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Litchi may be behind deadly Muzaffarpur epidemic. A toxin in litchi fruits may be linked to a mysterious and sometimes fatal brain disease that has afflicted children in Muzaffarpur, Bihar, and neighbouring districts since 1995, US researchers claim.
An association between the illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit producing region, according to a report by the US Centres for Disease Control and Prevention.
The Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks of the illness in 2013 and 2014. "Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin," the report said. A common laboratory finding was low blood glucose on admission, a finding associated with a poorer outcome; 44 per cent of all cases were fatal. A 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause, the report said. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur.
The 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies.
During May 17 - July 22, 2013, a total of 133 children were admitted to the two main referral hospitals in Muzaffarpur with illnesses that met the investigation case definition of acute onset seizures or altered mental status within 7 days of admission in a child aged 15 years. Of these, 71 per cent patients were from Muzaffarpur; other patients were from six neighbouring districts. Analysis of risk factors for death among 94 affected children showed that low blood glucose at admission was more common among those who died.
Data collected during the 2013 investigation suggested that the illness was more likely to be a noninflammatory encephalopathy than an infectious encephalitis, and raised concern for the possibility of a toxin-mediated illness. Building on the 2013 findings, NCDC and CDC again investigated this syndrome in 2014.
During May 26 - July 17, 2014, a total of 390 patients admitted to the two referral hospitals in Muzaffarpur with illnesses that met the same case definition used in 2013. Detailed clinical evaluation of 52 patients within 12 hours of admission elicited a history of generalised tonic or tonic-clonic seizures in 100 per cent, researchers said. "The 2013 and 2014 Muzaffarpur investigations indicate that this outbreak illness is an acute noninflammatory encephalopathy," the CDC said. The consistent finding of hypoglycemia among affected children underscores the importance of examining the possible role of compounds that might acutely result in low blood sugar, seizures, and encephalopathy, including the possible role of MCPG in litchis)
Tonic clonic or jerky movements of limbs, Altered consciousness, Loss of consciousness, Facial jerky movements, Uprolling of eyes, Froth in the mouth, Tongue bite, Urinary incontinence.
A. My daughter is now fit and fine thanks to Brains
"Our daughter Sundis was only 11 when we saw it happen for the first time. One moment she was up and about, dancing happily around our living room, and then the very next, she was down on the floor— limbs rigid, mouth frothing, her whole body convulsing. As we rushed to her we could see that she was not conscious. It was a moment of pure terror shock and terror," says Siddiq Mohammed, his voice trembling. "Back then we had not even heard of the word 'epilepsy', we had no idea what it was…we didn't know what had hit our little daughter…all we felt was pure chilling fear," continues Mohammed, a native of Kurdistan Zakho, a small town on the edge of the Iraqi-Turkish border district of Dohuk Governorate . Sure, given the huge strides neurological medicine has taken, you may not think epilepsy is such a big health crisis. "But that is only if you have access to the right medical attention," says Dr Shailesh A V Rao, senior neurosurgeon at BRAINS who was part of the team that took care of Sundis. "Back home in Iraq we went from doctor to doctor, hospital to hospital in search of answers, for the right diagnosis care and cure, but it was hopeless," says the now relieved father. "Our daughter continued to suffer from the terrible fits." "And then we met a former BRAINS patient," says Mohammed. "She told us about how she had recovered completely from epilepsy after being treated there." Soon after that, Sundis and her parents were on a plane to Bangalore. "It was definitely the moment that changed our lives," says Mohammed. "The doctors and facilities at BRAINS were top-class, everything and more than what we had expected".
"It's because of a combination of poor diagnosis, mis-matched drugs and wrong dosages that she had shown no improvement," says Dr Shailesh A V Rao, senior neurosurgeon at BRAINS who was part of the team that attended to the stricken girl. "Left untreated or improperly managed, epilepsy can be life threatening particularly if it were to strike during activities like swimming or driving." Sundis was on the path of recovery within days of reaching the hospital after a comprehensive medical exam and diagnostic tests confirmed her problem. "It is now more than a year since we left the hospital and she has not had a single attack of fits in all this time," says Mohammed, saluting the doctors and the facilities at the hospital for giving his daughter a new life. "I have only one word," he says. "Thanks." Epilepsy is a disorder of the central nervous system that causes repeated episodes of unprovoked seizures in people of all ages and backgrounds and is triggered by the disturbance of a brain's normal cell activity. During seizures patients experience abnormal behavior, symptoms and sensations, including loss of consciousness. There are many possible causes of epilepsy, including an imbalance of nerve-signaling chemicals called neurotransmitters, tumors, strokes, and brain damage from illness or injury, or a combination of these. To control and regulate all voluntary and involuntary responses in the body, nerve cells in the brain communicate with each other through electrical activity. A seizure occurs when part(s) of the brain receives a burst of abnormal electrical signals that temporarily interrupts normal electrical brain function.
