Molecular biomarkers for preeclampsia

Preeclampsia is a sudden pregnancy complication that can interfere with the blood flow to the placenta and possibly to the fetus, it can lead to low birth weight, prematurity and death. It is also a leading cause of maternal mortality. A new Tel Aviv University study identifies novel molecular biomarkers of preeclampsia, signaling the potential for an early diagnostic blood test.

Research for the study was led by Dr. Noam Shomron and Prof. Moshe Hod and conducted by Liron Yoffe and other lab members, all affiliated with TAU's Sackler School of Medicine, and in collaboration with Prof. Kypros Nicolaides of King's College, London. Preeclampsia is a serious disease that endangers the health, sometimes even the lives, of the mother and the fetus.

The causes of  preeclampsia is unknown if caught in time it has a simple and proven remedy: low doses of aspirin administered from the 16th week until the end of pregnancy. Medical practitioners have assessed a woman's risk of preeclampsia by referring to previous pregnancies, blood pressure levels and other general symptoms. Blood test could predict preeclampsia and, in turn, allow doctors to provide treatment that would prevent the  onset of the disease.

Researchers examined the blood samples from thousands of pregnant women in their first trimester, the team then narrowed their focused to 75 specific blood samples: 35 taken from women who eventually contracted preeclampsia, and 40 taken from those who completed their pregnancies in full health. The researchers extracted the RNA molecules (snippets of molecular information present in human cells) from the plasma of the samples and sequenced these using Next Generation Sequencing (NGS).

The scientists discovered the new biomarkers by analyzing the data using computational methods that included statistical analyses and machine learning algorithms. They identified 25 small RNA molecules that were differentially expressed between the preeclampsia and the control groups. Based on those RNA molecules, they developed a model for the classification of preeclampsia samples.

These findings indicate the predictive value of circulating small RNA molecules in the first trimester, and lay the foundation for producing a novel early non-invasive diagnostic tool for preeclampsia, which could reduce the life-threatening risk for the mother and fetus.
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Gene may protect against heart disease

Scientists have identified a gene that may play a protective role in preventing heart disease. Their research revealed that the gene, called MeXis, acts within key cells inside clogged arteries to help remove excess cholesterol from blood vessels.

UCLA-led study in mice found that MeXis controls the expression of a protein that pumps cholesterol out of cells in the artery wall. MeXis is an example of a "selfish" gene, one that is presumed to have no function because it does not make a protein product.

However, recent studies have suggested that these so-called "unhelpful" genes can actually perform important biological functions without making proteins and instead producing a special class of molecules called long non-coding RNAs, or lncRNAs.

lncRNAs are important for the inner workings of cells involved in the development of heart disease," said Dr. Peter Tontonoz, senior author of the study. Considering many genes like MeXis have completely unknown functions, the study suggests that further exploring how other long non-coding RNAs act will lead to exciting insights into both normal physiology and disease.

In the study, researchers found that mice lacking MeXis had almost twice as many blockages in their blood vessels compared to mice with normal MeXis levels. In addition, boosting MeXis levels made cells more effective at removing excess cholesterol.
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Gene expression may determine time of death

International team of scientists led by Roderic Guigó at the Centre for Genomic Regulation in Barcelona showed that changes in gene expression in different tissues triggered by death can be used to predict the time of death of an individual. Analyzing a few available tissues for example lung or skin tissue, the post-mortem interval-time elapsed since death can be determined with considerable accuracy and may have implications for forensic analyses.

It all started with the GTEx project, which aimed at creating a reference database and tissue bank for scientists to study how genomic variants affect gene activity and disease susceptibility. GTEx was designed to sample as many tissues as possible from a large number of individuals in order to understand the causal effects of genes and variants, and which tissues contribute to predisposition to disease.

To understand the tissue-specific changes to gene expression following the death of a person, Roderic Guigó and his colleagues studied RNA-sequencing data of over 7,000 samples from 36 different tissues obtained from 540 donor. They show that the time since death has an effect on gene expression and that this effect varies from tissue to tissue. Models for the prediction of the post-mortem interval based on these tissue-specific gene expression changes using high-throughput sequencing of the cell.
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Environmental influence can change gene behaviour

In a study of pregnant women, a team of Deakin scientists has shown in humans for the first time that pregnancy can induce long-term epigenetic changes to human body, with major implications for understanding, preventing and treating disease. Deakin University scientists have discovered that pregnancy can cause long-term changes to the way women's genes behave, which could affect the health of mother and children.

