Publisher Health

It’s the vitamin that we get from the sun, yet despite its ample availability, one in three Australian adults still suffer from mild, moderate or severe vitamin D deficiency.
Now, new research from the University of South Australia gives strong evidence that vitamin D deficiency is associated with premature death, prompting calls for people to follow healthy vitamin D level guidelines.
Published in Annals of Internal Medicine, the study found that the more severe the vitamin D deficiency, the greater the risk of mortality.
Vitamin D is an important nutrient that helps maintain good health and keep our bones and muscles strong and healthy.
First author and UniSA PhD candidate, Josh Sutherland, says while vitamin D has been connected with mortality, it has been challenging to establish causal effects.
“While severe vitamin D deficiency is rarer in Australia than elsewhere in the world, it can still affect those who have health vulnerabilities, the elderly, and those who do not acquire enough vitamin D from healthy sun exposure and dietary sources,” Sutherland says.

The UK’s most premature twins to survive, born at 22 weeks and five days, have just turned turned one year old. Harry and Harley spent five months in intensive care and weren’t expected to live. Parents Jade and Steve spoke to BBC Breakfast about their experience over the past year.

Patients with early-stage breast cancer who had a pathologic complete response (pCR) to neoadjuvant chemotherapy may be able to skip surgery and receive standard radiation treatment with a low chance of disease recurrence, according to a new study from researchers at The University of Texas MD Anderson Cancer Center.
The Phase II trial results, published today in Lancet Oncology, evaluated the likelihood of breast cancer returning in patients who are in complete remission after receiving chemotherapy and radiation without surgery. Each of the 31 patients followed had a complete response to chemotherapy and none had a breast tumor recurrence after a median follow-up of 26.4 months.
“The ultimate form of breast-conserving therapy is completely eliminating breast surgery for invasive disease,” said principal investigator Henry Kuerer, M.D., Ph.D., professor of Breast Surgical Oncology. “This research adds to growing evidence showing that newer drugs can completely eradicate cancer in some cases, and very early results show we can safely eliminate surgery in this select group of women with breast cancer.”
This is the first modern prospective trial of surgery omission in patients with early-stage breast cancer who respond favorably to chemotherapy. High responses are indicated by state-of-the-art breast imaging-guided, vacuum-assisted core biopsy (VACB). These results build on Kuerer’s previous research using an MD Anderson-developed biopsy protocol to accurately identify patients achieving a pCR after chemotherapy. Those patients, known as “exceptional responders,” are at a lower risk of breast cancer recurrence and are candidates for avoiding breast surgery.
Improved chemotherapy agents have increased pCR rates significantly, and patients with triple-negative or HER2-positive breast cancer now are achieving a pCR in 60% to 80% of cases. Combining these high response rates with selective image-guided VACB and stringent histologic processing has improved physicians’ ability to determine which patients may not need surgery.
The multicenter trial enrolled 50 women older than 40 with early stage triple-negative or HER2-positive breast cancer and a residual breast lesion less than 2 centimeters as determined by imaging after standard chemotherapy treatment. Patients had one image-guided VACB. If no disease was identified on biopsy, breast surgery was omitted, and patients proceeded to standard whole-breast radiotherapy.
The mean age of participants was 60.4 years; 21 patients had triple-negative breast cancer and 29 had HER2-positive breast cancer. Thirty-eight participants were white, 10 were Black and 2 were other ethnicities/races. The VACB identified a pCR in 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred.
“For the time being, standard breast cancer surgery is still necessary,” Kuerer said. “While these results are remarkable and quite promising, it’s important for patients to know this is the very beginning of a new type of treatment for select patients. Much longer follow-up and further studies will be necessary before this approach can be integrated into routine breast cancer care.”
The investigators will continue to follow trial participants for long-term outcomes. As a secondary aim of the study, the researchers also are measuring minimal residual disease from liquid biopsies to determine if they correlate with pCR.
Although this was a small, nonrandomized study, it shows the feasibility of this approach. A larger randomized study is needed to directly compare the treatments before any changes to standard of care are considered.
This study was funded by the National Cancer Institute/National Institutes of Health (P30 CA016672, UL1 RR024148), the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research, and funding from the MD Anderson Clinical Research Funding Award Program. Kuerer reports receiving consulting fees from Merck & Co., Inc., serving as an editor of NEJM Group, Inc. and receiving royalties from McGraw-Hill Professional, Inc. and Elsevier Publishing Inc. 

