Culture

Getting covered by health insurance may have a major impact on a low-income person's ability to get a job or enroll in school, according to a new study that gives the first direct look at the relationship between the two.

The percentage of low-income people enrolled in Michigan's Medicaid expansion program who had jobs or were enrolled in school jumped six points in one year, the study shows. That outpaced employment gains among the state's general population during that same time.

Even larger increases in employment and school enrollment happened among African-Americans, men, people in their late 30s and 40s, and those with the lowest incomes.

The study of low-income people enrolled in what the state calls the Healthy Michigan Plan was performed by a team at the University of Michigan Institute for Healthcare Policy and Innovation, and published in a new paper in JAMA Network Open.

Year-over-year gains

For the study, the researchers surveyed more than 3,000 people with Healthy Michigan Plan coverage from across the state, first in 2016 and again in 2017 or the first month of 2018. The program is open to all people over age 18 in Michigan who have incomes up to 133% of the poverty level, or about $15,800 for an individual and $32,000 for a family of four in 2017. About 670,000 Michiganders currently have the coverage.

The six-point jump in those who said they had a job or were in school was seen both in those who stayed in the program for the entire period studied, and among the 23% who had left the program by the time the researchers contacted them.

The findings have implications for states that have not expanded Medicaid under the Affordable Care Act, and for those that have applied for or received permission from the federal government to require enrollees to report whether they are working, or doing other qualifying activities, in order to keep Medicaid coverage.

"While on a statewide level, both in the general population and the low-income population, employment levels didn't change much between 2016 and 2017, we saw a clear increase in employment or student status among those in the Healthy Michigan Plan, even among those with health conditions who we might think would need more time to achieve this," says Renuka Tipirneni, M.D., M.Sc., the lead author of the new study and an assistant professor of internal medicine at U-M. "The ability to get access to care, attention for existing or new health issues, and to gain function, appears to have a clear impact on the chances of getting a job or studying or training to get a job later."

Tipirneni is a member of the IHPI team that is carrying out a full evaluation of the Healthy Michigan Plan's effects for the state government. She notes that the study is unique because it includes longitudinal data on the Medicaid expansion enrollee population, including those who have left the program. The team continues to gather data on the longer-term status of these enrollees and former enrollees.

Larger jumps in some groups

The team had previously published findings from their 2016 survey of Healthy Michigan Plan enrollees that showed that nearly 49% were working, 27% were out of work, 11% said they were unable to work and 5% were already enrolled as students. The rest were homemakers or retired.

The new study shows that the combined percentage of those who were employed or students in 2017 was 60%, which is an increase from the combined 54% who were employed or students in 2016.

When the researchers delved deeper into the survey results, they found that people aged 35 to 50 had an eight percentage point increase, people whose incomes were less than one-third of poverty level had a 9-point jump, and non-Hispanic black enrollees had nearly an 11-point jump. The increase among all men was 6.7 points, compared with 4.8 points for women.

The 6-point gain was an average for Medicaid expansion enrollees across the state. By comparison, the general Michigan population had a steady rate of employment from 2016 to 2017, with 75% of residents between the ages of 19 and 64 being employed or enrolled in school in 2017, according to data from the U.S. Census Bureau.

Among all Michiganders in this age range with incomes at or below a level that would be eligible for enrollment in Medicaid or the Healthy Michigan Plan, employment or student status didn't change from 2016 to 2017, when 43% of the entire group was employed or students.

"Our findings suggest states could achieve goals of fuller employment among low-income residents by expanding Medicaid coverage or maintaining an expansion program," says Susan Goold, M.D., MHSA, M.A., the senior author on the new paper and a professor of medicine, "Good health helps people gain employment or stay employed."

Goold and colleagues are looking at the patterns of coverage among those who enrolled in the Healthy Michigan Plan in its first five years, including how many left the plan because they obtained other coverage such as through an employer or for other reasons.

IHPI is conducting the evaluation required by the Centers for Medicare and Medicaid Services (CMS) of the Healthy Michigan Plan (HMP) under contract with the Michigan Department of Health and Human Services (MDHHS). Data collection for this paper was funded by MDHHS and CMS for the purposes of the evaluation, but the study findings do not represent the official views of either agency.

What The Study Did: Cancer registries representing about 28% of the U.S. population were used to examine how new cases of colorectal cancer increased from age 49 to 50, the age when many people of average risk for the disease historically began screening, although screening age recommendations vary.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Jordan J. Karlitz, M.D., of the Southeast Louisiana Veterans Health Care System and Tulane University School of Medicine in New Orleans, is the corresponding author.

(10.1001/jamanetworkopen.2019.20407)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

A year-by-year age analysis of colorectal cancer rates among U.S. adults finds a 46% increase in new diagnoses from ages 49 to 50, indicating that many latent cases of the disease are likely going undiagnosed until routine screenings begin at 50, according to a new study in JAMA Network Open.

Researchers found that almost 93% of the cases discovered at age 50 were invasive, meaning that most would require more aggressive treatment including surgery and were likely lingering for some time before diagnosis.

"Our findings suggest a high case burden of preclinical, undetected early onset colorectal cancers in patients younger than 50 that is not reflected in observed incidence rates," said lead study author Dr. Jordan Karlitz, associate clinical professor of Medicine at Tulane University School of Medicine and staff gastroenterologist at the Southeast Louisiana Veterans Health Care System.

