Day: December 7, 2023

Categories : Immune SystemTags : Leave a comment

Mucus is Snot a Problem for Bacteria, Which Swarm Through It

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Photo by Andrea Piacquadio on Pexels

The increase in mucus from sniffles and runny noses is exactly what bacteria use to mount a coordinated attack on the immune system, according to a new study from researchers at Penn State. The team found that the thicker the mucus, the better the bacteria are able to swarm. The findings could inform treatments to control the spread of bacteria.

The study, recently published in the journal PNAS Nexus, demonstrates how bacteria use mucus to enhance their ability to self-organise and possibly drive infection.

The experiments, performed using synthetic pig stomach mucus, natural cow cervical mucus and a water-soluble polymer compound called polyvidone, revealed that bacteria coordinate movement better in thick mucus than in watery substances.

According to the researchers, the findings provide insight into how bacteria colonise mucus and mucosal surfaces, and also show how mucus enhances bacterial collective motion, or swarming, which may increase antibiotic resistance of bacterial colonies.

“To the best of our knowledge, our study is the first demonstration of bacteria collectively swimming in mucus,” said Igor Aronson, Huck Chair Professor of Biomedical Engineering, of Chemistry and of Mathematics at Penn State and corresponding author on the paper.

“We have shown that mucus, unlike liquids of similar consistency, enhances the collective behaviour.”

Mucus is essential for many biological functions, explained Aronson. It lines the surfaces of cells and tissues and protects against pathogens such as bacteria, fungi and viruses. But it is also the host material for bacteria-born infections, including sexually transmitted and gastric diseases.

A better understanding of how bacteria swarm in mucus could lead to new strategies to combat infections and the growing problem of antibiotic resistance, according to Aronson.

“Our findings demonstrate how mucus consistency affects random motion of individual bacteria and influences their transition to coordinated, collective motion of large bacterial groups,” Aronson said.

“There are studies demonstrating that collective motion or swarming of bacteria enhances the ability of bacterial colonies to fend off the effect of antibiotics. The onset of collective behaviour studied in our work is directly related to swarming.”

Mucus is a notoriously challenging substance to study because it exhibits both liquid-like and solid-like properties, Aronson explained.

Liquids are typically described by their level of viscosity, how thick or thin the liquid is, and solids are described by their elasticity, how much force it can take before breaking. Mucus, a viscoelastic fluid, behaves as both a liquid and solid.

To better understand how mucus becomes infected, the team used microscopic imaging techniques to observe the collective motion of the concentrated bacteria Bacillus subtilis in synthetic pig stomach mucus and natural cow cervical mucus, which for this purpose are analogous to human mucus.

They compared those results with observations of Bacillus subtilis moving in a water-soluble polymer polyvidone at a wide range of concentrations, from high to low levels of polyvidone.

The researchers also compared their experimental results to a computational model for bacterial collective motion in viscoelastic fluids like mucus.

The team found that mucus consistency profoundly affects the collective behaviour of bacteria: the thicker the mucus, the more likely the bacteria would exhibit collective movement, forming a coordinated swarm.

“We were able to show how the viscoelasticity in mucus enhances bacterial organisation, which in turn leads to coherently moving bacterial groups that cause infection,” Aronson said.

“Our results reveal that the levels of elasticity and viscosity in mucus are a main driver in how bacterial communities organize themselves, which can provide insight into how we can control and prevent bacterial invasion in mucus.”

Aronson explained that the team expects human mucus to exhibit similar physical properties, meaning their findings are also relevant for human health.

“Our results have implications for human and animal health. We’re showing that mucus viscoelasticity can enhance large-scale collective motion of bacteria, which may accelerate how quickly bacteria penetrate mucus protective barrier and infect internal tissues.”

Source: Penn State

Categories : Allergies CancerTags : Leave a comment

Existing Allergy Medication Unleashes Antitumour Immunity against Lung Cancer

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Photo by Anna Shvets

Researchers from Mount Sinai report in Nature that they have identified an allergy pathway that, when blocked, unleashes antitumour immunity in mouse models of non-small cell lung cancer (NSCLC).

And in an early parallel study in humans, combining immunotherapy with dupilumab – an Interleukin-4 (IL-4) receptor-blocking antibody widely used for treating allergies and asthma – boosted patients’ immune systems, with one out of the six experiencing significant tumour reduction.