The conventional approach to fighting breast cancer is to deploy all the tools modern medicine has to offer. Surgery to excise the tumor is considered a critically important step, along with drugs, radiation, and hormone treatments and immunotherapy when appropriate.A new study questions that approach, suggesting surgery may not always be necessary for all patients. The study, an early-stage clinical trial, found that a carefully selected group of patients who responded remarkably well to chemotherapy could skip surgery altogether.Fifty patients over age 40 with two types of breast cancer and early-stage disease were enrolled in the trial.All patients underwent chemotherapy, followed by biopsies to determine whether their tumors had responded well to the treatment. Thirty-one patients — about 60 percent — responded remarkably well and were able to forgo surgery, the researchers found.The participants went on to receive radiation treatment and were still in remission after a median follow-up period of two years and two months, said Dr. Henry Kuerer, the principal investigator of the study, which was published on Tuesday in Lancet Oncology.The elimination of surgery for invasive breast cancer is “the ultimate form of breast-conserving therapy,” he said.Breast surgery can lead to complications like infections, and even breast-conserving procedures like lumpectomy can change the shape of the breast, leave scars or indentations, a tugging sensation or lasting nerve pain.New Developments in Cancer ResearchCard 1 of 5Progress in the field.

After decades of research and two previous drug development attempts, things are looking promising for a team of University of Arizona researchers working on a less toxic treatment for a specific type of breast cancer.
The researchers have developed a drug compound that appears to stop cancer cell growth in what’s known as triple-negative breast cancer. The drug, which has not yet been tested in humans, has been shown to eliminate tumors in mice, with little to no effect on normal healthy cells, making it potentially nontoxic for patients.
The therapy is based on a newly discovered way that a gene known as epidermal growth factor receptor, or EGFR, leads to cancer. EGFR is a long-investigated oncogene — a gene that in certain circumstances can transform a cell into a tumor cell.
The researchers’ findings are published in the journal Cancer Gene Therapy, and the team is working to get Food and Drug Administration approval to test the compound in phase 1 clinical trials in humans.
Triple-negative breast cancer accounts for about 10 to 15% of all breast cancers. Triple-negative refers to the fact that the cancer cells test negative for the three other types of breast cancer — those driven by too much estrogen, too much progesterone or too much of a protein called HER2, according to the American Cancer Society. Triple-negative breast cancer is more common in women under 40 who are Black or who have a specific mutation in a gene called BRCA1. About half of all cases of triple-negative breast cancer overexpress the EGFR oncogene, according to the National Institutes for Health.
The UArizona researchers devised a compound that blocks EGFR from going to a part of the cell that drives survival of the cancer. The compound shuts down functioning of the EGFR protein that acts in cancer cells but not normal cells.

Researchers at VCU Massey Cancer Center have set their sights on a new therapeutic target for an aggressive form of breast cancer with limited treatment options.
Breast cancer is the second most common cancer in U.S. women, and triple-negative breast cancer (TNBC) is a more aggressive and deadly form of disease that accounts for 10-15% of all breast tumors.
TNBC grows and spreads more quickly than other breast tumors and is associated with worse patient outcomes, accounting for nearly one-third of all breast cancer-related deaths.
Additionally, TNBC affects Black women disproportionately: Black women die from TNBC at a significantly higher rate than white women despite being diagnosed at a younger age. Finding an effective therapy that works well in all patients would be an important step in addressing this disparity.
Through a comprehensive and cutting-edge genomic screening method known as CRISPR/CAS9 screening, Massey scientists — led by Anthony Faber, Ph.D., and Jennifer Koblinski, Ph.D. — were able to identify a specific enzyme called UBA1 that revealed itself as an ideal therapeutic target. Using a novel UBA-inhibiting drug called TAK-243, they blocked the cellular function of UBA1 and effectively killed cancer cells in patient-derived breast tumors in mice.
Previous research has shown that UBA1 inhibitors can have a positive impact in hematological cancers such as acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML). This study — recently published in PNAS Nexus — is the first to suggest that UBA1 inhibitors could be effective in TNBC. TAK-243 has been tested recently in early phase trials, paving the way for potential testing in TNBC patients.

