Posted on Diet

Are Americans eating enough whole grains? It depends on who you ask


A diet rich in whole grains, which are naturally high in fiber, is associated with lowering a person’s risk for various health problems. Overall, Americans are eating more whole-grain foods than ever before, researchers from the Friedman School of Nutrition Science and Policy at Tufts University report in a new study, published November 30 in the American Journal of Clinical Nutrition. However, the increase in whole-grain intake over the past two decades could be 39.5% or 61.5%, depending on which definition of a whole-grain food is being used. In addition, Americans’ mean consumption of whole-grain foods remained far below the recommended consumption of at least three ounces each day and varied considerably by each definition.

The researchers say there’s a clear need to standardize how consumers, researchers, and policymakers talk about whole-grain foods. The study compared overlapping definitions from five institutions: the Dietary Guidelines for Americans, the U.S. Food and Drug Administration (FDA), the American Heart Association, the American Association of Cereal Chemists International, and the Whole Grains Council. The research team applied the various definitions of a whole-grain food to the dietary intakes of over 39,700 adults captured by the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018.

“We found that each definition captured very different types of grain- or flour-containing foods as whole-grain foods, resulting in differences in the average consumption of whole-grain foods and the associated trends,” says lead author on the study Mengxi Du, a PhD candidate in the Nutrition Epidemiology and Data Science program at the Friedman School. As a consumer, she said she has had the experience of struggling to identify what is or isn’t a whole-grain food via the packaging labels. Recent surveys suggest nearly half of American consumers have similar challenges.

When looking at the different categories of whole-grain foods identified by these definitions, while some similarities were identified—whole-grain bread consumption increased under all definitions—there were more differences. The government-led FDA’s definition was the strictest, categorizing the fewest foods as whole-grain foods compared to the industry-led Whole Grains Council’s, which was the most lenient but could be least healthy based on a prior study.

One surprising finding was how the foods of different population subgroups were classified depending on the applied definition. For example, individuals who are non-Hispanic white had a higher intake of whole-grain foods compared with other racial/ethnical groups under all definitions, except for the definition proposed by the American Heart Association, under which Hispanic individuals had the highest intake. The possible reason is that the American Heart Association’s definition is more sensitive to identifying dishes such as corn-based burritos, tacos, and nachos as whole-grain foods.

“We can’t say which is the best definition yet as we need to assess the nutrient profiles of each and how these different definitions are associated with health outcomes. Our findings, however, underscore the imperative need for a consensus on whole-grain food definition. A consistent definition across agencies is essential to further promoting whole-grain food consumption in the U.S. population,” says Fang Fang Zhang, senior author on the study and interim chair of the Division of Nutrition Epidemiology and Data Science at the Friedman School.

Posted on Autism, Pain Management

People with autism are not ‘indifferent or hypo-sensitive’ to pain

People with autism have normal pain thresholds but increased sensitivity to painful stimuli, concludes a study in PAIN®, the official publication of the International Association for the Study of Pain (IASP). The journal ispublished in the Lippincott portfolio by Wolters Kluwer.

“This evidence demonstrating enhanced pain sensitivity warrants changing the common belief that autistic individuals experience less pain,” according to the report by Prof. Irit Weissman-Fogel of University of Haifa, Israel, and colleagues. They believe their findings highlight the need for increased awareness, which may impact effective treatment of pain in people with autism.

New evidence questions the assumptions about pain in autism

The researchers aimed to test the “prevailing assumption” that people with autism are hypo-sensitive to pain. Current diagnostic criteria suggest that autistic people demonstrate “apparent indifference” to pain or temperature. Yet most previous studies have not shown differences in pain sensitivity in autistic individuals.

