Like it or not, e-bikes on Hilton Head are here – Charleston Post Courier

HILTON HEAD ISLANDPeople move to Hilton Head for all kinds of reasons. The beach, the golfing, the weather. Parker Wood came for the bike paths.

"Me being able to get around on a bicycle and having my independence was a big key," said Wood, 20. Because he was born before his eyes fully developed, he doesn't see perspective well enough to drive.

But he can hop on two wheels and zip the 18 miles to and from his two jobs busing tables and prepping drinks at restaurants. When Wood flips on his e-bike's pedal assist, the commute is both quicker and easier.

"My e-bike is my car," he said.

Parker Wood is seen in his reflector setting up the gadgets needed to ride his electric bike to work on Aug. 31, 2022, on Hilton Head. Wood uses his bike as his main form of transportation due to limited vision going between work and the gym routine. Andrew J. Whitaker/Staff

Not everyone is enthusiastic about sharing Hilton Head with e-bikes, which are heavier and can be faster than conventional bicycles.

But last month Town Council passed 5-1 an ordinance allowing them on the town's 64 miles of public pathways.

The one dissenting voter, Tamara Becker, told The Post and Courier the island has not figured out a way to ensure everyone's safety.

"If you don't have a solution that works, you don't put something on paper and call it a day," Becker said.

Small motorized vehicles are still not allowed on pathways.

However, for advocates the vote to allow e-bikes is not just a concession to South Carolina law, which considers"electric-assist bicycles" and "bicycles with helper motors" simply bicycles, not mopeds. Instead, enthusiasts like Wood hope the new ordinance ushers in a future in which e-bikes are a permanent part of the island's transportation ecosystem.

Parker Wood waves to a motorist while commuting to work on his electric bike on Aug. 31, 2022, on Hilton Head Island. Andrew J. Whitaker/Staff

Frank Babel, 80, is known for two things: biking and persistence.

When he retired to Hilton Head in 2004 he was appalled by its infrastructure for cycling. So he started a group called Squeaky Wheels.

"I was the guy who went to these meetings in the Town Hall and said 'You know, your maintenance is terrible. The pathways are dirty. We have no maps. How do you get across the street safely?'"

Eventually, he persuaded officials to his cause. The town invested in crosswalks, traffic signals and safety islands. It widened the pathways and added more of them.

Today a cyclist on Hilton Head can get pretty much anywhere on a paved trail that winds around neighborhoods and resorts, over wooden bridges and under tree canopies. Crashes have also gone down.

Thanks in large part to Babel and his organization, which morphed into Bike Walk Hilton Head Island, the League of American Bicyclists has three times named the island aBike Friendly Community.

Babel's success offers both an example of how the island can evolve and an explanation for why e-bikers want to come here.

"We plan (our vacations) around bike paths," said Deb Camp, 68, who'd come to Hilton Head from Florida with her husband, Warren Camp, 74. "He's enjoying it. We're getting out of the house."

Parker Wood rides down a bike path from work on Aug. 31, 2022, on Hilton Head Island. Andrew J. Whitaker/Staff

The Camps are exactly the kind of people e-bike advocates say the vehicles stand to benefit: those who wouldn't otherwise be able to ride.

"I'd gotten injured in the service and broke my back," said Warren Camp, who keeps a Vietnam Vet cap dangling from his bike frame. "Then I drove an e-bike in Fort Myers, and it changed my life forever."

Compared with a regular bike, Camp says e-bikes are more comfortable and easier to ride. He uses the pedal-assist feature "so I'm able to go twice, three times the distance without using a throttle," he said.

Camp pointed to a speedometer on the handlebar that shows how fast he's going usually around 11 mph on Hilton Head's pathways, he said.

And if he encounters walkers or slower-moving bikers on the trail?

Camp touched a lever and made a cheery ding. "Everybody likes a little bell," he said.

Jim Hall, owner of Hilton Head Electric Bicycle Co., wheels out one of the electric bikes from his shop on Aug. 31, 2022, in Hilton Head. Hall said recently electric bikes have been becoming more popular on the island as prices have been going down. Andrew J. Whitaker/Staff

The owner of Hilton Head Electric Bicycle Co., Jim Hall, said he sees a lot of folks like the Camps.

"The vast majority of (e-bike renters) were the older demographic," said Hall, who began building his fleet of e-bikes shortly after he and his wife bought the company in 2020. "Spouses that wanted to ride together, people with new hips and knees. ... We've outfitted bikes to allow folks to put their crutches on them."

The data the Halls collected from about 500 e-bike customers belied an image of buzzing swarms of young people tearing around the island; instead, "we had more people in their 80s than their 20s," Hall said.

Still, he acknowledged that some people react negatively to the sight of an e-bike. For someone used to the slender silhouette of a road bike or the easy-going attitude of a beach cruiser, e-bikes can appear like they've been injected with a growth hormone. Their tires are bigger and fatter, and the ones in Hall's shop can weigh 70 pounds.

"In fairness, people who are anti e-bike have concerns about colliding with someone on that," Hall said.

But e-bikes are not going away, at least as far as Hall can see. "There's more of them on the island every day, whether we're selling them or people are ordering them off of Amazon," he said.

The Halls do such a brisk business that they operate two separate shops now, what they call "the electric side" and "the acoustic side." The electric side makes more money.

"We've been blown away," Hall said. Ranging from about $1,000 to almost $4,000, his e-bikes both cost more and sell better.

Even he and his wife own a pair. With parking and traffic being such an issue on Hilton Head "it's a beautiful way to get around and go out," he said.

While e-bike enthusiasts can speak glowingly about their benefits for commuters, parents, people with disabilities, the environment the person responsible for dealing with collisions, the town'snew director of Public Safety, offered a more matter-of-fact perspective.

"I've been working (on Hilton Head Island) for over 30 years," said Bob Bromage. "I can assure you there have been numerous accidents involving bicycles and vehicles."

The way forward, Bromage said, is education.

On that assertion, he aligns both with the town's new ordinance, which requires anyone who rents or sells an e-bike to provide safety information, and with the national Bicycle Friendly America Program.

Amelia Neptune, who directs the program, said the organization now takes receptiveness to e-bikes into account when making Bicycle Friendly Community awards, which Hilton Head will apply for again in 2023.

"We want to see a community ... allowing e-bikes anywhere a bike would be, but coupling that with education," Neptune said.

For example, e-bike riders should know trail etiquette, how to be audible as they're passing, and why it's important to go at a reasonable speed.

Neptune pointed out that on a road with cars, bikers are at risk. On a trail with e-bikes, pedestrians are at risk. In either of those situations, education protects the most vulnerable.

In addition, town staff are looking at structural ways to enhance safety, said community planning manager Missy Luick. Those elements might include signs, rights of way, and centerline striping.

E-bikes are here already, Luick said. Insofar as the number and range of people using Hilton Head's pathways present difficulties, she said, "they're all good problems to have."

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Like it or not, e-bikes on Hilton Head are here - Charleston Post Courier

Ribociclib Can Add Almost 1 Year to Overall Survival for Patients With Aggressive Form of Breast Cancer – Pharmacy Times

Ribociclib with endocrine therapy was found to increase the median overall survival of patients with HR+/HER2- advanced breast cancer with visceral metastases to nearly 5 years.

Ribociclib (Kisqali; Novartis) was found to add nearly 1 year to overall survival (OS) in patients with aggressive hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (aBC).

In a pooled exploratory analysis of the MONALEESA phase 3 program presented at the 2022 European Society of Medical Oncology Congress (ESMO), researchers found that first-line treatment with ribociclib and endocrine therapy increased the median OS by 10.6 months, compared to endocrine therapy alone.

Patients who have visceral metastases typically have a worse prognosis and often demonstrate resistance to treatment, so as a clinician it is encouraging to see significant survival benefit with ribociclib in the first-line setting in patients with more aggressive disease, said Denise A. Yardley, MD, senior investigator, Breast Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, in a press release.

Ribociclib, a CDK4/6 inhibitor, is the only inhibitor that was found to benefit the OS of patients with HR+/HER2- aBC in all its phase 3 trials. National Comprehensive Cancer Network (NCCN) guidelines also recognize ribociclib as the only CDK4/6 inhibitor to benefit OS in patients with HR+/HER2- aBC.

The subgroup of patients with this aggressive form of aBC may have visceral metastases on the liver. Compared to endocrine therapy as a sole first-line treatment, ribociclib plus endocrine therapy increased the median OS from 38.1 months to 44.2 months.

Further, among patients who have 3 or more organs with visceral metastases, first-line treatment with ribociclib and endocrine therapy increased the median OS by 8.4 months compared to endocrine therapy alone, with the median OS rising from 49.3 months to 57.7 months.

According to Magnitude of Clinical Benefit Scale, which was created by ESMO, ribociclib had the highest ratings out of every CDK4/6 inhibitor on the scale.

Ribociclib is the only CDK4/6 inhibitor to show a consistent overall survival benefit in combination with endocrine therapy, while also maintaining quality of life across the phase 3 program, Yardley said in the press release.

