Typically developing infants perceive audio-video synchrony better than high-risk for autism infants, according to new research published in the European Journal of Pediatrics. The research from Rutgers University might enable far earlier autism diagnoses.
If follow-up research demonstrates that most infants who miss unmatched audio and video develop autism spectrum disorder (ASD), physicians may be able to diagnose the condition years earlier – a potentially important step as early treatment strongly predicts better outcomes.
“We’re a long way from validating this as a diagnostic tool, but the results definitely suggest it could be a diagnostic tool,” said senior author Michael Lewis, professor at Rutgers Robert Wood Johnson Medical School.
Lewis and other researchers have long known children with ASD struggle to perceive audio-visual speech as a unified event, and they’ve hypothesised that this difficulty may contribute to social impairments and language deficits in such children.
To study whether these difficulties arise before it’s currently possible to diagnose ASD, generally around age 3, the researchers assembled two groups of infants ages 4 to 24 months, one comprising children whose developmental delays indicate an elevated risk of ASD and the other comprising typically developing children.
The researchers showed that participants from both groups two types of videos with progressively longer time separation between image and sound. The first videos featured a ball making noises as it bounced against a wall. The second showed a woman talking.
When watching videos of the ball, the two groups performed similarly. When watching videos of the woman, however, the differences were stark. Typically, developing children perceive audio-visual gaps that are, on average, a tenth of a second smaller than those perceived by the kids with developmental delays.
Although this result confirmed the researchers’ initial hypothesis, some findings were surprising. The ability to perceive audio-visual mismatch wasn’t associated with vocabulary size in children old enough to have a vocabulary.
If a high percentage of the children who were slowest to identify mismatched audio and video go on to be diagnosed with autism – and the findings are repeated with far more children than the 88 who participated in this study – audio-visual tests might prove a revolutionary diagnostic tool for a condition that’s becoming far more common, Lewis said.
However, scientific validation is just the first step to adoption, he said. Insurers would need to pay for tests, and paediatricians would need to embrace them before they could be used to begin providing support services to children in need.
“Earlier diagnosis won’t allow us to cure ASD anytime soon, but it will allow for the earlier provision of support services that can help such children in areas of weakness and direct them toward areas of strength,” Lewis said. “The goal is to create happy people whose schooling and, eventually, careers are well suited to them, and that’s certainly an achievable goal for most.”
In research published in the Journal of the American Geriatrics Society, investigators developed and validated models that can predict the risk of fall-related injuries (FRI) in nursing home residents based on routinely collected clinical data.
The researchers conducted retrospective cohort study of long-stay US nursing home residents (mean age 85 years, 69.6% female) between January 1, 2016 and December 31, 2017 (n = 733 427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through statistical methods, from an original set of 70 predictors. To come up with a useful clinical tool, they calculated a score using the five strongest predictors in the model.
Within 2 years of follow-up, 6% of residents experienced one or more FRI. The prediction models achieved good discrimination and excellent calibration for accurately estimating individuals’ six-month and two-year risk of fall-related injuries. In the clinical tool to predict 2-year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14–2.41) and a history of non-hip fracture (HR 2.02; 95% CI 1.94–2.12). Performance results were similar in the validation sample.
“These models can be used by researchers and clinicians to accurately determine patient risk for fall-related injuries using routinely collected clinical assessment data,” the authors wrote. “In nursing homes, these models should be used to target preventive strategies.”
By Vincent Lali, Chris Gilili, Liezl Human, Tariro Washinyira, Nombulelo Damba-Hendrik, Thamsanqa Mbovane, and Mkhuseli Sizani
“You have shown the power of the people by closing all the hospitals,” National Education Health and Allied Workers’ Union (NEHAWU) Western Cape provincial secretary Baxolise Mali told striking union members on Wednesday. “The employer says people are dying. It is not our responsibility to keep people’s lives.”
