Lab Notes

April 2024

Insights from a community survey on gender-affirming hormone therapy with estrogen By developing a survey guided by community input, UCLA researchers lay the groundwork for more effective hormone therapy trials tailored to gender-diverse individuals seeking estrogen treatment. The survey was distributed online to individuals interested in gender-affirming hormone therapy. Over 1200 people responded. The top treatment goals included improving life satisfaction, appearing more feminine and enhancing mental health. The most desired physical changes were reducing facial hair, altering breast shape or size and modifying body shape. However, there was substantial variation in patient-centered goals. For example, while changing scalp hair patterns was the feature most frequently rated as “low priority” or “lowest priority,” almost 60% of individuals still rated it as “highest priority” or “high priority.” Participants also emphasized the importance of future research comparing different methods of estrogen administration for feminization. These findings highlight the diverse goals and experiences of those seeking gender-affirming hormone therapy. They underscore the need for future clinical trials to be closely aligned with the preferences and needs of the gender-diverse community. Read the study in Hormones.

March 2024

Researchers uncover regulation of lactate production by hexokinases binding to mitochondria in single cells During hypoxia, characterized by having low levels of oxygen in our body, accumulation of lactate may be a key factor in acidosis-induced tissue damage. According to new findings from a team of scientists from the Department of Physiology, the division of Cardiology and the CNSI at UCLA, the binding of hexokinase to the outer membrane of mitochondria may have a protective effect under these conditions. A previous study from this team found that pyruvate is required for the transformation and utilization of lactate by mitochondria. Building on these findings, researchers have uncovered another aspect of lactate metabolism which may be detrimental as a result of its accumulation when mitochondria are inhibited. Findings show that this process is regulated by the interaction of catalytic active hexokinases  with the outer mitochondrial membrane (OMM) and that lactate accumulation resulting from inhibition of mitochondrial function is prevented by binding of catalytically active hexokinase to OMM. These findings illuminate the role that this process can play in the protection against ischemic injuries. Read the study in Plos One.

Machine learning algorithm identifies individuals who experience the largest reduction in depression risk from Medicaid coverage Previous research has demonstrated that Medicaid coverage reduces the risk for developing depression among recipients, but the question is who benefits most from coverage. Using a tool called machine learning causal forest to analyze data from the Oregon Health Insurance Experiment, a research team that includes senior author Dr. Yusuke Tsugawa, associate professor in residence of medicine at David Geffen School of Medicine at UCLA and of health policy and management at the UCLA Fielding School of Public Health, found that people who were older and had more physical or mental health conditions at baseline were likeliest to experience the highest benefit. Causal forest is a machine-learning algorithm that estimates the effects of an intervention on an outcome based on the person’s characteristics, allowing for personalized predictions of how each individual will benefit from a given treatment. The study found that providing Medicaid coverage to individuals with high predicted benefit generated 2.4 times greater reduction in depression prevalence at the population level, with substantially lower cost, compared with providing coverage to everyone. The approach could be useful not just for depression but “in treatment effects across the full spectrum of individual-level demographic and health characteristics.” The researchers conclude that the machine learning causal forest approach could improve the effectiveness and efficiency of insurance expansion. Read the article in the American Journal of Epidemiology.

CT-guided ablation proves to be safe and effective for treating recurrent gynecologic cancers A recently published study led by scientists in the UCLA Health Jonsson Comprehensive Cancer Center found treating people diagnosed with recurrent oligometastatic gynecologic cancers with CT-guided high-dose-rate interstitial brachytherapy ablation was safe and effective, with few side effects. Brachytherapy is a type of radiation that allows for a more focused and customized dose to the cancer, while minimizing damage to surrounding tissues. The study included 34 patients who were diagnosed with either recurrent oligometastatic endometrial or ovarian cancer who underwent this treatment between 2012 and 2022. The team of researchers found the treatment helped control the cancer in about 73% of the cases. The average time before the cancer progressed again was eight months, and the overall survival rate was encouraging, with 58% of patients still alive at 43 months. The study suggests that CT-guided high-dose-rate interstitial brachytherapy ablation can be an effective treatment option for patients with recurrent gynecologic cancers, even in cases where patients had undergone multiple prior treatments. Read the study in Brachytherapy.

February 2024

Specific support cells can regulate behaviors involved in some human psychiatric disorders UCLA Health researchers have discovered a group of specialized support cells in the brain that can regulate behaviors associated with human neuropsychiatric disorders. The study focused on a group of cells known as astrocytes – star-shaped cells that tile the central nervous system and provide a support structure for the neural communication networks.  While neurons have long been understood to have primary control of behavior, the study found that a distinct group of astrocytes located deep in the central region of the brain, known as the central striatum, may also regulate communications between neurons. Unlike other astrocytes, this group of astrocytes express the gene Crym, which encodes for the protein known as μ-crystallin. This protein has been associated with several human diseases including neuropsychiatric disorders, but its influence on brain function has remained largely unknown. In the study, researchers genetically reduced the expression of the gene in this group of astrocytes in mice. Studying the behavior of mice, the researchers found they had significant increases in repetitive behavioral patterns or activities that serve little purpose or made it difficult for the mice to transition to other activities. This behavior, known as perseveration, is associated with neurological and psychiatric disorders including autism, obsessive-compulsive disorder, Huntington’s disease and Tourette’s syndrome. The study found that Crym-positive astrocytes in the central striatum regulated neurotransmitter communication at synapses from the cortex to the center of the brain within the striatum. Researchers say the findings could be starting points in the development of potential therapies to alleviate perseveration in different disorders. Further research is underway to understand the interactions and signaling cascades regulated by μ-crystallin. Read the study in Nature.

Making more genetically-diverse and clinically relevant bladder and prostate cancers A research team led by Dr. John Lee, associate professor of medicine at the David Geffen School of Medicine at UCLA, developed a new method to quickly create a variety of miniature tumor organoids that more closely mimic the characteristics of real tumors, which can provide more accurate and clinically relevant models for studying cancer. The new approach uses a combination of genetic techniques that allows tumors to be analyzed at a detailed level using advanced sequencing methods to identify multiple genetic factors influencing cancer traits. Using this approach in bladder and prostate cancer models, the team found that a mutated gene called Fgfr3 was linked to a certain type of differentiation in bladder cancer, while the loss of another gene called Kmt2c was associated with pleomorphic giant cell carcinoma in prostate cancer. Researchers hope this technique could be used to study more complex interactions between different genes, helping researchers understand how various genetic factors work together to influence the characteristics and behaviors of cancers and other diseases with multiple genetic contributors. Read the article in Nature Genetics.

Proprietary large language models outperform open-source counterparts on multi-choice nephrology questions In the field of natural language processing, it appears that some large language models (LLMs) are better than other artificial intelligence systems when applied to nephrology. A recently published study co-led by scientists at David Geffen School of Medicine at UCLA finds that the proprietary LLMs Claude 2 and GPT-4 outperformed open-source models in correctly answering multiple-choice questions in Nephrology. The researchers evaluated how well the open-source LLMs Llama2-70B, Koala 7B, Falcon 7B, Stable-Vicuna 13B, and Orca-Mini 13B performed on the 858-question multiple-choice Nephrology Self-Assessment Program compared with the proprietary models GPT-4 and Claude 2. The open-source LLMs correct answers ranged from 17.1% to 30.6%. By contrast, Claude 2 answered 54.4% of the questions correctly and GPT-4 achieved a score of 73.3% (human passing grade is 75%).  Still, the open-source models could be a promising tool for medical training and patient care with some fine tuning to eliminate “knowledge gaps” the researchers found in them. Read the article in NEJM-AI.

