Day: May 17, 2023

‘Errant’ Human DNA can be Found Everywhere, Posing an Ethical Dilemma

Source: Pixabay CC0

Researchers report in Nature Ecology and Evolution that human DNA traces can be found nearly everywhere, short of isolated islands and remote mountaintops. That ubiquity is both a scientific boon and an ethical dilemma, say the University of Florida researchers who sequenced this ‘errant’ DNA. The DNA was of such high quality that the scientists could identify mutations associated with disease and determine the genetic ancestry of nearby populations. They could even match genetic information to individual participants who had volunteered to have their errant DNA recovered.

David Duffy, the UF professor of wildlife disease genomics who led the project, says that ethically handled environmental DNA samples could benefit fields from medicine and environmental science to archaeology and criminal forensics. For example, researchers could track cancer mutations from wastewater or spot undiscovered archaeological sites by checking for hidden human DNA. Or detectives could identify suspects from the DNA floating in the air of a crime scene.

But this level of personal information must be handled extremely carefully. Now, scientists and regulators must grapple with the ethical dilemmas inherent in accidentally — or intentionally — sweeping up human genetic information, not from blood samples but from a scoop of sand, a vial of water or a person’s breath.

The paper by Duffy’s group outlines the relative ease of collecting human DNA nearly everywhere they looked.

“We’ve been consistently surprised throughout this project at how much human DNA we find and the quality of that DNA,” Duffy said. “In most cases the quality is almost equivalent to if you took a sample from a person.”

Because of the ability to potentially identify individuals, the researchers say that ethical guardrails are necessary for this kind of research. The study was conducted with approval from the institutional review board of UF, which ensures that ethical guidelines are adhered to during research studies.

“It’s standard in science to make these sequences publicly available. But that also means if you don’t screen out human information, anyone can come along and harvest this information,” Duffy said. “That raises issues around consent. Do you need to get consent to take those samples? Or institute some controls to remove human information?”

Duffy’s team at UF’s Whitney Laboratory for Marine Bioscience and Sea Turtle Hospital has successfully used environmental DNA, or eDNA, to study endangered sea turtles and the viral cancers they are susceptible to. They’ve plucked useful DNA out of turtle tracks in the sand, greatly accelerating their research program.

The scientists knew that human eDNA would end up in their turtle samples and probably many other places they looked. With modern genetic sequencing technology, it’s now straightforward to sequence the DNA of every organism in an environmental sample. The questions were how much human DNA there would be and whether it was intact enough to harbor useful information.

The team found quality human DNA in the ocean and rivers surrounding the Whitney Lab, both near town and far from human settlement, as well as in sand from isolated beaches. In a test facilitated by the National Park Service, the researchers traveled to part of a remote island never visited by people. It was free of human DNA, as expected. But they were able to retrieve DNA from voluntary participants’ footprints in the sand and could sequence parts of their genomes, with permission from the anonymous participants.

Duffy also tested the technique in his native Ireland. Tracing along a river that winds through town on its way to the ocean, Duffy found human DNA everywhere but the remote mountain stream where the river starts, far from civilization.

The scientists also collected room air samples from a veterinary hospital. They recovered DNA matching the staff, the animal patient and common animal viruses.

Now that it’s clear human eDNA can be readily sampled, Duffy says it’s time for policymakers and scientific communities to take issues around consent and privacy seriously and balance them against the possible benefits of studying this errant DNA.

“Any time we make a technological advance, there are beneficial things that the technology can be used for and concerning things that the technology can be used for. It’s no different here,” Duffy said. “These are issues we are trying to raise early so policy makers and society have time to develop regulations.”

Source: University of Florida

US to Trial Anti-radiation Pills That Could Protect Against Fallout from ‘Dirty Bombs’

The US National Institutes of Health is funding a new clinical trial of an oral anti-radiation treatment. So-called dirty bombs are nuclear weapons that release a cloud of radioactive isotopes, and are thought to be an attractive option for terrorists because they are far easier to build than true nuclear explosives.

