Month: February 2021

Categories : UrologyTags :

Relugolix Combination Therapy is Promising for Fibroid Symptom Relief

On By ModernMedia

A pair of clinical trials showed that combination therapy with relugolix reduced heavy bleeding and pain from uterine fibroids without the risk of side effects from low oestrogen levels.

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, currently approved for men with advanced prostate cancer.  Uterine fibroids are common in women, and a quarter of those who are affected by them experience symptoms such as heavy menstrual bleeding and pain.

Injectable long-acting GnRH agonists are effective treatments for uterine fibroids, but cause BMD loss and thus are not generally eligible for long term use.  
In the two trials done in North and South America, Africa, and Europe, 71% and 73% of patients, respectively, who received relugolix together with estradiol and norethindrone acetate had significantly lower blood loss, compared with 19% and 15% in the placebo group.
Similar bone mineral density (BMD) measures were seen in the placebo and relugolix combination therapy groups; but MD decreased among patients who received relugolix monotherapy.

“For the first time, we have an oral treatment that can effectively and safely improve the symptoms of uterine fibroids, particularly heavy menstrual bleeding,” Ayman Al-Hendy, MD, PhD, of the University of Chicago Medicine, stated in an interview. and added that relugolix may be a viable, long-term alternative to the current surgical treatments available for fibroids patients.

“The goal of this program from the beginning was to develop an effective and long-term treatment as a viable alternative to hysterectomy,” Dr Al-Hendy said. “Any patient with uterine fibroids would be a good candidate for this non-surgical treatment.”

Lauren Schiff, MD, associate professor of minimally invasive gynecologic surgery at the school of medicine at the University of North Carolina at Chapel Hill, said that relugolix seems to be a good option for non-surgical treatment of fibroids.

Dr Schiff, who was not involved with the study, said that understanding bone mineral density (BMD) is key for using relugolix past six months. “If the bone density safety measure is maintained for long-term use, then this would be really ideal medication,” she told MedPage Today.

The trial’s primary endpoint was less than 80 ml blood loss, and >50% reduction in total blood loss from trial start. The investigators assessed several secondary outcomes, including amenorrhea, volume of menstrual blood loss, distress, pain, anaemia, fibroid volume, and uterine volume.

Around 388 participants were randomised in the first trial, and 382 in the second.

Around three-quarters of patients who received relugolix combination therapy reached the primary endpoint, with the treatment effects appearing similar baseline characteristics.

Amenorrhea over the last 35 days of the trial occurred in 52% and 50% of participants who received relugolix combination therapy in each trial, respectively. Pain was also reduced in the treatment groups.

Patients who received the combination therapy also had improvements in pain, distress from bleeding and pelvic discomfort, anaemia, and experienced reduced uterine volume. However, significant shrinkage in fibroid volume was not observed.

The prevalence of side effects was similar in the relugolix combination therapy group and the placebo cohort, with hot flashes being the most commonly reported side effect in the trial.

Strict assessment criteria for patients meant generalisability was limited. Additionally, study duration was only six months. The researchers plan to release data from a 28-week extension study, as well as a 52-week randomised-withdrawal trial, and these may shed more light on safety and efficacy in the long term.

Source: MedPage Today

Journal information: Al-Hendy A, et al “Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy” N Engl Med 2021; DOI: 10.1056/NEJMoa2008283.

Categories : GeneticsTags :

Study Reveals How Thyroid Subtly Regulates Metabolism

On By ModernMedia

Thyroid hormone appears to regulate metabolism by acting as a ‘dimmer switch’ as opposed to an ‘on/off’ switch, as reported by a new study from the University of Pennsylvania.

The thyroid hormone has long been known to be an important controller of the body’s metabolism, as well development, but how exactly this is achieved remains something of a mystery. Part of this problem was that the thyroid hormone worked inside the nucleus, activating some genes and deactivating others. Being able to observe this process has been extremely challenging.

“We were able in this study to show that thyroid hormone doesn’t just turn things on or off, as the canonical model suggests, but instead more subtly shifts the balance between the repression and enhancement of gene activity,” said principal investigator Mitchell Lazar, MD, PhD, at Penn Medicine. “Yet, as people with hypothyroidism know, the lack of thyroid hormone can have profound effects on the body.”

