Year: 2023

Categories : AgeingTags :

Old Age Funding is Not Keeping Pace with Our Ageing Population, Report Finds

On By ModernMedia
Photo by Kampus Production on Pexels

South Africa’s population is ageing, yet government funding for community-based elder care services is not increasing to meet the demand.

This is a key finding by Family Caregiving, a programme at the University of Cape Town focused on the needs of older people, which has released two reports on funding for old age care and how care is experienced by older people in South Africa. 

“We want to work with the government and make useful suggestions about what is needed,” says Dr Elena Moore, who led the research together with Dr Gabrielle Kelly.

There are nearly 6 million people over the age of 60 in South Africa, about 10% of the population. The older population is expected to grow to over 15% of the total population by 2050. Also, 40% of older people have a significant need for care, says Moore.

The government currently provides subsidies to non-profit organisations that provide health and social services for older people. But according to Family Caregiving’s research, the overall amount spent on these subsidies by provincial governments, when adjusted for inflation and the growing ageing population, has decreased by 13% since 2007.

A lack of sufficient care for older people means that family members, often women, carry the burden of caring for older family members. The government does provide a Grant-in-Aid social grant of R510 a month, but few people who qualify for it know about it and the amount is too little to cover the cost of a full-time carer, according to the Family Caregiving report.

Family Caregiving is calling on the departments of social development and health to expand the implementation of the Older Persons Act of 2006. The Act provides for community-based care services, ensuring that older people can stay within their households and access the care they need in their communities.

According to the report, approximately 80 000 older people in South Africa receive care at a community centre and about 18 000 people receive state subsidies in care homes. But the report found that the subsidies do not come close to covering the running costs of these programmes and that existing programmes do not meet the growing demand.

Underfunding

Neighbourhood Old Age Home (NOAH), a non-profit organisation in the Western Cape, provides a variety of services. Its housing programme provides 94 beds. For this, it receives R440 000 from the provincial department for social development. But the actual cost of running the programme is nearly R850 000, so the organisation has to absorb almost half the running costs.

In Khayelitsha, NOAH runs a service centre that provides community-based care and support services to nearly 90 older people. The centre operates five days a week and offers meals, educational and skills development programmes, health and social services, and recreational opportunities.

The centre qualifies for an R2230 subsidy per person per year. It receives R190 000 from the government, but it costs R540 000 to run.

In Woodstock, the NOAH service centre has 29 beneficiaries. It operates three days a week and qualifies for a subsidy of R1419 per person per year. It received R59 300 in government funding, but it costs over R600 000 to run.

In KwaZulu-Natal, non-profit organisation The Association For The Aged (TAFTA) runs a variety of services for older persons. Its frail care services rely on a subsidy as well as the beneficiaries’ monthly old age grants, but this makes up only 40% of its running costs, creating a monthly shortfall of R6600 per person.

TAFTA’s assisted living programme is not subsidised. Beneficiaries contribute their old age grant (R2080) towards food and accommodation and TAFTA contributes another R2500 per person. TAFTA service centres receive R18 per person per day, leaving a shortfall of R35 per person per day.

According to Family Caregiving, smaller organisations that do not have the institutional networks of NOAH and TAFTA are often not able to absorb these shortfalls.

Esther Lewis, spokesperson for the Western Cape Department of Social Development, says the province subsidises 186 service centres, catering for 12 000 people. The province also supports financially struggling organisations with mentoring and training. This year, the Western Cape department provided additional grants to organisations for operational costs.

Although funding has increased in the Western Cape and KwaZulu-Natal since 2007, in most provinces subsidies are not paid or are not reported, Family Caregiving found.

Looking forward

Family Caregiving is calling for more funding for old-age care, from subsidies for care organisations to increased funding for health facilities for old age care.

Moore says a multi-disciplinary team is needed to address the challenges facing older people. The team should include representatives from the government departments and organisations as well as a range of experts, from economists to healthcare practitioners.

