11 Factors for Alzheimer’s Disease Discovered after a Large Study

The largest international study ever conducted on Alzheimer’s disease (AD), the I-GAP (International Genomics Alzheimer’s Project) consortium has identified 11 new regions of the genome involved in the onset of this neurodegenerative disease.

This study gives an overview of the molecular mechanisms underlying the disease, opening up to a better understanding of the pathophysiology of AD. These results detailed currently in Nature Genetics, could not have been obtained without this unique worldwide collaborative effort.

Since 2009, 10 genes for Alzheimer’s disease have been identified. However, much of the individual susceptibility to develop the disease remains unexplained. So in February 2011, the leaders of the four largest international research consortia on the genetics of AD joined forces to accelerate the discovery of new genes. Supported in part by the National Institute on Aging (NIA) and other components of the National Institutes of Health (NIH), in less than three years, the IGAP program identified more genes than had been identified over the previous 20 years. They collected genetic data on 74,076 patients and controls from 15 countries and were able to discover 11 new genes in addition to those already known, and identify 13 other genes, yet to be validated.

These 11 new confirmed genes may open new avenues to understanding the causes of AD. For example, one of the most significant associations was found in the region HLA-DRB5/DRB1 major histocompatibility complex. This finding is interesting in several ways. First, it strongly suggests the involvement of the immune system in AD. In addition, this same region has also been associated with two other neurodegenerative diseases, one known to have an immune mechanism, multiple sclerosis and another not previously thought to have a major immune component, Parkinson’s disease.

Some of the newly associated genes confirm biological pathways known to be involved in AD, including the amyloid (SORL1, CASS4 ) and tau (CASS4 , FERMT2 ) pathways. The role of the immune response and inflammation (HLA-DRB5/DRB1 , INPP5D , MEF2C ) already implied by previous work (CR1, TREM2) is reinforced, as are the importance of cell migration (PTK2B), lipid transport and endocytosis (SORL1 ). New hypotheses have also emerged related to hippocampal synaptic function (MEF2C , PTK2B), the cytoskeleton and axonal transport (CELF1 , NME8, CASS4) as well as myeloid and microglial cell functions (INPP5D).

Finally, this work demonstrates that, given the complexity of such a disease, only a global collaboration of research efforts will quickly find solutions to tackle this major threat.

The four founding partners in this international consortium are, in alphabetical order, the Alzheimer’s Disease Genetics Consortium (ADGC), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the European Alzheimer Disease Initiative (EADI) and the Genetic and Environmental Research in Alzheimer Disease (GERAD) consortium.

Boston University and the Framingham Heart Study are well-represented in this landmark international effort. The neurology working group of the Cohorts for Heart and Aging Research in Genomic Epidemiology is led by Sudha Seshadri, MD, professor of neurology at Boston University School of Medicine (BUSM), who is a senior investigator in the Framingham Heart Study and also one of the senior authors on this manuscript. Several other senior investigators, notably Anita L. DeStefano , PhD, professor of biostatistics Boston University School of Public Health (BUSPH) on behalf of CHARGE, and Lindsay A. Farrer, PhD, Chief of Biomedical Genetics and professor of medicine, neurology, ophthalmology, genetics & genomics, epidemiology, and biostatistics at BUSM and BUSPH on behalf of the ADGC, were key investigators in this effort. Farrer co-directs the data analysis effort for the ADGC which includes nearly all of the nation’s researchers working on the genetics of AD as well as many investigators and resources of the 29 NIA funded Alzheimer Disease Centers.

“This study clearly demonstrates that there really is strength in numbers to identify genes that individually have a small effect on risk of Alzheimer’s,” said Farrer. “But it’s not the magnitude of the odds ratio that’s really important. Each gene we implicate in the disease process adds new knowledge to our understanding of disease mechanism and provides insight into developing new therapeutic approaches, and ultimately these approaches may be more effective in halting the disease since genes are expressed long before clinical symptoms appear and brain damage occurs,” he added.

“This landmark international effort has uncovered new pathways and new genes in old pathways that are definitely associated with Alzheimer dementia, but we need to do much work to better understand how exactly these genes work in health and disease, and to perhaps make drugs from these genes and molecules,” said Seshadri. “We will continue to mine these results for new insights, even as we include more patients and use new technologies like whole genome sequencing to find more new pathways and genes,” she added.