Knowing how thyroid hormone regulates the body’s metabolism would be a great boon for new drug development, especially to tackle obesity. For four decades, scientists have known that thyroid hormone acts on thyroid hormone receptors, but these special proteins exist in small quantities and marking where they are on DNA has proven difficult.
In the new study, the researchers developed a mouse model in which a special tag was added to TRβ, the main thyroid hormone receptor in the liver, which is where important metabolic effects of thyroid hormone occur. With this tag, they marked the thousands of locations on DNA where TRβ binds, both in states when thyroid hormone was present and could bind to TRβ and also when no hormone was present. In this way, the team came up with strong evidence that shows the unexpectedly subtle manner in which thyroid hormone works with TRβ.

When it binds to a DNA site, TRβ will promote or suppress nearby gene activity by forming complexes with other proteins called co-activators and co-repressors. When thyroid hormone is bound to TRβ, it can alter the balance of these co-regulator proteins towards more gene activation at some sites, and more gene repression at others. Prior models of thyroid hormone / TRβ function in which thyroid hormone has a more absolute, switch-like effect on gene activity.

The researchers acknowledged that more work is needed to discover just how genes are activated or repressed at the sites. However, this is a significant advancement towards treatments which can directly influence the body’s metabolism.

Source: Medical Xpress

Categories : Diseases, Syndromes and Conditions VaccinesTags :

TB Vaccine Shown to Protect Against Common Infections

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The tuberculosis (TB) vaccine Bacillus Calmette-Guerin (BCG) could protect newborns against a variety of common infections, such as upper respiratory tract infections, chest infections, and diarrhoea, according to a new study from the London School of Hygiene and Tropical Medicine (LSHTM).

It has been known that BCG protects against diseases other than TB, offering protection against non-tuberculous mycobacteria infection like leprosy and Buruli ulcer. It is also used in the treatment of superficial carcinoma of the bladder.

However, this is the first research to rigorously investigate the full range. The results suggest that vaccinating all babies with BCG on their day of birth could save lives by reducing neonatal infections in areas with high rates of infectious disease.

The study involved a randomised control trial of 560 newborns in Uganda, who were monitored for a range of illnesses. After six weeks, infection rates from any disease were 25% lower in the group that received the vaccine at birth, compared to the group that had not yet received the vaccination. The most protected appeared to be vulnerable groups such as low birth weight babies, and boys. Importantly, BCG appeared to protect against even severe infections.

Sarah Prentice, the lead author from LSHTM, said: “Nearly a million babies die every year of common infections so we urgently need better ways to protect them. Our research suggests that ensuring that BCG is given at birth could make a big difference in low-income countries, potentially saving many lives.”

The newborns were randomly assigned to receive BCG either at birth or at six weeks of age. They were followed-up by doctors, blinded to the intervention, for 10 weeks, who looked for any type of illness or infection.

The research team then compared how often infants in the two groups presented to doctors with infections of any kind, except TB, to see whether having BCG made a difference. They also took blood samples from both groups, to look at differences in their innate immune system, the body’s first line of defense against infections.

Infants vaccinated with BCG at birth presented to doctors with any kind of infection 25% less often than infants who had not. BCG seemed to protect against all kinds of infections, such as common colds, chest infections, and skin infections.

After the delayed group had been vaccinated, the rates of infection were identical between the two groups: the delayed group’s immunity ‘brought up to speed’ when they received BCG.

Study co-author Prof Hazel Dockrell, LSHTM, said: “It’s very exciting to think that BCG vaccination might help keep newborns safe against other dangerous infections, in addition to providing protection against TB. Although BCG is recommended at birth in many countries, it is often delayed due to logistical difficulties. Ensuring that the vaccine is given on day one, in areas with high rates of infectious disease, could have a major impact on infections and deaths in the newborn period.”

Though the study could not definitely determine whether the BCG vaccine was responsible for the lowered rate of infections, there is nonetheless great interest in applying the vaccine as a protection for novel disease outbreaks, such as COVID or Ebola, before a specific vaccine can be developed.

