Colon cancer cells. Source: National Cancer Institute on Unsplash
Emodin, an active compound found in Chinese herbal medicine, can prevent colon cancer in mice, according to researchers, and may be applicable in humans as well, a study has found. The mechanism behind this is likely emodin’s ability to reduce the number of pro-tumour macrophages.
Emodin, a major bioactive anthraquinone derivative extracted from rhubarb, represents multiple health benefits in the treatment of a host of diseases, such as immune-inflammatory abnormality, tumor progression, bacterial or viral infections, and metabolic syndrome. Emerging evidence has made great strides in clarifying the multi-targeting therapeutic mechanisms underlying the therapeutic efficacy of emodin, including anti-inflammatory, immunomodulatory, anti-fibrosis, anti-tumor, anti-viral, anti-bacterial, and anti-diabetic properties.
Besides investigating if emodin could prevent colon cancer, the study’s researchers especially wanted to know whether its anti-cancer properties “could be attributed to its actions on immune cells and particularly macrophages,” said Angela Murphy, PhD, co-author of the study. In this murine model, emodin was shown to reduce both polyp count and size. Also, mice treated with emodin “exhibited lower protumorigenic M2-like macrophages in the colon,” researchers wrote in the study.
Roughly 70% of colon cancer cases can be attributed to diet or other lifestyle factors, said Dr Murphy. Because emodin is also found in some fresh fruits and vegetables, it is hoped that consuming these emodin-containing foods could prevent colon cancer in humans.
A new study calculates that exposure to car exhaust from leaded gas during childhood lowered the IQ levels of about half the population of Americans alive today.
The findings suggest that Americans born before 1996 may now be at greater risk for lead-related health problems, such as faster ageing of the brain. Leaded petrol was banned in the US in 1996, but anyone born in the US before the end of that era, and especially those at the peak of its use in the 1960s and 1970s, had worryingly high lead exposures as children, the researchers said. In South Africa, leaded petrol was only banned at the end of 2005.
Lead is a neurotoxin that can enter the bloodstream via a number of routes and there is no safe level of exposure at any point in life. Young children are especially vulnerable to lead’s ability to impair brain development and lower cognitive ability.
“Lead is able to reach the bloodstream once it’s inhaled as dust, or ingested, or consumed in water,” said study co-author Aaron Reuben, a PhD candidate in clinical psychology. “In the bloodstream, it’s able to pass into the brain through the blood-brain barrier, which is quite good at keeping a lot of toxicants and pathogens out of the brain, but not all of them.”
To answer the complex question of how more than 70 years of leaded petrol use may have left a permanent mark on human health, Reuben and co-authors Michael McFarland and Mathew Hauer, both professors of sociology at Florida State University, opted for a fairly simple strategy.
Using publicly available data on US childhood blood-lead levels, leaded-gas use, and population statistics, they determined the likely lifelong burden of lead exposure carried by every American alive in 2015. From this data, they estimated lead’s assault on our intelligence by calculating IQ points lost from leaded gas exposure as a proxy for its harmful impact on public health – a result which stunned the researchers.
“I frankly was shocked,” Prof McFarland said. “And when I look at the numbers, I’m still shocked even though I’m prepared for it.”
As of 2015, more than 170 million Americans (more than half of the U.S. population) had clinically concerning levels of lead in their blood as children, likely resulting in lower IQs and putting them at higher risk for other long-term health impairments, such as reduced brain size, greater likelihood of mental illness, and increased cardiovascular disease in adulthood.
Leaded gasoline consumption rose rapidly in the early 1960s and peaked in the 1970s. As a result, Reuben and his colleagues found that essentially everyone born during those two decades are all but guaranteed to have been exposed to pernicious levels of lead from car exhaust.
Even more startling was lead’s toll on intelligence: childhood lead exposure may have blunted America’s cumulative IQ score by an estimated 824 million points – nearly three points per person on average. The researchers calculated that at its worst, people born in the mid-to-late 1960s may have lost up to six IQ points, and children registering the highest levels of lead in their blood, eight times the current minimum level to initiate clinical concern, fared even worse, potentially losing more than seven IQ points on average.
While the loss of a few IQ points may seem negligible, the authors note that these changes are dramatic enough to potentially shift people with below-average cognitive ability (IQ score less than 85) to being classified as having an intellectual disability (IQ score below 70).