Prof. Weissman-Fogel and colleagues performed in-depth laboratory tests of pain perception in 104 adults, 52 with autism. This sample is the largest as of yet testing pain psychophysics in autism. The two groups had similar scores on a brief cognitive test. People with autism had higher use of psychiatric medications, and rated themselves as having greater anxiety as well as higher sensitivity to pain and to daily environmental stimuli (such as smell, noise, light). This research project was funded by the Israel Science Foundation (ISF; 1005/17).

On quantitative sensory tests, there were no differences in thermal and pain detection thresholds between the autistic and non-autistic groups. This indicates normal pain and thermal thresholds, suggesting “normal functioning of the peripheral nervous system” among participants with autism.

However, the autistic group gave consistently higher pain ratings in response to various stimuli above their pain threshold, proving pain hypersensitivity. The tests also provided evidence that people with autism can successfully inhibit short pain stimuli but not long-lasting pain stimuli. Importantly, experiencing long-lasting pain in daily life is a risk factor for developing chronic pain.

New findings may lead to early treatment and better quality of life

Together, the findings suggest that people with autism have a “pro-nociceptive” pain modulation profile: their brain appears more active in facilitating pain experience and less active in inhibiting continuous pain. This is consistent with the theory of excitatory/inhibitory imbalance as an underlying mechanism of autism spectrum disorder – but one that has been neglected in terms of pain processing.

The study questions the perception that people with autism experience less pain, and instead suggests that they may have enhanced pain sensitivity. Prof. Weissman-Fogel and colleagues write, “This misinterpretation can lead to late diagnosis and poor treatment causing suffering and exacerbating the autistic symptoms” – potentially increasing the risk of developing chronic pain conditions. While their study focused on a group of autistic people with essentially normal cognitive function, the researchers write, “these results may also apply to people with autism whose cognitive and verbal communication impairments may eliminate their ability to communicate their pain.”

Prof. Weissman-Fogel and coauthors conclude: “These findings may raise physician, parent, and caregiver awareness to the pain phenomenon in autism, and thus lead to early and effective treatment to improve the wellbeing and quality of life for autistic individuals and their families.”

Read [Indifference or hypersensitivity? Solving the riddle of the pain profile in individuals with autism]

Posted on Diabetes

Retinal cells may have the potential to protect themselves from diabetic retinopathy

Cells within retinal blood vessels are endowed with a previously unappreciated ability to acquire resistance against the damaging effects of hyperglycemia in patients with diabetes mellitus, researchers report in The American Journal of Pathology

Overview of the discoveries and their potential clinical relevance


Culturing primary human retinal endothelial cells under hyperglycemic conditions initially compromised their mitochondria. The cells respond by adapting, which includes clearance of the dysfunctional mitochondria via mitophagy. Such adaptation is a plausible contributor to the underlying mechanism responsible for the long delay between the onset of diabetes and the manifestation of diabetic retinopathy. Furthermore, loss of adaptation may be a prerequisite for the development of retinopathy in patients with diabetes. CREDIT The American Journal of Pathology

About one third of patients with diabetes mellitus (DM) develop diabetic retinopathy (DR), a leading cause of blindness in working-age individuals. DR typically develops after many years of DM, and some patients do not develop DR for more than 50 years. New research suggests that an endogenous system that protects human retinal endothelial cells from harmful effects of the hyperglycemia (an excess of blood sugar) may be responsible for the delayed onset of DR. Furthermore, degradation of this protective system over time may set the stage for development of DR. The new study appears in The American Journal of Pathology, published by Elsevier.

“The prevailing understanding of what causes DR predicts that it will develop soon after the onset of DM,” explained lead investigator Andrius Kazlauskas, PhD, Departments of Ophthalmology and Visual Sciences and Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA. “Yet this is not the case. Although the long delay from the onset of DM to the development of DR is a well-known clinical phenomenon, there is relatively little effort to investigate the underlying reason for this delay. Uncovering this information constitutes an exciting opportunity to improve current approaches to prevent DM from progressing to DR.”