The Family Caregiving report recommends that the government take steps to ensure that all provinces provide subsidies for old age care and that subsidies increase to meet the growing demand. It recommends that while subsidies focus on service centres and residential care, government support for home-based care services be expanded. Also, existing healthcare facilities, such as clinics and hospitals, can be better optimised to care for older people. Health workers should receive training and information on caring for older people, the report says.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : Diet and Nutrition GeneticsTags :

Going Vegetarian may be Down to Genetics

On By ModernMedia
Photo by Brad West on Unsplash

A person’s genetic makeup plays a role in determining whether they can stick to a strict vegetarian diet, a new study has found. The findings, published in PLOS ONE, open the door to further studies that could have important implications regarding dietary recommendations and the production of meat substitutes. It is the first fully peer-reviewed and indexed study to look at the association between genetics and strict vegetarianism.

“Are all humans capable of subsisting long term on a strict vegetarian diet? This is a question that has not been seriously studied,”said corresponding study author Dr. Nabeel Yaseen, professor emeritus of pathology at Northwestern University Feinberg School of Medicine.

A large proportion (about 48 to 64%) of self-identified “vegetarians” report eating fish, poultry and/or red meat, which Yaseen said suggests environmental or biological constraints override the desire to adhere to a vegetarian diet.

“It seems there are more people who would like to be vegetarian than actually are, and we think it’s because there is something hard-wired here that people may be missing.”

Several genes involved in lipid metabolism, brain function

To determine whether genetics contribute to one’s ability to adhere to a vegetarian diet, the scientists compared UK Biobank genetic data from 5 324 strict vegetarians (consuming no fish, poultry or red meat) to 329 455 controls. All study participants were white Caucasian to attain a homogeneous sample and avoid confounding by ethnicity.

The study identified three genes that are significantly associated with vegetarianism and another 31 genes that are potentially associated. Several of these genes, including two of the top three (NPC1 and RMC1), are involved in lipid (fat) metabolism and/or brain function, the study found.

“One area in which plant products differ from meat is complex lipids,” Yaseen said. “My speculation is there may be lipid component(s) present in meat that some people need. And maybe people whose genetics favor vegetarianism are able to synthesize these components endogenously. However, at this time, this is mere speculation and much more work needs to be done to understand the physiology of vegetarianism.”

Why do most people eat meat?

Religious and moral considerations have been major motivations behind adopting a vegetarian diet, and recent research has provided evidence for its health benefits. And although vegetarianism is increasing in popularity, vegetarians remain a small minority of people worldwide. For example, in the US, vegetarians comprise approximately 3 to 4% of the population. In the UK, 2.3% of adults and 1.9% of children are vegetarian.

This raises the question of why most people still prefer to eat meat products. The driving factor for food and drink preference is not just taste, but also how an individual’s body metabolises it, Yaseen said. For example, when trying alcohol or coffee for the first time, most people would not find them pleasurable, but over time, one develops a taste because of how alcohol or caffeine makes them feel.

“I think with meat, there’s something similar,” Yaseen said. “Perhaps you have a certain component – I’m speculating a lipid component – that makes you need it and crave it.”

If genetics influence whether someone chooses to be a vegetarian, what does that mean for those who don’t eat meat for religious or moral reasons?

“While religious and moral considerations certainly play a major role in the motivation to adopt a vegetarian diet, our data suggest that the ability to adhere to such a diet is constrained by genetics,” Yaseen said. “We hope that future studies will lead to a better understanding of the physiologic differences between vegetarians and non-vegetarians, thus enabling us to provide personalized dietary recommendations and to produce better meat substitutes.”

Source: Northwestern University

Categories : New Compounds and Treatments OphthalmologyTags : 3 Comments

Eyedrops instead of Injections for Age-related Macular Degeneration

On By ModernMedia
Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

A new compound potentially could offer an alternative to injections for the millions of people who suffer from wet age-related macular degeneration (AMD). The condition causes vision loss due to the uncontrolled growth and leakage of blood vessels in the back of the eye. A new paper in Cell Reports Medicine finds that a small-molecule inhibitor can reverse damage from AMD and promote regenerative and healing processes.

