Author: ModernMedia

Categories : Diseases, Syndromes and Conditions UrogenitalTags :

There is a ‘Worrying’ Resurgence of Sexually Transmitted Infections in Gauteng

On By ModernMedia
Photo by Cottonbro on Pexels

There’s a comeback of sexually transmitted infections (STIs) in South Africa and around the world. The Gauteng Department of Health recently reported an increase of newly acquired STIs, in particular gonorrhoea and chlamydia. This spike in cases call for management guidelines and awareness programmes to be reviewed, reports Ufrieda Ho.

A rise in reported cases of sexually transmitted infections in Gauteng in 2023 is a wake-up call that control and management strategies are not keeping pace with the growing disease burden in South Africa’s most populous province.

“The Gauteng information confirms the rise in STIs that we are seeing in South Africa and across the world, including in the United States and Canada,” said Dr Nomathemba Chandiwana, a director and principal scientist at Ezintsha Research Centre at Wits University. She is also a co-author of the 2022 guidelines on the management of sexually transmitted infections produced by the Southern Africa HIV Clinicians Society.

Chandiwana said any increase in STIs should raise alarms because it means “we simply don’t have control over the things we thought we had under control”.

The World Health Organization (WHO) in 2022 noted that countries reported low coverage for preventive, testing and treatment services related to  STIs, because of Covid-19 lockdown restrictions. The WHO confirmed that this had led to a “resurgence of STIs and the emergence of non-classical STIs [such as Shigella sonnei, hepatitis A, Neisseria meningitidis, Zika and Ebola] globally”. It also reported that currently more than 1 million new STIs are acquired around the world each day “posing a significant global health challenge”.

Since the middle of 2023, the WHO has pushed for low-cost point of care tests to be more readily available in low and middle income countries, saying this would improve screening and diagnosis, data collection and make STI services more effective. South Africa has not made such tests accessible, still relying on a syndromic approach, which is clinical diagnosis made by assessing a patient’s symptoms and other visible signs.

New public health threats

Chandiwana said a review of STI treatment and management guidelines is necessary because the rising numbers pose significant new public health threats. Of particular concern, she said, is that having  STIs pushes up a person’s risk to contract HIV, which is “a chronic and serious disease” as well as developing other long term or irreversible medical risks, including reproductive complications.

Earlier in February, the Gauteng Department of Health reported that the incidence of Male Urethritis Syndrome (MUS) in men aged 15 to 49 in the province had increased from 12% in 2020 to 15% in 2023. The department did not provide actual figures for the comparison, which is also somewhat complicated by the fact that in 2020 there were strict COVID-19 lockdowns and restrictions in place.

The department’s information from 2023 showed that 167 109 males aged 15 to 49 visited health facilities across the province from April to December. Of these patients, 67 400 (40% of the 167 109) were treated for MUS.

The diagnosis of MUS is an indicator of newly acquired STIs, in particular gonorrhoea and chlamydia, which according to the Gauteng Department of Health are the most prevalent STIs in South Africa.

Chandiwana said diagnosis of MUS in men and pelvic inflammatory disease (PID) among women, are made by assessing symptoms of pain, discomfort and genital discharge and sores. Conventionally, it’s treated with broad range antibiotics.

She explained South Africa’s guidelines to treatment and management is to make clinical decisions based on a patient’s symptoms and signs. “While this standard approach has worked, we are calling for a move to targeted diagnosis and targeted treatment. It’s because you want to know which STI someone has and to treat them for that particular disease,” said Chandiwana.

Different STIs can also result in different complications. Syphilis for instance, she said, can result in women giving birth to children who are deaf or blind or raises the risks for infertility. (Spotlight previously reported on congenital syphilis in South Africa in more depth here.)

“We also have STIs that are present but not visible, so asymptomatic STIs, including HPV (human papillomavirus­), which is the leading cause of cervical cancer in black women in South Africa,” Chandiwana said.

“Of course it’s complicated in a public healthcare system where we might not have lab services everywhere, and where there may be lab testing there is a long turnaround for results,” she added.

What to do

It means a multi-pronged approach is still necessary. This she said, has to include a shift from blaming and policing people’s sexual behaviour. Her comments are in response to Gauteng MEC for health and wellness Nomantu Nkomo-Ralehoko’s remarks in the same Gauteng Department of Health press release in which the MEC drew a link between a higher number of women coming forward to be initiated on Pre-Exposure Prophylaxis (PrEP) – an antiretroviral drug prescribed for HIV-negative people to stop HIV infection – and the higher recorded number of STIs. The MEC is quoted saying: “We believe that the high uptake of PrEP among women has led this group to having unprotected sex resulting in high incidence of MUS. The studies have reported that STI incidence is also high among young women receiving PrEP.”