Genetic score predicts Tobacco Use Disorder in some populations but not all UCLA Health researchers investigated the accuracy of a genetic score that predicts the likelihood of having Tobacco Use Disorder (TUD) among 24,202 participants from different backgrounds. Using a publicly available database that contains information on which genes are linked with TUD and the UCLA ATLAS biobank, the researchers found that the score was accurate in predicting TUD, and the risk of developing the disorder, in European American, and Hispanic and Latin populations, but not in East Asian American or African American groups. The researchers also found that the genes that predispose people to having TUD were also linked with people who exhibited cardiometabolic, respiratory, and neuropsychiatric issues. While there is potential to tailor prevention and therapy for someone who is genetically predisposed to develop TUD, the researchers say genetic research needs to include people from different ancestries for equitable clinical use. Read the article in Translational Psychiatry.

Cinnamon may help control blood sugar in prediabetes It seems that cinnamon has more to recommend it than simply tasting good on toast and other foods. A new UCLA-led study finds that it can help obese or overweight people with prediabetes to control their blood glucose. While previous studies have demonstrated that cinnamon can lower blood glucose in people with type 2 diabetes, others showed no significant results. And even those studies showing a positive outcome were inconsistent in terms of degree of effect and other factors. For this new study, the researchers conducted a randomized controlled trial with 19 participants who were overweight or obese and had prediabetes. Participants were randomly assigned a capsule containing either cinnamon or a placebo for four weeks, followed by a two-week “washout” phase. Afterward the intervention was switched for another two weeks, so that those who had taken the cinnamon capsules in the first phase were given the placebo and vice versa. The researchers monitored blood glucose continuously and found that cinnamon significantly reduced overall glucose levels over all time points in the cinnamon intervention compared with the placebo. Even adherence to the regimen was excellent among both groups, perhaps indicating that patients may be more willing to pop a cinnamon pill than a pharmaceutical. Read the study in The American Journal of Clinical Nutrition.

January 2024

Navigating new ways to treat cancer: How MRI-guided radiation therapy (MRgRT) is changing healthcare In this review article, UCLA physicians from the department of radiation oncology provide a comprehensive overview of the potential benefits, challenges, and economic considerations associated with MRgRT. Unlike traditional methods, MRgRT uses real-time imaging from magnetic resonance imaging (MRI) to guide and adapt radiation therapy, allowing for more precise and effective treatments. While the technology has the potential to revolutionize the field and may even change the standard process of treatment planning and delivery, the authors note that careful evaluation from a healthcare economic and policy perspective is required for its successful implementation, as incorporation of any type of new technology requires that it demonstrates value within the healthcare system. Current evidence suggests that while MRgRT may involve higher initial costs, its advantages in terms of improved outcomes and streamlined processes could ultimately make it cost-effective. Clinical trials, such as the MIRAGE trial, indicate potential benefits of MRgRT, including a reduction in acute genitourinary and gastrointestinal toxicities compared to CT-guided radiation therapy. While the MIRAGE trial demonstrated the toxicity benefits that MRgRT can provide, the SMART trial further demonstrated the potential advantages of MRgRT by incorporating adaptive planning with MRgRT for pancreatic cancer. This trial highlighted the capability for on-table adaptive radiation therapy in real-time, which allows for target dose escalation while reducing the risk of injury to surrounding tissues. While the advantages of MRgRT with respect to cancer outcomes make it appealing from the value perspective, the authors emphasize the need for additional evidence, including cost-effectiveness analyses and patient-reported outcomes, to support the widespread adoption of MRgRT. The study’s first author is Dr. Travis Courtney, a radiation oncology resident at UCLA. The senior author is Dr. Michael Steinberg, professor and chair of radiation oncology at the David Geffen School of Medicine. Read the article in Seminars in Radiation Oncology. 

December 2023 

November 2023

Blood flow changes in the eyes could influence visual symptoms of migraines Researchers found changes in blood flow in the retina could explain why some migraine patients experience visual symptoms. The study findings could represent a long-sought observable marker for migraines that doctors can use to aid in the clinical treatment of the condition. While patients with migraines often experience symptoms such as pain around the eye, sensitivity to light, blind spots and visual blurring, the mechanisms behind those symptoms have not been well understood. UCLA researchers used a non-invasive imaging technique, known as optical coherence tomography angiography, or OCTA, to visualize changes in the retinal blood vessels of migraine patients both during and between migraine attacks. The imaging was performed on 37 migraine patients with aura symptoms, 30 migraine patients without aura symptoms and 20 healthy patients for a control group. Researchers found that blood flow decreases in the retina during migraine attacks for both migraine patients with and without aura symptoms. However, patients with aura symptoms were found to have lower blood flow in certain areas of the retina compared to patients without aura symptoms. Additionally, asymmetrical blood flow in the retinas was also correlated with which side of the head that migraine patients experienced pain. The findings could indicate why some patients experience visual symptoms and may represent a biomarker for migraine attacks. The study was led by former UCLA Department of Neurology Clinical Instructor Dr. Katherine Podraza (now of the Hartford Healthcare Headache Center) and coauthored by former UCLA Health research scientist Nitin Bangera, UCLA Goldberg Migraine Program clinical research coordinator Akira Feliz and UCLA Goldberg Migraine Program Director Dr. Andrew Charles of the UCLA Department of Neurology. Read the study in Headache.

Researchers uncover pyruvate and hexokinases' role in how mitochondria metabolize lactate It was suggested form many decades that lactate is a waste product from glycolysis. However, it is now accepted that lactate is a major energy substrate for the mitochondria of cardiac and skeletal muscles and neurons. Utilizing real time live cell assays reliant on a highly sensitive fluorescent technologies called FRET- fluorescent Resonance energy transfer, and a variety of enzyme inhibitors, a team of scientists from the Department of Physiology, the division of Cardiology and the CNSI at UCLA has recently reported that pyruvate is required for the transformation and utilization of lactate by mitochondria. It was suggested that the transformation of lactate results from the activation of a lactate dehydrogenase by the malate aspartate shuttle, and the production of NAD+ in the mitochondrial’ intermembrane space. For this process to occur, pyruvate must be carboxylated by the malic enzyme. Furthermore, the study shows that binding of hexokinase- the first enzyme in the glucose utilization pathway- to the outer membrane of mitochondria blocks the effect of pyruvate on lactate utilization by mitochondria. This data suggest that hexokinases may play an important role in switching energy substrate utilization by mitochondria from lactate to glucose oxidation. This study of the regulation of lactate utilization by pyruvate and hexokinases has important implications for normal cellular physiology and may prove beneficial in understanding the disparate sensitivities of how cardiac cell respond to a lack of blood- ischemia- and how neurons obtain their energy. Read the study in PLOS ONE.  

October 2023

How Mpox began circulating in humans A multidisciplinary UCLA team has used a mathematical method they developed to analyze how Mpox, previously known as monkeypox, has changed over the years to become more infectious to humans. They found that while there have been occasional outbreaks in humans since at least 1971 coming from an unknown animal that had been its natural host, the virus established a persistent foothold in humans around 2016-2017 and has been circulating in humans since. The findings suggest that the virus has started circulating in humans directly for the past several years, as opposed to jumping periodically into humans from animals in the past. The implication is that there may need to be more careful surveillance to identify the persons in whom it is circulating, which would be important for containment efforts, said senior author Dr. Otto Yang, professor of medicine in the division infectious diseases and of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA. The findings also suggest that the virus may now have the opportunity to evolve to become more contagious in humans. Read the study in Virus Evolution.

September 2023

Cognitive changes in menopause A new study led by UCLA neurologist Dr. Rhonda Voskuhl sheds light on the underlying mechanisms linking menopause to cognitive deficits and brain atrophy, revealing a crucial role for estrogen receptor beta (ERβ) in astrocytes. The study, conducted on female mice, identified the specific brain regions and mechanisms responsible for the cognitive changes experienced during menopause. The research found that loss of ovarian hormones in female mice during midlife, but not at a younger age, induced cognitive impairment. This revealed that both aging and loss of estrogen were critical to cognitive deficits. Additionally, brain MRIs of these midlife female mice demonstrated atrophy of the dorsal hippocampus, a brain region central to memory and learning, and pathology revealed activation of astrocytes and microglia, with synaptic loss. Selective deletion of estrogen receptor beta (ERβ) in astrocytes, a supportive brain cell, had the same detrimental effects on the brain as hormone loss, suggesting that ERβ in astrocytes plays a pivotal role in maintaining hippocampal function during menopause. To translate their findings to humans, the researchers showed that changes in gene expression in the hippocampus of estrogen deficient midlife female mice involved abnormal glucose utilization, and expression of a key gene in this pathway also occurred in post-menopausal women. Aiming to prevent deleterious effects of estrogen deficiency at midlife, mice treated with an ERβ ligand had improved cognition and reversal of the neuropathological changes observed in the dorsal hippocampus. While further research is needed to translate these findings into clinical applications for human patients, the study marks a significant step toward understanding the brain's response to hormonal changes during menopause and offers hope for potential treatments in the future. Read the study in Nature Communications.