Mali was speaking to strikers outside the Khayelitsha District Hospital in Cape Town, as NEHAWU members continued a wage strike which has disrupted hospitals and government offices across the country. The government considers the wage negotiations for 2022 to be settled but NEHAWU and several other unions are still demanding up to 12%.
Police presence outside the hospital had kept protesters away, said hospital CEO David Binza. He said the situation was “better than yesterday”, when “things were bad”.
Binza said services at the hospital had been severely affected by the strike on Monday.
Protesters had prevented people coming in and out of the hospital. Staff had ended up working 24 hours because there were not enough nurses to relieve them, and there was a shortage of nurses in childbirth wards. “Yesterday they prevented night staff from gaining access into the facility. It was mostly doctors that they allowed in. Doctors alone can’t work properly,” he said.
Today things had been better, he said, as the police had arrived early and kept protesters away from the hospital.
Western Cape health spokesperson Mark van der Heever said shift changes at the hospital were being closely monitored after patients in critical condition had to be transferred to other hospitals such as Helderberg, Tygerberg, Mitchells Plain and Karl Bremer.
Striking workers outside Khayelitsha District Hospital on Wednesday. Photo: Vincent Lali
“On Tuesday night, 7 March, protesters disrupted services and blocked staff from entering Khayelitsha District Hospital until 11pm. The ongoing disruption has directly resulted in staff shortages as they are prevented from entering, backlogs building up and other operational challenges.”
He said protests had been reported at Karl Bremer and Tygerberg hospitals, but services had not been disrupted.
Mali said NEHAWU’s intention was to “collapse the provision of government services” to force the government to the negotiating table. “Our tactics involve closing workplaces, to force workers to get out and switch off their computers.”
Home Affairs offices in Khayelitsha were closed. Disappointed, Luthando Tiso said he has been going to Khayelitsha Home Affairs to collect his ID since Monday. “I can’t get a job without an ID,” he said.
In the city centre, the Home Affairs office in Barrack Street and the offices of the Department of Labour were closed and there was a strong police presence.
One man said he had been to the Mitchells Plain Labour Department offices on Monday and Tuesday only to find them closed because of the strike, and had come to Cape Town hoping for help. “I desperately need to claim from the Unemployment Insurance Fund. I lost my job in January. My rent and children’s school fees are already behind,” he said.
Eastern Cape
In the Eastern Cape, Department of Health spokesperson Yonela Dekeda said hospitals were being run by skeleton staff.
“We had an incident early in the morning where striking workers blocked the Cecilia Makiwane Hospital’s entrance in East London. But police were called to remove them.”
Dekeda said unions which were not supporting the strike action had raised concerns that their members were being intimidated and denied access to workplaces.
“We do appreciate responsible shop stewards who have called their members to order, where necessary, and ensured that critical services continue and that our patients receive necessary care,” she said. “However, we take very seriously those employees who intimidate others, and cause services to be affected negatively.
“Appropriate action will be taken in all such instances, and law enforcement agencies are being deployed.”
At Laetitia Bam Day Hospital in KwaNobuhle, Kariega, Eastern Cape deputy secretary of NEHAWU, Busiswa Stokwe told about 100 striking workers: “We know we will be attacked even in the community, accused of not caring for patients. But the same community when you are doing the work of ten people, whilst you are four, would insult you, saying you are lazy. We must put ourselves first.”
A patient who did not want to give his name said he had arrived at 5am to have three teeth removed but had been ordered out by striking workers at 7am. “They came by car and on foot and sang in the corridors. We realized that we should go back home, with aching teeth.”
“We were about ten and have no money to remove teeth at a private doctor, who charges R350 per tooth,” he said.
Gauteng
In Tshwane, striking workers closed down the offices of the Department of Public Service and Administration, shouting and insulting some workers who were inside the offices.
There was a stand-off between the striking workers and police, as the workers closed off Hamilton and Edmond Streets with huge stones and turned cars away. Police moved the workers away.
Phumuzo Malahleni, a registry clerk at the Department of Agriculture, said his R12,000-a-month salary was too low to cope with the soaring cost of living. “As public servants we can’t afford anything. Violence and going to the streets is the only language our government understands.”
