Medical-News

Study finds new genetic clues associated with asthma in African ancestry populations

2019-02-26T15:27:00.000-05:00

CU Anschutz scientists discover areas of chromosomes associated with asthma, a complex disease with striking disparities across racial/ethnic groups

In the largest study of its kind, researchers at the University of Colorado Anschutz Medical Campus have found new clues into the parts of the human genome associated with the higher rates of asthma in those of African ancestry.

The study was published today in the journal Nature Communications.

Using advanced new technology, scientists were able to identify loci or locations on a specific chromosome that may put those of African descent at a higher risk of asthma.

They also discovered four chromosomal regions usually found in whites and Asians associated with asthma. One of those chromosomal areas is known as the 17q12 - 21 region.

Despite the high incidence of asthma among those of African ancestry, it has been historically underrepresented in genome-wide association studies (GWAS) even though the African genome is the most diverse on earth.

"In the largest GWAS of asthma in African ancestry populations to date, we found strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, and we also identified two novel loci on chromosome 8 that may be specific to asthma risk in African ancestry populations," said the study's first author Michelle Daya, PhD, assistant professor in the division of Biomedical Informatics and Personalized Medicine at the CU School of Medicine.

According to Kathleen Barnes, PhD, the senior author on the study and director of the Colorado Center for Personalized Medicine at CU Anschutz, those of African ancestry in the Americas and elsewhere suffer a disproportionate burden of disability, disease and death from common chronic illnesses like asthma and diabetes.

Yet the group has been understudied.

To better understand this population and its genetic impact, Barnes worked with the National Institutes of Health's National Heart, Lung and Blood Institute (NHLBI) to create the `Consortium on Asthma among African-ancestry Populations in the Americas' or CAAPA.

"NHLBI has been promoting basic research to understand the genetic contribution to asthma disparities across racial and ethnic groups, and the CAAPA is one of our major investments in this area," said James Kiley, director of the Division of Lung Diseases at NHLBI and the NIH.They sequenced the genome of 642 people of African ancestry from 15 North, Central and South American and Caribbean populations plus Yoruba-speaking individuals from Ibadan, Nigeria.

In this latest study, researchers looked at 7,009 asthma cases and 7,645 controls.

"From this study we can say chromosome 17q is important for the development of asthma not just in populations of European or Asian ancestry, but also those of African ancestry," Barnes said. "This is a big step forward in untangling what is happening at this loci."

The researchers were able to make these findings due to new technology like the development of the African Diaspora Power Chip in partnership with Illumina Inc. which allows for improved tagging and coverage of African ancestry genetic variation.

"We need to understand what is driving asthma in these populations," Barnes said. "Now we have a much better genetic foundation for pursuing this."

Daya agreed.

"Ultimately, we hope that a better understanding of the genetic risk factors for asthma in African ancestry populations will lead to the development of better therapeutic interventions," she said.

Source:

https://www.ucdenver.edu/pages

New study finds how high-fat diets fuel colorectal cancer growth

2019-02-26T14:10:00.002-05:00

As cancer death rates drop overall, doctors have noted a frightening anomaly: deaths from colorectal cancer in people under 55 appear to be creeping up. According to the American Cancer Society, deaths in this younger group increased by 1 percent between 2007 and 2016.

A new study led by Salk Institute scientists suggests that high-fat diets fuel colorectal cancer growth by upsetting the balance of bile acids in the intestine and triggering a hormonal signal that lets potentially cancerous cells thrive. The findings, which appeared in Cell on February 21, 2019, could explain why colorectal cancer, which can take decades to develop, is being seen in younger people growing up at a time when higher-fat diets are common.

"This study provides a new way to lower inflammation, restore intestinal health and to dramatically reduced tumor progression," says Professor Ronald Evans, director of the Gene Expression Laboratory, Howard Hughes Medical Institute investigator and holder of Salk's March of Dimes Chair in Molecular and Developmental Biology.

The research, conducted in a mouse model, suggests how lifestyle and genetics converge. The researchers found that animals with an APC mutation, the most common genetic mutation found in humans with colorectal cancer, developed cancer faster when fed a high-fat diet.

"It could be that when you're genetically prone to get colon cancer, something like a high-fat diet is the second hit," says study co-author Ruth Yu, a staff researcher in the Gene Expression Laboratory at Salk.

The intestine and colon (commonly lumped together as the "gut") are hard-working organs. As you eat, your gut needs to constantly regenerate its lining to undo the damage done by digestive acids. To do this, the gut houses a population of stem cells that can replenish lining cells when needed.

Scientists have found that colorectal cancers often originate from mutations in these stem cells. The most common colorectal cancer-linked mutation is in a gene called APC, which normally acts as a "tumor suppressor" gene because it controls how often cells divide. Mutations in the APC gene can remove that control and allow cells to divide rapidly and become cancerous.

Over the last four decades, Evans and his colleagues have investigated the roles of bile acids. (30 types of bile acids float around in the gut to help digest food and absorb cholesterol, fats and fat-soluble nutrients.) Among the lab's discoveries was the revelation that bile acids send hormonal signals to intestinal stem cells through a protein called the Farnesoid X receptor (FXR). For the new study, the researchers uncovered how high-fat diets affect that hormonal signaling.

Study first author Ting Fu, a postdoctoral fellow at Salk, began by following a clue in a mouse model with an APC mutation. These mice develop early signs of colorectal cancer, so she decided to monitor bile acid levels in the mice at the same time. She discovered that types of bile acids known to interact with FXR increased at the same time as cancer initiation--and that the presence of additional bile acids accelerated cancer progression.