An international study led by a Rutgers scientist comparing new and older treatments against complicated urinary tract infections has found a new drug combination to be more effective, especially against stubborn, drug-resistant infections.
Describing the results in the Journal of the American Medical Association (JAMA), researchers in the ALLIUM Phase 3 clinical trial showed that a combination of the drugs cefepime and enmetazobactam was more effective in treating both complicated urinary tract infections and acute pyelonephritis (AP), a bacterial infection causing kidney inflammation, than a standard treatment combining piperacillin and tazobactam. Urinary tract infections are considered complicated when they are associated with risk factors — including fevers, sepsis, urinary obstruction or catheters — that increase the danger of failing antibiotic therapy.
“This new antibiotic was superior to the standard-of-care therapy,” said Keith Kaye, chief of the Division of Allergy, Immunology and Infectious Diseases and
a professor of medicine at Rutgers Robert Wood Johnson Medical School.
“It represents an exciting option for treatment,” said Kaye, the principal investigator of the study and lead author on the publication.
Kaye added this drug combination also fights an often-dangerous category of bacterial illnesses caused by pathogens known as extended spectrum beta-lactamase (ESBL) infections, named for an enzyme the bacteria produce. ESBL-producing bacteria can’t be killed effectively by many of the antibiotics conventionally used to treat infections, such as penicillins and cephalosporins.

Intermittent fasting has been shown to be an effective way to lose weight, but critics have worried that the practice may have a negative impact on women’s reproductive hormones. Now, a team of University of Illinois Chicago researchers has published a study in Obesity that brings new evidence to the table.
The researchers, led by Krista Varady, UIC professor of nutrition, followed a group of pre- and post-menopausal obese women for a period of eight weeks on the “warrior diet” method of intermittent fasting.
The warrior diet prescribes a time-restricted feeding window of four hours per day, during which dieters can eat without counting calories before resuming a water fast until the next day.
They measured the differences in hormone levels, obtained by analyzing blood sample data, in groups of dieters who stuck to four- and six-hour feeding windows against a control group that followed no diet restrictions.
Varady and her team found that levels of sex-binding globulin hormone, a protein that carries reproductive hormones throughout the body, was unchanged in the dieters after eight weeks. The same held true for both testosterone and androstenedione, a steroid hormone that the body uses to produce both testosterone and estrogen.
However, dehydroepiandrosterone or DHEA, a hormone that fertility clinics prescribe to improve ovarian function and egg quality, was significantly lower in both pre-menopausal and post-menopausal women at the end of the trial, dropping by about 14%.

The overexpression of a gene tied to cell division and the structure and function of neurons may prevent and protect against cognitive decline in both mice and humans with Alzheimer’s disease (AD), according to a new study by scientists at the University of Colorado Anschutz Medical Campus.
The gene, Kinesin-5 or KIF11, does this despite the presence of amyloid beta (Abeta), the main component of plaques in the brains of those with AD. Scientists have traditionally targeted the plaques when looking for treatments for the fatal disease. In this case, they went around them.
The study was published online last week in the journal iScience.
“Overexpressing KIF11 in mice did not affect the amyloid levels in the brain,” said the study’s co-senior author Huntington Potter, PhD, professor of neurology and director of the University of Colorado Alzheimer’s and Cognition Center and of Alzheimer’s research at the Linda Crnic Institute for Down Syndrome at the University of Colorado School of Medicine. “Yet they were still cognitively normal despite the plaques. This is one of the best indications that you can maintain cognition without getting rid of the plaques.”
KIF11 is a motor protein best known for its role in mitosis or cell division in non-neuronal cells. But it also plays a critical role in the formation of the dendrites and dendritic spines of neurons, which are used to communicate with other neurons and are important for learning and memory. Yet the main component of Alzheimer’s plaques, Abeta, can inhibit KIF11 and cause damage to these structures.
The researchers found that overexpressing the gene in mice with AD led to improved performance on cognitive tests compared to AD mice with normal levels of KIF11. Then they analyzed genetic data from human AD patients provided by the Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP) at Rush University in Chicago. They wanted to know if naturally occurring variations in KIF11 levels correlated with better cognitive performance in adults with or without amyloid plaques.
“Our results from analyzing the human data indicate that higher levels of KIF11 correlate with better cognitive performance in a cohort of older adults with amyloid pathology,” said the study’s lead author Esteban Lucero, PhD, from the University of Colorado School of Medicine.
“Thus, our results suggest that higher KIF11expression levels may partially prevent cognitive loss during the course of AD in humans, which aligns with our findings regarding the role of KIF11 in animal models of AD,” Lucero said.
Potter and co-senior author Heidi Chial, PhD, assistant professor of neurology and director of grant strategy and development at the University of Colorado Alzheimer’s and Cognition Center, said this information paves the way for researchers to begin testing new or existing drugs that can safely create this effect in humans.
“Many current experimental treatments for AD have focused on reducing Abeta production or on increasing the clearance of Abeta plaques,” Chial said. “Most of these approaches have failed to prevent or reverse cognitive decline in clinical trials. Clearly, alternative approaches to the development of AD therapeutics are needed.”
Story Source:
Materials provided by University of Colorado Anschutz Medical Campus. Original written by David Kelly. Note: Content may be edited for style and length.

