Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis

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Avi Gadoth, MD1; Beatrice Nefussy, PhD1; Margalit Bleiberg, PhD2; Tirza Klein, MD3,4; Irena Artman, MD1; Vivian E. Drory, MD1,4

[+] Author Affiliations

JAMA Neurol. Published online April 13, 2015. doi:10.1001/jamaneurol.2015.48

ABSTRACT

ABSTRACT | INTRODUCTION | METHODS | RESULTS | DISCUSSION | CONCLUSIONS |ARTICLE INFORMATION | REFERENCES

Importance  Celiac disease is an autoimmune disorder triggered by gluten in genetically predisposed individuals. Gluten sensitivity can cause neurologic manifestations, such as ataxia or neuropathy, with or without gastrointestinal symptoms. Many patients with gluten ataxia produce antibodies toward the newly identified neuronal transglutaminase 6 (TG6). Two case reports described patients initially diagnosed with amyotrophic lateral sclerosis (ALS) and ultimately with celiac disease who improved with a strict gluten-free diet.

Objective  To evaluate the prevalence of celiac disease–related antibodies and HLA antigen alleles, as well as TG6 antibodies, in patients with ALS and healthy individuals serving as controls to determine whether a neurologic presentation of a gluten-related disorder mimicking ALS might occur in some patients.

Design, Setting, and Participants  In a case-control study conducted in an ALS tertiary center, we measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase 2 (TG2) and endomysium, as well as IgA and IgG antibodies to deamidated gliadine peptide and TG6 and performed HLA antigen genotyping in 150 consecutive patients with ALS and 115 healthy volunteers of similar age and sex. Participants did not have any known autoimmune or gastroenterologic disorder and were not receiving any immunomodulatory medications. The study was conducted from July 1, 2010, to December 31, 2012.

Main Outcomes and Measures  Antibody levels and frequency of individuals with abnormal antibody values as well as frequency of HLA antigen alleles were compared between patient and control groups.

Results  All patients and control group participants were seronegative to IgA antibodies to TG2, endomysium, and deamidated gliadine peptide. Twenty-three patients (15.3%) were seropositive to TG6 IgA antibodies as opposed to only 5 controls (4.3%) (P = .004). The patients seropositive for TG6 showed a classic picture of ALS, similar to that of seronegative patients. Fifty patients and 20 controls were tested for celiac disease–specific HLA antigen alleles; 13 of 22 TG6 IgA seropositive individuals (59.1%) were seropositive for celiac disease–related alleles compared with 8 (28.6%) of the 28 seronegative individuals (P = .04). Mean (SD) levels of IgA antibodies to TG2 were 1.78 (0.73) in patients and 1.58 (0.68) in controls (normal, <10 21.0="" 29.3="" 6.08="" 7.46="" a="" and="" antibodies="" autoantibodies="" controls="" deamidated="" gliadin="" i="" iga="" in="" levels="" mean="" normal="" of="" participants="" patients="" peptide="" study="" style="border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; padding: 0px; vertical-align: baseline;" subset="" tg6="" to="" were="">P

= .02; normal, <26 span="">

Conclusions and Relevance  The data from this study indicate that, in certain cases, an ALS syndrome might be associated with autoimmunity and gluten sensitivity. Although the data are preliminary and need replication, gluten sensitivity is potentially treatable; therefore, this diagnostic challenge should not be overlooked.

Ketogenic diet

From Wikipedia, the free encyclopedia

This article is about a dietary therapy for epilepsy. For information on ketogenic low-carbohydrate diets as a lifestyle choice or for weight loss, see Low-carbohydrate diet.