Dr Prentice said, “Since the findings show that BCG seems to offer wider protection against a range of infections, our study also raises hopes it might be useful in protecting the general population against COVID-19 and future pandemics – though we will need to see the results of other, more specific studies to know for sure.”

Source: News-Medical.Net

Journal information: Prentice, S., et al. (2021) BCG-induced non-specific effects on heterologous infectious disease in Ugandan neonates: an investigator-blind randomised controlled trial. The Lancet Infectious Diseases. doi.org/10.1016/S1473-3099(20)30653-8.

Categories : Mental HealthTags :

Video Gamers Self-report Feelings of Wellbeing

On By ModernMedia

Volunteers playing video games reported feelings of wellbeing, and video games did not appear to negatively impact players’ wellbeing, a study by the University of Oxford has found.

The researchers sought to investigate the validity of a widespread perception that playing video games may result in addiction and poor mental health. There has been extensive prior research establishing the varying cognitive benefits of playing different types of video games.

The researchers obtained online gameplay statistics from game producers Electronic Arts and Nintendo, then surveyed over 3000 players of two popular games: Animal Crossing: New Horizons and Plants vs Zombies: Battle for Neighborville. These popular games are more ‘relaxed’ than the type of intense action-themed games that often come up in discussions about video games and mental health. 

The surveys queried players on their wellbeing, their motivations and need satisfaction as they played their video games. Each of the volunteers had their gameplay time recorded by the respective game producers. On analysis, the researchers found that players reported slightly more positive responses than expected, with a slight positive correlation between gameplay time and wellbeing.

The researchers stated that the game producers’ only involvement was providing anonymised telemetry data. They also noted that they did not suggest a causal relationship between subjective wellbeing and how much time a person plays video games, only that playing video games does not seem to negatively impact the wellbeing of players.

Instead of considering the amount of time playing, the researchers suggest that the focus should be on why people play games to begin with. The researchers suggest that people who monitor the playing time of others should rather consider if the game is meeting their needs.

A recent, separate study revealed that boys with low physical activity who regularly played video games at 11 had fewer depressive symptoms three years later.

Source: Medical Xpress

Journal information: Niklas Johannes et al. Video game play is positively correlated with well-being, Royal Society Open Science (2021). DOI: 10.1098/rsos.202049

Categories : NeurologyTags :

Long-term Anaesthesia Causes Changes in Neural Connections

On By ModernMedia

New research has shown that there may be neurological consequences after long-term anaesthesia.

Prolonged anesthesia, also known as medically induced coma, takes the brain to a state of deep unconsciousness beyond short-term anaesthesia for surgical procedures. It is used to treat refractory intracranial hypertension and status epilepticus.

Though they are life-saving practices performed in ICUs the world over, they are not without cognitive side effects. Family members often report that their loved ones are not quite the same when they are discharged from hospital following prolonged anaesthesia.

“It is long known that ICU survivors suffer lasting cognitive impairment, such as confusion and memory loss, that can languish for months and, in some cases, years,” said lead author Michael Wenzel, MD, a former postdoctoral researcher at Columbia University with experience as a physician in neuro-intensive care in Germany.

Dr Wenzel said cognitive dysfunction after hospitalisation will likely become more widespread in the wake of COVID, with large numbers of ventilated patients awakening from days to weeks of unconsciousness.

Senior author Rafael Yuste, a professor of Biological Sciences at Columbia and senior author of the paper said that to date there had been no research on the direct effects of anaesthesia on neural connections.

“This is because it is difficult to examine the brains of patients at a resolution high enough to monitor connections between individual neurons,” Yuste said.

Yuste and Wenzel sought to investigate the connections between neurons, or synapses, and related cognitive effects of prolonged anaesthesia, using mice. With a specially built miniature ‘ICU’ for mice, they performed continuous anaesthesia for up to 40 hours, much longer than the longest animal study so far.

The researchers used in vivo two-photon microscopy to observe cortical synapses in the sensory cortex, combined with repeated assessment of behaviour in the cortex.

They found that, contrary to the view that neural connections in adult brains are stable in short-term anaesthesia, in long-term anaesthesia there are significant changes in synaptic architecture at any age.

