Poor diet during teens, early adulthood may raise breast cancer risk

Previous studies have associated an unhealthful diet - particularly one that is low in vegetables, high in refined sugar and carbohydrates, and high in red and processed meats - with chronic inflammation, which may raise the risk of certain cancers.

According to the new study, it is this diet-induced inflammation that may increase a woman's risk of breast cancer prior to menopause.

Study co-author Karin B. Michels, Ph.D. - professor and chair of the Department of Epidemiology at the Fielding School of Public Health at the University of California-Los Angeles - and colleagues recently reported their findings in the journal Cancer Epidemiology, Biomarkers & Prevention.

After skin cancer, breast cancer is the most common cancer among women in the United States. This year, around 252,710 new cases of invasive breast cancer will be diagnosed, and more than 40,000 women will die from the disease.

"About 12 percent of women in the U.S. develop breast cancer in their lifetimes," notes Michels. "However, each woman's breast cancer risk is different based on numerous factors, including genetic predisposition, demographics, and lifestyle."

For this latest study, Michels and colleagues set out to determine how a pro-inflammatory diet during adolescence or early adulthood might influence women's risk of breast cancer in later life.

Up to 41 percent greater breast cancer risk with pro-inflammatory diet

The researchers analyzed the data of 45,204 women who were part of the Nurses' Health Study II.

Some of the women completed a food frequency questionnaire in 1991, when they were aged between 27 and 44 years, which disclosed details of their diet in early adulthood. The questionnaire was completed again every 4 years thereafter.

In 1998 - when aged between 33 and 52 - some women completed a food frequency questionnaire that detailed their diet during high school.

Using a technique that associates food intake with markers of inflammation in the blood, the researchers allocated an inflammatory score to each woman's diet. The women were then divided into five groups based on their inflammatory score.

Compared with women who had the lowest inflammatory diet score during adolescence, those who had the highest score were found to be at a 35 percent higher risk of developing premenopausal breast cancer.

Women with the highest inflammatory diet score during early adulthood were found to have a 41 percent increased risk of premenopausal breast cancer, compared with those who had the lowest inflammatory diet score.

A pro-inflammatory diet was not associated with the overall incidence of breast cancer or the risk of postmenopausal breast cancer, the team reports.

Although the study cannot prove cause and effect between a pro-inflammatory diet during adolescence or early adulthood and premenopausal breast cancer, the team believes that the results further highlight the importance of a healthful diet.

"Our study suggests that a habitual adolescent/early adulthood diet that promotes chronic inflammation may be another factor that impacts an individual woman's risk.

During adolescence and early adulthood, when the mammary gland is rapidly developing and is therefore particularly susceptible to lifestyle factors, it is important to consume a diet rich in vegetables, fruit, whole grains, nuts, seeds, and legumes and to avoid soda consumption and a high intake of sugar, refined carbohydrates, and red and processed meats."

Karin B. Michels, Ph.D.

There are a number of limitations to the study. For example, participants reported their adolescent diet years later, so their recollections could be subject to error. Additionally, the researchers did not have access to subjects' measurements of inflammatory blood markers during adolescence or early adulthood.

work work work 03:30 No comments

Ketogenic diet may protect against gout

Gout is a rheumatic disease that affects more than 8 million people in the United States. It is caused by either an excessive production or insufficient excretion of uric acid. In gout, the uric acid crystals sediment in tissues and fluids, triggering the body's immune cells. This results in disabling pain, inflammation, and fever.

These episodes of immune cell reactivation, also known as flares, are triggered by a protein complex called the NLRP3 inflammasome.

New research from the laboratory of Vishwa Deep Dixit - professor of comparative medicine and immunobiology at Yale School of Medicine in New Haven, CT - suggests that the so-called ketogenic diet may help to relieve the symptoms of gout.

A ketogenic diet is low in carbohydrates and typically used to lose weight. Ketogenic diets work by inducing "physiological ketosis" in the body - a state of the metabolism where the body's reserves of glucose are no longer enough for the body's central nervous system.

The central nervous system then needs an alternative source of energy, so it makes the liver turn fats into fatty acids and ketone bodies.

The new study - published in the journal Cell Reports - suggests that one of these ketone bodies, the beta-hydroxybutyrate (BHB), may alleviate urate crystal-induced gout.

Ketogenic diet increases BHB, protects against gout-related inflammation

The research team developed a new model of gout flares in rodents.