Chandiwana dismissed the conclusion of a causal relationship. “PrEP is a very important tool because it’s something people can take to prevent HIV. But before we had PrEP it was not like people were using condoms – people were using nothing. So I disagree, the uptake of PrEP is not directly involved with the increase of STIs,” she said.

What’s needed instead, she said, is to ask why people are not using condoms more often and why South Africa is not creating STI friendly services that include differentiated care for key populations such as sex workers, men who have sex with men, or people who inject drugs. There should also be more peer navigators, services that are quick, efficient and confidential as well as investment and development of rapid testing kits, she added.

Preliminary findings from the Sixth South African National HIV Prevalence, Incidence, and Behaviour survey released by the Human Sciences Research Council in November indicated that condom use had dropped substantially among young people from 2017 to 2022. It did prompt MEC Nkomo-Ralehoko to call for more uptake of PrEP.  “We would like to encourage more males to get initiated on PrEP to protect themselves against STI. Additionally, both men and women who are on PrEP should use condoms to protect themselves against STIs, HIV and unwanted pregnancies,” she was quoted in the press release.

Role of medical male circumcision

Meanwhile, the NGO Right to Care is promoting voluntary medical male circumcision as another strategy to combat the rise in STI cases. “Uncircumcised men are more susceptible to STIs than men who are circumcised, especially STIs that cause ulcers or wounds,” said Dr Nelson Igaba, senior technical specialist for voluntary medical male circumcision at the NGO.

He described the Gauteng statistics as “worrying” and said it should be read as a prompt for more men to opt for circumcision. The NGO will connect men to their nearest public facility to have the procedure done for free. (They can be contacted at 082 808 6152.)

Dr Tendesayi Kufa-Chakezha, a senior epidemiologist at the Centre for HIV and STIs at the National Institute of Communicable Diseases (NICD), also homes in on the need for more awareness building.

“As a country we are not talking about STIs enough, among ourselves or with our children. More healthcare workers are needed and more training can be made available. We also need a massive campaign to educate communities on the causes of STI syndromes, symptoms, where to get treatment, types of treatments, complications and to go back to facilities if they don’t get better.”

Kufa-Chakezha said South Africa’s STI treatment guidelines do conform with existing WHO guidelines. She said the NICD regularly collects information and specimens from health facilities, which  allows them to determine the most common causes associated with the symptoms that are most commonly seen. The NICD uses these findings to inform the country’s STI management and treatment strategies that are based on diagnosis and treatment of the most prevalent STIs.

“If as a country we are not able to get more people with or without STI symptoms screened and treated, we will continue to have people acquiring STIs, developing symptoms associated with them, becoming ill and developing complications from them,” she added.

Republished from Spotlight under a Creative Commons 4.0 Licence.

Source: Spotlight

Categories : Cardiovascular Disease ExerciseTags :

Anabolic Steroid Use can Increase Atrial Fibrillation Risk, Study Finds

On By ModernMedia
Photo by Jonathan Borba on Unsplash

People using anabolic steroids could be increasing their underlying risk of atrial fibrillation, according to new research published in the Journal of Physiology. 

The team found that male sex hormones, such as testosterone, also called androgenic anabolic steroids (AAS), which are misused for muscle building particularly among in young men can increase the risk of atrial fibrillation in individuals genetically predisposed to heart diseases.

Dr Laura Sommerfeld, Postdoctoral Researcher at the UKE Hamburg, who completed her PhD at the Institute of Cardiovascular Sciences at the University of Birmingham focusing on this work is lead author of the study.

Dr Sommerfeld said: “Our study can significantly contribute to understanding the impact on the heart health of young men who misuse anabolic steroids to increase muscle mass. Recent reports have shown that young men in particular are being targeted on social media such as TikTok being sold testosterone products, but we have shown how the misuse of steroids carries a specific risk that many people will not be aware of.”

Professor Larissa Fabritz, Chair of Inherited Cardiac Conditions at UKE Hamburg and Honorary Chair in the Institute of Cardiovascular Sciences at the University of Birmingham added:

“Heart muscle diseases like ARVC affect young, athletic individuals and can lead to life-threatening heart rhythm disturbances. Atrial fibrillation is a common condition in the general population. Elevated testosterone levels can result in an earlier onset of these diseases.”

The scientists examined potential effects on a condition called arrhythmogenic right ventricular cardiomyopathy (ARVC), which is genetically determined and primarily attributed to disruptions in the formation of cell connections critical for heart muscle stability.

The scientists initially confirmed, based on clinical patient data from UHB and elsewhere, that ARVC occurs more frequently and severely in men than in women.