Testing for ketone bodies in urine

The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fuelling brain-function. However, if there is very little carbohydrate in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures.^[1]
The original therapeutic diet for paediatric epilepsy provides just enough protein for body growth and repair, and sufficient calories^{[Note 1]} to maintain the correct weight for age and height. This classic ketogenic diet contains a 4:1 ratio by weight of fat to combined protein and carbohydrate. This is achieved by excluding high-carbohydrate foods such as starchy fruits and vegetables, bread, pasta, grains and sugar, while increasing the consumption of foods high in fat such as nuts, cream and butter.^[1]
Most dietary fat is made of molecules called long-chain triglycerides (LCTs). However, medium-chain triglycerides (MCTs)—made from fatty acids with shorter carbon chains than LCTs—are more ketogenic. A variant of the classic diet known as the MCT ketogenic diet uses a form of coconut oil, which is rich in MCTs, to provide around half the calories. As less overall fat is needed in this variant of the diet, a greater proportion of carbohydrate and protein can be consumed, allowing a greater variety of food choices.^[2][3]
The classic therapeutic ketogenic diet was developed for treatment of paediatric epilepsy in the 1920s and was widely used into the next decade, but its popularity waned with the introduction of effective anticonvulsant drugs. In the mid-1990s, Hollywood producer Jim Abrahams, whose son's severe epilepsy was effectively controlled by the diet, created the Charlie Foundation to promote it. Publicity included an appearance on NBC's Dateline programme and ...First Do No Harm (1997), a made-for-television film starring Meryl Streep. The foundation sponsored a multicentre research study, the results of which—announced in 1996—marked the beginning of renewed scientific interest in the diet.^[1]
Almost half of children and young people with epilepsy who have tried some form of this diet saw the number of seizures drop by at least half, and the effect persists even after discontinuing the diet.^[4] The most common adverse effect is constipation, affecting about 30% of patients—this was due to fluid restriction, which was once a feature of the diet, but this led to increased risk of kidney stones, and is no longer considered beneficial.^[4][5] There is some evidence that adults with epilepsy may benefit from the diet, and that a less strict regimen, such as a modified Atkins diet, is similarly effective.^[1] Clinical trials and studies in animal models (including C. elegans^[6]) suggest that ketogenic diets provide neuroprotective and disease-modifying benefits for a number of adult neurodegenerative disorders.^[7][8] As of 2012, there is limited clinical trial data in these areas, and, outside of paediatric epilepsy, use of the ketogenic diet remains at the research stage.^[5][9][10]

Contents

Catching a simple infection can damage your IQ for several YEARS, study warns

 

• The more infections a person suffers, the bigger the damage to brain power
• Damage can occur after any infection, but is worse after brain infection
• Those hospitalised with 1 infection had IQ scoreof 1.76 lower than average
• Those with in hospital five times or more due to infections had an IQ score of 9.44 lower than the average

 A simple infection in the body can have such a profound effect on the brain that a person's IQ can drop, new research claims.Danish researchers say the link is very real - and the more infections a person suffers, the bigger the damage to their brain power.This damage can last for 'many years', they warn.  While the effect was seen after infections in any part of the body - for example, the stomach, urinary tract or skin - the most 'damage' was seen following infections in the brain.

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Catching a simple infection can damage a person's IQ for several years, a study has found. And the more severe it is, the worse the damage
The researchers  found that people who were hospitalised due to infection had an IQ score of 1.76 lower than the average.And those with five or more hospital contacts with infections had an IQ score of 9.44 lower than the average.The average IQ is said to be no higher than 115.  The researchers say the study is the largest of its kind to date, and it shows 'a clear correlation' between infection levels and impaired mental abilities.And, unsurprisingly, the more severe the infection, the worse the damage, according to the study, published in the journal PLOS ONE.Explaining why this effect may occur, study author Dr Michael Eriksen Benrós, of the University of Copenhagen, said: 'Infections can affect the brain directly, but also through peripheral [surrounding] inflammation, which affects the brain and our mental capacity.

'Infections have previously been associated with both depression and schizophrenia, and it has also been proven to affect the cognitive ability of patients suffering from dementia.  
'This is the first major study to suggest that infections can also affect the brain and the cognitive ability in healthy individuals.'
He added it may be the immune system that causes the mental impairment, not just the infection.
Normally, the brain is protected from the immune system, but with infections and inflammation, the brain may be affected.  
Dr Eriksen Benrós added: 'We can see that the brain is affected by all types of infections. 
'Therefore, it is important that more research is conducted into the mechanisms which lie behind the connection between a person's immune system and mental health.'

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Researchers found that people who were hospitalised due to infection had an IQ score of 1.76 lower than the average. And those who'd suffered five serious infections had a score of 9.44 lower than the average

The research was conducted in collaboration with researchers from the University of Copenhagen and Aarhus University.It tracked 190,000 Danes born between 1974 and 1994, who had their IQ assessed between 2006 and 2012.Around 35 per cent of these people had been in hospital with an infection before the IQ testing was conducted.Commenting on the findings, Dr Eriksen Benrós added: 'Moreover, it seems that the immune system itself can affect the brain to such an extent that the person's cognitive ability measured by an IQ test will also be impaired many years after the infection has been cured.'He hopes that learning more about this connection will help to prevent the impairment of people's mental health and improve future treatment.Experiments on animals have previously shown that the immune system can affect cognitive capabilities, and more recent minor studies in humans have also pointed in that direction.

This incredibly difficult maths puzzle is somehow aimed at eight-year-olds in Vietnam

UPVOTE

The children of Singapore and Hong Kong have already proven themselves to be geniuses and now it’s the turn of kids from Vietnam.

A new, incredibly difficult, puzzle has emerged from the country, and according to reports it’s aimed at eight-year-old children.