The drug can also be delivered via eyedrops – an improvement over current treatments for AMD, which require repeated injections into the eye.

“The idea was to develop something that can be more patient-friendly and doesn’t require a visit to the doctor’s office,” said lead researcher Yulia Komarova, associate professor of pharmacology at University of Illinois Chicago.

Komarova’s compound targets the protein End Binding-3 in endothelial cells, which line the inside of blood vessels. In the new study, the researchers looked at whether inhibiting EB3 function could stop the damaging leakage associated with wet AMD.

Using computational drug design methods, the team developed a small molecule drug, End Binding-3 inhibitor (EBIN), that could be delivered externally via eyedrops instead of by injection. They then tested its effectiveness in animal models of wet AMD, finding that twice-daily treatment reduced eye damage within 2–3 weeks.

Further investigation found that the inhibitor worked by rolling back aging-related genetic modifications. Aging causes inflammation and hypoxia in the eye that leads to changes in gene expression associated with the cellular effects and symptoms of wet AMD. Komarova and colleagues found that the EB3 inhibitor they developed reversed these epigenetic changes, restoring gene expression to a normal, healthy state.

“We reduce the effects of the stressor on endothelial cells and we improve regenerative processes, accelerating healing,” Komarova said. “That can be tremendous for the function of the cells.”

Because blood vessel leakage and hypoxic stress also drive many other medical conditions, Komarova’s group is interested in testing the inhibitor in models of acute lung injury, diabetic retinopathy, stroke, heart disease and even the general effects of aging on the brain. They are also exploring whether an implantable lens, similar to a contact lens, could deliver the drug to the eye more effectively than eyedrops.

Source: University of Illinois Chicago

Categories : COVIDTags :

New SARS-CoV-2 Variant BA.2.86 not as Resistant to Antibodies as First Feared

On By ModernMedia
Image by Fusion Medical on Unsplash

Researchers studying the new SARS-CoV-2 variant BA.2.86 have found that the new variant was not significantly more resistant to antibodies than several other circulating variants. Their study, published in The Lancet Infectious Diseases, also showed that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86.

The recently emerged BA.2.86 is very different from any other currently circulating variants. It includes many mutations in the spike gene, reminiscent of the emergence of Omicron.  The virus uses the viral spike to infect cells and is the main target for our antibodies.  When the spike mutates, it comes with the risk that our antibodies are less effective against this new ‘variant’, and therefore that our protection from infection is reduced and that vaccines may need to be updated.

“We engineered a spike gene that matches that of the BA.2.86 variant and tested the blood of Stockholm blood donors (specifically those donations made very recently) to see how effective their antibodies are against this new variant. We found that although BA.2.86 was quite resistant to neutralising antibodies, it wasn’t significantly more resistant than a number of other variants that are also circulating”, says Daniel Sheward, lead author of the study and Postdoctoral researcher in Benjamin Murrell’s team at Karolinska Institutet.

An important question is whether upcoming updated vaccines that are based on the XBB variant will boost protection against BA.2.86.  To determine whether antibodies triggered by infection with XBB may be effective against this new variant, Ben Murrell’s team also compared samples taken before and after XBB spread in Sweden.

“We also found that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86. However, BA.2.86 was resistant to all available monoclonal antibody therapeutics that we tested,” says Daniel Sheward.

Public health agencies need to know what the current level of immunity to this new variant is, and whether the vaccines are sufficient must be updated.  Monoclonal antibodies also represent an important option for some patient groups, such as the immunocompromised – for the clinicians, it’s important to know which if any, monoclonal antibody therapeutics will be effective against the variants that are circulating.  

