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A China-U.S. joint research team reported the generation of germline-transmittable cynomolgus macaques with Shank3 mutations, known to cause a form of autism.

The study, published in Nature, was conducted by scientists from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences (CAS), Massachusetts Institute of Technology, Sun Yat-Sen University and South China Agricultural University.

Through the genome-editing system CRISPR, they engineered macaque monkeys to express a gene mutation linked to autism and other neurodevelopmental disorders in humans. These monkeys showed some behavioral traits and brain connectivity patterns similar to those in humans with these conditions.

Autism Spectrum Disorders (ASD) is complex developmental disorders with a strong genetic basis. Scientists have identified hundreds of genetic variants associated with ASD, many of which individually confer only a small degree of risk. In this study, the researchers focused on one gene with a strong association, known as Shank3.

"The new type of model, however, could help scientists to develop better treatment options for some neurodevelopmental disorders," said FENG Guoping, who is the James W. and Patricia Poitras Professor of Neuroscience, a member of MIT's McGovern Institute for Brain Research, and one of the senior authors of the study.

Mouse models of ASD, due to their neural and behavioral differences from primates, haven't worked out very well. The reported behavioral and neural traits of Shank3 mutant primates provide new insights into the circuit-based pathophysiological model of ASD.

The primate model is close to humans in evolution and has many similarities to humans in brain structure. For example, the prefrontal cortex in nonhuman primates is well developed, which plays important roles in decision-making, attention and social interactions. Deficits in these cognitive functions have been associated with brain disorders including autism. Therefore, "nonhuman primates are hopeful to become an ideal animal model for simulating some human brain diseases," said Prof. ZHOU Huihui from SIAT.

The Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) is a private, nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment programs. SIAT received AAALAC accreditation in 2018 for its primate experiment platform, which laid a foundation for collaboration with international pharmaceutical companies to pursue new treatments of brain disorders in the future.

"We urgently need new treatment options for autism spectrum disorder, and treatments developed in mice have so far been disappointing. While the mouse research remains very important, we believe that primate genetic models will help us to develop better medicines and possibly even gene therapies for some severe forms of autism," says Robert Desimone, the director of MIT's McGovern Institute for Brain Research, the Doris and Don Berkey Professor of Neuroscience, and an author of the paper.

CAMBRIDGE, MA -- Using the genome-editing system CRISPR, researchers at MIT and in China have engineered macaque monkeys to express a gene mutation linked to autism and other neurodevelopmental disorders in humans. These monkeys show some behavioral traits and brain connectivity patterns similar to those seen in humans with these conditions.

Mouse studies of autism and other neurodevelopmental disorders have yielded drug candidates that have been tested in clinical trials, but none of them have succeeded. Many pharmaceutical companies have given up on testing such drugs because of the poor track record so far.

The new type of model, however, could help scientists to develop better treatment options for some neurodevelopmental disorders, says Guoping Feng, who is the James W. and Patricia Poitras Professor of Neuroscience, a member of MIT's McGovern Institute for Brain Research, and one of the senior authors of the study.

"Our goal is to generate a model to help us better understand the neural biological mechanism of autism, and ultimately to discover treatment options that will be much more translatable to humans," says Feng, who is also an institute member of the Broad Institute of MIT and Harvard and a senior scientist in the Broad's Stanley Center for Psychiatric Research.

"We urgently need new treatment options for autism spectrum disorder, and treatments developed in mice have so far been disappointing. While the mouse research remains very important, we believe that primate genetic models will help us to develop better medicines and possibly even gene therapies for some severe forms of autism," says Robert Desimone, the director of MIT's McGovern Institute for Brain Research, the Doris and Don Berkey Professor of Neuroscience, and an author of the paper.

Huihui Zhou of the Shenzhen Institutes of Advanced Technology, Andy Peng Xiang of Sun Yat-Sen University, and Shihua Yang of South China Agricultural University are also senior authors of the study, which appears in the June 12 online edition of Nature. The paper's lead authors are former MIT postdoc Yang Zhou, MIT research scientist Jitendra Sharma, Broad Institute group leader Rogier Landman, and Qiong Ke of Sun Yat-Sen University. The research team also includes Mriganka Sur, the Paul and Lilah E. Newton Professor in the Department of Brain and Cognitive Sciences and a member of MIT's Picower Institute for Learning and Memory.

Gene variants

Scientists have identified hundreds of genetic variants associated with autism spectrum disorder, many of which individually confer only a small degree of risk. In this study, the researchers focused on one gene with a strong association, known as Shank3. In addition to its link with autism, mutations or deletions of Shank3 can also cause a related rare disorder called Phelan-McDermid Syndrome, whose most common characteristics include intellectual disability, impaired speech and sleep, and repetitive behaviors. The majority of these individuals are also diagnosed with autism spectrum disorder, as many of the symptoms overlap.