Genetic blindness in young adults In a new study, UCLA researchers used advanced computer tools to examine how molecules interact in the mutated protein that can lead to sudden and permanent blindness in young adults. Leber's hereditary optic neuropathy is a condition where a specific genetic mutation in the mitochondrial DNA can lead to sudden and permanent blindness in both eyes. This mutation affects the proteins responsible for mitochondrial function in key cells of the retina. However, scientists were uncertain about how this mutation causes impairment in mitochondria, which are like tiny power plants in our cells. The investigators discovered that this mutation slows down a crucial process called electron transfer to Coenzyme Q10. This slowdown creates conditions that favor the production of harmful substances called reactive oxygen species, which at a threshold leads to cell death by apoptosis. The findings help shed light on how the genetic mutation disrupts the functioning of mitochondria, setting off a chain reaction that can eventually lead to blindness. Read the study published in PNAS.

Single and biventricular congenital heart disease patients have same survival rate 10 years after heart transplant In a new study, UCLA Health researchers analyzed survival outcomes following heart transplantation in adults with single and biventricular congenital heart disease (CHD). CHD encompasses a complex group of structural abnormalities of the heart, with single-ventricle CHD patients considered to have the most complex anatomy.  As such, the researchers hypothesized that these patients would have worse outcomes following heart transplantation, compared to their biventricular counterparts. Analyzing national data from 2005 to 2020, this study is not only the largest of its kind but also the first to comprehensively assess the prognosis of single-ventricular CHD patients post-transplantation. The research confirmed that single-ventricle CHD patients did indeed have lower survival one year after heart transplantation compared to those with biventricular CHD. But after surviving the first year, the ten-year survival rates were the same for single and biventricular CHD patients. According to the authors, this convergence in long-term survival rates has far-reaching implications. These findings could potentially alleviate apprehensions surrounding heart transplantation in patients with single-ventricle CHD and might even play a role in shaping organ allocation policies. Read the study published in the Journal of the American College of Cardiology. 

August 2023

3D Organoid Model for Small Cell Lung Cancer UCLA Health researchers report that they developed a 3D organoid model that appears to mimic the behavior and response to treatment of small cell lung cancer, potentially creating a new way to study the disease and its treatment. Small cell lung cancer has posed a challenge to treat and study due to its high relapse rates and rarity. In the new study, first author Chandani Sen, senior author Brigitte Gomperts, and others report that they used tiny alginate microbeads as a scaffold to mimic lung structure, co-culturing lung cancer cells with lung fibroblasts. In just a week, they began to see the formation of tumors. These mini-tumors closely resembled patient tumors, with some surviving chemotherapy, mirroring what happens in patients. The authors found that lung fibroblasts played a crucial role in supporting the regrowth of cancer cells after treatment, likely through chemical signaling. They say the 3D model opens new doors for research, allowing scientists to study how small cell cancer cells interact and respond to treatments. Read the study published August 7 in Frontiers in Pharmacology.

Insights into penile health and tissue engineering A new study led by Dr. Sriram Eleswarapu, physician scientist in the department of urology at the David Geffen School of Medicine at UCLA, explored properties of the layer of the penis called the tunica albuginea (TA), the elastic layer affected by conditions such as Peyronie’s disease, penile fracture and other penile injuries. Disorders affecting the TA can lead to pain, deformity and erectile dysfunction. Investigators examined the structural, biochemical and mechanical characteristics of healthy TA by testing samples from pigs to provide insights for tissue engineering solutions. Results suggest that: collagen makes up a significant portion of the tissue; collagen crosslinks are important to the integrity of the tissues; collagen type I accounted for most of the tissue’s protein content; and TA had more tension along its length compared to its circumference. The study provides valuable data on the biochemical composition, mechanical properties and structural organization of healthy TA. The authors say this information may be helpful for developing engineered replacements for the TA to treat conditions such as Peyronie's disease, which causes deformities and dysfunction in the TA. Read the study published August 13 in Acta Biomaterialia. 

Sleep problems are associated with faster biologic aging A new study suggests that inadequate sleep, short sleep or insomnia symptoms, may accelerate biological aging, thereby potentially increasing health risks for older adults. For the study, scientists at the UCLA Fielding School of Public Health, the Cousins Center for Psychoneuroimmunology, and the USC Leonard Davis School of Gerontology, analyzed data from nearly 3,800 participants aged 56 to 100 years, comparing sleep duration and insomnia with aging at the biological level using an "epigenetic age acceleration clock," a recent innovation estimating biological age based on measurements of multiple epigenetic sites across an individual's genome. They identified insomnia as the presence of one or more insomnia symptoms such as difficulty falling asleep, frequent nighttime awakenings, and waking up too early, coupled with feeling unrested. Short sleepers were defined as those who spend less than six hours per night in bed. Individuals with insomnia appeared to experience an acceleration of aging equal to an increase of 0.5 year in GrimAge and a 0.02 faster rate of aging per year (Dunedin PACE). Those who reported short sleep duration showed a potential increase of 1.3 years in GrimAge and an increase in 0.02 faster rate in aging per year. Individuals that exhibited both trouble sleeping and short sleep faced an increase in aging equal to 1.0 year in GrimAge and a faster pace in aging of 0.03 per year. The research indicates that poor sleep patterns may contribute to a faster aging process at the biological level, thereby potentially elevating the likelihood of age-related health conditions and overall longevity. The study was published August 21 in Psychosomatic Medicine.

Eating patterns tested for for Alzheimer's disease symptoms A new study, co-authored by Christopher Colwell, Ph.D., professor in the Department of Psychiatry and Biobehavioral Sciences at UCLA, finds that time-restricted feeding (TRF), a specific eating schedule where food intake is restricted to certain times of the day without reducing overall calorie intake, had a positive impact on sleep patterns in mice bred to have Alzheimer’s disease-like characteristics. Disruptions in the body's natural daily rhythms, known as circadian rhythms, have a significant impact on many individuals with Alzheimer's disease. Those lead to difficulty sleeping and worsening cognitive function. There are no existing treatments that target this aspect of the disease. Emerging data indicate that these changes occur early in Alzheimer’s disease progression, potentially indicating they are not consequences but the cause of neurodegeneration. The new study, which focused on two different mouse models of Alzheimer’s disease, demonstrated that TRF was able not only to improve sleep quality and enhance memory, but also reduced the accumulation of amyloid plaques, promote the clearance of a specific protein linked to Alzheimer’s disease, and restore the daily patterns of gene activity in the hippocampus, a region crucial for memory. The authors say the approach holds promise for clinical application, offering a much-needed solution to the pressing need for accessible strategies to slow down or halt the advancement of Alzheimer's disease. Future studies, they say, should explore the potential of TRF in human patients, with the goal of bringing this non-invasive and accessible intervention to those affected by Alzheimer’s disease. Read more in this news story from UC San Diego, who led the study. Read the study published August 21 in Cell Metabolism.