As the researchers explain, these flares are triggered by the NLRP3 inflammasome. With the help of neutrophils - the most common type of white blood cell - NLRP3 activates the IL-1B pro-inflammatory cytokine, leading to episodes of intense pain, fever, and the destruction of joints.

In the rodent model, researchers induced gout by injecting 1.25 milligrams of monosodium urate into rats' knees. Researchers measured knee thickness and performed pathology analyses on the rats' ligaments and menisci.

The rodents were kept in pathogen-free conditions and fed a ketogenic diet 1 week before starting the experiments. Scientists measured the levels of BHB in the rodents' blood.

The scientists also examined human subjects. They recruited healthy, steroid-free adults aged between 18 and 45, as well as older adults aged 65 and over. Participants were not fasting when their peripheral blood was collected.

Dixit and colleagues also conducted statistical analyses and performed all of the experiments at least twice.

The team found that a ketogenic diet raised BHB levels, which in turn inhibited the NLRP3 inflammasome. As a consequence, the symptoms of urate crystal-induced gout were alleviated, without negatively impacting the immune system or its ability to defend against bacterial infections.

Additionally, BHB blocked IL-1B in the neutrophils of both mice and humans, regardless of age. Dixit and colleagues conclude that:

"Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout."

Emily Goldberg, co-author on the study, associate research scientist, and clinical veterinarian in comparative medicine, explains the findings:

"In isolated neutrophils, [BHB] completely blocked NLRP3 inflammasome activation, even when provided at low concentrations that are physiologically achievable through dietary modification."

She also suggests that targeting the NLRP3 inflammasome to reduce inflammation during a flare may improve the gout patients' symptoms. However, she admits that more studies are needed to test this possibility.

work work work 21:34 No comments

Schizophrenia begins in the womb, study suggests

By transforming skin cells from patients with schizophrenia into neuronal progenitor cells - cells that form neurons in early development - researchers identified an abnormal gene pathway called nuclear FGFR1 (nFGFR1) that impairs early brain development.

Senior study author Michal K. Stachowiak, Ph.D., of the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo in New York, and colleagues say that their findings may bring us closer to treatments that could prevent schizophrenia in utero.

The researchers recently reported their results in the journalSchizophrenia Research.

According to the National Institute of Mental Health, around 1.1 percentof adults in the United States have schizophrenia - a mental health disorder characterized by hallucinations, delusions, and abnormal thoughts.

While the exact causes of schizophrenia remain unclear, researchers have long known that the condition can run in families, suggesting a genetic origin. Furthermore, an increasing number of studies have uncovered genetic mutations associated with an increased risk of schizophrenia.

For their study, Stachowiak and colleagues sought to learn more about the genomic processes that occur in utero that might influence the risk of schizophrenia development.

Dysregulated nFGFR1 pathway impairs brain development

To reach their findings, the researchers collected skin cells from four adults with schizophrenia and four adults without the disorder.

The skin cells were reprogrammed into induced pluripotent stem cells, and these differentiated into neuronal progenitor cells. This enabled the team to assess the processes that occur during early brain development in people with schizophrenia.

The researchers pinpointed a dysregulated nFGFR1 pathway that targets and mutates numerous genes associated with schizophrenia. The team explains that just one of these gene mutations can impact brain development.

According to the authors, these findings provide proof of concept that schizophrenia may be caused by a dysregulated genomic pathway that influences the brain before birth.

"In the last 10 years, genetic investigations into schizophrenia have been plagued by an ever-increasing number of mutations found in patients with the disease. We show for the first time that there is, indeed, a common, dysregulated gene pathway at work here."

Michal K. Stachowiak, Ph.D.

Furthermore, the team says that these findings open the door to new schizophrenia treatments. For example, a drug could be administered to expectant mothers, whose offspring has a high risk of developing schizophrenia, that prevents processes related to the disease occurring in the developing fetus.

In future studies, the researchers plan to grow "mini brains" using the same processes used in the current study, with the aim of gaining a deeper understanding of how dysregulation of the nFGFR1 pathway influences early brain development, as well as to provide a model to test possible treatments.

work work work 21:31 No comments

WHO prioritize 12 treatment-resistant bacteria for drug development

The World Health Organization (WHO) developed the "priority pathogen list" after a request from UN member states.