In laboratory experiments, they discovered that six weeks of AAS intake, combined with impaired cell connections, could lead to reduced sodium channel function in heart tissue and a slowing of signal conduction within the atria.

Dr Andrew Holmes, co-author and Assistant Professor in the Institute of Clinical Sciences at the University of Birmingham said:

“This work implies that young male individuals with key inherited genetic changes have a greater risk of developing electrical problems in the heart in response to anabolic steroid abuse.”

The research was conducted by an interdisciplinary consortium of clinicians and researchers led by University of Birmingham and collaborators in Germany.

Source: University of Birmingham

Categories : Mental HealthTags :

New Tool Predicts Burnout Risk

On By ModernMedia
Photo by Mulyadi on Unsplash

It is not uncommon for people to “hit the wall” at work and experience burnout for short or long periods of time.

“We have found that approximately 13 per cent of Norwegian employees are at high risk of burnout,” says Leon De Beer, Associate Professor of Work and Organizational Psychology at the Norwegian University of Science and Technology (NTNU) Department of Psychology.

De Beer has contributed to a new study on burnout published in the Scandinavian Journal of Psychology with colleagues from the Healthy Workplaces research group.

They are working on a new tool that can identify people at risk of burnout. 

Signs that you might be at risk of burnout

If you are facing demands and stress at work that seem to be intractable, and you have frequently experienced the following symptoms in recent weeks, it might be a sign that you are on the verge of burning out:

  1. You feel mentally exhausted at work.
  2. You struggle to feel enthusiastic about your job.
  3. You have trouble concentrating when working.
  4. You sometimes overreact at work without meaning to.

Early intervention is key

It is important to identify the early signs of burnout in order to mitigate the harmful effects. The warning signs are often present before things have gone too far, as long as we manage to identify them.

“Not addressing the risk of employee burnout in time can have long-term consequences,” says De Beer.

The physical and psychological effects of burnout include cardiovascular disease, pain related to musculoskeletal injuries, sleeping problems, and depression. Organisations can also lose talented employees and experience an increase in sickness absence and lost productivity.

A new tool may become standard

De Beer’s research group has trialled a new measurement tool to identify the early warning signs of burnout. In the past, it has not always been that easy.

“Previously, we have not had a detailed enough measurement tool for use in both the field of practice and research that identifies workers who are at risk of burnout,” says De Beer.

There is currently no international standard for assessing burnout.

The new tool is called the Burnout Assessment Tool, or BAT among researchers who have a penchant for amusing abbreviations. The BAT consortium, of which the researchers are a part, is now testing the instrument in more than 30 countries.

https://burnoutassessmenttool.be/start_eng/

Start ENG

“Our studies show that BAT is a good tool for identifying the risk of burnout,” says De Beer.

Burnout is the body’s response to stress

BAT measures four main groups of risk factors: exhaustion, mental distancing, cognitive impairment and emotional impairment.

Burnout is not really an illness, but a feeling of being mentally or physically exhausted — the body’s response to a lasting, demanding situation.

Burnout is normally defined as a work-related syndrome, but there is evidence that work-life balance also plays a role. Stress and burnout don’t necessarily stop when you go home at the end of the day, as these effects often extend into other areas of life and vice versa.

Some may experience years of burnout

For some people, burnout can be stopped in its tracks and solutions found to improve their situation. For others, however, burnout can last for years if the problem isn’t addressed.

“We can deal with burnout through individual treatment, but it is of little use if people return to a workplace where the demands are too high and there are few resources. It is then highly likely that the employee will become ill again. Therefore, it is important to create good working conditions and structures that safeguard the health of employees,” says Professor Marit Christensen at NTNU’s Department of Psychology.

Culturally independent

The researchers studied a representative sample of 500 Norwegian workers. Norway is roughly on par with the EU average when it comes to mental health, but somewhat better when it comes to work-related matters.

A lower percentage of the Norwegian population struggles with exhaustion in connection with work. Somewhat fewer people than the EU average report health hazards at work, and we experience a better work-life balance.

“Using a recognised method, we found that around 13 per cent of the 500 surveyed workers were at high risk of burnout,” says Professor Christensen.

The tool can help identify who requires the most urgent follow up so that the risk of burnout can be reduced.

We do not yet know whether the prevalence of burnout in Norway is high in an international context. The Norwegian study is among several BAT studies that are currently taking place, so these answers will be available at a later date.

The tool is intended to be culturally independent, and it certainly works well in Norway. The researchers also found that the tool works regardless of gender.

“For entertainment and educational purposes, interested parties can use our online tool to test if they are at risk of burnout,” says Professor Christensen.

“Please note that the tool only gives an indication of risk and does not provide any type of formal diagnosis or medical advice. If you are concerned about your levels of work-related stress, we encourage you to visit a health care provider to discuss the matter,” says Professor Christensen.

