A new study from researchers with UCLA Health and collaborating organisations has found that asporin, a protein encoded by the ASPN gene, plays a protective role in pulmonary arterial hypertension (PAH).
Their findings, out now in the peer-reviewed journal Circulation, offer new insights into this incurable, often-fatal disease and suggest potential new ways to treat it. The ASPN gene is part of a group of genes associated with the cartilage matrix.
“We were surprised to find that asporin, which previously had not been linked to PAH, gets upregulated to increased levels as a response to counteract this disease process,” said Dr Jason Hong, a pulmonary and critical care physician at UCLA Health and the study’s corresponding author. “This novel finding opens up new avenues for understanding PAH pathobiology and developing potential therapies.”
Pulmonary hypertension is a serious medical condition characterised by high blood pressure in the arteries that supply the lungs. It causes these arteries to narrow or become blocked, which, in turn, slows blood flow to the heart, requiring it to work harder to pump blood through the lungs. Eventually, the heart muscle becomes weak and begins to fail.
Need for New Therapies
According to recent estimates, PAH affects about 1% of the global population, but that number climbs to 10% in people who are 65 or older.
There’s no cure for the disease, but medications and lifestyle changes can help slow progression, manage symptoms and prolong life.
The urgent need for new therapies, combined with the potential of multiomics – an integrated approach to drive discovery across multiple levels of biology – inspired Hong and research colleagues, including co-first author Lejla Medzikovic and senior author Mansoureh Eghbali to take a deep dive into the disease. Both work at UCLA’s Eghbali Laboratory.
Methodology
For the study, the researchers applied novel computational methods, including transcriptomic profiling and deep phenotyping, to lung samples of 96 PAH patients and 52 control subjects without the condition from the largest multicenter PAH lung biobank available to-date. They integrated this data with clinical information, genome-wide association studies, graphic models of probabilities and multiomics analysis.
“Our detailed analysis found higher levels of asporin in the lungs and plasma of PAH patients, which were linked to less severe disease,” Hong said.
Additionally, Medzikovic noted that their cell and living-organism experiments found that asporin inhibited pulmonary artery smooth muscle cell proliferation and a key signaling pathway that occurs with PAH.
“We also demonstrated that recombinant asporin treatment reduced PAH severity in preclinical models,” said Medzikovic.
Next Steps
Hong and colleagues plan to further investigate the mechanisms by which asporin exerts its protective effects in PAH and explore potential therapeutic applications, focusing on how to translate their findings into clinical trials.
“Asporin represents a promising new target for therapeutic intervention in pulmonary arterial hypertension,” he explained. “Enhancing asporin levels in PAH patients could potentially lead to improved clinical outcomes and reduced disease progression.”
ISO accreditation is a strategic investment that empowers businesses to enhance their competitiveness, mitigate risks, and seize new market opportunities. By adhering to globally recognised standards, organisations can build trust, streamline operations, and achieve sustainable growth. While the initial outlay may seem substantial, the long-term returns in terms of efficiency, customer satisfaction, and regulatory compliance far exceed the costs.
Building credibility and adherence to global standards
In today’s increasingly globalised business landscape, standing out from the competition is essential. ISO accreditation acts as a powerful endorsement, signifying a company’s commitment to quality, efficiency, and adherence to international best practices. By obtaining ISO certification, businesses can better mitigate risk while demonstrating their credibility and reliability to customers, suppliers, and stakeholders alike.
How ISO standards provide a framework for best practices
ISO standards provide a structured approach to managing various aspects of an organisation’s operations, ensuring consistent performance and compliance with customer and regulatory expectations. These standards offer a comprehensive framework that guides companies in identifying, managing, and continually improving their processes, which ultimately provides an effective means of identifying and managing risk throughout the business. Here’s a brief breakdown of how specific ISO standards contribute to this:
ISO 9001: Quality Management System
Customer focus: Defines processes to understand customer needs and expectations, ensuring products or services meet or exceed these requirements.
Process-based approach: Establishes a systematic approach to identifying, managing, and controlling processes to achieve desired outcomes.
Continuous improvement: Promotes a culture of continual improvement by monitoring processes, identifying opportunities for enhancement, and implementing changes.
ISO 14001: Environmental Management System
Environmental Impact Assessment: Requires organisations to identify, assess, and control environmental impacts of their activities.
Legal compliance: Ensures adherence to environmental laws and regulations.
Resource efficiency: Promotes the efficient use of resources and waste reduction.
Stakeholder engagement: Encourages dialogue with stakeholders to address environmental concerns.
ISO 22000: Food Safety Management System
Hazard Analysis and Critical Control Points (HACCP): Implements a systematic approach to identifying, assessing, and controlling food safety hazards.