The protein encoded by Shank3 is found in synapses -- the junctions between brain cells that allow them to communicate with each other. It is particularly active in a part of the brain called the striatum, which is involved in motor planning, motivation, and habitual behavior. Feng and his colleagues have previously studied mice with Shank3 mutations and found that they show some of the traits associated with autism, including avoidance of social interaction and obsessive, repetitive behavior.

Although mouse studies can provide a great deal of information on the molecular underpinnings of disease, there are drawbacks to using them to study neurodevelopmental disorders, Feng says. In particular, mice lack the highly developed prefrontal cortex that is the seat of many uniquely primate traits, such as making decisions, sustaining focused attention, and interpreting social cues, which are often affected by brain disorders.

The recent development of the CRISPR genome-editing technique offered a way to engineer gene variants into macaque monkeys, which has previously been very difficult to do. CRISPR consists of a DNA-cutting enzyme called Cas9 and a short RNA sequence that guides the enzyme to a specific area of the genome. It can be used to disrupt genes or to introduce new genetic sequences at a particular location.

Members of the research team based in China, where primate reproductive technology is much more advanced than in the United States, injected the CRISPR components into fertilized macaque eggs, producing embryos that carried the Shank3 mutation.

Researchers at MIT, where much of the data was analyzed, found that the macaques with Shank3 mutations showed behavioral patterns similar to those seen in humans with the mutated gene. They tended to wake up frequently during the night, and they showed repetitive behaviors. They also engaged in fewer social interactions than other macaques.

Magnetic resonance imaging (MRI) scans also revealed similar patterns to humans with autism spectrum disorder. Neurons showed reduced functional connectivity in the striatum as well as the thalamus, which relays sensory and motor signals and is also involved in sleep regulation. Meanwhile, connectivity was strengthened in other regions, including the sensory cortex.

Drug development

Within the next year, the researchers hope to begin testing treatments that may affect autism-related symptoms. They also hope to identify biomarkers, such as the distinctive functional brain connectivity patterns seen in MRI scans, that would help them to evaluate whether drug treatments are having an effect.

A similar approach could also be useful for studying other types of neurological disorders caused by well-characterized genetic mutations, such as Rett Syndrome and Fragile X Syndrome. Fragile X is the most common inherited form of intellectual disability in the world, affecting about 1 in 4,000 males and 1 in 8,000 females. Rett Syndrome, which is more rare and almost exclusively affects girls, produces severe impairments in language and motor skills and can also cause seizures and breathing problems.

"Given the limitations of mouse models, patients really need this kind of advance to bring them hope," Feng says. "We don't know whether this will succeed in developing treatments, but we will see in the next few years how this can help us to translate some of the findings from the lab to the clinic."

Osaka, Japan - The gut has a population of organisms that live within in it, called the gut microbiome, which are linked to human health and disease. Recent studies have shown that assessing the genetic changes in fecal samples can accurately reflect the status of the gut microbiome, and may be useful for the early diagnosis of diseases.

A group of researchers from Osaka University have recently reported increases in specific microbiome organisms that are linked to the malignancies associated with colorectal cancer, such as intramucosal carcinomas and polypoid adenomas. Their results, recently published in Nature Medicine Letters, reveal that these specific markers could help distinguish cases of colorectal cancer from healthy samples.

"We believe that colorectal cancer is fundamentally not only a genetic but also a microbial disease," says one of the study's corresponding authors, Shinichi Yachida. "Our results show that changes in the gut microbiome are present at the very early stages of colorectal cancer development, which could potentially provide vital diagnostic and causative clues for this disease."

Colorectal cancer, the third most prevalent cancer globally, is a relatively slow-moving disease--meaning it takes a long period of time before reaching its final, fatal stages. Therefore, early detection is crucial to ensuring effective treatment. The researchers used fecal samples from a little over 600 patients who underwent colonoscopy to assess the characteristics of their gut microbiota and how they relate to colorectal cancer.

"Our results revealed that colorectal cancer was linked to an increase in certain factors in the gut microbiome, as well as the presence of cancer-associated organisms," says the second corresponding author, Takuji Yamada. "Future studies will focus on the relationship between the gut microbiome and tumor characteristics in individual patients with colorectal cancer. This will help us understand the roles of the microbiome in the development of colorectal cancer."

Each year, 1 million men in the U.S. undergo biopsies to determine whether they have prostate cancer. The biopsy procedure traditionally has been guided by ultrasound imaging, but this method cannot clearly display the location of tumors in the prostate gland.

A multidisciplinary team of UCLA physicians has found that a new method, which includes biopsy guided by magnetic resonance imaging, or MRI, can be used together with the traditional method to increase the rate of prostate cancer detection.

Ultrasound has been used to visualize the prostate in order to take a representative sampling of tissue to biopsy. The introduction of MRI has allowed doctors to see specific lesions in the prostate and only take tissue samples from those spots. But the two sampling methods often aren't used in combination.

In the three-year study, published in JAMA Surgery, a strategy combining both sampling methods led to the detection of up to 33 percent more cancers than standard methods. According to senior author Dr. Leonard Marks, the findings could help lead to an important change in how prostate biopsies are performed.