NEHAWU Gauteng provincial chairperson Mzikayise Tshontshi told GroundUp that the battle for a wage increase was far from over.
He said NEHAWU had been called to the Public Sector Bargaining Council on Thursday. “Our negotiators will be there, but the rest of us will continue shutting down public services.
“We believe our strike has been resoundingly successful. From Monday to today, the numbers have been growing. Tomorrow we want to intensify the strike,” said Tshontshi.
Addressing the crowd outside the department, Tshontshi called out those who were still at work.
“We are also aware of ‘amagundwane’ (rats). Some are sitting in cosy offices, and then when we win this battle they are going to be first in the queue because they think they deserve what we have fought for. There have always been traitors in every struggle; this is no different.”
At Tembisa hospital, striking workers blocked the entrance with burning tyres and debris while chanting slogans. Calm was later restored.
Free State
Free State health spokesperson Mondli Mvambi said the province had obtained an interdict on Wednesday morning to prevent strikers from disrupting services at hospitals and clinics. “The order does not stop the strike but stops acts of intimidation, violence, disruptions and instigating.”
Mvambi said hospitals hardest hit were National District Hospital, Universitas, Pelonomi and Medical Depot in Bloemfontein. “There were no nurses at work and patient care was seriously compromised.” Mvambi said calm had been restored but services remained strained as nurses were still not at work.
“At Manapo in QwaQwa they are not allowing nurses into the hospital. At Boitumelo in Kroonstad, picketers were singing at the gate but services are said to be continuing. At Pelonomi Hospital, nurses in ICU were forced out by the strikers.”
North West
In the North West, services at least six hospitals were disrupted by the strike: Klerksdorp-Tshepong, Potchefstroom, Taung District, Moses Kotane, Ganyesa District, and Gelukspan. There were pickets outside several other clinics and hospitals.
Mpumalanga
In Mpumalanga, spokesperson Christopher Nobela said that all health facilities had been affected and hospitals were working with skeleton staff in hospitals.
Limpopo
Limpopo health spokesperson Neil Shikwambana said, “We do not have reports of disruptions in any of our facilities so far.”
KwaZulu-Natal
Workers stopped work at Inkosi Albert Luthuli Central Hospital in Durban for several hours on Wednesday morning, singing outside the hospital. Patients were allowed to enter.
NEHAWU branch secretary Sikhumbuzo Gumbi said workers decided to go back to work at midday so they could assist patients. “As workers we decided to protest in the morning then attend to patients around lunchtime.”
Gumbi said the staff would continue protesting in the mornings until the strike ends.
Prince Mthalane, Durban NEHAWU regional secretary, said clinics had been closed in KwaMashu and at Polyclinic workers had burned tyres. Police had been called but workers had talked to them and no-one had been arrested.
“The aim is to have a peaceful strike,” he said.
GroundUp was unable to reach the health department spokespersons in KwaZulu-Natal or the Northern Cape.
Police
“Innocent patients have been caught in the crossfire and inconvenienced by something which has nothing to do with them,” said Department of Health national spokesperson Foster Mohale. He said the Minister of Health had asked the Minister of Police to strengthen the police presence in areas affected by the strike.
“Skeleton staff has also been available to give care to patients who could not be discharged,” said Mohale.
South African Police Union spokesperson Lesiba Thobakgale said the union had joined NEHAWU in the protest. “As SAPU, from today we have served a strike notice and we are joining the other unions,” said Thobakgale.
A common method of detecting prostate cancer may not be accurate enough as a reliable screening tool by itself, scientists in Germany have warned. The digital rectal exam (DRE) is widely used by medical professionals to check the prostate gland with a finger for unusual swelling or lumps in the rectum as an initial check for the signs of prostate cancer in men.
But new research by scientists of the PROBASE trial coordinated at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, suggests the technique may be missing many cancers in their early stages.
