Scientists have long thought of the pleural cavity merely as a cushion from external damage. Turns out, it also houses macrophages that rush into the lungs during flu infections.
“We were surprised to find them in the lungs because nobody has seen this before, that these cells go into the lung when there’s an infection,” said UC Riverside virologist Juliet Morrison, who led the discovery team.
A paper published in the Proceedings of the National Academy of Sciences details how during an influenza infection, macrophages leave the exterior cavity and cross into the lungs where they decrease inflammation and reduce levels of disease.
“This study shows it’s not just what happens in the lung that matters, but also what’s outside of the lung. Cell types not normally connected to the lung can have outsized impacts on lung disease and health,” Morrison said.
There are three main cavities in the body: one around the heart, the abdominal cavity, and the pleural cavity surrounding the lungs.
“Because it contains fluid, it prevents the lungs from collapsing. However, people have not thought much about the pleural cavity being a whole organ within itself. This research may change that perception,” Morrison said.
Initially, the researchers set out to understand the more general question of what types of cells are present in the lungs during flu infections. They took existing data on lung-related genes from studies of mice that either died from the flu or survived. They then mined the data using an algorithm to predict cell types that change in the lungs during infections.
“We took big data and broke it down to assign which potential immune cells are in the lung tissues. That’s where I got a hint that maybe we had a previously unknown external source of cells in the lung,” Morrison said.
Next, using a laser-based technique, the team tracked macrophages going into the lungs of mice, and observed what happened if they took these cells out of the equation.
“When you take them out of the mouse you see more disease and more lung inflammation,” Morrison said.
Morrison says she hopes this study will encourage other scientists to reevaluate data sets from older studies.
“Our approach was to take information already out there and put it to new use, and we were able to see something new,” she said.
Moving forward, the research team is hoping to determine which proteins “tell” the macrophages to move into the lungs. Once the protein signals have been identified, it may be possible to create drugs that boost either the number of macrophages, or their activity.
The strategy of boosting human defences to infection, rather than developing another antiviral to which viruses could become resistant, could offer people a flu treatment that would be more effective for much longer.
“If we can boost what resolves infection in us, we probably have a better shot. We’re less likely to have resistance. The immune system is so complicated, but it’s our best bet in the long run to work with what we have rather than chase viruses that continue to escape our therapeutics,” Morrison said.
Athletes often suffer injuries to ligaments in their knees, particularly to the anterior cruciate ligament or ACL. While surgery to replace these torn ligaments is becoming increasingly common around the world it often needs to be repeated. That’s because it has proved challenging to anchor fibrous, soft and wet ligament grafting material into hard bone.
Now, McGill University researchers have new information from the eggshell membrane in chicken eggs that could help change this picture thanks to the potential it offers for improvements in tissue engineering and biomaterial grafts.
Their findings also have the potential to reduce losses for commercial egg and poultry producers.
Anchoring soft and wet fibres by “nailing” them in place
The researchers discovered how the hard shell of a bird egg attaches to the underlying wet fibrous membrane of the egg (the thin membranous layer found inside the shell seen when peeling a hard-boiled egg). By using advanced 3D imaging X-ray and electron microscopes together with cryo-preservation methods the research team were able to peer into this interface in three dimensions to visualize and quantify the interlocking phenomenon.
“Until now, no one had considered how this interface between these two very dissimilar substances, one a hard biorock, and the other a soft fibrous membrane, might be secured at the nanoscale,” says Marc McKee, a professor in the Faculty of Dental Medicine and Oral Health Sciences, and in the Department of Anatomy and Cell Biology, and the principal investigator of the study conducted by doctoral student Daniel Buss and published recently in iScience. “What we found about this soft-hard interface is quite remarkable.”
Nanospikes increase the surface area of contact between soft and hard materials and ensure food safety
The McGill team discovered that, at a certain stage in the development of an egg prior to laying, the shell sends mineral nanospikes into the soft and compliant surface fibres of the underlying eggshell membrane.
This membrane surrounds the soft contents of the egg interior, being either the egg white and yolk from table eggs, or the developing chick embryo in a fertilized and incubated egg.
This nanospiking attachment process between two highly dissimilar materials substantially increases the surface area of the interface between the soft and wet organic fibres and the hard and largely dry inorganic mineral.
Such an attachment importantly anchors and secures this soft-hard interface to prevent slipping and sliding of the fibres within the shell.