The aim is to fill the missing gaps in the snake with the numbers 1-9. You are only allowed to use each number once, and that colon sign represents division. There is no “complicated” maths involved, simply addition, subtraction, multiplication and division.

First posted by VN Express, and subsequently spotted by the Guardian, there are reportedly 362,880 combinations for placing nine different digits in nine slots.

Good night and good luck.

Scroll down for the solution

Solution

There are in fact many different solutions to this problem, with commenters on both Redditand the Guardian coming up with dozens - with many writing a computer script to provide the answers. The one above is adapted from thesilentcoder.

According to the Guardian’s Alex Bellos, the best way to solve this puzzle using a paper and pencil is to break it down into an equation - replacing the numbers with letters. From there it is simply a matter of trial and error to finding the solutions

Scores of Scientists Raise Alarm About the Long-Term Health Effects of Cellphones

PathDoc/Shutterstock

Are government officials doing enough to protect us from the potential long-term health effects of wearable devices and cellphones? Maybe not. A letter released today, signed by 195 scientists from 39 countries, calls on the United Nations, the World Health Organization (WHO), and national governments to develop stricter controls on these and other products that create electromagnetic fields (EMF).

"Based on peer-reviewed, published research, we have serious concerns regarding the ubiquitous and increasing exposure to EMF generated by electric and wireless devices," reads the letter, whose signatories have collectively published more than 2,000 peer-reviewed papers on the subject. "The various agencies setting safety standards have failed to impose sufficient guidelines to protect the general public, particularly children who are more vulnerable to the effects of EMF."

For decades, some scientists have questioned the safety of EMF, but their concerns take on a heightened significance in the age of ubiquitous wifi routers, the Internet of Things, and the advent of wearable technologies like the Apple Watch and Fitbitdevices, which remain in close contact with the body for extended periods.

"This is very much like studying tobacco back in the 1950s…The industry has co-opted many researchers."

Cellphones, among the most studied emitters of electromagnetic radiation, remain the standard for judging health risks. The federal Centers for Disease Control and Prevention maintains that "we do not have the science to link health problems to cell phone use." In a 2012 review of all available research, Timothy Moynihan, a doctor with the respected Mayo Clinic,concluded that "there's no consensus about the degree of cancer risk—if any—posed by cell phone use."

The WHO, on the other hand, classifies radio-frequency electromagnetic radiation (the type emitted by wifi routers and cellphones) as "possibly carcinogenic to humans" based on limited evidence associating cellphone use with an increased risk for glioma, a malignant type of brain cancer. "The conclusion means that there could be some risk," Dr. Jonathan Samet, a medical professor at the University of Southern California and chair of the WHO panel that made the determination,explained in 2011, "and therefore we need to keep a close watch for a link between cell phones and cancer."

Studies since then have highlighted the need for caution. Last year, French researchers found an almost three-fold increase in the incidence of brain cancer in people with more than 900 hours of lifetime cellphone use. Then, in March, Swedish researchers reported that the risk of being diagnosed with brain cancer increased by a factor of three in people who'd used cell or cordless phones for at least 25 years. Research on lab animals has caused similar concerns.

Respected medical groups are starting to pay attention. In 2013, the American Academy of Pediatrics urged the Federal Communications Commission, which regulates radiation levels in communication devices, to adopt cellphone standards that are more protective for children, and to better disclose products' EMF levels to consumers. In December, the California Medical Association urged regulators to "reevaluate microwave radiation exposure levels associated with wireless communication devices."

"We are really all part of a large biological experiment without our informed consent."

Most of the researchers who signed today's appeal letter believe that there's now enough evidence to classify radio-frequency EMF as "probably carcinogenic" or even just plain "carcinogenic," says Joel Moskowitz, director of the Center for Family and Community Health at the University of California-Berkeley, who played a central role in gathering the signatures. "All of them are clearly calling for the need for caution."

Reports about a lack of scientific consensus on the health effects of cellphones, which have appeared in Slate, Wired, the Verge, and elsewhere are somewhat misleading, Moskowitz contends. In a 2009 review for the Journal of Clinical Oncology, he parsed cellphone studies based on the funding source and quality of the science. He found that low-quality and industry-funded studies tended not to associate cellphone use with a heightened risk of tumors, while high-quality and foundation- or public-funded studies usually found the opposite result. "This is very much like studying tobacco back in the 1950s," he says. "The industry has co-opted many researchers."

In 2011, Moskowitz consulted for the San Francisco Board of Supervisors after it voted to pass the nation's first right-to-know cellphone ordinance. The law would have forced retailers to warn consumers about potentially dangerous radiation levels emitted by cell phones, but the supervisors agreed to effectively nix the law to settle a court challenge by the Cellular Telecommunications Industry Association; the industry's lead trade group argued that the law violated its free speech rights. (The CTIA did not return a call from Mother Jones requesting comment on today's appeal letter and the health effects of cellphones.)