Colorectal cancer is the second leading cause of cancer deaths in the United States. As rates for younger adults continue to rise, there is considerable debate about whether to lower the age for recommended screenings. In 2018, the American Cancer Society called for routine screenings to start at 45. However, the U.S. Preventive Services Task Force, which sets federal screenings standards, currently recommends average risk screening begin at age 50. The agency is studying the issue to determine whether changes will improve outcomes

Those against beginning screenings at age 45 have argued that incidence rates in those age 45 to 49 years have been considered relatively low compared to those aged 50 to 54 years. Study authors suspected the risks for those in their mid-to-late 40s are underestimated because incident data for those age ranges would likely only include cases caught because they presented symptoms and/or have a family history of cancer, in contrast to those 50 and older who have cancers also detected due to screening.

To assess this, they examined colorectal cancer incidence rates in one-year increments between the ages of 30 to 60 from the year 2000 to 2015. They suspected that if there were many asymptomatic cases of the disease undetected there would be a marked increase in cases between 49 and 50 when screenings begin.

Researchers found a steep increase from 34.9 diagnoses per 100,000 people at age 49 to 51 cases per 100,000 at age 50. Sharp increases were also seen in both men (52.9%) and women (39.1%), in white (46.2%) and black (47.3%) populations in colon (51.4%) and rectal (37.6%) cancers in this one-year age transition. These incidence increases from age 49 to 50 were not seen in prior studies because only age group ranges were analyzed.

Researchers also examined the stage at which the cancers were caught and found a spike in localized and regional cancers, which would require surgery and possibly chemotherapy and radiation treatment.

The study adds fuel to the debate about whether screenings should begin at age 45. Karlitz said the combined burden of undetected and detected early onset colorectal cancer cases for those 45-49 may actually approach that of individuals in their early 50s.

"Our data support that the incidence of colorectal cancer increases substantially among individuals in their early 50s compared with individuals in their late 40s, not because rates are truly lower among those aged 45 to 49 years, but because colorectal cancers are present but undetected until diagnosed when screening is ultimately initiated," he said.

A limitation of the study is its population-based design, which limited researchers' ability to determine exactly which patients had cancers detected at age 50 through screening versus diagnostic testing.

"Nevertheless, the significantly high rate of invasive cases supports that almost all cancers accounted for in the rate increase from age 49 to 50 required aggressive treatment, regardless of how they were detected," Karlitz said.

In the first comparative clinical trial of lung cancer screening decision aid versus standard educational information, researchers from The University of Texas MD Anderson Cancer Center have shown that a decision aid delivered through tobacco quitlines effectively reaches a screening-eligible population and results in informed decisions about lung cancer screening.

Lung cancer is the second most common cancer diagnosis among adults in the U.S. and is the most common cause of cancer-related deaths. Screening for lung cancer with low-dose CT scans is the only secondary preventive service shown to decrease mortality from lung cancer; the primary action to prevent lung cancer is to avoid, or quit using, tobacco products.

While lung cancer screening can save lives, it also carries potential harms. For this reason, the Centers for Medicare & Medicaid Services (CMS) covers lung cancer screening as a preventive service as long as certain requirements are met, including use of a decision aid during a shared decision-making visit between the patient and physician or qualified practitioner. The U.S. Preventive Services Task Force recommends the annual screening for adults aged 55 to 80 years who have a 30 pack-year smoking history, meaning the equivalent of smoking a pack of cigarettes a day for 30 years.

In the study published today in JAMA Network Open, the research team worked with 13 tobacco quitlines to identify callers eligible for screening. The 516 quitline clients who enrolled in the study were randomized to receive a decision aid video called "Lung Cancer Screening: Is It Right for Me?" or a standard lung cancer screening brochure for the control group.

Primary outcomes for the study were preparation for decision-making and decisional conflict. Secondary outcomes included knowledge of lung cancer screening, intentions to be screened and completion of screening within six months after receiving the decision aid or brochure.

At the one-week follow up, 67.4% of participants who received the decision aid reported they were well prepared to make a screening decision, compared to 48.2% of participants who received the standard educational material. Among those who received the decision aid, 50% felt informed about their decision choice and 68% reported being clear about their values related to the harms and benefits of screening, compared to 28.3% and 47.4%, respectively, among the control group.

"The quitline clients who received the decision aid were more assured about what was important to them in making the choice about screening and felt better informed," said Robert Volk, Ph.D., professor of Health Services Research and lead author of the study. "Their knowledge of the harms and benefits of screening was much greater than people who received standard educational information. The clients in the control group were making screening choices while being less prepared and aware of the trade-offs between benefit and harms. We want to head off the uninformed choice and help patients make good, informed decisions about screening."

The decision aid video explains eligibility for screening, lung cancer epidemiology and risk factors, and potential harms from screening, including false-positive results, radiation exposure and risks of invasive diagnostic procedures. The decision aid encourages patients to consider their values while weighing the benefits and harms of screening. The video also shows a patient receiving a CT scan.

By the six-month follow up, approximately 30% of participants in both groups had scheduled a lung cancer screening; the difference in screening rates between groups was not statistically significant. Nationally, about 6% of people at risk for lung cancer due to smoking undergo screening, according to the National Institutes of Health.

Based on the study results, funding was received to begin implementing the model nationally by training quitline staff to identify callers who are eligible for screening and provide them with the decision aid.

"We've demonstrated that this is a very effective way to identify people at risk for lung cancer," Volk said. "There's potential to reach thousands of people who are eligible for screening and already addressing their risk for lung cancer by seeking cessation services."

Limitations of the study included screening behaviors based on self-report. Quitline callers had to express interest in lung cancer screening when asked by quitline staff in order to participate in the study.