The findings of a recent study from Deakin's Centre for Cellular and Molecular Biology, within the School of Life and Environmental Sciences, showed women experience major molecular changes during pregnancy that could remain with them after their pregnancy has ended. The changes are "epigenetic"-they are not a mutation of the gene's structure, but a change to how genes behave.

Long-term epigenetic changes can lead to increased risks of disease for the next generation. Studies have previously shown the offspring of women with diabetes have an increased risk of developing obesity, glucose intolerance and type 2 diabetes. Epigenetic markers act like a switch that can alter the activity of genes and cells in the body. All individual cells have the same genetic material, but the behaviour of a gene is different in different tissues of the body. That behaviour can be determined by epigenetic factors, independent of the DNA sequences of the genes.

Epigenetics has implications for understanding, preventing and combatting many diseases, from diabetes to cancer, providing understanding of how adverse environmental factors, including lifestyle, can cause disease. Researchers compared groups of never-pregnant women, pregnant women, and women at 20 weeks postpartum, and made comparisons between the same groups of women at pregnancy, at eight to 10 weeks postpartum, and at 20 weeks postpartum. Similar comparisons were carried out among women with type 2 diabetes.

A significant finding was that women with type 2 diabetes had different epigenetic profiles from non-diabetic women, and their profiles underwent different changes during pregnancy. Pregnancy-induced epigenetic changes could lead to complications among these women with diabetes, such as downstream effects that may contribute to insulin resistance, as well as high risk pregnancy outcomes. Maternal malnutrition and other adverse events in pregnancy can cause problems for the next generation due to epigenetics.
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Grape-derived compounds may promote resilience against depression

Scientists from the Icahn School of Medicine at Mount Sinai describe an extensive analysis of novel grape-derived compounds, dihydrocaffeic acid (DHCA) and malvidin-3'-O-glucoside (Mal-gluc), which might be developed as therapeutic agents for the treatment of depression. The study results indicate that these natural compounds may attenuate depression by targeting newly discovered underlying mechanisms of the disease.

Conventional pharmacological treatments are estimated to produce temporary remission in less than 50 percent of patients, and they are often associated with severe adverse effects. Thus, there is an urgent need for a wider spectrum of novel therapeutics.

Depression is associated with a multitude of pathological processes, including inflammation of the peripheral immune system, a set of biological structures and processes in the lymph nodes and other tissues that protect against disease and abnormalities involving synapses, the structures that permit neurons to pass an electrical or chemical signal to other neurons.

However, currently available antidepressants are largely restricted to targeting the systems that regulate serotonin, dopamine, and other related neurotransmitters, and these treatments do not specifically address inflammation and synaptic maladaptations that are now known to be associated with MDD.

Previous research has found that grape-derived polyphenols have some efficacy in modulating aspects of depression, yet the mechanisms of action had largely remained unknown until now. The new study, led by Giulio Maria Pasinetti, PhD, Saunders Professor of Neurology, and a team of investigators from the Center for Integrative Molecular Neuroresilience at the Icahn School of Medicine at Mount Sinai, found that a bioactive dietary polyphenol preparation-a combination of three grape-derived polyphenol products, including a select Concord grape juice, a select grape seed extract, and trans-resveratrol was effective in promoting resilience against stress-induced depression in mice.

Specifically, researchers found that DHCA and Mal-gluc can promote resilience in mouse models of depression by modulating inflammation and synaptic plasticity, respectively. DHCA reduces interleukin 6 (IL-6), a pro-inflammatory substance secreted by T cells and macrophages to stimulate immune response, by epigenetically modulating the non-coding sequence of the IL-6 gene. Mal-gluc modulates histone acetylation of the Rac1 gene and allows transcription activators to access the DNA for increased transcription in the brain, which influences the expression of genes responsible for synaptic plasticity.

Researchers also demonstrated that DHCA/Mal-gluc treatment was effective in attenuating depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of cells from the bone marrow of stress-susceptible mice. The research shows that combination treatment with the two compounds can promote resilience against stress-mediated depression-like phenotypes by modulating systemic inflammatory responses and brain synaptic plasticity in a mouse model of depression.