In such a situation, as well as a nuclear accident, the danger is not so much from direct radiation in the form of X-rays, gamma rays and alpha and beta particles, but from radioactive materials which are absorbed into the body via contaminated air, food or water. Certain radioisotopes from radioactive fallout are readily absorbed by the body, and cause damage to DNA and cellular structures. Current treatment contain chemicals that bind to these radioisotopes, preventing them from being taken up by the body and instead rapidly excreted.

The Food and Drug Administration has approved two products for removing internal radioactive contamination. These drugs, both based on diethylenetriamine pentaacetate (DTPA), are administered intravenously by a healthcare provider and can remove three radioactive elements: plutonium, americium, and curium. 

In contrast, HOPO 14-1 is an oral capsule, which would be easier than an intravenous drug to stockpile and to deploy and administer during an emergency. Preclinical research has shown that HOPO 14-1 can effectively remove many radioactive contaminants, including uranium and neptunium in addition to plutonium, americium and curium. These studies also have found that HOPO 14-1 is up to 100 times more effective than DTPA at binding and removing these radioactive elements.

The trial will seek 42 healthy volunteers aged 18 to 65, who will of course not be exposed to radioactive fallout. They will be assigned into seven groups of six. Each participant in the first group will receive a 100-milligram (mg) dose of HOPO 14-1. The subsequent groups will receive increasingly higher doses of the study drug up to 7500 mg in the final group, if lower doses are deemed safe. Participants will undergo intensive safety monitoring and will be followed for 14 days to measure the absorption, distribution and elimination of the study drug. Results are expected in 2024.

Source: National Institutes of Health

Navigating the Maze of the Brain’s Glymphatic System

Photo by Robina Weermeijer on Unsplash

Like the lymphatic system in the body, the glymphatic system in the brain clears metabolic waste and distributes nutrients and other important compounds. Impairments in this system may contribute to brain diseases, such as neurodegenerative diseases and stroke.

A team of researchers has found a noninvasive and nonpharmaceutical method to influence glymphatic transport using focused ultrasound, opening the opportunity to use the method to further study brain diseases and brain function. Their findings are published in PNAS.

Hong Chen, associate professor of biomedical engineering in McKelvey Engineering and of neurological surgery in the School of Medicine, and her team, including Dezhuang (Summer) Ye, a postdoctoral research associate, and Si (Stacie) Chen, a former postdoctoral research associate, found the first direct evidence that focused ultrasound, combined with circulating microbubbles (FUSMB) could mechanically enhance glymphatic transport in the mouse brain.

Focused ultrasound can penetrate the scalp and skull to reach the brain and precisely target a defined region within the brain. Previously, Chen’s team found that microbubbles injected into the bloodstream amplify the effects of the ultrasound waves on the blood vessels and generate a pumping effect, which helps with the accumulation of intranasally delivered agents in the brain, such as drugs or gene therapy treatments.

“Intranasal delivery provides a novel, noninvasive route to investigate the glymphatic pathway in intact brains,” Chen said. “This route for investigating glymphatic transport has the potential to be utilised in the study of glymphatic function in humans, which is currently limited by the absence of noninvasive approaches to access the glymphatic system.”

In the new research, the team administered a fluorescently labelled tracer intranasally. Then they administered focused ultrasound waves aimed deep in the brain at the thalamus after intravenous injection of microbubbles. When they conducted 3D imaging of the brain tissue on the treated side, they found that FUSMB boosted the transport of the tracer in the perivascular space.

They compared this with three control groups with various combinations of focused ultrasound, microbubbles and the tracer. All of the mice in the three control groups showed lower tracer accumulation, which verified to the team that the enhanced tracer transport was the result of the focused ultrasound with microbubbles.

To further validate their results, they used the FUSMB treatment after injecting the tracer directly to the cerebral spinal fluid, an invasive yet commonly used method. They found that FUSMB also enhanced the transport of tracers along the vessels at the focused-ultrasound targeted brain site by about two- to threefold compared with the non-targeted side.

“Regardless of whether tracers were delivered via the intranasal or injected route, FUSMB consistently improved glymphatic transport,” Ye said. “Our study using confocal microscopy imaging combined with brain-tissue clearing obtained direct evidence that unequivocally proved that FUSMB enhanced the glymphatic transport of a labeled protein agent in mice.”