On Tuesday, the Berkeley City Council will vote on a right-to-know law that was carefully worded to thwart legal challenges. Harvard Law School Professor Lawrence Lessig, who helped craft the law, has volunteered to defend it in court pro bono. "We are really all part of a large biological experiment without our informed consent," says Columbia University EMF expert Martin Blank in a video released to coincide with today's letter. "To protect ourselves, our children, and our ecosystem, we must reduce exposure by establishing more protective guidelines."

Stanford University

Stanford University is a private research university in Stanford, California, and 

one of the world's most prestigious institutions, with the highest undergraduate selectivity and the top position in numerous surveys and measures in the United States.

Stanford is located in northern Silicon Valley near Palo Alto, California. The University's academic departments are organized into seven schools, with several other holdings, such as laboratories and nature reserves, located outside the main campus. Its 8,180-acre campus is one of the largest in the United States.  The University is also one of the top fundraising institutions in the country, becoming the first school to raise more than a billion dollars in a year.

Stanford was founded in 1885 by Leland Stanford, former governor of and U.S. senator from California and leading railroad tycoon, and his wife, Jane Lathrop Stanford, in memory of their only child, Leland Stanford, Jr., who had died of typhoid fever at age 15 the previous year. Stanford was opened on October 1, 1891 as a coeducational and non-denominational institution. Tuition was free until 1920. The university struggled financially after Leland Stanford's 1893 death and after much of the campus was damaged by the 1906 San Francisco earthquake. Following World War II, Provost Frederick Terman supported faculty and graduates' entrepreneurialism to build self-sufficient local industry in what would later be known as Silicon Valley. By 1970, Stanford was home to a linear accelerator, and was one of the original four ARPANET nodes (precursor to the Internet).

General Knowledge Quiz Questions 1 2 3 4

General Knowledge Quiz Questions 1

1. In which American city would you find the headquarters of General Motors?
2. The Maiwand Lion is a sculpture and war memorial in the Forbury Gardens, a public park in which English town?
3. Who became the Labour MP for Hampstead and Highgate in 1992?
4. Which newspaper, once the biggest selling English language newspaper in the world, ceased publication in 2011?
5. In which war was the Gatling gun first used?
6. Which country has a flag that is not rectangular?
7. Which desert covers much of Botswana and parts of Namibia?
8. Which rock band wrote and performed the theme for the long-running adult cartoon South Park?
9. Which viaduct carrying the M6 motorway in Birmingham is a quarter mile longer than the Second Severn Crossing?
10. Who was the 40th President of the United States?

General Knowledge Quiz Questions 2 

1. Where does an arboreal creature typically live?
2. In heraldry, what colour is vert?
3. Who asks the quiz questions in ITV's 'The Chase'?
4. Considered one of the founders of analytic philosophy, who won the 1950 Nobel Prize in Literature?
5. Who have their headquarters at One Brewer's Green, London?
6. What is the most widely recognized national symbol of Canada?
7. Which unit of the Roman army consisted of 480 men?
8. The mainland portion of which country is formed by Jutland?
9. Name the oldest equestrian weekly magazine in the UK?
10. In 1997, who announced he was leaving the BBC to stand as an independent candidate in the Tatton constituency in Cheshire?

General Knowledge Quiz Questions 3

1. In which city did Roger Bannister run the first sub-four-minute mile in 1954?
2. Which large animal kills more people than any other animal in Africa?
3. Which country do swallows migrate to when they leave Britain for the winter?
4. Which country has the second largest land mass in the world if water is excluded?
5. In fashion, what do the initials DKNY stand for?
6. Occurring twice yearly, what name is given to a day consisting of twelve hours of daylight and twelve hours of darkness?
7. How many X chromosomes do women have?
8. Which city is the largest port in Germany?
9. Which country is the natural habitat of the emu?
10. Where in the world does the Up Helly Aa Fire Festival take place, which culminates in the burning of a Viking long ship?

General Knowledge Quiz Questions 4

1. Which American film and television actress is best known for her role as Jennifer Hart in the 1980s television series Hart to Hart?
2. In 1872, which country played England in the first ever international game of football?
3. Who married comedian Les Dennis in 1995?
4. Claire Richards was the lead singer in which dance-pop group?
5. Who became First Minister of Scotland after Alex Salmond's resignation?
6. Which Irish novelist was personal assistant of actor Henry Irving and business manager of the Lyceum Theatre in London?
7. Which singer starred in the televison documentary From Riches to Rags?
8. Who said: "The history of the world is but the biography of great men."?
9. How many hurdles are there in a 400 metres hurdles race?
10. In 1811, nearly a quarter of all the women in Britain were called what name?Find the answers  below: