Body

During 2002-2014, there was a 13-fold increase in weight loss surgeries among women aged 15-44 years in New South Wales, Australia, and undergoing such surgery between a first and second pregnancy was associated with lower risks of hypertension, preterm birth, and other outcomes in the second pregnancy. The findings are published in BJOG: An International Journal of Obstetrics and Gynaecology.

The authors of the study noted that the likelihood of adverse pregnancy outcomes among women who underwent weight loss surgery did not decrease to the level observed in the general population of women who became pregnant, however.

"Weight loss surgery for the treatment of obesity is likely to improve outcomes in a subsequent pregnancy," said lead author Ibinabo Ibiebele, of The University of Sydney Northern Clinical School.

Daughters of women with polycystic ovarian syndrome (PCOS) are five times more likely to be diagnosed with PCOS as adults, and the generational transmission is driven by high androgen levels during pregnancy, researchers at Karolinska Institutet in Sweden report. Their results, which are based on register-based and clinical studies as well as transgenerational animal studies, are published in Nature Medicine.

PCOS affects more than ten percent of women of fertile age and is characterised by high levels of androgens (male sex hormones), ovulation disorders and difficulties conceiving. The syndrome is also associated with mental health conditions and a greatly increased risk of type 2 diabetes and obesity, which aggravate the symptoms. While the causes of PCOS are not fully known, the uterine environment plays a key role.

In this study, researchers at Karolinska Institute combined human and mouse studies to ascertain how and to what extent the syndrome is passed down to coming generations. A registry-based study and a case-control study show that daughters of women with PCOS are five times more likely to develop the syndrome in adulthood; they have higher levels of androgens and irregular menstrual cycles as well as abdominal obesity, higher BMI and higher blood pressure.

In the animal studies, pregnant mice were fed an obesogenic diet and exposed to high levels of androgens mimicking those conditions observed in pregnant women with PCOS. Their offspring were then fed with a regular diet and monitored into adulthood, at which point the females' reproductive and metabolic profiles were examined. To find out if PCOS-like symptoms are transmitted to coming generations, four groups of these mice were mated to study the reproductive and metabolic profile in second-generation offspring. The whole process was then repeated for a third generation to address whether a PCOS phenotype could be transmitted across several generations.

"By doing this we were able to demonstrate that the combination of high androgen levels during pregnancy and an obesogenic diet consumed by the grandmothers has a deleterious effect on the fetal development of the second generation, leading to intrauterine growth restriction and miscarriage partly due to placenta dysfunction, which is in line with previous observations of women with PCOS," says Professor Elisabet Stener-Victorin at the Department of Physiology and Pharmacology, Karolinska Institutet, who co-led the study with associate professor and departmental colleague Qiaolin Deng.

The results show that the main contributor to the generational transmission of PCOS symptoms are androgens.

"This is a formerly unknown biological mechanism that trigger us to explore in more detail how germ cells are programmed by androgens to cause daughters of women with PCOS developing reproductive and metabolic disorders as adults," says Qiaolin Deng.

Analyses of the mice oocytes revealed alterations in gene expression that are involved in the cellular stress response, type 2 diabetes and DNA stability, changes that are passed down to future generations. Some of these genes could also be identified in serum from daughters of women with PCOS, which the researchers say could provide potential biomarkers for predicting an increased risk of syndrome transmission.

The mechanism by which defense cells respond to infection by Mayaro virus has been described by a team affiliated with the Center for Research on Inflammatory Diseases - CRID in an article published in the journal PLOS Pathogens.

According to the authors, by establishing an experimental model of Mayaro fever in adult mice and identifying the processes involved in the immune response, the study provides a basis for the development of drugs against this disease.

CRID is one of the Research, Innovation and Dissemination Centers - RIDCs funded by FAPESP (São Paulo Research Foundation). It is hosted by the University of São Paulo's Ribeirão Preto Medical School (FMRP-USP) in São Paulo state, Brazil.

Mayaro fever is a mosquito-borne viral disease similar to chikungunya fever. The symptoms include fever, rash, headache and muscle pain. The most severe cases also involve joint pain (arthralgia) with or without edema. Mayaro virus recently emerged from the Brazilian Amazon forest to circulate in the Southeast Region. Two cases of Mayaro fever have been reported in Niterói (Rio de Janeiro state), and two have been reported in São Carlos (São Paulo state).

"Mayaro fever is highly inflammatory. Its symptoms can last for months. The good news is that the inflammation is triggered by a defense mechanism that has been widely studied and is well understood," said Dario Simões Zamboni, a researcher with CRID and the last author of the article.

Zamboni is referring to multiprotein intracellular complexes known as inflammasomes. When this cellular machinery is activated, proinflammatory molecules are produced to tell the immune system that it must send more defense cells to the infection site.

Inflammasomes are also involved in autoimmune disorders, neurodegenerative diseases, some kinds of cancer, and other infectious diseases, such as Zika virus disease and chikungunya fever. In regard to Mayaro virus, the group discovered that triggering inflammasomes by activating the protein NLRP3 increased the production of interleukin-1 beta (IL-1β), a proinflammatory cytokine that plays a key role in immune system signaling.

In this study, researchers developed models of cellular infection in macrophages (white blood cells that are part of the first line of defense) and mice. The experiments showed that Mayaro virus triggered expression of proteins NLRP3, ASC and CASP1, the ones responsible for activating the immune system's inflammatory response or inflammasomes. NLRP3 was particularly important because of its essential role in the production of immune system signaling molecules.

The authors also showed that the virus activated the NLRP3 inflammasome by inducing the production of reactive oxygen species and potassium efflux from cells into the extracellular space.

