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The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19, and all are free to access. The following were published between July 7 and August 1; all are free to access:

It's not just mortality: A call for comprehensive policy responses for COVID-19 among older people from Chile: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences and Social Sciences by Pablo Villalobos Dintrans, DrPH, Jorge Browne, MD, MSc, and Ignacio Madero-Cabib, PhD

Acute kidney injury is associated with in-hospital mortality in older patients with COVID-19: Research article in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Qi Yan, MD, Peiyuan Zuo, MD, Ling Cheng, MD, Yuanyuan Li, MD, Kaixin Song, MMSc, Yuting Chen, MMSc, Yue Dai, MMSc, Yi Yang, MMSc, Lun Zhou, MD, Weiwei Yu, MD, Yongsheng Li, MD, Min Xie, MD, Cuntai Zhang, MD, and Hongyu Gao, MD

The ups and downs of daily life during COVID-19: Age differences in affect, stress, and positive events: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences and Social Sciences by Patrick Klaiber, MSc, Jin H Wen, BA, Anita DeLongis, PhD, and Nancy L Sin, PhD

A Double Burden of Exclusion? Digital and Social Exclusion of Older Adults in Times of COVID-19: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences and Social Sciences by Alexander Seifert, Shelia R. Cotten, and Bo Xie

Preexisting Comorbidities Predicting Severe COVID-19 in Older Adults in the U.K. Biobank Community Cohort: Research article in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Janice L Atkins, PhD, Jane A H Masoli, MBChB, Joao Delgado, PhD, Luke C Pilling, PhD, Chia-Ling Kuo, PhD, George A Kuchel, MD, and David Melzer, MBBCh, PhD

More Vulnerable? The Life Story Approach Highlights Older People’s Potential for Strength During the Pandemic: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences and Social Sciences by Majse Lind, PhD, Susan Bluck, PhD, and Dan P. McAdams, PhD

Thrust into the Spotlight: COVID-19 Focuses Media Attention on Nursing Homes: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences and Social Sciences by Edward Alan Miller, PhD, MPA, Elizabeth Simpson, MPH, Pamela Nadash, PhD, BPhil, Michael Gusmano, PhD, MA

From "Coffin Dodger" to "Boomer Remover:" Outbreaks of Ageism in Three Countries with Divergent Approaches to Coronavirus Control: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences and Social Sciences by Bronwen Lichtenstein, PhD

Effectiveness of an on-site medicalization program for nursing homes with COVID-19 outbreaks: Research article in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by M. Bernabeu-Wittel, MD, PhD, J. E. Ternero-Vega, M. D. Nieto-Martín, MD, PhD, L. Moreno-Gaviño, MD, PhD, C. Conde-Guzmán, MD, PhD, J. Delgado-Cuesta, MD, PhD, M. Rincón-Gómez, MD, PhD, P. Díaz-Jiménez, MD, L. Giménez-Miranda, MD, J. M. Lomas-Cabezas, MD, PhD, M. M. Muñoz-García, MD, S. Calzón-Fernández, MD, PhD, M. Ollero-Baturone, MD, PhD

MADISON - Researchers at the University of Wisconsin-Madison have developed a method combining sticky nanoparticles with high-precision protein measurement to capture and analyze a common marker of heart disease to reveal details that were previously inaccessible.

The new method, a system known as nanoproteomics, effectively captures and measures various forms of the protein cardiac troponin I, or cTnI, a biomarker of heart damage currently used to help diagnose heart attacks and other heart diseases. An effective test of cTnI variations could one day provide doctors with a better ability to diagnose heart disease, the leading cause of death in the U.S.

UW-Madison Professor of Cell and Regenerative Biology and Chemistry Ying Ge, Professor of Chemistry Song Jin and chemistry graduate students Timothy Tiambeng and David Roberts led the work, which was published Aug. 6 in the journal Nature Communications. The researchers now plan to use their new method to associate the various forms of cTnI with specific heart diseases as a step toward developing a new diagnostic test.

Doctors currently use an antibody-based test called ELISA to help diagnose heart attacks based on elevated levels of cTnI in the patient's blood sample. While the ELISA test is sensitive, patients can have high levels of cTnI in the blood without having heart disease, which can lead to expensive and unnecessary treatments for patients.

"So we want to use our nanoproteomics system to look into more details at various modified forms of this protein rather than just measuring its concentration," says Ge, who is also director of the Human Proteomics Program in the UW School of Medicine and Public Health. "That will help reveal molecular fingerprints of cTnI from each patient for precision medicine."

Measuring low-concentration proteins in the blood like cTnI is a classic needle-in-a-haystack problem. Rare, meaningful biomarkers of disease are completely overwhelmed by common and diagnostically useless proteins in the blood. Current methods use antibodies to enrich and capture proteins in a complex sample to identify and quantify proteins. But antibodies are expensive, have batch-to-batch variations, and can generate inconsistent results.