Source: Norwegian University of Science and Technology

Categories : Implants and Prostheses NeurologyTags :

New Neural Prosthetic Device Can Help Restore Memory in Humans

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Source: CC0

Scientists have demonstrated the first successful use of a neural prosthetic device to recall specific memories. The findings appear online in Frontiers in Computational Neuroscience.

This groundbreaking research was derived from a 2018 study led by Robert Hampson, PhD, professor of regenerative medicine, translational neuroscience and neurology at Wake Forest University School of Medicine. That study demonstrated the successful implementation of a prosthetic system that uses a person’s own memory patterns to facilitate the brain’s ability to encode and recall memory, improving recall by as much as 37%.

In the previous study, the team’s electronic prosthetic system was based on a multi-input multi-output (MIMO) nonlinear mathematical model, and the researchers influenced the firing patterns of multiple neurons in the hippocampus, a part of the brain involved in making new memories.

In this study, researchers from Wake Forest and University of Southern California (USC) built a new model of processes that assists the hippocampus in helping people remember specific information.

When the brain tries to store or recall information such as, “I turned off the stove” or “Where did I put my car keys?” groups of cells work together in neural ensembles that activate so that the information is stored or recalled.

Using recordings of the activity of these brain cells, the researchers created a memory decoding model (MDM) which let them decode what neural activity is used to store different pieces of specific information.

The neural activity decoded by the MDM was then used to create a pattern, or code, which was used to apply neurostimulation to the hippocampus when the brain was trying to store that information.

“Here, we not only highlight an innovative technique for neurostimulation to enhance memory, but we also demonstrate that stimulating memory isn’t just limited to a general approach but can also be applied to specific information that is critical to a person,” said Brent Roeder, Ph.D., a research fellow in the department of translational neuroscience at Wake Forest University School of Medicine and the study’s corresponding author.

The team enrolled 14 adults with epilepsy who were participating in a diagnostic brain-mapping procedure that used surgically implanted electrodes placed in various parts of the brain to pinpoint the origin of their seizures.

Participants underwent all surgical procedures, post-operative monitoring and neurocognitive testing at one of the three sites participating in this study including Atrium Health Wake Forest Baptist Medical Center, Keck Hospital of USC in Los Angeles and Rancho Los Amigo National Rehabilitation Center in Downey, California.

The team delivered MDM electrical stimulation during visual recognition memory tasks to see if the stimulation could help people remember images better.

They found that when they used this electrical stimulation, there were significant changes in how well people remembered things. In about 22% of cases, there was a noticeable difference in performance.

When they looked specifically at participants with impaired memory function, who were given the stimulation on both sides of their brain, almost 40% of them showed significant changes in memory performance.

“Our goal is to create an intervention that can restore memory function that’s lost because of Alzheimer’s disease, stroke or head injury,” Roeder said.

“We found the most pronounced change occurred in people who had impaired memory.”

Roeder said he hopes the technology can be refined to help people live independently by helping them recall critical information such as whether medication has been taken or whether a door is locked.

“While much more research is needed, we know that MDM-based stimulation has the potential to be used to significantly modify memory,” Roeder said.

Source: Atrium Health Wake Forest Baptist

Categories : Immune SystemTags :

Scientists Peer into a Transporter Protein for Inflammatory Signals

On By ModernMedia

In the human body, a protein carrier called SPNS2 transports S1P molecules from endothelial cells to rally immune cell response in infected organs and tissues, resulting in inflammation. By enlarging the entire SPNS2 structure using nanoparticles, the S1P molecules contained within can be viewed via cryogenic electron microscopy. Using this information, small molecules can be developed to inhibit this signalling pathway and treat inflammatory diseases.

Scientists at the National University of Singapore and colleagues in China have analysed the structure of the SPNS2 protein at an atomic level that could provide greater insights into how S1P signalling molecules are released to communicate with the immune cells to regulate inflammatory responses. Their findings are published in Cell Research.

“Seeing is believing. This work shows that SPNS2 is directly exporting S1P for signalling and it is possible to inhibit its transport function with small molecules. This work provides the foundation for understanding of how S1P is released by SPNS2 and how this protein function is inhibited by small molecules for treatment of inflammatory diseases,” said team leader Dr Nguyen Nam Long.

The SPNS2 protein allows the binding of the S1P signalling molecules to trigger the immune cells to leave the lymph nodes and induce inflammation in different parts of the body when needed.

Made up of amino acids, the SPNS2 protein is malleable enough to change its shape and structure to release the S1P signalling molecules through small cavities found within the protein.