Otherwise, detachment of the membrane from the shell can be lethal for the embryonic chick, can weaken the shell, and/or can allow the invasion of pathogens (such as salmonella) into the interior contents of the egg.
Food safety of the table egg relies on an intact shell that is well-integrated with its underlying membrane.
Implications for medical procedures and commercial egg production
With this new understanding of the shell-membrane interface as being a characteristic feature of strong, safe and healthy eggs, losses for table egg producers and poultry breeders might be reduced through the establishment of commercial genetic breeding programs that maintain or maximize this interfacial structure.
The findings might also potentially lead to new engineered, hybrid composite material designs, and to new procedures to improve the outcomes of various medical and dental reconstructive surgeries, both of which may require attaching soft wet fibres to hard materials.
Using the old anaesthesia drug ketamine to pull people out of the depths of severe depression has gone from fringe idea to widespread use in just a few years. Sparked by promising studies and stories of lives transformed, clinics offering intravenous infusions of ketamine have popped up in the US. Some also offer a newer, more expensive, nasal spray version.
But major questions remain about who ketamine can help, why some people get tremendous relief within days or weeks while others don’t, and the costs and benefits of different ways of delivering the drug.
New findings just came out from a study that seeks to answer some of those questions. They add more evidence about the power of IV ketamine to help some of the most severely ill people with depression or bipolar disorder who haven’t gotten relief from other treatments, including many who have frequent suicidal thoughts.
Called Bio-K, the study involved 74 people treated at four clinics in Michigan, Maryland and Minnesota. After just three infusions of ketamine over 11 days, 52% of participants saw their severe depression ease so much they achieved remission. Another 15% responded somewhat.
Half of those who had thought often of suicide before receiving ketamine experienced a dramatic drop in those impulses. The results are published in the Journal of Affective Disorders.
“These participants are very representative of the sickest patients we see, with more than 80% reporting suicidality that would have excluded them from other depression treatment studies,” said University of Michigan Health psychiatrist and study leader Sagar Parikh, MD.
“As in other studies of ketamine, the initial response to treatment was a strong predictor of who would do well,” he added. “Two-thirds of those who responded after one infusion went on to achieve remission, while those who hadn’t responded measurably after two infusions were unlikely to start to respond after an additional one.”
Who responds and why?
What’s the difference between them and those who responded? That’s a key focus of Bio-K, which is funded by donors to the U-M Eisenberg Family Depression Center.
A third of all Bio-K participants didn’t respond to ketamine by the end of the three infusions provided under the study, leaving them to cope with one more failure in a series of attempted treatments.
The team’s in-depth interviews with some of these non-responders show how difficult that can be, as the team reported in a paper last year.
By studying molecules in blood samples from the study’s participants, the Bio-K team hopes to find biomarkers that could predict who is most likely to get relief from ketamine, and who should try other options.
The study is evaluating cell signaling proteins, inflammatory markers and molecules that can indicate rates of cell metabolism in mitochondria. Early results from those analyses should be available in the next year.
From research to clinical use
In the meantime, the strength of the response in Bio-K participants helped fuel the founding of an IV ketamine clinic at University of Michigan Health, says Parikh, who oversees the clinic.
U-M now accepts referrals from providers across the region who have patients with treatment-resistant depression and need another option after trying at least four medications.
Patients come to the main U-M medical campus around eight times during the span of a month for infusions under the care of psychiatrists, anaesthesiologists and other clinicians.
Parikh and his colleagues even wrote a guide for other hospitals on how best to set up and run such a clinic.
A newer version
Meanwhile, the nasal spray form of ketamine, called esketamine and sold under the name Spravato, has captured attention in recent years for its potential to ease disabling and life threatening symptoms without requiring an IV.
The spray involves a form of the drug manufactured by a pharmaceutical company in a way that isolates just one variety of the ketamine molecule, which allowed the company to seek a specific FDA approval.
Parikh notes that U-M was one of the sites for the original small study that led to Spravato’s approval by the FDA, and another larger study sponsored by Janssen, the drug’s manufacturer, that recently concluded. In addition to serving as the local principal investigator for these studies, Parikh also briefly served as a consultant to the company.
Based on the experience in these studies, U-M hopes to start offering Spravato alongside IV ketamine on a clinical basis. Even though it’s not given through an intravenous drip, the nasal spray still requires careful observation of patients under the FDA’s approval conditions.