To capture cTnI and overcome some of the limitations of antibodies, the researchers designed nanoparticles of magnetite, a magnetic form of iron oxide, and linked it to a peptide of 13 amino acids long designed to specifically bind to cTnI. The peptide latches onto cTnI in a blood sample, and the nanoparticles can be collected together using a magnet. Nanoparticles and peptides are easily made in the lab, making them cheap and consistent.

Using the nanoparticles, the researchers were able to effectively enrich cTnI in samples of human heart tissue and blood. Then they used advanced mass spectrometry, which can distinguish different proteins by their mass, to not only get an accurate measurement of cTnI, but also to assess the various modified forms of the protein.

Like many proteins, cTnI can be modified by the body depending on factors like an underlying disease or changes in the environment. In the case of cTnI, the body adds various numbers of phosphate groups, small molecular tags that might change the function of cTnI. These variations are subtle and hard to track.

"But with high-resolution mass spectrometry, we can now 'see' these molecular details of proteins, like the hidden iceberg beneath the surface," says Ge.

Tiambeng and Roberts decided to test if they could distinguish the various forms of cTnI that can be found in patient blood samples. They spiked blood serum with proteins from donor hearts that were normal, diseased, or from a dead donor. Then they used their nanoparticles to capture cTnI and measured the protein using mass spectrometry.

As hoped, the scientists could observe clearly different patterns in the types of cTnI prevalent in each type of heart tissue. The healthy hearts tended to have lots of cTnI with multiple phosphate groups attached, for example, while diseased hearts had cTnI that had less phosphate and the post-mortem heart had cTnI broken into pieces.

While this is still a proof-of-concept study and more research will be needed, it is this ability to associate a pattern of cTnI variations with heart health that the researchers hope could one day produce a new diagnostic tool to help when patients come to the hospital with suspected heart disease. The researchers have filed a patent application on the new technology through the Wisconsin Alumni Research Foundation.

"We like to think a future blood test based on our work here could be complementary to the current ELISA test," says Jin. "In the future, when ELISA shows an elevated cTnI level, your doctor might order a comprehensive nanoproteomics test to determine whether it is caused by heart disease or not, and identify different types of heart disease, for more precise treatment while avoiding unnecessary care and expense for patients".

Leesburg, VA, August 6, 2020--An "Original Research" article published in ARRS' American Journal of Roentgenology (AJR) concluded that the accuracy of breast cancer diagnosis via diffusion-tensor imaging (DTI) was equivalent both before and after the administration of a gadolinium-based contrast agent (GBCA), despite a value change in DTI parameters.

"However," wrote first author Anabel M. Scaranelo of Princess Margaret Cancer Centre's breast imaging division in Toronto, "the limitations in standardization of contrast enhancement implies that unenhanced diffusion measurements should be preferred."

In this pilot study, 26 women (age range 37-69 years) scheduled for a diagnostic breast MRI with BI-RADS categories 0, 4, 5, or 6 on conventional breast imaging were twice scanned using the same DTI sequence before and immediately after the breast dynamic contrast-enhanced MRI.

Using dedicated DTI software, quantitative image analysis yielded parametric DTI maps of each directional diffusion coefficient (DDC), mean diffusivity, and maximal anisotropy of the lesions and normal tissue. Using appropriate statistical tests, these color maps were evaluated and lesion DTI parameters were compared before and after GBCA administration.

Fifty-eight percent of the cohort had cancer (13 infiltrating ductal carcinoma, two ductal carcinoma in situ), and 42% had benign or normal results. All breast cancers were visually detected in the DDC λ1 maps before and after GBCA administration. Mean cancer size derived from λ1 maps before GBCA administration was 15.3 mm--not statistically significantly different from the size derived after GBCA administration.

After GBCA administration, the cancers exhibited statistically significantly lower DDCs, mean diffusivity, and b0 intensity (p

Compared with before dynamic contrast enhancement, Scaranelo and colleagues' results showed statistically significant reduction in the DDCs of breast cancers after dynamic contrast enhancement, "leading to equivalent or increased conspicuity of the cancer lesions in the visual assessment by the radiologist," they noted.

Acknowledging the accuracy of breast cancer detection using unenhanced or contrast-enhanced DTI datasets was not significantly different, Scaranelo added that since DTI parameters are intrinsic tissue characteristics, the use of DTI before dynamic contrast enhancement can be fully standardized.

Scaranelo et al. explained further: "The contrast-enhanced DTI parameters are less amenable to standardization because their values depend on the type and dose of contrast agent and on variations in the contrast agent dynamics among the various types of breast cancers."

Thus, due to the lack of standardization of contrast-enhanced DTI, the authors of this AJR article still preferred unenhanced diffusion measurements.

AURORA, Colo. (Aug. 6, 2020) - A non-hormonal therapy to treat hot flashes and other symptoms associated with menopause was found to be effective in a recent clinical trial, according to a published study by a team of researchers including faculty from the University of Colorado School of Medicine.

Fezolinetant, an oral, non-hormone therapy in clinical development, offers relief for hot flashes and night sweats, which are the most common menopause-associated symptoms for which women seek treatment. About 80 percent of American women experience these symptoms.

