New painkiller found in coffee – stronger than morphine .


Coffee contains a protein that has an effect similar to morphine, specialists at the University of Brasilia and Brazilian agriculture research company Embrapa have discovered. Moreover, the new substance’s effect lasts longer.

The research was conducted by Felipe Vinecky of the Molecular Biology Department at the University of Brasilia (UnB) in cooperation with the Genetics and Biotechnology Division of state owned agriculture and livestock research company Embrapa. The research involved searching for and combining coffee genes to affect quality. In the course of study, the scientists managed to find new substances in the product.

While analyzing the coffee genome sequence and corresponding proteins, Vinecky and his research adviser Carlos Bloch Junior found some proteins similar to those typical for humans. So they decided to synthesize their structural analogues and test their properties.

The researchers “identified previously unknown fragments of protein — peptides — in coffee that have an effect similar to morphine, in other words they have an analgesic and sedative activity,” the Embrapa company press release said.

Both the University and Embrapa applied for patents to the Brazilian government for seven proteins they called “opioid peptides.”

Those peptides “have a positive differential: their effects last longer in experiments with laboratory mice,”the press release said. According to the scientists, it lasted up to four hours and no side effects were recorded.

Embrapa believes their discovery has great “biotechnological potential” for the health food industry, and could also help to minimize stress in animals at slaughterhouses.

In 2004, Embrapa succeeded in determining the sequence of coffee’s functional genome and the discovery made it possible to combine coffee genes with a view to improving the quality of coffee grains. Thanks to this achievement, the researchers managed to discover the new peptides.

Embrapa is a state-owned company affiliated with the Brazilian Ministry of Agriculture. Embrapa conducts agricultural research in many areas including livestock and crops.

When bacteria-killing viruses take over, it’s bad news for the gut .


People with inflammatory bowel diseases carry more of some of these viruses, less good bacteria

Virome shapes graphic

VIRUS GUT-PUNCH  Bacteria-infecting viruses called bacteriophages may kill friendly bacteria in the gut, causing inflammation and disease, a new study shows.

Bacteriophages — viruses that infect and kill bacteria — are more diverse in people with Crohn’s disease or ulcerative colitis. Herbert “Skip” Virgin, an immunologist at Washington University in St. Louis, and colleagues reportthe finding online January 22 in Cell. In particular,Caudovirales bacteriophages were more diverse in people with the diseases than in healthy people living in the same households, the researchers found.

The viruses may kill friendly bacteria in the intestines, leading to inflammation and disease. Scientists already knew that people with Crohn’s and colitis tend to have fewer types of beneficial bacteria in their gut microbiomes. The microbiome is the complete collection of bacteria, viruses, fungi and other microorganisms that live in or on the body. What researchers hadn’t understood is why the bacterial diversity decreased.

The new results suggest some viruses may damage health not by infecting human cells, but by altering the microbial mixes in the body. The findings may also explain why fecal transplants from healthy people generally haven’t cured inflammatory bowel diseases; lingering viruses may destroy newly introduced bacteria before they can do the patient any good.

How Tesla is changing the world


The one thing that never quite seems to fit into London’s cityscape is the random sighting of the G-Wiz electric car. The peculiarly named G-Wiz was the top selling electric car in the UK for several years and is a product of India: it is just a renamed REVAi which was launched in 2001 by Bengaluru’s REVA Electric Car Company, which has now been acquired by Mahindra & Mahindra.

The reason why the G-Wiz doesn’t quite seem to fit in to London’s cityscape is that, frankly, it doesn’t quite seem like it would fit anywhere, other than tight parking spots. This Electric Vehicle (EV) isn’t a car that inspires the popular imagination: it looks like a miniature buggy and has a low range of 80km on a full charge.  It is neither aspirational nor ground breaking in any way. Perhaps, it wasn’t designed to be that. More accurately, it couldn’t have been designed to be that when launched in 2001, largely owing to inadequacy of available technology – but more on that later.

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Tesla Model S

With the overall transport sector contributing to approximately 22 per cent of CO2 emissions globally (as reported by the International Energy Agency), we can agree that there is merit in moving away from Internal Combustion Engine (ICE) based, fossil fuel-consuming, greenhouse gas-emitting automotive engines. This is especially true in the light of the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change (IPCC) strongly suggesting the role of the human hand in global warming and the required urgency in tackling this issue.

The discerning reader may be quick to point out that even if EVs went mainstream, carbon emissions may not change – and in fact may increase – as electricity is still largely sourced from coal based power plants in several countries, including India. Further, there are significant transmission losses in electricity supply systems.