“Our results should ring an alarm bell in the medical community, as they document a physical link between cognitive impairment and prolonged medically induced coma,” Wenzel said.

Further study is needed, the researchers said, adding that it will be important to test a range of anesthetics, as well as the combination of anesthetics administered to patients. Anaesthetics are not tailored to patients in any systematic fashion.

“We are well aware that anaesthesia is a life-saving procedure,” Wenzel said. “Refining treatment plans for patients and developing supportive therapies that keep the brain in shape during prolonged anaesthesia would substantially improve clinical outcomes for those whose lives are saved, but whose quality of life has been compromised.”

Source: Medical Xpress

Journal information: Michael Wenzel et al, Prolonged anesthesia alters brain synaptic architecture, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2023676118

Categories : COVIDTags :

Volunteers to Take Part in COVID Human Challenge Trial

On By ModernMedia

The first trial of its kind is set to start in the UK, with healthy volunteers being sought to be deliberately infected with COVID in a human challenge test.

The study will seek 90 healthy volunteers aged 18-30 to be infected with COVID in a safe, controlled environment. Among the study’s objectives is a desire to find out exactly how much of a viral load is needed to infect someone with COVID.

The window of opportunity in the UK for a large-scale study of this type is gradually closing because eventually it will no longer be possible to find people have not been vaccinated. However, a significant amount of information can be gleaned from even small-scale studies. This includes how second-generation vaccines compare to how well vaccines protect against new variants.

Human challenge tests have been an important part of developing understanding of and treatments for a number of diseases. The first human challenge trials for dengue fever took place in the 1900s. Although abandoned in favour of animal testing, animals were not sufficiently close to humans to advance research. Recent human challenge trials helped to develop an effective vaccine for the disease.

Clive Dix, interim chair of the Vaccines Taskforce, explained: “We have secured a number of safe and effective vaccines for the UK, but it is essential that we continue to develop new vaccines and treatments for Covid-19.

“We expect these studies to offer unique insights into how the virus works and help us understand which promising vaccines offer the best chance of preventing the infection.”

Applicants will be screened, including determining if they had COVID before, and then be intranasally infected with the virus. Volunteers will receive compensation of £4500 (about R90 000) over the course of a year, which will include follow-up tests.

Source: BBC News

Categories : Cancer Medical Research & TechnologyTags :

Neural Network Matches Dermatologists’ Assessment of Skin Lesions

On By ModernMedia

Researchers have developed an AI-based tool that can use smartphone camera pictures to spot suspicious pigmented lesions (SPLs) with an accuracy close to that of professional dermatologists.

Such technology would hardly put dermatologists out of work; on the contrary, there is a great need for readily available skin cancer screening. In the US, there are only 12 000 practising dermatologists, who would need to see over 27 000 patients each per year in order to screen the entire population for SPLs which could lead to cancer. Computer-aided diagnosis (CAD) has thus been developed over previous years to help assist in diagnosis, but thus far had failed to spot melanomas in a meaningful way. Such CAD programs only analyse individual SPLs, while dermatologists compare other lesions on the same patient to reach a diagnosis, called ‘ugly duckling’ criteria.

This shortcoming has been addressed in a new CAD system that uses convolutional deep neural networks (CDNNs) developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Massachusetts Institute of Technology (MIT).

The new system was able to distinguish SPLs from non-suspicious lesions in photos of patients’ skin at ~90% accuracy, and established an ‘ugly duckling’ criteria which could match three dermatologists’ consensus 88% of the time.

“We essentially provide a well-defined mathematical proxy for the deep intuition a dermatologist relies on when determining whether a skin lesion is suspicious enough to warrant closer examination,” said first author Luis Soenksen, PhD, a Postdoctoral Fellow at the Wyss Institute who is also a Venture Builder at MIT. “This innovation allows photos of patients’ skin to be quickly analyzed to identify lesions that should be evaluated by a dermatologist, allowing effective screening for melanoma at the population level.”