"An effective alternative to estrogen for the treatment of hot flashes is needed to provide better care," said Nanette Santoro, chair of the Department of Obstetrics and Gynecology at the University of Colorado School of Medicine, and an author of the study published online this week by the journal Menopause. "There are some medications that can be used, but all have significant side effects and are of lesser efficacy than estrogen."

The study, published online by the journal Menopause, reviewed the experience of 352 women with moderate to severe menopausal vasomotor symptoms, such as hot flashes, who were enrolled in a 12-week study that compared treatment with fezolinetant versus a placebo. The treatment was tested in a range of dosages.

"The occurrence of VMS [vasomotor symptoms] interfere with sleep, concentration, memory, work productivity, and personal relationships and has been linked to feelings of depression, irritability, anxiety, fatigue, and social embarrassment/isolation," Santoro and her co-authors write. "All of these factors contribute to the observed negative influence of VMS on psychological well-being and health-related quality of life."

VMS symptoms are triggered by neuron activity that affects the thermoregulatory functioning of the brain. Estrogen helps regulate that activity, but during menopause estrogen levels decline and no longer modulate as effectively. Fezolinetant works by blocking neurokinin B (NKB) signaling and normalizing KNDy (kisspeptin/NKB/dynorphin) neuron activity.

In this study, more than 80 percent of the women taking fezolinetant reported a reduction in symptoms and more than half of the women taking the treatment indicated a reduction of symptoms of 90 percent or greater. Participants recorded their symptoms daily in an e-dairy and filled out quality-of-life questionnaires. They had a mean age of 54.6 years old. A majority of women (73 percent) self-identified as white, 25 percent Black, 1 percent Asian and 1 percent other.

"This is an extraordinarily successful result and offers promise of relief to millions of women," said Santoro. "This study paves the way for further studies of a longer treatment duration and in a larger group of people."

A new study has found that HIV screening every three months compared to annually will improve clinical outcomes and be cost-effective among high-risk young men who have sex with men (YMSM) in the United States. The report, led by researchers at the Massachusetts General Hospital (MGH), is being published online in Clinical Infectious Diseases.

"Young men who have sex with men account for one in five new HIV infections in the United States. Yet, more than half of young men who have sex with men and who are living with HIV don't even know that they have it," says Anne Neilan, MD, MPH, investigator in the MGH Division of Infectious Diseases and the Medical Practice Evaluation Center, who led the study.

"With so many youth with HIV being unaware of their status, this is an area where there are opportunities not only to improve care for individual youth but also to curb the HIV epidemic in the U.S. Despite these numbers, the Centers for Disease Control and Prevention previously determined that there was insufficient youth-specific evidence to warrant changing their 2006 recommendation of an annual HIV screening among men who have sex with men."

HIV screening refers to testing of individuals who do not have symptoms of the infection. As defined by the study, high-risk refers to a recent history of condomless anal intercourse, sexually transmitted infection, or multiple sexual partners. Given the disproportionate impact of the HIV epidemic on YMSM, screening for HIV more frequently than current recommendations could identify infections that would otherwise be missed.

The study used data from the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) on how often HIV occurs in each age group, as well as the stage of disease at the time of diagnosis, to project the probable results of screening every three months, six months, or yearly.

Because a traditional study design to examine how often young men who have sex with men should be screened would be nearly impossible to conduct, the authors used a well-published computer microsimulation model developed by members of the research team.

The analysis revealed that HIV screening every three months, in addition to existing patterns of HIV screening among YMSM, would most improve HIV transmission and life expectancy among these men while remaining cost-effective. However, the results do not apply to youth who do not meet high-risk criteria.

Andrea Ciaranello, MD, MPH, investigator MGH Division of Infectious Disease, senior author of the study, says, "The improvements in life expectancy and reduction in HIV transmission were substantial. With more frequent screening, we also estimated that there would be additional, important improvements in the proportion of YMSM who are able to engage in HIV treatment and have excellent control of their HIV infection."

The authors also highlighted the opportunities for improved implementation of current annual screening recommendations. "If even the current CDC recommendations for annual HIV screening among YMSM could be fully met, important gains could be made both for the health of youth with HIV and in working toward our goal of ending the HIV epidemic," says Ciaranello. "Ultimately, our study underscores the value of ongoing research to examine the most effective ways to increase HIV screening among youth."

Neilan adds, "We found that screening every three months was cost-effective, even if the screening program itself cost up to $760 per person screened. The test itself cost $38-76; this suggests that a large additional investment in innovative HIV screening approaches for youth, including venue-based screening or mobile screening units, would be of good value in the U.S." Neilan is also an Instructor in Medicine, and Ciaranello is an associate pdrofessor of Medicine at Harvard Medical School.