The researchers showed that feeding these mice a high-fat diet was like adding fuel to a fire: high-fat diets increased levels of two specific bile acids that dampen the activity of FXR. The gut wants to repair itself, and FXR keeps the process slow, steady and safe. When bile acids inhibit FXR, a group of stem cells starts growing rapidly and accumulating DNA damage."We saw a very dramatic increase in cancer growth correlated to bile acid," says Michael Downes, a senior staff scientist at Salk and co-corresponding author of the study. "Our experiments showed that maintaining a balance of bile acids is key to reducing cancer growth."

"We knew that high-fat diets and bile acids were both risk factors for cancer, but we weren't expecting to find they were both affecting FXR in intestinal stem cells," says Annette Atkins, a staff researcher at Salk and co-author of the study.

The mice with APC mutations developed benign growths called adenomas. In humans, adenomas are common in the intestine and are routinely removed during colonoscopies. These growths normally take decades to turn into malignant adenocarcinomas. Yet the adenomas in these mice quickly turned cancerous when given high-fat diets.

At last, the researchers had found a possible cellular mechanism to explain the rise in colorectal cancer deaths in younger people. Their theory is that as high-fat diets have become more common in the United States, more people with an APC mutation are accelerating their cancer growth through these diets.

Next, the researchers decided to test a new cancer-fighting weapon. They used a molecule called FexD, developed at Salk, to activate FXR in intestinal stem cells. FexD appeared to counteract the damage done by unbalanced bile acids in both mouse organ models and human colon cancer cell lines.

While more experiments need to be done before FexD is tested in humans, the team says the drug candidate has some promising qualities: it can reach the colon and it only acts on FXR, so it should produce fewer side effects than other drugs.

"While colon cancer is considered 'incurable,' Ting's work opens up an entirely new frontier in the understanding and treatment of the disease," says Evans.

Source:

https://www.salk.edu/news-release/Salk-scientists-uncover-how-high-fat-diet-drives-colorectal-cancer-growth/

Hip fractures may serve as first sign of undiagnosed Alzheimer’s disease

2019-02-26T13:55:00.000-05:00

In a study of older people with no clinical diagnosis or signs of dementia when hospitalized to repair hip fractures, Johns Hopkins researchers say they found biomarkers of Alzheimer’s disease in most of the patients’ spinal fluid samples. The researchers say results of their study add to evidence that brain alterations that lead to poor balance in older people may underpin both increased risk of hip-fracturing falls and Alzheimer’s disease, and that hip fracture itself may therefore serve as a first sign of undiagnosed disease.

Credit: iStock

We studied a group of patients without a clinical diagnosis of dementia, meaning that many of our study participants were active and living independently without overt signs of Alzheimer’s disease.”
Esther Oh, M.D., Ph.D., associate professor of medicine at the Johns Hopkins University School of Medicine and associate director of the Johns Hopkins Memory and Alzheimer’s Treatment Center

Oh cautioned that her study does not suggest that every older person who has a hip fracture has Alzheimer’s, nor should everyone hospitalized for a hip fracture undergo spinal fluid tests for disease biomarkers at this time. But it does suggest that anyone facing hip repair surgery after a fall be monitored closely for signs of post-operative delirium or other mental or cognitive problems during recovery as some people may have underlying Alzheimer’s disease, which might make them more vulnerable.

Oh also noted that physicians are now diagnosing Alzheimer’s disease much earlier, and many people live for decades after diagnosis. Although there are no cures or proven treatments, early detection and health care planning may improve coping strategies and extend independent living time.

According to the National Institute on Aging, more than 5.5 million people¾most over the age of 65¾in the U.S. are estimated to have Alzheimer’s disease.

A report on the findings was published in fall 2018 in PLOS ONE.

Oh noted that several international studies have shown that up to a quarter of older adults hospitalized for hip fracture surgery are likely to die within the following year, results suggesting that a serious medical condition may have been simmering undiagnosed prior to the falls that sent them to the hospital.

Oh’s new study was in part a response to results of research published late 2018 in JAMA Surgery by Johns Hopkins researchers, which showed that 34 percent of hip fracture patients develop delirium during their hospital stay, a condition characterized by restlessness, delusions and incoherent thoughts and speech. Because patients with Alzheimer’s disease are more likely to experience these symptoms, and because of the higher than normal mortality rate associated with hip fracture compared with other surgeries, Oh and her team designed their study to directly test hip fracture patients for Alzheimer’s disease biomarkers.

For the research, the Johns Hopkins team recruited 200 hip fracture patients admitted to The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center from November 2011 to May 2016. Participants were an average of 82 years old, ranging from 65 to 102. Most of the participants, 74 percent, were women. Some 96 percent were white. The study also only included hip fracture patients who had received spinal (local) anesthesia before surgery so that spinal fluid samples could be collected at the time of anesthetic injection.

Before surgery, participants in the study also completed the Mini-Mental State Exam and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly, standard tests designed to determine mental state, memory and cognition.In 168 of the patients, the spinal fluid samples were tested for elevated levels of commonly accepted biomarkers of Alzheimer’s and other neurodegenerative diseases. The biomarkers included the proteins amyloid beta 42 (Aβ42), Aβ40, tau, and tau with a phosphate chemical group attached (p-tau). The amyloid proteins and tau are found in hallmark, tangled clumps in nerve cells, and in plaques that form in the brains of people with advanced Alzheimer’s. High levels of p-tau indicate brain injury or other types of brain cell damage.