The Mount Sinai study provides novel preclinical evidence supporting the targeting of multiple key disease mechanisms through DNA epigenetic modification for the treatment of depression. This study strongly supports the need to test and identify novel compounds that target alternative pathologic mechanisms, such as inflammation and synaptic maladaptation, for individuals who are resistant to currently available treatment.

Using combination treatment of DHCA and Mal-gluc to simultaneously inhibit peripheral inflammation and modulate synaptic plasticity in the brain works synergistically to optimize resilience against chronic stress-induced depression-like phenotypes. The discovery of these new, natural grape-derived polyphenol compounds targeting cellular and molecular pathways associated with inflammation may provide an effective way to treat a subset of people with depression and anxiety, a condition that affects so many people.
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Basal cell tumors return when treatment stops

A new study pinpoints a mechanism that controls how basal cell cancers respond to treatment and offers new ideas for controlling the disease. Basal cell carcinomas are common, they're often removed through surgery. In some cases, the cancer cannot be surgically removed, often because of where it's found. A small portion of patients have an inherited condition called basal cell nevus syndrome, or Gorlin syndrome, which causes hundreds of basal cell tumors to develop over their lifetime.

An early success story among targeted therapies, developed to hit a key pathway in basal cell carcinoma called Hedgehog. By blocking Hedgehog, the cancer cells die but when patients stop taking the drug, the cancer often grows back at the same site. Many patients have to stay on it for their entire life. Researchers describe two types of cell populations in basal cell tumors. The outer edge of the tumor is lined with cells that persist even in the face of Hedgehog blockade. The inner cells, on the other hand, are about three times more likely to undergo cell death from vismodegib treatment.

The relative location of a cell within a tumor can have such a big effect on its sensitivity to drug treatment. The difference stems from the Notch pathway and how each type of cell activates it. Higher levels of Notch were detected in the inner cells, while the outer cells had lower levels of Notch. When the researchers shut off Notch completely, tumors were more likely to persist despite vismodegib treatment.

When they turned on Notch, tumors shrank. The work was done in mice.The outer cells are anchored to the tumor's basement membrane, where Hedgehog signaling is high and Notch signaling is low. The researchers explain that this pattern allows cancer cells to persist in a largely dormant state while the patient takes the Hedgehog-inhibiting vismodegib. Once the drug treatment stops, the dormant cells re-activate.

The side effects of vismodegib are not life-threatening, many patients experience loss of taste, muscle cramps, weight loss and fatigue. The side effects drive some patients to discontinue the drug. Drug resistance and tumor persistence are both challenging issues with Hedgehog-blocking treatments. Eliminating persistent tumor cells is necessary to cure patients who have tough-to-treat cases of basal cell carcinom.
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How gene mutation triggers the immune system

Scientists discovered how a gene mutation affects T cell function to promote immune disorders and then tested a treatment based on the discovery-successfully fixing donated immune cells from a 16-year-old boy with an abnormally low level of white blood cells called lymphopenia. The discovery centers on mutation of the gene Gimap5, which is important to the healthy formation and function of CD4+ T cells, one of the immune system's super soldiers against infection and disease.

The protein associated with the Gimap5 gene (also Gimap5), is important because it regulates a protein that inactivates an enzyme called GSK3, researchers said. If GSK3 isn't inactivated it causes DNA damage in T cells that are expanding, causing the cells not to survive or function properly. In mice and human blood cells, the researchers tested drugs that inhibit GSK3, improving immune system function in mice and restoring normal T cell function in the human cells.

GSK3 inhibitors are used to treat other diseases like Alzheimer's, mood disorders and diabetes mellitus. GSK3 inhibitors will improve T cell survival and function and may prevent or correct immune-related disorders in people with Gimap5 loss-of-function mutations.Therapeutically targeting this pathway may be relevant for treating people with Gimap5 mutations linked to autoimmunity in Type 1 diabetes, systemic lupus erythematosus or asthma.

Hoebe led the study, together with Andrew Patterson, a PhD student in Hoebe's lab, and Jack Bleesing, MD, PhD, in the Division of Bone Marrow Transplantation and Immune Deficiency. Immune system disorders lead to abnormally low immune activity (deficiency) or overactivity (autoimmunity). Immune deficiency diseases decrease the body's ability to fight infection, while autoimmunity prompts the body to attack its own tissues. Both are common causes of illness, and malfunctioning T cells are linked to both.

