Scientistshave made an important breakthrough in understanding failures during the progression of inflammatory diseases and in doing so unearthed a potential new therapeutic target. The scientists report in Nature that an enzyme called Fumarate Hydratase is repressed in macrophages. These immune cells are already implicated in a range of diseases including Lupus, arthritis, sepsis and COVID.
Lead author Luke O’Neill, Professor of Biochemistry at Trinity said: “No-one has made a link from Fumarate Hydratase to inflammatory macrophages before and we feel that this process might be targetable to treat debilitating diseases like Lupus, which is a nasty autoimmune disease that damages several parts of the body including the skin, kidneys and joints.”
Joint first-author Christian Peace added: “We have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases. We found that when Fumarate Hydratase is repressed, RNA is released from mitochondria which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation. This process could potentially be targeted therapeutically.”
Fumarate Hydratase was shown to be repressed in a model of sepsis, an often-fatal systemic inflammatory condition that can happen during bacterial and viral infections. Similarly, in blood samples from patients with Lupus, Fumarate Hydratase was dramatically decreased.
“Restoring Fumarate Hydratase in these diseases or targeting MDA5 or TLR7 therefore presents an exciting prospect for badly needed new anti-inflammatory therapies,” said Prof O’Neill.
Excitingly, this newly published work is accompanied by another publication by a group led by Professor Christian Frezza, now at the University of Cologne, and Dr Julien Prudent at the MRC Mitochondrial Biology Unit (MBU), who have made similar findings in the context of kidney cancer.
“Because the system can go wrong in certain types of cancer, the scope of any potential therapeutic target could be widened beyond inflammation,” added Prof O’Neill.
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.”