Exposing cultured cells, such as vascular endothelial cells, to high glucose is a common in vitro model of DR. The investigators cultured human retinal endothelial cells in either normal glucose or high glucose–containing media. Unexpectedly, they found that prolonged exposure to high glucose was beneficial, not detrimental. After one day, the health of the cells declined, but as the duration of exposure was prolonged, the cells recovered and acquired resistance to DM-related damage such as inflammation and death.

The investigators found that the adaptation was associated with improved mitochondria functionality. Mitophagy is the process in which cells remove damaged mitochondria, and disruption of this intrinsic quality control system is associated with many diseases. Though initially compromised, mitochondrial functionality was improved after 10 days of exposure to high glucose, with increased clearance of damaged mitochondria. Interfering with the mitochondrial dynamics compromised the cells’ ability to endure high glucose. Susceptibility to cell death increased, and responsiveness of vascular endothelial growth factor deteriorated.

Dr. Kazlauskas said these observations indicate the existence of an endogenous system that protects human retinal endothelial cells from the deleterious effects of hyperglycemia. “The compelling role of mitochondrial dysfunction in the development of DR supports our central concept of a hyperglycemia-induced mitochondrial adaptation (HIMA) system, the purpose of which is to preserve the functionality of mitochondria. We posit that the loss of HIMA sets the stage for advancing to DR.”

An important component of the HIMA concept is that improving the functionality of a subset of retinal cells will be beneficial for the whole retina. Previous research has found even a small reduction in degree or type of insult to the retina can protect animals that have DM from developing DR. Together these discoveries suggest that the development of DR involves a relatively small shift in the balance between exogenous insults and the endogenous systems that prevent DM-driven damage and drivers of pathogenesis. 

Dr. Kazlauskas observed that the increasing incidence of DM, and consequently of DR, around the world exacerbates the need for effective approaches to protect patients from this serious complication. “Does HIMA exist in vivo, does it protect patients from DR, and is its demise a prerequisite for progression to DR? Our ongoing research is focused on answering these open questions,” he concluded.

Posted on Pain Management

Positive media coverage of cannabis pain studies, regardless of therapeutic effect


In cannabis trials against pain, people who take placebos report feeling largely the same level of pain relief as those who consume the active cannabinoid substance. Still, these studies receive significant media coverage regardless of the clinical outcome, report researchers from Karolinska Institutet in Sweden in a study published in JAMA Network Open.

“We see that cannabis studies are often described in positive terms in the media regardless of their results,” says the study’s first author Filip Gedin, postdoc researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”

The study is based on an analysis of published clinical studies in which cannabis has been compared with placebo for the treatment of clinical pain. The change in pain intensity before and after treatment were the study’s primary outcome measurement.

The analysis drew on 20 studies published up to September 2021 involving almost 1,500 individuals.

The results of the study show that pain is rated as being significantly less intense after treatment with placebo, with a moderate to large effect. The researchers also observed no difference in pain reduction between cannabis and placebo, which corroborates results from another recently published meta-analysis. 

“There is a distinct and clinically relevant placebo response in studies of cannabis for pain,” says Dr Gedin.

The researchers also examined a possible connection between the magnitude of the therapeutic effect shown by the cannabis studies and the coverage they receive in the media and in academic journals. Media presence was measured through Altmetric, which is a method of evaluating mentions in the media, in blogs and on social media. Academic impact was measured in terms of citations by other researchers.

The analysis of media presence included a total of 136 news items in traditional media and in blogs and was categorised as positive, negative or neutral, depending on how the results were presented concerning the effectiveness of cannabis as a treatment for pain.

The researchers found that the cannabis studies received much greater media attention than other published studies. The coverage was substantial regardless of the magnitude of the placebo response and regardless of the therapeutic effect of cannabis. They also observed no link between the proportion of positively described news about a study and the effect it reported. 

The researchers add the caveat that their study combined trials of varying designs and quality and therefore the results should be interpreted with caution.