"Our research suggests that the different biopsy methods identify different tumors," said Marks, who holds the Jean B. deKernion Chair in the department of urology at the David Geffen School of Medicine at UCLA. "To maximize our ability to identify prostate cancer, we need to take advantage of all the information we can. Our cancer detection rate, while using different methods in tandem, surpasses that from using either method alone. In this case, one plus one equals three."

The study is the first to directly compare the different biopsy sampling methods in the same group of men. Previous research demonstrated the advantages of MRI-guided biopsy, but exactly how to employ the new technology has not been clear. This trial establishes that lesion-targeted and systematic sampling are both required to maximize the accuracy of prostate biopsy.

In the past decade, MRI-guided biopsy methods, which are more targeted because they can precisely show the locations of lesions in the prostate, have been used more commonly. However, some tumors are not visible as lesions on MRIs, so such cancers may not be detected.

In the 300-person study, 248 men had a prostate lesion visible on MRI. By using all available biopsy information and methods together, the researchers detected cancer in 70 percent of those men. An additional 52 men in the trial had no lesion visible on MRI, yet 15 percent of those men were found to have cancer via the traditional ultrasound method, confirming that MRI does not identify all tumors.

"Men being assessed for prostate cancer should first receive an MRI before biopsy," said Marks, who is a member of the UCLA Jonsson Comprehensive Cancer Center. "When there's a lesion on MRI, physicians should take systematic and targeted biopsies together for the best chance at finding cancer. Even if the MRI is negative for lesions, men at risk -- including those with elevated levels of prostate-specific antigen, a prostate nodule, or family history -- should still receive a traditional, systematic biopsy."

Identifying the precise location of cancerous tissue in the prostate is especially important as treatments become increasingly targeted. While the surgical removal of the entire gland, known as prostatectomy, is a common method of treatment, emerging treatments like focal therapy aim to eliminate only cancerous tissue in the gland while sparing healthy tissue.

"Improving our ability to see the location of cancer in the prostate in real time opens up the door for treatment innovations," Marks said. "If we can identify the location of tumors and put biopsy needles directly into them, why not find a way to destroy the tumor on the spot?"

CLEVELAND, Ohio (June 12, 2019)--If you're wondering why you entered menopause earlier or later than other women, blame your mother. That's because numerous studies have confirmed the role of genetics in determining a woman's age at menopause. A new study not only reconfirms this association but additionally suggests a link to familial longevity. Results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

The age of menopause is clinically defined as one year after the final menstrual period and is, on average, about 52 years. However, every year thousands of women outperform this statistic by entering menopause later in life, whereas many others naturally enter menopause much earlier in life.

Although menopause can occur earlier as the result of various conditions such as smoking, chemotherapy, and an elevated body mass index, the age of menopause is generally accepted to be most influenced by family history. So, if your mother experienced her menopause early, chances are you will also begin the transition earlier in life.

The goal of this latest study focused on reproductive life was to identify genetic variants associated with the delayed age of menopause based on familial longevity. Results were based on a meta-analysis of several larger studies, including the Long Life Family Study, the Health and Retirement Study, and the Framingham Heart Study. These studies found that women who were able to have children beyond the age of 40 years were four times more likely than average women of living to 100 years or older and that women who had children at age 35 years or older were 1.5 times more likely to live past 100 years.

In this study, researchers performed a meta-analysis for genetic variants associated with age of menopause in women who ultimately lived to a very old age. The findings provided further evidence for genetic basis of age of menopause. In addition, the discovery of new variants suggests that there may be genetic mechanisms of age of menopause that are linked to human longevity.

Findings were published in the article "Genetic associations with age of menopause in familial longevity."

"Genetic variants associated with later menopause have been found to be associated with longer life. Although early menarche and total number of reproductive years have not been associated with slower aging, later menopause (longer reproductive potential) appears to be associated with slower aging." says Dr. JoAnn Pinkerton, NAMS executive director.

Your blood pressure does not drop during a sauna visit - it rises, as well as your heart rate. This increase is even comparable to the effect of a short, moderate workout. This is the result of a new study conducted by researchers at Martin Luther University Halle-Wittenberg (MLU) and the Medical Center Berlin (MCB). For their study, the researchers placed their participants both in a sauna and on a bicycle ergometer.

Contrary to the previous assumption, blood pressure does not drop during a sauna session - it rises. And this increase is even comparable to the increase caused by a short, moderate workout. This is one of the conclusions of a recent study carried out by sports scientists at the Martin Luther University Halle-Wittenberg (MLU) in collaboration with the Medical Center Berlin (MCB). On separate days, the participants were sent to a sauna and placed on a bicycle ergometer. In addition to higher blood pressure levels, an increase in heart rate was measured both during the sauna visit and during exercise. The study was recently published in the international journal Complementary Therapies in Medicine.