Ribociclib, combined with an aromatase inhibitor or fulvestrant, is approved by the FDA as a first-line endocrine-based therapy for HR+/HER2- advanced or metastatic breast cancer. It has also been approved in more than 95 countries worldwide.

The goal for advanced breast cancer treatment is to help people live longer, and we are proud that Kisqali continues to deliver a significant survival benefit while also maintaining quality of life, even for those with harder-to-treat disease, said Jeff Legos, executive vice president, global head of Oncology and Hematology at Novartis, in the press release. We are committed to demonstrating what makes Kisqali a unique CDK4/6 inhibitor, thus providing patients and oncologists confidence in this therapeutic option.

Reference

Novartis. Novartis Kisqali adds one more year of survival benefit for broadest set of patients, including those with aggressive HR+/HER2- advanced breast cancer. Novartis website. September 9, 2022. Accessed on September 9, 2022. https://www.novartis.com/news/media-releases/novartis-kisqali-adds-one-more-year-survival-benefit-broadest-set-patients-including-those-aggressive-hrher2-advanced-breast-cancer

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Ribociclib Can Add Almost 1 Year to Overall Survival for Patients With Aggressive Form of Breast Cancer - Pharmacy Times

Discover the Mental and Physical Health Benefits of Fasting – Intelligent Living

Healthy fasting is therapeutic if appropriately done, and evidence supports this. Our body can cure itself if given the correct nourishment, movement, sleep, emotional wellness, and surroundings; fasting boosts its curing capabilities. Its vital for holistic health.

It has beneficial effects on physical, emotional, brain, and spiritual health. In fact, it exists as a practice in most religions (religious fasting). For example, Muslims reduce caloric intake for a period of time during Ramadan to cleanse the mind, body, and soul. Other religious fasts include Christians, Greek Orthodox Christians, Jews, Hindus, and Buddhists, reducing caloric intake on certain days of the week or year.

Fasting has been performed for millennia with favorable effects, but only lately have studies shown its significance in adaptive cellular responses that minimize oxidative damage and inflammation, optimize energy metabolism and heart health, and bolster cellular defense. Furthermore, it helps with weight loss because it depletes liver glycogen, causing lipolysis and ketone body production, which reduces body fat (fat percentage) and hip circumference.

Fasting is such a popular scientific research topic today that the number of these studies demonstrating how good it is for holistic health keeps growing. The outcomes of these studies show that it can make you smarter, increase longevity by slowing down the aging process, and heal diseases, digestive issues, neurodegenerative disorders, and neurological disorders (mood disorders). Other health effects include the prevention of cardiovascular disease and chronic diseases.

Fasting activates our inner intelligence via calorie restriction. Its straightforward science. Fasting lets the digestive system rest by halting calorie intake. This break saves energy that would have gone toward digesting food. This conserved energy is used for repair, recovery, development, rejuvenation, and healing, which are needed for curing every human disease.

What happens first when were sick? Reduced appetite. So, what does this tell us? Our body reduces appetite to save energy that would have gone to digestion for mending and repair instead. Fasting does the same thing. It activates good genes with protective mechanisms, such as the SIRT1 gene, which regulates longevity, inflammation, fat and glucose metabolism, and other health effects.

A PLOS One study found that fasting reduces hunger hormones, improves metabolism, and helps people lose weight. Chicago researchers tested intermittent fasting on 20 obese adults for eight weeks. It enhanced the participants insulin resistance and glucose regulation, reduced cravings, and increased the feeling of fullness. Furthermore, they felt better overall and experienced no side effects.

Most people today overeat by incessantly munching and nibbling. Constant and excessive eating and out-of-balance dietary intake can overload the digestive system, leading to illness and a majority of health-related problems. Fasting helps mend this damage.

Chronic fasting (long-term fasting) enhances the lower eukaryote lifetime by altering metabolic and stress resistance pathways. Intermittent fasting (short-term fasting) protects against diabetes, malignancies, heart disease, neurodegeneration, obesity, hypertension, asthma, and rheumatoid arthritis.

Most people fast by only drinking water, dubbed water fasting. Other versions include juice fasting (apple cider vinegar, lemonade, carrot juice, celery juice, etc.) and eating light, where participants primarily eat vegetables, fruits, and lean meats like fish and chicken. However, real fasting involves going without food, solid, and liquid (aside from water) for at least 12 hours.

Several variations exist. Sometimes spiritual disciplines like prayer and meditation are included, turning it into a ritual. These disciplines make the process easier by calming the psyche.

As mentioned, various methods (diets) exist; all deliver positive effects. Here are a few examples:

This is the most common style of fasting and the most accurate form. Except for water, no solids or liquids are consumed. For those doing an extended water fast (over three days), sometimes herbal teas, tonics, and broths are consumedbut absolutely no caffeine or alcohol.

People following this diet will only drink vegetable and fruit juices for the duration of the fast.

This variation allows anything liquid, like broth or pureed soups, smoothies, and juices.

Its odd to call this one a fast because you can eat. Nevertheless, this diet is for people looking to purify their bodies. They must eliminate all non-plant-based foods (only things like fruits, vegetables, nuts, seeds, and legumes are allowed).

Skipping meals regularly, known as intermittent fasting or partial fasting, is becoming increasingly popular worldwide. People realize its physical and mental health benefits. It enhances energy, moods, sleep, and sex life. However, it involves a set daily fasting time.

Intermittent fasting also has the following benefits:

There are over twenty variations of intermittent fasting. The most popular include:

This strategy entails daily periods of fastingof 18 hours and then eating a light meal every other day. On alternate days you can eat healthy things like vegetables, berries, nuts, lean protein, etc.

Every day, you consume within specific periods of time. For example, your daily fast may be limited to eating from midday to 8:00 p.m..

You follow a schedule of regular eating for five days, then two days of fasting (preferably water fasting).

This fast allows one meal a day, but not breakfast. It is also commonly referred to as the One Meal a Day diet (OMAD).

You designate a six-hour window per day in which you can eat.

Most people fast to shed weight, regulate blood sugar, cleanse themselves of toxins, or regain mental clarity and emotional stability. However, it is a difficult thing to do alone. For those that need a little motivation, inspiration, and guidance, there are many fasting or detox retreats worldwide.

In addition, a growing number of medical clinics are offering guided fasting treatments. During these rehabilitation sessions, physicians supervise patients while undertaking water-only or very low-calorie (less than 200 kcal/day) fasting periods of one week or more. People participate for help in weight management or disease treatment and prevention.

Mexico has fasting pods, aka Fast incubators. These locations surround individuals with nature and block out food odors and noise. One can fast for 10 to 30 days. As a result, various disorders have reportedly healed faster. Many even experience improved eyesight and hearing.

While fasting is a simple concept, it can perplex many people due to the abundance of claims, methods, and precautions floating around the internet. However, it does not have to be challenging. On the contrary, it should be second nature to us.

Circadian rhythm fasting is the most natural and realistic technique to fast. In laymans terms, sunset to sunrise fasting involves eating ones last meal of the day early (near to or with sundown) and breaking it after sunrise. This provides for a minimum of 12-hour fasting and is one of the most efficient strategies to incorporate the practice into your lifestyle.

If you are still not hungry after 12 hours, gently extend your fast until you experience actual physical hunger, and then break youre fast correctly. You are not required to have breakfast if you arent hungry. Not feeling hungry in the morning indicates that your body is still detoxifying and processing your evening meal. Respect your body by fasting accordingly.

Fasting while sleeping is ideal since all critical detoxification, repair, and recovery processes occur during deep sleep. Our bodies detoxify at night, and the physical health benefits are more noticeable when fasting.

When you want to break the fast, however, it is entirely up to you and the signs your body is sending. Some people wake up hungry, while others do not till the afternoon. Pay attention to your body. There is a distinct distinction between fasting and starvation. If you are not hungry, respect your hunger and continue your fast for a few more hours.

Breaking a fast gently awakens your digestive system. So, gorging after a fast is terrible. It could overwhelm your stomach. Water breaks a dry fast best. Take a few sips, then eat fruit or 1-2 fresh dates. After 30-40 minutes, cook a wholesome meal. This is particularly important for long fasts.

Some fasters drink tea, coffee, or juice. Acidic drinks can damage stomach linings. Therefore, one should fast appropriately or not at all. If opting for juice fast, stick with vegetable juice like celery, green juice, or non-acidic fruits. Likewise, teas should be caffeine-free and herbal only (lavender, jasmine, etc.).

Theres no one-size-fits-all answer. Some find fasted workouts beneficial, while others find them hazardous. Fasted workouts depend on objectives, energy and hunger levels, training, and health conditions. However, do it if you can because fasted workouts are fantastic for insulin resistance, weight loss, and abdominal fat.

Note: Your body needs time to acclimate to a fast before you experience mental changes. You may get headaches or discomfort early on. Your brain is granted a cleaner bloodstream after your body eliminates toxins. This improves your thoughts, emotions, memory, and other senses.

Fasting causes ketogenesis, promotes potent changes in metabolic pathways and cellular processes such as stress resistance, lipolysis, and autophagy, and can have medical applications that are as effective as approved drugs, such as dampening seizures and seizure-associated brain damage, alleviating rheumatoid arthritis, and maximizing holistic health, as explained in the rest of this page.