The findings, presented at the European Association of Urology Annual Congress in Milan, could have implications for the early detection of prostate cancer, say the researchers. They are calling for other testing methods to be used in routine screening instead.
“One of the main reasons for screening for prostate cancer is to detect it in patients as early as possible as this can lead to better outcomes from treatment,” said Dr Agne Krilaviciute, a researcher at DKFZ and lead author of the study. “But our study suggests that the DRE is simply not sensitive enough to detect those early stage cancers.”
The PROBASE trial is a multicentre German prostate cancer screening study involving 46 495 men aged 45 years who were enrolled between 2014 and 2019. The men have since been had follow ups to assess their health in the years after the screening. Half of the participants in the trial were offered prostate specific antigen (PSA) blood test immediately at age 45 while the other half were initially offered DRE with delayed PSA screening at age 50.
Ultimately, 6537 men in the delayed screening group underwent DRE and only 57 of these men were referred for a follow-up biopsy due to suspicious findings. Only three were found to have cancer.
When compared to the detection rate using other methods, such as a PSA test, the rate of detection using DRE was substantially lower, says Dr Krilaviciute.
“The DRE was giving a negative result in 99% of cases and even those that were deemed to be suspicious had a low detection rate,” says Dr Krilaviciute. “Results we’ve seen from the PROBASE trial show that PSA testing at the age of 45 detected four times more prostate cancers.”
The researchers believe one of the reasons why the DRE might be failing to detect cancers, particularly in younger men, is because the changes in the tissue in the prostate may be too slight to detect with a finger. In addition, some cancers occur in a part of the prostate that cannot be easily reached by a finger.
“Early stage cancer may not have the size and stiffness to be palpable,” said Professor Peter Albers, a urologist at Düsseldorf University who was the senior author of the study.
“Separate analysis that used MRI scans before biopsies to locate cancers in the prostate showed that about 80% of these are in an area that should be easy to reach with a finger and still cancers were not detectable by DRE.”
The researchers are now calling for widespread use of PSA testing and MRI scans as part of screening programmes instead of DRE.
“If the aim of a screening programme is to pick up cancers as early as possible and the current screening tool isn’t doing that job, then that is a fundamental failure of that approach,” said Professor Albers. “We speculate in our paper that not only is the DRE not useful for detecting cancer, but it may also be one reason why people don’t come to screening visits – the examination probably puts a lot of men off.
“In Germany, for example, the participation rate is less than 20% in the screening programme for men 45 to 50 years. If we were to offer PSA testing instead, more of them might be willing to come.”
Striking members of the National Education, Health and Allied Workers Union (NEHAWU) blocked the department of Home Affairs offices in Cape Town on Tuesday. Photo: Thomas Kachere
Patients were turned away from some hospitals as members of the National Education, Health and Allied Workers Union (NEHAWU) and other unions pressed forward with their wage strike, in spite of a court interdict.
Many government offices were closed for several hours.
NEHAWU has approached the Labour Appeal Court to appeal against a decision to enforce the interdict against the strike granted by the Labour Court to the Department of Public Service and Administration.
In Cape Town, police intervened after a scuffle broke out after a member of the public who was queuing for service at the Department of Home Affairs office in Cape Town called protesters names.
The police warned the protesters not to engage in any violence.
Provincial General Secretary of NEHAWU, Baxolise Mali said, “Today we have escalated matters”. He said hospitals including Khayelitsha Day Hospital and Somerset Hospital had closed, and the offices of Home Affairs and Labour were closed. “SASSA offices will close soon for social grants,” he said.
NEHAWU served the department with a notice to strike on 24 February after wage negotiations deadlocked. The department offered a 4.7% increase while unions demanded between 10% and 12%.
Ronald Ruiters had queued at the Home Affairs office in Cape Town for hours for a temporary ID, without getting help, he said. “Yesterday I was here at 4:30am. I am an old man. What about people who are suffering now including sick people in hospitals? There should be a better way of dealing with these issues.”
“Since morning the police were here but they could not control the protesters, nothing is working here.”