However, in spite of these concerns, there are short and medium term gains to be made with the increased adoption of EVs (there are long term advantages too, but in the words of John Maynard Keynes, in the long run, we are all dead). In the short run, greater adoption of EVs would lead to lowering Local Air Pollution levels where there are greater concentrations of personal vehicles, ie. in urban areas. This is important in the light of the fact that over 53 per cent of the global population in 2013 was based in urban areas (up from 43 per cent in 1990, as reported by World Bank), and this will keep rising over time. In the short run, there may be merit in displacing pollution from heavily concentrated urban areas to areas with low population densities, where coal-based power plants are based. Undoubtedly, this is a privileged suggestion – more likely to be proposed by an urban resident – and one that ignores the social justice angles of industrialisation and urbanisation. For this reason, this author would like to focus on the medium term argument, which is also of academic interest to him.

The global economy today is “locked-in” to carbon based energy systems. There is a techno-institutional inertia in place, which will ensure fossil fuel based energy systems continue to be the mainstream long after alternate energy systems have proven commercial viability. Such techno-institutional inertia exists due to the co-evolution of legislation, investments, demand-side technology and culture, which has led to the society being locked into a fossil fuel dominant economy. In order for this lock-in to break and for renewable technologies to take centre stage, the demonstration of commercial viability will not be enough. Specifically in the case of private road transport, apart from changes in legislation and investment patterns, the cultural notion of mobility will have to change. This, unfortunately, will take much longer than the expected time for renewable fuels to meet grid parity with coal (ie. the cost of producing electricity from renewables becoming equal to electricity from coal).

Electricity from solar technology, for instance, is expected to become as cheap as electricity from coal by 2020. Once such grid parity is achieved, the transformation of electricity supply will prove to be far less difficult than changing the demand patterns of automobile consumers. Since the transformation of the private transport industry may take longer than the transformation of electricity supply systems once grid parity is achieved, there is good reason to start the process of the adoption of EVs sooner, even if there are more carbon emissions in the short run from greater consumption of coal-based electricity. After all, the breaking through of EVs into the mainstream is not going to be easy.

Let’s face it: consumer acceptability is a very important determinant of popularity of a product. On average, automobile consumers want cars to look “normal”, and they want to not have “range anxiety”. This is where Telsa comes into the picture. Telsa Motors is an American electric car company that was founded in 2003 and their popular sedan Model S was released in 2008. The Model S is succeeding at going mainstream where others have failed in the past. Firstly, their popular Model S looks like regular cars do: it has a front compartment where the internal combustion engine (ICE) would normally be, and is as long and wide as any other car in its segment. Indeed, Tesla’s Model S is as “inefficiently” designed as cars that run on motor spirit or diesel. EVs do not need to be designed like traditional cars, but Tesla has understood that it is important to do so in order to find acceptability at the marketplace. In doing so, Tesla has not challenged the cultural notions of personal mobility, which is far harder to change.

EVs before Tesla looked far too much like golf carts, or were far too quirky – much like the G-Wiz. Others – like Nissan’s Leaf – are named, marketed and designed look “green”. Such cars thus have a niche market among those who care about the environment and efficiency over performance. However, in order to go mainstream, EVs need to look and perform like the next car, perhaps marginally better.

Telsa has successfully done that with its Model S, and is on track to launch an SUV and a cheaper sedan in the coming years. The SUV – named Model X – also looks like a “regular” car which could have a petrol or diesel engine in it. Tesla’s cars also perform like ICE cars. In fact, they perform better on acceleration, speed, safety tests and other indicators than many cars in its class.

Secondly, Tesla has solved the “range anxiety” issue by installing charger stations strategically in a manner that ensures inter-state highway travel becomes possible in the United States, Europe, China and Japan, where they operate. Even without charging stations, the Model S has enough battery life to travel more than the distance from Delhi to Jaipur – and back – on a single charge. Tesla is also introducing “battery swap” stations that would automatically replace batteries faster than it takes to refuel a traditional car with petrol or diesel.

Tesla is thus creating the institutional infrastructure that is required for the EV technology to become mainstream. This had never been attempted at such a scale before: so far, charging stations were unorganised, rare and localised. The lack of charging infrastructure along highways and the time taken to charge are two of the key reasons why electric cars did not succeed in the past. Indeed, it is why the new hydrogen fuelled cars being launched by Toyota and other manufactures will in all likelihood fail to go mainstream: there simply isn’t enough infrastructural support, and these cars do not look like the next car.

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Nissan Leaf is the best selling Electric Vehicle

To be sure, Tesla’s Model S – which has sold over 50,000 units so far – is not the best selling EV.  That honour goes to the far more moderately priced Nissan Leaf. However, unlike other EV manufacturers, Tesla is addressing the techno-institutional lock-ins that are characteristic to the ICE dominated automobile industry. Further, it is creating an ecosystem which can be taken advantage of by other EV manufacturers: Telsa has stated that it will allow its technology patents to be used by other companies in good faith in order to deepen the EV industry.