The Gimap5 gene controls its associated protein Gimap5 (GTPase of immunity associated protein 5). As the name suggests, its role is mainly linked to immune system function, lymphocyte white blood cell survival and T cell formation in the thymus. Genetic variants in Gimap5 were already associated with autoimmunity and colitis.
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Genetic basis of glaucoma

Northwestern Medicine scientists and international collaborators discovered mutations that cause improper drainage and a buildup of ocular pressure leading to one form of congenital glaucoma, and identified a path towards future treatments for the disease. Susan Quaggin, MD, chief of Nephrology and Hypertension in the Department of Medicine and director of the Feinberg Cardiovascular Research Institute, was senior author on the studies.

Glaucoma is a leading cause of blindness around the globe, and elevated intraocular pressure (IOP) is an important risk factor for the disease. Developmental defects in the anterior chamber of the eye, including a drainage vessel called Schlemm's canal, can lead to a particularly severe form of glaucoma in children known as primary congenital glaucoma (PCG).

Previous studies from Quaggin and her collaborators have shown loss-of-function mutations in the angiopoietin (ANGPT) receptor TIE2/TEK in families with PCG, and that ANGPT/TIE2 pathway activity is critical for Schlemm's canal development.

 In the JCI study, Quaggin and her colleagues used mice models to explore the importance of individual components of the ANGPT/TEK pathway, finding mice without the growth factor ANGPT1 had severely deformed and small Schelmm's canals. In addition, loss of TIE2/TEK, the angiopoietin receptor, had a similar effect.

Both ANGPT1 and TIE2/TEK are essential to form the drainage system of the eye to regulate intraocular pressure and prevent Glaucoma. Researchers found two human subjects with loss-of-function mutations in ANGPT1 within an international group of PCG patients, further supporting a causative role for ANGPT1 in the disease.

In the PNAS study, Quaggin and her colleagues searched for ways to influence the molecular pathway they'd identified. In particular, inhibition of TIE2/TEK has been linked to vessel leakage and inflammation, so finding a way to activate TIE2/TEK was a priority. Using mouse models, investigators found inhibition of a protein called VEPTP allowed ANGPT2 to be used as a TIE2/TEK activator, providing a blueprint for a pharmacological solution.
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Source of Huntington's disease

Huntington's disease is a fatal hereditary disorder for which there is currently no treatment, it is associated with jerky movements and as these patients increasingly lose brain neurons, they slide into dementia. But the new research suggests that these symptoms may be a late manifestation of a disease that originates much earlier, in the first steps of embryonic development.

A team at Rockefeller led by Ali Brivanlou, the Robert and Harriet Heilbrunn Professor, developed a system to model Huntington's in human embryonic stem cells for the first time. Researchers describe early abnormalities in the way Huntington's neurons look, and how these cells form larger structures that had not previously been associated with the disease.

Huntington's is one of the few diseases with a straightforward genetic culprit: One hundred percent of people with a mutated form of the Huntingtin (HTT) gene develop the disease. The mutation takes the form of extra DNA, and causes the gene to produce a longer-than-normal protein. The DNA itself appears in the form of a repeating sequence, and the more repeats there are, the earlier the disease sets in.

Research on Huntington's has thus far relied heavily on animal models of the disease, and has left many key questions unanswered. For example, scientists have not been able to resolve what function the HTT gene serves normally, or how its mutation creates problems in the brain. Suspecting that the disease works differently in humans, whose brains are much bigger and more complex than those of lab animals, researchers developed a cell-based human system for their research. They used the gene editing technology CRISPR to engineer a series of human embryonic stem cell lines, which were identical apart from the number of DNA repeats that occurred at the ends of their HTT genes.

In cell lines with mutated HTT, we saw giant cells. It looked like a jungle of disorganization. When cells divide, they typically each retain one nuclei. However, some of these enlarged, mutated cells flaunted up to 12 nuclei-suggesting that neurogenesis, or the generation of new neurons, was affected. The disruption was directly proportional to how many repeats were present in the mutation: The more repeats there were, the more multinucleated neurons appeared.

There is an unrecognized developmental aspect to the pathology. Huntington's may not be just a neurodegenerative disease, but also a neurodevelopmental disease. Treatments for Huntington's have typically focused on blocking the activity of the mutant HTT protein, the assumption being that the altered form of the protein was more active than normal, and therefore toxic to neurons. However, Brivanlou's work shows that the brain disruption may actually be due to a lack of HTT protein activity.

To test its function, the researchers created cell lines that completely lacked the HTT protein. These cells turned out to be very similar to those with Huntington's pathology, corroborating the idea that a lack of the protein not an excess of it is driving the disease. The findings are significant because existing treatments that were designed to block HTT activity may actually do more harm than good.
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Links between gum disease and cancer

Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists Dominique Michaud at Tufts University School of Medicine and Elizabeth Platz of the Johns Hopkins Bloomberg School of Public Health and Kimmel Cancer Center.

Researchers used data from comprehensive dental exams performed on many participants from Maryland, Minnesota, Mississippi, and North Carolina, as part of their participation in the Atherosclerosis Risk in Communities (ARIC) study who were then followed from the late 1990s until 2012.

 During the follow-up period, 1,648 new cancer cases were diagnosed. The research team found a 24 percent increase in the risk of developing cancer among participants with severe periodontitis, compared to those with mild to no periodontitis at baseline.

Among patients who had no teeth-which can be a sign of severe periodontitis, the increase in risk was 28 percent. The highest risk was observed in cases of lung cancer, followed by colorectal cancer. When the researchers did sub-group analyses, they found that participants with severe periodontal disease had more than double the risk of developing lung cancer, compared with no periodontitis.

An 80 percent increase in risk of colon cancer observed for participants who were edentulous at baseline, which is consistent with prior findings, and among never smokers, a two-fold higher risk was noted for participants with severe periodontitis, compared to those who had no periodontitis.

The research team accounted for the impact of smoking among the participants, since people who smoke are more likely to get periodontal disease, and smoking raises the risk of lung and colon cancers. Looking at data for the people who had never smoked, they also found evidence that having severe periodontal disease was related to an increased risk of lung cancer and colorectal cancer.

The researchers found no links between increased risk of breast, prostate or blood/lymphatic cancer and periodontitis. The link between periodontitis and increased cancer risk was weaker or not apparent in African-American participants from the ARIC study, except in cases of lung and colorectal cancer. Advanced gum disease-periodontitis, is caused by bacterial infection that damages the soft tissue and bone that support the teeth.
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Links between Crohn's and Parkinson's disease

Mount Sinai Researchers have just discovered that patients in the Ashkenazi Jewish population with Crohn's disease (a chronic inflammatory of the digestive system) are more likely to carry the LRRK2 gene mutation. This gene is the major genetic cause of Parkinson's disease, which is a movement disorder.

Crohn's disease is a complex disorder with multiple genes and environmental factors involved, which disproportionally affects individuals of Ashkenazi Jewish ancestry. The presence of shared LRRK2 mutations in patients with Crohn's disease and Parkinson's disease provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.

Researchers used international data from the last decade up to the present to analyze the occurrence of some coding genetic mutations in the human genome of many  patients with Crohn's disease and compared them to people without the disorder. They identified mutations in the LRRK2 gene that are more frequently found in Crohn's disease cases as compared to unaffected individuals.

When they discovered a link between Crohn's and the LRRK2 gene mutations they went further to assess the possible genetic link between Crohn's and Parkinson's. The team then looked at a much larger sample of people including patients with Crohn's, Parkinson's, and no disease.

The study found two mutations of the LRRK2 gene in Crohn's disease patients. One of them called the risk mutation was more common in patients with Crohn's, while the other (the protective mutation) was more prevalent in patients without the disease. Most Crohn's disease patients who carried the risk mutation developed the disease on average six years earlier than those who did not carry this mutation.

The research also shows that more Crohn's patients with the risk mutation developed the disease in the small intestine, compared to those without the mutation. If the disease starts in the small intestine, it becomes more difficult to manage and often leads to complications and surgeries.
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Gene therapy for type 1 diabetes

Type 1 diabetes is a chronic disease in which the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. A gene therapy approach can lead to the long-term survival of functional beta cells as well as normal blood glucose levels for an extended period of time in mice with diabetes. The researchers used an adeno-associated viral (AAV) vector to deliver to the mouse pancreas two proteins, Pdx1 and MafA, which reprogrammed plentiful alpha cells into functional, insulin-producing beta cells.

A clinical trial in both type 1 and type 2 diabetics in the immediate foreseeable future is quite realistic, given the impressive nature of the reversal of the diabetes, along with the feasibility in patients to do AAV gene therapy. Approximately 9% of the world's adult population has diabetes, which can cause serious health problems such as heart disease, nerve damage, eye problems, and kidney disease.

