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Study Identifies Cause for Mysterious Cases of Epilepsy in Children

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International collaboration uncovers mosaicism, a condition in which cells within the same person have a different genetic makeup, as a cause for pediatric seizures

Credit: Pixabay
By studying resectioned brain tissue for mutations, researchers have identified genetic factors that may cause malformations of cortical development, a form of pediatric epilepsy.
« Study Identifies Cause for Mysterious Cases of Epilepsy in Children

Newswise — Epilepsy is present in 4% of the population, and is among the most common brain disorders in children. Modern medicine can prevent most seizure recurrences, but approximately 20% of patients do not respond to treatment.

In these cases, the reason may originate in patches of damaged or abnormal brain tissue known as “malformations of cortical development” (MCD), which results in a diverse group of neurodevelopment disorders. Surgical resection or removal of the patch can cure the seizures, and epilepsy surgery to improve neurological outcomes is now a key part of the modern medical armamentarium, but what causes the patches has largely remained a mystery.

Writing in the January 12, 2023 issue of Nature Genetics, researchers at University of California San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine, collaborating with an international consortium of more than 20 children’s hospitals worldwide, report a significant breakthrough in understanding the genetic causes of MCD.

Members of the Focal Cortical Dysplasia Neurogenetics Consortium investigated 283 brain resections from children across a range of MCD types, with parental consent, looking for potential genetic causes. Because most brain tissue in these children is normal, the scientists focused on mutations present in a small subset of brain cells, a phenomenon termed genetic somatic mosaicism.

“This was a decade-long journey, bringing specialists together from around the world, to recruit patients for this study,” said senior study author Joseph Gleeson, MD, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine. “Until recently, most hospitals did not study resected brain tissue for genetic causes. The consortium organized a biobank to store tissue for high-throughput mosaicism analysis.”

Previous research by Gleeson and colleagues had shown that genetic somatic mosaicism in the mTOR signaling pathway was a contributing factor, said co-first author Changuk Chung, PhD, a postdoctoral fellow in the Gleeson lab.

“But most patients remain undiagnosed, which hinders treatment. We tested for hidden mutations, detectable only by greatly expanding the cohort size and improving methods so that the results could be meaningful. We collaborated to solve technical and logistical bottlenecks. The pieces fell into place, but it took 10 years.”

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The team conducted intensive genomic discovery using state-of-art somatic mosaic algorithms developed by the National Institutes of Health-sponsored Brain Somatic Mosaicism Network, of which UC San Diego is a member.

“We tried our best to detect mutations in as little as 1 percent of cells,” said co-first author Xiaoxu Yang, PhD, a postdoctoral scholar in Gleeson’s lab. “Initially we failed. To solve these problems, we needed to develop novel artificial intelligence methods to overcome barriers in sensitivity and specificity.”

The team ultimately identified 69 different genes carrying somatic brain mutations, the majority of which have never previously reported in MCD.

“We can draw parallels with the cancer field because these mutations disrupt cellular function and need to be resected,” said co-first author Chung. “However, unlike cancer cells, brain cells mostly do not divide so these cells misbehave by stimulating epileptic seizures. The question that arose was whether the newly found gene mutations were sufficient to cause MCD disease.”

Gleeson said the scientists found that the genes converged on calcium signaling, gene expression and synaptic functions, and noted that when the mutations were introduced into a mouse model, abnormalities similar to those seen in patients were observed. The study authors suggest the findings could be used to improve diagnosis and develop cures for MCD disease.

“The MCD genes in patient brains have demonstrated critical roles during cortical development,” said Gleeson. “These findings could lead to new molecular classifications for MCD, and ultimately to personalized therapies for epilepsy.”

For a complete list of co-authors, see full study.

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Funding for this research came, in part, from the National Institutes of Health (grants NIMH U01MH108898 and R01MH124890, NIA R21AG070462, NINDS R01NS083823), the San Diego Supercomputer Center and UC San Diego Institute of Genomic Medicine.

Source: University of California San Diego

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Set Children Up for Day Care Success: 6 ways parents can prep little ones for child care

Long days of school, first trips to day care or even a return from a period of at-home care can be difficult or downright nerve-wracking for parents and children alike.

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(Family Features) Long days of school, first trips to day care or even a return from a period of at-home care can be difficult or downright nerve-wracking for parents and children alike. This new adventure can bring challenges from keeping children healthy to supporting their nutrition and more. Sending a little one to day care can even result in maternal separation anxiety.

