obesity increases the risk of heart disease, diabetes, kidney complications, joint disorders and certain cancers.

Both studies analyzed data from a nationally representative survey of the U.S. population that includes questions about weight and height. Researchers looked at participants’ body mass index (BMI), a measure of weight relative to height, to assess trends in obesity over time.

For adults, a BMI between 18.5 and 24.9 is considered healthy, 25 to 29.9 is overweight, 30 or above is obese and 40 or higher is morbidly obese.

An adult who is 5’9” tall and weighs from 125 to 168 pounds would have a healthy weight and a BMI of 18.5 to 24.9, according to the U.S. Centers for Disease Control and Prevention. An obese adult at that height would weigh at least 203 pounds and have a BMI of 30 or more.

Almost 6 percent of men and 10 percent of women have what’s known as “class 3” obesity, with a BMI of at least 40 and the most severe risk of health complications tied to their weight, the CDC study of adults found.

If there’s a sliver of good news in all this data, it’s for the youngest children, ages 2 to 5, the CDC youth study found.

For these kids, obesity rates declined from about 14 percent a decade ago to 9 percent in the most recent survey.

Over that period, obesity rates for children ages 6 to 11 dipped slightly, but not enough to rule out the possibility that this was due to chance.

One limitation of both studies is that people in surveys tend to say they are taller and lighter than they really are, which can downplay obesity rates calculated from BMI, the authors note. BMI also doesn’t distinguish between fat and muscle.

Even so, the two studies suggest that huge investments to reverse the U.S. obesity epidemic over the past three decades haven’t done much to diminish the problem, Dr. Jody Zylke and Dr. Howard Bauchner, deputy editor and editor-in-chief of JAMA, respectively, wrote in an editorial.

“The rates among children and adults are driven by the same factors,” said Dr. Lili Lustig, a family medicine researcher at Cleveland Clinic in Ohio who wasn’t involved in the study.

Lack of exercise is part of the problem, and so is what people eat, Lustig added by email.

“We have done a deplorable job of helping parents understand food as a prescription for health,” Lustig said by email. “If a parent does not understand the value of food choices, how can you expect their children and the next generation to have any better understanding?”

SOURCE: bit.ly/1c9i5E4 Journal of the American Medical Association, online June 7, 2016