Mali said workers were angry at a statement by acting Public Service Minister Thulas Nxesi who had described the strike as reckless.
“The acting minister called people reckless and said they need to go back to work … go back to work on what basis? Come with an offer: we are willing to negotiate.”
“It is reckless for the government to impose salaries on people. It is reckless for the government to expect the people who have been praised during the time of Covid for having to work hard in very difficult conditions to serve our people to get peanuts.”
“The ‘no work no pay’ principle is not a new thing. Let them deduct the money, we are used to poverty. “
Mali said members of the public did not understand. “They stand in long queues because the government is refusing to employ more people to work for Home Affairs, [Department of] Labour and SASSA. Instead they increase the cabinet. Too many deputy ministers and what work do they have to do?”
“What needs to be done is to create employment so that people get served quickly. That is all we are fighting for. We are not going to compromise.”
In Pretoria, striking workers occupied the Department of Labour Head office, singing and shouting at workers inside to come out. They also closed entrances to the offices of the Department of Higher Education and Training, and disrupted traffic on Francis Baard Street.
A striking cleaner at the Department of Labour, Boitumelo Motaung said she earns R6000 a month and supports a family of four people. She says she spends about R1000 on transport from Ga-Rankuwa to Pretoria for work.
“We are suffocating, and we are earning peanuts. I have three kids that are attending school and their father is unemployed. I am taking care of everything and a few days after payday, I am left without a penny and survive off loan sharks. We need government to recognise our value as people. Sometimes I am forced to do the work of three people where I work because they are not employing enough cleaning staff. That is why I am supporting this NEHAWU strike,” said Motaung.
Motaung said she has been working as a cleaner for seven years.
In a statement, DPSA director general Yoliswa Makhasi said work stoppages and pickets by NEHAWU and its members would be contempt of court.
“We will strike until our demands are met”
NEHAWU deputy secretary-general December Mavuso
Spokesperson for the department Moses Mushi said the minister had called on unions to return to the negotiating table.
NEHAWU deputy secretary-general December Mavuso said the strike had expanded. He said the union’s lawyers and government lawyers were in discussion about an appeal to the Labour Appeal Court. “We don’t know when an outcome will be available . In the meantime, our workers are on the picket lines,” said Mavuso. “We will strike until our demands are met”.
Department of Health spokesperson Foster Mohale said the department was working with provincial health authorities and law enforcement agencies to monitor the situation to ensure rapid response and if necessary urgent intervention.
In Fort Beaufort in the Eastern Cape, community health care workers were ordered to stop their services at clinics and hospitals. Striking NEHAWU members blocked the entrance of the Fort Beaufort Provincial Hospital and turned away patients. Top management was allowed to enter but other staff were locked outside the gates.
NEHAWU also shut down several government offices in the Eastern Cape.
Mphakamisi Shooter, regional NEHAWU treasurer, told GroundUp the union had used its resources to put President Cyril Ramaphosa in power. “But now he is failing to give us what we deserve.”
“We have over 5,000 members in this region. Today we made sure that we shut down all government departments in this region until Ramaphosa gives us a decent wage.”
MEC for Health Nomakhosazana Meth condemned the unprotected strike. “We understand that workers have a right to demonstrate but when they do they cannot infringe on the rights of others. We cannot afford to have a situation where the lives of patients and staff not on strike are in danger as a result of the action of those who have embarked on this action.”
She said there were reports of disruptions and acts of intimidation in some areas.
In Makhanda, clinics were closed as were the offices of the departments of Home Affairs, Labour, and Social Development by a group of about 80 protesters.
Madoda Toni, who was part of the protest, said the government cannot continue to pay workers low salaries while prices of food and other items were rising so fast. “We need permanent jobs, decent wage increases, and contract workers should be absorbed to be full time government employees and paid decent salaries,” said Toni.
In Qonce (King Williams Town) it was also reported that SASSA and Home Affairs offices were closed down by the protesters.