In experiments with mice engineered to not express NLRP3, the group confirmed the protein's role in foot pain, swelling and inflammation. "In addition to the experiments in cultured cells and the animal model, we also compared the results with findings for blood serum collected from patients infected by Mayaro virus in the state of Mato Grosso," Zamboni explained. "The patients were found to have far higher levels of CASP1, IL-1β and interleukin-18 [IL-18] than healthy subjects, evidencing activation of the NLRP3 inflammasome in response to infection by Mayaro virus in humans."

Emerging virus

According to Luiza Castro-Jorge, a virologist and the first author of the article, Mayaro virus is considered an emerging virus that at any moment may cause major outbreaks in Brazil. "Researchers at the Federal University of Rio de Janeiro [UFRJ] and FMRP-USP have discovered that Mayaro virus is circulating in the Southeast Region," she said.

The virus is transmitted to humans by the bite of an infected wild mosquito of the genus Haemagogus, which also transmits sylvatic yellow fever.

Although several inflammasomes have been described, the NLRP3 inflammasome is the most studied, which is noted by the researchers in the article. "Drugs are being tested to inhibit the gene for NLRP3 and could, in the future, be used to make the disease less severe in patients," Zamboni said.

There are effective treatments to stop life-threatening epilepsy seizures when the initial treatment has failed, a sweeping new study reveals.

The study offers important answers about three such emergency drugs that are used to treat prolonged seizures, known as status epilepticus, even though physicians have had little understanding of the drugs' effectiveness. Until now, there has been no clear indication of which is best or how much should be given.

The study found that the three drugs - intravenous levetiracetam, fosphenytoin, and valproate - were all about equally effective at stopping the potentially deadly seizures when the default choice, benzodiazepines, proved unable to do so. The results were so clear that the shocked researchers stopped their trial early.

"When we planned the study, we didn't even know if these drugs work 10%, 25% or 50% of the time," said investigator Jaideep Kapur, MBBS, PhD, the head of the University of Virginia Brain Institute. "So the big, big takeaway is that each of these drugs works about 45 percent of the time. And this is an important finding because it tells us patients can get better. They don't have to be placed on a on a ventilator [breathing machine]."

Effect on Clinical Practice

The study's findings, published in the prestigious New England Journal of Medicine, both affirm existing clinical practices and suggest a major change. Doctors can feel confident that their preferred drug of choice is as effective as the other options, Kapur noted, but they also should significantly increase how much levetiracetam they give when they choose it. "Prior to this, people were using their best guess as to which drug to use and how much of it to use. And this puts those things to rest and tells you exactly how much of which to use, and what to expect," said Kapur, of the UVA School of Medicine's Department of Neurology.

The trial organizers tested the maximum safe dose of each of the drugs so there would be no question whether too little had been used to gauge the medicine's effectiveness. In so doing, they gave twice as much levetiracetam as many doctors administer.

"When I started 25 years ago, there was not a single scientifically proven drug [for status epilepticus]. We didn't know which drug to use, even for the first-line treatment, and how much of them to use," Kapur said. "And 25 years later, we can treat more than 80% of the patients - 85% of the patients - using scientifically proven drugs. 85% of our patients will get better, will stop having seizures and start waking up. That is the effect of scientific research on improving care of patients, and this is real."

About the Epilepsy Seizure Trial

The randomized, double-blinded trial looked at the effect of the drugs in 384 patients at 57 emergency departments in the United States between November 2015 and the end of October 2017. The researchers originally planned to study 795 patients over five years, but the results were so clear that was deemed unnecessary. "Clinical trials are notorious for going over long and over budget, and we came in under budget," Kapur said.

That was possible, he said, because of the participation of many top experts in both the United States and Europe. Participating sites included the University of Michigan, Medical University of South Carolina, UVA, Children's National Medical Center in Washington, D.C., and many more.

"It was an amazingly accomplished group of people," Kapur said. "We had the best experts from all over the United States and Europe. For me, it's been a great joy working with the team as the leader of the Brain Institute. That's the spirit I want to bring to UVA. That's really what motivated me to start the Brain Institute: to fashion these teams within UVA, so that we can do really significant, societally impactful research."

UVA Emergency Medicine physician Stephen Huff, MD, led the study at the UVA site, which enrolled seven subjects. Amy Fansler, Emily Gray and Lea Becker helped organize the study.

Kapur expressed his gratitute to all the patients who participated in the study. "President Ryan [UVA President Jim Ryan] has said we must be great and good," Kapur said, "and this is the kind of good we want to do."

Next Steps

The researchers are now looking more closely at the drugs' effectiveness and dosing in children. That will offer important information on how best to treat the young patients, as the causes of status epilepticus in adults and children often differ.

An international team led by Professor Jerome Estaquier from Universite Laval's Faculty of Medicine and the CHU de Quebec-Universite Laval Research Center may have discovered where in the body HIV takes refuge during antiretroviral treatment. Research conducted using an animal model indicates that the virus may hide in lymph nodes in the spleen and gut. The researchers believe those lymph nodes are the staging ground from which the virus prepares to relaunch the infection after treatment has stopped, according to the study published in Mucosal Immunology from publisher Nature Research.

The researchers conducted their research using macaques infected with simian immunodeficiency virus (SIV), a close cousin of HIV. They found that during antiretroviral treatment, two types of cells in the spleen and gut lymph nodes serve as reservoirs replication sites for the virus. These cells belong to the family of CD4 T lymphocytes, the preferred target of HIV.

"These cells are involved in mounting the immune response," said Professor Estaquier. "We don't know why the viruses taking refuge in these cells are able to escape antiretroviral drugs. They may have a mechanism that limits the flow of drugs or eliminates them faster. To improve treatment, we'll need a better understanding of what allows these cell populations to escape antiretroviral drugs."