On the basis of those test results, participants were given a Clinical Dementia Rating, with a score of 0 being completely healthy (representing 70 participants); 0.5 meaning mild cognitive symptoms (81 participants); a score of greater than 1.0 meaning early dementia (13 participants); and a score of 2.0 meaning moderate dementia (four participants). Of the people in the study, 86 percent had abnormal Aβ levels, 65 percent had abnormal tau and 35 percent had abnormal p-tau. When the researchers specifically looked at biomarker levels in the group with a Clinical Dementia Rating of 0, they found 62 out of 70 patients, or 88.6 percent, had abnormal levels of any one of the biomarkers. In the Clinical Dementia Rating group with a score of 0.5, indicating mild cognitive impairment, 98.8 percent or 80 out of 81 participants had abnormal levels in any one of the biomarkers.

The researchers ruled out older age as a possible factor skewing their results; normally 23 to 32 percent of people between 65 and 74 years old have abnormal Aβ levels. However, in the hip fracture patients, 68 percent of people in this same age range with a Clinical Dementia Rating of 0 had abnormal levels of Aβ.

Oh’s group plans to monitor study participants for a year after each surgery to document progression and clinical dementia ratings.

Testing for Alzheimer’s disease biomarkers is not covered by Medicare and isn’t routinely performed on older adults. It can be done by an amyloid PET scan or by using biomarkers from spinal fluid, such as in this study. The PET scan test costs at least $3,000. The spinal fluid analysis is still mostly used for research, although it is commercially available in some laboratories.

Source:

https://www.hopkinsmedicine.org/news/newsroom/news-releases/hip-fractures-may-be-an-early-sign-of-alzheimers-disease-for-older-people

Virtual reality shows promise for reducing fears and phobia in autistic adults

2019-02-26T13:48:00.000-05:00

In a new pilot study, autistic adults showed real-life, functional improvement after a combination treatment approach that included graded exposure to fear and anxiety-producing experiences in a virtual reality environment. The design and preliminary results of this novel approach are published in Autism in Adulthood, a new peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

In the article entitled "Using Virtual Reality Environments to Augment Cognitive Behavioral Therapy for Fears and Phobias In Autistic Adults," a team led by Professor Jeremy Parrfrom Newcastle University and NHS Foundation Trust, Newcastle upon Tyne, U.K. describe a pilot study in which they tested a combined cognitive behavioral (CBT) therapy and immersive virtual reality approach in adults aged 18-57 on the autism spectrum. The participants received one educational session followed by four 20-minute therapeutic sessions of gradually increasing exposure to the feared stimulus to minimize anxiety.

Source:"Phobias commonly co-occur with autism and often cause significant distress. While results are very preliminary, it is exciting to see innovative strategies for an issue that has been so hard to treat. Emerging Practices papers, such as this one, look towards the future by highlighting new avenues of research that have potential for improving quality of life for autistic adults," says Christina Nicolaidis, MD, MPH, Portland State University and Oregon Health & Science University, Portland, Oregon and Editor-in-Chief of Autism in Adulthood.

https://home.liebertpub.com/news/virtual-reality-a-promising-tool-for-reducing-fears-and-phobia-in-autism/3509

age 1 hypertension may predict 10-year incidence of cardiovascular disease

2019-02-26T10:55:00.000-05:00

This population-based, prospective cohort study enrolled 3042 participants of which 2583 participants were followed up for 10 years. Following the 10-year follow-up, 2020 participants were assessed for the incidence of non-fatal and fatal CVD. Participants were classified into the following groups: (a) HNBP (systolic BP [SBP], 120-139 mmHg and diastolic BP [DBP], 80-89 mmHg) and no prior history of high BP (b) Elevated BP (SBP, 120-129 mmHg and DBP, <80 mmHg) and (c) Stage 1 hypertension (SBP, 130-139 mmHg or DBP, 80-89 mm Hg). The analytic sample (n=1403) excluded patients with hypertension.

At baseline, the prevalence rate of HNBP, elevated BP and stage 1 hypertension was 44.6%, 29.0% and 15.5%, respectively. During the follow-up period, the 10-year combined (fatal or non-fatal) CVD incidence rates in patients with HNBP, elevated BP and stage 1 hypertension were 15.6%, 12.0% and 22.5%, respectively, vs 6.3% in normotensives (P<.0001 for all). After adjustment for confounders, patients with HNBP had a 1.5- fold (adjusted HR [aHR], 1.49; 95% CI, 1.00-2.20) increased risk for 10-year CVD events vs normotensive individuals. Similarly, patients with stage 1 hypertension were at 2-fold (aHR, 1.90; 95% CI, 1.16-3.08) increased risk for 10-year CVD, particularly in men (aHR, 2.03; 95% CI, 1.08-3.83). Elevated BP did not show a difference in the risk for 10-year CVD events (aHR, 1.28; 95% CI, 0.82-2.02).

Authors commented, “Considering the notable increased risk for 10-year fatal and non-fatal CVD with HNBP and stage 1 hypertension, targeted primary and secondary prevention interventions are required particularly among HNBP and stage 1 hypertension individuals to prevent CVD and related adverse health outcomes.”