In Durban, patients were prevented from entering Prince Mshiyeni Memorial Hospital by NEHAWU members. The protest started about 6am and ended just before lunchtime when workers dispersed and returned to work. By 1pm, everything was back to normal.
Researchers have found that a simple injection of hormone called fibroblast growth factor 21 (FGF21) protects mice against ethanol-induced loss of balance and righting reflex, effectively sobering them up.
“We’ve discovered that the liver is not only involved in metabolising alcohol but that it also sends a hormonal signal to the brain to protect against the harmful effects of intoxication, including both loss of consciousness and coordination,” says co-senior study author Steven Kliewer of the University of Texas Southwestern Medical Center, regarding the study results published in the journal Cell Metabolism.
“We’ve further shown that by increasing FGF21 concentrations even higher by injection, we can dramatically accelerate recovery from intoxication. FGF21 does this by activating a very specific part of the brain that controls alertness,” says Kliewer.
The consumption of ethanol produced by the natural fermentation of simple sugars in ripening fruits and nectars can cause intoxication, impairing mobility and judgement. Animals that consume fructose and other simple sugars have evolved liver enzymes to break down ethanol.
FGF21 is a hormone that is induced in the liver by a variety of metabolic stresses, including starvation, protein deficiency, simple sugars, and ethanol. In humans, ethanol is by far the most potent inducer of FGF21 described to date. Previous studies showed that FGF21 suppresses ethanol preference, induces water drinking to prevent dehydration, and protects against alcohol-induced liver injury.
In the new study, Kliewer and co-senior study author David Mangelsdorf of the University of Texas Southwestern Medical Center show that FGF21 plays a broader role in defending against the harmful consequences of ethanol exposure than previously thought. In mice, FGF21 stimulated arousal from intoxication without changing the breakdown of ethanol. Mice lacking FGF21 took longer than their littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduced the time needed for mice to recover from ethanol-induced unconsciousness and lack of muscle coordination.
Surprisingly, FGF21 did not counteract sedation caused by ketamine, diazepam, or pentobarbital, indicating specificity for ethanol. FGF21 mediated its anti-intoxicant effects by directly activating noradrenergic neurons in the locus coeruleus region in the brain, which regulates arousal and alertness. Taken together, the results suggest that the FGF21 liver-brain pathway evolved to protect against ethanol-induced intoxication. According to the authors, this pathway may modulate a variety of cognitive and emotional functions to enhance survival under stressful conditions.
Whether activation of the noradrenergic system contributes to FGF21’s other effects is yet to be determined. Although both FGF21 and noradrenergic nervous system activity are induced by ethanol in humans, additional studies will also be required to determine whether FGF21’s anti-intoxicant activity translates to humans.
“Our studies reveal that the brain is the major site of action for FGF21’s effects,” Mangelsdorf says. “We are now exploring in greater depth the neuronal pathways by which FGF21 exerts its sobering effect.”
A study published in the Journal of Orthopaedic Research has identified a bone matrix protein called Secreted phosphoprotein 24 kD (Spp24) that may help to treat osteosarcoma, the most common type of bone cancer.
In experiments conducted in cells and mice, investigators found that Spp24 inhibits the proliferation and invasiveness of osteosarcoma tumour cells and promotes their apoptosis, or death. Mechanistically, Spp24 binds to and neutralises a protein called bone morphogenetic protein 2, which has tumour-enhancing properties.
“Spp24 and its proteolytic products have a number of effects on bone metabolism that have been elucidated to various degrees. They have the potential to be engineered into bone therapeutics, and this anti-tumour effect through bone morphogenetic protein 2 sequestration is only one such example,” said co–corresponding author Haijun Tian, MD, PhD, of Shanghai Jiao Tong University School of Medicine. “Like many other bone matrix proteins, the more we look into the function of Spp24, the more surprising roles we find even though the primary function of Spp24 remains uncertain.”
A new study from Copenhagen University may have found a new treatment for the sickest patients with sarcomas. Sarcomas are cancer tumours found in bones, muscles or fatty tissue. Sarcomas are cancer tumours found in bones, muscles or fatty tissue. Complex and difficult to treat, it is a rare type of cancer seen in only one per cent of cancer patients.