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How bacteria with sweet tooth keeps us healthy

A new study is providing insights into the interaction between bacteria and mucus building mucins – proteins that have sugars associated with them – and how the specificity of these interactions affects health.

Dr Nathalie Juge and her team at the IFR have shown that the ability to use mucins in the human gut varies between different gut bacteria strains.

The IFR researchers looked at Ruminococcus gnavus. This is a common species of gut bacteria found in over 90 percent of people, including infants just a few days old. It has also been implicated in gut-related health conditions.

A number of studies have shown that patients suffering from Inflammatory Bowel Diseases have a disproportionate representation of R. gnavus.

This study looked at two different R. gnavus strains. Although both R. gnavus strains can use mucins, only one had the ability to survive when mucins were the sole source of food.

Comparing the genomes of the R. gnavus strains identified gene clusters used to breakdown mucins. Differences in these genes explain the different abilities of the strains to use mucins.

The mucin sugar structures change in different parts of the gut and over time, suggesting the strains may be adapted for different environments or to colonize us at different times.

A better understanding of which strains use mucins and exactly how they do this will give us new insights into what makes a healthy gut bacteria population, and how fluctuations from this might link to gut diseases like Crohn’s disease and ulcerative colitis.

The study has been published in the journal PLOS ONE

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Theatre could help autistic youth improve social deficits

A novel autism intervention program is using theatre to teach reciprocal communication skills to improve social deficits in adolescents with the disorder, a new study has revealed.

The newly released study assessed the effectiveness of a two-week theatre camp on children with autism spectrum disorder and found significant improvements were made in social perception, social cognition and home living skills by the end of the camp.

Called SENSE Theatre, the Social Emotional Neuroscience and Endocrinology (SENSE) program evaluates the social functioning of children with autism and related neuro developmental disorders.

Camp participants ages 8 to 17 years join with typically developing peers who are specially trained to serve as models for social interaction and communication, skills that are difficult for children with autism.

The camp uses techniques such as role-play and improvisation and culminates in public performances of a play.

Lead author Blythe Corbett, Ph.D., associate professor of Psychiatry and Vanderbilt Kennedy Center investigator, said that the findings show that treatment can be delivered in an unconventional setting, and children with autism can learn from unconventional ‘interventionists’ – their typically developing peer.

Corbett said that their findings show that the SENSE Theatre program contributes to improvement in core social deficits when engaging with peers both on and off the stage.

The study has been published in the journal Autism Research

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High altitude sickness: detected before physical symptoms

Researchers have found that hypoxia can be detected prior to the appearance of physical symptoms.

Jan Stepanek, M.D., the Aerospace Medicine Program Director and Co-Director of the Aerospace Medicine and Vestibular Research Laboratory, said that this study opens the door for objective assessments of hypoxia and additional safeguards for military and commercials pilots and others working in high altitudes.

Hypoxia is a lower than normal level of oxygen in your blood. To function properly, your body needs a certain level of oxygen circulating in the blood to cells and tissues.

When this level of oxygen falls below a certain amount, hypoxia can cause a variety of symptoms including shortness of breath, impaired speech, slowed reaction time and passing out.

The Mayo Clinic study team used the King-Devick neurocognitive performance test , commonly used to identify cognitive changes related to sports-related concussions, and to assess cognitive function under conditions of low oxygen-simulating altitude.

The King-Devick test assesses the time in viewing, identifying and reading aloud a series of numbers on three consecutive test cards. Based on test times of 25 participants, the study concluded that the King-Devick test is an effective tool to detect “impairment of cognitive performance at a presymptomatic stage of hypoxia.”

The findings have been published in journal Aviation, Space, and Environmental Medicine.

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First human trial of new bone-marrow transplant method

Doctors at London’s Great Ormond Street Hospital have carried out a pioneering bone-marrow transplant technique.

They say the method should help with donor shortages since it does not require a perfect cell match.

Mohammed Ahmed, who is nearly five years old, was among the first three children in the world to try out the new treatment.

He has severe combined immunodeficiency syndrome and had been waiting for a suitable donor for years.