Exercise helps cancer survivors

2019-02-26T10:34:00.002-05:00

Exercise helps cancer survivors

3 FEBRUARY 2019

Survival rates for a number of cancers continue to improve, in part because of more effective treatments. While cancer treatments can improve survival rates, they often come with side effects that can compromise quality of life and physical functioning. These can include loss of appetite, fatigue and reduced strength and physical function. Guidelines recommend that cancer survivors complete at least 150 minutes of moderate intensity exercise each week. This recommendation, however, doesn’t take into account the needs and challenges of cancer survivors and the potential requirement for different doses and types of exercise. Researchers looked at how the quantity of exercise undertaken by cancer survivors may affect their side effects including fatigue, inflammation and functional abilities.

A systematic review of existing studies was undertaken. The studies involved the effect of different types of exercise in adults with cancer. Primary outcomes analysed in the studies included fatigue and inflammation levels. The trials studies included a mixture of different exercise types including aerobic exercise, resistance exercise, and combinations of the two. Exercise was undertaken in a variety of settings like outpatient rehabilitation centres, fitness centres, in-hospital and at home.

The analysis showed that exercise had a positive effect on fatigue in cancer survivors when compared to usual care. There was also low-quality evidence that exercise improved walking endurance in this group.

Implications

These findings add to the growing body of evidence that suggests exercise is a safe and beneficial activity to help reduce treatment-related symptoms and improve physical function in people with cancer. The quantity and type of exercise may need to be adjusted according to the person’s capacity. If you have cancer, you can talk to members of your care team to put together a program that you’re going to be able to stick with on an ongoing basis.

Last Reviewed: 3 February 2019
© Norman Swan Medical Communications.

Prostate cancer treatment needs to be tailored

2019-02-26T10:33:00.002-05:00

Prostate cancer treatment needs to be tailored

6 FEBRUARY 2019

Prostate cancer is the most commonly diagnosed cancer in men in Australia. It’s estimated that more than 16,000 new cases of prostate cancer will be diagnosed in Australia this year. There are various approaches to treating prostate cancer that depend largely on the individual involved and how advanced the cancer is at the time of diagnosis. Options include surgery, radiation therapy, active surveillance and watchful waiting. There is some confusion as to whether watching and waiting is a viable approach and how it fares compared to surgery. The evidence reporting outcomes associated with each approach is mixed and varies depending on the individual’s circumstances.

A recently published study reported health outcomes and death in men with prostate cancer over close to two decades of follow up including treatments they received. Men with localised prostate cancer who received either radical prostatectomy or observation were analysed. At baseline, for inclusion in the study, they had to have a PSA value of less than 50 ng/mL, be younger than 75 years and have a life expectancy of at least 10 years. Data were collected on disease progression, treatment received and outcomes reported by the patient. All cause death rates and death due to prostate cancer was recorded.

During the 20 year follow up, in men with localised prostate cancer, radical prostatectomy was not associated with significantly lower all cause or prostate cancer caused death than observation. Death due to prostate cancer was uncommon among men with low-risk disease who undertook observation however surgery may have been associated with lower deaths in men with intermediate disease risk.

Implications

This research is not intended to advise people to take one course of action over another. It rather shows that there are various approaches to treatment that can be taken – some involving action and others involving watching, waiting and reassessing over time. There is no one size fits all solution so it’s important that you have all the information and make a decision that is going to best suit your circumstances. Have a conversation with your doctor about what your level of risk is, what all of your treatment options are, the potential outcomes of each option and the likelihood of each outcome occurring.

Last Reviewed: 6 February 2019
© Norman Swan Medical Communications.

Gut bacteria may influence your mental health

2019-02-26T10:33:00.000-05:00

Video: Gut bacteria may influence your mental health

11 FEBRUARY 2019

Video transcript

The gut microbiome, the diverse colony of bacteria that live in your gut could affect your mental health and well being.

How so you say?

It’s thought gut microbes ‘talk’ to our central nervous system and signal the production of neurotransmitters like dopamine and serotonin, the ‘happy’ chemicals.

A Belgian study of 1000 people found that people with depression had low levels of gut bacteria called Coprococcus and Dialister. People with good mental health had high levels of Coprococcus and Faecalibacterium.

But the question is - are the bugs affecting a person’s mental health? or is a person’s mental health affecting the bugs?

Regardless of what causes the low levels of these ‘good’ bacteria, could probiotics help? Probiotics (live bacteria) help restore the ‘normal’ gut microbial balance. So, in theory probiotics could help with the symptoms of depression. However, mental health treatment is often a combination of therapy and medication.

Probiotics may help in conjunction with these treatments, but at this stage probiotics are not a replacement.

Last Reviewed: 11 February 2019
myDr

How do baby flutters feel?

2019-02-21T18:55:00.002-05:00

One of the most exciting moments of pregnancy for many women is feeling the baby move for the first time. Often, it can be difficult for a woman to distinguish these first movements from other sensations, such as indigestion or gas.

However, when a woman is certain that she is feeling the fetus move, she may describe the feeling as baby flutters.

These soft initial movements are generally a sign that the pregnancy is going well. As the pregnancy progresses, a doctor may instruct a woman to be aware of the movements that the fetus is making. A sudden or gradual reduction in activity can indicate that the fetus is in distress.

Read on to learn more about baby flutters and what to expect from these movements as the pregnancy progresses.

What are baby flutters?

A woman may feel her fetus moving after 20 weeks.

Baby flutters occur when a pregnant woman feels the movement of the fetus.