PHILADELPHIA--The majority of patients who followed an "Enhanced Recovery After Surgery" (ERAS) protocol did not need opioids for pain management at multiple time points following elective spinal and peripheral nerve surgery. The findings come from an expanded analysis and study from researchers in the Perelman School of Medicine at the University of Pennsylvania, published in Pain Medicine. Researchers found that when an ERAS protocol was employed--which optimizes patients' surgical care before, during, and after surgery--fewer patients needed pain medications at one, three, and six months after surgery.

The ERAS protocol developed at Penn includes a personalized, safe, and effective pain management plan to help prevent opioid addiction, which is an ongoing public health crisis in the United States. ERAS engages patients in their care before, during, and after their hospitalization--this process includes patient education, text reminders, nutrition information, early mobilization, and recovery plans. ERAS also relies on collaborative care between all individuals involved in the patient's surgical journey, including anesthesiologists, rehabilitation therapists, nurses, and neurosurgeons, to improve clinical outcomes and optimize a safe recovery.

"We know from our clinical experience and previous literature that programs like ERAS work, but we didn't expect the impact on opioid use to be so sizeable," said senior author Zarina S., Ali, MD, an assistant professor of Neurosurgery at Penn. "The most important outcome from this study is the decrease in opioid use. Furthermore, patients following the ERAS protocol reported less opioid use without higher pain scores. This represents an important advance in the context of the current nationwide opioid epidemic."

For this study, a total of 1,141 patients were enrolled in the ERAS protocol, compared to 149 historical controls who received the standard of care. Both groups had similar surgical procedures and demographics. Preliminary findings summarizing opioid use after one month of the ERAS protocol were published in the Journal of Neurosurgery: Spine in 2019. This Pain Medicine paper reports on continued benefits over an 18-month period utilizing the ERAS pathway in elective spinal and peripheral nerve surgery.

The researchers found a significant reduction in use of opioids by following the ERAS protocol at one, three, and six months following surgery--only 38.6 percent of those following ERAS needed pain medications one month after surgery, whereas 70.5 percent of the control group needed pain medications at one-month post-op. At three months after surgery, 36.5 percent in the ERAS cohort needed pain medication, compared to 70.9 percent of the controls, and six months after surgery only 23.6 percent of patients following the ERAS protocol needed pain medication, compared to 51.9 percent in the control group.

In addition to the significant reduction of opioid use, use of patient-controlled analgesia (PCA)--known as a pain pump--was nearly eliminated in the ERAS group (1.4 percent) compared to 61.6 percent of patients in the control group. ERAS patients were up and moving faster compared to control patients (63.5 percent vs. 20.7 percent), fewer ERAS patients required postoperative catheterization (40.7 percent vs 32.7 percent), and the ERAS group also had shorter hospital stays (3.4 vs. 3.9 days).

"Previous publications have demonstrated ERAS implementation in neurosurgery practices primarily through minimally invasive spinal surgery, but our neurosurgical practice has been actively applying ERAS principles to elective spine and peripheral nerve surgery since 2017, in coordination with a variety of departments across the health system," said Tracy M. Flanders, MD, first author and Neurosurgery resident at Penn. "This study captures the exciting benefits of this protocol for minimizing opioid use, decreasing length of stay, and more--without impacting patient satisfaction."

Additional Penn co-authors include Joseph Ifrach, Saurabh Sinha, Disha S. Joshi, Ali K. Ozturk, Neil R. Malhotra, Rachel Pessoa, Michael J. Kallan, Lee A. Fleisher, Michael A. Ashburn, Eileen Maloney, and William C. Welch.

WASHINGTON (Aug. 5, 2020) -- Genetic modifier HDAC6 was found to control tumor growth and halt metastasis in triple-negative breast cancer in vivo, according to a new study published in the top-tier journal Cancer Research by investigators at the George Washington University (GW) Cancer Center.

Immunotherapy - the use of drugs to stimulate one's own immune system to recognize and destroy cancer cells - has been wildly successful in melanoma and other cancers. However, it has been less effective in breast cancer.

"There is an urgent medical need to find new ways to potentiate or increase the efficacy of immunotherapy in breast cancer, especially in aggressive and highly metastatic triple-negative breast cancer," said Alejandro Villagra, PhD, member of the Cancer Biology Program at the GW Cancer Center and assistant professor of biochemistry and molecular medicine at the GW School of Medicine and Health Sciences. "Our research lays the groundwork for a clinical trial that could lead to new, life-saving treatment options for breast cancer patients that do not respond to conventional immunotherapies."

Molecularly targeted agents, such as HDAC6 inhibitors, have been widely described in the research literature as cytotoxic - toxic to both cancerous and healthy cells. Villagra and his research team found new non-canonical regulatory properties of these epigenetic drugs, discovering that the inhibition of HDAC6 has a powerful and strong effect on the immune system unrelated to the previously cytotoxic properties attributed to HDAC inhibitors.

This research demonstrates for the first time that HDAC6 inhibitors can both improve response to immunotherapy and diminish the invasiveness of breast cancer, with minimal cytotoxic effects.

"We are excited about the work because, in addition to the potency of immunotherapy, this drug alone is capable of reducing metastasis," said Villagra. "This could have implications beyond breast cancer."