CHICAGO (January 31, 2020): Virtual antibody crossmatching is a safe and efficient way of selecting kidney transplant recipients. Two years after implementing the process, the Medical University of South Carolina (MUSC) division of transplant surgery, Charleston, concluded that the technique was just as accurate and sensitive as physical crossmatch, the current gold standard, and much quicker. Virtual crossmatching reduced the time kidneys were kept on ice while awaiting identification of a suitable recipient, improved scheduling for surgeons and operating room staff, and alleviated emotional and logistical stress on patients who were called to the hospital only to be sent home hours later after a more suitable recipient was identified. A study of the process and its effects on clinical and surgical practice outcomes appears in an "article in press" on the Journal of the American College of Surgeons website in advance of print publication.

Since 1969, physical crossmatching has been used to determine if the immune systems of an organ donor and an intended recipient were compatible. Blood from donor and recipient are mixed in a test tube. If a match is incompatible, recipient blood cells attack and destroy donor cells.1

However, virtual crossmatching applies the recipient's serum to microbeads that detect signals from the donor's antibodies using a specialized device to find antibodies that may react. The process does not reveal an actual reaction between donor and recipient cells. Rather, it forecasts whether such a reaction would occur.2

A physical crossmatch is highly sensitive, but it eats up valuable time. Donor lymph nodes are shipped to the transplant center, cells are mixed with serum from the potential recipient, and surgeons, recipient, and the transplant center then must wait six hours to learn whether there is an antibody reaction before scheduling the operation.

Because of the concern about potential immune system incompatibility, transplant centers typically call in three possible recipients for every donated organ. "We ask three patients who are next on the transplantation list to come into the hospital just in case there are problems with incompatibility. Think about the time, effort, and stress that puts on a patient. It's not uncommon for a patient to be called in two, three, or four times before they actually go forward with transplantation," said David J. Taber, PharmD, a study coauthor and an associate professor of surgery in the division of transplant surgery at MUSC.

The delay prolongs the time a donated organ is kept on ice, called cold ischemia time (CIT). "You want to minimize the amount of time an organ is on ice because the longer it is outside the body, the lower quality it becomes. After prolonged CIT, there is the chance the organ will not function right away, called delayed graft function (DGF), which leads to poor outcomes in the long run," said Vinayak S. Rohan, MD, FACS, lead author of the study and an assistant professor of surgery in the division of transplant surgery at MUSC.

Delays are particularly problematic since the Kidney Allocation System was revised in 2014 and now allows transplantations to patients who are highly sensitized.3 "Previously, donor organs were obtained locally, so transplant centers could afford to wait six hours for the physical crossmatch results. Now, in South Carolina, we are getting organs from California. Shipping them takes long enough. If you cannot predict what is going to happen for six more hours, you may not be able to give the organ to the intended recipient and do a disservice to the purpose of the allocation system," said Dr. Rohan.

The study is a before-and-after comparison of patient outcomes two years after the transplant surgery team implemented virtual crossmatching. Of 825 patients who received a kidney transplant between 2014 and 2018, 505 underwent surgery before-- and 227 after--virtual crossmatching was instituted.

Standard measures of clinical quality were the same in both groups. The incidence of delayed graft function was 19 percent before and 17 percent after implementation; graft failure within a year was 4 percent before and 3 percent after; mortality within a year was 2 percent before and 1 percent after.

CIT for long-distance donor organs decreased by 2.4 hours, and delayed graft function declined by 26 percent. Importantly, despite a highly sensitized population, there were no hyperacute rejections. "Hyperacute rejection is an extremely rare but catastrophic event when an organ rejects while the surgeon is operating. With sizable segments of patients who were already highly sensitized, there were similar rates of graft survival, patient survival, and kidney graft survival, confirming at a patient-outcomes level that we can employ virtual crossmatching without inducing any potential harm or risk to the patient," Dr. Taber said.

"Because we don't need to do physical crossmatching for the majority of patients, we also can improve surgeons' quality of life by being able to schedule the operation even before an organ arrives," Dr. Rohan said.

"This technique also reduces the time and money spent on having backup patients traveling to and waiting in the hospital. Emotionally, this approach helps patients a lot," Dr. Taber said.

Dr. Rohan's coauthors are Nicole Pilch; PharmD, Omar Moussa; PhD, Satish N. Nadig, MD, FACS; Derek Dubay, MD, FACS; and Prabhakar K. Baliga, MD, FACS.

The cover for issue 4 of Oncotarget features Figure 8, "Model for biological function categorization of PMEPA1 isoforms (c, d, and e) in the context of prostate cancer," by Sharad, et al.

In addition to 4 reported PMEPA1 isoforms, one novel isoform PMEPA1-e was identified with RNA Seq analysis of hormone-responsive VCa P, LNCa P cells and human prostate cancer samples from The Cancer Genome Atlas dataset.

The researchers analyzed the structures, expressions, biological functions and clinical relevance of PMEPA1-e isoform and less characterized isoforms c and d in the context of prostate cancer and AR/TGF- signaling.

The expression of PMEPA1-e was induced by androgen and AR.

Taken together, their findings first defined the prostate tumorigenesis mediated by PMEPA1-d and -e isoforms, providing novel insights into the new strategies for prognostic evaluation and therapeutics of prostate tumor.

Dr. Hua Li and Dr. Shashwat Sharad from the Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences as well as the Walter Reed National Military Medical Center, Bethesda, Maryland, USA said in their Oncotarget article, "Prostate cancer is the most commonly diagnosed male malignancy and second leading cause of cancer-related deaths in the USA."

It was shown that the methylation of PMEPA1 gene promoter accounted for the silencing of PMEPA1 in prostate cancer cells in vitro and in vivo.

PMEPA1 was also reported as a TGF- regulated gene in the context of both prostate cancer and non-prostate solid tumors including colon, lung and breast cancers.

Further, a recent study showed that the loss of membrane-anchored PMEPA1 protein facilitated metastasis of prostate cancer via activating TGF- signaling by sequestering SMAD2/3 in proteasome independent way.