It is generally assumed that a sauna visit leads to a continuous fall in blood pressure. "It was thought that the heat dilates the blood vessels and that this lowers the blood pressure", says Dr Sascha Ketelhut, lead author of the new study and a sports scientist at MLU. People with low blood pressure or cardiovascular disorders have traditionally been advised not to use saunas, as a further fall in blood pressure can lead to fainting. "However, it is important to distinguish between the acute effects of a sauna session and the effects that were noted during the rest period after the sauna session. Many previous assumptions have been made about the acute effects of sauna use, but so far little research has been done", continues Ketelhut.

The scientists conducted their study by recruiting 19 volunteers to measure the immediate effects of sauna use on the cardiovascular system: The participants were exposed to a 25-minute sauna session, while having their blood pressure and heart rate measured. Both rose immediately during the sauna visit. After the sauna session, both blood pressure and heart rate began to drop below participant's baseline levels that were measured before the sauna session.

In the second part of the study the participants completed a short exercise program on an exercise bike while also having their blood pressure and heart rate assessed. "Comparing the two conditions, the participants' blood pressure and heart rate reached the same levels during the sauna session as they did with a load of about 100 watts during the exercise test", says Ketelhut. This shows that a sauna session is kind of a burden on the body. Still, even people with low blood pressure may occasionally have a shvitz, as Ketelhut says: "Saunas can actually be used by anyone who can tolerate moderate physical stress without discomfort. However, people with low blood pressure should be cautious afterwards, as their blood pressure may then fall below the levels registered before the sauna visit".

The observations made by the researchers are supported by previous studies that focused primarily on the long-term effects of sauna use, demonstrating positive effects on the cardiovascular system, for example. "A sauna session is a physical strain. Its long-term positive effects are similar to sports activities", explains Ketelhut. Nevertheless, the healthy sweating does not contribute to weight loss: "The effect is too low as there is no muscle activity. Although we lose weight in the sauna, but these are just the fluids that we sweat out. One should rehydrate after a sauna session, though", concludes Ketelhut.

Madrid, Spain, 12 June 2019: The results of a study presented today at the Annual European Congress of Rheumatology (EULAR 2019) suggest maintenance therapy with cyclosporine (CYA) results in more rapid remission of proteinuria compared to mycophenolate mofetil (MMF) or azathioprine (AZA) in patients with lupus nephritis. The efficacy of CYA, MMF and AZA in obtaining and maintaining remission of lupus nephritis (LN) is comparable over the long term.

"Our study is the first to compare these three drugs as maintenance therapy in the long term," said Lorenza Maria Argolini, Rheumatology Consultant of the Lupus Clinic, ASST Pini CTO, Milan, Italy. "Of interest are the results achieved in the CYA group where, despite worse clinical conditions at the beginning of maintenance therapy, we observed a rapid achievement of remission in the great majority of patients."

The study followed 104 patients with lupus nephritis over 10 years who, after six months of induction therapy, received maintenance therapy of either CYA, MMF or AZA (32, 36, and 36 patients respectively). At the beginning of maintenance therapy complete, partial and no response rates were 28.2%, 59.3%, and 12.5% in CYA, 50%, 44.5% and 5.5% in MMF and 38.8%, 55.2% and 6% in AZA group. At one year, after six months of maintenance therapy, in CYA the percentage of patients in complete remission increased to 72% (vs. 64% in MMF and 44.2% in AZA), at five years it was 81.5% (vs. 86% in AZA and 81% in MMF) and 84.5% at 10 years vs. 72% in MMF and 70% in AZA.

"Lupus nephritis is a serious condition requiring early aggressive therapy to achieve remission, however, the type and duration of immunosuppression after achieving response remain a matter of controversy," said Professor John D. Isaacs, Chairperson of the Abstract Selection Committee, EULAR. "It is great to see these long-term data which will help further our understanding in this complex area."

Lupus nephritis is inflammation or swelling in the kidneys that stops them working properly. It is a serious complication of systemic lupus erythematosus (SLE), an autoimmune disease that can affect different organs and parts of the body. Treatment often consists of a period of intensive immunosuppressive therapy (induction therapy) followed by a longer period of less intensive maintenance therapy.

This multi-centre retrospective observational study included patients with SLE and biopsy proven lupus nephritis who entered the study either at diagnosis or during a flare. At induction there were no significant differences between the three groups in histological classes at renal biopsy, mean serum creatinine, eGFR and proteinuria, and type of induction therapy. Renal response was measured at one, five, and 10 years and recorded as total response (eGFR>60ml/min and proteinuria 60ml/min and proteinuria >0.5g/die), or no response (eGFR

Annual European Congress of Rheumatology
(EULAR 2019)
Madrid, Spain, 12-15 June 2019

Madrid, Spain, 12 June 2019: The results of a randomised controlled trial presented today at the Annual European Congress of Rheumatology (EULAR 2019) demonstrate high levels of treatment success in approximately two thirds of patients despite tapered glucocorticoid (GC) discontinuation, while a small loss of disease control was observed at the total study population level.1

"On the basis of our results, we believe that all patients achieving low disease activity or remission with tocilizumab should be offered glucocorticoid tapering," said Professor Gerd R. Burmester, Department of Rheumatology and Clinical Immunology, Charité - University Medicine Berlin, Germany.