To help alleviate some of the anxiety and parental concerns, the childhood nutrition experts at Gerber teamed up with Dr. Whitney Casares – a board-certified practicing pediatrician and creator of “Modern Mommy Doc” – to share these tips for families preparing their little ones for child care.

Keep Important Factors Top of Mind
As part of appreciating the milestone of the first time at day care, Casares encourages parents to remember that, while daunting, day care means new experiences, new friends and opportunities for growth, fun and healthy development. As part of the transition, she suggests paying attention to critical factors like sleep, nutrition, illness prevention and emotional development.

Support Their Immune Systems
Offer little ones a diverse array of nutritious foods during the transition to day care. A diet rich in fruits, vegetables and whole grains is essential for building immune systems. Additionally, iron-rich foods like iron-fortified baby cereals, eggs, beans and meat are critical for a strong body. Caregivers should frequently wash hands and focus on good sleep hygiene.

Put Nutrition on the Menu
When packing lunch boxes for a day of care, it’s important to keep nutrition in mind. Once children transition to finger foods, Casares recommends snacks from Gerber like Peach Puffs, Fruit and Veggie Melts and Wonderfoods Superfood Hearts, which come in a variety of flavors and include vital nutrients to optimize health.

Be Prepared for Separation Anxiety
Not all infants and toddlers experience separation anxiety, but many can, so it’s good to be prepared. Casares encourages parents to pack a familiar swaddle blanket in infants’ diaper bags to help ease those anxieties. Some toddlers benefit from having a beloved stuffed animal or blanket with them. Try introducing these transitional objects to little ones early so they smell and feel familiar when drop-off comes around.

Pack the Essentials
While nutritious foods, like Gerber Fruit and Veggie Pouch Blends, are certainly near the top of the list, there are plenty of other essentials to pack for each day. Don’t forget to add breast milk or formula, bottles and extra nipples alongside snacks and meals. Also remember to pack extra sets of clothes, diapers, wipes and those anxiety-soothing must-haves like blankets and stuffed animals.

Prepare for Appetite Changes
It’s common for children’s appetites to decrease during their first few days of child care as they may eat a little less while growing accustomed to their new environment and surroundings. There’s no need to worry – parents can adapt to these changes by understanding they’re often a natural part of the transition. While you may find little ones are hungrier before and after day care, this behavior should ease over time. If it doesn’t, schedule an appointment with your pediatrician to be sure babies stay on track.

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To find more childhood nutrition advice, visit Gerber.com.

Photos courtesy of Getty Images


SOURCE:
Gerber

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CVS Health survey finds more than two-thirds of Americans plan to get a flu shot this season

CVS Pharmacy® and MinuteClinic® encourage consumers to get an annual flu shot and stay up to date on routine vaccinations

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WOONSOCKET, R.I. /PRNewswire/ — CVS Health® (NYSE: CVS) is prepared to meet patients’ vaccination and other preventive health care needs as flu season approaches. CVS Pharmacy® and MinuteClinic® are offering the annual flu vaccine at locations nationwide. CVS Pharmacy is also offering the new respiratory syncytial virus (RSV) vaccine, which has been approved for adults ages 60 and up. In addition, CVS Pharmacy and MinuteClinic are preparing to offer a new CDC-recommended COVID-19 vaccine once approved and available. To help patients plan ahead, appointments can be scheduled in advance using the digital scheduler at CVS.com or in the CVS Pharmacy app. MinuteClinic is offering the flu vaccinations and routine wellness visits with appointments available at MinuteClinic.com. 


Experience the full interactive Multichannel News Release here: https://www.multivu.com/players/English/9196451-cvs-health-minuteclinic-flu-and-rsv-vaccinations/ 

“Receiving vaccinations for common illnesses like flu and RSV is a cornerstone of preventive care, and helps patients protect not only themselves, but also the health of their broader community,” said Sree Chaguturu, Executive Vice President and Chief Medical Officer, CVS Health. “Access is key, and with our national footprint of pharmacies and retail medical clinics, we’re making it easier than ever to get vaccinated in a timely, safe and convenient way.”