IV vs nasal spray
Even as researchers search for biomarkers to predict ketamine response, clinicians find themselves with a conundrum: Which patients should start with IV ketamine, and which with Spravato? And how do the two compare head to head in actual response to treatment?
That’s what researchers at Yale University, U-M and their colleagues will soon try to find out, through a new study just funded by the federal Patient-Centered Outcomes Research Institute.
The study, which will begin enrolling up to 400 people at six sites nationwide later this year, will randomly assign people with treatment resistant depression to either the IV or nasal spray form of the drug. They’ll then receive that treatment for about four weeks, and have their symptoms monitored during treatment and for months afterward.
Such a head-to-head study might help inform insurers that haven’t yet started covering one or both forms of ketamine, Parikh noted.
More about the Bio-K results
In the meantime, the treatment response results from the Bio-K study and other studies can help more patients and clinicians understand the impact of IV ketamine.
Although Bio-K accepted people who were suicidal, which many antidepressant medication studies do not, it did not include people who use cannabis or those who have an active substance use disorder, schizophrenia or psychosis. But participants had to have failed to respond to at least two antidepressant or mood stabilising medications after at least eight weeks, or failed to respond to six sessions of ECT, the treatment based on electric stimulation of the brain that has been seen as the last resort for many patients.
The study found that it did not matter if they got their infusions slowly over 100 minutes or in a standard session of 40 minutes.
At the start of the study, the average score of participants on a standard depression scale called MADRS was 28; that average dropped to 11 at 24 hours after the third infusion. A score of 10 or below is considered depression free, or remission, and a drop in score of at least 50% of the total score is considered response. In all, 67% achieved what is considered response, and 52% reached remission.
Chronic exposure of human skin to ultraviolet light causes premature aging, or photoaging. As the skin undergoes photoaging, type I collagen bundles, which are found in the dermis beneath the top layer of the skin and provide strength and support to skin, become fragmented. This leads to wrinkles, fragility and loss of support and elasticity.
“The best way to prevent damage to type I collagen by sunlight is to wear sunscreen consistently, daily if possible and particularly when spending time outdoors,” said Frank Wang, MD, the William B. Taylor Endowed Professor of Clinical Dermatology at U-M Medical School.
Experts observed in a new study that injection of the most popular type of dermal filler, cross-linked hyaluronic acid, into photoaged skin could reverse the dermal changes associated with photoaging.
These fillers are typically injected into the skin to reduce lines and wrinkles.
They are thought to provide clinical improvement by adding volume to the skin, but researchers have found that cross-linked hyaluronic acid also stimulates production of new type I collagen in the dermis.
The filler does so rapidly, stimulating collagen production within several weeks of injection, and is long-lasting, promoting the accumulation of more collagen over the course of a year.
These findings indicate how the filler improves the appearance of skin in the short-term – a combination of space-filling and collagen.
Additionally, since newly formed dermal collagen lasts many years, the findings also provide insight into how the filler can promote long-term clinical improvement, months or even a year after injection.
“A single injection of cross-linked hyaluronic acid dermal filler can lead to rapid and long-lasting improvement of skin by stimulating collagen deposition, and furthermore, repeat injections may add more collagen, eventually reducing the need for re-treatment,” Wang said.
The common yellow commelina, one of the popular plants used to treat children. Photo by Bernard DUPONT via Wikimedia Commons. CC2.0
In 2021, almost 33 of every 1 000 South African children under five years old died.
This under-five mortality rate is far worse than in similar middle-income countries such as Brazil (14.4 per 1000 births), Cuba (5 per 1000), India (30.6), Indonesia (22.2) and Egypt (19.0).
South Africa’s under-five mortality rate also lags behind the UN’s Sustainable Development Goal of reducing these figures worldwide by 2030 to 25 deaths per 1000.
Significant progress has been made. In 1994, South Africa’s under-five mortality rate was 60.4 per 1000. The government’s Expanded Programme on Immunisation was one health intervention that made a difference.
However, inequalities persist. The underfunded public health sector has been stretched to serve 71% of the population.
Worldwide, many people, particularly those in rural settlements, depend on medicinal plants for their health. In August 2023, the World Health Organization held the first global summit on traditional medicine, in India.
Of the province’s population, 49.2% live below the poverty line with no access to proper housing, water and sanitation. These conditions have an impact on children’s health.
Despite the high reliance on traditional medicine by rural populations, the role of medicinal plants for the treatment of childhood diseases remains speculative and lacks systematic documentation.