Results demonstrate, after 24 weeks, a small but significant difference in disease activity following GC tapering with a between arm difference of 0.6 DAS28-ESR units (95% confidence interval (CI):0.3-0.9; p

"The risk to benefit profile of glucocorticoid therapy in rheumatoid arthritis is very controversial," said Professor John D. Isaacs, Chairperson of the Abstract Selection Committee, EULAR. "We welcome these data to inform our understanding in this area and ultimately the better management of patients suffering with this disease."

Rheumatoid arthritis is a chronic inflammatory disease that affects the joints, causing pain and disability. It can also affect internal organs. The efficacy of GC therapy in these patients is well established. However, it is recommended that it should be gradually reduced and ultimately stopped, ideally within three to six months. This is due to many potential risks including osteoporosis, infections, diabetes, and cardiovascular disease.

CLEVELAND, Ohio (June 12, 2019)--Vitamin D and estrogen have already shown well-documented results in improving bone health in women. A new study from China suggests that this same combination could help prevent metabolic syndrome, a constellation of conditions that increases the risk of heart disease, stroke, and diabetes in postmenopausal women. Results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Metabolic syndrome has emerged as a major public health concern, affecting 30% to 60% of postmenopausal women worldwide. The progression of abdominal obesity and heart disease that lead to metabolic syndrome increases significantly as women age and appears to be directly associated with estrogen loss in postmenopausal women. This has led some researchers to recommend estradiol treatment for women who are fewer than 6 years postmenopausal as a means of preventing heart disease.

Similarly, vitamin D has been associated with several markers of metabolic syndrome, including obesity, hyperglycemia, insulin resistance, and type 2 diabetes mellitus. Supplementation with vitamin D has been shown to reduce the risk of metabolic syndrome over a 20-year follow-up.

Because the synergistic benefits of vitamin D and estrogen are already documented to improve bone health in women, researchers in this newest study from China hypothesized that the same interaction might affect metabolic syndrome. The cross-sectional study included 616 postmenopausal women aged 49 to 86 years who were not taking estrogen and vitamin D/calcium supplements at the beginning of the trial. It concluded there was a positive correlation between vitamin D and estradiol.

Specifically, higher vitamin D was associated with a favorable lipid profile, blood pressure, and glucose level. Estradiol was negatively associated with cholesterol, triglycerides, and blood pressure. These results suggest a synergistic role of vitamin D and estradiol deficiency in developing metabolic syndrome in postmenopausal women.

Findings are published in the article "The synergistic effects of vitamin D and estradiol deficiency on metabolic syndrome in Chinese postmenopausal women."

"In this cross-sectional study, low estradiol increased the risk of metabolic syndrome in postmenopausal women who had vitamin D deficiency," says Dr. JoAnn Pinkerton, NAMS executive director. "The Endocrine Society recommends vitamin D levels of 30 ng/mL for postmenopausal women. Whether adequate levels of vitamin D improve nonskeletal cardiovascular or cognitive benefits remains the subject of debate, and answers await randomized clinical trial data."

Annual European Congress of Rheumatology
(EULAR 2019)
Madrid, Spain, 12-15 June 2019

Madrid, Spain, 12 June 2019: The results of a study presented today at the Annual European Congress of Rheumatology (EULAR 2019) demonstrate that remission in patients with rheumatoid arthritis is associated with an 80% reduction in risk of cardiovascular outcomes.1

Rheumatoid arthritis is a chronic inflammatory disease that affects the joints, causing pain and disability. Patients with rheumatoid arthritis have an increased risk of premature death compared with the general population, mainly due to cardiovascular disease.

"The heightened risk of cardiovascular disease in patients with rheumatoid arthritis is in large part a consequence of uncontrolled inflammation. By demonstrating that remission of rheumatoid arthritis is associated with a reduction in cardiovascular complications, these results really emphasise the importance of more effective control of disease, beyond symptom management alone," said Professor John D. Isaacs, Chairperson of the Abstract Selection Committee, EULAR.

The study analysed data from 797 patients with rheumatoid arthritis over three years and found that patients in remission had an 80% reduced risk of clinical cardiovascular disease, defined as heart attack, congestive heart failure, or stroke (Odds Ratio (OR):0.20, 95% Confidence Interval (CI): 0.09-0.95, p=0.041). The authors also demonstrated a 75% reduced risk of pre-clinical cardiovascular disease in patients in remission, defined as lesions on arteries detected by ultrasound (OR:0.25, 95% CI: 0.11-0.56, p=0.001).1