Mohammed, who lives in Milton Keynes, was referred to Great Ormond Street Hospital when he was a year old.

We waited for a full match but it did not come. By the grace of God, we took the decision to have the treatment” Jamil Ahmed, Mohammed’s dad

His condition – a weak immune system – makes him more susceptible to infections than most, and a bone marrow transplant is the only known treatment.

While Mohammed was on the transplant waiting list, he became extremely sick with swine flu.

At that time, his doctors decided Mohammed’s only real hope was to have a mismatched bone-marrow transplant, with his father acting as the donor.

Mohammed’s dad, Jamil, agreed to give the experimental therapy a go.

Before giving his donation, Jamil was first vaccinated against swine flu so that his own bone-marrow cells would know how to fight the infection.

Mohammed’s doctors then modified these donated immune cells, called “T-cells”, in the lab to engineer a safety switch – a self-destruct message that could be activated if Mohammed’s body should start to reject them once transplanted.

Safety net

Rejection or graft-v-host disease is a serious complication of bone-marrow transplants, particularly where tissue matching between donor and recipient is not perfect, and is one of the most difficult challenges faced by patients and their doctors.

Mismatched transplants in children – where the donor is not a close match for the child – are usually depleted of T-cells to prevent graft-v-host disease, but this causes problems in terms of virus infections and leukaemia relapse.

The safety switch gets round this – plenty of T-cells to be transfused and later killed off if problems do arise.

Thankfully, the transplant carried out in 2011 was a success – Mohammed’s doctors did not need to use the safety switch.

Although Mohammed still has to take a number of medicines to ward off future infections, his immune system is now in better shape.

Jamil said: “We waited for a full match but it did not come. By the grace of God, we took the decision to have the treatment.

“Now he is all right. Sometimes we forget what he has been through. We are just so grateful.”

He said Mohammed would still need close monitoring and regular health checks over the coming years, but his outlook was good.

Dr Waseem Qasim, ‎consultant in paediatric immunology at Great Ormond Street Hospital and lead author for the study, said the new approach should hopefully mean children who received a mismatched transplant could enjoy the same chance of success as those given a fully matched transplant.

“We think Mohammed is cured of his disorder. He should be able to lead a fairly normal life now.”

A full report about Mohammed’s therapy and the research by Great Ormond Street Hospital, King’s College London and the Institute of Child Health has just been published in PLoS One journal.

There are currently about 1,600 people in the UK waiting for a bone-marrow transplant and 37,000 worldwide.

Just 30% of people will find a matching donor from within their families.

Donations involve collecting blood from a vein or aspirating bone marrow from the pelvis using a needle and syringe.

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Fat pledge ‘a drop in the ocean’

Someone eating a cheeseburger

A pledge by food manufacturers to cut saturated fat levels is “a drop in the ocean” in the fight against obesity, a top public health expert has said.

Morrisons, Subway and Nestle are among firms signed up to the voluntary “responsibility deal” between industry and government.

But Prof John Ashton, president of the Faculty of Public Health, said the approach “lacked credibility”.

The Department of Health (DoH) said it would “make a huge difference”.

It says the average man should eat no more than 30g of saturated fat a day, while the average woman should eat no more than 20g.

According to the British Dietetic Association, most people eat about 20% more than the recommended maximum levels – and a survey of 2,000 people for Sainsbury’s found 84% of those questioned did not know how much saturated fat was a healthy amount.

‘Healthy options’

The DoH said cutting the amount of saturated fat in people’s diets by 15% could prevent around 2,600 premature deaths every year from conditions such as heart disease and stroke.

Almost half of the food manufacturing and retail industry – based on market share – has signed up to this latest pledge to reduce the amount of saturated fat in products, the DoH said.

Measures planned by companies include Nestle altering the make-up of KitKat biscuits, Morrisons reformulating its range of spreads and Subway replacing biscuits and crisps in its Kids’ Pak with healthier options.

Other firms which are cutting saturated fat or have pledged to do so include Tesco, Sainsbury’s, Aldi and Mondelez International – which will alter products including its Oreo biscuits.

Prof Ashton said that, while it was “a good thing that some companies are making food that has less saturated fat than before”, the pledge did not go far enough.