Researchers noticed that people with certain rare disorders were both more likely to have early grey hairs and wrinkles as well as having a high risk of developing cancer.
“We have learned that sarcoma patients whose cancer cells have a high expression of the cep135 protein are worse off. But inhibiting a gene called plk1 also inhibits growth of the sarcoma cells, and this suggests that we can target the treatment of the sickest sarcoma patients,” says Associate Professor Morten Scheibye-Knudsen, lead researcher of the new study which is published in Nature.
Methods for identifying sarcoma patients’ prognoses are already available, as are different forms of treatment. But the new study has identified a new method.
“This is a new way of stratifying and possibly a new and better way of treating sarcoma. And the introduction of yet another method is always good news to patients. Because no two cancers are alike. Ideally, treatment should always be tailored to the individual patient,” Morten Scheibye-Knudsen stresses.
He hopes other researchers with access to the necessary test facilities will study his results in more detail and eventually design a new treatment. If the method turns out to work, he believes a new treatment may be available to patients in five to 10 years.
Grey hair, wrinkles and loss of fatty tissue at an early age
Morten Scheibye-Knudsen and his colleagues started out by studying patients suffering from the rare neurological disorders Werner’s syndrome, Nijmegen breakage syndrome and Ataxia-telangiectasia syndrome.
These patients experience symptoms of early ageing such as grey hair, wrinkles and loss of fatty tissue – and they have a high risk of developing cancer at an early age.
“Age-associated diseases such as cancer is one of my main areas of interest as a researcher at the Center for Healthy Aging. As we grow older, a lot of things happen to the body, and determining causality can be difficult. But in people suffering from, eg Werner’s syndrome, it is easier to see which genes are responsible for which processes. This gives us a molecular handle, so to speak,” says Morten Scheibye-Knudsen.
In order to establish why these patients develop cancer at an early age, the researchers compared gene expressions across the three disorders. Here they worked together with the company Insilico Medicine, whose large Pandaomics platform made it possible to identify gene mutations in thousands of different disorders. It turned out that cep135 is a common denominator for the cancer genes of the three disorders.
“This made us study the gene expressions of various cancers, and we learned that cep135 is associated with high mortality in, inter alia, sarcoma, but also in bladder cancer. Sarcoma was particularly interesting, as many Werner’s syndrome patients develop sarcoma,” explains Morten Scheibye-Knudsen.
Finally, the researchers sought to find ways to inhibit the sarcoma. Cep135 is not a useful target, as it is a so-called structural protein, which are difficult to target. Instead, the researchers learned that by inhibiting the plk1 gene they were able to target the sarcoma.
“The study indicates that we can use genetic diseases that exhibit accelerated aging to identify new treatment targets. In this study, we investigated cancer, but the method can in principle be used for all age-related diseases such as dementia, cardiovascular diseases and others,” says Morten Scheibye-Knudsen.
Researchers in Sweden have performed a nation-wide study of patients who underwent bioprosthetic aortic valve replacement between 2003 and 2018. The study, published in the Journal of the American College of Cardiology, shows that it is less dangerous than previously believed to receive a small bioprosthetic aortic valve in relation to the patients size.
During surgical aortic valve replacement, the patient receives a valve prosthesis that matches the size of the aortic root. Sometimes, that size is too small in relation to the patient’s body size. This puts strain on the heart to pump enough blood that the body needs through a narrow valve. The level of “narrowness” is measured as Prosthesis Patient Mismatch, PPM.
“Prior studies have shown that both moderate and severe PPM decreases survival and increases the risk for heart failure. In our study, we can confirm that severe PPM decreases survival and increases the risk for heart failure, while moderate PPM has a very limited effect on survival and no effect on the risk for heart failure”, says Michael Dismorr, postdoctoral researcher at the Department of Molecular Medicine and Surgery and first author of the study.