This research was financed by Riksbankens Jubileumsfond (Karin Jensen). The researchers report no potential conflicts of interest.

Posted on autoimmune conditions, Cancer, Rheumatoid arthritis

Rogue immune cells linked to leukaemia are a key driver of autoimmune diseases like RA

Killer T Cell

A killer T cell (centre) hunting a target cell. Credit: NIH Image Gallery CREDIT NIH Image Gallery

Gene variants associated with leukaemia can produce ‘rogue’ immune cells that drive autoimmune diseases, according to a new study from the Garvan Institute of Medical Research.

Scientists had previously noticed that leukaemia patients were also likely to develop an autoimmune disease, such as rheumatoid arthritis or aplastic anaemia. Research into this link revealed that immune cells called killer T cells – responsible for destroying harmful cells and pathogens – were a key player.

This new research provides insight into the role these killer T cells play in leukaemia and autoimmune disease. Gene variations affecting a protein that controls the growth of killer T cells can turn them rogue, the researchers found.

“We showed that these rogue killer T cells are driving the autoimmunity. They’re probably one of the cell types most directly contributing to autoimmune disease,” says Dr Etienne Masle-Farquhar, a postdoctoral researcher in the Immunogenomics and Genomic Medicine Labs at Garvan.

“Our research also narrows down a few pathways that might be helpful in targeting these cells for future treatments,” he says.

The findings are published in the journal, Immunity.

Cancers can grow when tumour cells are not identified or destroyed by the immune system. Autoimmune diseases occur when the immune system attacks the body’s own cells, mistaking them for harmful or foreign cells.

“We knew that people with various autoimmune diseases acquire these rogue killer T cells over time, but also that inflammation can cause immune cells to proliferate and develop mutations. We set out to discover whether the rogue T cells were causing these autoimmune conditions, or simply associated with them,” says Dr Masle-Farquhar.

The researchers used new high-resolution screening methods to look at blood from children with rare inherited autoimmune diseases.

They then used a technique called CRISPR/Cas9, a genome editing tool, in mouse models, to find out what happens when the protein STAT3 is genetically altered.

STAT3 is found throughout the body and is critical for various cell functions, including controlling the immune system’s B cells and T cells.

The team found that if these proteins are altered, they can cause rogue killer T cells to grow unchecked, resulting in enlarged cells that bypass immune checkpoints to attack the body’s own cells.

In addition, even just 1-2% of a person’s T cells going rogue could cause autoimmune disease.

“It’s never been clear what the connection between leukaemia and autoimmune disease is – whether the altered STAT3 protein is driving disease, or whether leukaemic cells are dividing and acquiring this mutation just as a by-product. It’s a real chicken-and-egg question, which Dr Masle-Farquhar’s work has been able to solve,” says Professor Chris Goodnow, Head of the Immunogenomics Lab and Chair of The Bill and Patricia Ritchie Foundation at Garvan.

“This gives some really good cracks in the coalface of where we might do better in terms of stopping these diseases, which are sometimes life threatening,” he says.

Future applications could include better targeting of medication, like already TGA-approved JAK inhibitors, based on the presence of these mutations. “We can now go and look for T cells with STAT3 variations. That’s a big step forward in defining who’s the bad guy,” says Professor Goodnow.

The study also identified two specific receptor systems – ways for cells to talk to one another – that are linked to stress.

“Part of what’s driving these rogue cells to expand as killer T cells is the stress-sensing pathways. There is a lot of correlation between stress, damage and ageing. Now we have tangible evidence of how that’s connected to autoimmunity,” Professor Goodnow says.

The team’s research may help develop screening technologies that clinicians could use to sequence the complete genome of every cell in a blood sample, to identify which cells might turn rogue and cause disease.

Further study is needed to determine whether rogue killer T cells are involved in all autoimmune diseases, and what proportion of people with rheumatoid arthritis and other autoimmune conditions have rogue cells and STAT3 variations.