The researchers used a database of 33 000 images to train the system, which also included background elements and non-skin elements. These extraneous elements were left in so that the CDNN would be able to use normal images taken by consumer-grade cameras. The images contained SPLs and non-suspicious skin lesions identified by three certified dermatologists.
The software then developed a ‘map’ of how far away a lesion was from the others in terms of similarity, giving an ‘ugly duckling’ criteria. To test the software, they used 135 photos from 68 patients, which assigned an ‘oddness’ score to each lesion. This was then compared to dermatologists’ assessments of those lesions, matching individual dermatologists 88% of the time and their consensus 86% of the time
“This high level of consensus between artificial intelligence and human clinicians is an important advance in this field, because dermatologists’ agreement with each other is typically very high, around 90%,” said co-author Jim Collins, PhD, of the Wyss Institute, who is also the Termeer Professor of Medical Engineering and Science at MIT. “Essentially, we’ve been able to achieve dermatologist-level accuracy in diagnosing potential skin cancer lesions from images that can be taken by anybody with a smartphone, which opens up huge potential for finding and treating melanoma earlier.”

Source: Medical Xpress

Journal information: “Using deep learning for dermatologist-level detection of suspicious pigmented skin lesions from wide-field images” Science Translational Medicine, 2021.

Categories : Diet and Nutrition General InterestTags :

Health Experts Call for a Sugar Tax Increase to 20%

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In advance of Finance Minister Tito Mboweni’s annual budget presentation on 24 February, health specialists have been calling for an increase in the health promotion levy from 11% to 20%. 

The health promotion levy (or ‘sugar tax’) was put into effect in April 2018, and imposes an 11% tax on sugar sweetened beverages. Specialists called for an increase in this tax on Tuesday at a webinar rub by the Healthy Living Alliance (Heala), saying that this was a prudent time to do it because the health sector is currently battling the COVID pandemic.

Most people hospitalised with COVID in SA have comorbidities such as diabetes and hypertension, said Karen Hofman, director of the Wits Centre for Health Economics and Decision Science (Priceless SA). Sugar, especially in liquid form, is a risk factor for obesity, diabetes, hypertension, cardiovascular disease, a number of common cancers and dental decay. She added that had those comorbidities had been prevented, the country could have been in a much better position.

Hofman said that people think they have “control over what [they] are eating and drinking”, but in fact don’t, having been heavily influenced by their environment from an early age. For the tax to have any effect, it should be increased to 20%, based on the World Health Organization and other health experts’ recommendations.

Heala head, Lawrence Mbalati, said the sugar tax had created R5.4-billion for the government within its first two years. This would have been enough to finance South Africa’s downpayment for COVID vaccines from the Covax facility almost 20 times over, in spite of its minimal contribution to the overall budget. 

A doubling of the sugar tax would net an additional R2 billion to help fight COVID, Mbalati said.

“This is a watershed moment for the country,” Mbalati continued. “Government revenues are under immense pressure and funding the fight against Covid-19, including vaccines, remains critical.”

Hofman said that research in other countries with a sugar tax had shown a fall in volume of taxable beverages by 51%, and a 29% reduction in sugar intake.

“SA must address commercially driven epidemics with taxes, mandatory food labelling and mandatory comprehensive marketing bans,” Hofman said.

Source: Mail & Guardian

Categories : CancerTags :

Osmium in Cancer Cells May Be a Useful Weapon

On By ModernMedia

Using powerful X-ray beams to probe inside a cancer cell, researchers have determined that osmium could be a viable element for new cancer drugs.

About half of all chemotherapy drugs use platinum, but this has platinum which reacts in the nucleus, possibly leading to undesirable side effects. Osmium is a rare metal which could replace platinum in chemotherapy drugs, but first researchers needed to know where the osmium would wind up. To determine this, the researchers used the Diamond synchrotron to precisely track osmium in human lung cancer cells with a precision of 100 nanometres.

The researchers revealed the functioning of osmium in the cells using synchrotron X-ray Fluorescence (XRF) imaging. This enabled the researchers to observe the osmium in a single lung cancer cell. However, since osmium’s reactivity is determined by its ligand coating, these were labelled with bromine.

Once in the cell, the researchers observed that the osmium stayed in the cytoplasm, while the ligands penetrated into the nucleus, suggesting a twin attack on the cell.