“I think the main message is that there is currently no reason to be alarmed over this new variant and that it’s probably a good idea to get a booster vaccine when they are offered.  However, another ‘omicron-like’ event is also a reminder that we shouldn’t get complacent”, says Benjamin Murrell, Principal researcher at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

Source: Karolinska Institutet

Categories : Cancer PaediatricsTags :

The Urgent Need for Early Detection Emphasised this Bone Marrow & Leukaemia Awareness Month

On By ModernMedia
Credit: National Cancer Institute

Leukaemia has been identified as the most prevalent cancer among the country’s youth, according to the latest report from the National Cancer Registry (NCR) of South Africa (2021). However, approximately half of children with cancer remain undiagnosed, with the majority of cases only being detected during the advanced stages of the illness. This is partly attributed to a lack of awareness of the early warning signs of childhood cancer.

As the world observes Bone Marrow & Leukaemia Awareness Month until the 15th of October, Dr Candice Hendricks, Paediatric Haematologist and Medical Spokesperson for DKMS Africa shares that leukaemia can be categorised as acute leukaemias or chronic leukaemias, each with varying symptoms. “Acute leukaemias are far more common in children and can further be divided into acute lymphoblastic- (ALL) and acute myeloid leukaemia (AML). Among children, especially those aged between two and 10, Acute Lymphoblastic Leukaemia (ALL) is the most common blood cancer in this age group.

“This disease arises from genetic mutations in immature lymphocytes called lymphoblasts which are located in the bone marrow. The mutations lead to uncontrolled growth of these lymphoblasts,” she explains. “Lymphoblasts are abnormal blood stem cells that lose the ability to make mature blood cells. The uncontrolled growth of these cells in the bone marrow displaces normal blood cell development and leads to a decrease in properly functioning red blood cells, white blood cells, and platelets. Patients may potentially present with an elevated white blood cell count on blood results, however, their impaired function leaves the body vulnerable to infections.”

Aligned with the NCR, Dr Hendricks emphasises that early symptoms often go unnoticed, as they mimic common, mild conditions, causing many patients and those who care for them to overlook them. “However, the severity of these symptoms escalates rapidly with acute leukaemias and persist even after standard treatment for infections. A high index of suspicion is required in diagnosing patients, and if any symptom persists, an immediate full blood count test is necessary, followed by additional tests if irregularities are detected.”

Prominent symptoms indicating the disease include:

  • Blood clotting disorders or blood diathesis characterised by easy bruising from minor impacts and the appearance of small reddish spots on the skin. Other signs encompass blood in urine, as well as uncontrollable gum and nose bleeding.
  • Muscle and joint pain, particularly in the limbs, along with frequent limb numbness.
  • Fever and night sweats.
  • Anaemia caused by a deficiency of red blood cells, leading to constant fatigue, reduced exercise capacity, lethargy, sleepiness, and pale skin.
  • Recurrent infections that persist despite antibiotic treatment due to cancer cells impairing the immune system. Pathological cancer cells displace healthy leukocytes, rendering the body susceptible to various viral, bacterial, and fungal infections.
  • Loss of appetite and weight loss.
  • Enlarged lymph nodes.
  • Stomach pain resulting from spleen and/or liver enlargement.

In support of Bone Marrow & Leukaemia Awareness Month, DKMS Africa continues to raise awareness and funds to cover the registration costs for as many potential stem cell donors as possible. Stem cell donations offer the best chance of survival for children afflicted by high-risk leukaemia which does not respond to or recurs after standard treatment. Answer the call! If you’re aged between 17 and 55 and in good general health, please register at https://www.dkms-africa.org/register-now. Registration is entirely free and takes less than five minutes.

For further information, get in touch with DKMS Africa at 0800 12 10 82.

About DKMS
DKMS is an international non-profit organisation dedicated to saving the lives of patients with blood cancer and blood disorders. Founded in Germany in 1991 by Dr. Peter Harf, DKMS and organisations of over 1,000 employees have since relentlessly pursued the aim of giving as many patients as possible a second chance at life. With over 11 million registered donors, DKMS has succeeded in doing this 100,000 times to date by providing blood stem cell donations to those in need. This accomplishment has led to DKMS becoming the global leader in the facilitation of unrelated blood stem cell transplants. The organisation has offices in Germany, the US, Poland, the UK, Chile and South Africa. In India, DKMS has founded the joint venture DKMS-BMST together with the Bangalore Medical Services Trust. International expansion and collaboration are key to helping patients worldwide because, like the organisation itself, blood cancer knows no borders.