One fundamental goal of diabetes treatment is to preserve and restore functional beta cells, thereby replenishing levels of a hormone called insulin, which moves blood glucose into cells to fuel their energy needs. But in patients with type 1 diabetes, beta-cell replacement therapy is likely doomed to failure because the new cells might fall victim to the same autoimmunity that destroyed the original cells.

A potential solution to this problem is to reprogram other cell types into functional beta-like cells, which can produce insulin but are distinct from beta cells and therefore are not recognized or attacked by the immune system. To explore the feasibility of this approach, Gittes and first author Xiangwei Xiao of the University of Pittsburgh School of Medicine engineered an AAV vector to deliver to the mouse pancreas proteins called Pdx1 and MafA, which support beta cell maturation, proliferation, and function.

The goal was to generate functional beta-like cells from pancreatic alpha cells, which may be the ideal source for beta cell replacement. For example, alpha cells are plentiful, resemble beta cells, and are in the correct location, all of which could facilitate reprogramming.

By comparing the gene expression patterns of normal beta cells and insulin-producing cells derived from alpha cells, the researchers confirmed nearly complete cellular reprogramming. This gene therapy approach restored normal blood glucose levels in diabetic mice for an extended period of time, typically around four months, and the new insulin-producing cells derived almost exclusively from alpha cells. Moreover, the strategy successfully generated functional insulin-producing cells from human alpha cells.

The viral gene therapy appears to create these new insulin-producing cells that are relatively resistant to an autoimmune attack. This resistance appears to be due to the fact that these new cells are slightly different from normal insulin cells, but not so different that they do not function well. Several features of this approach could facilitate translation to humans. For one, AAV vectors like those used in this study are currently undergoing various gene therapy trials in humans.

Moreover, the viral vectors can be delivered directly to the human pancreas through a routinely performed non-surgical endoscopic procedure; however, this procedure can elicit pancreatic inflammation. In addition, no immunosuppression is required, so patients would avoid related side effects such as an increased risk of infection. However, one major concern was that the mice did eventually return to the diabetic state, suggesting that this treatment would not represent a definitive cure for the disease.
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Kidney disease can cause diabetes

Urea plays a role in the two-way link between the two diseases. Urea comes from the breakdown of protein in food. Kidneys normally remove urea from the blood, but poor kidney function can lead to increased levels of urea.

The study involved the analysis of medical records of adults who did not have diabetes. About 9 percent had elevated urea levels, a sign of reduced kidney function. That's the same rate as in the general population, according to the researchers.

People with high urea levels were 23 percent more likely to develop diabetes than those with normal urea levels, the study found. Diabetes is a major risk factor for kidney disease, elevated levels of urea, also raises the risk of diabetes.

When urea builds up in the blood because of kidney dysfunction, increased insulin resistance and impaired insulin secretion often result.
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Cancer survivors age faster and die younger

Childhood cancer survivors naturally age faster and are more likely to die sooner than those who have not had the disease, according to a new study. The research also showed that survivors are three to six times more likely to develop cancer again. Researchers from the Mayo Clinic in Rochester, Minnesota, found that hormonal/gland disorders (endocrinopathies), heart problems, lower bone mineral density, lung scarring (pulmonary fibrosis) and secondary cancers are more likely to occur in childhood cancer survivors later in life.

Frailty to bones and joints may also occur at an earlier age than the general population due to the damage caused by chemotherapy and radiotherapy to normal healthy tissues. The cancer and harsh treatments diminishes 'physiological reserve', the capacity in organs and biological body systems given to us at birth. These are the body's natural resilience to overcome internal and external biological stressors.

Other findings showed that childhood cancer survivors' estimated life expectancy is 30 percent lower than that of the general population. Also, the risk of frailty among bone marrow transplant recipients is around eight times as high as that of their siblings. Radiation therapy is associated with dementia, memory loss and secondary bone marrow cell and blood cancers, while long-term steroid treatment is linked to a higher risk of cataracts, osteoporosis, nerve damage and infection.
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Juluca for treating virologically suppressed HIV-1 Infection

FDA Approves Juluca (dolutegravir and rilpivirine) for the maintenance and treatment of virologically suppressed HIV-1 Infection. This is the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of three or more drugs included in standard HIV treatment.

Juluca is a fixed-dose tablet containing two previously approved drugs (dolutegravir and rilpivirine) to treat adults with HIV-1 infections whose virus is currently suppressed on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.

Limiting the number of drugs in any HIV treatment regimen can reduce toxicity for patients, HIV weakens a person’s immune system by destroying important cells that fight disease and infection. Juluca’s safety and efficacy in adults were evaluated in two clinical trials of 1,024 participants whose virus was suppressed on their current anti-HIV drugs.

 Participants were randomly assigned to continue their current anti-HIV drugs or to switch to Juluca. Results showed Juluca was effective in keeping the virus suppressed and comparable to those who continued their current anti-HIV drugs. The most common side effects in patients taking Juluca were diarrhea and headache.

Serious side effects include skin rash and allergic reactions, liver problems and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.
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Genome editing improves T-cell for cancer immunotherapy

Researchers have discovered a way to boost the cancer-destroying ability of the immune system's T-cells, offering new hope in the fight against a wide range of cancers. Using CRISPR genome editing, the team took the genetic engineering of killer T-cells one step further by removing their non- cancer specific receptors and replacing them with ones that would recognize specific cancer cells and destroy them.T-cells engineered to fight cancer had two kinds of receptors – the therapeutic one that was added in the lab, and their own naturally existing one.

Since there is only limited 'space' on a cell for receptors, cancer-specific ones need to compete with the cell's own receptors to perform their function. More often than not, the cell's own receptors win that competition, and leave 'space' for only a very limited number of newly introduced, cancer-specific receptors, which means that T-cells engineered with the current technology never reach their full potential as cancer killers. The T-cells we made using genome editing do not have any of their own T-cell receptors left, and therefore the only receptor they can use is the one specific for cancer. As a result, these cells can be  better at seeing and killing cancer than the cells prepared using the current methodology.

T-cells are a part of the immune system that helps human to fight off bacterial and viral infections, such as the flu virus. Some T-cells are also able to attack cancer cells. Augmenting and harnessing the anti-cancer activity of the body's own T-cells has led to the development of so-called immunotherapies which are now transforming the field of cancer treatment, even giving hope to patients with final stage disease.

The team believe that in time new improvements in gene editing technology are set to revolutionise cancer immunotherapy, making the treatments, which are unprecedented in their effectiveness, applicable to wider cohorts of patients suffering from different types of the disease. The improvement in the sensitivity of cancer recognition that can be achieved by editing out the existing natural receptor and then replacing it with one that sees cancer cells is remarkable. Immunotherapy-harnessing the body´s own immune cells has become the most potent and promising new treatment for a range of cancers and represents one of the biggest breakthroughs in cancer treatment.
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Age and diseases may be responsible for curve penis

According to a doctor, the penis can become curve naturally as a man gets older, it can be a sign of a serious disease which has recently been linked to cancer. Some men have a more bent penis for a harmless reason-the two tubes that fill with blood to give an erection can be different sizes. The skin on the organ can affect how curved it appears, aging makes skin gets looser, the curve can look more pronounced.

But a bent penis can be a symptom of a condition known as Peyronie's disease, which is estimated to affect up to seven percent of males. Researchers recently linked this with a higher risk of various cancers-including testicular, melanoma and stomach. Signs of  Peyronie's include scar tissue, a significant bend, erection problems and pain.

When the penis becomes erect, it's because two tubes called the corpora cavernosa fill up with blood,
the resultant curve may not be too noticeable when a man is flaccid but become more obvious when he is hard. As we all age, the skin all over our body produces less collagen and as a result, the skin becomes thinner and more fragile and starts to sag. So the natural curve can be more prominent as the skin hangs down looser.

Peyronie's disease occurs when a scar formation in penis prevents straight erection. It can make sex painful and cause erectile dysfunction. But in many cases men have no recollection of a specific trauma. In some, Peyronie's comes on gradually and doesn't seem to be related to an injury. Researchers therefore suspect it can be related to genes. In some men, injury and genetics could both be involved.

A recent study of different men found Peyronie's disease brought a higher risk of testicular cancer by 40 percent, melanoma by 29 percent and stomach cancer by 40 percent. A gene that may trigger the complaint could also be linked to the development of tumors.
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High levels of air pollution increases the risk of heart attack

People with certain blood types are more likely to suffer a heart attack when exposed to high levels of pollution, people who have A, B, or AB blood types have an 'elevated risk', compared to those with the O blood type. Pollution is linked to a raised chance of a heart attack but it is the first time that the risk has also been linked to blood type.