Researchers at the University of Illinois College of Veterinary Medicine have demonstrated in a mouse model that a specific type of T cell, one of the body’s potent immune defenses, produces cytokines that are necessary for the body to acquire immunity against fungal pathogens. This finding could be instrumental in developing novel, effective fungal vaccines.
Despite vaccines being hailed as one of the greatest achievements of medicine, responsible for controlling or eradicating numerous life-threatening infectious diseases, no vaccines have been licensed to prevent or control human fungal infections.
This lack proved especially deadly during the COVID-19 pandemic. In countries where steroids were widely used to suppress inflammation of the lungs, COVID-19 patients with preexisting conditions such as uncontrolled diabetes showed a greater likelihood of developing lethal fungal infections.
T Cells Could Produce Protective or Pathological Response
“A particular type of T cell [TH17 cells] that expresses GM-CSF [granulocyte-macrophage colony-stimulating factor] was linked to greater severity of illness in people infected with the virus that causes COVID-19,” said Dr. Som Nanjappa, an assistant professor of immunology at the University of Illinois.
“Our study shows that IL-17A+ CD8+ T cell (Tc17), which also expresses GM-CSF, is necessary for mediating fungal vaccine immunity without instigating hyperinflammation. So clearly, the antigen specificity of T cells — whether they target viral vs. fungal or bacterial pathogens — has a huge impact on whether they play a protective or detrimental role.”
The article, “GM-CSF+ Tc17 cells are required to bolster vaccine immunity against lethal fungal pneumonia without causing overt pathology,” appeared in Cell Reports on October 25. Dr. Nanjappa’s coauthors on the study are Srinivasu Mudalagiriyappa, a former graduate student now a scientist with Insmed Incorporated, a global biopharmaceutical companyfocused onserious and rare diseases; Jaishree Sharma, a graduate student in the Department of Pathobiology; and Miranda D. Vieson, a Clinical Associate Professor in the Department of Pathobiology as well as a boarded veterinary pathologist in the college’s Veterinary Diagnostic Laboratory.
T Cells for Fungal Vaccine Immunity
In the study, colonies of mice were given an experimental fungal vaccine. The mice were then exposed to virulent fungal pathogen to cause lethal pulmonary infection. Researchers could determine the necessity of GM-CSF+ Tc17 cells to mediate vaccine immunity. Further, they found that IL-1 and IL-23 cytokines are necessary for eliciting GM-CSF+ Tc17 cells to vaccine. While IL-23 is dispensable for the long-term memory homeostasis of these cells, it is essential for vaccine immunity against pulmonary fungal infection.
This study identifies a beneficial subset of T cells for fungal vaccine immunity that bolsters efforts to develop a vaccine platform containing suitable adjuvants to potentiate such a T cell subset.
“In line with this, we have identified a functional phenotypic marker that could be targeted to enhance this subset to augment vaccine efficacy,” said Dr. Nanjappa. He recently received NIH-R01 funding to pursue this strategy for a fungal vaccine.