Saturated fat

“They need to ensure that at the same time they lower the sugar and salt that they have used to make foods tastier as a result of lowering the fat content.”

He added: “This announcement is a drop in the ocean in comparison with the scale of the obesity crisis.

“We cannot rely on the voluntary approach of the responsibility deal to solve this problem.

“It now lacks credibility and can be seen as a feeble attempt by the industry to save face.”

Labour public health spokeswoman Luciana Berger said: “A few company names on a non-binding plan with no timescale stands little chance of delivering the fundamental change needed to improve our national diet.

“In the week that the chief medical officer warned of the long-term dangers of childhood obesity, we need to go much further.”

She said Labour had put forward “bold ideas to set legal limits on our food’s fat, sugar and salt content and achieve a cross-party ambition for a more physically-active nation”.

‘Huge progress’

Tam Fry of the National Obesity Forum, also called for regulation, adding: “The much-vaunted voluntary responsibility deal will never succeed until the government takes a grip and makes everybody sign up to it.”

The DoH said that “by reducing the amount of saturated fat in everyday foods, manufacturers and retailers are helping us lead healthier lives”.

“We have already made huge progress through the responsibility deal – there are reduced salt levels in many products, calories on high street menus and better information about alcohol units and drinking guidelines,” a spokesperson said.

“We know there is more to be done but today’s pledge will make a huge difference to our health.”

Prof Susan Jebb, chairwoman of the Responsibility Deal Food Network, said the manufacturers’ commitments to help reduce saturated fat were “an important step forward”.

The announcement of the pledge comes days after cardiologist Aseem Malhotra, a member of the Academy of Medical Royal Colleges’ obesity steering group, wrote in the British Medical Journal that the risk from saturated fat in non-processed food was “overstated and demonized”.

He said there was too much focus on the fat with other factors such as sugar often overlooked.

He told Radio 4’s Today on Saturday that “a sugary drinks tax, banning junk food advertising to children, ensuring compulsory nutritional standards in schools and hospitals… are things that are going to overcome the problems that we face”.

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Nestle to change Kit Kat recipe

KIT Kats are to undergo a recipe change in a bid to make the York-produced bars healthier.

Nestlé has announced that it is reformulating the Kit Kat following a three-year research program at its innovation centre in York.

The new recipe will see 0.4g of saturated fat cut from each two-fingered milk chocolate bar, the equivalent of 3,800 tones of saturated fat being removed from the nation’s diet.

The reduction has been made by changing the recipe of the wafer filling.

York’s Nestlé Confectionery factory in Haxby Road will manufacture the new bars, which will be on sale from early next year.

The move by Nestlé comes as the firm signs up to the Department of Health’s new Responsibility Deal Pledge on saturated fats.

Ciaran Sullivan, managing director of Nestlé Confectionery, said: “This is the next step on the journey where we are improving the nutritional profile of our products.

“Kit Kat is our biggest confectionery brand and therefore the obvious choice to identify a sat-fat reduction.

“Improving the nutritional profile of Kit Kat does not come at the expense of quality and taste and consumers will continue to enjoy the same Kit Kat as they have for over 75 years.”

Bosses say the new Kit Kats are the latest in an “ongoing commitment” to improve the nutritional composition of its confectionery portfolio. As a result of this all Nestlé confectionery chocolate biscuit bars are low in salt and meet the Responsibility Deal 2012 salt targets.

Nestlé has also reduced the portion size of many of its products such as Kit Kat, Aero, Yorkie, Lion Bar, and Rolo and is working to expand its range of 99-calorie biscuit bars, which last year included the addition of Blue Riband Caramel, Aero Biscuit Peppermint and Aero Biscuit Orange.

More than a billion Kit Kat bars are made in the York factory per year, with the site producing up to six million every day.

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FDA approves Abbott device for leaking heart valve

The U.S. Food and Drug Administration has approved Abbott Laboratories’ MitraClip medical device, used to stop heart valve leakage in patients deemed unable to endure valve repair through open heart surgery, the company said on Friday.

The MitraClip treats mitral regurgitation, a condition in which the mitral valve of the heart does not close properly, causing blood leakage that can lead to stroke, heart attack or even death.

It has estimated the disorder affects about one in 10 people aged 75 and older.