Our study yielded the first comprehensive inventory of medicinal plants and indigenous knowledge related to children’s healthcare in the area.
Evidence shows traditional health practitioners continue to play an important role in managing childhood illness in sub-Saharan Africa.
South Africa is endowed with a rich wealth of flora and is often acclaimed as a biodiversity hotspot. Thousands of plants are used for traditional medicine for the management of diverse health conditions.
In the North West, we interviewed 101 participants, including traditional health practitioners, specifically those with expertise in managing and treating diseases among children, and herbal vendors operating in the selected study areas.
Gender distribution among the participants was 78% female and 21% male. This signifies the importance of women as active custodians of indigenous knowledge related to childhood health needs.
Of the participants, 63% had completed a secondary level of education, 21.8% had no formal education and 5% had attended primary school. Although 79% of the participants lived in villages, 15.8% were based in urban areas.
The participants were asked which plants they used to treat children. Of the 61 plants identified, 89% were recorded for the first time as botanicals used for childhood-related diseases by traditional health practitioners.
Carpet plant (Geranium incanum), common yellow commelina (Commelina africana) and elephant’s root (Elephantorrhiza elephantina) were the most popular medicinal plants.
Carpet plant was used as a treatment for diverse health problems such as umbilical cord conditions, muscle fits, measles, weight loss and appetite loss.
Roots and rhizomes were the parts most frequently used as treatments (40%), followed by leaves (23%) and whole plants (20%).
Boiling plants or softening them in liquid were the main preparation methods. The plant remedies were mainly administered orally (60%) and used on the skin (39%).
The study also confirmed there are similarities in indigenous practices, techniques and plant matter for specific conditions that were previously reported in other provinces: KwaZulu-Natal and the Eastern Cape.
The way forward
There is increasing support from governments for promoting traditional medicine as part of primary healthcare in African countries such as Cameroon and South Africa.
We recommend that:
Government provide institutional and financial support to determine the role of herbal medicine in primary healthcare. Working with traditional health practitioners, medicinal plants must be documented and testing laboratories need to be set up to establish their efficacy and to determine appropriate dosages.
Botanical gardens should be created to ensure the sustainability of plants and their continued role in providing much-needed medical care. In the North West province, 40% of the ecosystems are under severe stress, with 11 of the 61 vegetation and 14 of the 18 river types classified as threatened. Medicinal plants are mostly harvested from the wild, so it’s possible that many could face extinction from uncontrolled harvesting.
Authors
Tshepiso Ndhlovu Lecturer and researcher, University of Mpumalanga
Detection of the viruses that infect the typhoid fever bacterium in sewage indicates disease burden
Researchers can accurately track where typhoid fever cases are highest by monitoring environmental samples for viruses called bacteriophages that specifically infect the bacterium that causes typhoid fever. Senjuti Saha of the Child Health Research Foundation in Bangladesh and colleagues report these findings in a new study published February 15 in the open access journal PLOS Neglected Tropical Diseases.
Typhoid fever is a common infection in many low- and middle-income countries and causes an estimated 135 000 deaths and 14 million infections globally each year. The World Health Organization has prequalified two typhoid vaccines, but for policymakers to plan effective vaccination strategies, they need accurate, high-resolution estimates of where the burden is highest.
Traditionally, people have cultured the bacterium that causes typhoid fever from blood samples to determine where the infection is most common, but in the new paper, researchers tried a more cost-effective surveillance approach. They tested environmental water samples from sewage and other locations to detect bacteriophages specific to the water-borne pathogen that causes typhoid fever, Salmonella Typhi.
The team tested 303 water samples from two locations in Bangladesh: the urban capital city, Dhaka, and a rural district, Mirzapur. They found that bacteriophages specific for Salmonella Typhi were present in 31% of environmental samples in Dhaka, compared to just 3% of samples from Mirzapur. This corresponds to results from more than 8,400 blood cultures, in which 5% of cultures from Dhaka and 0.05% from Mirzapur tested positive.
The new results suggest that detecting bacteriophages specific for Salmonella Typhi may be a rapid environmental surveillance method that could help decision makers understand the presence of typhoid fever in the community. The researchers propose that environment monitoring of bacteriophage could be a simple, cost-effective and scalable tool to assist policy decisions on typhoid control.
The authors add: “Looking for bacteriophages in wastewater is a low-cost method for identifying typhoid hotspots without doing expensive blood cultures on thousands of people.”
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