This research was a multidisciplinary effort, made possible by collaborators across the GW Cancer Center, the GW School of Medicine and Health Sciences and the GW School of Engineering and Applied Sciences. The project was funded by grants from the GW School of Medicine and Health Sciences, the National Institutes of Health, and the Melanoma Research Foundation.

What The Study Did: Characteristics and response to treatment of persistent radiation-induced hair loss in patients with primary central nervous system tumors or head and neck cancer were examined in this observational study.

Authors: Mario E. Lacouture, M.D., of Memorial Sloan Kettering Cancer Center in New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamadermatol.2020.2127)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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PHILADELPHIA -- Painful gallstones are common during pregnancy. The pain can be intense, coming on suddenly, increasing and often radiating to the back. When gallstones cause inflammation of the gallbladder, a condition called cholecystitis, the symptoms can worsen, with fever nausea and vomiting in addition to the pain. Surgical removal of the gallbladder is the most effective treatment, but surgery during pregnancy is often feared and at times postponed. In the largest US study to date, Jefferson surgeons observed that mothers experiencing cholecystitis during pregnancy had better outcomes if they had surgery during their pregnancy than if surgery was delayed until after childbirth.

"Current guidelines recommend surgery for acute cholecystitis during pregnancy, but many patients and providers delay surgery," says senior author on the study, Francesco Palazzo, MD, Vice Chair of Surgery at Thomas Jefferson University Hospital. "We wanted to know how often the guidelines were followed, and whether following those guidelines did indeed improve outcomes for pregnant women."

The study was published in the Annals of Surgery.

The study examined the records of a national sample of 6,390 pregnant women admitted to a hospital with acute cholecystitis from the Nationwide Readmission Database between the dates of January 2010 and September 2015. Despite national guidelines, only 38.2% of women had surgery to remove their gallbladders at the time they presented with cholecystitis during pregnancy.

Pregnant women with cholecystitis who did not undergo gallbladder surgery were three times more likely to have maternal-fetal complications relative to those who did have surgery. The maternal-fetal complications investigated included a combination of stillbirth, poor fetal growth, abortion, preterm delivery, C-section, obstetric bleeding, venous thromboembolism and intraamniotic infection. These differences were mostly driven by an increase in poor fetal growth, preterm delivery and C-section among those pregnant women who did not have gallbladder surgery.

"The data doesn't tell us exactly why these complications occurred, just that they were more common in women whose surgeries were delayed after accounting for differences between the groups," says first author Arturo J. Rios-Diaz, MD, a 4th year resident in the department of Surgery. Women who did not have surgery during their pregnancy were also 61% more likely to be readmitted to the hospital within 30 days of being discharged, and 95% more likely to be readmitted with a maternal-fetal complication.

"It can be quite scary and painful for pregnant women to experience cholecystitis," says co-author Vincenzo Berghella, director of the Division of Maternal Fetal Medicine at Jefferson. "Many physicians are uncomfortable recommending surgery for pregnant women. But these data clearly show that there are risks with waiting out surgery. Patients and physicians should always first discuss the management option which would be chosen if the patient were not pregnant. Like for almost all other medical conditions which can occur in pregnancy, the best option, in this case surgery with removal of the gallbladder, should be done regardless of being pregnant or not."

"Classically, physicians have been trained that surgery should be discouraged in the first trimester, and third trimester," says Dr. Palazzo. "But those beliefs have been based on poor-quality and outdated studies. The data suggest that the risks may be much greater for women with cholecystitis who don't get surgery until after childbirth."

More than 70 million people worldwide suffer from glaucoma, a condition that causes a build-up of fluid and pressure inside the eye and can eventually lead to blindness. Treatment options have traditionally included eye drops to reduce the fluid the eye produces or surgery to unclog the eye's drainage. But a new study from the University of Missouri School of Medicine and MU Health Care provides insight into which patients might benefit most from a noninvasive treatment called selective laser trabeculoplasty (SLT), which relieves pressure by using a laser to alter the eye tissue, resulting in better fluid drainage.

"There's been a lack of evidence about how well SLT works, how safe it is and the ideal candidate," said senior author Jella An, MD, an assistant professor of ophthalmology and a fellowship-trained glaucoma specialist at MU Health Care's Mason Eye Institute. "Because so little is known about SLT, there is a lot of apprehension among specialists about using it as a first-line treatment for glaucoma. Our research findings have helped me redefine the ideal patient for this procedure."

An's research team reviewed 252 SLT procedures on 198 adult patients with open-angle glaucoma to determine what percentage of these surgeries achieved a 20% or greater reduction in intraocular pressure (IOP). Two months after surgery, 33.6% of patients met success criteria. At the six-month mark, 38.5% achieved the threshold. The researchers discovered patients with a higher baseline IOP had larger reductions in pressure.

"We discovered significant improvement in patients with more severe cases, which convinced me that patients with the highest pressure will benefit the most from this laser therapy," An said.

Age, type and severity of glaucoma did not significantly predict a successful outcome. In addition, less than 5% of patients studied experienced the most common adverse event of an IOP spike after the procedure.