Through the discovery of how the SPNS2 protein releases S1P molecules, the SPNS2 structure can be exploited for future drug development.

Similar to discovering how the shape of the lock looks like before the key can be designed, this finding sheds more light into how future drugs can be designed to better target the protein to increase drug efficacy.

This finding builds on previous research which found that deleting SPNS2 protein from a pre-clinical model effectively blocks the S1P signalling pathway so that the S1P signalling molecules are unable to be transported to prompt immune cells to leave the lymph node to induce inflammation.

Both SPNS2 protein and S1P signalling molecule are required for immune cell recruitment to inflammatory organs, which goes towards treating various inflammatory diseases.

“Using pre-clinical models, we have shown that targeting SPNS2 proteins in the body blocks inflammatory responses in disease conditions, such as multiple sclerosis. This work has provided us a possibility to inhibit its transport function with small molecules that will go a long way to treating inflammatory diseases more efficiently and effectively,” said Dr Nguyen.

Source: National University of Singapore, Yong Loo Lin School of Medicine

Categories : Cancer NeurologyTags :

Removing a Protein Lets Glioblastoma Chemo Remain Effective for Longer

On By ModernMedia
Photo by Anna Shvets on Pexels

New research by the University of Sussex could help to increase life expectancy and improve treatment for glioblastoma. In the study, published in the Journal of Advanced Science, researchers have discovered that an understudied protein, called PANK4, is able to block cancer cells from responding to chemotherapeutic treatment for the highly intrusive brain cancer, glioblastoma.

Scientists at Sussex have demonstrated that if the protein is removed, cancer cells respond better to temozolomide, the main chemotherapy drug for the treatment of glioblastoma.

Prof Georgios Giamas, Professor of Cancer Cell Signalling at the University of Sussex explains: “Glioblastoma is a devastating brain cancer, and researchers are working hard to identify ways to delay progression of the disease, and tackle cell resistance to treatment. As this is the first time that PANK4 has been linked to glioblastoma, the next step is to develop a drug targeting this protein to try to reverse chemo-resistance and restore sensitivity, ensuring that patients receive the best treatment and have better outcomes.”

Glioblastoma is one of the most aggressive forms of brain cancer. Approximately 250 000 – 300 000 globally are diagnosed with it annually, with a best-case survival rate of just one to 18 months after diagnosis.

Following surgery to remove the tumour, glioblastoma patients are typically treated with radiation and the chemotherapeutic drug, temozolomide. Although patients initially respond well to the drug, the cancer cells quickly develop resistance to this treatment.

The University of Sussex scientists led an international research team to understand the possible reasons for this resistance, helping to guide future therapies to improve quality of life and increase life expectancy for those with glioblastoma.

The team identified a protein called PANK4 which, when removed from the cancer cells, can lead to the cell’s death, and saw patients better responding to temozolomide. Linked to this, the researchers found that patients expressing high levels of the PANK4 protein had lower survival rates.

Dr Viviana Vella, research fellow at the University of Sussex explains: “There are a multitude of under-investigated proteins that may hold great potential for therapeutic intervention. Our study sheds light on this understudied protein, PANK4, unveiling a protective role in temozolomide-resistant cancer cells. Ultimately, PANK4 depletion represents a vulnerability that can now be exploited to restore sensitivity to the drug and improve treatment.”

Source: University of Sussex

Categories : Healthcare Politics and RegulationsTags :

Worst of Hiring Freeze Over, Western Cape Health Department Assures Health Workers

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By Daniel Steyn for GroundUp

Dr Keith Cloete, head of the Western Cape Department of Health and Wellness, has told health workers in the province that the “severe and drastic measures” taken to “constrain the filling of posts” in the past three months has brought the department back within budget.

Cloete was speaking in a video update circulated to the department’s employees on Thursday. Health workers in the province have raised concerns over a “near-complete” freezing of vacant posts to curb budget cuts imposed by National Treasury.

Initial cuts to provincial budgets and conditional grants that fund hospitals were made at the start of 2023/24 and were further exacerbated by in-year cuts.

Provincial governments also had to absorb within their existing budgets a mandatory public sector wage increase. National Treasury recommended in November that provincial departments freeze hiring.

Since November, posts in the Western Cape could only be filled on approval by head office, but Cloete said in his video that those decisions will now be “decentralised” again.

Line managers may again fill vacant posts on condition that they “apply their minds” and work within “a tight framework”, said Cloete. He added that he was mindful of the impact the hiring constraints have had on services.

In January, GroundUp reported on significant staff shortages at Groote Schuur Hospital and Red Cross War Memorial Hospital. Senior hospital managers in the province complained that there had been a lack of communication from the department’s management on how long budget cuts would last and what would be done to mitigate their impact.