For the purposes of the study, the researchers focused on the tissues and lymph nodes that harbour CD4 T cells. Other organs of the body that are not linked to the lymph system may also serve as reservoirs for HIV. Professor Estaquier's team is pursuing its research, with more results expected in the coming months.

If the results obtained with SIV can be confirmed with HIV in humans, they would bring us one step closer to a cure for AIDS. "Finding the cells and anatomical sites where HIV takes refuge and destroying them are the main obstacles to developing therapies to cure AIDS," said Professor Estaquier.

The vast majority of in-use make-up products such as beauty blenders, mascara and lip gloss are contaminated with potentially life threatening superbugs, new research from Aston University published in the Journal of Applied Microbiology has revealed.

Make-up products used every day by millions of people in the UK are contaminated with potentially deadly bugs, such as E.coli and Staphylococci, because most are not being cleaned and are used far beyond their expiry dates, new research led by Dr Amreen Bashir and Professor Peter Lambert of Aston University's School of Life and Health Sciences has shown.

Bacteria that can cause illnesses ranging from skin infections to blood poisoning if used near eyes, mouth or cuts or grazes were found in nine out of ten of the products. This risk is amplified in immunocompromised people who are more likely to contract infections from opportunistic bacteria.

The relatively new beauty blenders - sponges used to apply skin foundation products - were found to have the highest levels of potentially harmful bacteria - with the vast majority (93 per cent) not having ever been cleaned, despite more than two thirds (64 per cent) being dropped on the floor at some point during use.

The research is the first to look at beauty blender products - hugely popular make-up sponges used to blend foundation and contouring on the face. Often endorsed by celebrities, these sponges are estimated to have sold over 6.5million worldwide. The Aston researchers found these products are particularly susceptible to contamination as they are often left damp after use, which creates an ideal breeding ground for harmful bacteria.

Researchers say the findings reveal that consumers are unwittingly putting themselves at risk, and that manufacturers and regulatory bodies should do more to protect their customers by making expiry dates and cleaning requirements more prominent on packaging. EU guidance holds make-up brands to strict hygiene standards of manufacture and states that E.coli in particular should not be found in any concentration in new cosmetic products. However, there is currently limited consumer protection around the risks of contaminating products while in use.

Post-Brexit, UK consumers could be at even greater risk as they will no longer be protected by EU regulations and could find themselves purchasing more beauty products from the US - for example - where there are no regulatory requirements to put expiry dates on make-up packaging at all.

Commenting on the new findings, Dr Bashir said: "Consumers' poor hygiene practices when it comes to using make-up, especially beauty blenders, is very worrying when you consider that we found bacteria such as E.coli - which is linked with faecal contamination - breeding on the products we tested.

"More needs to be done to help educate consumers and the make-up industry as a whole about the need to wash beauty blenders regularly and dry them thoroughly, as well as the risks of using make-up beyond its expiry date."

When prostate cancer spreads, it most often spreads to bone. And while the 5-year survival rate for prostate cancer that has not spread is nearly 100 percent, once the disease reaches bone, the 5-year survival rate is only 29 percent. Now a University of Colorado Cancer Center study published in the Journal for Immunotherapy of Cancer suggests a new approach, or, possibly two new approaches against these bone metastases: While targeted therapies and anti-cancer immunotherapies have not been especially successful against primary prostate cancers, the study suggests that both these approaches may be effective against the bone metastases that grow from primary prostate cancers, and, in fact, the type of bone metastasis may dictate which targeted therapies and immunotherapies work best.

There are two types of bone disease from metastases: lytic metastases, which destroy bone tissue, and blastic metastases, which build new bone-like tissue with cancer cells. Currently, it doesn't matter if a bone metastasis is lytic or blastic - they are both treated the same way. But the current study shows that the genetic and cellular landscapes of these two types of metastases are different, providing different drug targets and suggesting different treatments.

"The genetic and immune checkpoint changes are like those seen in other solid tumors, making it potentially possible to apply new strategies to prostate cancer patients with metastatic bone disease," says paper first author Claire Ihle, PhD student in the lab of CU Cancer Center investigator and paper senior author Philip Owens, PhD.

Lytic metastases were characterized by over-activity in a genetic signal called pAKT and its larger signaling pathway called PI3K-AKT, both of which have been targets for drug development in other cancers. Meanwhile, blastic lesions had over-activity in another genetic signal called pSTAT3 and its signaling pathway JAK-STAT, for which FDA-approved drugs already exist.

"I was really shocked by the increase in pSTAT3 in the blastic patients. I expected that these bone-producing (blastic) lesions would have little to no specific targets. I am glad I was wrong as these are the most common lesions in prostate cancer patients," Ihle says. "I would love to see STAT3 inhibitors go to blastic-type patients if we have more data showing a good response."

Importantly, both types of bone metastases also had characteristics that predict response to immunotherapy. Doctors and researchers call primary prostate cancers "cold," meaning they tend not to provoke an immune response. However, both blastic and lytic bone metastases had high levels of the protein PD-L1, which could mean they are more likely to respond to the class of anti-cancer immunotherapy known as checkpoint inhibitors.

"The other interesting point of our studies is that we developed a test that can directly measure immunotherapy and pathway targets in bone metastases," Owens says. "This is significant because we could potentially use this as a test to determine which of the many immunotherapies could be best for an individual patient, one at time, and truly provide a personalized therapy. If I had metastatic disease in bones, I would like a pathology department to know that the immunotherapy they wish to treat me with has a good level of target in the tissue they are hoping to treat."