Cumulatively, these findings underscored the multi-function features of the PMEPA1 gene and further suggested its expressions and biological functions were dependent on the cellular context centering androgen and TGF- signaling.

The alternative splicing variant mechanism had also been shown to be important for diversifying functions of tumor-associated genes.

Further, earlier studies from their and other groups explored PMEAP1 gene isoforms in the initiation and development of prostate tumors via interrupting AR and/or TGF- signaling.

Here, the Oncotarget authors focused on defining the expressions, regulations and biological behaviors/functions of understudied PMEPA1 isoforms in the context of both androgen and TGF- signaling, and further exploration of the clinical significances and relevance of these isoforms in prostate tumor.

The Li/Sharad Research Team concluded in their Oncotarget study that gene isoform ratio could potentially predict the gene functional consequences and disease progression.

Weightlifters could do less and get stronger by changing the amount they lift each session, according to new research.

Sports scientists from the University of Lincoln, UK, compared the average weights lifted by two groups over six weeks: one using a traditional training method of a "one rep max" - the maximum weight an athlete could lift - and one using a load velocity profile, where the weights were tailored so they lift either more or less at each session.

All who used the load velocity profile became stronger despite lifting less overall during the six week period.

Traditionally, the one rep max would be used to dictate the weight load for all sessions.

Researchers established the one rep max in the two groups. They then used a linear positional transducer - essentially a specialised stopwatch and tape measure - to record the length of time it took to lift the weight, and the distance the weight was moved to establish a "velocity measurement" in one of the groups. That coupled with the one rep max established the load velocity profile for the athlete.

At each session, the load velocity group completed a warm-up consisting of a series of repetitions where the weight load was gradually increased and their velocity measurement taken. Each rep was recorded and compared with their pre-established load-velocity profile.

This comparison enabled the participants' training load to be adjusted based on their performance that day: if the athlete was moving the same load at a faster velocity, the weight was increased, but if they were lifting slower, the weight load would be reduced.

The findings can be used to improve muscular strength and power, and have positive implications for the management of fatigue during resistance training.

Dr Harry Dorrell from the University of Lincoln's School of Sport and Exercise Science led the study. He said: "There are a lot of factors which can contribute to an athletes' performance on a particular day, such as how much sleep they have had, nutrition, or motivational factors, but with traditional percentage-based methods we would have no insight into how this effects their strength.

"The velocity-based training enabled us to see if they were up or down on their normal performance and thus adjust the load accordingly. It's about making sure the athlete is lifting the optimal load for them, on that particular day. If you lift too little then you won't stimulate the body as you intend to; but if you lift too much you'll be fatigued, which increases the risk of injury.

"This fatigue won't necessarily happen immediately, either. You could lift too much regularly, and three weeks down the line this will catch up with you and you'll find that the muscles are too fatigued to manage what you believe should be in your ability."

Sixteen men aged between 18 to 29 years, with body masses ranging from 70kg to 120kg with at least two years' weight training experience, took part in the trial which included two training sessions a week over a course of six weeks.

They performed a back squat, bench press, strict overhead press, and a conventional deadlift, and the results at the start and end of the six weeks training were recorded.

Researchers also recorded the athlete's countermovement jump, a term used to describe the explosive lower-body power, and found that only the velocity group's had improved.

Following the trial, those using the velocity based training method could lift an average of 15kg more on the back squat than when they started, rising from 147kg to 162kg, despite their training loads being an average of nine per cent less at each session; they lifted six per cent less on the bench press per session but could take on an extra 8kg by the final session; the overhead press saw a 4kg increase in the one rep max despite lifting six per cent less during training; and the deadlift rose from 176kg to 188kg even with an average decrease of two per cent on their training loads.

Dr Dorrell added: "While some of these changes could be considered as only "small improvements" and were similar to the group using the traditional training method, the velocity group lifted significantly less in order to see the gains they made. The idea of velocity based training has been around for a while, but until now there hasn't been any science to prove that it actually works; the science has finally caught up."

Commercially available kinetic measuring devices, including apps, now mean that anyone could easily carry out the same training method at home or in the gym.

31 January 2020, Cambridge - Researchers at EMBL's European Bioinformatics Institute (EMBL-EBI) and Queen Mary University of London have led a study to categorise which genes are essential for supporting life. The results from this study could be a useful new resource to help researchers identify mutations responsible for rare childhood diseases.

Identifying which genes are linked to a rare disease is one of the most difficult challenges geneticists face. The low prevalence of these diseases within the population makes it difficult to research and fully understand their causes. However, huge advances in the diagnosis of rare diseases are now being made thanks to innovations in sequencing technology.

This research, published in Nature Communications, compares knockout mice viability and phenotyping data from the International Mouse Phenotyping Consortium (IMPC) with human cell lines provided by the Broad Institute's Project Achilles to create categories indicating how crucial a gene is to producing viable life.

The researchers also identified new mutations likely responsible for rare childhood diseases by comparing their data with unsolved cases of genetic disorders identified in the 100,000 Genomes Project and the Deciphering Developmental Disorders (DDD) datasets.

Defining genes essential for life

"Loss of gene function is often referred to as a binary concept; lethal or viable," says Violeta Muñoz-Fuentes, Biologist, Mouse Informatics at EMBL-EBI. "In this study we show that gene essentiality is more of a spectrum ranging from cellular lethal, developmental lethal, subviable, viable with a visible phenotype, and viable without a visible phenotype."

The scientists define these categories for 3819 genes to create an open access database that can be used to benefit other researchers and provide insight for clinical applications.

"When you sequence a person's genome it's not always one mutation that stands out as altering a gene's function," says Terry Meehan, Coordinator of Mouse Informatics at EMBL-EBI. "We currently don't have a handle on which genes are important for development and which have a minor impact."