The risk of a heart attack or chest pain doubled for people of type A, B, or AB blood when pollution hits high levels. In comparison, the risk rose by 40 percent for those with type O, according to researchers. The primary mutation we studied differentiates between O blood types and non-O, which includes positive and negative A, B, and AB blood types.

Dozens of genes have been shown in large international studies to predict the onset of coronary artery disease in people who are free of the disease. But the vast majority of people won't have a heart attack unless they already have coronary artery disease. Nor is a heart attack a certainty even with heart disease.

 A level of pollution at which the increased risk occurred for people with non-O blood types is threshold 25 micrograms of pollution per cubic metre. At levels higher than 25 micrograms per cubic metre of pollution, the increase in risk is linear, while below that level there's little if any difference in risk. During a winter inversion, the PM2.5 pollution level can occasionally reach as high as 100 micrograms per cubic metre, but 50 to 60 is more typical.

The researchers found that people with type O blood also have higher risk of heart attack or unstable chest pain in times of high air pollution. Their level of risk is much smaller, at 10 per cent instead of the non-O blood type's 25 per cent per 10 additional micrograms per cubic metre.
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IUDs may prevent cervical cancer

IUDs are safe and highly effective contraception method, intrauterine devices (IUDs) may also be quietly offering protection against the third-most common cancer in women worldwide.

The number of women diagnosed with cervical cancer is steadily rising. According to the World Health Organization WHO, approximately 528,000 women were diagnosed with cervical cancer worldwide in 2012, and 266,000 women died from the disease. By 2035, the WHO projects that those numbers will climb to more than 756,000 and 416,000, respectively.

For women in developing countries, where cervical cancer prevention resources such as the human papillomavirus HPV vaccine or regular cervical screenings are scarce, and where populations are increasing rapidly, a contraceptive that offers protection against cervical cancer could have a profound effect.

IUDs could be a tool to combat cervical cancer. Some scientists speculate that the placement of an IUD stimulates an immune response in the cervix, giving the body an opportunity to fight an existing HPV infection that could lead to cervical cancer. Another possibility is that when an IUD is removed, some cervical cells that contain HPV infection or precancerous changes may be scraped off. The body mounts an immune response to having an IUD placed.
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Breast cancer gene

Breast cancer is caused by complex interactions between a large number of genetic variants and our environment. The inherited component of breast cancer risk is due to a combination of rare variants in genes such as BRCA1 and BRCA2 that confer a high risk of the disease, and many genetic variants that each confer only a small risk.

The newly identified risk regions nearly double the number that are already known, thereby bringing the number of known common variants associated with breast cancer to about 180.
One in five women are in greater danger of getting breast cancer because of faults in their genes. Women are at risk of breast cancer if their mother, daughter or sister has breast cancer.

For one in five women, the errors written into their genes mean they have almost a third higher chance of getting breast cancer. An unlucky one per cent have three times the risk of the other 99 per cent of the population.

These gene changes now have the potential to be incorporated into existing models to accurately predict an individual's risk, and to improve both prevention and early detection of the disease. The study looked at 11.8 million single-letter 'spelling mistakes' in women's DNA which increase their risk of breast cancer.

The researchers discovered nine more variations affecting the gene BRCA1. In total, they have confirmed 107 genetic variants and discovered 72 new ones. The discovery allowed the team to calculate that one in ten women have a 70 per cent higher risk of getting breast cancer.

About 70 per cent of all breast cancers are fuelled by the sex hormone oestrogen and respond to hormone therapies such as tamoxifen.
Others, known as oestrogen-receptor negative, are not affected by the hormone and are more difficult to treat.

In a second study, the researchers found 10 new variants linked to these cancers, the two cancer types are biologically distinct and develop differently.
Breast cancer susceptibility is due to the effect of a large number of inherited genetic variants, each of which may only confers a slight increase in breast cancer risk, when the strongly predisposing genes such as BRCA1 and BRCA2 are not considered.

The study discovered 65 new variants, some of which are common, have each of which has only a small effect on breast cancer risk, but cumulatively they could be very important in altering a woman's risk of breast cancer.
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