Supply chain management: Addresses food safety throughout the entire supply chain.
Regulatory compliance: Ensures compliance with food safety regulations and standards.
ISO 45001: Occupational Health and Safety Management System
Risk assessment: Identifies and assesses occupational health and safety risks.
Legal compliance: Ensures compliance with occupational health and safety legislation.
Emergency preparedness: Develops and implements emergency procedures.
Employee involvement: Encourages employee participation in health and safety initiatives.
ISO standards incorporate several fundamental elements to ensure consistent performance and improvement. These include the Plan-Do-Check-Act (PDCA) cycle for continuous enhancement, robust risk management practices, comprehensive documentation, regular internal and external audits to assess effectiveness, as well as periodic management reviews to evaluate overall performance and identify areas for improvement. By adopting these standards, organisations can leverage this robust framework for managing their operations, ensuring consistent performance, which positions the organisation to be able to meet the evolving needs of customers and regulatory authorities.
The benefits of working with ISO-certified suppliers
Choosing ISO-certified suppliers can significantly enhance a business’s supply chain resilience. This choice gives companies the peace of mind that their new suppliers adhere to rigorous standards, which ensures improved product and service quality, as ISO certification guarantees consistent product or service quality, reducing the risk of defects or errors.
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The bottom line of ISO accreditation
While the initial costs of ISO accreditation may be substantial, the long-term benefits are undeniable. By investing in ISO certification, businesses can enhance their credibility, improve operational efficiency, mitigate risks, and gain a competitive edge. Just as important, working with ISO-certified suppliers strengthens a company’s supply chain, ensuring the delivery of high-quality products and services. This in turn leads to increased customer satisfaction, loyalty, and business growth.
As such, ISO accreditation is not merely a compliance exercise; it is a strategic investment that empowers businesses to thrive in today’s challenging market. By understanding the value of different ISO standards and the advantages of working with ISO-certified suppliers, companies can make informed decisions to drive sustainable success.
Whether dialysis is the best option for kidney failure and, if so, when to start, may deserve more careful consideration, according to a new study published in Annals of Internal Medicine.
For older adults who were not healthy enough for a kidney transplant, starting dialysis when their kidney function fell below a certain threshold, rather than waiting, afforded them roughly one more week of life, Stanford Medicine researchers and their colleagues found.
More critically, perhaps, they spent an average of two more weeks in hospitals or care facilities, in addition to the time spent undergoing dialysis.
“Is that really what a 75- or 80-year-old patient wants to be doing?” asked lead author Maria Montez Rath, PhD, a senior research engineer. Manjula Tamura, MD, a professor of nephrology, is the senior author.
“For all patients, but particularly for older adults, understanding the trade-offs is really essential,” Tamura said. “They and their physicians should carefully consider whether and when to proceed with dialysis.”
Patients with kidney failure who are healthy enough for transplantation may receive a donated kidney, which will rid their blood of toxins and excess fluid. But that option is unavailable to many older adults who have additional health conditions such as heart or lung disease or cancer.
For those patients, physicians often recommend dialysis when patients progress to kidney failure – when estimated glomerular filtration rate (eGFR), a measure of renal function, falls below 15.
Patients and their family members sometimes assume that dialysis is their only option, or that it will prolong life significantly, Montez Rath said. “They often say yes to dialysis, without really understanding what that means.”
But patients can take medications in lieu of dialysis to manage symptoms of kidney failure such as fluid retention, itchiness and nausea, Tamura said. She added that dialysis has side effects, such as cramping and fatigue, and typically requires a three- to four-hour visit to a clinic three times a week.
“It’s a pretty intensive therapy that entails a major lifestyle change,” she said.
Lifespan and time at home
The researchers conducted the study to quantify what dialysis entails for older adults who are ineligible for a transplant: whether and how much it prolongs life, along with the relative number of days spent in an inpatient facility such as a hospital, nursing home or rehabilitation center.
The team evaluated the health records, from 2010 to 2018, of 20 440 patients (98% of them men) from the U.S. Department of Veterans Affairs. The patients were 65 and older, had chronic kidney failure, were not undergoing evaluation for transplant and had an eGFR below 12.
Simulating a randomised clinical trial with electronic health records, they divided patients into groups: those who started dialysis immediately, and those who waited at least a month. Over three years, about half of the patients in the group who waited never started dialysis.
Patients who started dialysis immediately lived on average nine days longer than those who waited, but they spent 13 more in an inpatient facility. Age made a difference: Patients 65 to 79 who started dialysis immediately on average lived 17 fewer days while spending 14 more days in an inpatient facility; patients 80 and older who started dialysis immediately on average lived 60 more days but spent 13 more days in an inpatient facility.
