Tag: UC Davis Health

Software developed at UC Davis analyzes calcium ‘sparks’ that can contribute to arrhythmia
[ad_1]
The image on the left shows raw data, and the image on the right shows how SparkMaster 2 detects calcium sparks, miniwaves and waves.

(SACRAMENTO) A team of UC Davis and University of Oxford researchers have developed an innovative tool: SparkMaster 2. The open-source software allows scientists to analyze normal and abnormal calcium signals in cells automatically.

Calcium is a key signaling molecule in all cells, including muscles like the heart. The new software enables the automatic analysis of distinct patterns of calcium release in cells. This includes calcium “sparks,” microscopic releases of calcium within cardiac cells associated with irregular heartbeats, also known as arrhythmia.

A research article demonstrating the capabilities of SparkMaster 2 was published in Circulation Research.

Jakub Tomek, the first author of the research article, is a Sir Henry Wellcome Fellow in the Department of Physiology, Anatomy and Genetics at the University of Oxford. He spent his fellowship year at UC Davis, working with Distinguished Professor Donald M. Bers.

“It was great to present SparkMaster 2 at recent conferences and see the enthusiastic response. I felt it would be an outlier and that few people would care. But many people were excited about having a new analysis tool that overcomes many of the limitations they have experienced with prior tools,” Tomek said.

Jakub Tomek, the first author of the research article, is a Sir Henry Wellcome Fellow at the University of Oxford.

Fellowship at UC Davis leads to updated tool

Problems with how and when calcium is released by cells can have an impact on a range of diseases, including arrhythmia and hypertension. To understand the mechanisms behind these diseases, researchers use fluorescent calcium indicators and microscopic imaging that can measure the calcium changes at the cellular level.

However, the resulting data files are large and challenging to analyze by hand, so customized software analysis tools are essential.

At the Bers Lab at UC Davis, Tomek discussed analysis tools with Christopher Y. Ko, an assistant project scientist. They identified the need for better, more user-friendly software, which led to the development of SparkMaster 2.

The new tool builds upon the success of SparkMaster, which was released in 2007 by Bers and Eckard Picht. Picht is a physician-scientist who worked with Bers, first at Loyola University Chicago and then for a few years at UC Davis. At the time, there was no user-friendly free software that could analyze calcium sparks — a crucial part of their research — so they developed one.

To create the new software, SparkMaster 2, Tomek worked with Bers, Ko, Manuel F. Navedo and Madeline Nieves-Cintron in the Department of Pharmacology at the UC Davis School of Medicine.

Although much of the new interface resembles the original SparkMaster, they started from scratch for the programming. Using Python, an open-source programming language that has grown in popularity, they were able to utilize many existing tools and libraries to create the unique features they wanted.

The UC Davis team: Donald M. Bers (sitting), Manuel F. Navedo (standing left), Christopher Y. Ko (standing middle), Madeline Nieves-Cintron (right).

They ended up with software that can analyze calcium sparks recorded using different microscopy approaches and from cells from different tissues and genetically modified mice. Some key features of the new version include:
- improved user interface
- higher accuracy at identifying calcium release events than previous tools
- ability to identify multiple types of calcium-release events
- ability to accurately split and analyze individual sparks within spark clusters
“SparkMaster 2 is even easier to use and is much more powerful in the variety of event types it can analyze quantitatively — sparks, waves, mini-waves and latencies. And it has higher accuracy and sensitivity, resulting in fewer missed events and fewer erroneous positives,” Bers said.

Bers anticipates the primary users of the software will be scientists who study calcium in muscle. “But it may be useful for researchers who study other cell types, such as neurons, that exhibit local calcium events that are important in regulating cellular function,” Bers said.

Ko, who is a co-developer of the new tool, is also interested in the broader research applications for the new software.

“I’m particularly excited about the new scientific questions that SparkMaster 2 will enable the biomedical research community to answer and, in turn, the ability to more completely and accurately understand the biology that underlies human physiology in health and disease,” Ko said.

Additional authors on the paper include Nieves-Cintron and Navedo from UC Davis. They were instrumental in demonstrating how the software can be used outside cardiac research, and across distinct cell types, showing its wide range of possible uses.

Resources
[ad_2]

UC Davis Health

Source link
September 1, 2023
UC Davis Eye Center tests experimental gene therapy for wet age-related macular degeneration (AMD)

[ad_1]

Newswise — (SACRAMENTO, Calif.) — Ophthalmologists at UC Davis Health used an experimental gene therapy last month to treat a patient with wet age-related macular degeneration, or wet AMD. It was the first time the UC Davis Eye Center had used gene therapy.

The treatment was part of a randomized, partially masked, controlled, phase 3 clinical study evaluating the efficacy and safety of an experimental therapy, ABBV-RGX-314, for wet AMD. UC Davis Health is one of 93 sites in the U.S. participating in the clinical trial.

This investigational treatment is not FDA approved, and the efficacy and safety have not been established.

Wet AMD affects approximately 2 million people in the United States, Europe and Japan. It is a leading cause of vision loss among older adults.

“The current treatments for wet AMD may be life-long, and injections can be as frequent as every month,” said Glenn Yiu, professor of ophthalmology at UC Davis Health and principal investigator for the new clinical trial. “If approved, a gene therapy solution has the potential to maintain vision while reducing the number of injections, by allowing the eye to continuously produce the medicine on its own,” Yiu said.

In AMD, the macula, an area of the eye’s lining that helps you see, becomes damaged. This can blur the central part of your vision, making it hard to drive or read. An early symptom of wet AMD is that straight lines look distorted and wavy.