DKMS is also heavily involved in the fields of medicine and science, with its own research unit focused on continually improving the survival and recovery rate of patients. In its high-performance laboratory, the DKMS Life Science Lab, the organisation sets worldwide standards in the typing of potential blood stem cell donors.

Categories : Gender Metabolic DisordersTags :

Study Suggests Lowering Type 2 Diabetes Diagnosis Threshold in Women under 50

On By ModernMedia
Photo by National Cancer Institute on Unsplash

New research published in the journal Diabetes Therapy suggests that the diagnosis threshold for type 2 diabetes (T2D) should be lowered in women aged under 50 years, since natural blood loss through menstruation could be affecting their blood sugar management.

Analysis of the national diabetes audit results has shown that women of younger age with type 2 diabetes mellitus (T2D) seem to have a higher mortality rate than men. The underlying mechanisms remain unclear. However, it is known that women are on average diagnosed with T2D at a later age than men. In this new study, the authors investigated whether a contributing factor to this late diagnosis may be a sex difference in the levels of glycated haemoglobin (HbA1c) due to haemoglobin replacement linked to menstrual blood loss.

This mechanism behind this could be shorter erythrocyte (red blood cell) survival which results in shorter exposure of haemoglobin to glucose compared with individuals who do not menstruate. Given that the diagnosis of T2D is also based on HbA1c, the use of the same reference range irrespective of age and sex, when a slightly lower point for T2D for premenopausal women may be appropriate, could potentially lead to under diagnosis of T2D in women and missed opportunities for intervention.

The study, by Dr Adrian Heald, Salford Royal Hospital, UK, and colleagues, examined HbA1c testing across seven UK laboratory sites (representing 5% of UK population). They conducted an exploratory analysis in two cohorts: cohort 1 was from one laboratory tested between 2012 and 2019 (146 907 participants). They assessed the sex and age differences of HbA1c in individuals who underwent single testing only, that had not been diagnosed with diabetes and had an HbA1c result of equal to or less than 48mmol/mol (the cutoff for diagnosing diabetes). The process was replicated in cohort 2 results from six laboratories with individuals tested between 2019 and 2021 (total people included 938 678). The possible national impact was estimated by extrapolating findings based on the Office of National Statistics (ONS) England population data and National Diabetes Audit published T2D prevalence and related excess mortality.

At age 50 years, average HbA1c levels in women lag by approximately five years compared to men. The data also show women aged under 50 years old had an HbA1c distribution that was lower than that of men by an average of 1.6mmol/mol (4.7% of the overall mean) while the difference in the distribution of HbA1c for individuals aged 50 years and over was less pronounced.  Further analysis showed that, at HbA1c of 48mmol/mol, 50% fewer women could be diagnosed with T2D than men under the age of 50, whilst only 20% fewer women could be diagnosed with T2D than men over or equal to the age of 50. These findings were consistent with those in cohort 2.

Based on these observations, the authors estimated the effects of lowering the threshold for diagnosis of diabetes from HbA1c (48mmol/mol) by 4.2% to 46mmol/mol for women under the age of 50. This analysis showed that an additional 35 345 currently undiagnosed women in England would be reclassified as being diagnosed with T2D (17% more than the current 208 000 recorded women with T2D aged under 50 years). Lifestyle changes and treatment for diabetes would then be initiated for these women enabling improvement in health outcomes over both the short and longer term.

The authors also highlight that sex and gender difference in adverse cardiovascular risk factors are known to be present prior to the development of T2D. Once diagnosed, the prevalence of atherosclerotic cardiovascular disease is twice as high in patients with diabetes mellitus compared to those without diabetes mellitus. For women, diabetes mellitus is a stronger risk factor for cardiovascular disease than for men: women with diabetes aged 35–59 years have the highest relative cardiovascular death risk across all age and sex groups.