Patients who never underwent dialysis on average died 77 days earlier than those who started dialysis immediately, but they spent 14 more days at home.
“The study shows us that if you start dialysis right away, you might survive longer, but you’re going to be spending a lot of time on dialysis, and you’re more likely to need hospitalization,” Montez Rath said.
Tamura noted that physicians sometimes recommend dialysis because they want to offer patients hope or because the downsides of the treatment haven’t always been clear. But the study indicates physicians and patients may want to wait until the eGFR drops further, Tamura said, and should consider symptoms along with personal preferences before starting dialysis.
“Different patients will have different goals,” she said. “For some it’s a blessing to have this option of dialysis, and for others it might be a burden.”
It may be helpful, she added, if clinicians portray dialysis for frail, older adults as a palliative treatment – primarily intended to alleviate symptoms.
“Currently, dialysis is often framed to patients as a choice between life and death,” she said. “When it’s presented in this way, patients don’t have room to consider whether the treatment aligns with their goals, and they tend to overestimate the benefits and well-being they might experience. But when treatment is framed as symptom-alleviating, patients can more readily understand that there are trade-offs.”
Noise exposure is a known occupational hazard in some jobs, particularly for hearing loss, physical and psychological stress, and reduced concentration. A new study presented at the ACC Asia 2024 conference found in adult power loom weavers, chronic noise exposure not only increased their blood pressure overall, but also each year of exposure increased their odds of having high blood pressure by 10%.
“While the mechanism is still not well-explored, it is thought that the stress response by the body to chronic sound exposure causes hormonal imbalances that gradually leads to a permanent elevation of blood pressure,” said Golam Dastageer Prince, MBBS, MPH, medical officer at DGHS Bangladesh and the study’s lead author. “High blood pressure impacts more than a billion people worldwide and just 1 in 5 have it under control, yet it is a major cause of premature death. In addition to treating the high blood pressure through appropriate means, we must find ways to mitigate the exposure to the noise if we want to reduce the cardiovascular risk of these patients.”
Researchers at the Directorate of General Health Services in Bangladesh looked at 289 adult workers in selected weaving factories in the Araihazar sub-district of Narayanganj, Bangladesh, from January to December 2023. Participants took a face-to-face interview to complete a questionnaire covering sociodemographic variables, behaviour, dietary habits and family medical history. Blood pressure, height, weight and noise intensity were measured following standard procedures by the researchers.
The study cohort was predominantly male and married and were about 34 years of age on average. According to the researchers, a notable proportion of the cohort was illiterate. Workplace exposure duration averaged nearly 16 years, with noise intensity ranging from 96–111 decibels. In the United States the National Institute for Occupational Safety and Health has established the recommended exposure limits for occupational noise exposures to be 85 decibels on average over an eight-hour workday. Sounds at or below 70 decibels are generally considered safe.
According to Prince, none of the study population was found to be wearing ear protection personal protective equipment.
“Hopefully we can raise awareness of not only noise-induced hearing loss, but the impact of noise on blood pressure and workers’ behaviors and attitudes towards using personal protective equipment,” Prince said. “Pushing for structural improvements to industries may also help us improve the health safety of these workers.”
The study population had a 31.5% rate of high blood pressure with an additional 53.3% being prehypertensive. The study also found a positive correlation between blood pressure and noise exposure duration. Each year of exposure was found to increase high blood pressure odds by 10%, even after adjusting for age, body mass index and smoking status.
“As the study focused on workers exposed to more than 85 decibels noise for long periods of time, any profession causing workers to experience similar exposure might experience similar blood pressure impacts,” Prince said. “We definitely need more exploratory studies to reveal more information about the potential mechanisms and long-term health outcomes.”
Recent studies have shown that living near noise pollution, including highways, trains and air traffic, can have an impact on cardiovascular health. However, the current study may not apply to noise experienced during daily life. Noise pollution experienced near home typically ebbs and flows, while the industrial exposures in the study are typically continuous in pattern due to the machinery and remain at a constant sound level, according to Prince.
Two new studies from UC San Francisco are pointing the way toward round-the-clock personalised care for people with Parkinson’s disease through an implanted device that can treat movement problems during the day and insomnia at night.
The approach, called adaptive deep brain stimulation, or aDBS, uses methods derived from AI to monitor a patient’s brain activity for changes in symptoms.
When it spots them, it intervenes with precisely calibrated pulses of electricity. The therapy complements the medications that Parkinson’s patients take to manage their symptoms, giving less stimulation when the drug is active, to ward off excess movements, and more stimulation as the drug wears off, to prevent stiffness.