Can speaking more than one language delay Alzheimer’s disease? A new review suggests speaking multiple languages might delay Alzheimer's Disease. A new review examines the current, sometimes conflicting literature on whether the regular use of two or more languages increases cognitive reserve, a protective effect thought to emanate from the long-standing executive control involved in managing multiple languages in the brain. The review finds that while studies are not consistent in their assessment of length and use of a second language, most support the presence of increased cognitive capacity and resilience of the brain's frontal lobe and associated executive functions that compensates for the development of AD neuropathology and, thereby, delays the emergence of clinical symptoms of dementia by about 4 to 5 years. Although regularly speaking more than one language does not protect against the neuropathology of Alzheimer’s disease, the delay in its clinical expression has a potentially significant impact on the lifelong morbidity from this age-related disease. Learning other languages may be an important modifiable factor for delaying the clinical expression of AD in later life. The study was published August 1 in the Journal of Alzheimer's Disease.

July 2023

Medical students pilot antiracism curriculum  A new report finds adding a group of required discussion sessions can help first-year medical students build proficiency in addressing racism in medicine and building and antiracist skills. In the wake of police killings of unarmed African American citizens and the ever-present structural and interpersonal racism in healthcare, students and faculty at the UCLA David Geffen School of Medicine developed an antiracism curriculum to combat bias in medical settings. The curriculum was based on Ibram X. Kendi’s How to be an Antiracist and the course was composed of six two-hour seminars over the course of the year. The first-year medical students that participated were given a survey before and after the completion of the course. The second survey found that the students became more comfortable discussing racism with patients and addressing racism in patient care, and had a greater ability to identify strategies for discussing racism with patients after completing the course. The researchers say that the curriculum and subsequent findings may better equip medical students in addressing racism in health care. Read the study in Medical Science Educator.  

Blood test may help predict outcomes in emergency department admissions A new study links a part of the complete blood count (CBC) with risk of hospital admission and in-hospital mortality. The test is called red blood cell distribution width (RDW). It measures the variation in size of red blood cells. Researchers in the Department of Emergency Medicine at UCLA David Geffen School of Medicine conducted a retrospective analysis of more than 200,000 adult emergency department visits with complete blood count results from March 2013 to February 2022. The primary focus of the study was to explore the relationship between the initial RDW value obtained during the emergency visit and two key outcomes: hospital admission and in-hospital mortality. The researchers found that the RDW value was significantly higher in visits that resulted in hospital admission, and among those patients who were admitted, the RDW was even higher for those who required intensive care unit (ICU) stay or experienced in-hospital mortality. An RDW value above 16 achieved 90% specificity for hospital admission, while an RDW value above 18.5 achieved 90% specificity for in-hospital mortality. The study's findings align with previous research linking elevated RDW to increased mortality risk in conditions such as myocardial infarction, pulmonary embolism, heart failure, sepsis, and COVID-19. The current research, however, establishes the association of RDW with overall hospital admissions and in-hospital mortality across all-cause adult ED visits. The authors say while elevated RDW alone might not be sensitive enough to serve as a comprehensive diagnostic tool, using it in combination with other clinical information may help doctors be better equipped to predict hospital admissions and identify patients at risk of in-hospital mortality. Read the story published July 13 in JAMIA Open.

Advanced imaging uncovers complex 3D structure of vision's initial signals The first electrical signals of vision and hearing are transmitted by cells that are specifically designed to transduce light (photoreceptor cells) or mechanical (cochlear hair cells) stimuli. The signals are transmitted from the receptor cells across rather unusual synapses to secondary neurons. These synapses contain a dense structure that looks like a piece of ribbon in two-dimensions on the receptor side of the synapse. Synaptic vesicles cluster around the ribbons, which guide them to their release site. Despite their crucial role in sensory physiology, the three-dimensional ultrastructure of these synapses, especially the complex organization of the photoreceptor synapse, is not well understood. In a new study, scientists from three UC campuses (UCSB and UCSD, as well as UCLA) generated tomograms with intermediate-voltage electron microscopes to obtain 3-D images at nanoscale resolution to resolve the organization of rod photoreceptor synapses in normal and detached retinas.  This approach enabled the researchers to show that, in the normal retina, a single ribbon, shaped like a thick horseshoe, opposes a tetrad of post-synaptic processes from the secondary neurons. In addition, their novel approach enabled them to provide a 3-D perspective of the ultrastructural changes that occur in response to retinal detachment.  They say their analysis of these changes makes clear the importance of rapid retinal reattachment, following retinal detachment from injury. Read the study in the Journal of Neuroscience.

Early pregnancy MRI scans could predict risks for baby's growth and health In a new study, UCLA researchers explored whether MRI scans could predict ischemic placental disease (IPD), which can lead to problems like preeclampsia, fetal growth restriction (FGR) and placental abruption during pregnancy. These issues can result in premature births and can have negative health effects for both the mother and the baby. The study used special images from MRI scans to look at the placenta and its function in early pregnancy. MRI scans were performed on 199 pregnant women at around 14 to 16 weeks and again at 19 to 24 weeks of pregnancy. The researchers found that women who later developed FGR and/or delivered smaller-than-expected sized babies showed changes in placental structure, blood flow and oxygen levels in the early stages of pregnancy compared to those with normal pregnancies. These changes in the placenta that occurred prior to the development of any clinical features may help predict if a baby will have slow growth or be born smaller than expected. The study suggests that MRI scans in early pregnancy could provide valuable information about the health of the placenta and the baby's development, with far reaching consequences to the mother beyond pregnancy, and the offspring throughout their life’s course. The findings will need further validation through larger studies. If successful, the authors say this approach could potentially lead to better interventions and outcomes for both mothers and babies. The work was led by a multidisciplinary team at UCLA including Dr. Brian Lee, neonatology fellow; Arya Aliabadi, medical student; Dr. Carla Janzen, associate professor, department of obstetrics and gynecology, division of maternal-fetal medicine; Kyung Sung, MRI physicist, department of radiology; and Dr. Sherin Devaskar, corresponding author, physician-in-chief of UCLA Mattel Children's Hospital and distinguished professor of pediatrics. Read the study in Placenta.  

June 2023

Declines in colorectal cancer incidence are slowing  A study co-authored by UCLA Health gastroenterologists provides timely evidence to suggest the decades-long decline in incidence and mortality rates of CRC has slowed among adults in their 50s and 60s, in addition to the extensively reported increases among younger adults. The study also finds racial and ethnic disparities were apparent for Black persons, among whom incidence and mortality remain highest. The authors say their observations point to an urgent need to strengthen efforts to increase screening participation, identify novel risk factors, and address racial and ethnic disparities. Read the study in Clinical Gastroenterology and Hepatology

Nonalcoholic fatty liver disease: What we know Nonalcoholic fatty liver disease (NAFLD) is a rapidly growing public health concern and is the most common form of chronic liver disease in the United States. Prior studies have highlighted differences in NAFLD prevalence among various ethnicities, with the highest prevalence seen in Hispanics and the lowest prevalence seen in African Americans. Compared to non-Hispanic whites and Hispanics, African Americans have the lowest NAFLD prevalence despite equal or higher rates of diabetes and metabolic syndrome. The precise reasons are not known but are thought to be multifactorial, involving metabolic, genetic, and socioeconomic factors. A new review led by Sammy Saab, MD, MPH, medical director of the Pfleger Liver Institute, and medical director of the Adult Liver Transplant Program highlights potential explanations for the lower NAFLD prevalence, describes disease severity and frequency of complications, and discusses the frequency of liver transplantation for NASH in African Americans. Read the review in published in Clinical Liver Disease.

Physical activity appears to prompt the microbiome to inhibit appetite in people with high BMI A new study from Arpana Gupta, PhD, co-director of the Goodman-Luskin Microbiome Center, and colleagues explored whether physical activity can result in psychological benefits through the brain-gut microbiome (BGM) system in a population with high BMI. The study reports that higher physical activity was significantly associated with increased connectivity in inhibitory appetite control brain regions, while lower physical activity was associated with increased emotional regulation network connections. Higher physical activity was also associated with microbiome and metabolite signatures protective towards mental health and metabolic derangements. The greater resilience and coping and the lower levels of food addiction seen with higher physical activity may be explained by BGM system differences. Read the study, "Improved psychosocial measures associated with physical activity may be explained by alterations in brain-gut microbiome signatures," in Nature.