The group is now focused on testing therapies in mouse models of lytic and blastic bone metastases to determine the most promising drugs and drug combinations.

"The pathway-targeted therapies could be used in combination with immunotherapy or alone and we really don't know if or how to combine them," Owens says.

Previously, the field assumed that bone metastases could be treated the same as the primary prostate cancers from which they grow. Now, the current study shows that's not the case, and even pinpoints signaling pathways and immunologic weaknesses of various types of metastases. If these findings stand the test of ongoing work, the line of research may point to new therapies and drug combinations for these metastases that represent the most dangerous aspects of prostate cancer.

HOUSTON -- Researchers at The University of Texas MD Anderson Cancer Center have found that a protein involved in immune response to microbes also can fuel cancer development and suppress immune response to the disease.

Working in mouse models of lung cancer, the team found TANK-binding kinase 1 (TBK1) and its adaptor protein TBK-binding protein 1 (TBKBP1) contribute to tumorigenesis when they are activated by growth factors rather than by innate immune mechanisms. Their findings are reported today in Nature Cell Biology.

"Our work also provides the first evidence that TBK1 functions in cancer cells to mediate immunosuppression, suggesting that targeting TBK1 will both inhibit tumor growth and promote antitumor immunity," says senior author Shao-Cong Sun, Ph.D., professor of Immunology.

Recent research indicated that TBK1, which normally mediates induction of type 1 interferon in response to viruses or bacteria, also promotes the survival and reproduction of KRAS-dependent cancer cells. Sun and colleagues set out to identify TBK1's impact on cancer cells and its role in cancer development in vivo.

They first found that knocking out TBK1 in a mouse model designed to spontaneously develop lung cancer driven by KRAS mutations sharply reduced the number and size of tumors. Knockdown in a human lung cancer line promoted programmed cell death and suppressed tumor growth.

In a series of experiments, the researchers showed that TBK1 and TBKBP1 form a growth factor signaling axis that activates mTORC1 to promote tumor development. The pathway consists of TBKBP1 recruiting TBK1 to protein kinase C-theta (PKCθ), through a scaffold protein called CARD10, enabling PKCθ to activate TBK1.

Amlexanox inhibits TBK1, shrinks tumors

To test the protein's therapeutic potential, they treated mice with KRAS-driven lung cancer with amlexanox, a drug approved by the Food and Drug Administration as a paste to treat certain oral ulcers. The drug was recently identified as a TBK1 inhibitor. Mice injected with amlexanox had a steep reduction in the number and size of lung tumors.

KRAS-driven cancer is resistant to immune response, but the researchers found amlexanox sensitized tumors to blockade of the CTLA-4 checkpoint on immune T cells.

Knocking down TBK1 in the KRAS-driven mouse model increased the frequency of effector CD4 helper T cells and CD8 cell-killing T cells in the lungs of the mice. A similar experiment in another mouse model also reduced the frequency of immune-suppressing myeloid-derived suppressor cells.

Additional experiments implicated TBK1 in promotion of glycolysis - a sugar-burning metabolic process that also suppresses the immune system - and the increased presence of PD-L1, a protein on tumor cells that turns off attacking T cells by connecting with the PD-1 protein on their cell surface.

Treatment with amlexanox and anti-CTLA-4 immunotherapy stimulated immune response and reduced tumor size and frequency in the mouse models.

"We're continuing to examine the signaling function of TBK1 in different types of immune cells using animal models and to assess the therapeutic potential of TBK1 using preclinical cancer models," Sun says.

While amlexanox has been tested in a clinical trial for treatment of type 2 diabetes and obesity, there are no clinical trials open to test the drug against cancer. Sun says his team continues preclinical research necessary to lay the groundwork for clinical trials, including research to determine whether amlexanox might work against other cancer types.

Researchers at the Lady Davis Institute have identified a key protein that is required for resistance to chemotherapy in the most aggressive form of breast cancer. This holds the promise of opening the door to new therapies for overcoming drug resistance.

Using tumor biopsies from patients with chemotherapeutic resistant triple negative breast cancer (TNBC), researchers at the Lady Davis Institute of the Jewish General Hospital (JGH) have identified changes to the form of the cancer cells that appear to be associated with their capacity to resist usual drug treatment. This discovery is featured on the cover of the December issue of Molecular Cancer Research, where it is highlighted for its importance.

"When patients with TNBC respond to treatment, their prognosis is very good," explains Dr. Mark Basik, a surgical oncologist and Medical Director of the Inter-disciplinary Breast Cancer Team at the Segal Cancer Centre at the JGH, who led the research. "However, resistance to treatment is quite common. Chemotherapy resistant TNBC constitutes the most aggressive form of breast cancer, and the prognosis for those patients is not that good. Therefore, it is critical that we determine the processes that promote resistance and target it directly to overcome its influence on the tumor."

The researchers observed that the onset of resistance to the two most common drugs deployed against TNBC is associated with changes in the shape of the cancer cells and the manner in which they process fat. The cells are able to store fat droplets that they can exploit as a source of energy to fight off the effects of chemotherapy. These cells were also seen to develop a dependence on the protein perilipin4, which is highly expressed in resistant tumors. The protein is used by the cancer cell to stabilize the fat droplet, which would otherwise leak free fat into the cell, which is toxic to it and would kill the cell. Dr. Isabelle Sirois, a postdoctoral fellow in Dr. Basik's lab and the first author on the paper, and her colleagues determined that targeting this protein caused nearly all of the resistant cells to stop growing, and most to die.

"This is very promising," said Dr. Basik, who is also the Herbert Black Professor of Surgical Oncology at McGill University, "because if we can eliminate the resistant cells, we will be able to successfully treat far more TNBC patients."

