Undetected Zika infections may be triggering miscarriages and stillbirths. A collaborative study among six of the National Primate Research Centers shows pregnancy loss due to Zika A infections that don’t cause women any symptoms may be a common but unrecognized cause of miscarriages and stillbirths.
Collecting data from several species of nonhuman primates (rhesus macaques, pigtail macaques, and marmosets), scientists found that 26 percent of female nonhuman primates inoculated with Asian/
American Zika virus (ZIKV) in the early stages of pregnancy experienced miscarriage or stillbirth later, despite the fact that the animals showed few clinical signs of infection.
During the pregnancies of the Zika-infected monkeys, scientists monitored their progress through ultrasounds, amniocentesis, and blood draws.
“The primary conclusion from this multi-center study with important implications for pregnant women infected with ZIKV is that stillbirth and miscarriage occur more frequently in infected nonhuman primates than animals not exposed to the virus,” explains lead author Dawn Dudley, PhD, with the Wisconsin National Primate Research Center.
The study is published in the journal Nature Medicine. The authors conclude that “the high rates of fetal loss among ZIKV-infected nonhuman primate (NHP) pregnancies raise concern that Zika-associated pregnancy loss in humans may be more frequent than currently thought.”
The results parallel human reports of more significant adverse outcomes in babies exposed to ZIKV during the first trimester. No treatments or vaccines for Zika exist, although scientists are experimenting to find ways to cope with this emerging mosquito-borne infectious disease.
Chemistry
Urinary markers predict bone problems after hip replacement. In a study published in the Journal of Orthopaedic Research, investigators have identified urinary markers that differentiate total hip replacement patients who eventually develop bone tissue destruction, or osteolysis, from patients who do not.
For the study, researchers used a repository of 24-hour urine samples collected prior to surgery and annually thereafter in 26 patients, 16 who developed osteolysis and 10 who did not.
The levels of certain markers helped the investigators identify patients at risk for osteolysis long before the emergence of signs through imaging tests—in some cases, six years before a diagnosis was made. Although single markers showed moderate accuracy, the combination of α-CTX, a bone resorption marker, and IL-6, an inflammatory marker, led to high accuracy in the differentiation of patients who eventually developed osteolysis from those with no signs of osteolysis.
“We are hopeful that early biomarkers for implant loosening will alert surgeons to be especially vigilant in their follow-up of at-risk patients and may eventually lead to treatments delaying or avoiding the need for revision surgery,” says senior author Dr. D. Rick Sumner, of Rush University Medical Center, in Chicago.
“Perhaps even more intriguing is that the two biomarkers we identified also differed before surgery among patients who eventually developed peri-implant osteolysis and those who did not, supporting the concept that other researchers have proposed of genetic risk factors for loosening.”
HPV
No link between HPV vaccination and risk of autoimmune disorders. A new study in the Canadian Medical Association Journal (CMAJ) found no increased risk of autoimmune disorders in girls who received quadrivalent human papillomavirus (HPV4) vaccination, adding to the body of evidence for the safety of the vaccine.
Human papillomavirus (HPV) is the most common sexually transmitted disease (STD) worldwide, affecting 50 percent to 75 percent of sexually active people. The HPV4 vaccine is effective at protecting against 90 percent of the strains that cause cervical and anal cancer. Despite studies showing the safety of the vaccine, there have been concerns about a possible link to autoimmune disorders.
To determine whether the HPV4 vaccination triggered autoimmune conditions such as lupus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis, researchers looked at data on 290,939 girls aged 12 to 17 years in Ontario who were eligible for vaccination between 2007 and 2013. Of the total 180,819 girls who received the HPV4 (Gardasil and Merck) vaccination in school-based clinics, there were 681 diagnosed cases of autoimmune disorders between one week and two months after vaccination. This rate is consistent with the general rate of diagnosed cases in this age group.
Hematology
Scientists create blood with potential for future treatments. Researchers at Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago have discovered a way to increase the efficiency of mature blood production in a dish. They first converted human skin cells to pluripotent stem cells, which are stem cells that have the potential to develop into many different kinds of cells. Then they coaxed these stem cells into becoming a variety of blood cells, including immune cells called “natural killer” cells that are part of the body’s natural defense against cancer and infection. Results of their study, which hold promise for future treatments, were published in Experimental Hematology.