Those with the condition who are too frail for open heart surgery are typically treated with medicines and have high rates of heart failure and rehospitalizations.

“We think longer term in the U.S., (MitraClip) could be a $500 million product,” said RBC Capital Markets analyst Glenn Novarro. “This approval is sooner than we thought. It’s a pleasant surprise.”

Novarro said the timing of the FDA green light was excellent as it came just ahead of a major U.S. medical meeting for interventional cardiologists where Abbott will be able to showcase the device.

A panel of advisers to the FDA in March voted 5-3 to recommend approval of the implantable heart device. Some panel members questioned whether MitraClip would be effective.

The MitraClip was approved in Europe in 2008 under a system in which medical devices often reach the market several years ahead of the United States.

International sales are running at about $30 million a quarter, with sales growth at about 50 percent over 2012, Abbott said.

U.S. sales are likely to grow slowly at first as the company seeks reimbursement for the device, primarily from the Medicare healthcare program, and as more physicians are trained in its use. The MitraClip is implanted using a minimally invasive procedure in which it is threaded by catheter through a vein into place in the heart to stop the leak.

There are currently 50 centers in the United States that have experience with the device through clinical trials. That number is expected to double over the next year, John Capek, Abbott’s head of medical devices, said in an interview.

There are 20,000 to 30,000 patients in the United States who would likely qualify for MitraClip implantation, Capek said.

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HIV drugs may get new role in fighting cancer

A type of HIV medicine that stops the AIDS virus from entering immune system cells could in future be put to work against cancer in new combination therapies being developed by drug companies.

Interest in using so-called CCR5 inhibitors to fight tumors was fuelled last year when U.S. researchers, testing the drugs on mice, reported a marked reduction in aggressive breast cancer cells spreading to the animals’ lungs.

Researchers from the Thomas Jefferson University Kimmel Cancer Center described the results as “dramatic” after they were published in the Journal of Cancer Research.

Now industry analysts at Citi believe Merck & Co Inc is set to take things to the next stage by testing its CCR5 drug vicriviroc in cancer patients. The product was abandoned as a treatment for HIV in 2010 following an unsuccessful study.

Pfizer Inc and Bristol-Myers Squibb – which also have similar drugs in their portfolios – could follow suit, Citi said in a note on Friday.

Asked to comment on the suggestion that it would start testing vicriviroc in patients in 2014 as part of a combination therapy for cancer, a spokesman for Merck said: “We have not disclosed any such plans.”

Citi said it expected vicriviroc to re-enter clinical testing in combination with cancer immunotherapy as Merck explores its potential across multiple tumor types, including melanoma, colorectal, breast, prostate and liver cancer.

Immunotherapy, which harnesses the body’s immune system to fight cancer, is a hot new area for cancer research, with some experts predicting the approach will in future form the backbone of many cancer treatments.

However, drug combinations are expected to be critical to its success as oncologists will need to block cancer cells on several fronts at once.

One option is to combine two immunotherapies, while another approach, also being pursued by other companies like Roche Holding AG and AstraZeneca Plc, is to combine immunotherapy medicines with different drug types.

CCR5 inhibitors are one such option, given the encouraging signals from pre-clinical research. As these drugs have already been studied in HIV, their development could be relatively rapid.

Pfizer could also start clinical trials in cancer with its approved CCR5 drug Selzentry, which is currently marketed for HIV via the ViiV Healthcare alliance with GlaxoSmithKline Plc and Shionogi & Co Ltd.

Bristol, meanwhile, has a dual CCR2/5 inhibitor in mid-stage Phase II development, which is being tested for diabetes and kidney disease.

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7 Healthy Habits to Pass on to Your Kids

Turn everyday situations into opportunities to teach your children about healthy living

7 Healthy Habits to Pass on to Your Kids Intro

With 1 in 3 children and teens considered overweight or obese in the United States, it’s time to do something, and doctors agree that parents need to take the lead when it comes to educating children about staying healthy: Up to 90% of doctors agree that weight is the most important health topic for parents to discuss with their children, even more than safe sex, cigarette smoking, drug use, and alcohol consumption, according to the 2011 Raising Fit Kids survey by WebMD and Sanford Health. In addition to having an open dialogue, it’s important to lead by example. “Kids definitely take on the behaviors of their parents,” says Susan Bartell, PhD, a parenting and child psychologist in New York. To set your child on the right path, turn everyday activities like dinnertime, playtime, or grocery shopping into real-life lessons on health, nutrition, and fitness. Here’s how.