Prof McFarland is continuing by analysing the racial disparities of childhood lead exposure, hoping to highlight the health inequities suffered by Black children, who were exposed more often to lead and in greater quantities than white children.
Reuben’s next step will be to examine the long-term consequences of past lead exposure on brain health in old age, based on evidence showing that adults with high childhood lead exposure may experience accelerated brain aging.
“Millions of us are walking around with a history of lead exposure,” Reuben said. “It’s not like you got into a car accident and had a rotator cuff tear that heals and then you’re fine. It appears to be an insult carried in the body in different ways that we’re still trying to understand but that can have implications for life.”
Researchers have found that found that patients developing persistent postural-perceptual dizziness (PPPD) are likely to have exacerbating factors soon after the onset of balance disorder symptoms. The results were reported in Laryngoscope Investigative Otolaryngology.
When people experience vestibular symptoms, it can develop into persistent postural-perceptual dizziness (PPPD), a chronic disorder where patients experience dizziness and non-spinning vertigo, particularly during moving, maintaining an upright posture, and when exposed to complex visual stimuli. However, not all individuals suffering from vestibular symptoms go on to develop PPPD, and it unclear whether people showing exacerbating factors for PPPD tend to develop PPPD or not.
Assistant Professor Kayoko Kabaya led a team that analysed medical records of patients who were tested for vestibular symptoms for the first time to identify predictive factors for developing PPPD later on, and to see if the presence of exacerbating factors early on increases the likelihood of developing chronic PPPD. “PPPD is often severe and resistant to treatment. We believe that it is important to provide preventive interventions before PPPD develops, and wanted to identify the characteristics of patients who are prone to PPPD,” explained Dr Kabaya.
In their study, the severity of the symptoms experienced by the patients was scored with a questionnaire which involved questions on the exacerbating factors. Additionally, the perceived handicap due to dizziness was evaluated using a self-assessment scale. There was three months of follow-up, and the symptom scores of patients developing PPPD during the follow-up were compared with that of patients who did not develop PPPD.
More than half of the patients reported experiencing exacerbating factors shortly after the vestibular symptoms. About 10% of these patients developed PPPD during the follow-up period, and the exacerbating factors were found to have a more severe effect on the vestibular symptoms. Notably, the symptom scores of those who developed PPPD were significantly higher than that of those who did not.
“Our results suggest that patients who develop PPPD are likely to have its exacerbating factors at the early stages of the disease following the onset of vestibular symptoms,” said Dr Kabaya.
The researchers believe the results could lead to preventive measures against the disease. “PPPD is a disease that causes long-term social loss and occurs following acute vestibular symptoms. Based on our finding that patients with exacerbating factors during acute vestibular symptom are more likely to develop PPPD, our study could encourage the development of intervention protocols for such patients before they develop PPPD,” said Dr Kabaya.
In a new study published in Arthritis & Rheumatology, scientists have found that two biomarkers predict cardiovascular disease (CVD) risk in people with psoriatic disease. People with psoriatic disease, which includes psoriasis and psoriatic arthritis, are more likely to develop CVD than the general population.
The study, which included 1000 adults with psoriatic disease, found that elevated blood levels of two indicators of cardiovascular health, namely, cardiac high-sensitivity troponin I (cTnI) and N-terminal pro-brain-type natriuretic peptide (NT-proBNP), were associated with higher risks of experiencing cardiovascular problems independent of traditional risk factors such as hypertension and high cholesterol.
These findings pave the way for further studies exploring the clinical potential of measuring cTnI and NT-proBNP levels in helping assess the heart health of individual patients with psoriatic disease.
“Our study provides new insights regarding the pathophysiology of cardiovascular diseases in psoriasis and psoriatic arthritis. However, at this time, ordering tests of cardiac biomarkers is not recommended for risk stratification of asymptomatic patients with psoriatic disease,” said senior Lihi Eder, MD, PhD, associate professor of medicine at Women’s College Hospital and University of Toronto.
According to a large study published in The BMJ, mRNA vaccines are highly effective in preventing COVID hospital admissions related to the alpha, delta, and omicron variants. However, three doses are needed to achieve similar protection against omicron that two doses provide against delta and alpha.
The results also show that, although severity of disease among patients admitted to hospital is lower with the omicron versus delta variant, patients with omicron are still at risk of critical illness and death.
In order to guide vaccination policies and development of new vaccines, it is essential to understand COVID variants and vaccine efficacy.
Early studies suggested reduced vaccine effectiveness against infection and hospital admissions for omicron compared with earlier variants, but little is known about the effectiveness of vaccines to prevent the most severe manifestations of COVID, including respiratory failure and death, for patients with infection due to the omicron variant.
To address this, the researchers assessed COVID severity in the alpha, delta, and omicron variants among hospitalised adults and compared the effectiveness of two and three doses of mRNA vaccines (Pfizer-BioNTech and Moderna) in preventing hospital admissions related to each variant.
Their findings are based on 11 690 adults admitted to 21 hospitals across the United States between March 2021 and January 2022: 5728 cases with COVID and 5962 controls without COVID.
Patients were classified into alpha, delta or omicron based on viral gene sequencing or by the predominant circulating variant at the time of hospital admission.
Effectiveness of two doses of an mRNA vaccine to prevent COVID hospital admission was found to be lower for the omicron variant than alpha and delta variants (65%, 85%, and 85%, respectively), whereas three doses were found to achieve 86% effectiveness against the omicron variant, similar to two doses against the alpha and delta variants.
Among unvaccinated adults hospitalised with COVID, the delta variant was associated with the most severe disease, followed by the alpha variant and then the omicron variant.
The omicron variant was, however, associated with substantial critical illness and death, with 15% of patients admitted to hospital with the omicron variant (vaccinated and unvaccinated) progressing to invasive mechanical ventilation, and 7% dying in hospital.
Nevertheless, vaccinated patients hospitalised with COVID had significantly less sever disease than unvaccinated patients across all variants.
As an observational study, cause cannot be established, and some variant misclassification may have occurred. Changes in clinical management during the periods when the alpha, delta, and omicron variants predominated were not accounted for. These could have affected outcomes, the researchers acknowledged.
Nevertheless, this was a large study with rigorous evaluation of vaccination status and of outcomes beyond hospital admission, suggesting that the results are robust.
As such, they say that mRNA vaccines “were associated with strong protection against hospital admissions with COVID due to the alpha, delta, and omicron variants” and that vaccination against COVID including a third dose of an mRNA vaccine, “is critical for protecting populations against COVID-associated morbidity and mortality.”
They concluded: “As the COVID pandemic continues to evolve, routine monitoring of vaccine effectiveness, especially against severe disease, and surveillance programmes to identify viral variants will be essential to inform decisions about booster vaccine policies and vaccine strain updates.”
Research into how the body’s DNA repair process works has made a discovery into how the process works, and by understanding how cancer cells repair their DNA so rapidly may lead to potent new chemotherapy treatments.
One of the great mysteries of medical science is the ability of DNA to be repaired after damage, but complicating the study of this is how different pathways are involved in the repair process over the cell’s life cycle. In one of the repair pathways known as base excision repair (BER), the damaged material is removed, and proteins and enzymes work together to create DNA to fill in and then seal the gaps.
In a study appearing in Proceedings of the National Academy of Sciences, Eminent Professor Zucai Suo led a team that discovered that BER has a built-in mechanism to increase its effectiveness: it just needs to be captured at a very precise point in the cell life cycle.
In BER, an enzyme called polymerase beta (PolyB) fulfils two functions: It creates DNA, and it initiates a reaction to clean up the leftover ‘chemical junk’. Through five years of study, Prof Suo’s team learned that by capturing PolyB when it is naturally cross-linked with DNA, the enzyme will produce new genetic material 17 times faster than when the two are not cross-linked. This suggests that the two functions of PolyB are interlocked, not independent, during BER.
The research improves the understanding of cellular genomic stability, drug efficacy and resistance associated with chemotherapy.
“Cancer cells replicate at high speed, and their DNA endures a lot of damage,” Prof Suo said. “When a doctor uses certain drugs to attack cancer cells’ DNA, the cancer cells must cope with additional DNA damage. If the cancer cells cannot rapidly fix DNA damage, they will die. Otherwise, the cancer cells survive, and drug resistance appears.”
This research examined naturally cross-linked PolyB and DNA, unlike previous research that mimicked the process. Studies had previously identified the enzymes involved in BER but did not fully grasp how they work together.
“When we have nicks in DNA, bad things can happen, like the double strand breaking in DNA,” said Thomas Spratt, a professor of biochemistry and molecular biology at Penn State University College of Medicine who was not a part of the research team. “What Zucai found provides us with something we didn’t understand before, and he used many different methods to reach his findings.”