Fasting uses up excess carbohydrates. The body burns fat. The metabolic rate rises, unlike with caloric restrictionweight loss results.

Half of our energy goes into digestion. This energy can be used to heal and regenerate, which happens during a fast. The human body recognizes what needs mending.

Sick and weaker cells are killed after 24-36 hours via apoptosis and autophagy, then recycled into new cells. Its natural. Apoptosis kills 50 to 70 billion human cells daily. Fasting boosts this rate.

Stem cell production and activation rise after fasting. The number of new stem cells and HGH peak during days 3-5 of a fast, then fall. Additional research shows that new white blood cells are created with increased stem cell growth, boosting the immune system.

Besides fat burning and strengthening the immune system, it reduces inflammation, rebalances the gut microbiome and hormones, protects the brain from neurological diseases, reduces cancer risk, slows aging, and promotes cell maintenance and repair.

Fasting is the best medicine, and its free!

Fasting has many powerful benefits, but its not for everyone. It should be avoided or done only under medical supervision in the following situations. People who are:

If you think you can do it, go for it! Fasting is the bodys natural stem cell therapy, renewing and regenerating the body. It is the ultimate biohack. Theres no better method to restore cells, improve healing, and increase energy and focus.

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Discover the Mental and Physical Health Benefits of Fasting - Intelligent Living

Biosimilars Global Market Opportunities and Strategies Report 2022: Long-term Forecast to 2026 & 2031 – ResearchAndMarkets.com – Business Wire

DUBLIN--(BUSINESS WIRE)--The "Biosimilars Global Market Opportunities And Strategies To 2031" report has been added to ResearchAndMarkets.com's offering.

The global biosimilars market reached a value of nearly $11,418.9 million in 2021, having grown at a compound annual growth rate (CAGR) of 34.8% since 2016. The market is expected to grow from $11,418.9 million in 2021 to $25,985.2 million in 2026 at a rate of 17.3%. The market is then expected to grow at a CAGR of 18.0% from 2026 and reach $59,555.8 million in 2031.

This report describes and explains the biosimilars market and covers 2016-2021, termed the historic period, and 2021-2026 termed the forecast period, along with further forecasts for the period 2026-2031. The report evaluates the market across each region and for the major economies within each region.

Growth in the historic period resulted from an increase in cancer prevalence, strong economic growth in emerging markets, an increase in pharmaceutical R&D expenditure, increased healthcare expenditure, growing government initiatives, strong pipeline of drugs, low cost of biosimilars and an increase in patent expiration.

Factors that negatively affected growth in the historic period were regulatory changes, low healthcare access, lack of awareness on biosimilars among primary care physicians and specialists, reimbursement challenges, the coronavirus pandemic and low healthcare reimbursements.

Going forward, increasing prevalence of cancer, increasing demand for prophylaxis with granulocyte colony-stimulating factor (G-CSF), a rise in healthcare expenditure, high potential of emerging economies, technology advances, high penetration of biological drugs, aging population and an increase in healthcare access will drive the growth. Factors that could hinder the growth of the biosimilars market in the future include high costs of drugs, high cost of drug development with threat of failure, pricing pressures from regulators and insufficient and outdated health system.

The biosimilars market is segmented by type into monoclonal antibodies, insulin, erythropoietin, granulocyte-colony stimulating factor, other hormones and others. The monoclonal antibodies market was the largest segment of the biosimilars market segmented by type, accounting for 39.6% of the total in 2021. Going forward, the erythropoietin segment is expected to be the fastest growing segment in the biosimilars market segmented by type, at a CAGR of 28.2% during 2021-2026.

The biosimilars market is also segmented by application into oncology, chronic and autoimmune diseases, growth hormone deficiency, infectious diseases, and other applications. The chronic and autoimmune diseases market was the largest segment of the biosimilars market segmented by application, accounting for 45.6% of the total in 2021. Going forward, infectious diseases segment is expected to be the fastest growing segment in the biosimilars market segmented by end-user, at a CAGR of 24.8% during 2021-2026.

Western Europe was the largest region in the biosimilars market, accounting for 66.0% of the total in 2021. It was followed by North America, and then the other regions. Going forward, the fastest-growing regions in the biosimilars market will be Africa and Eastern Europe where growth will be at CAGRs of 117.0% and 60.1% respectively. These will be followed by South America and Middle East where the markets are expected to grow at CAGRs of 53.854% and 53.851% respectively.

The global biosimilars market is concentrated, with a small number of large players in the market. The top ten competitors in the market made up to 76.98% of the total market in 2021. The market concentration can be attributed to the high barriers to entry in terms of high costs associated with the research and development of pegfilgrastim biosimilars and the stringent regulations set up by the regulatory authorities.

Going forward the market is expected some fragmentation with the rising number of new entrants. Amgen was the largest competitor with 21.23% of the market, followed by Pfizer with 13.37%, Novartis AG with 10.13%, Samsung Bioepis Co., Ltd. with 9.90%, Viatris with 7.37%, Biocon with 3.60%, Celltrion, Inc. with 3.24%, Coherus Biosciences with 4.17%, Elli Lilly and Company with 1.99%, and Dr. Reddy's Laboratories with 1.98%.

The top opportunities in the biosimilars market segmented by type will arise in the monoclonal antibodies segment, which will gain $8,508.0 million of global annual sales by 2026. The top opportunities in the biosimilars market segmented by application will arise in the oncology segment, which will gain $6,889.0 million of global annual sales by 2026. The biosimilars market size will gain the most in the USA at $6,677.4 million.

Market-trend-based strategies for the biosimilars market include focus on robust R&D activities for the development of effective and innovative drugs, focus on focus on M&A growth strategies, focus on establishing strategic partnerships, focus on increasing investments and focus on artificial intelligence.

Player-adopted strategies in the biosimilars market include strengthening product portfolio by new products launches, focusing on expansion strategies in different geographies and increasing research and development for new product development by collaborating with companies having same business.

To take advantage of the opportunities, the publisher recommends the biosimilars companies to launch new products, invest in robotics and artificial intelligence (AI), expand in emerging markets, scale up through merger and acquisition activity, provide competitively priced offerings, continue to participate in events and conferences, take initiatives to educate consumers, target high-growth application areas and increase strategic partnerships.

Key Topics Covered:

1. Biosimilars Market Executive Summary

2. Table of Contents

3. List of Figures

4. List of Tables

5. Report Structure

6. Introduction and Market Characteristics

6.1. General Market Definition

6.2. Summary

6.3. Market Segmentation By Type

6.3.1. Monoclonal Antibodies

6.3.2. Insulin

6.3.3. Erythropoietin

6.3.4. Granulocyte-Colony Stimulating Factor

6.3.5. Other Hormones

6.3.6. Other Types

6.4. Market Segmentation By Application

6.4.1. Oncology

6.4.2. Chronic and Autoimmune Diseases

6.4.3. Growth Hormone Deficiency

6.4.4. Infectious Diseases

6.4.5. Other Applications

7. Major Market Trends

7.1. Robust Research & Development

7.2. Demand For Biosimilars In The Treatment Of Neutropenia

7.3. Growing Mergers And Acquisitions

7.4. Revised FDA Regulations To Facilitate Biosimilar Drug Development

7.5. Large Number Of Strategic Partnerships

7.6. Increasing Investments In Biosimilars Market

7.7. Use of Robots and AI

8. Global Market Size And Growth

8.1. Market Size

8.2. Historic Market Growth, 2016 - 2021, Value ($ Million)

8.2.1. Market Drivers 2016 - 2021

8.2.2. Market Restraints 2016 - 2021

8.3. Forecast Market Growth, 2021 - 2026, 2031F Value ($ Million)

8.3.1. Market Drivers 2021 - 2026

8.3.2. Market Restraints 2021 - 2026

9. Global Biosimilars Market Segmentation

9.1. Global Biosimilars Market, Segmentation By Type, Historic And Forecast, 2016 - 2021, 2026F, 2031F, Value ($ Million)

9.2. Global Biosimilars Market, Segmentation By Application, Historic And Forecast, 2016 - 2021, 2026F, 2031F, Value ($ Million)

10. Biosimilars Market, Regional And Country Analysis

10.1. Global Biosimilars Market, By Region, Historic and Forecast, 2016 - 2021, 2026F, 2031F, Value ($ Million)

10.2. Global Biosimilars Market, By Country, Historic and Forecast, 2016 - 2021, 2026F, 2031F, Value ($ Million)

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/7k2tzs

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Biosimilars Global Market Opportunities and Strategies Report 2022: Long-term Forecast to 2026 & 2031 - ResearchAndMarkets.com - Business Wire

Lumos Pharma to Participate in the HC Wainwright 24th Annual Global Investment Conference – GuruFocus.com

AUSTIN, Texas, Aug. 31, 2022 (GLOBE NEWSWIRE) -- Lumos Pharma, Inc. (LUMO, Financial), a biopharmaceutical company advancing a novel oral therapeutic candidate, LUM-201, through Phase 2 clinical trials for Pediatric Growth Hormone Deficiency (PGHD), announced that the Company will present and host one-on-one meetings at the H.C. Wainwright 24th Annual Global Investment Conference in September.

The webcast for the presentation can also be found on the Companys website under Events & Presentations in the Investors & Media section. Please contact your H.C. Wainwright salesperson, or Lumos Pharma Investor Relations, to schedule one-on-one meetings with the management team during the conference or thereafter.

About Lumos Pharma

Lumos Pharma, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of therapeutics for rare diseases. Lumos Pharma was founded and is led by a management team with longstanding experience in rare disease drug development and received early funding from leading healthcare investors, including Deerfield Management, a fund managed by Blackstone Life Sciences, Roche Venture Fund, New Enterprise Associates (NEA), Sant Ventures, and UCB. Lumos Pharmas lead therapeutic candidate is LUM-201, an oral growth hormone stimulating small molecule, currently being evaluated in a Phase 2 clinical trial, the OraGrowtH210 Trial, a PK/PD trial, the OraGrowtH212 Trial, and a switch trial, the OraGrowtH213 Trial for the treatment of Pediatric Growth Hormone Deficiency (PGHD). If approved by the FDA, LUM-201 would provide an orally administered alternative to recombinant growth hormone injections that PGHD patients otherwise endure for many years of treatment. LUM-201 has received Orphan Drug Designation in both the US and EU. For more information, please visit https://lumos-pharma.com/.

Investor & Media Contact:

Lisa MillerLumos Pharma Investor Relations512-792-5454[emailprotected]

Source: Lumos Pharma, Inc.

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Lumos Pharma to Participate in the HC Wainwright 24th Annual Global Investment Conference - GuruFocus.com

The Global External Fixation Systems Market to Witness Growth at a CAGR of 5.62% During the Study Period (20192027) | DelveInsight – Yahoo Finance

DelveInsight Business Research LLP

The external fixation systems market is anticipated to surge due to the factors such as the increasing prevalence of degenerative bone disorders such as osteoporosis and osteoarthritis. Another prominent factor contributing to product demand growth is the surge in the global increase in the geriatric population base, who form a major section of the patient pool of fractures due to frequent falls and degenerative bone diseases. The increasing focus on product development activities with the latest innovation with respect to external fixators also plays a key role in establishing a positive growth trend in the external fixation systems market during the forecast period from 2022 to 2027.

New York, USA, Sept. 01, 2022 (GLOBE NEWSWIRE) -- The Global External Fixation Systems Market to Witness Growth at a CAGR of 5.62% During the Study Period (20192027) | DelveInsight

The external fixation systems market is anticipated to surge due to the factors such as the increasing prevalence of degenerative bone disorders such as osteoporosis and osteoarthritis. Another prominent factor contributing to product demand growth is the surge in the global increase in the geriatric population base, who form a major section of the patient pool of fractures due to frequent falls and degenerative bone diseases. The increasing focus on product development activities with the latest innovation with respect to external fixators also plays a key role in establishing a positive growth trend in the external fixation systems market during the forecast period from 2022 to 2027.

DelveInsight's External Fixation Systems Market Insights report provides the current and forecast market, forthcoming device innovation, individual leading companies market shares, challenges, external fixation systems market drivers, barriers, and trends, and key external fixation systems companies in the market.

Key Takeaways from the External Fixation Systems Market Report

As per DelveInsight estimates, North America is anticipated to dominate the global external fixation systems market during the forecast period.

Notable external fixation systems companies such as DePuy Synthes (Medical Devices Business Services, Inc), Orthofix Medical Inc, Stryker Corporation, Smith & Nephew, Acumed, Zimmer Biomet, Baumer S.A., Globus Medical, Orthosynthesis (Ortosintese), Mikai S.p.A, SOFEMED, Advanced Orthopaedic Solutions., Fixus B.V., Tasarimmed Tbbi Mamuller San. Tic A.., Zimed Medikal, NUTEK ORTHOPEDICS, Double Medical Technology Inc., Auxein Medical, Wishbone Medical Inc, Aike (Shanghai) Medical Equipment Co., Ltd., Orthospin, and several others are currently operating in the external fixation systems market.

In March 2022, Orthofix Medical Inc received regulatory approval from the U.S. Food and Drug Administration 510(k) and the first patient cases with the TrueLok EVO Ring Fixation System. Designed for complex limb reconstruction and deformity correction procedures, the TrueLok EVO system. It is the market's only circular fixator that features radiolucent rings and struts to enable clear radiographic visualization.

In November 2021, Paragon 28, Inc was granted regulatory approval by the US FDA for its circular external fixation system. The system was expected to be launched in early 2022.

In January 2021, Orthospin received US FDA approval for their robotic external fixation system.

In October 2020, Wishbone Medical Inc received product approval from the US FDA for their pediatric external fixation system.

Thus, owing to such market developments, rapid growth will be observed in the external fixation systems demand during the forecast period.

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To read more about the latest highlights related to the external fixation systems market, get a snapshot of the key highlights entailed in the Global External Fixation Systems Market Report

External Fixation Systems

An external fixator device is screwed into fractured bones to exit the skin and connect to a stabilizing structure outside the body. External fixation is a well-established technique for stabilizing a variety of fractures and also aids in bone lengthening.

External fixators shorten treatment time and necessitate less surgical intervention. Computer-aided external fixators have become increasingly popular for fracture fixation and deformity correction in recent years. External fixators that are computer-aided can work with or without computer-aided solution software. A computer-aided external fixator is a six-axis external fixator with multi-planer corrections, increased accuracy, and fewer complications.

External Fixation Systems Market Insights

The global external fixation systems market is studied geographically for North America, Europe, Asia-Pacific, and the Rest of the World. North America is expected to amass a significant revenue share in the global external fixation systems market during the forecast period, with the largest market share. This can be attributed to the region's high prevalence of osteoarthritis, osteoporosis, and other bone diseases, rising elderly population, increasing number of road accidents and trauma cases, and other factors. Furthermore, high disposable income, sophisticated healthcare infrastructure, and increased awareness of new treatments are expected to contribute to the growth of the external fixator devices market in this region. However, the European external fixation systems market will majorly challenge North America's dominance.

The high prevalence of osteoporosis in North American countries such as the United States is one of the key factors driving the growth of the North American external fixator devices market. Furthermore, the Asia Pacific region has future growth potential in the external fixation systems market. This is due to the presence of a large patient pool suffering from musculoskeletal conditions.

To know more about why North America is leading the market growth in the external fixator devices market, get a snapshot of the External Fixation Systems Market Share

External Fixation Systems Market Dynamics

The global external fixation systems market is expected to expand significantly due to an increase in the number of road accidents and trauma cases resulting in extremity fractures. Furthermore, the global increase in the geriatric population plays a significant role in the growth of external fixation systems, as aging increases the chances of developing degenerative bone disorders, which may increase the chances of bone fractures in the elderly population. Furthermore, technological advancements have increased interest in developing devices made using computer-aided design (CAD)- smart external fixation systems, which is another factor driving the growth of the external fixation systems market.

However, the high maintenance and compliance costs associated with external fixators and the high risk of infection at attachment sites may be some of the external fixators market's limiting factors.

Additionally, the external fixation systems market suffered a temporary setback as lockdown restrictions were imposed as a necessary step to slow the spread of COVID-19. One of the most significant steps taken during this period was the suspension of numerous elective procedures and outpatient visits, which reduced demand for external fixation systems in the market because a large number of surgeries across various medical specialties were suspended during the initial lockdown period, thereby limiting market growth for a short period. Furthermore, the lockdowns restricted outdoor recreational activities and road movement, resulting in fewer incidents of road accidents in general compared to previous years and fewer cases associated with orthopedic injuries during the lockdown period.

Nonetheless, the external fixators devices market is in a period of recovery, with the resumption of activities across various domains, including healthcare services, as a result of the approval and administration of numerous COVID-19 vaccines around the world, presenting a positive future outlook for the external fixation systems market from 20222027.

Scope of the External Fixation Systems Market Report

Coverage: Global

Study Period: 20192027

Market Segmentation By Product Types of External Fixator Devices: Unilateral, Circular, Hybrid, and Others

Market Segmentation By Application: Upper Extremity, Lower Extremity, and Other

Market Segmentation By Manufacturing Technique: Conventionally-Made and Computer-Aided

Market Segmentation By End User: Hospitals, Specialty Clinics, and Others

Market Segmentation By Geography: North America, Europe, Asia-Pacific, and Rest of World

Key External Fixation Systems Companies: DePuy Synthes (Medical Devices Business Services, Inc), Orthofix Medical Inc, Stryker Corporation, Smith & Nephew, Acumed, Zimmer Biomet, Baumer S.A., Globus Medical, Orthosynthesis (Ortosintese), Mikai S.p.A, SOFEMED, Advanced Orthopaedic Solutions., Fixus B.V., Tasarimmed Tbbi Mamuller San. Tic A.., Zimed Medikal, NUTEK ORTHOPEDICS, Double Medical Technology Inc., Auxein Medical, Wishbone Medical Inc, Aike (Shanghai) Medical Equipment Co., Ltd., Orthospin, among others

Porters Five Forces Analysis, Product Profiles, Case Studies, KOLs Views, Analysts View

DelveInsight Analysis: The external fixation systems market size is expected to grow at a CAGR of 5.62% to reach USD 1.26 billion by 2027.

Which MedTech key players in the external fixation systems market are set to emerge as the trendsetter explore @External Fixation Systems Companies

Table of Contents

1

Report Introduction

2

Executive summary

3

Regulatory and Patent Analysis

4

Key Factors Analysis

5

Porters Five Forces Analysis

6

COVID-19 Impact Analysis on External Fixation Systems Market

7

External Fixation Systems Market Layout

8

Global Company Share Analysis Key 3-5 Companies

9

External Fixation Systems Market Company and Product Profiles

10

Project Approach

11

About DelveInsight

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The Global External Fixation Systems Market to Witness Growth at a CAGR of 5.62% During the Study Period (20192027) | DelveInsight - Yahoo Finance

Role of Sirtuins in Diabetes and Age-Related Processes – Cureus

Intermittent fasting is a rapidly growing health practice worldwide that consists of alternating periods of eating and fasting done on a regular basis[1]. According to the International Food Information Councils (IFIC) Food and Health Survey, 43% of Americans claim to be following a specific diet or eating pattern and 10% of those individuals follow intermittent fasting, making it the most popular diet[2]. Intermittent fasting is not a traditional type of diet in which food intake is limited, but instead controls the timing of food consumption. Common fasting regimens include alternate day fasting, fasting two out of seven non-contiguous days of the week, and eating during limited time intervals of each day[3]. With decreased energy intake, the body continues to consume glucose from glycogen stores. As glycogen stores are depleted, the mobilization of fatty acids and the creation of ketone bodies begins[3]. These processes trigger an increase in growth hormone and a decrease in insulin that results in the promotion of fat usage and loss to create more efficacious energy.

One of the main reasons for the rise in popularity of intermittent fasting is the feasibility of following such a program. For instance, limiting food intake to eight hours a day is doable even with a busy schedule. Similar to the ways of hunter-gatherers facing periods of food shortage, fasting promotes evolutionarily conserved adaptations for increasing weight loss, decreasing insulin resistance, and preventing age-related processes and diseases[1]. During periods of feeding, cells engage in growth processes regardless of cell conditions. However, during fasting, cell pathways are activated to defend against meal-induced oxidative and metabolic stress and promote tissue repair[3].

Aside from the postulated health benefits of intermittent fasting,certainforms of caloric restriction cause an increase in sirtuin proteins. Sirtuin proteins (SIRTs) are a class of nicotinamide adenine dinucleotide (NAD) dependent lysine-specific deacetylases and represent homologs of yeast silent information regulator (SIR2)[4]. These class three histone deacetylases are enzymes that remove an acetyl group from N-acetyl-lysine residues on protein substrates[5]. Currently, seven isoforms of SIRTs exist in mammals. SIRT1, SIRT6, and SIRT7 are localized to the nucleus, SIRT2 is cytoplasmic, and SIRT3, SIRT4, and SIRT5 are mitochondrial proteins[5]. Since SIRTs are located throughout the cells, a wide variety of cell functions exist. Some of these physiological functions include regulation of healthy aging, genome stability, mitochondrial physiology and biogenesis, and cellular metabolism[4]. The wide expanse of SIRT functions also leads to implications for certain pathological processes and possible novel targets for therapy. SIRT activation can be useful against aging-related disorders of metabolism, cardiovascular and neurodegenerative diseases, and other vascular processes. On the other hand, SIRT inhibition can be of use in controlling the progression of cancer, HIV, and other muscular diseases[6]. Some of these effects will be further explored in this review.

As previously mentioned, intermittent fasting may help alleviate obesity, insulin resistance, inflammation, and other age-related processes. Specifically, intermittent fasting has been reported to reverse insulin resistance in people with type 2 diabetes mellitus[3]. Caloric restriction leads to lower levels of insulin-like growth factor, growth hormone, and inflammatory markers that are in part responsible for the pathogenesis of type 2 diabetes[3]. One study in 2003 reported significant reductions in percent body fat, hemoglobin A1c (HbA1c), and triglyceride levels from intermittent fasting[7]. By measuring various health markers at baseline and after periods of intermittent fasting, beneficial effects have been reported in the form of increasedcell and tissue resistance against common diseases associated with aging, sedentary lifestyles, and overconsumption[1].

Many SIRT activators currently exist and are in use for their health benefits such as green tea, turmeric, and kale. Currently, SIRT1 is the most studied isoform for its role in caloric restriction and as a target in preventing age-related diseases[6]. Resveratrol, a plant polyphenol made in response to infections, also acts as an activator of SIRT1[8]. Dietary sources of resveratrol can be found in grapes, red wine, and peanuts. Resveratrol has been reported to delay age-related diseases through its actions as a SIRT1 activator, and its use and features have become a popular field of interest in recent years[9].

This review will explore and detail the vast effects of intermittent fasting and caloric restriction mimetics such as resveratrol and other SIRT activators as they relate to the pathogenesis of age-related processes and their potential as useful therapeutics. The specific aim of this review is to elucidate the role of sirtuin proteins on various disease processes including type 2 diabetes mellitus and certain forms of cancer. The goal is to clarify the interaction between intermittent fasting resulting in an increase in sirtuin proteins throughout the body and how these increased levels affect the progression of disease in both positive and negative ways.

The PubMed database was searched for peer-reviewed articles written in English using the following criteria. Five separate searches were conducted for different areas of interest. Each search used the keyword Sirtuin in the title as sirtuins are of primary focus in this review. The five searches conducted were as follows: Sirtuin and Diabetes in the title, Sirtuin and Fasting in the title, Sirtuin and Vascular in the title, Sirtuin and Age in the title, and Sirtuin and Review in the title. A total of 116 papers met the keyword search criteria. References used by the resulting papers were also accessed as needed.

SIRTs are evolutionarily conserved proteins that exist in a wide variety of organisms ranging from bacteria to humans[10]. SIRTs are NAD+ dependent deacetylases and since NAD+ is needed for most enzymatic activitiesSIRTs may also function as metabolic sensors that affect the pathophysiology of aging[11]. Of the various precursors for NAD, nicotinamide was reported to be more effective than nicotinic acid in regulating glucose metabolism and the SIRT1 pathway[11]. Numerous experiments on multiple species including yeast, flies, and mice have indicated that deleting SIRTs removes the beneficial effects of caloric restriction resulting in reduced longevity[4]. Substrates of various processes are specific to each SIRT; the role of SIRT1 in chromatin remodeling and DNA damage response is one example[10]. Some SIRT-related functions overlap between the seven isoforms of SIRTs, such as SIRT1 and SIRT2 both regulating hepatic gluconeogenesis. Furthermore, organ systems can be grouped to study how various SIRTs affect processes. For instance, SIRT1 through SIRT6 have metabolic functions in the liver and can be further studied for the possible development of novel therapies against age-related diseases of the liver[10].

As shown inFigure 1, SIRTs can be categorized into specific locations by organ system throughout the body[10]. In these organ systems, SIRTs have specific deacetylation activities on protein substrates that are vital to metabolic processes. These diverse biological functions play a crucial role in DNA repair, mitochondrial biogenesis, antioxidant production, and cellular metabolism[12]. Some functions of SIRTs specific to each organ are included in the figure to provide examples of organ-specific roles. Although redundancy exists between protein substrates and SIRTs, each has a specific role in modulating oxidative stress, inflammation, and dysfunction[13].By acting on the multifactorial processes of aging, pathological changes and progressive decline can be minimized.

Due to the numerous reported health benefits of SIRTs, research has been directed towardthe discovery of SIRT activators, with activators of SIRT1 being the most studied. One such activator is resveratrol, a small polyphenol, which can increase SIRT1 activity 13-fold resulting in beneficial effects on cataracts, bone structure, vascular health, and locomotor activity leading to improvements in general health[4]. One of the most abundant natural sources of resveratrol is from grape seeds of Vitis vinifera, the common grape vine used to make wine[4]. To test resveratrols impact on energy metabolism and mitochondrial function, 11 healthy, obese men consumed 150 mg of resveratrol per day for 30 days[14]. In this study, resveratrol was reported to activate SIRT1, decrease triglyceride levels, and improve muscle mitochondrial respiration. These metabolic changes mimic the effects of caloric restriction associated with intermittent fasting. Resveratrol can be absorbed in the gastrointestinal tract and distributed throughout the body to prevent cardiovascular disease, protect pancreatic cells by inhibiting poly-ADP ribose polymerase, a family of proteins involved in cellular processes, and alleviate metabolic syndrome all by acting as a free radical scavenger[15].

In addition, a SIRT1 activator with 1000-fold greater potency compared to resveratrol called SRT1720 has been synthesized and reported to be efficacious against type 2 diabetes mellitus and cancer in mice[4]. SRT1720 was also reported to improve cognitive function in mice with type 2 diabetes mellitus along with increasing body weight, reducing fasting blood glucose, and minimizing proteins associated with oxidative stress and inflammatory damage[16]. Much is yet to be learned regarding SIRTs and their various roles.

When studying the pathogenesis of age-related diseasesin mice, different methods were used to demonstrate the effects of a deletion of SIRT1 in various organs. Withthe utilization of myeloid cell-specific SIRT1 knockout mice, deletion of SIRT1 resulted in increased transcription of proinflammatory target genes, reactive oxygen species, and an amplified inflammatory response[17]. These changes mimic those experienced in many chronic inflammatory diseases and predispose the mice to developing insulin resistance and metabolic disorders.An additional result of SIRT1 deletion is an increase in nuclear factor kappa beta (NF-kB) dependent proinflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and many others[18]. The potential importance of such changes is exemplified by considering the role of NF-kB in regulating inflammation involved in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis[19]. Overexpression of SIRT1 in the liver helps decrease these proinflammatory cytokines by downregulating NF-kB, but deletion of SIRT1 exacerbates hepatic inflammation[19]. A similar trend of different transcription factors affecting disease processes can be seen with pancreatic and duodenal homeobox factor 1 (PDX1) and Forkhead box class O (FOXO). PDX1 plays an important role in pancreatic development and beta cell differentiation, and mutation in the PDX1 gene can cause maturity-onset diabetes in the young[19]. SIRT1 expression in beta cells helps enhance insulin production to manage glucose levels and prevent the onset of diabetes. SIRT1 regulates FOXO transcription, and FOXO controls biological responses to prevent neurodegeneration in response to oxidative stress[18]. Specifically, FOXO prevents the accumulation of alpha-synuclein in the brain and age-mediated memory deficits[19]. A number of these processes will be further elucidated in this review.

SIRT6, a sirtuin protein that localizes to the nucleus, has recently been a topic of interest due to its confounding roles in metabolic homeostasis. Since SIRT6 is found in the nucleus, it is primarily involved in modulating transcription by histone deacetylation of chromatin[20]. SIRT6 levels increase in response to nutritional stress through the regulation of SIRT1. SIRT6 is increased in the heart, kidney, brain, and white adipose tissue after periods of caloric restriction and is decreased in insulin-resistant mice and humans. Overexpression of SIRT6 in mice provides protection against metabolic pathologies from diet-induced changes, but SIRT6 knockout mice have increased glucose transport and decreased levels of TNF-alpha in the serum which has a negative effect on insulin resistance[21]. The controversy regarding activation or inhibition of SIRT6 activity as a therapeutic against type 2 diabetes mellitus stems from the idea that SIRT6 inhibition is able to prevent the repression of glucose transporters and enzymes[20]. One study administered a SIRT6 inhibitor to mice for 10 days and saw an improvement in glucose tolerance, increased expression of glucose transporters, and decreased insulin, triglycerides, and cholesterol levels in serum[22]. On the other hand, another study monitored diabetic wound healing in SIRT6 knockdown mice and found increased levels of oxidative stress, decreased angiogenesis and vascularization, and impaired wound closure[23]. With these increased levels of oxidative stress in the vasculature, SIRT6 deficiency leads to endothelial dysfunction seen in various aging processes[24]. As activators and inhibitors of specific SIRTs are still lacking, more research is needed to fully understand methods to improve glycemic control in type 2 diabetes.

SIRT1 plays a major role in the regulation of metabolic homeostasis, and as a result, any changes causing downregulation can stimulate pathways leading to chronic complications of diabetes mellitus and its comorbidities. Specifically, during a fasting state, decreased insulin and increased glucagon stimulate gluconeogenesis. Increased caloric restriction causes a SIRT1-dependent decrease in glucose, increased catabolism of fatty acids, decreased cholesterol uptake into the intestine, and limited fatty liver disease and inflammation[25]. A link between FOXO, signal transducer and activator of transcription 3 (STAT3), and SIRT1 has been identified to regulate gluconeogenesis[26]. Specifically, SIRT1 regulates the deacetylation of STAT3, deactivating it, and preventing transcription of genes involved in gluconeogenesis in normal conditions. However, in a fasting state, SIRT1 triggers deacetylation of FOXO and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1a) which induces gluconeogenesis and inhibits glycolysis in the liver. These changes reflect the beginning stages of type 2 diabetes mellitus with insulin resistance and hyperglycemia.

Many commonly used agents for the treatment of type 2 diabetes mellitus can alter SIRT1 levels and activity. For example, research suggests that SIRT1 mediates metformins effects in suppressing hepatic gluconeogenesis, activating fatty acid oxidation, and preventing hyperglycemia-induced retinal damage[10]. Furthermore, metformin used with caloric restriction, such as intermittent fasting, increased the expression of SIRT1 and furthered these beneficial effects[25]. Incretin mimetics, also known as glucagon-like peptide-1 (GLP-1) agonists, and dipeptidyl peptidase-4 (DPP4) inhibitors are both common classes of drugs used in the treatment of diabetes. Both stimulate pathways leading to upregulation of SIRT1 to limit oxidative stress and alleviate the progression of insulin resistance[25]. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are another class of medications used in type 2 diabetes mellitus. This class of drugs has dual effects on slowing the progressive loss of renal function in those with diabetes. Compared to both GLP-1 agonists and DPP4 inhibitors, SGLT2 inhibitors are accompanied by comparable decreases in blood glucose but increased benefit in maintaining glomerular function and preventing adverse renal outcomes[27]. Specifically, SGLT2 inhibitors trigger a fasting-like state that induces both SIRT1 and adenosine monophosphate-activated protein kinase (AMPK) activation. SIRT1 and AMPK decrease cellular stress reducing possible glomerular and tubular injury seen in diabetic chronic kidney disease.

Another drug class commonly used to treat diabetes is thiazolidinediones, a class of oral hypoglycemics that promote adipogenesis and fatty acid uptake. One agent in this class is pioglitazone. A study was conducted on 44 obese, postmenopausal females who had or did not have type 2 diabetes to investigate the effects of fenofibrate, a medication to lower cholesterol, alone or in conjunction with pioglitazone on SIRT1 levels[28]. Fasting glucose, HbA1C, serum lipids, and SIRT1 were all measured following eight weeks of a protocol of fenofibrate alone or fenofibrate with pioglitazone. All treatment groups reported an increase in SIRT1 and decreases in inflammatory markers such as interleukin 6 (IL-6) [28]. These changes produce a beneficial effect in decreasing chronic inflammation associated with type 2 diabetes and obesity.

Diabetic nephropathy is one of the main complications associated with diabetes mellitus and accounts for many cases of end-stage renal disease[29]. Metabolic derangements associated with diabetes can lead to chronic low-grade inflammation from cytokines such as TNF-alpha, IL-1, and IL-6. Periods of caloric restriction can activate nutrient-sensing pathways like AMPK and SIRT1 to induce autophagy to protect against these deleterious processes in the body. However, in diabetic mice, AMPK levels are suppressed due to hyperglycemic conditions, and autophagy does not occur[30]. The suppression of AMPK triggers lipogenesis and further lipotoxicity associated with diabetic kidney disease. When metformin, a SIRT1 activator of the AMPK pathway is given, effects on glomeruli can be reversed. SIRT1 is expressed in kidney podocytes but its function is unclear. Mice with knockdown of renal SIRT1 expression had normal glomerular function under normal basal metabolic conditions[31]. However, diabetic mice with renal SIRT1 knockdown developed more albuminuria and mitochondrial dysfunction than diabetic mice with SIRT1 intact. This indicates that SIRT1 in podocytes plays a role in maintaining homeostasis under conditions of mitochondrial stress. Although some renal changes can be alleviated, long-standing diabetes and concurrent diabetic nephropathy are currently lacking effective treatment.

Honokiol, a natural biphenolic compound isolated from magnolia bark, activates SIRT3 and acts as an antioxidant and anti-inflammatory with reno-protective effects[32]. Honokiol administration to mice activated SIRT3 which limited podocyte damage and the progression of nephropathy, but it did not activate SIRT1 or SIRT6. Selective activation of SIRT3 also provided protection against albuminuria and glomerular lesions. Other studies have demonstrated further effects of honokiol in alleviating cardiac hypertrophy and neurodegenerative disorders[33]. In addition, soluble epoxide hydrolase, an enzyme with both hydrolase and phosphatase activities that metabolize anti-inflammatory acids, can be inhibited to prevent vascular calcification in chronic kidney disease[34]. Mice with genetic deletion of soluble epoxide hydrolase had preserved SIRT3 expression which prevented vascular calcification associated with chronic kidney disease.

As life expectancy continues to increase, the aging population has a proportional increase. With increasing age, the incidence of dementia continues to rise. Alzheimers disease is the main type of dementia and is characterized by severe cognitive impairment over time. SIRT1 is ubiquitously expressed in the brain and regulates many processes that are altered in the pathogenesis of Alzheimers disease such as action potential propagation, neurodegeneration, and mitochondrial dysfunction[35]. In mice, overexpression of SIRT1 led to decreased formation of beta-amyloid plaques characteristically seen in Alzheimers disease. Furthermore, upon autopsy of human brains with Alzheimers disease, expression of SIRT1 and SIRT3 were decreased[36]. In addition, dysregulation of SIRT1 influences neuronal plasticity and increases IL-1 levels involved in brain diseases such as multiple sclerosis[37]. Compared to insulin resistance in peripheral tissues, central insulin resistance is a recent discovery that is sometimes classified as type 3 diabetes. Peripheral insulin resistance seen in type 2 diabetes may trigger insulin resistance in the brain that is associated with neurodegenerative diseases. Insulin in the brain is not only responsible for energy metabolism but also for synaptic plasticity. Therefore, insulin plays a role in the pathophysiology of diabetes-related cognitive decline. Specifically, decreased SIRT1 was seen in the hippocampus of diabetic mice leading to lower learning and memory capabilities[38]. However, with intranasal administration of insulin, SIRT1 levels increased in the hippocampus of diabetic mice, and previous cognitive impairment was improved. SIRT1 also increased hippocampus dendritic spine length and density to improve memory and learning and prevent further cognitive decline.

SIRT3 is also highly expressed in the nervous system and plays a role in neuronal processes regulating brain function. As neurons age, mitochondrial malfunction occurs with decreased SIRT3 levels and the promotion of neurodegeneration[39]. Along with decreased SIRT3, increased levels of oxidative stress contribute to age-related hearing loss from inner ear neuron damage. However, caloric restriction can delay age-related hearing loss by decreasing reactive oxygen species and increasing glutathione via proper mitochondrial antioxidant functioning[39]. Numerous studies indicate caloric restriction from intermittent fasting increases SIRT3 in the hippocampus which maintains synaptic plasticity and improves cognition.

Many serious complications of type 2 diabetes mellitus are related to chronic hyperglycemia. Diabetic cardiomyopathy is one such example that is associated with hyperglycemic memory. Hyperglycemic memory is a phenomenon where the negative effects of hyperglycemia persist even after blood sugar levels return to controlled levels[40]. With this form of metabolic memory, epigenetic changes can continue to cause damage. SIRT1 exerts a positive effect by deacetylating histones along with other protein substrates to repress catalytic activity involved in diabetic cardiomyopathy. Concomitantly with long-standing diabetes, vascular endothelial dysfunction and ischemia-reperfusion injuries occur throughout the body. In the cardiovascular system, orexin B, a hypothalamus-derived neuropeptide that regulates food intake, the sleep-wake cycle, and glucose homeostasis, and SIRT1 were both decreased following an ischemia-reperfusion injury in diabetic mice[41]. Treatment with an orexin type 2 agonist and SIRT1 activator improved vascular function and decreased myocardial injury. Further treatment with a SIRT1 antagonist and orexin agonist eliminated all improvement and elucidated the actions of orexin as a possible activator of SIRT1[41].

Metabolic syndrome, which consists of cardiovascular and metabolic risk factors such as obesity and insulin resistance, is associated with an increased risk of developing cardiovascular disease[42]. Arterial stiffness that is commonly seen in obese, diabetic individuals is associated with a loss of compliance to blood flow and is predictive of further complications such as hypertension, heart failure, stroke, and kidney failure. To mimic this metabolic syndrome and study the effects of SIRT1 on vascular smooth muscle cells, mice were given a high fat, high sucrose diet for two months[42]. After two months, these mice developed stiff aortic walls and increased inflammation. If a normal diet was subsequently started, these changes were reversible within four months indicating arterial stiffness related to obesity can be altered. If mice maintained the high fat, high sucrose diet but added overnight fasting to mimic caloric restriction, acute activation of SIRT1 in vascular smooth muscle cells led to an associated acute decrease in arterial stiffness compared to knockout mice without SIRT1 in vascular smooth muscle cells. Furthermore, overexpression of SIRT1 or administering resveratrol or SRT1720, both SIRT1 activators, reversed previous changes and prevented arterial stiffness[42].In another study by the same group of researchers, the effects of SIRT1 in vascular smooth muscle cells in response to angiotensin 2, a potent oxidant and inflammatory stimulus, were studied[43]. Mice lacking SIRT1 in vascular smooth muscle cells had disorganized aortic walls with increased aortic stiffness and oxidant production. SIRT1 activator administration was able to suppress the oxidant-induced damage to the aorta. In addition, SIRT1 activators provide a potential therapeutic approach to prevent aortic dissection in people at risk such as those with hypertension or genetic disorders like Marfans syndrome[43].

Aging is one of the main risk factors associated with cardiovascular disease. Deterioration is linked to lifestyle stressors along with increased inflammation and oxidative stress within the body. SIRT1 exerts cardioprotective effects by decreasing oxidative stress and improving mitochondrial function[13]. Age-related changes of increased vascular stiffness and oxidative stress make blood vessels more susceptible to vascular diseases like atherosclerosis and increase the risk of progression to abdominal aortic aneurysm. Activation of SIRT1 serves to limit vascular endothelial cell and smooth muscle cell senescence[44]. In this same study, six human abdominal aortic aneurysm samples, taken during open surgical repair, had decreased SIRT1 activity and expression. Another study obtained samples from human vessels with and without plaques undergoing carotid endarterectomy or coronary artery bypass grafting or valve replacement respectively[45]. SIRT1 expression was decreased in samples with plaques leading to increased DNA double-strand breaks and decreased subsequent DNA repair. On the other hand, overexpression of SIRT1 in endothelial cells increases nitric oxide leading to vasodilation and anti-inflammatory actions against the progression of atherosclerosis[46]. This leads to a decrease in calcification in vascular smooth muscle cells. SIRT1 activators can also upregulate endothelial cell nitric oxide synthase to increase nitric oxide and cause vasodilation. Therefore, SIRT1 activators have been proposed as therapeutic strategies against vascular calcification.

The factors of older age, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, coagulopathy, and others are all common risk factors for many other vascular conditions throughout the body. In varied vascular conditions, a commonality of low SIRT levels is seen. For instance, retinal vein occlusion, one of the most common types of retinal disease leading to possible permanent vision loss, is characterized by decreased SIRT1 and increased reactive oxygen species[47]. Lower levels of SIRT1 are also associated with age-related cataracts, macular degeneration, diabetic retinopathy, glaucoma, and many others[48]. SIRT1 plays a protective role against pathological processes in ocular diseases involving inflammation, oxidative stress, and neurodegeneration. In a mouse study, administration of resveratrol enhanced SIRT1 expression and protected against retinal degeneration[49]. Furthermore, hemorrhagic shock, a severe, life-threatening complication of multiple organ failure, is associated with mitochondrial dysfunction and decreased SIRT1 and SIRT3 levels[50]. However, administration of a SIRT1 activator, can restore SIRT1 activity and improve SIRT3 activity to protect against mitochondrial injury and improve survival.

Although most SIRT activators studied are SIRT1 activators, apelin gene therapy is one method of upregulating SIRT3[51]. Apelin, a bioactive peptide and endogenous ligand of G-protein coupled receptors widely expressed on cells of many organs, has numerous functions based on receptor expression in vascular endothelial cells, cardiac tissue, adipose tissue, osteoblasts, and many others. Administration of apelin gene therapy causes overexpression of SIRT3 and increased myocardial density. Both effects together alleviated diabetic cardiomyopathy in mice and reduced myocardial ischemia-reperfusion injury by decreasing reactive oxygen species.

One of the main controversial actions of SIRTs is the promotion of cancer via deacetylation and inactivation of proapoptotic factors that would normally provide protection[6]. SIRTs normally protect against oncogenic transformation but too much activity can have tumorigenic properties. SIRT1 is overexpressed in many tumors such as prostate, breast, lung, leukemia, and lymphoma. Liposarcoma, a locally malignant mesenchymal tumor of soft tissue, is associated with increased SIRT1 and vascular endothelial growth factor (VEGF) levels[52]. SIRT1 contributes to chromatin remodeling and VEGF promotes angiogenesis which in turn promotes the progression of cancer. Increased levels of both SIRT1 and VEGF were correlated with a poor patient prognosis in this study.

SIRT2 has varied expressions and can act as a tumor promoter or tumor suppressor based on the cell type. It is downregulated in breast and non-small cell lung cancers but upregulated in pancreatic cancer and acute myeloid leukemia[6]. The role of SIRT3 is not fully elucidated but some evidence points to overexpression in head and neck squamous cell carcinoma. SIRT7 is upregulated in breast and thyroid cancers due to hypoacetylation of an aggressive tumor marker. On the other hand, most evidence regarding SIRT6 demonstrates action as a tumor suppressor and is downregulated in many cancers[53]. Specifically, histone deacetylation activity of SIRT6 protects against abnormal telomere metabolism which is characteristic of cancer cells. New evidence indicates inhibition of SIRT5 has the potential to suppress malignant transformation of cells and provides an area for future study of cancer therapy[54]. Overall, SIRTs play a controversial role in the progression of cancer, and more information is needed to further explain this negative factor amongst all the positive impacts against age-related processes.

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Role of Sirtuins in Diabetes and Age-Related Processes - Cureus

Hasbulla Magomedov: Who is Hasbulla? Why is the Russian an online sensation? Whats his medical condition? – The Scotsman

Despite being small in stature, Hasbulla boasts a huge online fan base with three million followers on Instagram.