It is the first time a so-called “closed loop” brain implant technology has been shown to work in Parkinson’s patients as they go about their daily lives. The device picks up brain signals to create a continuous feedback mechanism that can curtail symptoms as they arise. Users can switch out of the adaptive mode or turn the treatment off entirely with a hand-held device.
For the first study, researchers conducted a clinical trial with four people to test how well the approach worked during the day, comparing it to an earlier brain implant DBS technology known as constant or cDBS.
To ensure the treatment provided the maximum relief to each participant, the researchers asked them to identify their most bothersome symptom. The new technology reduced them by 50%. Results appear August 19 in Nature Medicine.
“There’s been a great deal of interest in improving DBS therapy by making it adaptive and self-regulating, but it’s only been recently that the right tools and methods have been available to allow people to use this long-term in their homes,” said Starr, who was recruited by UCSF in 1998 to start its DBS program.
Earlier this year, UCSF researchers led by Simon Little, MBBS, PhD, demonstrated in Nature Communications that adaptive DBS has the potential to alleviate the insomnia that plagues many patients with Parkinson’s.
“The big shift we’ve made with adaptive DBS is that we’re able to detect, in real time, where a patient is on the symptom spectrum and match it with the exact amount of stimulation they need,” said Little, associate professor of neurology and a senior author of both studies. Both Little and Starr are members of the UCSF Weill Institute for Neurosciences.
Restoring movement
Parkinson’s disease affects about 10 million people around the world. It arises from the loss of dopamine-producing neurons in deep regions of the brain that are responsible for controlling movement. The lack of those cells can also cause non-motor symptoms, affecting mood, motivation and sleep.
Treatment usually begins with levodopa, a drug that replaces the dopamine these cells are no longer able to make. However, excess dopamine in the brain as the drug takes effect can cause uncontrolled movements, called dyskinesia. As the medication wears off, tremor and stiffness set in again.
Some patients then opt to have a standard cDBS device implanted, which provides a constant level of electrical stimulation. Constant DBS may reduce the amount of medication needed and partially reduce swings in symptoms. But the device also can over- or undercompensate, causing symptoms to veer from one extreme to the other during the day.
Closing the loop
To develop a DBS system that could adapt to a person’s changing dopamine levels, Starr and Little needed to make the DBS capable of recognising the brain signals that accompany different symptoms.
Previous research had identified patterns of brain activity related to those symptoms in the subthalamic nucleus, or STN, the deep brain region that coordinates movement. This is the same area that cDBS stimulates, and Starr suspected that stimulation would mute the signals they needed to pick up.
So, he found alternative signals elsewhere in the brain – the motor cortex – that wouldn’t be weakened by the DBS stimulation.
The next challenge was to work out how to develop a system that could use these dynamic signals to control DBS in an environment outside the lab.
Building on findings from adaptive DBS studies that he had run at Oxford University a decade earlier, Little worked with Starr and the team to develop an approach for detecting these highly variable signals across different medication and stimulation levels.
Over the course of many months, postdoctoral scholars Carina Oerhn, PhD, Lauren Hammer, PhD, and Stephanie Cernera, PhD, created a data analysis pipeline that could turn all of this into personalised algorithms to record, analyse and respond to the unique brain activity associated with each patient’s symptom state.
John Ngai, PhD, who directs the Brain Research Through Advancing Innovative Neurotechnologies® initiative (The BRAIN Initiative®) at the National Institutes of Health, said the study promises a marked improvement over current Parkinson’s treatment.
“This personalised, adaptive DBS embodies The BRAIN Initiative’s core mission to revolutionise our understanding of the human brain,” he said.
A better night’s sleep
Continuous DBS is aimed at mitigating daytime movement symptoms and doesn’t usually alleviate insomnia.
But in the last decade, there has been a growing recognition of the impact that insomnia, mood disorders and memory problems have on Parkinson’s patients.
To help fill that gap, Little conducted a separate trial that included four patients with Parkinson’s and one patient with dystonia, a related movement disorder. In their paper published in Nature Communications, first author Fahim Anjum, PhD, a postdoctoral scholar in the Department of Neurology at UCSF, demonstrated that the device could recognise brain activity associated with various states of sleep. He also showed it could recognise other patterns that indicate a person is likely to wake up in the middle of the night.
Little and Starr’s research teams, including their graduate student Clay Smyth, have started testing new algorithms to help people sleep. Their first sleep aDBS study was published last year in Brain Stimulation.
Scientists are now developing similar closed-loop DBS treatments for a range of neurological disorders.
“We see that it has a profound impact on patients, with potential not just in Parkinson’s but probably for psychiatric conditions like depression and obsessive-compulsive disorder as well,” Starr said. “We’re at the beginning of a new era of neurostimulation therapies.”