A key element in treating cancer is finding the active protein that makes possible the disease's unchecked growth. With that, the vulnerability of the cell is revealed, opening the door to new therapies and better patient outcomes.

CHICAGO - A novel MRI-guided procedure that uses therapeutic ultrasound effectively treats prostate cancer with minimal side effects, according to a new study presented today at the annual meeting of the Radiological Society of North America (RSNA). Researchers said the incision-free technique could also be used to treat benign enlargement of the prostate gland.

Prostate cancer is the second-leading cause of cancer death in men after lung cancer. Treating disease in the small gland that surrounds the urethra just outside the bladder is challenging. Surgery and radiation are not always effective and can result in incontinence, impotence and bowel dysfunction. Other currently available techniques lack sophisticated imaging guidance and temperature monitoring.

In recent years, a minimally invasive method called MRI-guided transurethral ultrasound ablation (TULSA) has emerged as a promising treatment option. TULSA works by delivering precise doses of sound waves to diseased prostate tissue while sparing the healthy nerve tissue surrounding the prostate.

TULSA relies on a rod-shaped device that is inserted into the urethra. The novel device has 10 ultrasound-generating elements that can cover the entire prostate gland. One or more of the elements are used to send out sound waves that heat and destroy the target prostate tissue. The elements are controlled automatically by a software algorithm that can adjust the shape, direction and strength of the therapeutic ultrasound beam. The entire procedure takes place in an MRI scanner so that doctors can closely monitor treatment and assess the degree and location of heating.

"Unlike with other ultrasound systems on the market, you can monitor the ultrasound ablation process in real time and get immediate MRI feedback of the thermal dose and efficacy," said study co-author Steven S. Raman, M.D., professor of radiology and urology, and director of Prostate MR Imaging and Interventions and Prostate MR Imaging Research at the University of California at Los Angeles (UCLA). "It's an outpatient procedure with minimal recovery time."

In the new multicenter study, researchers reported on the 12-month outcomes from the TULSA-PRO® ablation clinical trial (TACT). The trial enrolled 115 men, median age 65, with localized low or intermediate risk, gland-confined prostate cancer. Clinicians delivered TULSA treatment to the entire gland. Treatment time averaged 51 minutes.

Prostate volume in the study group decreased on average from 39 cubic centimeters pre-treatment to 3.8 cubic centimeters a year after treatment. Overall, clinically significant cancer was eliminated in 80% of the study participants. Seventy-two out of 111 men, or 65%, had no evidence of any cancer at biopsy after one year. Blood levels of prostate-specific antigen (PSA), a marker of prostate cancer, fell by a median of 95%. There were low rates of severe toxicity and no bowel complications.

"We saw very good results in the patients, with a dramatic reduction of over 90 percent in prostate volume and low rates of impotence with almost no incontinence," Dr. Raman said.

Approved for clinical use in Europe, TULSA has just received FDA 510(k) clearance for prostate tissue ablation in the United States. Assuming follow-up studies support the preliminary results, the technique could develop into an important tool for treating both prostate cancer and benign prostatic hyperplasia, or enlargement of the prostate.

"There are two very unique things about this system," Dr. Raman said. "First, you can control with much more finesse where you're going to treat, preserving continence and sexual function. Second, you can do this for both diffuse and localized prostate cancer and benign diseases, including benign hyperplasia."

TULSA also has the benefit of allowing further treatment if needed, Dr. Raman said. If it fails, then the procedure can be repeated, and more aggressive invasive approaches like surgery and radiation therapy can still be used. Alternatively, TULSA may enable noninvasive treatment for localized radiation failure.

The study also supports the use of MRI for post-treatment monitoring of patients who undergo TULSA. MRI at one year after treatment had a negative predictive value of 93 to 96% for detecting residual cancer, meaning it was very accurate for ruling out disease recurrence in patients.

The investigational therapeutics mAb114 and REGN-EB3 offer patients a greater chance of surviving Ebola virus disease (EVD) compared to the investigational treatment ZMapp, according to published results from a clinical trial conducted in the Democratic Republic of the Congo (DRC). The new report also shows that early diagnosis and treatment are associated with an increased likelihood of survival from EVD.

The results appear online this week in The New England Journal of Medicine. An announcement made on August 12, 2019, noted that the study leaders halted the trial early, on August 9, 2019, as recommended by an independent data and safety monitoring board based on its review of preliminary data from 499 study patients. The preliminary analysis found that both mAb114 and REGN-EB3 performed better than ZMapp. The fourth drug, remdesivir, performed similarly to ZMapp. Today's publication provides a comprehensive analysis of the full dataset from nearly 200 additional patients enrolled in the clinical study.

The clinical trial known as PALM, short for "Pamoja Tulinde Maisha," a Kiswahili phrase that translates to "together save lives," was organized by an international research consortium coordinated by the World Health Organization (WHO). It is led and funded by the DRC's National Institute for Biomedical Research (INRB) and Ministry of Health, and the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health. Professor Jean-Jacques Muyembe-Tamfum, M.D., Ph.D., director-general of the INRB and head of the DRC's Ebola response, and Richard T. Davey, Jr., M.D., deputy director of NIAID's Division of Clinical Research, are co-principal investigators for the study.

"Response teams have faced unprecedented challenges in ongoing efforts to save lives and control the outbreak of Ebola in a highly insecure region of the Democratic Republic of the Congo," said NIAID Director Anthony S. Fauci, M.D. "Although effective treatments alone will not end this outbreak, the PALM study findings identify the first efficacious treatments for Ebola virus disease and therefore mark a significant step forward in improving care for Ebola patients. We thank the study team for their extraordinary efforts to conduct this landmark trial."