For the first 18 to 20 weeks, a woman is not likely to feel any fetal movement. During the early stages of pregnancy, the fetus is not big or strong enough to make noticeable movements.

However, these timelines are relative. A woman who is pregnant for the first time may not feel anything until around 25 weeks, whereas a woman who has had previous pregnancies may recognize baby flutters as early as week 13.

Other factors, such as the position of the placenta, having twins or triplets, and the woman's body type, may affect when she feels the fetus move for the first time.

For example, a woman with an anterior placenta may notice movement later than a woman with a posterior placenta. A woman carrying more than one fetus may feel movement at an earlier stage of the pregnancy. Petite women may also notice movement sooner.

How do they feel?

The feeling of baby flutters can vary among women. Some common descriptions include:

feeling like gas pains but without passing any gas
feeling as though there are butterflies in the stomach
a tickling sensation on the inside
a popping or bubbling sensation
feeling pokes from the inside

The exact location of the flutters will depend on where the fetus is in the womb. They may be slightly higher or slightly lower in different women. Sometimes, a woman will feel flutters in the center or off to one side.

Flutters typically get stronger over time. Eventually, other people who touch the woman's stomach will be able to feel the movements.

Anti-cancer immunotherapy could be used to fight HIV

2019-02-20T10:14:00.002-05:00

Researchers at the University of Montreal Hospital Research Centre (CRCHUM) have shown that immunotherapy treatments against cancer could reduce the amount of virus that persists in people on triple therapy. In a study published in the journal Nature Communications, they show, in the cells of people living with HIV, how these therapies reveal the virus - until now hidden in the hollows of infected cells - to the immune system.

"We identified the mechanism by which anti-cancer immunotherapy 'awakens' the virus from its hiding places and reduces the size of HIV reservoirs in people on triple therapy. Although most of our experiments have been performed in vitro, our approach could lead to the development of new therapies," stated Nicolas Chomont, a CRCHUM researcher and Université de Montréal professor.

HIV reservoirs are cells and tissue in which the virus persists despite triple therapy. This treatment prevents the infection from developing into acquired immunodeficiency syndrome (AIDS). To survive and replicate, HIV needs to be hosted in a cell. As a rule, it infects CD4+ T lymphocytes, white blood cells responsible for activating the body's defenses against infections.

The virus remains dormant in these cells and builds a reservoir that is controlled, but not eliminated by antiretroviral drugs. The subject of intense study, these reservoir cells are the last hurdle in eradicating the virus and force people living with HIV to take antiretroviral drugs for the rest of their lives.

In 2016, Rémi Fromentin, a research associate in Nicolas Chomont's laboratory, showed that the cells housing the persistent viruses have specific immunological characteristics: three proteins called PD-1, LAG-3 and TIGIT, that are frequently expressed at their surface. Today these molecules are the target of immunotherapies used to treat cancer. The researchers decided to evaluate the effect of these therapies on HIV reservoirs.

A strategy evaluated in a small number of people with HIV and cancer

In this article, Rémi Fromentin and Nicolas Chomont also present data from a patient in Montreal infected with HIV and treated by immunotherapy for a melanoma."Our results prove that immunotherapies targeting molecules such as PD-1 could reduce the amount of virus persisting in people on triple therapy. One of the next steps would be to combine immunotherapy with molecules that, up to now, have been ineffective in eradicating HIV reservoirs. This combination of immunotherapy and chemical molecules could 'awaken' the virus and help remove the cells infected by HIV," added Chomont.

"The size of the patient's HIV reservoirs decreased significantly, which is encouraging. However, we must remain cautious, because this doesn't work with all patients. These treatments also cause considerable side effects," indicated Fromentin. The results of clinical trials currently underway in the United States on patients with cancer and HIV should help guide future research.

Nearly 37 million people around the world live with HIV. Every day, 5,000 cases are reported to global health authorities.

Source: https://www.chumontreal.qc.ca/

Testosterone is not the only hormone needed for penis development

2019-02-20T10:11:00.001-05:00

A new study has revealed that testosterone, which is produced and released by the testes, is not the only hormone involved in fetal development of the male penis. It is now thought that the masculinization process also involves a hormone called androsterone, which originates in other tissues, including the placenta.

Sebastian Kaulitzki | Shutterstock

The results not only shed light on a previously unknown “backdoor” pathway of masculinization, but could also explain the link between placental dysfunction and disorders of male genital development.

These insights have the potential to make a big difference to how we treat sexual disorders in male babies in future – and are also relevant to the whole debate about male and female identity.
Paul Fowler, Study Author.

During male fetal development, testosterone from the testes is converted into the male sex hormone 5α-dihydrotestosterone (DHT) by the genital tubercle – the primordial structure that either develops into a penis or clitoris.

In one in a few thousand cases, babies are born with “ambiguous” genitalia, where their gender is not quite clear. Previously, the understanding was that this is caused by problems associated with testosterone.

However, recent studies have shown that penis development also relies on a second, alternative or “backdoor” pathway, where DHT is produced independently of testosterone from the testicles. However, the details of this other pathway remained unclear, including the source DHT.

As reported in the journal PLOS Biology, Fowler and collaborators in Glasgow, France and Sweden have conducted a study that explains more about this second process.

Using mass spectrometry, the team measured levels of steroid hormones in fetal plasma and tissue during the second trimester - the most vital phase for penis development. The researchers also measured gene expression in tissues known to be involved in hormone synthesis.