“Immunotherapy using checkpoint blockade has revolutionised treatment for non-small cell lung cancer, the most common form of lung cancer, but currently only about a third of patients respond to it alone, and in most patients, the benefit is temporary,” says senior study author Miriam Merad, MD, PhD, at the Icahn School of Medicine at Mount Sinai.

“A big focus of our program TARGET is to use single cell technology and artificial intelligence to identify molecular immune programs that can dampen tumour immune response to checkpoint blockade.”

Also known as a PD1 inhibitor, checkpoint blockade is a type of cancer immunotherapy that can unleash the cancer-killing activity of T cells.

“Using single cell technologies, we discovered that the immune cells infiltrating lung cancers, as well as other cancers we studied, exhibited characteristics of a ‘type 2’ immune response, which is commonly associated with allergic conditions like eczema and asthma,” says first study author Nelson LaMarche, PhD, a postdoctoral research fellow in the lab of Dr Merad.

“These results led us to explore whether we could repurpose a medication typically used for allergic conditions to ‘rescue’ or enhance tutor response to checkpoint blockade,” says Thomas Marron, MD, PhD, co-senior author of the study.

“Strikingly, we found that IL-4 blockade enhanced lung cancer response to checkpoint blockade in mice and in six lung cancer patients with treatment-resistant disease. In fact, one patient whose lung cancer was growing despite checkpoint blockade had nearly all their cancer disappear after receiving just three doses of the allergy medication, and his cancer remains controlled today, over 17 months later.”

The researchers are encouraged by the initial results but emphasise the need for larger clinical trials to validate the drug’s efficacy in treating NSCLC.

Beyond the clinical trial findings reported in the current Nature paper, the investigators have now expanded the clinical trial, adding dupilumab to checkpoint blockade for a larger group of lung cancer patients, and are starting to investigate its use in early-stage lung cancer as well. Through these trials, they are searching for biomarkers to identify those cancer patients who might benefit from dupilumab treatment.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : Addiction Pain ManagementTags : Leave a comment

One in Six Patients with Opioid Use Disorder Leave the Hospital too Early

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The number of patients admitted with opioid use disorder (OUD) and injection-related infections who left the hospital before completing treatment increased significantly between 2016 and 2020 (from 9.3% to 17%) according to analysis from researchers at the Perelman School of Medicine at the University of Pennsylvania. One in six of these patients now leave the hospital before medically advised (BMA).

The findings, published in JAMA, also reveal that the rate at which patients with any opioid-related issues (patients presenting with other issues but exhibiting opioid dependence) left the hospital BMA increased more than 50% (from 7.5 to 11.3%). In both of these groups, nearly half of BMA discharges occurred before the third day, when withdrawal symptoms are most severe. Now that fentanyl has become the dominant opioid causing overdoses, the findings illustrate the need for patient-centred care that adequately manages pain and withdrawal symptoms so that patients can complete treatment.

Approximately 500 000 patients are discharged against medical advice, or in the United States annually, and those circumstances are associated with increased likelihood of death and hospital readmission. Previous research shows that patients with addiction cite withdrawal and pain as their reason for BMA discharge.

“The rapid increase in early discharges is alarming; in 2016, less than one in ten patients admitted for OUD and injection-related infections left the hospital before their care team considered it safe. By 2020, one in six were leaving early,” said lead author Ashish Thakrar, MD. “What’s more, since the study period ended, the COVID-19 pandemic caused the opioid crisis to escalate, underscoring just how urgent it is to understand how we might be able to reverse this trend and get patients the treatment they need.”

Using nationally representative data from the National Readmissions Database, researchers compared the rate of discharge BMA in patients admitted for OUD to the BMA discharge rate for non-opioid admissions. They also evaluated changes in the proportion of BMA discharges before the third admission day, when opioid withdrawal is most severe, and changes in the proportion of discharges BMA in patients with stimulant use disorder.

They identified opioid-related admissions as those with opioid use, dependence, abuse, or overdose. To account for patients who were more likely to have severe OUD and fentanyl use, they also included patients with OUD and an injection related infections, such as bacteraemia, endocarditis, or osteomyelitis.

Between 2016 and 2020, they found that the number of patients admitted with OUD and injection-related infections who left the hospital BMA increased 82%, from 9.3% to 17%. They also found that the discharge BMA rate for all opioid-related admissions increased 50% during this period, from 7.5% to 11.3%. The proportion of BMA discharges occurring before the third day also increased for individuals with OUD and an injection-related infection, from 42.6%, to 48%.

In contrast, the BMA rate increased only marginally for non-opioid mental health or substance use admissions, and all non-opioid admissions (from 3.1 to 3.5%, and 1.1 to 1.5%, respectively).

“These data didn’t allow us to discern which type of opioid that individuals were using when admitted for OUD, but we know that fentanyl, an opioid 25 to 50 times more potent than heroin, has spread in unregulated drug supplies and is now involved in 88 percent of opioid overdoses in the US. Withdrawal symptoms from fentanyl are more difficult to manage than from other opioids like heroin and oxycodone,” said Thakrar. “This study illustrates why we need more research on how to manage individuals withdrawing from fentanyl and other substances in the unregulated drug supply.”

“The drugs that individuals are using have changed over the past decade, and how we treat them should change, too,” said senior author M. Kit Delgado, MD, MS. “Health systems can expand the use of interventions that are already proven to treat withdrawal and reduce but not widely used, such as medications like buprenorphine and methadone.”

Thakrar and Delgado also suggest that hospitals could be incentivised to reduce discharges BMA and to support specialty services such as addiction consult services that have been proven to reduce BMA discharges and that can reduce the risks of future readmission or death.

Source: Penn University Medicine

Categories : Injury & Trauma PaediatricsTags : Leave a comment

Vitamin D Supplements don’t Prevent Fractures in Children

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Photo by cottonbro studio

A major clinical trial has found that vitamin D supplements do not increase bone strength or prevent bone fractures in children with vitamin D deficiency. The findings, published in Lancet Diabetes & Endocrinology, challenge widely held perceptions relating to the effects of vitamin D on bone health.

Around one-third of children have at least one fracture before the age of 18. This is a major global health issue, as childhood fractures can lead to life years of disability and/or poor quality of life. The potential for vitamin D supplements to improve bone strength has attracted growing interest in recent years, based on vitamin D’s role in promoting bone mineralisation. But there have been no clinical trials to test whether vitamin D supplements can prevent bone fractures in children.

Working with partners in Mongolia, a setting with a particularly high fracture burden and where vitamin D deficiency is highly prevalent, researchers from led by Queen Mary University of London and the Harvard T.H. Chan School of Public Health conducted a clinical trial to determine if vitamin D supplementation would decrease risk of bone fractures or increase bone strength in schoolchildren.

This study is also the largest randomised controlled trial of vitamin D supplementation ever conducted in children. Over the course of three years, 8851 schoolchildren aged 6-13 living in Mongolia received a weekly oral dose of vitamin D supplementation.

Testing revealed that 95.5% of participants had vitamin D deficiency at baseline, and study supplements were highly effective in boosting vitamin D levels into the normal range. No effect was seen on fracture risk or on bone strength, measured in a subset of 1438 participants using quantitative ultrasound.

The trial findings are likely to prompt scientists, doctors and public health specialists to re-consider the effects of vitamin D supplements on bone health.

Dr Ganmaa Davaasambuu, Associate Professor at the Harvard T.H. Chan School of Public Health, said:

“The absence of any effect of sustained, generous vitamin D supplementation on fracture risk or bone strength in vitamin D deficient children is striking. In adults, vitamin D supplementation works best for fracture prevention when calcium is given at the same time – so the fact that we did not offer calcium alongside vitamin D to trial participants may explain the null findings from this study.”

Professor Adrian Martineau, Lead of the Centre for Immunobiology at Queen Mary University of London, added:

“It is also important to note that children who were found to have rickets during screening for the trial were excluded from participation, as it would not have been ethical to offer them placebo (dummy medication). Thus, our findings only have relevance for children with low vitamin D status who have not developed bone complications. The importance of adequate vitamin D intake for prevention of rickets should not be ignored, and UK government guidance recommending a daily intake of 400 IU vitamin D remains important and should still be followed.”