The study enrolled 681 people with Ebola virus disease between November 2018 and August 2019 at four Ebola treatment centers (ETCs) in the cities of Beni, Butembo, Katwa and Mangina. Staff from The Alliance for International Medical Action (ALIMA), International Medical Corps (IMC), Médecins Sans Frontières/Doctors Without Borders (MSF) and the DRC Ministry of Health implemented the trial at the ETCs with support from Congolese staff, the World Health Organization, the Frederick National Laboratory for Cancer Research and The Mitchell Group.

The study was designed to compare mortality among patients who received one of three investigational Ebola drugs with that from a control group of patients who received the investigational monoclonal antibody cocktail ZMapp, developed by Mapp Biopharmaceutical, Inc. The other therapies were mAb114, a single monoclonal antibody product developed for clinical use by NIAID's Vaccine Research Center and the INRB and licensed to Ridgeback Biotherapeutics and Mapp Biopharmaceutical; REGN-EB3, a monoclonal antibody cocktail developed by Regeneron Pharmaceuticals, Inc.; and remdesivir, an antiviral drug developed by Gilead Sciences, Inc. The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also has provided support for the development of REGN-EB3, ZMapp and mAb114.

The four therapies are administered as intravenous infusions. REGN-EB3 and mAb114 are administered as single infusions and ZMapp and remdesivir are administered as infusions over multiple days. Study participants also received optimized supportive care, including oral and/or intravenous fluids, electrolyte replacement, monitoring of oxygen levels and blood pressure (with supportive measures as needed), blood transfusions, pain management, and antibiotics and antimalarials as indicated.

The final analysis included 673 participants. The trial began in November 2018 with randomized administration of remdesivir, mAb114 and ZMapp, and the protocol was amended to include REGN-EB3 in January 2019. As a result, the number of outcomes included in the ZMapp comparator group was slightly different for the initial arms (remdesivir and mAb114) relative to the number of outcomes in the ZMapp comparator group for REGN-EB3, based on time of enrollment. Overall mortality was 50% (84/169) in all patients treated with ZMapp and 51% (79/154) in patients who received ZMapp during the time that REGN-EB3 was included as another trial arm. Mortality rates were lower for mAb114 and REGN-EB3 compared to their respective ZMapp cohorts: 35% (61/174) of patients in the mAb114 treatment group and 34% (52/155) of patients in the REGN-EB3 group died by 28 days post-treatment. The mortality rate in the remdesivir treatment group, 53% (93/175), was similar to ZMapp.

Overall, mortality rates were lower in patients who had less virus in their blood at the time of enrollment (19% overall, with 10% for mAb114, 11% for REGN-EB3, 29% for remdesivir and 25% for ZMapp overall). Mortality rates were higher in patients with more virus in their blood at the time of enrollment (76% overall, 70% for mAb114, 64% for REGN-EB3, 86% for remdesivir and 85% for ZMapp). The analysis also showed that patients receiving either mAb114 or REGN-EB3 cleared the virus from their blood more quickly than participants receiving ZMapp.

"These results bring more than hope, they show what powerful tools we have now to save lives in the Democratic Republic of the Congo, and in future Ebola outbreaks. We must make sure everyone affected by the virus knows about these treatments and is able to access them," said WHO Director-General, Dr. Tedros Adhanom Ghebreyesus.

Investigators note that the trial data demonstrate the importance of early diagnosis and treatment. Patients arriving at the ETC within one day of reported onset of symptoms had a mortality rate of 19%, while patients arriving after five days of symptoms had a mortality rate of 47%. The odds of death increased 11% each day that a person delayed going to an ETC.

"The PALM trial results confirm that it is extremely important for people who have symptoms of Ebola to go to a treatment center as soon as possible to receive advanced supportive care and life-saving therapeutics and increase their chances of survival," said Professor Muyembe.

All four study drugs were generally well tolerated. There were a total of four serious adverse events that were judged to be potentially related to the experimental drugs. Three of these were in two of the patients who received ZMapp. One was in a patient who received remdesivir.

The authors note that despite encouraging findings regarding mAb114 and REGN-EB3, approximately one-third of patients who received these therapeutics died, highlighting the potential to improve upon these results, whether through further optimization of supportive care, combination therapy using agents with complementary mechanisms of action or other strategies.

"Despite unprecedented challenges--including an unstable electrical power grid and evacuations of staff and patients from treatment centers due to violent attacks--the PALM trial demonstrates that scientifically rigorous and ethically sound clinical research can be conducted during disease outbreaks," said H. Clifford Lane, M.D., NIAID deputy director for Clinical Research and Special Projects. "We thank the patients and the medical staff in the field and at the treatment sites for their participation and exceptional commitment to the trial."

With their expertise in the safe and effective use of medications, pharmacists can help in the management of chronic diseases. A review and analysis published in the British Journal of Clinical Pharmacology indicates that initiatives--such as patient education, medication review, and physical assessments--led by pharmacists can make important contributions to the prevention of cardiovascular disease.

To assess the potential of pharmacists to help prevent cardiovascular diseases in general practice, Abdullah Alshehri, of the University of Birmingham, in the UK, and his colleagues searched the medical literature for relevant randomised controlled clinical trials.

The team identified 21 trials with a total of 8,933 patients. Pharmacist-led interventions included patient education, medication review and counselling, physical assessment, assessing adherence, lifestyle modification, and medication management (such as prescribing, adjusting, monitoring, and administering therapy, and identifying drug-related problems). The most frequently used pharmacist-led interventions were medication review and medication management.