The study revealed that the hormone androsterone, which can also be converted to DHT, was the main steroid hormone present in the blood of the male fetus and that both androsterone and testosterone were present at lower levels in the female circulation.

In addition, the enzymes required to convert androsterone to DHT were mainly present in non-gonadal tissues including the placenta and the liver.

Given that androsterone can be made from progesterone, Fowler and colleagues suggest that placental progesterone is the androsterone source in the alternative pathway.

Our results demonstrate that masculinization of the male fetus depends not only on the testes, but also on other tissues, especially the placenta. They also suggest an explanation for why disorders of placental insufficiency can lead to hypospadias and other abnormalities of growth of the male external genitalia.”

Source:

Fowler, P. Move over testosterone, another hormone is also vital for making boys – and it doesn’t come from the testes. The Conversation.

New protocol could help physicians to rule out bacterial infections in infants

2019-02-20T10:09:00.001-05:00

A new protocol could help emergency room physicians to rule out life-threatening bacterial infections among infants up to 2 months of age who have fevers, potentially eliminating the need for spinal taps, unnecessary antibiotic treatments or expensive hospital stays. Researchers from the Pediatric Emergency Care Applied Research Network (PECARN) developed the protocol from a study of more than 1,800 infants seen at 26 emergency departments around the country. Their study was funded by two agencies of the U.S. Department of Health and Human Services: the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health, and the Maternal and Child Health Bureau, part of the Health Resources & Services Administration. PECARN, a research network of 18 pediatric emergency departments and 9 emergency medical services agencies, is funded by the Maternal and Child Health Bureau. The findings appear in JAMA Pediatrics.

The new protocol measures the levels of bacteria in urine, of procalcitonin (a substance produced in response to bacterial infection) in serum, and of neutrophils (an infection-fighting white blood cell). The researchers ruled out an SBI if tests showed low levels of bacteria and procalcitonin and a normal neutrophil count. They were able to accurately rule out all but three of the 170 cases of SBI ultimately detected, including all cases of meningitis. The authors note that their findings need to be verified in a larger sample before they can be applied to medical practice.Previous studies suggest that 8 to 13 percent of infants up to 2 months of age who have a fever may have a serious bacterial infection (SBI). These include urinary tract infections, bacteremia (bacteria in the blood) and bacterial meningitis (bacterial infection of the membrane housing the brain and spinal cord). Often, a physician will need to confirm a diagnosis with a spinal tap (lumbar puncture), in which a small amount of fluid is extracted from the spinal canal. Although complications of the procedure are rare, they include inflammation of the spinal canal, bleeding and headache. In addition, an infant may be given antibiotics when a bacterial infection is suspected and may be admitted to a hospital for observation.

Source:

https://www.nichd.nih.gov/

New study reveals high success rate for hip and knee replacements

2019-02-20T10:08:00.001-05:00

After reviewing thousands of case studies going back 25 years across six countries, generalizable survival data is now available for the first time to estimate how long hip and knee replacements are likely to last.

The findings of researchers, funded by the National Joint Registry, from the Musculoskeletal Research Unit at the University of Bristol have been published in The Lancet. These findings show that eight out of ten total knee replacements and six out of ten total hip replacements will still be in place after 25 years.

"Over two million hip and knee replacements have been performed in the UK since 2003 and patients often ask clinicians how long their hip or knee replacement will last, but until now, we have not had a generalizable answer." said lead author Dr Jonathan Evans, National Joint Registry Research Fellow and Clinical Research Fellow at the Bristol Medical School; Translational Health Sciences (THS), based at Southmead Hospital.

"Previous studies have been based on much smaller samples. At best, the NHS has only been able to say how long replacements are designed to last, rather than referring to actual evidence from multiple patients' experiences of joint replacement surgery. Given the improvement in technology and techniques in the last 25 years, we expect that hip or knee replacements put in today may last even longer."

Hip and knee replacements are two of the most common and effective forms of surgery. Yet even in the best-case scenarios, they will ultimately fail due to processes such as infection, fracture, normal wear and tear or reaction to wear particles. In many of these cases, patients require revision surgery which is more prone to failure, associated with poorer function and more expensive than primary surgery.

Knowing how long a hip or knee replacement is likely to last is therefore key for patients, orthopedic surgeons and commissioners when deciding whether surgery should be done and when. This will become increasingly relevant to more people given the longer life expectancy of a growing population.

A hip replacement principally consists of two components, one that replaces the ball and another that replaces the socket. There is variation in how these parts are fixed to the bone, as well as in the materials used to create the bearing (contact) surface. There are two main types of knee replacement used in the UK. A total knee (TKR) replaces all the patient's own joint surface whereas a unicondylar knee replacement (UKR) only replaces the damaged part of the knee. There is considerable variation in how long different designs of hip and knee replacements last and these factors were accounted for in Bristol's study.

This involved the reports of 215,676 people whose cases were followed up for 15 years after undergoing total hip replacements; 74,052 who were followed up for 20 years; and 51,359 who were followed up for 25 years.A total of 150 case series (a type of research study) were reviewed relating to hip replacements and 33 relating to knee replacements, as well as six national joint replacement registries (large databases of all patients who have had a joint replacement) from Australia, Denmark, Finland, New Zealand, Norway and Sweden - countries which hold more than 15 years' worth of data.

Of the total hip replacements, 89 per cent were found to last 15 years, 70 per cent lasted 20 years, and 58 per cent lasted 25 years.