Loss of function gene categories

Cellular lethal: genes essential for cell viability

Developmental lethal: genes essential for organism development

Viable: organisms fully develop

Subviable: organism survival is less than expected

Diagnosing rare disorders

"This study combines multiple sources of data from large scale projects to identify new candidate genes that, when mutated, are likely to have a causal relationship with rare human disorders," says Pilar Cacheiro, Research Fellow at Queen Mary University of London. "Nearly 6% of the population are affected by these diseases during their lives."

Advances in whole genome sequencing (WGS) are changing the way we research and diagnose rare genetic diseases. However, the majority of rare disease patients remain undiagnosed due to a lack of detection or because a previously unknown gene is disrupted. This study furthers our understanding of rare disease genes by providing clinicians and researchers with an open access resource, which can be used to identify high-quality candidates for rare disease mutations.

"Of particular interest for application to healthcare, we demonstrate that the set of genes that are essential for organism development is particularly associated with known human developmental disorders," says Damian Smedley, Reader in Computational Genomics at Queen Mary University of London. "This provides candidates for undiscovered causative genes for these conditions."

Several high-scoring candidates from this study have been added to the open access resource GeneMatcher, used by researchers and clinicians all over the globe to share gene information. You can also freely access the study data in EMBL-EBI's Biostudies and at the International Mouse Phenotyping Consortium.

CHAMPAIGN, Ill. -- Artificial sweeteners such as sucralose provide the seductive taste of sweetness without the calories contained in sugar - a seeming win-win for people who need to control their blood sugar and insulin levels or weight.

However, simply tasting or consuming sucralose may affect blood glucose and insulin levels on glucose tolerance tests, scientists at the University of Illinois found in a new study.

The findings suggest that despite having no calories, sucralose may have metabolic effects in some users, said M. Yanina Pepino, a professor of food science and human nutrition at the U. of I., who led the research.

"The most important take-home message is that sweet taste in itself may have an impact on carbohydrate metabolism and glucose control," Pepino said. "Even though the sample population in our study was small, the findings add to a body of evidence that suggests sweetness should be consumed in moderation, regardless of the calories."

The study included 10 people of healthy weight and 11 people with obesity; none of the participants had diabetes or were regular users of artificial sweeteners.

The participants underwent three oral glucose tolerance tests on separate days spaced about a week apart. Prior to one test they consumed distilled water; prior to another, sucralose; and prior to a third test they tasted but did not swallow sucralose.

They performed one of these actions 10 minutes before drinking a solution containing 75 grams of glucose.

The amount of sucralose - 48 milligrams - that the study participants ingested provides a level of sweetness equivalent to that in a typical diet soda, Pepino said.

At each visit, a catheter was inserted into a radial artery to obtain blood samples at regular intervals during the hour before and five hours after the participants drank the glucose. The scientists measured participants' blood concentrations of sucralose, insulin, glucose and other hormones.

Sucralose had differing effects depending on whether participants ingested it or only tasted it and whether they had obesity, the researchers found.

When people of healthy weight swallowed the sucralose, their blood insulin levels decreased modestly during the first hour, and their insulin sensitivity increased by about 50%, said graduate student Clara Salame, who co-wrote the study.

However, when people with obesity swallowed the sucralose, their insulin levels increased significantly more than when they drank water or when they tasted the sucralose but spit it out.

"While insulin responses to either tasting or swallowing the sucralose were similar in those of normal weight, those responses were very different in people with obesity," Pepino said. "Therefore, we hypothesize that some post-ingestive effects of sucralose may occur only in people with obesity.

"However, our study included people who were not habitual consumers of artificial sweeteners, and further studies are needed to explore what happens with this acute effect of sucralose after long-term use."

Pepino cautioned that since the various artificial sweeteners have very different chemical structures and the body may handle them differently - some are broken down in the stomach while others remain unabsorbed in the intestine - the findings on post-ingestive effects may be unique to sucralose.

However, since all artificial sweeteners activate the sweet taste receptors in the mouth, the metabolic effects associated with sweetness may be more generalizable, she said.

Pepino said she had expected that tasting sucralose and spitting it out would have similar effects to consuming water; thus, she was surprised to discover that participants' insulin levels were affected by taste alone.

"Interestingly, we found that in both groups of people - those with obesity and those of normal weight - there was a reduction in insulin response to the glucose tolerance test when they just tasted sweetness before drinking the glucose solution. It was the most surprising finding, and we are following up on that in a new study," Pepino said.

"What our data suggest is that there are mechanisms that we don't understand clearly about how the human body regulates glucose and the potential metabolic effects of tasting something sweet beyond providing a sense of pleasure," Pepino said.

On January 24, 2020, the French Ministry of Health confirmed the first three cases of patients affected by the Wuhan coronavirus. On January 29, 2020, the Institut Pasteur, which is responsible for monitoring respiratory viruses in France, sequenced the whole genome of the coronavirus known as "2019-nCoV", becoming the first institution in Europe to sequence the virus since the start of the outbreak. The virus was sequenced at the Institut Pasteur's Mutualized Platform for Microbiology (P2M), which performs genome sequencing on bacterial, viral, fungal and parasite strains received by National Reference Centers and World Health Organization Collaborating Centers for the purpose of infectious disease surveillance.

In December 2019, an outbreak of apparently viral pneumonia of unknown etiology emerged in the city of Wuhan, in the Chinese province of Hubei.

On January 9, 2020, the Chinese health authorities and the World Health Organization (WHO) announced the discovery of a novel coronavirus, known as 2019-nCoV, which was confirmed as the agent responsible for the pneumonia cases (see the Institut Pasteur's fact sheet on the "Wuhan coronavirus" - page in French).