Source: Queen Mary University of London

Categories : Healthcare Politics and RegulationsTags : Leave a comment

BHF Responds to the Imminent Approval of the NHI Bill

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The National Health Insurance (NHI) Bill was approved by the National Council of Provinces today and is due to be signed into law by the president shortly after. The Board of Healthcare Funders (BHF) is deeply disappointed. We are not happy with the various sections of the Bill. Despite submissions to government in this regard, the recommendations of the BHF and other stakeholders have largely been ignored and the bill is being passed virtually unchanged from its originally drafted form.

While the BHF fully supports the concept of universal health coverage (UHC) as defined by the World Health Organization (WHO) and believes that it must be a strategic imperative for all those directly or indirectly involved in healthcare, it does not support the NHI Bill in its current form. The bill restricts medical schemes to the provision of complementary cover potentially rendering them unsustainable, further to which the enormous economic value that medical schemes currently add to the health sector would be lost to South Africa if the bill goes ahead unchanged, BHF strongly believes this section should be removed as well as all references to complementary cover contained in the bill.

Additionally, a number of the Bill’s provisions are unconstitutional. These were detailed in the BHF’s submission to government. South Africa needs a strong, vibrant private health sector because government resources will never be unlimited. . The incredibly wide powers it bestows on the Minister of Health grossly undermine the board of the NHI fund and its accountability. The power of the Benefit Advisory Committee to determine health benefits under NHI similarly undermines this accountability. In addition, the BHF is perturbed by the demonstrated inability of the state to adequately operate national public entities and state-owned enterprises, as well as the endless levels of relentless corruption in the public sector.

Other concerns

The Bill allows the Minister of Health and the NHI fund to issue directives that override all other legislation, except the PFMA and the Constitution, including legislation specifically mandated by the Constitution.

There are proposed amendments to the Medical Schemes Act that unfairly discriminate against pregnant women. 

In many instances, the language of the bill creates significant legal uncertainty, which is itself unconstitutional due to the principle of the rule of law upheld by the Constitution. The BHF provided specific examples of this in the body of its submission.

The NHI Bill allows the national sphere of government to encroach on the geographical, functional and institutional integrity of provincial governments. This is not permitted by Section 41 of the Constitution.

The bill tries to dictate to the President in Cabinet (the National Executive) what new legislation must be made or how to amend existing legislation. This is also unconstitutional, as the Constitution itself grants the National Executive its powers. Nothing can change this except an amendment to the Constitution.

The registration system proposed by the bill creates unconstitutional barriers to access to health care that do not currently exist. The certification, accreditation and contracting system proposed by the bill is unwieldy, and it too will create unconstitutional barriers to access to health care that currently do not exist. Both these points are explained further in the body of the BHF’s submission.

Dr Katlego Mothudi, BHF CEO, underscores these serious implications of the bill’s being passed unchanged. “We have consistently given input into this proposed law and are disappointed that our concerns and those of other stakeholders appear not to have been considered or even tested. The bill in its current form will have a negative impact on healthcare access for everyone. There are many areas of uncertainty that have not been clarified, not least with regard to funding and affordability. We are also concerned specifically that the bill may prejudice the rights of women,” he says. “The proposed amendments to the Medical Schemes Act exclude access to pregnancy-related healthcare services for women who are medical scheme members. This means that these women would have to access reproductive health care from the public sector at their own cost, which is in conflict with the provisions of the National Health Act.

“The bill also has the potential for a wider negative economic impact. There is still uncertainty around how the NHI will be funded, but it will very likely be through additional taxation, something that will unavoidably have a detrimental effect on the economy at large – companies, individual employees and the general public – in the form of job losses. This phenomenon has already been discussed in various papers, including one published by the World Bank in 2001. It cited Colombia’s experience in this regard. A 10% increase in payroll taxes resulted in a 4.9% reduction in employment. Those who remained employed experienced a reduction in their disposable income, while the decrease in the overall number of employees saw a reduction in revenue from personal tax. Should the bill pass in its current form, South Africa will almost certainly experience something very similar.

“More specifically, this phenomenon will also impact the health sector. With medical schemes reduced to providing only complementary cover, not only will the schemes industry itself shrink, but all the other private entities it does business with, including hospitals, pharmaceutical companies and health practitioners,” he concludes.

Provided by the Board of Healthcare Funders