On 4 February, more than 1200 doctors wrote an open letter to Western Cape Premier Alan Winde, Western Cape Finance Minister Mireille Wenger and national Finance Minister Enoch Godongwana, calling for an end to “catastrophic budget cuts”.

The health workers warned that the cuts will cause surgical operations to be cancelled or postponed; patients in need of specialist medical care to wait longer; cancer treatment to be delayed and cancers diagnosed at later stages with less chance of successful treatment; and gains in neonatal, infant and paediatric care would be “reversed”, among many other issues.

In Thursday’s video update, Cloete said that the budget for the 2024/25 financial year has not yet been finalised. The final budget allocation will be tabled in the provincial legislature in early March.

Budget cuts are expected to continue into the foreseeable future. Over the next three years, the Western Cape government faces cuts amounting to R6.7-billion. According to premier Alan Winde, 37% of the province’s budget goes to healthcare.

Cloete announced that a meeting will be held with managers, clinicians and support staff “to have a discussion of how do we redesign our healthcare services across the entire system in the Western Cape” on 21 February.

“I understand anxieties that everyone will experience in this specific area. I call on everyone to please attempt to get a slightly bigger view …. And for us to do this together. Together, we can actually navigate this successfully.”

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

Source: GroundUp

Categories : CancerTags :

Extract of Sandalwood Oil Prevents Prostate Cancer Progression

On By ModernMedia
Ccancer-associated fibroplasts surrounding a prostate tumour. Credit: Moscat and Diaz Meco lab.

Extracted from the core of sandalwood trees (santalum album tree), sandalwood oil has been used for many centuries by several cultures throughout the world for perfume, soaps, incense and candles. With its earthy sweet scent, this essential oil also is used in the food industry and topically in various cosmetic preparations.

Importantly, this natural oil is known for its health benefits and medicinal applications from antibacterial to anticancer because of its phytochemical constituents. In addition to containing esters, free acids, aldehydes, ketones and santenone, sandalwood oil primarily (> 90%) constitutes santalol, equal amounts of two compounds, alpha and beta-santalol.

Now, researchers from Florida Atlantic University’s Schmidt College of Medicine and collaborators are the first to demonstrate in vivo the chemo-preventive properties of alpha-santalol against prostate cancer development using a transgenic mouse model.

Results of the study, published in the journal Phytomedicine Plus, showed that administration of alpha-santalol decreased the incidence of prostate tumours by decreasing cell proliferation and inducing apoptosis, without causing weight loss or any noticeable side effects.

Apoptosis (programmed cell death) is a method the body uses to get rid of unneeded or abnormal cells such as cancer cells. Findings revealed that the area occupied by normal tissue in alpha-santalol-treated mice was 53% compared to 12% in control mice.

This suggests that administering alpha-santalol protected the normal tissue and delayed progression from prostatic intraepithelial neoplasia, a precancerous condition, to poorly differentiated carcinoma, a high-grade form of cancer where cancer cells and tissue look very abnormal.

These results are significant because mortality in prostate cancer patients is mainly attributable to advanced stages of the disease.

In prior studies, the researchers demonstrated the efficacy of alpha-santalol in suppressing growth and inducing apoptotic cell death in cultured human prostate cancer cells.

Based on these observations, they selected a genetically engineered mouse model that resembles many features similar to human prostate cancer, eliciting different lesion grades and cancer progression.

“Although our cellular studies provided important mechanistic insights, relevant in vivo models are vital for developing novel chemo-preventive agents for clinical use and to determine if alpha-santalol offers protection against prostate cancer development,” said senior author Ajay Bommareddy, PhD, associate professor of pharmacology in the Department of Biomedical Science, FAU Schmidt College of Medicine.

“Prior to this new study, alpha-santalol’s in vivo efficacy against prostate cancer development had not yet been established.”

Additional findings of the current study showed alpha-santalol reduced the incidence of visible prostate tumors compared to control-treated mice.

Only 11% in the treated group developed prostate tumours whereas more than half in the control group developed the tumours.

The differences in urogenital and prostate weights were statistically significantly different in alpha-santalol-treated mice compared with controls.

The average wet weight of urogenital tract in alpha-santalol treated mice was about 74.28% lower compared with control mice.

Similarly, the average wet weight of the prostate gland was lower by 52.9% compared with control mice.

Current treatment methods for prostate cancer include androgen ablation, chemotherapy, radiotherapy and radical prostatectomy, but are ineffective against advanced prostate cancers.

Early detection and local therapy have resulted in improved outcomes but has been challenging with the management of advanced stages.

“Identifying agents that have the ability to selectively target cancerous cells and delay onset and progression of prostate cancer is greatly needed,” said Bommareddy.