May 2023

Lactation induction in a transgender woman A new study looked at the nutritional quality of milk produced by lactation induction with positive findings. Induction of lactation refers to using specific methods and medications to stimulate the production of breast milk in someone who is not carrying a pregnancy. The ability to produce breast milk can have important benefits, including bonding with the child, providing optimal nutrition, and promoting the health of both the child and the breastfeeding parent. For transgender women and nonbinary people on estrogen-based hormone therapy, being able to produce one’s own milk can also be a significant gender-affirming experience. While previous case studies have described induced lactation in transgender women, this study additionally evaluates the nutritional quality of the produced milk, and includes the participant's perspective in her own words. The participant in this study successfully induced lactation through a combination of medication therapy, breast pumping and eventually direct breastfeeding. Analysis of the participant's milk showed robust nutrient levels, similar to those seen with lactation following pregnancy. The findings suggest that the milk produced by non-gestational transgender women and nonbinary people on estrogen-based hormone therapy is nutritionally adequate for their infants, and highlights the importance of this experience on a personal level. Read more in the case study published May 3, 2023 in the Journal of Human Lactation. 

Negative test results impact adherence to lung cancer screening Screening with low-dose computed tomography (LDCT) has been shown to reduce mortality from lung cancer by at least 20% in large randomized clinical trials but with an important caveat: those reductions show up as long as patients show up for annual screening. Failing to maintain annual adherence to recommended screening may diminish the lifesaving ability of these tests to achieve the same mortality benefits found in large clinical trials. A new study led by UCLA investigators aimed to identify factors associated with risk for patient nonadherence to screening recommendations. The findings suggest that patients with consecutive negative screening results are more likely to become nonadherent to screening over time. The authors say individuals who have consecutive negative results are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening. Read the May 25 study in JAMA Network Open.

Axillary ultrasound may be unnecessary in diagnostic screening for breast cancer  Adding axillary scanning –scanning under the armpits—in patients undergoing a diagnostic breast ultrasound had minimal impact on cancer detection in a large retrospective study. Only a single cancer, a lymphoma, was incidentally found during a two-year period with 19,692 diagnostic ultrasounds performed. No otherwise occult breast cancers were found. Axillary ultrasound is often used to evaluate the lymph nodes in the axilla, the area under the arm or armpit, as it has the potential to provide important information about the presence or spread of breast and other cancers. Studies have shown it does not provide additional cancer detection in women undergoing routine screening, but the effectiveness of axillary scanning in diagnostic testing–in women with mammographic findings—remains unknown, even as some hospitals use the test routinely. A new study, led by Dr. Iris Chen, radiology resident at the David Geffen School of Medicine at UCLA, is the first to evaluate routine axillary scanning on all diagnostic breast ultrasounds in a large patient population. The authors say the results demonstrate that decreasing unnecessary axillary scanning would lead to fewer false positives without missing any occult breast cancers. “Omitting routine scanning of the axilla for all diagnostic breast ultrasounds may save time and reduce patient anxiety related to unnecessary follow-up and biopsies, without adversely affecting patient care,” they write. Read the study in Clinical Imaging.

Using AI to checking endotracheal tube placement Despite the many papers published on artificial intelligence (AI) for radiology, there are very few systems in routine clinical use. Systems have limited experimental testing and very few undergo evaluation in real-world use. In a previous study, UCLA researchers developed and tested an AI system that can assist in checking endotracheal tube placement and issue alerts to physicians if the tip is not correctly positioned. This new study deployed AI to assist in checking endotracheal tube placement in clinical practice and evaluate its real-world performance with user feedback to determine if broader usage is appropriate. The clinical evaluation showed good performance of the chest x-ray AI system and consistency with previous experimental testing. The user survey results indicated overall agreement with the AI outputs and appropriateness of the alerts by both radiologists and ICU physicians. In terms of the usefulness of the system, user ratings suggest that while the AI does not save them time, it does increase their confidence and works the way they would expect AI to in their workflow. The variability among user responses suggests that larger surveys of more users are warranted. Read the April 25 study in the Journal of Medical Imaging

New Insights on Mitochondrial DNA Deletion Mutations and Aging  Somatic mitochondrial DNA (mtDNA) deletion mutations have long been associated with aging and age-related diseases. However, due to the low frequency of these mutations in tissue homogenates and the need for DNA amplification, mapping and quantifying them has remained a challenge. A new study led by UCLA Health dermatologist Dr. Amy Vandiver explores a new approach to tackle this problem. The researchers employed nanopore Cas9-targeted sequencing (nCATS) to map and quantitate mtDNA deletion mutations, yielding a more comprehensive picture of the spectrum and quantity of these mutations. The study analyzed mtDNA in muscle samples from 15 men ranging in age from 20 to 81 years, as well as brain samples from six men aged 20 to 79 years. The results showed that mtDNA deletion mutations increased exponentially with age and mapped to a wider region of the mitochondrial genome than previously thought. To address the challenge of identifying these mutations, the study developed two algorithms that identify both previously reported and novel mtDNA deletion breakpoints. The identified mtDNA deletion frequency measured by nCATS strongly correlates with chronological age and predicts the deletion frequency as measured by digital PCR approaches. The study provides new insights into the relationship between mtDNA deletion frequency, mtDNA deletion genomic location, and chronological aging. It also highlights the importance of developing more accurate methods for studying these mutations, which may help us better understand the mechanisms underlying aging and age-related diseases. Ultimately, this research may pave the way for the development of new therapeutic approaches for these conditions. Read the study in Aging Cell 

April 2023

Health policies on gender-affirming care Within the United States, access to gender-affirming surgeries covered by health insurance has increased over the past decade. However, the rapidly changing landscape and inconsistencies of individual state health policies guiding private and public insurance coverage present a lack of clarity for reconstructive surgeons and other physicians attempting to provide gender-affirming care. This study looked at the current policies in the United States regarding health insurance coverage for gender-affirming care. Researchers analyzed policies from each state and found that about half of the states had protective policies for gender-affirming care, while a number of states restricted state health insurance coverage for gender-affirming care, despite federal law prohibiting gender discrimination under the Affordable Care Act. There were also regional differences, with the Northeast and West having more protective policies and the Midwest and South having more restrictive policies. The findings suggest that clear and consistent policies are important for healthcare providers care for transgender and gender-diverse individuals. Read the study published April 25, 2023 in Plastic and Reconstructive Surgery.

Feminizing rhinoplasty Findings from UCLA investigators in a new study emphasize the importance of tailoring rhinoplasty to individual patients' needs and gender identity to alleviate gender dysphoria effectively. Researchers focused on feminizing rhinoplasty, a surgical procedure aimed at altering the appearance of the nose to align with the gender identity of transgender females and non-binary individuals. After conducting a systematic review of existing literature and analyzing data from UCLA, researchers found that the main goals of feminizing rhinoplasty included reducing the dorsal hump of the nose, refining the nasal tip and achieving balance with other facial features. Techniques involved open rhinoplasty, dorsal reduction, and tip refinement through various grafts and sutures. The study reported low complication rates, with only a small percentage of patients requiring revision surgery. Read the study published in FACE. 

Retinal pigmented epithelium “nibbles” away outer segment tips The retinal pigmented epithelium (RPE) serves a key support role in the retina, nourishing and maintaining photoreceptor cells in ways that are crucial for vision. This includes “nibbling” away at the tips of the outer segment (OS) of rods and cones. Photoreceptors are made up of stacks of membranous discs that contain photoreceptive proteins. UCLA researchers studied a process in the retina in which the photoreceptor outer segment tips are ingested by the RPE. Interactions between the photoreceptors and RPE are crucial for retinal health, and many retinal diseases are caused by disruptions in this interaction. Investigators developed high-speed 3D imaging to examine live RPE cells for the first time. Thus, they resolved a long-standing question of the mechanics underlying how the photoreceptor outer segment tips are ingested by the RPE. Read the study published April 14, 2023 in The Journal of Neuroscience.