Patients receiving pharmacist-led interventions experienced significant reductions in their systolic blood pressure (by an average of -9.33 mmHg); Hemoglobin A1c, a measure of blood sugar levels (by an average of -0.76%); and LDL-cholesterol (by an average of -15.19 mg/dl). Pharmacist-led interventions also helped patients correctly follow their prescribed medication regimens.

"The evidence presented in this review provides an important message to health systems and policy makers regarding the effectiveness of general practice-based pharmacists' interventions," said Alshehri. "The significant reductions in blood pressure, blood glucose, and blood cholesterol reported in this meta-analysis, if sustained in clinical practice, could have significant implications for managing hypertension, diabetes and dyslipidaemia that could prevent cardiovascular morbidity and mortality."

Alshehri noted that the findings support a greater involvement of pharmacists in general practice. "This will benefit health organisations by providing cost-effective care associated with greater control of patients' conditions and their medications," he said.

Traumatic brain injury (TBI) is a significant global cause of mortality and morbidity with an increasing incidence, especially in low-and-middle income countries. The most severe TBIs are treated in intensive care units (ICU), but in spite of the proper and high-quality care, about one in three patients dies.

Patients that suffer from severe TBI are unconscious, which makes it challenging to accurately monitor the condition of the patient during intensive care. In the ICU, many tens of variables are continuously monitored (e.g. intracranial pressure, mean arterial pressure and cerebral perfusion pressure) that indirectly give information regarding the condition of the patient.

However, only one variable, such as intracranial pressure, may yield hundreds of thousands of data points per day. Thus, it is impossible for the human brain to comprehend the resulting millions of daily collected data points from all monitored data. This is why researchers at Helsinki University Hospital (HUS) started to develop an artificial intelligence (AI) based algorithm that could help doctors treat patients with severe TBI. At its best, such an algorithm could predict the outcome of the individual patient and give objective data regarding the condition and prognosis of the patient and how it changes during treatment.

"A dynamic prognostic model like this has not been presented before. Although this is a proof-of-concept and it will still take some time before we can implement algorithms like this into daily clinical practice, our study reflects how and into what direction modern intensive care is evolving", says Rahul Raj, Adjunct Professor of Experimental Neurosurgery from HUS and one of the authors of the paper.

The algorithms can predict the probability of the patient dying within 30-days with accuracy of 80-85%.

"We have developed two separate algorithms. The first algorithm is simpler and is based only upon objective monitor data. The second algorithm is slightly more complex and includes data regarding the level of consciousness, measured by the widely used Glasgow Coma Scale score. As expected, the accuracy of the more complex algorithm is slightly better than for the simpler algorithm. Still, the accuracy of both algorithms is surprisingly good, considering that the simpler model is based upon only three main variables and the more complex upon five main variables", tells Eetu Pursiainen, Data Scientist from the Analytics and AI Development Department at HUS, one of the authors and main coders of the algorithms.

In the future, the algorithms still have to be validated in national and international external datasets.

"Finland is one of the world leaders in artificial intelligence solutions in specialized healthcare and Helsinki University Hospital, as one of the largest hospitals in Europe, plays an important role in bringing Finnish excellence into the world. Because of this, we think that it is important act ethically and share our algorithms openly and free of charge for further development, both nationally and internationally", states Miikka Korja, Chair of the HUS Artificial Intelligence Steering Group and Adjunct Professor of Neurosurgery at the University of Helsinki.

As bookstores and libraries continue to line their shelves with self-help literature, most month-by-month pregnancy guides have one thing in common -- recommendations to follow medical guidance over mom's advice, often arguing for a "generational disconnect" between pregnant women and their mothers.

But according to sociology research at the University of Cincinnati, most pregnant women still rely on their mothers for emotional support and guidance -- many weighing mom's advice as equal to or even over medical recommendation. "And often for good reason," says Danielle Bessett, UC associate professor of sociology.

During the study, funded by the National Science Foundation and recently published in the journal Reproduction, Health, and Medicine (Advances in Medical Sociology), Bessett investigated the complexities within mother-daughter dynamics during pregnancy in relation to potentially harmful advice from many pregnancy guidebooks, looking specifically at the emotional and health care risks to certain groups.

Bessett performed in-depth interviews with pregnant women and their mothers while following the pregnant women for nine months. Her research is an example of the innovation and academic excellence that are tenets of UC's Next Lives Here strategic direction.

"I found that most pregnancy self-help books, best known for their month-by-month guidance on fetal development and lifestyle coaching, are also empathic about following medical advice exclusively over what they consider the outdated advice of a mother or friend," says Bessett, who calls the books' narrow perspective the "generational disconnect."

"This advice is limited and can result in an increased level of stress and discomfort for some soon-to-be moms."

Pervasive link

While looking at two groups -- pregnant women with at least a bachelor's degree and women with no college or higher education -- Bessett found that all pregnant women took steps to have a healthy pregnancy. But while she identified a pervasive link to a mother's influence on her daughter's health and well-being in both groups, it was especially strong for minorities and women with less than a college degree who had little trust in their medical personnel.

"It was not the case at all that these mothers were anti-science or against medicine, but for minority women and those with lower levels of education there is clear evidence of not being listened to or feeling cared for by physicians and clinics as much as pregnant women with higher education," says Bessett. "This all ties back to why women with lower education might be relying more on their mothers -- because their moms listen to them more."

Women with higher education engaged with their mothers in ways much more similar to how they are framed in common self-help books, Bessett says, but not a total disconnect as the books suggest. Their relationship was more specific.

"They leaned more on their doctors for advice about what to eat and what tests to have, but turned to their moms for advice on child care and for emotional support and talked a lot about the ways in which bodies change as a result of pregnancy," she says.