Leave Some Food on the Plate

In an attempt to make sure they don’t miss out on any nutrients, many parents ask kids to clean their plates, making them more likely to overeat later in life, says Sarah Krieger, RD, spokesperson for the American Dietetic Association and director of the Fit 4 All Kids program at All Children’s Hospital in St. Petersburg, FL. If your kids say they’re not hungry, wrap up their plates, says Krieger, but make them stay at the table until the rest of the family finishes (to avoid a situation in which they choose playtime over full tummy). And if they’re hungry later, warm up the plate of food instead of offering a snack.

Recognize the Difference between Hunger and Boredom

Even if you had to tape a stop sign on your fridge to get there, you learned to give yourself time to decide if you’re hungry or just need to pick up a hobby. Children shouldn’t have free access to the snack drawer, says Krieger, and should ask parents for permission to have a snack. “The first thing parents should offer is a piece of fruit and a reminder of the time for the next meal,” she says. If children are actually hungry, they’ll take the fruit. If they’re bored, they’ll wait until dinner.

 

Don’t Use Food as a Reward

Congratulating yourself with a sweet treat after a day of healthy eating is a little bit nuts. Rewards should help you work toward your goal—not against it, says Bronco. And making dessert—or anything edible—the pot of gold at the end of the eating rainbow could affect your child’s food preferences. One study published in the European Journal of Clinical Nutrition found that children who were rewarded with stickers for eating sweet red peppers consumed fewer pieces of the vegetable and had greater dislike for it than children who were told only that they could eat as much as they wanted. In other words, there’s a chance you could turn your child off broccoli if eating it puts him on the fast track to a brownie. If an after-dinner treat is standard in your household, downplay dessert by serving sweet, in-season fruit and small cookies only a few times a week, say Krieger.

Avoid Distracted Eating

Multitasking while you munch can lead to unwanted extra pounds. Distracted eaters—like those who surf the web or watch TV—have a hard time recalling what they eat, are less likely to feel satiated, and more likely to consume extra calories throughout the day, according to a study published in the American Journal of Clinical Nutrition. Good advice for adults and youngsters alike: Eat only when sitting at the table. No iPods, cell phones, or gaming systems allowed—just food and family. This helps encourage mindful eating, says Michael Bronco, a personal trainer and owner of Bronco’s Gym in Madison, NJ.

Stick to the List When You Go Grocery Shopping

Experts agree that shopping with a list helps you avoid fattening impulse buys and guarantees you have all the ingredients you need to make healthy meals. Get the kiddos involved in the grocery shopping by helping you compile the list, says Bronco. Make columns for proteins, fruits, vegetables, and whole grains, and ask your children to make recommendations for foods they’d like to eat that fit each category. It’s a great way to learn about the food groups and get familiar with the healthy options that fill them. It also doesn’t hurt that your kids get the sense that they “chose” the peas rather than feeling like victims of the vegetables on their plates.

Read Food Labels

Sneaky sugars and sodium can transform a seemingly harmless item into a diet disaster—that’s why reading nutrition labels is crucial to healthy grocery shopping. Turn a trip to the market into a nutritional scavenger hunt by asking reading-age children to find cereals with less than 8 g of sugar, canned soup with less than 300 mg of sodium, or a loaf of bread that clearly states it’s 100% whole grain. They’ll learn how to navigate a nutrition panel and be too busy to complain that the sleeve of cookies they wanted didn’t make it into the cart.

Find a Workout You Enjoy

Let’s face it, if you hate the gym you’re not going to go—and the same goes for your kids and soccer practice. “The adults who are most successful with their workouts found something they really love doing,” says Bronco. “It’s worth it to find an activity that your kid really loves, and if it becomes not so fun anymore, try something else. I think if you get too strict about sticking with one sport and it becomes a chore, you run the risk of turning your child off fitness completely.” When people are having fun, they stop worrying about how many calories they’re burning.

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