With total knee replacements, the 15-year results related to 299,221 people who had total knee replacements (TKRs) and 7,714 who had unicondylar, or partial, knee replacements (UKRs); the 20-year results related to 88,532 TKRs and 3,935 UKRs; whilst the 25-year data related to 76,651 TKRs and 3,935 UKRs.

Ninety-three per cent of total knee replacements (TKRs) and 77 per cent of unicondylar knee replacements (UKRs) were found to last 15 years. Ninety per cent of total knee replacements and 72 per cent of unicondylar knee replacements were found to last 20 years. Eighty-two per cent of TKRs and 70 per cent of UKRs were seen to last 25 years.

Mr Michael Whitehouse, Reader in Trauma and Orthopaedics at the Bristol Medical School: THS and joint senior author on the studies feels this information is critical to understanding the long-term outcomes of joint replacement: he said "This information is incredibly useful to me as a researcher to understand the life course of people undergoing joint replacement. Additionally, as a clinician, it gives me the information that I need, to give my patients a reliable and evidence-based answer to one of the questions they consider most important when deciding whether it is the right time for them to have a joint replacement."

Dr Evans hopes that further studies will help advance understanding and improve outcomes for patients and medical practitioners internationally: "We would like to work together with all the other countries who hold long term data on hip or knee replacement survival to expand our understanding of the long-term outcomes of joint replacement."

Source:

http://www.bristol.ac.uk/

MDMA users have higher levels of empathy than other drug users

2019-02-20T10:06:00.000-05:00

Long-term MDMA users have higher levels of empathy than cannabis and other drugs users, new research suggests.
MDMA users have higher levels of empathy than other drug users University of Exeter scientists compared the empathy levels of 25 people who used multiple drugs including MDMA, 19 people who used multiple drugs not including MDMA and 23 people who used alcohol only. Users of MDMA reported feeling much more empathy - and were better at identifying the emotions of others on a computer task - than people who took multiple drugs not including MDMA.The other drugs were cannabis, cocaine and ketamine. MDMA (3,4-Methylenedioxymethamphetamine, also known as ecstasy) is known to increase empathy for a short period, and these findings about longer-term effects could have implications for possible medical uses. MDMA is a Class A banned drug in the UK and is not currently licensed for any medical use. Lead author Molly Carlyle, of the University of Exeter, said: "We recruited long-term but mild users (a minimum of ten times), in order to reflect doses that may be used for medical purposes, "It has been suggested that MDMA, combined with therapy, might be an effective treatment for psychological trauma and alcoholism, but it has previously been suggested that MDMA may cause heightened social distress. Our findings indicate that isn't the casein our study, MDMA users were better able to understand the emotions of others and had better emotional empathy than people using other drugs, and on a similar level to those who only drink alcohol." The study's 67 participants completed a questionnaire about their own empathy, and took computerised tasks in which they had to identify emotions on the faces of others. They also reported how strongly they felt emotions based on seeing others in emotional states. The researchers wanted to measure both cognitive empathy (the ability to understand the emotions of others) and emotional empathy (experiencing emotions due to the emotions of others). MDMA users reported feeling significantly greater emotional empathy, and computer tasks revealed greater cognitive empathy, compared to people who used multiple drugs not including MDMA (there was little difference between the MDMA group and the alcohol-only group)The study says: All participants showed declines in mood and self-esteem in response to social exclusion, but there were no differences between the three groups. The levels of empathy and social pain in MDMA users were consistent with "normal psychosocial functioning". The findings contradict previous suggestions that long-term MDMA use may cause heightened social distress. Professor Celia Morgan, senior author of the research, said: "Our study suggests that mild MDMA use is not associated with any problems in how we function socially. Instead, it seems to make people better at empathy when compared to drug users who don't use MDMA, with a suggestion of better empathy compared to alcohol users. "We cant say whether differences in empathy are due to taking MDMA, or whether there were already differences in the people who use MDMA and those who don't before they started taking the drug. But importantly this study suggests that MDMA may be used safely as a treatment without side effects on these crucial social processes." Source: http://www.exeter.ac.uk/news/featurednews/title_704161_en.html

Unraveling the Relationship Between COPD and Stroke

2019-02-20T10:03:00.002-05:00

Emerging evidence suggests that chronic obstructive pulmonary disease (COPD) could be a risk factor for stroke.1,2 COPD is the fourth leading cause of death worldwide, and up to 80% of patients with the disease have at least one comorbidity.2 Many of the commonalities between COPD and stroke portend poor outcomes for patients with both diseases: age, indoor and outdoor pollution exposure, tobacco smoke, asthma and airway hyper-reactivity, and lower socioeconomic status.