The team also investigated various types of vessels, including arterioles, capillaries and venules, that facilitate FUSMB-enhanced transport of the tracer using both intranasal and injected delivery of the tracer. They saw improved glymphatic transport of the tracer in both arterioles and capillaries with both types of delivery. They found that the fluorescence intensity was higher along arterioles than capillaries and venules.

“This study opens new opportunities to use ultrasound combined with microbubbles as a noninvasive and nonpharmacological approach to manipulate glymphatic transport,” Ye said. “Focused ultrasound-activated microbubbles have the promise to enhance waste clearance in the brain and potentially mitigate brain diseases caused by impairments in glymphatic system function.”

Chen said the team will now focus on applying this noninvasive and nonpharmacological method for brain waste clearance to potentially combat neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases.

Source: University of Washington in St. Louis

Study Finds Healthy Diet is Independently Linked to Fitness

Photo by Charlotte Karlsen on Unsplash

A healthy diet is associated with greater physical fitness in middle-aged adults, according to research published in the European Journal of Preventive Cardiology.

“This study provides some of the strongest and most rigorous data thus far to support the connection that better diets may lead to higher fitness,” said study author Dr Michael Mi of Beth Israel Deaconess Medical Center. “The improvement in fitness we observed in participants with better diets was similar to the effect of taking 4000 more steps each day.”

Cardiorespiratory fitness reflects the body’s ability to provide and use oxygen for exercise, and it integrates the health of multiple organ systems, such as the heart, lungs, blood vessels and muscles. It is one of the most powerful predictors of longevity and health. While exercise increases cardiorespiratory fitness, it is also the case that among people who exercise the same amount, there are differences in fitness, suggesting that additional factors contribute. A nutritious diet is associated with numerous health benefits, but it has been unclear whether it is also related to fitness.

This study examined whether a healthy diet is associated with physical fitness in community-dwelling adults. The study included 2380 individuals in the Framingham Heart Study. The average age was 54 years and 54% were women. Participants underwent a maximum effort cardiopulmonary exercise test on a cycle ergometer to measure peak VO2. This is the gold standard assessment of fitness and indicates the amount of oxygen used during the highest possible intensity exercise.

Participants also completed the Harvard semi-quantitative food frequency questionnaire to assess intake of 126 dietary items during the last year ranging from never or less than once per month to six or more servings per day. The information was used to rate diet quality using the Alternative Healthy Eating Index (AHEI; 0 to 110) and Mediterranean-style Diet Score (MDS; 0 to 25), which are both associated with heart health. Higher scores indicated a better quality diet emphasising vegetables, fruits, whole grains, nuts, legumes, fish and healthy fats and limiting red meat and alcohol.

The researchers evaluated the association between diet quality and fitness after controlling for other factors that could influence the relationship, including age, sex, total daily energy intake, body mass index, smoking status, cholesterol levels, blood pressure, diabetes and routine physical activity level. The average AHEI and MDS were 66.7 and 12.4, respectively. Compared with the average score, an increase of 13 points on the AHEI and 4.7 on the MDS was associated with a 5.2% and 4.5% greater peak VO2, respectively.

Dr Mi said: “In middle-aged adults, healthy dietary patterns were strongly and favourably associated with fitness even after taking habitual activity levels into account. The relationship was similar in women and men, and more pronounced in those under 54 years of age compared to older adults.”

To discover the potential mechanism linking diet and fitness, the researchers performed further analyses. They examined the relationship between diet quality, fitness and metabolites, which are substances produced during digestion and released into the blood during exercise. Researchers measured 201 metabolites (eg amino acids) in blood samples collected in a subset of 1154 study participants. Some 24 metabolites were associated with either poor diet and fitness, or with favourable diet and fitness, after adjusting for the same factors considered in the previous analyses. Dr Mi said: “Our metabolite data suggest that eating healthily is associated with better metabolic health, which could be one possible way that it leads to improved fitness and ability to exercise.”

“This was an observational study and we cannot conclude that eating well causes better fitness, or exclude the possibility of a reverse relationship, i.e. that fit individuals choose to eat healthily.”