Furthermore, there is disparity in cardiovascular risk factor management between men and women, including in high-risk groups such as women with T2D.  Women are less likely than men to receive treatment and cardiovascular risk reduction interventions that are recommended by international guidelines on diabetes. In addition, concordance with medication or prescription treating cardiovascular risk factors is lower in women than men with T2D, with less use of statins, aspirin and beta blockers. The authors say taken together, these factors mean “timely diagnosis of type 2 diabetes and initiation of preventative treatment has the potential to improve cardiovascular risk profile over lifetime and facilitate longer life quality and expectancy in women. Our findings provide evidence that the HbA1c threshold for this group should be re-evaluated.”

Source: EurekAlert!

Categories : HospitalsTags :

Department of Health in Last-minute Bid to Avoid Stand-off with Nurses over Uniforms

On By ModernMedia
Photo by Jeshoots Com on Unsplash

By Marecia Damons for GroundUp

The Department of Health is scrambling to avoid a stand-off with nurses who have threatened to work in their own clothes if a dispute over the provision of uniforms is not resolved.

Since 2005, nurses had received an annual allowance to buy their uniforms. But this ended on 31 March this year, after a new agreement was signed in the Public Health and Social Development Sectoral Bargaining Council in terms of which they would get uniforms instead.

As a result, nurses did not get the usual allowance in April – R2600 a year, according to Spokesperson for the Democratic Nursing Association of SA (DENOSA) Sibongiseni Delihlazo.

Instead, they were supposed to be provided with uniforms by 1 October 2023. The agreement stated that in the first year, government must provide nurses with four sets of uniforms, one pair of shoes, and one jersey. In the second year, government must provide three sets of uniforms, one belt, and one jacket.

The plan was that the procurement process would be centralised. But at another bargaining council meeting, in June 2023, the health department said it would be difficult to provide the uniforms on time.

Then on 12 July, Sandile Buthelezi, director-general for the DOH, issued a circular to all provincial health departments notifying them that the uniforms would be provided from January 2024 to January 2025.

The circular stated that the DOH would use a decentralised approach to providing uniforms by using provincial tenders.

“Provincial heads are responsible for participating and facilitating in tender processes through the bid specification in terms of colour, fabric composition and garment, development, review of the policy and monitoring and evaluation,” Buthelezi wrote.

Until January 2026, the circular said, nurses would be expected to wear the new uniform from Monday to Thursday and wear their old uniform from Friday to Sunday. From January 2026, when they would have both years’ issue, nurses would be expected to wear the new uniforms every day.

DENOSA responded to this a week later, and said the department’s circular went against the bargaining agreement.

Delihlazo said they proposed that if the department is unable to supply the uniform by 1 October, they must pay nurses an allowance as previously.

If the department failed to provide uniforms or pay an allowance, DENOSA said, its 84 000 members would embark on an indefinite protest action by wearing their own clothes to work from 1 October.

Delihlazo said the yearly allowance did not cover the cost of a full uniform. “Their uniforms are tearing and the colour is fading. So how can you expect nurses to wear uniforms if you don’t pay them a uniform allowance?”

He said the tender process meant the colour of the nurses’ uniforms and the quality of the fabrics might differ from one province to the next. The process also “opens a window of opportunity for corruption,” Delihlazo said. “Money may be given for uniforms but the tender process is porous.”.

Then, at a last-minute meeting of the bargaining council last Thursday, the department proposed to put on hold the supply of uniforms until 2024, according to a DENOSA statement. Meanwhile the health department would pay nurses an allowance of R3,153 by 30 November.

DENOSA said the agreement should be signed by the end of the week. If not, the union said, nurses would work in their own clothes.