Medical experts who were under the impression they were contracted by the Road Accident Fund (RAF) to provide expert medical opinions, have written to acting chief justice Raymond Zondo to withdraw their completed opinions that have not yet been used in court because the RAF refuses to pay them or has charged penalties to reduce the amounts owed.
These qualified specialists provided expert medico-legal services, such as consultations and injury assessments, preparation of expert witness reports, attended expert witness meetings, prepared joint minutes of expert meetings, and presented expert evidence in court for the former panel of attorneys rendering this service for the RAF.
The experts say they have had enough of struggling for payments from the RAF and they state in the letter that their work “may not and should not be used as evidence in any matter” in the future because it is said to be unauthorised and not paid for. In effect, this means that RAF cases can no longer progress until these experts have been paid or until new medical expert opinions are obtained.
The RAF only recently informed all medical experts appointed by its former panel of attorneys that they were not authorised to perform these services which were conducted since 2015 and will therefore not be paid.
Mariëtte Minnie, director of MMB Made Easy, which handles medical accounts of medical-legal service providers says accounts she deals with have a total outstanding value of R63.5 million, with some accounts dating back as far as 2015. The biggest outstanding balance among her clients is R10,7 million the RAF owes to one neurosurgeon.
As a result of ongoing non-payment, some experts have shut down and sold their houses and cars due to huge overdrafts and VAT owed to SARS for opinions for which the RAF has not yet paid.
Minnie adds, “The RAF has stolen thousands of medico-legal reports from hundreds of experts which they do not intend to pay for.”
Medical experts have always been instructed by the panel attorneys as RAF representatives, but the RAF never renewed its expert contracts in time. The RAF then terminated the services of the panel of attorneys who had to obtain RAF authorisation for the experts but still asked experts to continue assessing claimants to avoid delays and send their reports directly to the RAF.
Minnie says that invoices for work done in previous years are met with delaying tactics and even denial of payment. “The RAF now implements terms of the service level agreement with the experts to fine them with 5% for every day that their reports are submitted after the due date although submission of reports is subject to factors such as obtaining necessary documentation to finalise the report.”
The RAF has also instituted steps to eradicate “irregular expenditure”, suggesting that experts assessed claimants and wrote reports without authorisation although the RAF failed to implement adequate systems to instruct and remunerate them.
Minnie comments, “The RAF is shambolic and has been unable to operate ethically or effectively since 2015. We will also be bringing this matter to the attention of the Minister of Transport, the Special Investigations Unit, the Public Protector, the National Prosecuting Authority and the National Treasury. New leadership is required to turn around the RAF.”
In a real world study, patients taking oral corticosteroids for severe asthma, taking mepolizumab reduced the need for those steroids by 75%. These findings were presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology.
By the end study, patients on a median 10 mg maintenance dose of oral corticosteroids at baseline reduced their intake to 2.5 mg, reported Mark Liu, MD, of Johns Hopkins Medicine, who presented the findings.
And those on a median 5 mg maintenance dose at the start of the trial reduced their use to 0.4 mg by study end, Dr Liu said.
In the high steroid dose group, 36% were able to be weaned off the drugs by the end of the study, he reported. In the lower dose group, 49% were able to discontinue steroid use.
Treatment with the interleukin-5 (IL-5) antagonist mepolizumab reduced clinically significant annual exacerbations from a mean of 4.3 in the 12 months prior to the trial to 1.5 with mepolizumab use. This reduction from baseline was seen across all patient groups, said Dr Liu, including those with high and low steroid use and those who were not taking steroids at baseline to control symptoms.
Dr Liu suggested that despite the limitation of being a single-arm study, the “clinically important real-world findings indicate that patients with severe asthma treated with mepolizumab can reduce their oral corticosteroid use, potentially reducing the risk of side effects associated with their use, while improving their asthma control.”
The co-moderator of the presentation session, William Anderson, MD, of Children’s Hospital Colorado, said the study was important – “especially for our adult patients who are on chronic steroids, because the side effects of chronic steroids are so profound and oftentimes can lead to equal if not worse effects than the underlying asthma itself.”
“The ability to use a biologic agent to decrease the dose of an oral steroid for our patients is certainly extraordinarily promising,” Dr Anderson said to MedPage Today. “Our ultimate goal is to get patients off oral steroids.”