March 2023

Facial feminization surgery for the chin A new study led by UCLA researchers highlights various techniques used in genioplasty, a procedure to reshape the chin, such as surgical incisions and bone adjustments, and provides an updated understanding of how chin feminization is performed in transgender women and non-binary individuals. Investigators conducted a comprehensive review of existing medical literature and analyzed institutional data to understand how this procedure is performed and its outcomes. They found that the key goals in feminizing the chin involve reducing its size both horizontally and vertically, while ensuring it complements the rest of the face. Importantly, facial feminization procedures, and particularly genioplasty, play an important role in distinguishing between cis-masculine and cis-feminine faces, and can help address gender dysphoria for transgender women and non-binary patients. Read the study published in FACE. 

Mixed ancestry study provides clues to genetic traits A new multi-institutional study led by scientists at the Bioinformatics Interdepartmental Program at UCLA has found that individuals of mixed ancestry, such as African Americans, inherit a mosaic of ancestry segments from multiple ancestral populations, providing a unique opportunity to investigate the similarity of genetic effects on traits across different ancestries within the same population. The study, which analyzed 38 complex traits in African-European admixed individuals, found very high correlations of causal genetic effects across local ancestries, much higher than the correlation of causal effects across continental ancestries. The findings have implications for the inclusion of ancestry-diverse individuals in genetic studies and suggest that genetic analyses should assume minimal heterogeneity in causal effects by ancestry. The study was conducted by researchers using a new approach called radmix to estimate the correlation of causal genetic effects across local ancestries. The results were replicated using regression-based methods from marginal genome-wide association study summary statistics. The study also found scenarios where regression-based methods yielded inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects and/or polygenicity. Read the study published March 20, 2023 in Nature.

Sex rarely considered in obesity studies A review of medical literature on neuroimaging investigations of obesity showed that the sex of the participant was rarely considered as a variable, a factor that may provide useful information in developing sex-specific biomarkers and interventions. Arpana Gupta and colleagues analyzed approximately 200 online studies using specific search terms, finding that only 13 percent considered sex in their analyses or even controlled for it, despite documented evidence that obese men and women show increased activity and connectivity in markedly different areas of their brains. The researchers, who reviewed literature from 2010 to the present, noted that while the number of studies that include sex as a criteria began to increase slightly after 2015, gender- specific information that could lead to better understanding of the neural correlates of obesity and response to its treatment of men and women is currently limited – and should be considered relevant in future research. Read the article published March 18, 2023 in Current Obesity Reports 

Medicaid, low-volume hospitals and surgical outcomes In a new study, UCLA researchers examined how the Affordable Care Act impacted the clinical and financial outcomes of children surgically treated for congenital heart disease. The researchers analyzed the Nationwide Readmissions database from 2010-2018 and found that patients with Medicaid coverage who received congenital heart surgery had increased mortality, hospital readmissions, fragmented care, and higher costs compared to those with private insurance. They also noted that those covered by Medicaid went to low-volume hospitals and may have received lower-quality care. Given these findings, the researchers are calling efforts to refer Medicaid patients to high-performing centers. Read the study in published March 12, 2023 in Pediatric Cardiology. 

Limiting ECMO to experienced centers may reduce treatment disparities A new UCLA Health study has found patients who require extracorporeal membrane oxygenation (ECMO) are more likely to survive at high-volume hospitals compared to low-volume hospitals. ECMO -- a machine that acts as an artificial pump by providing oxygenated blood to the heart and lungs – requires resources-intensive care and surgical expertise. Given the rising use of the device, especially among critically ill COVID-19 patients, and better outcomes at high-volume hospitals, the researchers are calling for centralizing care to reduce disparities in rural or economically disadvantaged communities. The hub and spoke model entails a referral center that will acquire patients who are on or about to be put on ECMO at low-volume hospitals. While this model would require collaboration among hospitals and infrastructural changes, the researchers say there has been significant interest in centralized care among doctors that treat patients with ECMO. Read the March 11, 2023 study in Surgery. 

Influenza vaccination rates are low A new study finds that patient portal interventions to remind patients to receive the influenza vaccine during the COVID-19 pandemic did not raise influenza immunization rates. UCLA researchers evaluated three health system-wide interventions using the electronic health record's patient portal to improve influenza vaccination rates. The investigators examined different interventions to test messaging strategies based upon behavioral economic principles, plus strategies to make influenza vaccinations more accessible. The strategies included pre-commitment messages, monthly patient reminders, allowing patients to directly schedule their own flu vaccine appointments or get the vaccine at multiple UCLA sites, and flu vaccine reminders sent just prior to existing appointments. However, after analyzing the data of 213,773 patients, the results suggest these interventions did not work to raise flu vaccination rates. The authors conclude that more intensive or tailored interventions are needed to increase influenza vaccination rates beyond just using patient portals. Read the study in the March 2, 2023 issue of Preventive Medicine. 

February 2023

Visual loss and mask-wearing practices Face mask-wearing practices and their impact on the visual field bear particular importance in the COVID-19 pandemic era. This case series examines 10 participants with no history of ocular impairment or visual field defects who underwent age-corrected visual field testing in both eyes with different types of face masks. Wearing duckbill N95 masks was consistently associated with errors in the inferior visual field, the lower area of peripheral vision that identifies potential obstacles such as curbs and other uneven pavement, when compared to wearing surgical masks or no masks. These findings support public health guidance that has attributed increased risks of falls and accidents to face mask wearing. Read the study in the February 2023 issue of Indian Journal of Ophthalmology.

Childhood trauma linked to worse outcomes among Parkinson’s patients: A new study of people with Parkinson’s disease finds that those who experienced childhood trauma had more symptoms, both motor and non-motor, as well as a decreased quality of life compared to others with the disease. While previous research has found people with neurological disorders have higher rates of adverse childhood events (ACE) compared to the general population, this new study – based on a survey of patients with Parkinson’s – is the first to examine the relationship between ACEs and Parkinson’s and adds to our understanding of the long-term health impacts of childhood traumas. The authors say additional research is needed to understand practical clinical implications, which could pave the way for mental health and social support referral of Parkinson’s patients. Read the study published Feb. 20 in Neurology: Clinical Practice.

Body composition, not BMI, may signal risk for cardiovascular disease  Body mass index has long been a measure of a person’s risk of developing cardiovascular disease, but body composition and its role in the disease have not been well studied. In a new study, UCLA researchers predicted higher fat mass would be linked to higher levels of coronary artery calcification (CAC) -- a marker of subclinical cardiovascular disease – and higher fat-free mass would be linked to lower levels of CAC. Using computed tomography scans and bioelectrical impedance analysis to study CAC and body composition in 3,129 non‐Hispanic Whites, Blacks, Hispanics, and Chinese patients, the researchers unexpectedly found that higher fat-free mass and, to a lesser extent, higher fat mass were linked to high levels of CAC. The researchers cautioned that bioelectrical impedance analysis could not identify the quality of fat or fat-free mass. Given these findings, the researchers say measuring body composition rather than using BMI to assess obesity may be a better approach to evaluating cardiovascular disease risk. Read the study published Feb. 8, 2023 in the Journal of the American Heart Association.

Bariatric surgery reduces risks of hospitalization for heart failure Bariatric surgery has been found to reverse the ill effects of diabetes and may be protective against obesity-related cancers. Because obesity rates are on the rise across the globe, UCLA researchers set out to study other health benefits weight loss surgeries confer, in particular the link between the procedures and acute heart failure hospitalizations. After analyzing data from the Nationwide Readmissions Database from 2016 to 2019, the researchers found bariatric surgery was associated with lower odds of being hospitalized with acute heart failure. Among patients hospitalized with acute heart failure, prior bariatric surgery was associated with lower risks of death, prolonged ventilation, and acute renal failure. Beyond the health benefits, those who had undergone surgery stayed one fewer day in the hospital and incurred about $1,200 less in hospital costs compared to age matched cohorts. Read the study in Surgery for Obesity and Related Diseases. 