While this was also true for the women with lower education, Bessett found those women turning to their mothers for other realms of guidance, sometimes over standard medical advice.

"Self-help books are giving us a really terrible picture of soon-to-be grandmothers that pregnant women themselves don't really fully endorse regardless of who they are," says Bessett. "I argue that books are strictly endorsing medical guidance exclusively and that's not the only place where women are getting their information."

Mother knows best

While highly educated women engaged with their mothers in a more limited way, women with lower education engaged with their mothers more in-depth about everything and ranked their mothers as the most valuable source of information, Bessett adds.

Within the group of women with lower education Bessett found a common denominator -- the lack of being listened to and often feeling discounted by medical personnel, especially when they told their doctors that their mothers said this or suggested that.

By and large, self-help guides argue that the womens' mothers will only offer outdated advice, she says, but the books do not factor in the emotional value that those mothers provide.

"One particular woman in the lower educated research group had a borderline hypertensive disorder and was advised to shift to the high-risk clinic, which meant more frequent appointments and giving up her current clinician for the remainder of her pregnancy," says Bessett. "But her mother advised against it knowing the emotional cost to her daughter. She encouraged her to continue with the usual prenatal routine and fed her liver, which she believed would keep her nutritional levels up and her blood pressure down. Her mother's support avoided adding stress to a pregnancy that ultimately resulted in the birth of a healthy baby boy."

Other caveats within the lower-educated mother-daughter dyads include a number of women who didn't have as much distance between their mother's last pregnancy and their own, which resulted in advice and support that was much more current.

"Their mothers often had their children at a younger age and the pregnant women themselves are now giving birth younger," says Bessett. "If the mother and daughter are only 18 to 20 years apart, the mother may also have continued to have children not long before her older daughter gave birth. In that regard, mom's advice is still very current."

Conversely, women with higher education typically wait until the age of 30 to give birth, which Bessett found to follow suit with their daughters. In that case the mother's advice may be somewhat outdated and less relevant to today's modern medical guidelines.

Even so, women with higher education still found a great value in what their mothers could tell them about how their bodies would be changing and were a valuable source for details related to their familial or genetic inheritance -- information that only their mothers could contribute, she adds.

Best of both worlds

"One of the most distinctive differences between the two groups showed how much more women with higher education valued how scientific information and modern technology could contribute to a healthy pregnancy," says Bessett. "But instead of a 'generational disconnect' they tended to read self-help books along with their mothers who also enjoyed a vicarious engagement with science that they didn't have when they were pregnant decades ago."

These mothers recognized that their birth experiences were much different from the medical interventions women have today, so Bessett found they were less likely to try to call the shots or endorse their pregnancy experiences as more appropriate.

"The overarching gain from the study shows how damaging self-help books can be for certain groups who take the 'generational disconnect' seriously," says Bessett. "In a context of considerable health misinformation, we have to understand in what circumstances extended family can be the source of this misinformation and when they provide an important sounding board for expectant parents.

"These books don't take into account how damaging it can be to sever bonds with their mothers during a time when they need low stress, warm bonding and emotional support more than ever for a healthy pregnancy."

Conducting future research on grandparents can help to insure that new parents have all the support they need by demonstrating that the "generational disconnect" is not a given and knowledge and investment in pregnancy practices is highly variable, suggests Bessett.

"Medical advice is not always black and white," she adds. "Doctors and medical personnel who use a more holistic approach and actually listen and really hear their patients, no matter how much they may rely on their mothers, would do more for their [patients'] emotional as well as medical well-being -- because sometimes 'mothers really do know best.'"

MINNEAPOLIS - Researchers have identified nine cases of people who lost their ability to swim after having a deep brain stimulation device implanted to control symptoms of Parkinson's disease. The new research is published in the November 27, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology. All nine people had been good swimmers even after their Parkinson's disease diagnosis. But once they had deep brain stimulation surgery, researchers found while other movement symptoms improved, their swimming skills deteriorated.

"Until more research is done to determine why some people with deep brain stimulation can no longer swim, it is crucial that people be told now of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water," said author Daniel Waldvogel, MD, of the University of Zurich in Switzerland.

For deep brain stimulation, electrodes are placed in certain areas of the brain to control abnormal movements. The electrodes are connected to a device placed under the skin in the upper chest. The device controls the electrical impulses.

Of the nine documented cases, three are highlighted in the research paper. Each person's movement symptoms improved after deep brain stimulation.

A 69-year-old man who was a good swimmer and lived on a lake jumped into the water after deep brain stimulation. Since his movement symptoms had improved, he thought would be able to swim. But he could not. He told researchers he would have drowned if he hadn't been rescued by a family member.

A 59-year-old woman who was a competitive swimmer and continued to swim after being diagnosed with Parkinson's disease was no longer able to swim after deep brain stimulation. Even after practice, she never regained her former ability level.

A 61-year-old woman who swam in competitions crossing Lake Zurich, which is two miles wide, could barely swim two-tenths of a mile after deep brain stimulation. She complained of awkward posture when trying to swim.

Three of the nine people turned off their deep brain stimulation devices and were immediately able to swim. But because their other movement symptoms worsened, they switched on their devices again.

"Swimming is a highly coordinated movement that requires complicated arm and leg coordination," said Waldvogel. "Exactly how deep brain stimulation is interfering with this ability needs to be determined."

Waldvogel noted that the report includes only a few cases. More research is needed in large groups of people to determine the percentage of people with Parkinson's disease who lose their ability to swim with deep brain stimulation.

"Even though these reports affected only a few people, we felt this potential risk was serious enough to alert others with Parkinson's disease, as well as their families and doctors," he said.