The study also looked at traditional cardiovascular risk factors and the analysis identified type II diabetes as being significantly associated with both cardiovascular outcomes, clinical (OR:6.21, 95% CI:2.19-17.71, p=0.001) and pre-clinical cardiovascular disease (OR:4.50, 95% CI:1.74-11.62, p=0.002). In addition, pre-clinical cardiovascular disease was significantly associated with high blood pressure (OR:2.03, 95% CI:1.04-4.14, p=0.042), ACPA (OR:2.36, 95% CI:1.19-4.69, p=0.002) and mean values of CRP during follow-up (OR:1.07, 95%CI:1.03-1.14, p=0.040).1

"Our study supports the idea that systemic inflammatory processes and more traditional cardiovascular risk factors work together to increase the cardiovascular risk in patients with rheumatoid arthritis," said Dr. Piero Ruscitti, University of L'Aquila, L'Aquila, Italy. "This is important because it highlights the need for the effective coordination of care between rheumatologists, internists, cardiologists and primary-care physicians to optimise management of cardiovascular risk in patients with rheumatoid arthritis."

This three-year, prospective, observational study included patients who were initially part of the GIRRCS cohort study which assessed the cardiovascular risk profile of consecutive patients with rheumatoid arthritis admitted to Italian Rheumatology units during 2015. The median age was 60 and 82.7% were female. The median rheumatoid arthritis disease duration was 8.35 years, 70.9% showed rheumatoid factor and 55.7% ACPA in their blood. The BMI was 27.21+4.05, 33% were smokers, 49.3% had high blood pressure and 12.3% had type II diabetes. Remission was reached and maintained in 42.6% of patients. 1

Abstract number: OP0090

Annual European Congress of Rheumatology
(EULAR 2019)
Madrid, Spain, 12-15 June 2019

Madrid, Spain, 12 June 2019: The results of a study presented today at the Annual European Congress of Rheumatology (EULAR 2019) demonstrate significant correlation between body mass index (BMI) and disease severity in psoriatic arthritis.1

Psoriatic arthritis is a chronic inflammatory disease that affects the skin and joints, causing pain and disability. The disease often causes swelling of the fingers and toes, mainly because of joint inflammation. Although psoriatic arthritis has been associated with an enhanced prevalence of obesity and being overweight, few studies have assessed the relationship between weight and the severity of disease in these patients.

Results of this study demonstrate BMI is independently correlated to disease activity (p=0.026), patient-perceived disease impact (p1

"Our results highlight the impact of obesity and need for lifestyle-directed approaches to manage weight in psoriatic arthritis in parallel to joint and skin focused treatments," said Dr Stefan Siebert, Clinical Senior Lecturer in Inflammation and Rheumatology, University of Glasgow, United Kingdom.

The study included 917 patients across eight European countries as part of the PsABio study, an ongoing prospective observational study evaluating patients with PsA receiving ustekinumab or tumour necrosis factor inhibitors. Data were collected on disease severity and impact, and analysed using multiple regression models adjusted for age, sex, smoking, body surface area, c-reactive protein, disease duration and biologic treatment.1

"There is growing evidence describing how fat tissue acts as an active organ involved in metabolic and inflammatory disorders," said Professor John D. Isaacs, Chairperson of the Abstract Selection Committee, EULAR. "Furthermore, with fixed-dose drug regimens, as with self-injected biologics, obesity can reduce efficacy for pharmacokinetic reasons." These factors, alongside the global epidemic of overweight and obesity, makes research in this area of great relevance and interest."

Another study presented today at EULAR 2019 provides evidence for the adipokine, adiponectin, in predicting the development of rheumatoid arthritis in overweight subjects.

Adipokines are signalling molecules that are secreted by fat tissue and act in a similar way to hormones. Raised levels of adiponectin, a type of adipokine, have been shown in subjects with rheumatoid arthritis, however, results of this study suggest it could have a role in predicting the onset of disease.4

"Early detection and management of rheumatoid arthritis is very important to improve disease outcomes in patients," said Cristina Maglio, MD, PhD, University of Gothenburg, Gothenburg, Sweden. "Our analysis suggests that serum adiponectin in overweight patients might have a role as a biomarker for early rheumatoid arthritis."

The analysis included two studies, the first included 82 subjects with obesity and available measurements of adiponectin before the development of rheumatoid arthritis and 410 matched controls and demonstrated a 10% increased risk of developing rheumatoid arthritis in those with raised serum adiponectin at baseline. The second study included 88 sex- and age-matched pairs and demonstrated a 20% increased risk, but only in those with a BMI greater than 25.4

Finally, another interesting study presented today at EULAR 2019, looked at overweight and obesity in young patients with juvenile idiopathic arthritis (JIA).

Results found the rate of being overweight, and obesity in children and adolescents with JIA is comparative to the general population. However, further analysis revealed a number of factors are significantly associated with being overweight in the JIA group including increasing age (OR:1.06, 95% CI:1.04-1.09), male gender (OR:1.21, 95% CI:1.04-1.44), functional limitations (OR:1.29, 95% CI:1.04-1.59), therapy with biological DMARDs (OR:1.48, 95% CI:1.22-1.80), and systemic glucocorticoids (OR:1.40, 95% CI:1.14-1.71). The implications of these findings on the long-term outcome of JIA requires further study.