Over the weekend of January 11-12, the Chinese authorities shared the full sequence of the coronavirus genome, as detected in samples taken from the first patients. "Sequencing the genome of pathogens is crucial for the development of specific diagnostic tests and the identification of potential treatment options," explains Sylvie van der Werf, Director of the National Reference Center (CNR) for Respiratory Viruses at the Institut Pasteur.

Friday January 24, 2020. Detection of the virus confirmed in France

On Friday January 24, late in the morning, the Institut Pasteur received samples of three suspected cases (two patients in Paris and one in Bordeaux). "Using the samples taken from these patients, we detected the novel coronavirus," says Sylvie Behillil, Deputy Director of the CNR at the Institut Pasteur.

From Friday January 24, 2020. Viral genome sequenced at the Institut Pasteur

That same Friday evening, scientists launched the process of sequencing the viral genome based on the samples. The CNR prepared the material for sequencing, ready for P2M to begin work immediately the following Monday. The sequencing run was completed by early evening on the Tuesday, and the scientists used data analysis to obtain the sequence of the whole genome in two of the first three confirmed cases in France. "This proves the efficacy of the CNR's process of analysis based on viral sequencing," continues Vincent Enouf.

Thursday January 30, 2020. The Institut Pasteur obtains and shares the whole sequence of the virus

The P2M platform (see inset below) currently performs at an extremely high level; the average time taken to produce sequences ranges from three days (for emergencies) to a maximum of ten days. In this case, it took just three days for the whole sequence to be determined: "We performed data analysis during the night from Tuesday to Wednesday, then corroborated the results on Wednesday with counter analysis," explains Vincent Enouf. "The whole sequence was confirmed in just three days."

What can we learn from it? "The sequences were identical in all our samples. One member of the couple must have contaminated the other, as the virus is the same." The two full sequences of the virus isolated in two of the first French cases were submitted to the Global Initiative on Sharing All Influenza Data (GISAID) platform,1 which was initially developed to share sequences and monitor the genetic evolution of influenza viruses, a process that is vital to determine the composition of the influenza vaccine. A special "coronavirus" tab has been created so that the scientific community can work together and advance at a quicker pace.

"Around twenty other sequences of the novel coronavirus genome have been obtained worldwide, and if we compare them with ours, we can see that they are all very close; there is not much diversity in the viruses analyzed, which suggests that coronavirus 2019-nCoV did not need to mutate in order to adapt and spread," continues Vincent Enouf.

The National Reference Center (CNR) for Respiratory Viruses at the Institut Pasteur in Paris is one of WHO's reference laboratories for coronavirus 2019-nCoV.

A total of eight people from the CNR and two from the P2M sequencing platform have been working on the virus this week and will continue to monitor the outbreak in France.

P2M, a state-of-the-art mutualized platform for microbiology also open to external CNRs

P2M is also available to external CNRs for sequencing. In 2019 it worked with four CNRs based outside the Institut Pasteur. The platform sequences bacteria, viruses, parasites and fungi. Thanks to experience gained over the past five years (since 2015), P2M today offers a highly efficient service, as shown by a first-pass success rate (i.e. a high-quality sequence providing comprehensive information on the entire genome) of more than 95% in 2019. Sequence production takes between three days (for emergencies) and ten days at most.

In 2019, P2M sequenced around 25,000 pathogens. Genome sequencing increases the sensitivity threshold for outbreak detection. Early identification of outbreaks by the Institut Pasteur's scientists (clustered cases in a short space of time caused by the same pathogen) enables epidemiologists to get to work immediately to determine the origins of the outbreak, and the authorities to coordinate the public health response.

Simple sequence repeats (SSRs) are regions of DNA with high diversity, and they have long been a mainstay for botanists examining the genetic structure of plant populations. However, as the cost of sequencing DNA continues to plummet and genetic technologies advance, newer techniques for mapping genetic diversity such as genotyping-by-sequencing (GBS) or RAD-seq have begun to rival the traditional use of SSRs. In research presented in a recent issue of Applications in Plant Sciences, Dr. Mark Chapman optimized the process of identifying SSRs from genomic and transcriptomic data, helping to assure the continued use and relevance of SSRs in the age of high-throughput sequencing (HTS).

Sequence data generated using HTS can be used to identify candidate SSRs, for which researchers can design primers to examine genetic structure in a species. However, little work has been done to calibrate or optimize this process, both in terms of guidelines for reasonable parameters to specify, or what kind or depth of sequencing may be sufficient and appropriate to identify a workable set of SSRs.

"I've used transcriptome data for over a decade to generate molecular markers and have often wondered whether using genomes or transcriptomes would be preferable," said Dr. Chapman, Associate Professor in Ecology and Evolutionary Biology at the University of Southampton. This study found that each data source had its benefits; genomic data may be preferable in species with low polymorphism, but transcriptomic data usually assembles into longer sequences more amenable to designing primers, and these primers may be more transferable across species.

"In addition, I always generate thousands of markers and only use a dozen or so, so I've always wondered what depth of sequencing would one have to generate to be sure of identifying a small number of markers for a basic population genetic study," said Dr. Chapman.

Researchers on a budget may look to generate the minimum necessary sequence data for SSR identification. Now these researchers have some guidance as to how many reads are sufficient: this study found that small assemblies of two million read pairs could generate about 200-2000 potential markers from the genome assemblies and about 600-3650 from the transcriptome assemblies.