“Additional studies are essential to systemically explore the feasibility of alpha-santalol as a promising chemo-preventive and anti-tumour agent against human prostate cancer development and to elucidate the mechanisms surrounding the role of pro-apoptotic and antiapoptotic proteins.”

Source: Florida Atlantic University

Categories : HIVTags :

New Trial Highlights Incremental Progress Towards a Cure for HIV-1

On By ModernMedia
Colourised transmission electron micrograph of an HIV-1 virus particle (yellow/gold) budding from the plasma membrane of an infected H9 T cell (purple/green).

Antiretroviral therapies (ART) stop HIV replication in its tracks, allowing people with HIV to live relatively normal lives. However, despite these treatments, some HIV still lingers inside cells in a dormant state known as “latency.” If ART is discontinued, HIV will awaken from its dormant state, begin to replicate, and cause acquired immunodeficiency syndrome (AIDS). To create a cure, researchers have been attempting to drive HIV out of latency and target it for destruction.

A new clinical trial led by Cynthia Gay, MD, MPH, associate professor of infectious diseases, David Margolis, MD, the Sarah Kenan Distinguished Professor of Medicine, Microbiology & Immunology, and Epidemiology, and other clinicians and researchers at the UNC School of Medicine suggests that a combination of the drug vorinostat and immunotherapy can coax HIV-infected cells out of latency and attack them.

The immunotherapy was provided by a team led by Catherine Bollard, MD, at the George Washington University, who took white blood cells from the study participants and expanded them in the laboratory, augmenting the cells’ ability to attack HIV-infected cells, before re-infusion at UNC.

Their results, published in the Journal of Infectious Diseases, showed a small dent on the latent reservoir, demonstrating that there is more work to be done in the field.

“We did show that this approach can reduce the reservoir, but the reductions were not nearly large enough, and statistically speaking were what we call a “trend” but not highly statistically significant,” said David Margolis, MD, director of the HIV Cure Center and senior author on the paper. “We need to create better approaches to flush out the virus and attack it when it comes out. We need to keep chipping away at the reservoir until there’s nothing there.”

DNA inside cell nuclei is kept in a tightly packed space by chromosomes, which act as highly organised storage facilities. When you unfurl a chromosome, you’ll find loop-de-loop-like fibres called chromatin. If you keep unfurling, you’ll see long strands of DNA wrapped around scaffold proteins known as histones, like beads on a string. Finally, when the unfurling is complete, you will see the iconic DNA double helix.

Vorinostat works by inhibiting a lock-like enzyme called histone deacetylase. By stopping this mechanism, tiny doors within the chromatin fibres unlock and open up, effectively “waking up” latent HIV from its slumber and making it vulnerable to an immune system attack. As a result, a tiny blip of HIV expression shows up on very sensitive molecular assays.

But the effects of vorinostat are short lived, only lasting a day per dose. For this reason, Margolis and other researchers are trying to find safe and effective ways to administer the drug and keep the chromatin channels open for longer periods of time.

For the study, six participants were given multiple doses of vorinostat. Researchers then extracted immune cells from the participants and expanded the cells that knew how to attack HIV-infected cells.

This immunotherapy method, which has been successful against other viruses such as Epstein-Barr virus and cytomegalovirus, involves giving participants back their expanded immune cells in the hopes that these cells will further multiply in number and launch an all-out attack on the newly exposed HIV-infected cells.

However, in the first part of this study, only one of the six participants saw a drop in their HIV reservoir levels. To test whether the result was simply random or something more, researchers gave three participants their usual dose of vorinostat, but introduced five times the amount of engineered immune cells. All three of the participants had a slight decline in their reservoirs.

But, statistically speaking, the results were not large enough to be definitive.

“This is not the result we wanted, but it is research that needed to be done,” said Margolis. “We are working on improving both latency reversal and clearance of infected cells, and we hope to do more studies as soon as we can, using newer and better approaches.”

Many of the participants in the study have been working with Margolis’s research team for years, sacrificing their own time and blood for research efforts. Their long-term partnership and commitment have been essential for data collection. The data, which follows the size of the viral reservoir in these people over years prior to this study, makes the small changes found more compelling.

“People living with HIV come in a couple of times a year, and we measure residual traces of virus in their blood cells, which doesn’t have any immediate benefit to them,” said Margolis. “It’s a very altruistic action and we couldn’t make any progress without their help.”

Source: University of North Carolina Health Care

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

New Findings on Cardiovascular Risk, Menopause and Migraines Ease Concerns

On By ModernMedia
Photo by Karolina Grabowska on Pexels

Research suggesting a link between migraines and menopause symptoms and cardiovascular disease has gotten a lot of attention. But a pair of new studies in the journal Menopause suggest that most women experiencing these symptoms can rest easier, especially if they don’t have both migraines and long-term hot flashes and night sweats.