Pulmonologists and neurologists should work together to improve care for patients with stroke.2 Pulmonologists and neurologists should work together to improve care for patients with stroke.Pulmonologists and neurologists should work together to improve care for patients with stroke. One of the preventable confounders for COPD and stroke risk is smoking, which contributes to fatal events and stroke.2 Indeed, in a systematic review of 30 studies, Ann D. Morgan, MSc, of the National Heart and Lung Institute at the Imperial College London, and colleagues, found that COPD increased the prevalence and incidence of stroke. Even when the researchers adjusted for smoking, COPD was still a risk factor for stroke.1 In a recent interview with Pulmonology Advisor, coauthor Jennifer Quint, MD, clinical senior lecturer in respiratory epidemiology at the National Heart and Lung Institute in London, United Kingdom, explained, “Independently of COPD, smoking increases the risk of having a stroke. There is something about having COPD, too, though, that also increases the risk. This may be linked to inflammation that occurs as a result of having COPD.” CONTINUE READING BELOW “Tobacco smoking is a risk factor both for ischemic stroke and COPD. Patients who are hospitalized for either condition should receive intensive tobacco cessation education and support both during the hospital and as they make the transition to their postdischarge residence,” neurologist Dawn M. Bravata, MD, of Indiana University School of Medicine and the Richard L. Roudebush VA Medical Center in Indianapolis, told Pulmonology Advisor. Exacerbations and Comorbidities That Increase Stroke Risk Current and former smokers with a 10-pack-year history were included in a cohort study of 16,485 patients with COPD (age range, 40-80 years) with cardiovascular disease (CVD) or multiple CVD risk factors to determine whether acute exacerbations of COPD (AECOPD) increased the risk for CV events.3 Kunisaki and colleagues found that when people with COPD needed additional antibiotics or corticosteroids, they were at higher risk of having a CV event, including CV death, myocardial infarction (MI), unstable angina, transient ischemic attack, or stroke 30 days after the exacerbation (hazard ratio, 3.8; 95% CI, 2.7-5.5). For those who required hospitalization, the risk more than doubled 30 days after AECOPD (hazard ratio, 9.9; 95% CI, 6.6-14.9).3 “We still do not know how to prevent these strokes, so we need more studies to determine what specific medications or changes in lifestyle/environment we should be recommending. For now, it makes sense to pursue a healthy lifestyle (exercise, smoking cessation, and a healthy diet) and management of general medical issues like blood pressure and cholesterol in patients with COPD,” advised lead author and pulmonologist Ken M. Kunisaki, MD, MS, associate professor of medicine at the University of Minnesota and medical director of the COPD case management program at the Minneapolis VA Health Care System. To determine which patients with COPD have even an higher risk than the general population of those with COPD, Rothnie and colleagues categorized AECOPD by severity in a self-controlled case series study.4 The participants included 5860 adults with COPD who had a first MI (n=2850) or ischemic stroke (n=3010) and at least one AECOPD.4 As they theorized, the researchers found a dose-response relationship between the severity of the AECOPD and the risk for MI or stroke 91 days after the acute exacerbation.4 For patients who had a severe AECOPD, the incidence rate ratio (IRR) was 2.58 (95% CI, 2.26-2.95) for MI and 1.97 (95% CI, 1.66-2.33) for ischemic stroke.4 Patients with a moderate AECOPD had slightly lower risk for MI (IRR 1.58; 95% CI, 1.46-1.71) and ischemic stroke (IRR 1.45; 95% CI, 1.33-1.57).4 Which Stroke Subtypes Are More Prevalent With COPD? Orea-Tejeda and colleagues conducted a case-control study of 162 patients with COPD and determined that right ventricular heart failure increased the risk for ischemic stroke (odds ratio, 3.03; 95% CI, 1.13-10.12; P =.044).5 While the researchers included only ischemic stroke in the study, coauthor Dulce González-Islas, PhD, from the Heart Failure and Respiratory Distress Clinic at the Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” in Mexico City, confirmed what she had observed in the COPD literature: “The information from several trials on stroke in patients with COPD are usually the ischemic (thrombotic) type.” However, pulmonologist Dr Kunisaki offered another perspective: “A few studies looked at stroke subtypes in COPD and found that, compared [with] people without COPD, those with COPD had a higher risk for both ischemic strokes and hemorrhagic strokes. However, we cannot be very confident about stroke subtypes in COPD because there are not a lot of data about this.” Oxygen Therapy for Comorbid Stroke and COPD Clinicians and researchers are still attempting to demystify the associations between COPD and stroke, including hypoxia, systemic inflammation, hypercapnia, and oxidative stress.2 Whereas some studies extoll the benefits of oxygen therapy for COPD, others have suggested that hypoxia and hypercapnia or hypercapnia alone may offer neuroprotection to patients with stroke.2 Pulmonologist Dr Quint cautioned, “Some people with COPD are at risk of having increased carbon dioxide levels if they receive high doses of oxygen, so sometimes oxygen therapy has to be closely monitored in people with COPD. This is not the case in all people with COPD, though, and some patients can tolerate high doses of oxygen therapy.” Interdisciplinary Collaboration Is Essential A Veterans Health Administration study highlighted the critical need for interdisciplinary health teams to better manage patients after an ischemic stroke and after an MI (N=40,230).6 Bravata and colleagues found that more patients who had an MI (n=4169) received successful hypertension treatment compared with 2127 patients after stroke (77%; 95% CI, 0.75-0.78 vs 64%; 95% CI, 0.62-0.67; P <.0001, respectively). Although hypertension control should be the foundation of secondary stroke prevention, the researchers theorized that cardiologists may be more comfortable titrating hypertension medications compared with neurologists.6 Lead author Dr Bravata explained how pulmonologists and neurologists might improve care for patients with stroke: “The 2 specialties have a shared interest in the diagnosis and management of sleep apnea. The American Heart Association/American Stroke Association 2014 Stroke Prevention Guidelines7 recommend the diagnosis and treatment of sleep apnea among patients with cerebrovascular disease. Creating systems of care to provide for the rapid assessment and management of stroke and transient ischemic attack [in] patients with sleep apnea should be a focus of collaboration for pulmonologists and neurologists.”