Dr Mi concluded: “There are already many compelling health reasons to consume a high-quality diet, and we provide yet another one with its association with fitness. A Mediterranean-style diet with fresh, whole foods and minimal processed foods, red meat and alcohol is a great place to start.”

Source: European Society of Cardiology

Loadshedding Hits Clinic Waiting Times

Photo by Jarl Schmidt on Unsplash

By Peter Luhanga for GroundUp

Loadshedding is affecting waiting times at the Dunoon Community Health Centre in Cape Town, with patients saying they queue for hours and are still sent home without their medication.

Dunoon resident Mavis Matomane, 54, said she woke up early on Thursday 11 May to be at the clinic in time for an appointment made five months ago.

When she arrived at 7am, she joined a long queue standing outside in the rain. Matomane needs medication for arthritis and high blood pressure. She said the clinic was serving people who had arrived the day before but had not been seen to and had been told to return on 11 May.

She was seen by nurses for diagnosis after 11am and only left the hospital with her medication at 3pm.

Neliswa Bobotyana, who lives in Ibaleni informal settlement in the township, said she accompanied her boyfriend to the Dunoon centre on Monday 8 May. He was seen by a doctor and told to wait to get X-rays, but the X-ray facility closed while he was still waiting. On Tuesday his condition had deteriorated and she took him back to the health centre where he was told to open a new folder. He was sent back home and returned on Wednesday 10 May and was taken to the New Somerset Hospital where he was finally given medication.

Other residents have complained on a neighbourhood online group.

Western Cape Department of Health spokesperson Natalie Watlington said as a result of loadshedding and problems with the data centre in George, pharmacy applications for patient medication were offline on 10 May.

“Our pharmacist therefore requested patients to return the next day for their medication. We acknowledge that at times loadshedding may affect our phone lines and IT systems. It may take more time to draw your folder or process your details as a patient,” said Watlington.

She said on average 150 adults and 180 children arrived without appointments every day. This was on top of about 120 clinician appointments and 100 family planning appointments per day.

She said there were problems when patients who did not arrive on their appointment day arrived as walk-in patients on other days. There were an average of 80 missed appointments a day, Watlington said.

Watlington said patients sticking to appointment times did not need to arrive early. Waiting times differed according to the nature of the complaint and the treatment.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

New WHO Guideline Advises Against Non-sugar Sweeteners for Weight Management

The World Health Organization (WHO) has released a new guideline on non-sugar sweeteners (NSS), which recommends against using NSS to control body weight or reduce the risk of noncommunicable diseases (NCDs).

This comes as WHO conducts its first review of obesity management guideline in more than two decades. Last week, Francesco Branca, WHO director of nutrition and food safety, had also warned that weight-loss drugs such as Wegovy are “not a silver bullet” in tackling obesity.

The recommendation is based on the findings of a systematic review of the available evidence which suggests that use of NSS does not confer any long-term benefit in reducing body fat in adults or children. Results of the review also suggest that there may be potential undesirable effects from long-term use of NSS, such as an increased risk of type 2 diabetes, cardiovascular diseases, and mortality in adults.

“Replacing free sugars with NSS does not help with weight control in the long term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” says Francesco Branca, WHO Director for Nutrition and Food Safety. “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.”

The recommendation applies to all people except individuals with pre-existing diabetes and includes all synthetic and naturally occurring or modified non-nutritive sweeteners that are not classified as sugars found in manufactured foods and beverages, or sold on their own to be added to foods and beverages by consumers. Common NSS include acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, sucralose, stevia and stevia derivatives.

The recommendation does not apply to personal care and hygiene products containing NSS, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols), which are sugars or sugar derivatives containing calories and are therefore not considered NSS.

Because the link observed in the evidence between NSS and disease outcomes might be confounded by baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as conditional, following WHO processes for developing guidelines. This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups.

The WHO guideline on NSS is part of a suite of existing and forthcoming guidelines on healthy diets that aim to establish lifelong healthy eating habits, improve dietary quality and decrease the risk of NCDs worldwide.

Source: WHO