Instead, they should focus on tackling the other factors that can raise their cardiovascular risk by getting more sleep, exercise and healthy foods, quitting tobacco, and minding their blood pressure, blood sugar, cholesterol and weight.

For women who have experienced both migraines and hot flashes or night sweats over many years, one of the new studies does suggest an extra level of cardiovascular risk.

That makes heart disease and stroke prevention even more important in this group, says study leader Catherine Kim, MD, MPH, of the University of Michigan.

And for women currently in their 20s and 30s who experience migraines, the new research suggests that they might be heading for a higher risk of long-term menopause-related symptoms when they get older.

Long-term study yields important insights

Kim and her colleagues at Michigan Medicine, U-M’s academic medical centre, published the new pair of studies based on an in-depth analysis of data from a long-term study of more than 1900 women who volunteered to have regular physical exams and blood tests, and to take yearly health surveys, when they were in their late teens to early 30s.

Those women, now in their 50s and 60s, have provided researchers with a priceless view of what factors shape health in the years leading up to menopause and beyond, through their continued participation in the CARDIA study.

“The anxiety and dread that women with migraines and menopausal symptoms feel about cardiovascular risk is real – but these findings suggest that focusing on prevention, and correcting unhealthy habits and risk factors, could help most women,” said Kim, who is an associate professor of internal medicine at U-M and a primary care physician.

“For the subgroup with both migraines and early persistent hot flashes and night sweats, and for those currently experiencing migraines in their early adulthood, these findings point to an added need to control risks, and address symptoms early,” she adds.

Just over 30% of the middle-aged women in the study reported they had persistent hot flashes and night sweats, which together are called vasomotor symptoms or VMS because they relate to changes in the diameter of blood vessels.

Of them, 23% had reported also having migraines. This was the only group for whom Kim and her colleagues found extra risk of stroke, heart attack or other cardiovascular events that couldn’t be explained by other risk factors that have long been known to be linked to cardiovascular problems.

In addition to those with persistent vasomotor symptoms starting in their 40s or before, 43% of the women in the study had minimal levels of such symptoms in their 50s, and 27% experienced an increase in VMS over time into their 50s and early 60s.

The latter two groups had no excess cardiovascular risk once their other risk factors were taken into account, whether or not they had migraines.

Use of hormone-based birth control and estrogen to address medical issues did not affect this risk.

Controlling destiny

In the study of data from the same women in their earlier stages of life, the researchers found that the biggest factors in predicting which ones would go on to have persistent hot flashes and night sweats were having migraines, having depression, and smoking cigarettes, as well as being Black or having less than a high school education.

“These two studies, taken together, underscore that not all women have the same experiences as they grow older, and that many can control the risk factors that might raise their chances of heart disease and stroke later in life,” said Kim.

“In other words, women can do a lot to control their destiny when it comes to both menopause symptoms and cardiovascular diseases.”

She notes that the American Heart Association calls these risk factors the “Essential 8” and offers guides for what women, men and even children and teens can do to address them.

Evolving knowledge and treatment

The long-term study that the two new findings come from was specifically designed to look at cardiovascular risks when it launched in the mid-1980s. CARDIA stands for Coronary Artery Risk Development in Young Adults.

Back in the 80s, knowledge about the biology of blood vessels, down to the cellular and molecular level, was nowhere near where it is today. Both vasomotor symptoms in menopause and migraines have to do with blood vessel contraction and dilation.

But decades of research has shown the microscopic impacts on blood vessels of years of smoking, poor sleep, poor eating habits and lack of activity, as well as a person’s genetic inheritance, life experiences and hormonal history.

Newer injectable migraine medications called calcitonin gene-related peptide (CGRP) antagonists have reached the market in recent years. Using monoclonal antibodies, they target a key receptor on the surface of blood vessel cells to prevent migraines and cluster headaches. But they are expensive and not covered by insurance for all people with migraines.

While the new study is based on data from years before these medications became available, Kim said she recommends them to her patients with persistent migraines, as well as working with them to understand what triggers their migraines and how to use other medications including pain relievers and antiseizure medications to prevent them.

She also notes that the paper on future risk of persistent hot flashes and night sweats echoes the recent trend of using antidepressant medications to try to ease these menopause effects.

Kim also says that evidence has grown about the importance of healthy sleep habits for reducing hot flashes, as well the short-term use of oestradiol-based hormone therapy patches, which have not been shown to have a link to cardiovascular risk. And, she notes that research has not shown any over-the-counter supplement or herbal remedy to be effective, and that these are far less regulated than medications.

Source: Michigan Medicine – University of Michigan