While studying the earliest steps of how blood cells develop from pluripotent stem cells, which mimic embryonic stem cells, researchers observed that in vitro what is called “definitive” or mature blood forms independently from “primitive” blood, which normally appears early in the development of an embryo. Previously it was not clear whether primitive blood was a precursor to definitive blood or they developed separately.
“In our study we found that developmental pathways toward definitive and primitive blood diverge early in the process, confirming that in vitro definitive blood does not develop from primitive blood,” says first author Yekaterina Galat, BS, Research Associate at Manne Research Institute at Lurie Children’s. “We showed that by inhibiting the development of primitive blood we can increase the amount of definitive blood and expand the number of definitive cell types, including red blood cells and immune cells like macrophages and natural killer cells.
“Our ability to differentiate large quantities of blood cells from induced human pluripotent stem cells could be important for drug testing, pharmaceutical research, and disease modeling, as well as developing therapies for cancer, blood disorders, and immune deficiencies,” says senior author Vasil Galat, PhD.
Alzheimer’s disease
Viruses may play a role in Alzheimer’s disease. Analysis of large data sets from post-mortem brain samples of people with and without Alzheimer’s disease has revealed new evidence that viral species, particularly herpesviruses, may have a role in Alzheimer’s disease biology.
Researchers funded by the National Institute on Aging, part of the National Institutes of Health, made the discovery by harnessing data from brain banks and cohort studies participating in the Accelerating Medicines Partnership-Alzheimer’s Disease consortium.
Reporting in the journal Neuron, the authors emphasize that their findings do not prove that the viruses cause the onset or progression of Alzheimer’s. Rather, the findings show viral DNA sequences and activation of biological networks—the interrelated systems of DNA, RNA, proteins and metabolites—may interact with molecular, genetic, and
clinical aspects of Alzheimer’s.
The research group, which included experts from Icahn School of Medicine at Mount Sinai, New York City, and Arizona State University, Phoenix, originally set out to find whether drugs used to treat other diseases can be repurposed for treating Alzheimer’s. They designed their study to map and compare biological networks underlying Alzheimer’s disease.
What they found is that Alzheimer’s biology is likely impacted by a complex constellation of viral and host genetic factors. They also identified specific testable pathways and biological networks.
The researchers used multiple layers of genomic and proteomic data from several NIA-supported brain banks and cohort studies. They began their direct investigation of viral sequences using data from the Mount Sinai Brain Bank and were able to verify their initial observations using datasets from the Religious Orders Study, the Memory and Aging Project, and the Mayo Clinic Brain Bank.
They were then able to incorporate additional data from the Emory Alzheimer’s Disease Research Center to understand viral impacts on protein abundance.
Through the application of sophisticated computational model modeling the researchers made several key findings, including:
- Human herpesvirus 6A and 7 were more abundant in Alzheimer’s disease samples than non-Alzheimer’s.
- There are multiple points of overlap between virus-host interactions and genes associated with Alzheimer’s disease risk.
- Multiple viruses impact the biology of Alzheimer’s disease across domains such as DNA, RNA and proteins.
Cancer
New study shows higher vitamin D levels could lower risk for breast cancer. Results from a new study published in PLOS ONE shows women who have higher vitamin D blood levels have a significantly lower risk for breast cancer.
Analyses were done combining data from two randomized trials conducted at Creighton University with data from a cohort from GrassrootsHealth. The combined data included more than 5,000 women, aged 55 and older, who had a broad range of vitamin D blood levels.
The study found that those women with a blood level of >60 ng/ml had an 80 percent lower risk for breast cancer than those with levels of 20 ng/ml or less. There was a dose response relationship between blood levels of vitamin D and cancer incidence, i.e., between 20 and 60 ng/mL. The higher the blood vitamin D level, the lower the risk of breast cancer.
Joan M. Lappe, PhD, RN, was the principal investigator of the two NIH-funded randomized trials conducted at Creighton University that were included in the study. Her 2007 study on bone health and vitamin D blood levels found, in a secondary analysis, that women who took vitamin D and calcium supplementation for four years had a 60 percent lower risk of all-type cancer than women who took placebos. In her 2017 study of cancer and vitamin D, she and her team found that women with a vitamin D blood level of 55 ng/ml had a 35 percent significantly lower risk for all-type cancer than those with levels of 30 ng/ml. Lappe says the study provides strong support that vitamin D plays an important role in breast cancer prevention and demonstrates that blood levels of vitamin D for breast cancer prevention need to be higher than currently recommended.