"This study really increased my comfort level to offer SLT as a primary therapy," An said. "Prior to this research, I would prescribe these patients multiple medications, creating the possibility of side effects and poor adherence, which could lead to disease progression. Now I offer this laser first if they are a good candidate because of its safety profile. If it doesn't work, we can always move forward with other options."

In addition to An, the study's lead author was MU School of Medicine ophthalmology resident Matthew Hirabayashi, MD. Vikram Ponnusamy, MD, a recent graduate of MU School of Medicine, also contributed to the findings.

Amsterdam and Costa Mesa, CA, August 5, 2020 - As a person's weight goes up, all regions of the brain go down in activity and blood flow, according to a new brain imaging study in the Journal of Alzheimer's Disease.

One of the largest studies linking obesity with brain dysfunction, scientists analyzed over 35,000 functional neuroimaging scans using single-photon emission computerized tomography (SPECT) from more than 17,000 individuals to measure blood flow and brain activity. Low cerebral blood flow is the #1 brain imaging predictor that a person will develop Alzheimer's disease. It is also associated with depression, ADHD, bipolar disorder, schizophrenia, traumatic brain injury, addiction, suicide, and other conditions.

"This study shows that being overweight or obese seriously impacts brain activity and increases the risk for Alzheimer's disease as well as many other psychiatric and cognitive conditions," explained Daniel G. Amen, MD, the study's lead author and founder of Amen Clinics, one of the leading brain-centered mental health clinics in the United States.

Striking patterns of progressively reduced blood flow were found in virtually all regions of the brain across categories of underweight, normal weight, overweight, obesity, and morbid obesity. These were noted while participants were in a resting state as well as while performing a concentration task. In particular, brain areas noted to be vulnerable to Alzheimer's disease, the temporal and parietal lobes, hippocampus, posterior cingulate gyrus, and precuneus, were found to have reduced blood flow along the spectrum of weight classification from normal weight to overweight, obese, and morbidly obese.

Considering the latest statistics showing that 72% of Americans are overweight of whom 42% are obese, this is distressing news for America's mental and cognitive health.

Commenting on this study, George Perry, PhD, Editor-in-Chief of the Journal of Alzheimer's Disease and Semmes Foundation Distinguished University Chair in Neurobiology at The University of Texas at San Antonio, stated, "Acceptance that Alzheimer's disease is a lifestyle disease, little different from other age-related diseases, that is the sum of a lifetime is the most important breakthrough of the decade. Dr. Amen and collaborators provide compelling evidence that obesity alters blood supply to the brain to shrink the brain and promote Alzheimer's disease. This is a major advance because it directly demonstrates how the brain responds to our body."

This study highlights the need to address obesity as a target for interventions designed to improve brain function, be they Alzheimer disease prevention initiatives or attempts to optimize cognition in younger populations. Such work will be crucial in improving outcomes across all age groups.

Although the results of this study are deeply concerning, there is hope. Dr. Amen added, "One of the most important lessons we have learned through 30 years of performing functional brain imaging studies is that brains can be improved when you put them in a healing environment by adopting brain-healthy habits, such as a healthy calorie-smart diet and regular exercise."

WASHINGTON -- Researchers have demonstrated a new high-resolution x-ray imaging technique that can capture the motion of rapidly moving objects and quickly changing dynamics. The new method could be used for non-destructive imaging of moving mechanical components and to capture biological processes not previously available with medical x-ray imaging.

"The technique we demonstrated can be used with any x-ray source, plus it is low cost, simple and robust," said research team leader Sharon Shwartz from Bar-Ilan University in Israel. "Thus, it opens up the possibility of using x-rays to measure fast dynamics outside the lab."

In The Optical Society (OSA) journal Optics Express, the researchers describe their new x-ray imaging approach, which uses a non-traditional imaging method known as ghost imaging to achieve fast imaging speeds with high spatial resolution. They demonstrate the technique by creating an x-ray movie of a blade rotating at 100,000 frames per second.

"Medical imaging systems based on this technique could offer a new diagnostic tool for physicians," said Shwartz. "Our approach could, for example, be used to acquire high-resolution movies of the heart while greatly reducing the radiation dose for patients."

Seeing through surfaces

X-rays are useful for imaging because of their unique capability to penetrate surfaces that are opaque to visible wavelengths. Traditional x-ray imaging typically uses a pixelated camera with each pixel measuring the intensity level of the x-ray beam at a specific position.

Capturing higher resolution x-ray images requires more pixels, which, in turn, creates huge amounts of data that take time to transfer. This creates a trade-off between imaging speed and spatial resolution that makes it impossible to capture high-speed events with high resolution. Although very specialized techniques involving extremely powerful x-rays can overcome this trade-off, these x-ray sources are only available at large synchrotrons found at a few facilities around the world.