Pesticides may also worsen Parkinson’s symptoms: While researchers have consistently found an association between pesticide exposure and higher risk of developing Parkinson’s disease, there has been little study of whether such exposure can accelerate the course of the disease. In a new study of 53 pesticides associated with Parkinson’s onset, researchers led by UCLA assistant professor of neurology Kimberly Paul, PhD, identified 10 pesticides that are associated with faster progression of motor and non-motor symptoms. Furthermore, exposure to six of those pesticides was associated with worsening of multiple endpoints researchers measured. Two pesticides, copper sulfate (pentahydrate) and MCPA (dimethylamine salt), were associated with all three endpoints measured: motor function, cognitive function, and depressive symptoms. Read the study in the journal Science of the Total Environment.

January 2023

Gender affirming surgery in nonbinary patients UCLA research sheds light on the diverse treatment preferences and needs of nonbinary patients and underscores the importance of individualized care in gender health. UCLA physician scientists conducted an analysis of 375 patients with gender dysphoria – 67 (18%) identified as nonbinary. Most nonbinary patients were assigned male at birth, and nearly half preferred they/them/theirs pronouns. Approximately 66% of nonbinary patients received hormone therapy, primarily estrogen. Most nonbinary patients expressed an interest in gender-affirming surgery, with the most common procedures including facial feminization surgery, vaginoplasty, mastectomy and orchiectomy. Notably, nonbinary patients assigned male at birth were more likely to receive hormone therapy, while those assigned female at birth were more likely to undergo surgical intervention. Read the study published in Archives of Plastic Surgery. 

Repurposing an old drug for a rare disease: A drug used to treat epilepsy, retigabine, may help manage episodic attacks of paralysis in patients with the rare inherited muscle disease Hypokalemic Periodic Paralysis (HypoPP), according to a new study that tested retigabine in genetically engineered mice. There’s a strong need to identify new HypoPP treatments since existing ones only improve symptoms in about half of patients and have considerable side effects. HypoPP is often marked by reduced potassium levels in the blood during episodes of muscle weakness. While it was known that retigabine affects a potassium channel that plays an important role in the heart and brain, the channel wasn’t previously known to exist in skeletal muscle. However, the new study led by Dr. Stephen C. Cannon, chair of the physiology department at the UCLA David Geffen School of Medicine, found that retigabine helps stabilize the membrane potential of skeletal muscle, thereby protecting against attacks of muscle weakness. Read the study, published online Jan. 30, in the journal Brain.

A new clue about Parkinson’s progression The transmission of misfolded proteins in the brain is a key mechanism for the progression of various neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. Chao Peng, PhD, an assistant professor of neurology, found a novel mechanism that regulates the transmission of one of these pathological proteins, misfolded alpha-synuclein, which leads to disease progression in Parkinson’s. This mechanism is the discovery that many modifications that a cell makes in these proteins alter their ability for transmission in the brain and disease progression. This discovery not only provides critical insights into disease mechanism but also facilitates the development of novel therapy for neurodegenerative diseases. Read the study, published Jan. 23, in Nature Neuroscience.

Gender-affirming hormones tied to mental health for transgender youth Transgender and nonbinary teens who receive gender-affirming hormones experience improvement in body satisfaction, life satisfaction and less depression and anxiety than before treatment. These findings are according to newly-published research by a four-site prospective, observational study and co-authored by Marco A. Hidalgo, PhD. Dr. Hidalgo is a clinical psychologist and Associate Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA. Read the study published January 19, 2023 in the New England Journal of Medicine.

Urban heat islands, redlining and kidney stones The persistent rise in kidney stone prevalence in recent decades has prompted much speculation as to the causes. There has been some discussion about the effect of heat on nephrolithiasis. A review of recent data suggests that heat may play a role in stone formation on a large scale and among African-Americans in particular. A new UCLA-led study led by Dr. Kymora B. Scotland states that African-Americans are the race/ancestry group with faster rates of increasing incidence and prevalence of kidney stones. Researchers also found that urban heat islands in the United States have resulted in part from the effects of redlining, a practice of systematic segregation and racism in housing that led to the development of neighborhoods with substantial disparities in environmental conditions. Dr. Scotland and her team hypothesize that the increased temperatures experienced by residents in redlined communities, many of whom are African American may contribute to the 150% increase in the prevalence of kidney stones in African Americans in recent decades. Read the study in the January 1, 2023 issue of Current Opinion in Nephrology and Hypertension.

Women treated with thrombectomy for pulmonary embolism fare worse A new study led by UCLA researchers analyzed the different outcomes in men and women with a pulmonary embolism who are treated by a percutaneous pulmonary artery thrombectomy- a procedure in which a catheter is placed in a patient’s lung to dissolve or remove a blood clot. After analysis of a national cohort of US patients from an inpatient claims-based database, researchers reported that women had higher rates of procedural bleeding, vascular complications, and needed more blood transfusions compared to men. They also found that women had higher in-hospital death rates and were more likely to go a nursing home or an assisted living facility instead of returning home after discharge. Given these disparities in outcomes, study authors are calling for more sex-based research. Read the study in the January 1, 2023 issue of CHEST. 

October-December 2022

Masks for COVID also prevented whooping cough A new analysis by researchers at UCLA Health finds public health prevention measures taken during the COVID pandemic led to a dramatic drop in whooping cough cases in their health system. Whooping cough, or pertussis, spreads rapidly through droplet transmission, impacting individuals of all ages. Whooping cough is vaccine preventable, however immunity wanes over time. When patients seek care, the risk of transmission to other patients and health care workers can be high. The researchers sought to evaluate the impact of COVID-19 mitigation measures, like masking and school closures, on the number of primary pertussis cases in patients and secondary cases in staff members at ambulatory clinics at their institution before and after the COVID-19 pandemic. Pertussis cases for 2019, 2020, and 2021 were 1,008, 87, and 0 respectively. There were no reported health care worker exposures after March 2020. The authors say their findings demonstrate that masking can impact respiratory disease transmission outside of COVID-19, and that the results are of clinical importance in health care as they show how wearing a mask with symptomatic respiratory patients can be beneficial in reducing exposure to health care workers. Read the study in the American Journal of Infection Control

Microbiome approaches to food allergies The prevalence of food allergies continues to rise, and with limited existing therapeutic options there is a growing need for new and innovative treatments. Food allergies are, in a large part, related to environmental influences on immune tolerance in early life, and represent a significant treatment challenge. This review, led by Dr. Diana Chernikova, pediatric allergy and immunology fellow at the David Geffen School of Medicine at UCLA, discusses the intersection between the gut microbiome and the development of food allergies, with particular focus on microbiome therapeutic strategies. These emerging microbiome approaches to food allergies are subject to continued investigation and include dietary interventions, pre- and probiotics, microbiota metabolism-based interventions, and targeted live biotherapeutics. Read about the findings in the Dec. 3, 2022 issue of Nutrients.

Medicaid expansion, increased access may reduce HIV infections Enacting Medicaid expansion and increasing the use of preventive and antiviral medications could result in a decline of new HIV infections among young Black gay, bisexual, and other men who have sex with men (MSM), reports a study co-authored by Dr. Nina Harawa, professor of Medicine and Epidemiology at the UCLA David Geffen School of Medicine and the Fielding School of Public Health. Led by Francis Lee, PhD, of the University of Chicago, the study used a technique called "agent-based network modeling" to simulate the effects of alternative Medicaid expansion strategies on HIV transmission among young Black gay, bisexual, and other MSM in Houston. Simulations projected the effects of Medicaid expansion alone and with the addition of two further strategies that have shown promise in increasing engagement with ART and PrEP. In the study models, all three scenarios were projected to lead to considerable declines in HIV transmission among young Black gay, bisexual, and other MSM. With Medicaid expansion alone, the HIV incidence rate (new cases per 100 uninfected) was projected to decrease by 17.5% by the tenth year, while the number of new infections would decrease by 14.9%. The most aggressive scenario modeled would nearly halve rates of new infections. Read the study in the journal Medical Care.