The study
The study included all patients who underwent bioprosthetic aortic valve replacement in Sweden between 2003 and 2018. Patients were identified from the Swedish cardiac surgery register, part of the SWEDEHEART register. The database was enriched with data from other national health data registers. By using the statistical method regression standardization we were able to estimate the risk for the outcomes death, heart failure and reintervention in absolute terms between the groups no, moderate and severe PPM.
The study shows that the estimated risk difference between no and moderate PPM for death after 10 years of follow-up was -1.7% (-3.3% to -0.1%) compared to -4.6% (-8.5% to -0.7%) for severe PPM.
The risk difference for heart failure after 10 years of follow-up was -1.1% (-2.5% to 0.2%) between patients with no and moderate PPM.
“A risk difference of a single percent after 10 years of follow-up cannot be said to be of clinical significance, even if it is statistically so. However, it is important to note that these are hard clinical outcomes. We did not have access to “soft” outcomes such as quality of life, which might be decreased in patients with moderate PPM, and in that case of course of great importance to those patients”, says Michael Dismorr.
Next steps
“Now we want to study the effect of PPM in patients who underwent transcatheter aortic valve replacement, a so called TAVR procedure. This is important knowledge when deciding which patients will benefit the most from a surgical replacement, and which patients will benefit the most from a transcatheter replacement”, says Michael Dismorr.
Adding to the growing body of evidence on sleep disturbances and cognitive impairment, new research published in the American Journal of Preventive Medicine, finds significant links between three measures of sleep disturbance and the risk for developing dementia over a 10-year period. Difficulties falling asleep were linked to higher risk, but not falling asleep again after waking.
The results associate sleep-initiation insomnia (trouble falling asleep within 30 min) and sleep medication use with higher dementia risk. An additional, surprising finding was that people who reported having sleep-maintenance insomnia (trouble falling back to sleep after waking) were less likely to develop dementia over the course of the study.
“We expected sleep-initiation insomnia and sleep medication usage to increase dementia risk, but we were surprised to find sleep-maintenance insomnia decreased dementia risk,” explained lead investigator Roger Wong, PhD, MPH, MSW, an Assistant Professor in the Department of Public Health and Preventive Medicine, SUNY Upstate Medical University. “The motivation behind this research was prompted on a personal level. My father has been experiencing chronic sleep disturbances since the COVID pandemic began, and I was concerned how this would affect his cognition in the future. After reading the existing literature, I was surprised to see mixed findings on the sleep-dementia relationship, so I decided to investigate this topic.”
This research is novel because it is the first to examine how long-term sleep disturbance measures are associated with dementia risk using a nationally representative US older adult sample. Previous research has associated REM sleep behavior, sleep deprivation (less than five hours of sleep), and the use of short-acting benzodiazepines with cognitive decline. Their results for sleep-maintenance insomnia support other recent studies using smaller, separate data samples.
This study used 10 annual waves (2011–2020) of prospective data from the National Health and Aging Trends Study (NHATS), a longitudinal panel study that surveys a nationally representative sample of Medicare beneficiaries aged 65 years and older within the USA. This study included only people who were dementia-free at baseline in 2011.
While the mechanism for decreased dementia risk among those with sleep-maintenance insomnia is still unknown, the investigators theorise that greater engagement in activities that preserve or increase cognitive reserve may thereby decrease dementia risk.
Recent evidence indicates there is a higher prevalence of sleep disturbances among older adults than among other age groups. This could be attributed to a variety of factors including anxiety about the COVID pandemic or warmer nights as a consequence of climate change.
“Older adults are losing sleep over a wide variety of concerns. More research is needed to better understand its causes and manifestations and limit the long-term consequences,” added Dr Wong. “Our findings highlight the importance of considering sleep disturbance history when assessing the dementia risk profile for older adults. Future research is needed to examine other sleep disturbance measures using a national longitudinal sample, whether these sleep-dementia findings hold true for specific dementia subtypes, and how certain sociodemographic characteristics may interact with sleep disturbances to influence dementia risk.”