Professor Peter Sadler, from the Department of Chemistry at the University of Warwick explained the use of osmium and their research process: “Osmium is a rare precious metal, however, since it can act as a catalyst, a very little amount is needed for reactions in the cancer cell, therefore it could be a sustainable treatment going forward. We wanted to see how exactly it worked in a single cancer cell, which involved a variety of novel techniques, including taking water molecules out of the cell and rapidly flash-freezing it. Whereas usually cells are chemically altered to see the reactions, in our method they are close to their natural state, making our results more authentic.”

It was hard work, as Dr Elizabeth Bolitho, from the Department of Chemistry and Diamond explained: “We worked 24 hours a day, 5 days a week to collect these exciting data, allowing us to see inside cancer cells to a nanoscale resolution. This has provided crucial insights into potential cellular targets of such Osmium catalysts.

“Not only were we able to track the osmium in a lung cancer cell, but more widely in breast cancer, ovarian and prostate cancer cells, for example, which provides hope that in the future osmium could be used to treat a range of different cancer.”

Source: News-Medical.Net

Journal information: Bolitho, E. M., et al. (2021) Tracking Reactions of Asymmetric Organo‐Osmium Transfer Hydrogenation Catalysts in Cancer Cells. Angewandte Chemie. doi.org/10.1002/anie.202016456.

Categories : COVID ImmunologyTags :

COVID Antibody Drugs Work Best with Immune Cells

On By ModernMedia

Research into the current antibody-based drugs for COVID treatment shows that they need to be designed to work in concert with immune cells to be effective.

Three drugs using monoclonal antibodies are approved by the FDA to treat COVID, which provide the patient’s body with ready-made antibodies faster than can be produced by their own immune systems.

The distinctive Y shape of antibodies comes from their two short arms, which latch on to foreign molecules to clear them out, and a long effector arm which interacts with immune cells, inducing them to attack infected cells and release molecules that modulate the immune response.

In antibody-dependent enhancement, the long arm of antibodies can interfere with immune cells, such as in tropical dengue fever. Immunity against one strain against dengue fever causes life-threatening illness if infected with the other strain.

To investigate the possibility of this in COVID, some companies altered the long arm of their antibodies to prevent interaction with immune cells. Other companies took the opposite approach and strengthened antibody effector functions to boost the potency of their drugs.

“Some of the companies removed the effector functions from their antibodies, and other companies are trying to optimise the effector functions,” said senior author Michael S Diamond, MD, PhD, the Herbert S Gasser Professor of Medicine. “Neither of these strategies is backed by data in the context of SARS-CoV-2 infections. Based on our findings, if you have a potently neutralising antibody without effector functions and you give it before infection, as a preventive, it will probably work. But if you give it after infection, it won’t work well; you need to optimise effector functions to get maximal benefit.”

“‘Effector functions’ refers to a complex set of interactions between antibodies and other elements of the immune system,” said Prof Diamond, who also is a professor of molecular microbiology and of pathology and immunology. “You can introduce different point mutations to augment certain kinds of effector functions, and some might be harmful to the immune response while others might be beneficial. There’s a lot of nuance. We are still learning how to harness effector functions so you get what you want but not what you don’t want.”

To find how antibody effectors work with COVID, the researchers took an antibody which was known to be effective against the virus and disabled the effector so it could not interact with immune cells.

They administered the original antibodies, the disabled antibodies and placebo antibodies each to a different group of mice, which were infected a day later with SARS-CoV-2. Both normal and disabled effector antibodies were able to protect against the disease. There were no signs of antibody enhancement of the disease, fortunately.

To find out whether the effector function was needed for treatment after infection, they infected mice with SARS-CoV-2 and administered one of the three sets of antibodies to mice  one, two or three days later. Only the original antibodies protected the mice from the disease. The tests were run in hamsters with the same results.

The researchers discovered in the study that losing effector functions changed the types of immune cells recruited to fight the COVID infection and the way they behaved.

Source: Medical Xpress

Journal information: Emma S. Winkler et al, Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection, Cell (2021). DOI: 10.1016/j.cell.2021.02.026