In the new work, the researchers turned to ghost imaging because it uses single-pixel detectors that can improve the imaging speed. Ghost imaging works by correlating two beams -- in this case, X-ray beams -- that do not individually carry any meaningful information about the object. One beam encodes a random pattern that acts as a reference and never directly probes the sample. The other beam passes through the sample. Because very little x-ray power comes into contact with the object being imaged, ghost imaging can also help reduce x-ray exposure when used for medical imaging.

"Although single-pixel detectors can be much faster than pixelated detectors, they do not provide the spatial resolution necessary for image reconstruction," said Shwartz. "We used ghost imaging to overcome this problem and showed that we can image fast dynamics with spatial resolution comparable to or even better than the state-of-the-art x-ray pixelated detectors."

A simple solution

To create the reference beam needed for ghost imaging, the researchers used standard sandpaper mounted on motorized stages to create a random pattern that was recorded with a high-resolution, slow framerate pixelated x-ray camera. As the stage was moved to each position, the x-ray beam hit a different area of the sandpaper, creating random x-ray transmissions, or intensity fluctuations.

They then removed the pixelated camera from the x-ray beam and inserted the object to be imaged and a single-pixel detector. They moved the motorized stages to irradiate the object with the intensity fluctuation patterns introduced at the various positions of the sandpaper and then measured the total intensity after the beam hit the object by using the single-pixel detector.

To use this approach to image a fast-moving blade, the researchers synchronized the measurements with the blade's movement. A final image could then be reconstructed by correlating the reference pattern with the intensity measured by the single-pixel detector for each position of the blade.

The researchers created a movie of the moving blade by performing image reconstruction frame-by-frame to capture the blade at different positions. The resulting movie clearly shows the motion with a spatial resolution of about 40 microns -- nearly an order of magnitude better than the resolution of currently available medical imaging systems.

The researchers are continuing to make improvements to the overall system as well as the image reconstruction algorithm to improve resolution and shorten measurement times.

(Boston)-- Bisphosphonates (a class of drugs that prevent the loss of bone density and used to treat osteoporosis and similar diseases) appear to be safe and beneficial for osteoarthritis patients.

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide with more than 300 million suffering with the condition, yet there are no effective treatments to stop the disease or its progression. One of the lesions in OA that causes pain and progression of the structural pathology of the disease are bone marrow lesions.

Researchers believe bisphosphonates may alter bone marrow lesions, and thereby could improve pain in OA and halt its progression. Alternatively, they could also alter the mechanical properties of bone, thereby potentially contributing to detrimental effects.

Using data from the Osteoarthritis Initiative, a longitudinal cohort of people with or at risk for knee OA, the researchers identified women who started bisphosphonates and matched them to women who weren't on the drug. Measurements in bone marrow lesion volume were taken when they first started on bisphosphonate and then a year later. Changes in bone marrow lesion volume between the two groups were then compared.

"When we looked at those who had bone marrow lesions at baseline, we found that the women who started bisphosphonates had had more bone marrow lesions that decreased in size than the women who did not start bisphosphonates," explained corresponding author Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University Schools of Medicine and Public Health. "These results suggest that bisphosphonates do not appear to be harmful, at least over one year, and perhaps may even help decrease bone marrow lesions in those that have them."

According to the researchers, effective treatments for osteoarthritis are desperately needed. "By examining existing data for potential signals of efficacy and safety, we can identify potentially promising therapies that should be further tested in trials with the aim to ameliorate the pain of osteoarthritis and improve the quality of life for the millions of people worldwide that have this disease," added Neogi, chief of rheumatology at Boston Medical Center.

A study led by the Seaver Autism Center for Research and Treatment at Mount Sinai found that two different blood epigenetic signatures associated with ADNP syndrome (also known as Helsmoortel-Van Der Aa syndrome) have only a modest correlation with clinical manifestations of the syndrome. The study results were published online August 5 in the American Journal of Human Genetics.

ADNP syndrome, one of the most common single-gene causes of autism spectrum disorder, is a neurodevelopmental condition that is also associated with intellectual disability, developmental delay, and multiple medical comorbidities.

Researchers at the Seaver Center first replicated previously published findings demonstrating that individuals with ADNP syndrome have profound DNA methylation changes in their blood, and these changes are contingent on the type of activity dependent neuroprotective protein (ADNP) mutation that they carry. Individuals with the disorder segregate into two groups based on the location of their mutations.

"DNA methylation is a chemical modification of the DNA molecule, and is one of the epigenetic mechanisms that control the activity of our genes, defining where and when they are expressed. In the past few years, several neurodevelopmental disorders have been associated with specific changes in DNA methylation," said Silvia De Rubeis, PhD, Assistant Professor of Psychiatry, at the Seaver Autism Center and co-senior author of the paper.

The team then used behavioral and neurobiological data from two cohorts of individuals with a genetic diagnosis of ADNP syndrome to examine the relationship between these epigenetic signatures and clinical presentation. Results showed limited differences between the two ADNP groups, and no evidence that individuals with more widespread methylation changes were more profoundly affected.