CVS Health flu survey data

According to a survey of U.S. consumers commissioned by CVS Health*, timing, convenience and scheduling were cited as important factors when choosing when and where to get a flu vaccine. Other findings include:

  • 75% of people who plan to receive their flu shot, plan to do so before November
  • Seniors are the demographic most likely to get vaccinated (74%); but 2/3 of those over age 18 expect to get a shot
  • 42% of patients are likely to visit a retail pharmacy for their flu shot, followed by a doctor’s office (33%)
  • 78% of patients said convenient hours that work with their schedule was an important factor when choosing a pharmacy for their flu shot
  • Of those planning to get a flu shot, 62% plan to schedule their appointment online, up 43% over the last two years

Digital scheduling at CVS.com and in the CVS Pharmacy app offers the flexibility to schedule multiple patients at once, allowing families, caregivers and other groups to get vaccinated together. Patients can also schedule multiple vaccinations in one appointment, such as flu and RSV, as recommended by the Centers for Disease Control and Prevention (CDC). In addition, patients can choose to walk into their local CVS Pharmacy and request a vaccination, seven days a week, including during evening and weekend hours. MinuteClinic flu vaccination and sick symptom visits (during which patients can get tested for flu, COVID-19, strep throat, etc.) are available by appointment at MinuteClinic.com.

“Pharmacists are trusted community health providers, thanks to their frequent and meaningful interactions with patients,” said Prem Shah, Executive Vice President and Chief Pharmacy Officer, CVS Health, Co-President, Pharmacy and Consumer Wellness. “As a result of their long-standing relationships with patients, our pharmacy teams can help identify vaccination gaps and recommend other care interventions on the spot, ensuring that patients always have access to advice and support.”

In addition to flu and RSV, CVS Pharmacy and MinuteClinic offer more than 15 of the most common recommended vaccinations, including shingles, pneumonia (pneumococcal), hepatitis B and more. Patients who receive any CDC-recommended vaccine at CVS Pharmacy will also receive a $5 off $20 to use on in-store purchases.*

According to the CDC, patients should get their flu vaccination early in the fall, before flu season begins, and ideally no later than the end of October. CVS Pharmacy and MinuteClinic offer multiple flu vaccine options, including the adjuvanted and higher dose vaccine which is recommended by the CDC for seniors. COVID-19 vaccinations are available at no cost for all patients, and flu vaccines are available at no cost with most insurance plans, including Medicare Part B. 

About CVS Health
CVS Health® is the leading health solutions company, delivering care like no one else can. We reach more people and improve the health of communities across America through our local presence, digital channels and over 300,000 dedicated colleagues – including more than 40,000 physicians, pharmacists, nurses and nurse practitioners. Wherever and whenever people need us, we help them with their health – whether that’s managing chronic diseases, staying compliant with their medications or accessing affordable health and wellness services in the most convenient ways. We help people navigate the health care system – and their personal health care – by improving access, lowering costs and being a trusted partner for every meaningful moment of health. And we do it all with heart, each and every day. Follow @CVSHealth on social media.

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Amy Thibault
401-318-2865
[email protected]

___________________________
*”Flu Intention” Survey, commissioned by CVS Health in July 2023
* FOR $5 OFF $20 COUPON: Redeemable in store at CVS Pharmacy® and Longs Drugs® locations only for one-time use only between 8/14/23-12/31/23. Coupon received via email after vaccination. Limit one per customer per eligible vaccine visit. $5 savings applied to total qualifying purchase of at least $20 (after other coupons and discounts are applied). Reward cannot be issued in AR, NJ, NY, at Target or Schnucks locations, or at MinuteClinic® locations in AR, MA, NJ, NY, PA and RI. Coupon is void if copied or transferred and where prohibited by law. Internet printed or counterfeit coupons prohibited. Original must be relinquished with purchase. ExtraCare® card required to receive savings. Coupon cannot be combined with any other CVS Pharmacy coupon, Coupon excludes alcohol, lottery, money orders, prescriptions and copays, pseudoephedrine/ephedrine products, postage stamps, prepaid cards, gift cards, newspapers and magazines, milk (where required by law or regulation), sale/promotional merchandise, bottle deposits, bus passes, hunting and fishing licenses and any imposed governmental fees or items reimbursed by a government health plan. Tax charged on precoupon price where required. No cash back. Retailer’s coupon. Bearer assumes all sales/use tax liability. CVS reserves the right to modify this offer.

SOURCE CVS Health

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Child Health

FDA Issues Warning Letters to Three Infant Formula Manufacturers

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Today, the U.S. Food and Drug Administration issued warning letters to three infant formula manufacturers as part of the agency’s ongoing commitment to enhance regulatory oversight to help ensure that the industry is producing infant formula under the safest conditions possible.

These warning letters for violations of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the FDA’s Infant Formula regulations were issued to ByHeart Inc.Mead Johnson Nutrition (Reckitt), and Perrigo Wisconsin, LLC. They reflect findings from FDA inspections of these facilities over the last several months. At the time of each inspection, the FDA issued inspectional observations and exercised oversight of each firm as they initiated recalls (in December 2022February 2023 and March 2023) to remove product potentially contaminated with Cronobacter sakazakii from the marketplace. 

Importantly, the FDA does not advise parents and caregivers to discard or avoid purchasing any particular infant formula at this time. The agency is not aware of any distributed product where contamination was confirmed and believes that the recalls were effective in removing the potentially contaminated batches of product from the market. Additionally, these warning letters are not associated with any current recalls and therefore the FDA does not anticipate any impact to the availability of infant formula on the market. 

The FDA is issuing these letters now as part of its normal regulatory process and to reinforce to these firms the importance of instituting and maintaining appropriate corrective actions when they detect pathogens to ensure compliance with the FDA’s laws and regulations. As part of this, the firms must, among other things, thoroughly conduct root cause investigations and perform subsequent cleaning and sanitation activities. Notably, firms also need to properly evaluate their cleaning and sanitation practices, schedules, and procedures before releasing product. Each company will have 15 working days to respond to the FDA to explain what corrective actions they are taking. The FDA will assess the adequacy of the companies’ corrective actions in the agency’s review of the responses and during the FDA’s next inspection of each facility. During these inspections the agency will verify proper implementation of appropriate corrective actions taken by each company.

“Infant formula manufacturers are responsible for ensuring they make safe products, and the agency has remained in ongoing discussions with the infant formula industry to address the agency’s concerns. The FDA is committed to identifying and acting on issues early to prevent any firms from reaching the level of concern that prompted last year’s large-scale recall and contributed to the infant formula shortage,” said Donald Prater, acting director of the FDA’s Center for Food Safety and Applied Nutrition. “Over the last year the FDA has continued to increase our oversight of powdered infant formula facilities. These letters are a reflection of this enhanced oversight and are intended to help the industry continuously improve the safety of their manufacturing practices, so that parents and caregivers can be confident that the formula they feed their children is safe and nutritious.”

Today’s actions are the latest in the FDA’s ongoing effort to strengthen the safety and resiliency of the infant formula supply in the U.S. In November 2022, the agency released an outline of a prevention strategy to prevent Cronobacter sakazakii illnesses associated with consumption of powdered infant formula. As part of that strategy, the FDA has been working with Congress to strengthen our regulatory tools and increase funding to oversee the infant formula industry and has worked closely with the U.S. Center for Disease Control and Prevention (CDC) to support the Council of State and Territorial Epidemiologists decision to add invasive Cronobacter infections among infants under one year of age to the Nationally Notifiable Conditions List. The agency has already started to hire staff as part of our work to establish a dedicated cadre of infant formula investigators and an Office of Critical Foods, both of which will strengthen the regulatory oversight of infant formula. 

Healthy supply of infant formula available in the U.S. market

Consumers should know that the U.S. infant formula supply is healthy with in-stock rates at 85% or higher since the beginning of 2023. The current strength of this market can be largely attributed to the many actions taken by the FDA and other U.S. government partners through 2022 and 2023, which are outlined in the FDA’s National Strategy to Increase the Resiliency of the Infant Formula Market.

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Ensuring the safety of powdered infant formula at home

Parents and caregivers should follow manufacturer instructions for preparing powdered infant formula. For babies less than 2 months old, born prematurely, or with weakened immune systems the CDC recommends, if possible, using ready-to-feed liquid infant formula. Liquid infant formula is made to be sterile (without germs) and is the safest option for infants not receiving breast milk. However, parents and caregivers can also take extra steps to prepare powdered formula for these infant groups by heating water to at least 158°F/70°C to help protect against Cronobacter, adding the powdered infant formula and mixing, and then cooling the formula to body temperature (98.6°F) before feeding. 

However, certain metabolic and specialty products include statements on their packaging warning consumers against heating because heating that particular product above 100°F could result in a loss of vitamins and nutrients. Therefore, caregivers should be especially mindful of the manufacturer’s instructions included on the packaging for metabolic and specialty formulas.

The FDA will continue its regulatory oversight and engagement with industry to enhance infant formula safety, including continuing to conduct annual inspections of infant formula facilities, maintaining a dialogue with infant formula manufacturers on these issues, and furthering prevention-based research and activities.

In addition to around-the-clock regulatory work, the FDA remains steadfast in upholding the commitment to unify and strengthen the FDA Human Foods Program. This new vision comes as a result of the agency’s review of findings and recommendations from an external evaluation conducted by the Reagan-Udall Foundation, at the request of the FDA Commissioner, following the agency’s infant formula supply chain response. 

Source: FDA

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