The health department did not respond to GroundUp’s questions.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : Cancer UrogenitalTags :

New Treatment Combination could Prevent Cystectomy in Invasive Bladder Cancer

On By ModernMedia
Photo by cottonbro studio

Mount Sinai investigators have developed a new approach for treating invasive bladder cancer without the need for surgical removal of the bladder, they report in their study published in Nature Medicine. At present, cystectomy (removal of the bladder) is currently a standard approach when cancer has invaded the muscle layer of the bladder.

In a phase 2 clinical trial that was the first of its kind, doctors found that some patients could be treated with a combination of chemotherapy and immunotherapy without the need to remove their bladder. Radical cystectomy can be curative in muscle-invasive bladder cancer, but the procedure is a life-changing operation due to the need for urinary diversion and is associated with a 90 day mortality risk of up to 6–8%.

“Treatment for muscle-invasive bladder cancer is in need of major improvements from both a quality-of-life and an effectiveness standpoint,” said Matthew Galsky, MD, Co-Director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute, a part of the Tisch Cancer Center at Mount Sinai. “If additional research confirms our findings, this may lead to a new paradigm in the treatment of muscle-invasive bladder cancer.”

The 76 patients received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Approximately 43% (33 patients) achieved a complete response (no detectable cancer) when treated with this combination of chemotherapy and immunotherapy. Patients with a clinical complete response were offered the opportunity to proceed with additional immunotherapy, without surgical removal of the bladder. Among patients opting to proceed without surgical removal of the bladder, about 70% had no evidence of recurrent cancer after two years.

The most common adverse events were fatigue, anaemia, neutropenia and nausea. Somatic alterations in pre-specified genes or increased tumour mutational burden did not improve the positive predictive value of complete response.

Based on the results of this trial, two follow-up studies were launched to build on this approach; one is ongoing, and another will open in the next six months.

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

Categories : GeneticsTags :

A Gene for ‘Explosive’ Cell Death Drives Runaway Inflammation

On By ModernMedia

Australian researchers at Walter and Eliza Hall Institute have found that a genetic change that increases the risk of inflammation, through necroptosis, a process described as ‘explosive’ cell death, is carried by up to 3% of the global population.

The study, which is published in Nature Communications, may explain why some people have an increased chance of developing conditions like inflammatory bowel disease or suffer more severe reactions to infections with bacteria like Salmonella.

Immune power of ‘explosive’ cell death

Programmed cell death is a normal part of the body’s immune system and maintenance, removing unwanted, damaged or dangerous cells, and preventing the spread of viruses, bacteria, and even cancer.

First author WEHI’s Dr Sarah Garnish is first author on the paper and said that while there are various types of cell death, necroptosis is distinguished by its ferocity – the cells essentially explode, which sounds an alarm for other cells in the body to respond.

“This is a good thing in the case of a viral infection, where necroptosis not only kills the infected cells but instructs the immune system to respond, clean things up, and start a more specific, long lived immune response,” Dr Garnish said.

“But when necroptosis is uncontrolled or excessive, the inflammatory response can actually trigger disease.”

Genetic brakes

The gatekeeper of necroptosis is the gene MLKL. When the body needs to trigger a cell death response with plenty of firepower, the cellular brakes that normally keep MLKL in-check are released. However, some of us make a form of MLKL with flimsy brakes.

Dr Garnish and her co-authors have been able to quantify this at a population level for the first time.

“For most of us, MLKL will stop when the body tells it to stop, but 2-3% of people have a form of MLKL that is less responsive to stop signals,” Dr Garnish said.

“While 2-3% doesn’t seem like much, when you consider the global population, this adds up to many millions of people carrying a copy of this gene variant.”

Project leader Dr Joanne Hildebrand said the research proposes that a common genetic change like this can combine with a person’s lifestyle, infection history and broader genetic makeup to increase the risk of inflammatory diseases and severe reactions to infections.

This is known as polygenic risk, the combined influence of multiple genes on developing a certain trait or condition.

“Taking Type 2 diabetes as an example, it’s rare that just one gene change determines whether someone will develop the condition,” Dr Hildebrand said.