Recently, Hasbulla made headlines after taking a trip down under to Australia as part of his international tour, he said: I cant wait to see all my Aussie fans and visit these amazing cities, I come from a tiny town in Russia, so I am looking forward to experiencing a different culture.

I also know there are kangaroos, I would like to meet them.

Even if the name doesnt ring a bell its likely youve seen social media starring Hasbulla at some point.

Who is Hasbulla?

Hasbulla Magomedov, or Mini Khabib, is from Makhachkala in the republic of Dagestan which is located in the Russian Federation.

He became an online sensation in 2020 during the COVID-19 pandemic after his videos on TikTok went viral, seeing him become the subject of thousands of memes, posts and tweets.

Although not formally affiliated, Hasbulla is widely associated with the international Ultimate Fighting Championship (UFC) community after one of his most viral videos reenacting a weigh-in of UFC champion Khabib Nurmagomedov went viral.

Why is Hasbulla so famous?

Hasbulla has built up over 3 million followers on Instagram since November 2020.

Last year he went viral on TikTok by building his platform based on mocking MMA (mixed martial arts) content.

He picked up the name Mini Khabib after he replicated pro MMA fighter Khabib Nurmagomedovs iconic weigh-in. The two now regularly create content together.

Hasbulla suffers from a debilitating condition that makes him abnormally short, yet he embodies confidence and charm which has added to his fame.

He is also a devout Muslim and often shares his love of Islam, which has seen him gain a large Muslim following.

In Scottish pop culture, Hasbulla can regularly be seen featuring in meme-posting accounts.

In 2022, a Scottish newspaper was pranked by someone submitting a photo of the Russian star after the paper requested snaps from parents of their kids enjoying the snow.

A user who spotted the picture tweeted: Our local paper asked for pics of kids enjoying last week's snow and someone's sent in a pic of Hasbulla I'm dead.

What is Hasbullas medical condition?

Hasbullas unusual features like his very short height (around 100cm) are caused by Growth Hormone Deficiency or Dwarfism.

Growth hormone deficiency (GHD) is a rare condition characterised by the inadequate secretion of growth hormone from the anterior pituitary gland, resulting in abnormally short statures with otherwise normal body proportions.

Those with this condition can suffer a variety of symptoms including fatigue, anxiety or depression, or intense feelings of being isolated from other people.

Hasbulla, however, is famed for taking the disorder in his stride with great humour and confidence; another reason for his massive popularity.

How tall is Hasbulla?

Hasbulla is 3 feet and 4 inches according to an interview he did with SportsKeeda, meaning he measures at just over 100cm.

Dwarfism in adults is defined as a height of 4 feet 10 inches (147cm) or less, while the average height among such adults is 4 feet (122cm).

How old is Hasbulla?

The young Russian is approximated to be 19 years old, but an exact date of birth is unknown.

Many websites state that he was born in 2003.

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Hasbulla Magomedov: Who is Hasbulla? Why is the Russian an online sensation? Whats his medical condition? - The Scotsman

$250 million Peyton Manning was accused of using doping drug HGH by his former pharmacist and having it mailed… – The Sportsrush

NFL icon Peyton Manning was accused of using performance-enhancing drugs by his former pharmacist. However, the league cleared him after a detailed 7-month long investigation.

Peyton Manning is an iconic quarterback who made a name for himself at the highest level. Nicknamed The Sheriff, Peyton was active for almost two decades in the league.

Although he was with the Broncos for four years in the final phase of his career, the 14-year stint he had with the Indianapolis colts really established him as one of greats of the game.

The two-time Super Bowl champion who currently has a gigantic net worth of $250 million, was named the most valuable player of the league on five occasions. He broke innumerable records during his illustrious career.

However, back in 2016, Peyton was named in what could have turned out to be a massive controversy. He was accused of using performance-enhancing drugs during the 2011 season.

Also Read: Lamar Jackson deserves to be the highest paid $230 million plus player in the league according to former Super Bowl hero James White

Al Jazeera America came up with a documentary titled The Dark Side in which one of Peytons former pharmacists reportedly claimed that he provided performance-enhancing drugs to Manning by mailing them to his wife.

He accused Manning os using HGH (human growth hormone) during the 2011 season when he was recovering from a neck surgery. HGH is a doping drug which was banned by the NFL back in 1991

It is said that HGH aids in muscle building and also improves metabolic function. However, scientific evidences to verify such claims are not available in abundance.

The allegations against Manning were made by a man who was, at that time, an employee at the Guyer Institute of Molecular Medicine. He even claimed that he shipped HGH to a number of NFL stars along with Peyton.

Peyton and other players involved in the controversy categorically denied all the allegations. The NFL decided to launch an investigation into the matter.

However, the league had started testing for HGH only in 2014, even when it was banned in 1991 only. So proving any of the allegations was a tough task.

After a seven-month investigation, the NFL claimed that no credible evidence was found that could prove Manning guilty. As a result, he was eventually cleared.

Manning decided to retire from the sport back in March, 2016.

Also Read: Colin Kaepernick will follow in Kobe Bryants footsteps and join Spike Lee for a documentary about his social justice struggle

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$250 million Peyton Manning was accused of using doping drug HGH by his former pharmacist and having it mailed... - The Sportsrush

Home-run stud Aaron Judge is doing it the right way we think – Chicago Sun-Times

Home runs are the coolest part of baseball.

The run scored is important. But the emotional thrill is witnessing the launching of something out of the boundaries of the game and into the real world, breaking down the barrier that separates athlete and observer, performance and life.

So think for a moment about Aaron Judge.

You may not have been paying much attention, but the big Yankees slugger 6-7, 282 pounds has 54 homers this season, and hes mashing them at a pace that puts what a lot of us consider to be the authentic, un-steroided major-league record of 61 in jeopardy.

Those 61 were hit by Yankee Roger Maris in 1961, breaking Yankee Babe Ruths record of 60 set in 1927. Along came the juiced-up era of the late 1990s and early 2000s, and we got the home run gong show featuring Sammy Sosa (63 and 66 HRs), Mark McGwire (65, 70), and Barry Bonds (73, the current record). It was devious. It was ridiculous.

Noted steroid-taker Alex Rodriguez kept the show going with his 57 homers in 2002, and then the muscle parade began to atrophy. Lets just say the Mitchell Report, drug testing, congressional hearings and suspensions for performance-enhancing drug-taking slowed the home run display substantially.

League-leading home run numbers dropped quickly into the 40s after 2002, with only random jumps into the 50s. Judges huge Yankees teammate, Giancarlo Stanton 6-6, 245 hit 59 while with the Marlins in 2017, the most since Bonds 73 from 21 years ago.

And now Judge stands alone, way out in front of everyone in both leagues. The closest in the American League is the Astros Yordan Alvarez with 31. In the National League, its the Phillies Kyle Schwarber with 36.

Is Judge juiced? There has never been a speck of evidence, even suspicion about the big man. But sadly, everybody is tainted by the cynicism created during the Steroid Era. Former MLB commissioner Bud Selig disregarded the doping mess for so long that the festering muscle madness meant only a fool would believe anything any player said about steroids, human growth hormone and the like.

The drug plague seems to be under control, but who knows? Passing a drug test these days means almost nothing. We look at players and get a sense, a feel, and thats usually what we go on.

And Judge just feels like a non-doper. He has always been huge. Asked why there arent other giant men in baseball, he replied, Because theyre either playing basketball or football.

Well call him squeaky-clean for now.Hopefully forever.

If Sosa, McGwire and Bonds hadnt come along and given the stats an asterisk, Judges home run journey assuredly would have our sports-loving nation fascinated, kids tracking each of his homers like detectives, newscasts leading off with his numbers.

Right now, hes on pace to hit 65 home runs. Hes red hot, with five in his last seven games, well ahead of both Maris and Ruths paces, with 27 games to go.

A right-hander, Judge hits his bombs in all kinds of ways, to all fields. He got his first one April 13 off the Blue Jays Jose Berrios. On April 26, he homered on his 30th birthday. He has had monster launches, and he has had tidy little ones, like No. 25, which traveled only 364 feet and wouldnt have cleared any other park wall in that spot except Yankee Stadiums.

He has hit them off journeymen and pitching stars. He jacked No. 47 against Mets ace Max Scherzer two weeks ago.

I thought if I kept the ball down on Judge, I could keep him in the ballpark, Scherzer said.

Sorry.

Judge got to the White Sox on back-to-back days in May (Nos. 11 and 12), leading manager Tony La Russa to say, We got torched.

I remember spending time with Maris, after hed retired as home run king and was running a beer distributorship in Gainesville, Florida. The race for him, he said, against an idol like Ruth, had been traumatic and pressure-packed, filled with taunts that he wasnt worthy. It bothered him still that critics said he hadnt been consistent with home run numbers through the years that he wasnt worthy of the crown.

How many times you supposed to do a thing? he asked me.

Judge is worthy of Maris record. If he breaks 61, lets call him the king. And hope he enjoys it.

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Home-run stud Aaron Judge is doing it the right way we think - Chicago Sun-Times