Abstract numbers: OP0007, THU0061, OP0259

Cardiovascular health and physical activity levels of prostate cancer patients improve following successful interventions by community pharmacies, new research in the British Medical Journal reports.

In the first study of its kind, researchers from the University of Surrey, funded by the Movember Foundation in partnership with Prostate Cancer UK, developed and tested the feasibility of community pharmacies delivering programmes to improve levels of physical activity and diet of men with prostate cancer and those who have successfully completed treatment for the disease. NICE recommends that men with prostate cancer follow a 12-week exercise programme to reduce symptoms after treatment and improve overall wellbeing, but this is hard to support in a hospital setting.

Nine community pharmacy teams in the south of England were trained to deliver health assessments and lifestyle prescriptions to men with prostate cancer or those who had undergone treatment. Pharmacy teams checked the weight, BMI, blood cholesterol and blood pressure of 116 men and assessed their upper-limb strength (grip strength), lower-limb strength (chair sit to stand) and overall fitness. To help improve strength and fitness levels, a computer algorithm developed by the research team used this assessment data to generate a personalised lifestyle prescription, including exercise and dietary advice, for the participants. In support of the lifestyle changes, pharmacy teams made regular phone calls to assist participants and offer guidance.

After a three-month period, participants were invited back to the pharmacy to assess progress. Moderate and vigorous physical activity levels amongst the group were found to have increased significantly by 34 minutes over three months. A reduction in weight by 1kg on average was observed amongst participants, with BMI down by 0.3kg/m2 and cholesterol decreasing by 0.4mmol/l. Grip strength increased on average by 0.2kg (meaning that men were stronger in their arms) and more chair sit to stands reflected better leg strength. These results indicate that support offered by community pharmacies can make a real difference in improving the physical fitness and wellbeing of men.

Sara Faithfull, Professor of Cancer Nursing Practice at the University of Surrey, said: "Exercise and diet have been shown to reduce symptoms of prostate cancer treatment and lessen chances of cardiovascular disease. It is understandable that men who have successfully beaten cancer are reluctant to embark on an exercise regime by themselves, so they need help to know what to do and how much is required to make a difference."

"Community pharmacies can make a really positive impact to this issue by providing valuable guidance and support for increasing activity levels and ensuring more informed dietary decisions are made. It is encouraging to see a measurable improvement over only three months, but we need to examine further how this could be effective in the longer term."

Heather Blake, Director of Support and Influencing from Prostate Cancer UK said: "We know that regular exercise and a healthy diet can help some men manage many of the side effects of prostate cancer treatments, as well as improving their mental health and wellbeing.

"We are therefore pleased that this study shows that community pharmacies can support men with prostate cancer to improve their physical activity and cardiovascular health. We now need to determine how this improvement can be sustained over longer periods of time."

Most studies into the impact of technology use on psychological wellbeing rely on flawed measures say researchers.

Surveys are often used to understand how people use their smartphone, but these are poorly related to actual smartphone use when measured with an app.

This means that existing evidence suggesting that screen time is "addictive" cannot be used to justify any change of policy.

The UK Parliament's Science and Technology Committee recently held an inquiry into social media use including the effects of screen time on the health of young people.

But Dr David Ellis of Lancaster University and Brittany Davidson from The University of Bath say official policy should not solely rely on existing studies using self reports.

Dr Ellis said "Knowing how much someone thinks or worries about their smartphone use leaves many questions unanswered"

The team examined 10 "addiction" surveys for measuring people's technology use such as the Smartphone Addiction Scale and the Mobile Phone Problem Use Scale, which generate scores that determine use.

They then compared these self-reports with data from Apple Screen Time which provides an objective measurement of:

How many minutes people used their phones

How often they picked it up

How many notifications they received

The researchers discovered weak relationships between how much people think they use their smartphones and how much they actually do.

Miss Davidson added "Our results suggest that the majority of these self-report smartphone assessments perform poorly when attempting to predict real-world behaviour. We need to revisit and improve these measurements moving forward."

High smartphone usage has been previously linked to anxiety and depression but Dr Ellis said there is insufficient evidence to support these conclusions.

"Scales that focus on the notion of technology 'addiction' performed very poorly and were unable to classify people into different groups (e.g, high vs low use) based on their behaviour."

Just as women can turn to a suite of procedures, known as the "Mommy Makeover," more men are embracing their own set of treatments, the "Daddy-Do-Over," to boost their confidence and improve their physical appearance. A new report from the American Society of Plastic Surgeons reveals that more than 1.3 million cosmetic procedures were performed on men last year alone, representing a 29 percent increase since 2000.

Similar to a Mommy Makeover, the "Daddy-Do-Over" consists of surgical and non-surgical body contouring and facial procedures that are typically performed in a single surgery. Due to this rising trend, plastic surgery is becoming a common Father's Day request as more men consider a surgical assist to enhance their physique and fend off the "dad bod" for a while longer.