For the year-long study, Dr Liu and colleagues enrolled 822 adults with asthma and a new prescription for mepolizumab with at least 12 months of previous medical records. Mepolizumab was given at the standard 100mg subcutaneous dose.
“Patients with severe asthma often rely on oral corticosteroids to control their symptoms despite a well-recognized risk of complications even at low daily doses,” Dr Liu explained. The goal of the study, he said, was to determine what happened in a real-world setting when these patients were treated with mepolizumab, stratified by steroid use. The researchers enrolled patients from December 2016 through October 2019.
About 10% of patients experienced adverse events, but serious adverse events occurred in less than 1%, Dr Liu noted.
In a news release, pharma giant Aspen has announced that it has concluded an agreement with Johnson & Johnson to manufacture an Aspen-branded COVID vaccine, Aspenovax, and to make it available throughout Africa.
This follows on from the November 2021 announcement of an agreement of terms between the two companies. This new agreement will expand the existing technical transfer and manufacturing agreements between the companies.
The agreement will grant Aspen’s South African subsidiary the rights to manufacture finished Aspenovax product from drug substance supplied by J&J. It will also make Aspenovax available to markets in Africa through transactions with designated multilateral organisations and with national governments of member states of the African Union.
Under the agreement, Aspen has secured the necessary intellectual property from Johnson & Johnson for production. There is also a good faith undertaking between the companies to expand the agreement to cover any new versions of the drug substance, such as those developed for new variants or a different formulation for administration as a booster.
The agreement will last through to the end of 2026.
Commenting on this agreement, Dr Matshidiso Moeti, World Health Organization Regional Director for Africa said: “This important agreement on sharing know-how and technologies for the production of COVID vaccines is a huge leap forward towards realising our shared vision for medicines and vaccines to be manufactured on the African soil for the African people. Vaccines are our best way out of this pandemic and local production is an essential recipe for our success.”
Stephen Saad, Aspen Group Chief Executive said: “Even with all the support in the world, none of this would be possible without the competence of our teams at Gqeberha. They knew the weight of a continent’s ambitions rested on their shoulders. They persevered and succeeded in becoming a significant supplier within the Johnson & Johnson network. Aspenovax has become a reality due to the confidence placed in their abilities. They are our African heroes.”
Like women in every other sector of the economy, the COVID pandemic has negatively impacted those working in academic medicine according to a commentary which appears in Nature Medicine.
Co-author Anne B. Curtis, MD, professor at the University at Buffalo, laid out the problem: “During the first year of the pandemic, when schools shut down and went to 100% remote learning, we saw that it affected women disproportionately, having to stay home and teach their children while their research languished.”
Even before the COVID pandemic, women in academic medicine were paid less than men in comparable positions, received lower startup funds for laboratory research and were promoted later.
Additionally, they wrote that, compared to men, women have fewer “conventional markers of achievement” in academia, such as principal investigator positions on research grants. Women write fewer grant applications; they have fewer grant renewals; they get lower funding amounts for initial grants; and are first or last author on fewer papers.
The reasons for these are well known, the authors wrote.
“Society expects women to assume the major portion of the burden for child rearing, and women themselves feel an obligation to put family above their own needs, to the detriment of their own career development,” she said. “There still isn’t the sharing of responsibilities in two-career families to mitigate these problems.”
The paper includes a detailed ‘menu’ of proposed solutions. These include providing financial support to hire technicians for two to three years to carry on lab research while women researchers focus on child care at home, or otherwise supporting child care at home so women can continue their lab research.
The paper also proposes slowing down tenure clocks, delaying the tenure decision by two to three years to make up for lost time while women give birth and care for young children.
In addition to such programs, the list includes a category of solutions termed “cultural,” described as creating the cultural expectation that gender equity is a shared responsibility and incorporating those expectations into bonuses and merit raises of institutional leaders. Also included is the need to engage university and hospital boards of trustees to support gender equity.
Prof Curtis said that the paper aims to highlight the persistence of these gender differences persist and that global phenomena like the pandemic only worsen them.
“As much as we would like to think that gender differences in career development no longer exist, they do, and they adversely affect women more than men,” she said. “Understanding these issues and implementing solutions are the best ways to minimise potentially adverse effects on women’s careers.”
As the pandemic and its associated restrictions ease, Prof Curtis warned, “The situation is improving now that schools are open, but the next pandemic may only be a mutation away.”