To date, decisions about which pathogens to prioritize for research and development (R&D) have been made by individual drug companies, large and small. These decisions tend to be variously influenced by perceived or unmet medical needs, pressure from investors, potential for scientific discovery, availability of technology, and market size, say the WHO.

Dr. Marie-Paule Kieny, assistant director-general for Health Systems and Innovation at the WHO, says that:

"Antibiotic resistance is growing, and we are fast running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time."

The idea of a priority pathogen list is not new; in 2013, for instance, the Centers for Disease Control and Prevention (CDC) published an antibiotic resistance threat list for the United States. However, this is the first time that a list has been produced by a global health agency from the point of view of threat to worldwide public health.

In a report on how they compiled it, the WHO note that the main objective of the global priority pathogen list is to "guide the prioritization of incentives and funding, help align R&D priorities with public health needs, and support global coordination in the fight against antibiotic-resistant bacteria."

The problem of growing antimicrobial resistance

Antimicrobial drugs have been used effectively for more than 70 years and have greatly reduced illness and death from infection. However, many of them - such as antibiotics designed to kill disease bacteria - have been used so widely and for so long that the microbes have adapted and become highly drug-resistant.

New mechanisms of drug resistance are emerging and spreading around the world, threatening our ability to treat even common infections. This is resulting in lengthier illnesses, longer hospital stays, costlier and more intensive care, disability, and death.

The new WHO list highlights the particular threat of bacteria that are resistant to more than one drug. These bacteria have not only evolved built-in mechanisms that resist treatment, they can also pass their genetic material to other bacteria so that they, too, become drug-resistant.

Growing antimicrobial resistance is already complicating the treatment of tuberculosis (TB), HIV, and malaria. According to the WHO, there are now 480,000 new cases of multidrug-resistant TB worldwide every year.

Also, without effective drugs to prevent and combat infection, medical procedures such as cancer treatments, organ transplants, diabetes management, cesarian sections, hip replacements, and other major surgical operations, become very high risk.

According to the CDC, at least 2 million people per year in the U.S. become infected with drug-resistant bacteria and around 23,000 people per year die as a direct result of these infections. Many others die from conditions that are complicated by antibiotic-resistant infections.

Critical, high, and medium priority pathogens

The WHO have categorized the 12 bacteria in terms of urgency of need for new drugs: critical, high, and medium priority.

The critical group includes infection-causing bacteria that are resistant to several drugs and pose a particular threat in hospitals and nursing homes, and specifically to patients on ventilators or fitted with blood catheters.

The bacteria in the critical group include: Acinetobacter, Pseudomonas, and some Enterobacteriaceae (including E. coli,Klebsiella, Proteus, and Serratia).

These pathogens can cause severe and often fatal infections, including pneumonia and bloodstream infections.

The high and medium priority groups contain other bacteria that are becoming increasingly resistant to available drugs, and that cause more common infections such as gonorrhoea, food poisoning (caused by salmonella), and Staphylococcal infections (caused by resistant forms of Staphylococcus aureus, such as MRSA).

Drug-resistant strains of the following bacteria are also in the high and medium priority groups: Enterococcus faecium,Helicobacter pylori, Campylobacter species, Streptococcus pneumoniae, Haemophilus influenzae, and Shigella species.

Decision criteria for pathogen inclusion

Researchers from the University of Tübingen in Germany collaborated with the WHO in compiling the list, using criteria and a decision-making method that was vetted by international experts.

The criteria used included: the deadliness of the pathogen; the length of hospitalization they cause; frequency of resistance to antibiotics when spread in the community; ease of spread in animals, from animals to humans, and among humans; how easy it is to prevent infection; how many treatment options are available; and whether new drugs to tackle them are already in development.

The list does not include the bacterium that causes TB because this is already targeted by existing, dedicated programs. Other bacteria - such as Streptococcus A and B and chlamydia - are also excluded because they have low levels of resistance to current drugs and do not pose a significant threat to public health, say the WHO.

Evelina Tacconelli, a professor, head of the division of infectious diseases at Tübingen, and a major contributor to the work, concludes:

"New antibiotics targeting this priority list of pathogens will help to reduce deaths due to resistant infections around the world. Waiting any longer will cause further public health problems and dramatically impact on patient care."

The WHO also point out that new drugs on their own will not solve the problem of antimicrobial resistance. We also need to continue efforts to prevent infection and avoid inappropriate use of existing and future antibiotics.

work work work 21:29 No comments