Hope for a highly lethal brain cancer A study led by Dr. Linda Liau of the UCLA Health Jonsson Comprehensive Cancer Center finds a cancer vaccine co-developed by Dr. Liau at UCLA led to meaningful increases in survival for patients with glioblastoma multiforme (GBM), a highly lethal brain cancer with a nearly 100% recurrence rate and dismal patient survival. Glioblastomas are aggressive and rapidly lethal; there is a pressing need for new treatments and for novel clinical trial designs to streamline their development. This phase 3 nonrandomized controlled trial of 331 patients found newly-diagnosed GBM patients who received DCVax-L had a median overall survival of 19.3 months after randomization (22.4 after from surgery) compared to 16.5 months survival among a group of external control patients treated with standard care.  For patients with recurrent GBM, median overall survival was 13.2 months from relapse in the DCVax-L group vs 7.8 months in the external control cohort. Meaningful increases in the long-term tails of the survival curves in both nGBM and rGBM were also observed. Read the study in JAMA Oncology and hear Dr. Liau discuss its results and implications in this JAMA podcast.

UCLA Health's response to unaccompanied children at the border A new report details the University of California Health (UCH) system-wide, rapid response to the humanitarian crisis of unaccompanied children crossing the southern U.S. border in the midst of the COVID-19 pandemic in 2021.  In collaboration with multiple federal, state, and local agencies, UCH mobilized a multidisciplinary team to deliver acute general and specialty pediatric care to unaccompanied children at two Californian emergency intake sites. The response, which did not disrupt normal UCH operations, mobilized the capacities of the system and resulted in a safe and developmentally appropriate environment that supported the physical and mental health of migrant children during this traumatic period. Overall, 260 physicians, 42 residents and fellows, four nurse practitioners participated as treating clinicians and were supported by hundreds of staff across the 2 sites. Over five months and across both sites, a total of 4,911 children aged 3–17 years were cared for. A total of 782 children had COVID-19, most infected prior to arrival. Most children (3,931) were reunified with family or sponsors. Read more in the Nov. 15, 2022 report in Academic Medicine.

When congenital heart disease patients get cancer: A new study of cancer outcomes in people with adult congenital heart disease (ACHD) indicates the need for more concerted efforts to appropriately screen and care for this unique population. This collaborative study from the UCLA Adult Congenital Heart Disease and cardio-oncology programs found that all cardiac events in this population were able to be addressed successfully without permanent discontinuation of cancer therapy. In this cohort of adults with both conditions, the median age of cancer diagnosis was only 43.5 years. Only 10% of cancers were detected through screening, and a quarter of all patients had metastatic disease at time of diagnosis. Despite predominantly moderate or great anatomic complexity of congenital heart disease and a high incidence of adverse cardiac events, most deaths occurred due to cancer rather than cardiovascular causes. The authors say the data shows that it is feasible to administer systemic cancer therapy to such a cohort and manage cardiotoxicity without prolonged discontinuation of therapy. Additionally, the authors underscore the need to better define cancer screening in this high-risk population to ensure timely diagnosis and improved outcomes. Read the study in Cardio-Oncology.

Diversity in Gastroenterology A new survey of more than 1,200 gastroenterology (GI) and hepatology professionals in the United States assessed current perspectives of racial and ethnic workforce diversity and health care disparities. It finds the most frequently reported barriers to increasing racial and ethnic diversity in GI and hepatology were insufficient representation of underrepresented racial and ethnic minority groups in the education and training pipeline (reported by 35.4% of respondents), in professional leadership (27.9%), and among practicing GI and hepatology professionals (26.6%). The survey also underscored the discrepancy in satisfaction with workplace diversity among GI and hepatology physicians by race and ethnicity. While 63% of Black physicians were very or somewhat unsatisfied with workplace diversity, 78% of white physicians were very or somewhat satisfied. Read the study in the December 2022 issue of Gastroenterology.

An unexpected Alzheimer’s discovery Little is known about how non-neuronal brain cells known as astrocytes – distinguished by their “bushy” star-like shape – differ in structure or function across the brain, or how these cells may contribute to neurological disease. In a new UCLA-led study aimed at better understanding the molecular similarities and differences between astrocytes, researchers found gene networks correlated with the cells’ shape unexpectedly contained Alzheimer’s disease risk genes. When researchers working with mice reduced the expression of key genes related to the cells’ shape in the hippocampus, making the astrocytes less complex, cognitive function was reduced. They also found the expression of the same genes was reduced in human brains of Alzheimer’s patients. The findings suggest that therapies restoring astrocyte structure may help fight Alzheimer’s. The study was led by Fumito Endo, a project scientist in the lab of UCLA professor of physiology and neurobiology Baljit Khakh. Read the Nov. 4, 2022 study in Science.

Environmental risk of neurodegeneration While scientists increasingly recognize long-term exposure to air pollution as contributing to the development of neurodegenerative diseases like Parkinson’s and Alzheimer’s, how this exposure increases the risk is not well understood. A new UCLA study of air pollution exposure in a novel animal model found that the exposure caused neuronal loss, which was at least partly due to a buildup of protein aggregates in the brain. The researchers, led by Dr. Jeff Bronstein, director of the Movement Disorders Program at UCLA, also found that pollution exposure activated inflammatory cells that can be both good and bad, indicating that any medications to combat inflammation should be highly targeted to cells that can damage neurons. Read the study in Scientific Reports

New approach to bladder cancer A new UCLA-led study of 82 patients with a high-risk form of bladder cancer shows that 71% of the patients, all of whom had not responded to typical therapy, responded to an experimental immunotherapy drug called NAI, which works by activating the body’s natural killer cells. After two years, 90% of the patients who responded to the drug avoided surgery to remove the bladder and there were no deaths from bladder cancer among all 82 patients. The study was funded by ImmunityBio and the results appear in the Nov. 10, 2022 issue of NEJM Evidence.

Housing & Health: It's complicated Previous evidence has shown that housing insecurity—that is, difficulty with housing affordability and stability—is prevalent and results in increased risk for both homelessness and poor health. But a new study finds weak evidence that interventions to boost housing affordability and stability make a difference in improving health. Led by Dr. Katherine Chen, health sciences clinical instructor at the David Geffen School of Medicine at UCLA, the authors conclude that existing strategies to prevent housing insecurity, while necessary, are not sufficient to achieve long-term health gains for vulnerable populations and may need to be both modified and partnered with other policies to redress social inequity, including racism in housing. Read the study in the Nov. 2, 2022 issue of JAMA Network Open

A lab in the palm of your hand Using swarms of pinhead-sized magnets inside a handheld, all-in-one lab kit, UCLA researchers have developed a technology that could significantly increase the speed and volume of disease testing, while reducing the costs and usage of scarce supplies. Read more in this Nov. 10, 2022 press release from the UCLA Samueli School of Engineering here.

Young investigator award October 26, 2022: Roni Haas, PhD, postdoctoral scholar in the lab of Paul Boutros has received a 2022 Young Investigator Award from the Prostate Cancer Foundation. The award will support Haas’s prostate cancer research project, Associating Germline Variants with Prostate Tumor Evolution and Lethality, at total of $225,000 over three years. Read more about the PCF Young Investigator Awards here.

Do celebrity endorsements increase vaccination? In the year between October 2020 and October 2022, Americans’ willingness to be vaccinated (defined as being vaccinated or planning to be) increased from 47.6% to 81.1%. A new survey led by Arash Naeim at the Center for SMART Health at UCLA’s Clinical and Translational Science Institute looked at how much impact five strategies had on increasing the willingness of unvaccinated adults to get their shots. It found endorsements by members of the scientific community, healthcare professionals, or celebrities had no positive effect. What did? The chance to relax the need for masks and social distancing, financial incentives, and vaccine requirements for attending sporting events traveling and work. Read the study in Vaccine.