In wet, or neovascular AMD, abnormal blood vessels grow underneath the retina. These vessels lead to bleeding or fluid leakage in the back of your eye, causing vision loss. This process, known as “neovascularization,” is largely driven by a growth factor called vascular endothelial growth factor (VEGF).

Treatments for wet AMD rely on repeated injections of drugs that block VEGF in the diseased eye.

In wet or neovascular AMD, abnormal blood vessels grow underneath the retina, leading to bleeding or fluid leakage in the eye.

Gene therapy may offer different approach

Unlike stem cell therapies used to treat eye diseases — which involve injecting cells with regenerative or restorative capabilities into the eye — gene therapy generally uses an empty viral envelope (a vector) to deliver a gene with specific genetic instructions for making protein.

ABBV-RGX-314 contains genetic instructions for making anti-VEGF proteins. After a single injection of ABBV-RGX-314 gene therapy, the eye can start to make the medicine on its own.

Yiu performed the first experimental gene therapy eye surgery at UC Davis Health in July. The procedure is more complex than administering a monthly injection. It includes a vitrectomy, where the viscous gel in the eye is removed and replaced with a saline infusion. The experimental treatment with its gene delivery vector is then injected underneath the retina.

Yiu will monitor whether the participant will continue to need monthly anti-VEGF injections in the coming months.

Paul Sieving is the former director of the National Eye Institute and is now a professor of ophthalmology at UC Davis Health. He established the Center for Ocular Regenerative Therapy (CORT) for pursuing cell and gene therapies.

“It is noteworthy for patients in Northern California that UC Davis Health is doing experimental ocular gene therapy studies in the Department of Ophthalmology and Vision Sciences. What excites me most about this is the potential of Dr. Yiu’s work to reduce the repeated eye injections currently required for wet age-related macular degeneration,” Sieving said.

UC Davis Health has enrolled three patients in the clinical trial and plans to enroll more. Individuals aged 50 to 88 with wet AMD who have had prior anti-VEGF injections may be eligible to participate.

For more information, visit the study page, or email Denise Macias, clinical research supervisor, at [email protected].

Resources

[ad_2]

UC Davis Health

Source link

August 29, 2023
New UC Davis documentary set to air on PBS

[ad_1]

Newswise — A new documentary from the UC Davis Environmental Health Sciences Center (EHSC) will premiere on PBS stations beginning Jan. 14.

“Dignidad: California Domestic Workers’ Journey for Justice” follows domestic workers in California as they organize for job protections during the COVID-19 pandemic.

Viewers in the greater Sacramento area can watch the broadcast on Thursday, Jan. 19 at 10:30 p.m. PST on KVIE. It is also available for viewing on the PBS website.

“Domestic workers lack virtually any protections from arbitrary and unsafe working conditions. This film highlights their struggle to achieve dignity, respect, and safe and humane working environments before and throughout the unprecedented COVID public health crisis,” said Irva Hertz-Picciotto, a professor of public health sciences and director of EHSC.

Hertz-Picciotto is the executive producer for the film. Jennifer Biddle, digital strategist at EHSC, is the producer. Paige Bierma, an award-winning filmmaker and journalist, directed the documentary.

“Dignidad” is the second film for the team. Their previous documentary, “Waking Up to Wildfires,” premiered on PBS in 2019. Since then, it has aired more than 300 times on 160 PBS stations and is currently available on PBS Viewfinder.

Kim Alvarenga, director of the California Domestic Workers Coalition, and domestic workers Mirna Arana and Rock Delgado are featured in the new film.

Mirna Arana fled deadly gang violence in Guatemala and resettled in California. She started working as a cleaner, where she experienced wage theft, and is now an activist with Mujeres Unidas y Activas. Rock Delgado, a caregiver in Los Angeles, survived a severe bout of COVID-19 after being exposed on the job. He’s now an activist with the Pilipino Workers Center.

Their stories illustrate the struggles many domestic workers face in California. Domestic workers are predominantly female and persons of color. Many are new immigrants. Laboring in other people’s homes often includes risks such as unsafe working conditions, exceedingly long hours, wage theft and other forms of abuse.

Exclusion from Cal/OSHA

The California Division of Occupational Safety and Health, known as Cal/OSHA, is responsible for enforcing California laws and regulations related to workplace safety. In 2020, during the first year of the COVID-19 pandemic, the California Legislature passed SB 1257. The bill was designed to extend Cal/OSHA protections to domestic workers.

California Governor Gavin Newsom vetoed the bill. In his statement, Newsom said: “SB 1257 would extend many employers’ obligations to private homeowners and renters, including the duty to create an injury prevention plan and the requirement to conduct outdoor heat-trainings. Many individuals to whom this law would apply lack the expertise to comply with these regulations.”

Domestic workers in the state organized in response to the veto. “Dignidad” touches on some of the EHSC research findings about the vulnerabilities faced by domestic workers during the pandemic. It also chronicles domestic workers’ efforts to pass a subsequent bill introduced by California Senator María Elena Durazo: the Health and Safety for All Workers Act (SB 321).

In 2021, Governor Newsom, after amending the bill, signed SB 321 into law. The measure did not fully bring domestic workers under Cal/OSHA standards. However, it mandates the creation of an advisory committee comprised of members of the public and experts to develop recommendations on protecting the occupational health and safety of domestic workers.

“It was heartening that after more than a century of having virtually no rights as workers, domestic employees are now recognized as needing occupational protections. While this new law does not actually guarantee those protections, it is a small first step toward that goal and toward the dignity domestic workers deserve,” Hertz-Picciotto said.

Resources

[ad_2]

UC Davis Health

Source link

January 12, 2023