“Instead many different genes play a role, as do environmental factors, like diet and smoking.”

Dr Hildebrand said it’s not as simple as directly connecting this difference in the MLKL gene with the chance of someone developing a specific condition.

“We haven’t tagged this MLKL gene variant to any one particular disease yet, but we see real potential for it to combine with other gene variants, and other environmental cues, to influence the intensity of our inflammatory response.”

Towards personalised medicine

Our understanding of MLKL has come a long way since it surfaced by chance in a WEHI lab more than 20 years ago. Today’s research opens the door for future tests and screening to determine disease risks.

Genome sequencing is becoming cheaper and more readily accessible. As more genomic data becomes available to researchers, it increases the likelihood that they can link common genetic variants, like the one described for MLKL, with disease.

In the future researchers hope to pinpoint the genetic changes that might mean someone is more likely to have a severe case of COVID-19, or less likely to bounce back after chemotherapy.

“Every piece of information like this helps us make personalised medicine more of a reality,” said Dr Garnish.

The WEHI team is also investigating whether uncontrolled necroptosis could be beneficial in some circumstances. For example, could people with the MLKL gene variant have a stronger cellular defensive response to certain viruses?

“Gene changes like this don’t usually accumulate in the population over time unless there is a reason for it – they generally get passed on because they do something good,” said Dr Garnish.

“We’re looking at the downsides of having this gene change, but we’re looking for the upsides as well.”

Source: Walter and Eliza Hall Institute

Categories : DermatologyTags :

The Untapped Potential of Phages for the Treatment of Atopic Dermatitis

On By ModernMedia
Credit: CC0

Researchers in Austria have discovered a new approach to treating atopic dermatitis: bacteriophages, which colonise the skin as viral components of the microbiome and can drive the development of innovative atopic dermatitis therapies. The research results were recently published in the scientific journal Science Advances.

Until now, the importance of bacteriophages in the human body has been known primarily from analyses of the intestine. In the search for innovative therapeutic measures for atopic dermatitis (AD), the MedUni Vienna research team led by Wolfgang Weninger, Head of the Department of Dermatology, has now investigated the interaction of phages and bacteria in the skin for the first time. After all, it has long been known that the progression of AD is accompanied by massive changes in the skin microbiome. The microbiome is the sum of all microorganisms on the skin and has been primarily investigated for its bacterial constituents. It has been unknown whether viruses also contribute to the nature of the bacterial microbiome in healthy and diseased skin. Phages are viruses of different types and functions whose sole aim is to infect bacteria, thereby either destroying them – or stimulating them to multiply.

New phages identified

“In our study, we discovered previously unknown phages in the microbiome of the skin samples of AD patients, which help certain bacteria to grow faster in different ways,” note first authors Karin Pfisterer and Matthias Wielscher from the Department of Dermatology at MedUni Vienna. The resulting shift in the balance between phages and bacteria was not detected in the comparative samples from healthy individuals and may be one explanation for the overpopulation of the skin microbiome with bacteria called Staphylococcus aureus found in AD. These findings contribute significantly to a better understanding of the skin bioflora in AD patients and pave the way for the development of new targeted therapeutic interventions: By identifying and culturing phages specialised for Staphylococcus aureus, a promising new option is available.

Specialists for targeted therapy

Bacteriophages are found not only in the body, but in every habitat populated by bacteria. There are a staggering 1031 different phage species. One of their characteristics is that they prove to be extremely specific when it comes to choosing their target of infection: most phages specialise in a particular genus, and in many cases in only a single species of bacteria. While that makes it a challenge for scientists to identify the type of phage needed for a particular purpose, it also enables them to use them in a targeted manner. Bacterial viruses do not make any difference between antibiotic-resistant and other bacteria, thus they are being researched as possible weapon in the fight against multi-resistant pathogens. Further studies are now planned to confirm phage therapy for topical use in atopic dermatitis.

Source: Medical University of Vienna