As the cost of sequencing falls below the cost of labor for sample preparation, researchers are increasingly using newer techniques such as GBS and RAD-seq to map genetic diversity in populations. However, Dr. Chapman still sees a place for SSRs in the future of population genetics research. "SSRs have advantages over those other technologies that are unlikely to change even if costs go down, for example, the SSRs can be designed from specific genes of interest," said Dr. Chapman. "Also GBS and RAD-seq aren't really being explored for polyploids, whereas SSR scoring in polyploids can be done, with a bit of background information or careful design of primers. The untailored approach of GBS and RAD-seq is likely to resolve a lot of unscorable alleles in polyploids."

SSRs are a relatively inexpensive and efficient way to map genetic diversity in populations. The deluge of genetic data available from HTS can help to efficiently identify sets of SSRs, but until now there have not been clear guidelines for researchers seeking to do this work. In optimizing protocols and laying out major considerations in generating SSRs from genomic and transcriptomic data, Dr. Chapman has helped to bring SSR studies up to date.

As well as sequencing the whole genome of coronavirus 2019-nCoV, the Institut Pasteur continued to work on the samples taken from the first confirmed cases. The quality of these initial samples enabled rapid cell-culture isolation of the new virus. The Institut Pasteur's scientists now have access to the virus responsible for the infection. The isolation of the virus paves the way for new diagnostic, therapeutic and prophylactic approaches.

With the whole viral genome of coronavirus 2019-nCoV having recently been sequenced at the Institut Pasteur, the isolation of strains of coronavirus 2019-nCoV detected in France has now been successfully finalized, in a very short space of time, using the samples taken from the first confirmed French cases.

Coronavirus 2019-nCoV, responsible for the cases of pneumonia that emerged in China (see the Institut Pasteur's fact sheet on the Wuhan coronavirus - page in French), differs from two other viruses that are well known for causing respiratory outbreaks in recent years: the SARS-CoV virus, responsible for the SARS outbreak in 2003, and MERS-CoV, responsible for an outbreak that has been under way since 2012 in the Middle East.

The Institut Pasteur was actively involved in tackling these previous outbreaks, which yielded valuable lessons for the current situation. "For both SARS-CoV and MERS-CoV, cells known as Vero E6 were identified to culture the two coronaviruses," explains Sylvie van der Werf, Director of the National Reference Center (CNR) for Respiratory Viruses at the Institut Pasteur. "In January 2020, we brought them out of our collection, which is kept under strictly controlled conditions, so that we would be ready as soon as we detected a positive sample for coronavirus 2019-nCoV."

Extremely rapid growth of the virus in culture

The Institut Pasteur was therefore well prepared, and on Friday January 24, 2020, the very day that the first cases were confirmed, it began the process of culturing the samples that had tested positive for the virus on Vero E6 cells. "Using detection methods, we had observed a high viral load in the samples taken from the patients in hospital in Paris. This enabled us to identify which samples should be cultured first," says Sylvie Behillil, Deputy Director of the CNR at the Institut Pasteur.

The viruses continued to be cultured over the weekend of January 25-26, 2020. By the morning of Monday January 27, the culture had already grown! "We didn't think that it would grow so quickly," continues Sylvie Behillil. The rapid growth of the culture may be explained by "the high viral load in the samples," but also by "the quality of the samples," adds Vincent Enouf, Deputy Director of the CNR at the Institut Pasteur.

"We could see the cells becoming damaged and then grouping together, which can indicate that they have been infected. But we did not observe this cytopathic effect for all the inoculated samples; that reassured us that we had managed to isolate the strains, and this was then confirmed by additional analyses."

Virus 2019-nCoV now available for research

Now that the Institut Pasteur's scientists have access to coronavirus 2019-nCoV, they can set out to improve scientific knowledge about the virus.

Research will focus on four main areas.

Serology. Analyzing antigen-antibody reactions based on the antibodies found in patients' blood serum, and developing an effective serology test to screen for the infection among the population.NB: This is not a rapid diagnostic test for hospital use; it is a test to identify seroconversion in the population.

Development of specific treatments. Testing known antiviral molecules that act on the replication cycle of some viruses to assess their therapeutic or even prophylactic potential, and looking for antibodies that may have therapeutic applications.

Vaccination. Based on the virus, developing vaccine approaches that have already been explored for other viruses – Ebola, MERS-CoV and SARS-CoV –, with the aim of proposing a vaccine candidate.

Viral pathogenesis. Understanding how the virus works, how it replicates and interacts with the cell and the host organism, to gain a clearer picture of its pathogenic nature and identify biomarkers for infection or new targets for the development of treatments.

Studies have shown a rapid increase in new cases of type 1 diabetes worldwide. However, scientists and researchers have struggled to identify a direct cause. Many have questioned if changes in the environment or lifestyle have impacted the disease. In a newly released review paper published in The Lancet Diabetes & Endocrinology, faculty from the Colorado School of Public Health at the Anschutz Medical Campus examined whether any environmental exposures can explain why type 1 diabetes is on the rise.

"The incidence of type 1 diabetes has increased 3 percent per year over the past three decades. This increase is too rapid to be due to genetic factors, suggesting that environmental factors may play a role," said Jill Norris, MPH, PhD, professor and chair of epidemiology at the Colorado School of Public Health and lead author of the paper.

Identifying environmental factors associated with type 1 diabetes that influence its incidence can inform future preventive trials and searches for other environmental risk factors. In this paper, researchers reviewed the literature on environmental factors like air pollution, diet, childhood obesity, the duration of breastfeeding, the introduction of cow's milk, infections, and many others that showcase an impact on type 1 diabetes.

The researchers then looked at prevalence of an exposure over time while varying its annual increase under simulated scenarios. Using the simulated data, the research showed that if a single factor were to explain the changes in the incidence of type 1 diabetes over the past few decades, it would have to be very strongly associated with the risk of type 1 diabetes.