Ever since Tesla succeeded with Model S, other manufactures – such as BMW and General Motors – have released or are working on releasing mainstream EVs. BMW and Volkswagen are even planning to develop fast-charging stations. As Henry Ford did to the automobile industry in the early 1900s by creating a standard industrial line, Tesla’s founder Elon Musk is doing towards mainstreaming EVs today.

It is true that the natural progression of battery capacity was a necessary condition in the mainstreaming of EVs. It is the reason why REVA’s fourteen year old G-Wiz is petite and has a low mileage. Newer batteries permit the construction of larger cars like the Model S, which can go much further. However, the breaking of techno-institutional barriers which was needed for the mainstreaming of EVs has been facilitated by Telsa. The necessary conditions are now being met. If the breaking of techno-institutional lock-in in the automobile sector is made possible by the EV industry, it could lead to significant gains in curbing CO2 emissions from the transport sector in the medium run. And Tesla is poised to lead the way and make it happen.

Have Difficulty Swallowing Pills? How A Spoonful Of Water Can Help The Medicine Go Down


Swallowing pills could be one of the most dreaded things you come face-to-face with when you’re ill. Whether you used to hide them under your tongue and spit it out as a kid or just refuse to take them now as an adult, science has given merit to the “Mary Poppins method.” According to a recent study published in the journal Annals of Family Medicine, “a spoonful of [water] makes the medicine go down” simply by using the pop-bottle method for tablets or the lean-forward method for capsules.

Red and blue pill on hand

“A hard pill to swallow” isn’t just a metaphor in medicine. One in three people tend to gag, vomit, or choke, according to a review published in Therapeutic Delivery, when it comes to swallowing oral medication. This keeps people from sticking to their medication, which can lead them to become sicker. The difficulty of swallowing pills happens to people who can swallow food and liquid just fine. However, some people have an aversion to swallowing pills and others have physical limitations that inhibit their swallowing capabilities.

In an effort to make swallowing pills easier for patients, Dr. Walter Haefeli, lead author of the study and clinical pharmacologist at the University of Heidelberg, Germany, and his colleagues aimed to evaluate the influence of two techniques on swallowing tablets — the pop-bottle method for tablets and the lean-forward method for capsules. A total of 151 adults were given 16 differently shaped placebos, adding up to 283 pills between them in the study. The participants were taken from the general German population, including those with complications swallowing and those without.

They were asked to compare swallowing these pills against swallowing 20 milliliters, or about a tablespoon of water. The participants were instructed to swallow the most difficult pills using either the pop-bottle or lean-forward techniques and rate this against just water on an 8-point Likert scale. The pop-bottle method involved filling a plastic bottle with water, placing the tablet on the tongue and clamping the lips tightly around the opening of the bottle before beginning to drink, The Guardian reported. The lean-forward technique is where the capsule is again placed on the tongue before taking a sip of water. The participants had to tilt their chins toward their chests and swallow with the head bent forward.

The findings revealed tablet swallowing improved by up to 60 percent using the pop-bottle method compared with standard techniques such as using a sip of water from the glass. The lean-forward method proved to be 88 percent more effective at helping patients swallow capsules than more common techniques. These findings could help ensure patients who struggle to take all of their medication actually take their prescription effectively.

“Almost 10 percent of patients with swallowing difficulties report that this is a reason for not taking the drugs at all. Both the techniques we describe were remarkably effective in participants with and without reported difficulties in swallowing pills and should be recommended regularly,” Haefeli told The Guardian. He does warn this study isn’t the last word on pill-swallowing techniques, but it’s a bold start.

However, it’s important to acknowledge the way tablets and capsules are swallowed does matter because of their density. Most of the time, tablets have higher densities than water, so it is vital to swallow the medicine into the pharynx — the cone-shaped passageway that goes from the nose and mouth toward the esophagus and voice-box. Unlike tablets, capsules are less heavy than water, which makes it more probable they float on the water in the mouth. Tilting your head back will allow it to float toward the teeth and then tilting your head forward will help the capsule move toward the throat.

Researchers still remain inconclusive as to why some people have difficulties swallowing pills. However, the majority of the people simply face a mental barrier that could easily be overcome, Medical Daily previously reported. A trigger for the fear response ignites because of the disconnect between the body and mind when the brain realizes the pill isn’t food but it is yet asked to treat it as such.

It seems patients without a physical dysfunction need to train themselves to mentally block out their pill-swallowing fears, and pharmaceutical companies need to consider making tablets smaller to encourage patients to adhere to a full course of prescription.

Sources: Haefeli WE, Quinzler R, Reich G, Schiele JT, Schneider H. Two Techniques to Make Swallowing Pills Easier. Annals of Family Medicine. 2014.

Scientists seeking soil (and bacteria) from your backyard .


Scientists seeking soil (and bacteria) from your backyard

Could the microbial key to the world’s next big drug discovery be lying in the soil in your backyard?

A citizen science project led by researchers at Rockefeller University in New York is interested in mapping the genetic riches of soil from all around world.

The objective is to uncover new bacteria in unexpected (and hard to reach) places, which could lead to the development of new types of antibiotics and other drugs.

The Drugs from Dirt project was started by microbiologist Sean Brady.

In a sample from New Mexico, for instance, they found gene clusters similar to those that produce a substance known as epoxomicin, which the researchers say is a “natural molecule used as the starting point for a number of recently approved anti-cancer agents”.

In soil samples from Brazil, the team also found genes that could be useful to make a variant of bleomycin, which is used to treat several different types of cancer.

“The unbelievable diversity we found is a first step towards our dream of building a world map of chemicals produced by microbes – similar to Google Earth’s and others’ maps of the world’s geography,“ said Brady, in a press release.

They team recently published a report documenting these initial analyses  in the journal eLife Sciences.

But the team is nowhere near finished.

They want to collect thousands of soil samples (and you could help them, by signing up and sending in a couple of teaspoons of your own local dirt).

The goal is to learn more about the “enormous untapped reservoir” of biosynthetic gene clusters in the environment – something the researchers call “biosynthetic dark matter”.

These biosynthetic genes, known to be present in soil bacteria, are hugely important for the development of new drugs and therapeutic compounds.

The majority of antibiotics in use today are derived from soil bacteria, but the development of new antibiotics has been relatively stagnant, which is problematic given the increasing problem of drug resistance.

In a report chaired in December 2014, economists and scientists predicted that antimicrobial resistance will kill 300 million people and cost the global economy US$100 trillion by 2050 unless government action is taken immediately.

One of the reasons why fewer drugs are being developed is the incredible diversity of microbial life in soil that remains undiscovered.

According to the Rockefeller University team’s press release, “for every cultured bacterial species, there are 100 uncultivated species in the environment”.

The amazing value of seemingly mundane soil samples for drug discovery was highlighted earlier this month when a team of US researchers reported the discovery of a new class of antibiotic, which was shown to kill staph and strep throat in mice with incredible efficiency.

It was the result of bacteria found dwelling in the soil of a grassy field in Maine, US.

“They found a rare compound that does a really neat thing – but maybe it’s not the best one that nature made,” Brady told New Scientist.

Martians, Monsters or Methane: Mysteries of the Bermuda Triangle Explained .


 

Few areas in the world are as mysterious as the deadly Bermuda Triangle. The area, which is also known as the Devil’s Triangle, is a section of Atlantic Ocean located between Miami, Bermuda, and Peurto Rico of around 1.5 million square miles. Since mid-way through the 20th century, the vast area has reportedly become the watery grave of countless planes and ships – many of which disappeared in mysterious and unusual circumstances. Is the Bermuda Triangle simply another urban legend, or is there really something sinister going on in the West Atlantic?

As with anything slightly enigmatic, many different non-scientific theories have been suggested to explain the Bermuda Triangle’s apparently insatiable appetite for ships and planes. Alien abductions have been cited, as have ghost ships and sea monsters. Some have even suggested the ancient denizens of the sunken city of Atlantis could also be responsible.

To examine these claims, let’s look at some of the most common mysteries.

The Bermuda Triangle’s Victims

Flight 19

The case of Flight 19, which famously featured in Steven Spielberg’s Close Encounters of the Third Kind, is perhaps the most enduring Bermuda Triangle mystery.

On December 5th 1945, a training flight of five TBM Avenger torpedo bombers disappeared within the Triangle. The flight, which consisted of 5 aircrafts and 14 crew, was led by United States Navy Lieutenant Charles Carroll Taylor, who had over 2,500 hours of flight experience.

The plan was to fly out east from Fort Lauderdale, commence some bombing practice and then fly north over Grand Bermuda island before returning to base. However, after turning north, Taylor claimed his compass had malfunctioned and he was now lost. He stated he believed he was over the Florida Keys far to the south-west of where he should be. Despite the students begging him to simply head west (one was heard radioing “Dammit, if we could just fly west we would get home; head west, dammit.”), Taylor continued to head east, until eventually the flight disappeared without a trace.

A search plane, with 13 men on board. also went missing in an attempt to find any survivors.

Ellen Austin

In 1881, the Ellen Austin encountered a derelict and abandoned ship floating in the Triangle. It placed a prize crew aboard the ship with the hope of returning it to New York.

However, it is claimed the derelict then disappeared with the prize crew on board. Some accounts claim the ship then reappeared later (minus the crew) and later disappeared once a second prize crew was placed aboard.

USS Cyclops

The largest loss of life in US Naval history (not resulting from combat) also occurred in the Bermuda Triangle. The USS Cyclops, a collier transport ship carrying a full load of manganese ore, was disappeared without a trace on March 4, 1918 with the loss of all 309 on board. Some suggested the vessel could have been sunk by a German U-boat raider, however the German authorities subsequently claimed they had no knowledge of the ship.

Carroll A. Deering

A five-masted schooner built in 1919, the Carroll A. Deering was found hard aground and abandoned at Diamond Shoals with no trace of the crew. On board the ship, the log and navigation equipment was gone, as had the crew’s personal effects and the ship’s two lifeboats.

The mystery is compounded by the fact a strange steamer was later seen in the same area as the Carroll A. Deering was found in. The ship ignored all signals from a lightship in the area, and subsequently was never seen again.

Great Isaac Cay Lighthouse

However, the mysteries of the Bermuda Triangle are not limited to ships and planes. In 1969, the two lighthouse keepers of a remote lighthouse on Great Isaac Cay, a small Bahamian island, went missing without a trace.

The lighthouse has always attracted supernatural superstition. Some claim the full moon brings strange noises to the island, while there are also stories it is haunted by the Grey Lady – the mother of a child which was the sole survivor of a 19th century ship that wrecked on the island.

What Actually Happened?

Although many have suggested there is something strange going on in the Triangle, there are several scientific explanations for the phenomena, as well as these individual cases.

For example, regarding the above examples, here are the established scientific solutions. They’re not as exciting as Atlantis or aliens, but they’re probably right:

Flight 19: Crashed in the sea, following pilot error.

Although Taylor thought he was in the Gulf of Mexico, it is most likely he was in the East Atlantic. Most agree he turned north too late, meaning he mistook the Great Abaco Island as the Florida Keys and assumed his compass was wrong.

The rescue plane was later seen to explode, which was likely due to overloading with fuel, an event not unheard of for that type of aircraft.

Ellen Austin: Likely misreporting.

The story only reemerged once interest in the Bermuda Triangle grew in the 1940s and ’50s. This suggests much of the story may have been fabricated. A ship called the Ellen Austin did exist, but it never listed any casualties or missing people.

USS Cyclops: Sank due to overloading.

The Cyclop’s sister ships, the Proteus and Nereus, were also lost during WWII. Both were transporting heavy loads of metallic ore, and both sank due to structural failure resulting from overloading. This is likely what happened to the Cyclops.

Carroll A. Deering: Likely pirate attack or mutiny.

It’s believed the Deering may have been involved in prohibition era rum-smuggling, and it’s suggested the unknown steamer may have raided the vessel, or a mutiny aboard took over the ship and transported the goods to another.

Great Isaac Cay Lighthouse: Likely storm.

During their disappearance, the island was at the outer edge of a large hurricane. It is likely they were swept off the small island.

Explaining the Bermuda Triangle

First of all, let’s start with some numbers. According to researcher Lawrence David Kusche, the area known as the Bermuda Triangle is not statistically more dangerous, proportionately speaking, than any other part of the ocean. In fact, it is one of the most nautically traveled areas in the world, which means inevitably there will be instances of disappearances and sinkings, especially when navigation and communication equipment was in its infancy.

Furthermore, the area is frequented by tropical storms for parts of the year, which is likely to account for many of the disappearances. The Bermuda Triangle is also known for sudden powerful downdrafts of cold air. National National Hurricane Center satellite specialist, James Lushine, stated

“during very unstable weather conditions the downburst of cold air from aloft can hit the surface like a bomb, exploding outward like a giant squall line of wind and water.”

This is enough to sink some ships, but isn’t unique to the Bermuda Triangle.

Ongoing interest in the mystery of the Bermuda Triangle also means the mainstream reporting of incidents is often sloppy. For example, boats which disappear in the area are often reported, but their subsequent rediscoveries are not, resulting in skewed numbers.

Is Methane Gas Responsible?

One oft cited reason which attempts to explain the Bermuda Triangle’s ship-sinking tendencies is the presence of large fields of methane hydrates (a type of natural gas) in the continental shelves around the area.

If this methane is to be released, it would cause turbulence in the water surface, and a sudden lose of buoyancy for any vessels in the area. Theoretically, this could sink even large ships, especially those carrying heavy loads, extremely rapidly. The debris from such sinkings, would then be carried out of the area by the Gulf Stream – meaning it would appear as if the ship had simply vanished. The BBC conducted a small scale experiment to show if this is possible:

However, although large fields of methane are in the area, the United States Geographic Society claim there hasn’t been a large eruption of methane gas for the past 15,000 years.

So there you have it, perhaps the Bermuda Triangle isn’t the nautical and aviation death trap we’ve been made to think it is. But do you agree?

Age Of Woman’s First Period Linked To Heart Disease Risk: Menstruation’s Impact On Heart Health


First Period Indicates Heart Health
Heart health can be predicted with when a girl first gets her period. 

A girl’s first period marks a monumental time in her life when she transitions into womanhood, but it may be more important to focus on the age it all happens. Researchers from the University of Oxford spent over a decade studying how menstrual cycles affect a woman’s overall health and published their findings in the journal Circulation.

Menstruation, more commonly known as a period, is a major stage of puberty for girls at the average age of 13. It took researchers over 10 years to analyze and observe data from 1.3 million women between the ages of 50 to 64, in order to figure out how their first period age could affect their health. It turns out, if any girl’s first menstrual cycle wavers too far from the age of 13, they are at increased risk for a slew of heart problems.

Girls who had their first period when they were 10 years or younger, or at the age of 17 and older, were 27 percent more likely to end up in the hospital or even dead due to heart disease. The same age ranges were also 20 percent more likely to become hospitalized or die because of high blood pressure complications. Lastly, girls were 16 percent more likely to become hospitalized or die of a stroke. Researchers believe it’s because the first menstruation age indicates a level of health.

“The size of our study, the wide range of ages considered, and the vascular diseases being examined made it unique and informative,” the study’s lead author Dr. Dexter Canoy, and cardiovascular epidemiologist at the Cancer Epidemiology Unit at the University of Oxford, said in a press release. “Childhood obesity, widespread in many industrialized countries, is linked particularly to early age at which the first menstrual cycle occurs. Public health strategies to tackle childhood obesity may possibly prevent the lowering of the average age of first menstrual cycle, which may in turn reduce their risk of developing heart disease over the long term.”

The research team consistently found throughout the study that those who were healthy and lean had a first menstruation age closer to 13 than those who were overweight or obese. It could be that as childhood obesity continues to take over America, more and more girls will have their menstruation cycles further away from the age of 13. In the past 30 years, childhood obesity has more than doubled in children and more alarmingly, quadrupled in adolescents, according to the Centers for Disease Control and Prevention.

Source: Canoy D, Beral V, Balkwill A, Wright FL, Phil D, and Kroll Me. Circulation.

India: first to adapt the Global Monitoring Framework on noncommunicable diseases (NCDs)


Every year, roughly 5.8 million Indians die from heart and lung diseases, stroke, cancer and diabetes. In other words, 1 in 4 Indians risks dying from an NCD before they reach the age of 70.

Illustration about urbanization in India.

“Heart diseases, diabetes, cancers, and chronic respiratory diseases now affect younger and younger people,” says Dr Poonam Khetrapal Singh, Regional Director of WHO South-East Asian Region. “The millions of productive individuals lost prematurely to NCDs are seriously undermining social and economic development.”

But the country is not watching and waiting for the burden to grow. Instead, the Government of India is taking immediate action and targeting the greatest risk factors contributing to NCDs—unhealthy diets, physical inactivity, tobacco and alcohol use, and air pollution.

Specific national targets and indicators

In line with WHO’s Global action plan for the prevention and control of NCDs 2013-2020, India is the first country to develop specific national targets and indicators aimed at reducing the number of global premature deaths from NCDs by 25% by 2025. A National Multisectoral Action Plan that outlines actions by various sectors in addition to the health sector, to reduce the burden of NCDs and their risk factors, is in the final stage of development.

“It is heartening to see the Government of India taking the leadership role in the prevention and control of NCDs,” says Dr Nata Menabde, WHO Representative to India. “As a partner to the global agenda on prevention and control of NCDs, we are committed to supporting national efforts towards strengthening the health systems to address the growing burden of NCDs and comorbidities.”

“Heart diseases, diabetes, cancers, and chronic respiratory diseases now affect younger and younger people.”

Dr Poonam Khetrapal Singh, Regional Director of WHO South-East Asian Region

10th target: household air pollution

The global action plan lists 9 targets for countries to set. But India has taken the unprecedented step of setting a tenth target to address household air pollution —a major health hazard in the South-East Asian Region due to burning of solid biomass fuel and secondhand smoke.

Globally, 4 million deaths are caused by exposures to household (indoor) air pollution and 3.7 million deaths are attributed to outdoor air pollution. Approximately 40% of the deaths from indoor air pollution and 25% of those attributed to outdoor air pollution occur in the WHO South-East Asia Region.

“We must act to protect people from air pollution. The poor, living near busy roads or industrial sites, are disproportionately affected by air pollution,” says Dr Poonam Khetrapal Singh. “Women and children pay the heaviest price, as they spend more time at home breathing in smoke and soot from cooking stoves.

India’s National Monitoring Framework for Prevention and Control of NCDs calls for a 50% relative reduction in household use of solid fuel and a 30% relative reduction in prevalence of current tobacco use by 2025. Countries in the South-East Asia Region have also committed to reducing household air pollution as part of the Regional Acton Plan for the Prevention and Control of Noncommunicable Diseases 2013-2020.

Implementing WHO’s Framework Convention on Tobacco Control

Additionally, India has implemented WHO’s Framework Convention on Tobacco Control aimed at reducing the demand for tobacco products. The country has prohibited sales of tobacco products around educational institutions, restricted tobacco imagery in films and TV programmes, banned some smokeless tobacco products and developed tobacco-free guidelines for educational institutions.

In April 2015, the country will go a step further and require tobacco pictorial warnings to cover 85% of the package. This effort is an excellent example of a “best buy” or cost effective, high impact intervention for combating NCDs.

Induced Pluripotent Stem Cells for Neurodegenerative Disease Modeling


 

Induced Pluripotent Stem Cells for Neurodegenerative Disease Modeling

Scientists have identified a number of genes that are associated with Parkinson’s, resulting in the discovery of three genes and the mapping of five others that are linked to rare familial forms of the disease. [Designua/Fotolia]

  • Scientists continue to progress toward the goal of using human stem cells to treat incurable human diseases. But these cells, particularly neural stem cells, may also provide models for a variety of disorders, including psychiatric, neurodegenerative, and cardiovascular.

    To date, a dearth of representative models for many of these diseases has impeded the discovery and development of effective therapeutics. The most common adult neuroeurodegenerative disorders, Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), have proven particularly difficult to model either in animals or in vitro. Most drugs entering the AD drug development pipeline have failed; only one agent specifically for AD has received approved over the past 10 years—Axona (caprylidene) from Accera, approved in March 2009—for an overall candidate drug failure rate of about 99.6%.

    Recently, induced pluripotent cell lines (iPSC) lines have been generated from skin cells of individuals with a variety of degenerative diseases, including AD and PD. Investigators say that when a disease-specific phenotype is detectable in differentiated cells, reprogramming technology provides a new opportunity to identify aberrant disease-associated pathways and drugs that can block them. By studying the differences between normal and diseased cells, researchers can better understand what causes cells to die and identify key points in the process that may lead to treatments to change the course of the disease.

    Some of the first diseases modeled with iPSCs have been neurodegenerative that affect children (e.g., Retts Syndrome, or RTT, a severe X-linked neurodevelopmental disorder that affects 1 in 10,000–20,000 girls worldwide, making it one of the most common forms of mental retardation in females). A key discovery in 1999 identified a causative link between mutations in the methyl-CpG binding protein, MeCP2, and RTT, thereby enabling mechanistic studies and providing a target for potential treatments.

    MeCP2 protein functions as a transcriptional repressor critical for normal neurological function. Prior studies demonstrated that either loss or doubling of MeCP2 results in postnatal neurodevelopmental disorders; restoration of MeCP2 function in a mouse model of the disease reverses the neurological symptoms in adult mice raising the possibility that this disorder may be treatable in humans.

    Maria C.N. Marchetto, Ph.D., and colleagues working at The Salk Institute, UCSD, and Penn State, developed a human model of RTT by generating iPSCs from fibroblasts of RTT patients carrying different MeCP2 mutations and unaffected individuals. The investigators reported that the RTT-iPSCs retained the capacity to generate proliferating neural progenitor cells (NPCs) and functional neurons that underwent the X-inactivation typical of differentiated cells in females.

    In the iPSC neurons, they observed a reduced number of dendritic spines and synapses in iPSC-derived neurons and detected an altered frequency of intracellular calcium spikes and electrophysiological defects in RTT-derived neuronal networks. Their data indicate a potential imbalance in the neuronal networks associated with RTT pathology, according to the scientists, and their findings provide valuable information for RTT and, potentially, autistic spectrum disorder (ASD) patients, since they suggest that presymptomatic defects may represent novel biomarkers to be exploited as diagnostic tools and that early intervention may be beneficial.

    Last April, Bristol-Myers Squibb (BMS) announced that it had acquired iPierian, a biotech company focused on the discovery and development of new treatments for tauopathies, which represent a class of neurodegenerative diseases associated with the pathological aggregation of Tau protein in the human brain.

    IPierian has developed its monoclonal antibody program based on Tau discoveries made using the company’s iPSC technology. The company used iPSC disease models that combine human cortical neurons, motor neurons, microglia, and astrocytes in a dish to discover and validate novel therapeutic targets or mechanisms of disease. Leveraging the company’s iPSC capabilities, the company said, can provide insight into the earliest drivers of diseases such as Alzheimer’s, in contrast to conventional autopsy samples that typically only allow for study of end-stage pathophysiology.

    The acquisition gives BMS full rights to iPierian’s lead preclinical monoclonal antibody, IPN007, that may offer a promising new approach to treat progressive supranuclear palsy and other tauopathies, and that could potentially enter Phase I clinical trials this year.

    The antibody, BMS says, represents a new approach to Alzheimer’s by targeting a novel form of secreted Tau protein that is differentially regulated in Alzheimer’s disease patients to slow the spread of Tau throughout the brain and, therefore, inhibit the associated disease progression.

    Parkinson’s Disease

    In most individuals, PD occurs idiopathically, arising sporadically with no known cause. However, about 15% of individuals have family members with Parkinson’s disease. By studying families with hereditary Parkinson’s disease, scientists have identified several genes that are associated with the disorder, resulting in the discovery of three genes and the mapping of five others that are linked to rare familial forms of the disease (FPD).

    The products of the identified genes, including α-synuclein (PARK 1), parkin (PARK 2), and ubiquitin-C-hydrolase-L1 (PARK 5), remain the subject of intense studies designed to elucidate the underlying mechanism of FPD pathogenesis. Particularly noteworthy was the discovery reported in 2006 in The New England Journal of Medicine of an “astonishing high” prevalence of a single mutation in leucine-rich repeat kinase 2 (LRRK2), G2019S, in North African Arabs and Ashkenazi Jews with PD.

    While the function of the LRRK2 protein is not yet fully determined, it occurs in brain areas most affected by PD. The G2019S mutation is believed to be responsible for upregulation of LRRK2 kinase activity, which may ultimately play a role in neuronal loss. The authors noted that the G2019S mutation appeared to be an important cause of both familial and sporadic Parkinson’s disease in this group of Ashkenazi Jewish individuals.

    Several laboratories have developed iSPC models from individual PD patients. These models, the scientists say, have the potential to enable characterization of the complex pathophysiologic mechanisms underlying the disease, allowing identification of potential interventions earlier in its course.

    Because PD is characterized by loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), investigators have generated iPSC-derived midbrain dopaminergic neurons to investigate pathogenic mechanisms in cell type as a means of modeling PD.

    Byers et al. working at Stanford University reported the generation of iPSC-derived midbrain dopaminergic neurons from a patient with a triplication in the α-synuclein gene (SNCA). They observed that the iPSCs readily differentiated into functional neurons, and the PD-affected line exhibited disease-related phenotypes in culture. These included α-synuclein accumulation, inherent overexpression of markers of oxidative stress, and sensitivity to peroxide-induced oxidative stress.

    They concluded, based on these findings, that the dominantly acting PD mutation can intrinsically perturb normal cell function in culture and confirmed that these features reflect, at least in part, a cell autonomous disease process that is independent of exposure to the entire complexity of the diseased brain.

    Other investigators, in a further refinement of iPSC neurodegenerative modeling, say that the immaturity of neurons differentiated from human induced pluripotent stem cells presents difficulties for modeling late-onset neurodegenerative disorders such as Parkinson’s disease.

    The investigators say this raises concerns as to how well iPSC-derived cells can model diseases where patients do not develop symptoms until later in life, implicating age as a necessary component to disease progression. They note that several studies of these cells have shown loss of age-associated characteristics during iPSC induction, including increase in telomere length, loss of mitochondrial fitness, and loss of senescence markers in iPSCs derived from older donors.

    Justine D. Miller and colleagues working at Memorial Sloan Kettering, Boston Children’s Hospital, Weill Cornell Medical College, DNAVEC, and other institutions developed a strategy for inducing age-related features based on Progerin expression in iPSC-derived fibroblasts and neurons. Progerin, a mutated version of the normal cellular protein lamin A, functions to maintain the structure of a cell’s nucleus. A truncated form of the protein is a hallmark of the early aging disease, Progeria.

    The investigators found that by use of synthetic mRNA to overexpress progerin they could reestablish age-related markers in iPSC-fibroblasts, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body-precursor inclusions. Thus, they concluded, their study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models.

    As investigators continue to refine iPSC models for degenerative diseases, the possibility of developing drugs to prevent these disorders, halt their advancement, and even reverse them may be closer to realization.

Prehospital Thrombolysis for Stroke: An Idea Whose Golden Hour Has Arrived


Soon after thrombolytic therapy was established as a therapy for ischemic stroke, our colleague Anthony Furlan, MD, famously circulated a cartoon of a computed tomographic (CT) scanner visible through the back doors of an ambulance, where a happy stroke physician had hung a bottle dripping tissue plasminogen activator (tPA) into the scanned patient’s arm. Because the time interval from stroke onset to initiation of thrombolysis after ischemic stroke is inversely related to the probability of disability-free recovery, prehospital initiation of thrombolytic therapy seemed a compelling and logical ambition, if one could rule out intracranial hemorrhage prior to treatment.

 

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From the desk of Zedie.

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