"Obviously, men don't go through the same physical changes that women experience during pregnancy and post-pregnancy, but their lifestyle does change, which can impact their appearance," said Alan Matarasso, MD, president of the American Society of Plastic Surgeons. "Diet and exercise patterns fluctuate, and they don't sleep as much. Men notice their body changes due to aging and parenting, and it starts to look completely different in their 30s and 40s. That is the point of a Daddy-Do-Over."

After struggling to lose stubborn fat around his mid-section through dieting, 57-year-old Scott, a restaurateur in New York City, pursued plastic surgery when diet and exercise couldn't help him reach his goals.

"I realized I was never going to lose the weight on my own," he said. "Plastic surgery is a personal decision, but I know guys my age who have done different cosmetic procedures. I think an open dialogue about plastic surgery is becoming more acceptable, especially for men."

With more than 200,000 surgical procedures performed on men in 2018, rhinoplasty was the most popular with more than 52,000 procedures. Eyelid surgery ranked second, followed by liposuction (up 5 percent). Breast reduction (gynecomastia) ranked number four with more than 24,000 procedures, up 22 percent since 2000, and hair transplantation ranked fifth, up 17 percent since 2017.

Dr. Matarasso says he finds more men are seeking plastic surgery to help them professionally as well as they feel more confident about advancing in their careers and competing in the workplace after surgery.

Despite his lean physique, Dennis, 59, a creative director in New York City, also found it challenging to lose weight in specific areas. With a desire for a natural outcome, he underwent chin surgery and buccal fat removal surgery, as well as an eye lift to achieve a more youthful, toned appearance.

"I've been in fashion my entire career, and it makes me feel good when I walk in the room and I don't feel as if I look 60 in a room of 25- to-30-year-olds," said Dennis. "I always carried weight in my neck and chin, and my droopy eyelids made me look more tired than I actually was. I've gained unexpected confidence from the small changes I took."

Nearly half a million Botox procedures were performed on men last year, and more than 100,000 men had filler injections to reduce the signs of aging. Dr. Matarasso says male patients today embrace nonsurgical and minimally-invasive procedures to the same degree as female patients.

"Men are embracing the idea of surgery more than before," he added. "Regardless of the reason though, I always stress the importance of consulting with a member of the American Society of Plastic Surgeons. Our unique training and qualifications allow us to perform cosmetic procedures of all types. We are committed to providing plastic surgery patients with the safest outcomes, and we want them to have peace of mind as we help them achieve their aesthetic goals."

ATLANTA--A unique adjuvant, a substance that enhances the body's immune response to toxins and foreign matter, can prevent vaccine-enhanced respiratory disease, a sickness that has posed a major hurdle in vaccine development for respiratory syncytial virus (RSV), according to a study led by the Institute for Biomedical Sciences at Georgia State University.

The study suggests that combining this adjuvant, which was created by the research team, with RSV vaccination might prime the body for protective immune responses and prevent inflammatory RSV disease after infection. The findings, published in the journal Virology, could lead to advances in RSV vaccine development.

RSV, a common respiratory virus that causes cold-like symptoms, is the leading cause of serious respiratory diseases such as bronchiolitis and pneumonia in children younger than 1 year of age in the United States. Each year in the U.S., an estimated 57,000 children younger than 5 years old are hospitalized with an RSV infection. RSV is also a significant cause of respiratory illness in older adults, resulting in 177,000 hospitalizations and 14,000 deaths each year, according to the Centers for Disease Control and Prevention (CDC). There is no vaccine to prevent RSV.

Progress on a vaccine for RSV almost ceased in the 1960s after a formalin-inactivated RSV vaccine being tested in the U.S. not only failed to protect children, but resulted in many infants experiencing worse symptoms than usual, requiring hospitalization after natural infection with the virus. Two toddlers died from enhanced disease symptoms. Other RSV vaccines have been known to cause enhanced disease after RSV infection.

This study investigated the effects of a unique adjuvant on vaccine-enhanced respiratory disease after infant and adult mice were vaccinated against RSV and exposed to the virus. The adjuvant was created by combining pathogen-recognizing receptor agonist adjuvants monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG (CpG), which are known to activate innate immune responses.

Infant and adult mice were injected with either RSV fusion proteins only, RSV fusion proteins plus adjuvant or a control phosphate buffered saline solution. Blood samples were taken after three weeks. Four weeks after vaccination, mice were intranasally infected with RSV and samples were taken to determine the efficacy of protection.

The adjuvant was found to be effective in promoting the induction of protective antibodies, clearing the lungs of the virus after exposure to RSV and avoiding disease in lung tissue.

"RSV subunit vaccination adjuvanted with a unique combination pathogen-recognizing receptor agonist might provide protection against RSV, preventing inflammatory RSV disease after infection. However, its efficacy in larger animal models and in humans remains unknown," said Dr. Sang-Moo Kang, lead author and a professor in the Institute for Biomedical Sciences at Georgia State.