The simulated scenarios showed that an environmental factor that increased at a constant rate from nearly absent in the population to nearly ubiquitous would have to confer a relative risk of 5 to explain an approximately 3 percent annual increase in the incidence of type 1 diabetes. However, most of the environmental factors reviewed had a relative risk of less than 2.

"While several factors have been associated with type 1 diabetes, none of the associations are of a magnitude that can explain the rapid increase in incidence alone," Norris said. "Moreover, evidence of the changing prevalence of these same exposures over time is not convincing nor consistent."

The paper explains that more research is required, and it is possible that multiple factors simultaneously may account for the increase in type 1 diabetes cases. Other factors are that the magnitude of observed associations may have been underestimated due to exposure measurement error or mismodeling of complex exposure-time-response relationships.

The study concludes that the identification of environmental factors influencing type 1 diabetes risk and increased understanding of the etiology at the individual level, regardless of the ability to explain the changing incidence at the population level, is important because of the implications for prevention.

Therapeutic horseback riding combined with brain-building exercises can improve the dexterity, coordination and strength of children with neurodevelopmental disorders, shows a study in Frontiers in Veterinary Science.

Neurodevelopmental disorders - such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) - affect as many as one in six American children. Physical activity is known to benefit these patients in a variety of ways, but this is the first study showing the short and long-term effects of a program combining horseback riding and cognitive training.

"We wanted to investigate how a combination of equine-assisted activities and various brain-building tasks, administered by a speech therapist, would affect motor skills in children with disorders including autism spectrum disorder and attention deficit hyperactivity," says Dr. Brandon Rigby, of the Texas Woman's University in the United States.

"Our findings should be helpful to therapists and other healthcare professionals who are tasked with implementing strategies and interventions to improve motor skill proficiency in children and youth with ADHD and ASD, which were the most common diagnoses in our study."

For their study, Rigby and his collaborators recruited 25 children with neurodevelopmental disorders between the ages of 5 and 16. Each child completed one of several different programs ranging in length from eight weeks to one year. The programs included weekly introductory horseback riding, as well as sessions with a speech therapist two to three times per week.

During the horseback riding, the children learned about horse anatomy, riding equipment, and the basics of riding. The brain-building activities focused on exercises that train the brain to process sensory information such as sound, sight, balance and spatial orientation. These sessions included music therapy, eye tracking exercises and hand-eye coordination tasks. The children and their parents were also given daily exercises that they could perform at home.

After eight weeks of the program, the children showed improved motor skills, although there was sometimes a delay before the changes became apparent. For the participants that continued the program for one year, these benefits continued for the duration of the study. These participants also showed improvements in their behavior and academic performance, including social and communication skills. Additionally, anecdotal responses from parents and caregivers suggested that the children were more positive, focused and calm both in and outside of the program.

Given the small size of the study, larger-scale research is still needed to better understand the potential benefits to the range of neurodevelopmental disorders. Some limitations include the varying diagnoses of the participants (as opposed to looking at benefits per ADHD or autism specifically), and the allowance to continue prescribed medications or therapies outside the scope of this program. Despite this, the program's results are promising, and the researchers hope that this will inspire further interest in cross-disciplinary programs.

"These findings may allow for a greater demand for these programs, ultimately making them more accessible and affordable," says Rigby.

Unlike what we commonly refer to as 'genes', these phantom genes or 'Long noncoding RNA' (LncRNAs) do not lead to the production of proteins that our cells, and thus our entire bodies are made of.

Previously, it was believed that LncRNAs served no major purpose in cells, but new research now shows that one of these LncRNAs termed 'LincIRS2' is important for safeguarding our metabolism as LincIRS2 loss favors development of metabolic complications in mice.

In my estimate, only the function of less than 100 of the nearly 60,000 LncRNAs encoded in our genomes has been truly understood says Jan-Wilhelm Kornfeld, Danish Diabetes Academy (DDA) professor for Molecular Biology of Metabolic Diseases at University of Southern Denmark.

In clear comparison, researchers have largely understood the function of the 20,344 genes that encode proteins.

That's why it's so exciting that we were able to identify the key role of this particular LncRNA using mice as a model organism, he says.

In addition, we were able to delineate a new, exciting mechanisms for how LncRNAs themselves are controlled.

Editing mice with CRISPR

Using the 'molecular scissor' CRISPR/Cas9, Jan-Wilhelm Kornfelds research team succeeded in cutting out LincIRS2 from the mouse's genome. Next, the researchers observed that mice lacking LincIRS2 developed metabolic complications like elevated blood sugar levels when the LncRNA had been deactivated. Conversely, when performing treatments that activate LincIRS2, mice maintained healthy blood sugar levels even when becoming obese.

It is difficult to predict exactly how this new knowledge can be used, but it is intriguing to speculate that restoring or inhibiting specific LncRNAs could be used to treat diabetic patients or other metabolic disorders one day, says Jan-Wilhelm Kornfeld.

His research team just published these new findings in the prestigious journal Nature Communications. The lead author of the article is Dr. Marta Pradas-Juni, who is a postdoc in Jan-Wilhelm Kornfelds' research team.

Fact: What is a Long noncoding RNA?

DNA serves as blueprint for producing proteins that constitute the essential building blocks all cells are made of. The molecular intermediary that converts DNA information into proteins is called RNA. Thus, RNA's primary purpose is to translate the 'genes' DNA into protein.

In our bodies, 20,344 different genes are specifically designed to create the many different proteins that our bodies require. The majority of these so-called protein-coding RNAs have been mapped by scientists. That is why, we today largely understand exactly which proteins these RNAs give rise to.

However, nearly 60,000 RNAs called 'Long noncoding RNAs' are written into our genomes that never contribute to the formation of a protein. How they function, and how they are involved in disease development is largely unknown.