The lack of correspondence between blood molecular signatures and clinical manifestations cautions against making phenotypic inferences based on the blood-based methylation profiles. This is important to consider when evaluating the use of these episignatures as biomarkers for patient stratification and response to pharmacological agents in clinical trials.

The Seaver researchers concluded that while the two unique blood epigenetic signatures may be valuable for complementing clinical genetics and enhancing accuracy of diagnosis, they need to be carefully evaluated before being considered as a tool to predict behavioral outcomes or to stratify patients with ADNP syndrome into clinically meaningful subgroups.

"As clinical trials in ADNP syndrome begin, understanding the utility of biomarkers and their relationship to clinical symptoms becomes critical. Our results caution against using episignatures as a biomarker for clinical trials," said Paige Siper, PhD, Chief Psychologist at the Seaver Autism Center and senior co-leading author on the study.

To date, ADNP syndrome has no FDA-approved treatment options, but the Seaver Center recently began recruitment for the first-ever clinical trial for ADNP syndrome. The trial will evaluate the safety, tolerability, and efficacy of a low dose of ketamine in children with the disorder.

"The Seaver Autism Center is making huge strides forward every day in ADNP research, unlike anywhere else in the world," said Sandra Bedrosian Sermone, Founder and President of the ADNP Kids Research Foundation. "Our Foundation's open collaboration with the Center has helped us rally patient participation and financial support for their research to help improve the lives of children around the world with this rare disorder."

Eosinophils residing in the airways of mice respond to influenza A virus (IAV) infection through alterations in surface expression of various markers necessary for migration and cellular immunity responses, according to research published in the Journal of Leukocyte Biology by researchers from Le Bonheur Children's Hospital and the University of Tennessee Health Science Center.

Previous research explored the effects of IAV infection in patients with allergic asthma. During the 2009 influenza pandemic, patients hospitalized with influenza experienced lower morbidity if allergic asthma was an underlying condition. In mice, the researchers reported that the beneficial effect of this co-morbidity correlated with a dramatic increase in eosinophils in the airways, which is a hallmark of allergic asthma. Eosinophils were susceptible to IAV infection and also presented IAV antigens to CD8+ T-cells which are heavily involved in resolving viral infections. This implied that eosinophils actively contribute to the antiviral response during influenza. While once considered to be a cell that degranulated after allergen encounters and incidentally promoted host pathology during allergy, this research contributed to expand the role of eosinophils to that of anti-viral mediators and specifically showed that eosinophils are active participants in the resolution of influenza. Many of processes that cumulate in eosinophils making this valuable contribution are unclear.

"Very little is known about how eosinophils respond to direct exposure to IAV or the microenvironment in which the viral burden is high," said Le Bonheur and UTHSC researcher Amali Samarasinghe, PhD. "We hypothesized that eosinophils would dynamically respond to the presence of IAV through phenotypic, transcriptomic and physiologic changes."

Researchers investigated eosinophil characteristics in different niches in mice using a mouse model of fungal asthma and influenza, in addition to responses when exposed to IAV in vitro.

Results of the study included the following:

1. Mice with fungal allergic asthma have a lower pro-inflammatory cytokine profile in their lungs during influenza than non-allergic mice.

2. Eosinophil surface antigens are differentially regulated in mice with fungal asthma and influenza. During influenza, eosinophils changed the surface expression of proteins involved in antigen presentation, activation and survival depending on both niche and allergic environment.

3. Following virus exposure, a discrete subset of eosinophils that decreased their surface expression of Siglec-F were also more active. Siglec-Flo expressors also increased expression of eosinophil survival receptor IL-5R and downregulated CD62L which is associated with activation. These data suggest that subpopulations of eosinophils may have differing functions during IAV infection.

4. IAV exposure alters the eosinophil transcriptome. IAV-infected eosinophils reduced overall transcriptional activity but up-regulated transcription of mRNAs encoding viral recognition proteins.

5. Eosinophils reduce mitochondrial respiration in response to IAV. Eosinophils had a lowered basal respiration rate and an overall reduction in mitochondrial respiration.

6. Flu-PB-1 pulsed eosinophils promote the generation of cytotoxic CD8+ T-cells by causing demethylation of the Tbx21 locus. IAV-exposed eosinophils can communicate with CD8+ T-cells, resulting in epigenetic changes that allow the differentiation of IAV-specific CD8+ T-cells into effector cells.

Overall, mice with fungal asthma that were protected from severe IAV morbidity had reduced levels of cytokines - which can contribute to pathology when present in excess. When exposed to IAV, eosinophils initiate self-preservation mechanisms to survive viral infection, such as conserving energy by reducing transcription activity and mitochondrial respiration. Concurrently, they increase their ability to recognize IAV and induce epigenetic changes in CD8+ T-cells that initiate their differentiation into cytotoxic cells known to be a critical component of the antiviral response.

"Our research shows that eosinophils respond dynamically to IAV infection and contribute to antiviral host defense mechanisms during influenza" said Samarasinghe. "This information is important for selecting effective therapeutics for asthmatics that may benefit from eosinophil presence in airways during IAV infection."