B. Neural stem cell implants create hope in Epilepsy treatment
University of Florida Health researchers have successfully transplanted human stem cells in a mouse model, which developed into fully functional neurons. This is being seen as a promising advance in the direction of unlocking new treatments for epilepsy and other neurological disorders. According to Dr Steven N. Roper, a neurosurgeon and professor in the UF College of Medicine department of neurosurgery, the news is particularly encouraging because the human stem cells not only survived after the transplant but also developed into neurons that behaved normally within the brain. Transplantation of this sort may someday prevent seizures among patients of epilepsy, marked by uncontrolled muscle contractions and even unconsciousness. Even when they are effective medications only control the symptoms of epilepsy. In severe cases, seizures are curtailed by surgically removing part of the brain. In the study the human neural implants survived in a mouse model for eight weeks and developed into three types of interneurons or “connector” neurons. These are the neurons that could in the future be used to treat several neurological diseases.
Among epilepsy patients the implanted cells could be deployed to create inhibitory neurons to soothe the firestorm of overexcited brain cells that trigger seizures. “The study proves that human stem cells have the capability to provide the cell types required to treat many diseases. This is what makes us optimistic that these cells can eventually be used for treating a number of human conditions including Parkinson’s and Alzheimer’s that require superior control of brain function,” Roper said. The big advantage with neural stem cells in the area of research into neurological disorders is that limitless quantities of them can be grown in labs, said Brent Reynolds, a professor in the department of neurosurgery. Although researchers have earlier implanted human neural stem cells the knowledge that they can ultimately bond with the brain and become active is crucial. However, there are still a number of challenges to be dealt with. The survival rate of transplanted cells was just 1 per cent, a figure Roper said is “fairly low” but can be improved. “We need to find out how to manage the fate of the transplanted neural stem so that we are able to use a specific type of neuron to treat a specific disease,” Roper said.
Headache, Fever, Tenderness of scalp, Pain in the jaw and tongue while chewing, Blurred vision, Visual loss, Myalgias / body aches
Headaches, Nausea, Vomiting, Slow and steady impairment of motor abilities and seizures, Weakness on one side of the body, Cognitive impairment, Confusion, Personality changes, Difficulty in speech, Loss of vision.
A. Now an enzyme bullet to hit glioblastoma
An enzyme key to the survival and spread of glioblastoma cancer has been identified by a team of multicenter researchers. Since this enzyme is absent in healthy brain cells, it presents a promising target for ant-cancer drugs.
"The discovery of this may have opened a way to ensure that these cancer cells do not turn as aggressive," says Alfredo Quinones-Hinojosa, M.D., professor of neurological surgery and oncology at the Johns Hopkins University School of Medicine. Glioblastoma is the most devastating of all human cancers and patients very rarely make it past 14 months after diagnosis. "The latest findings show us a way to starving the cancer cells of the energy they need to grow."
Many other cancers have an enzyme named glucose-6-phosphatase (G6PC), which enables the diseased cells top devour glucose 200 times faster than do the normal, healthy cells. However, so far there was nothing to suggest that this enzyme was present in glioblastoma. Because Hinojosa was certain that it was in his patients' tumors, his team set out to study glioblastoma cells from patients.
"Cancer need energy to proliferate much like normal cells" says Sara Abbadi, Ph.D, a research fellow on the team. “But cancer cells are able to survive in conditions where normal, healthy cells cannot.” This is the reason why glioblastoma is so difficult to treat.
When G6PC production is inhibited the viability of the cells and also their mobility is reduced, the team observed. Also, when the team subjected glioblastoma cells with 2DG, a form of glucose that transforms glioblastoma cells into a less malignant form making them sensitive to other treatments, they saw that the cells with uninhibited G6PC production were able to recover their malignancy and could move even faster than they had before. Dual treatment with 2DG and blocking G6PC expression, however, not only prevented those cells from recovering their malignancy but also killed them.
"Part of the problem in treating cancer is that it's going to be virtually impossible to find one magic bullet," says Quinones-Hinojosa, "but at least we're beginning to dismantle the different mechanisms that these cells use".
B. Tetanus shot may boost brain cancer survival
A glioblastoma patient has survived 9 years after she was diagnosed with the deadly cancer. She was given a simple tetanus shot in combination with a vaccine treatment. Invariably, glioblastoma kills its victims within a maximum of 15 months post diagnosis regardless of the treatment.
And this is not a stray case. In their recently published study, researchers from the Duke Cancer Institute have reported that the administration of tetanus along with a vaccine procedure dramatically extends the survival of glioblastoma patients. In their study three of the patients lived years longer than expected after receiving a tetanus shot, which they say enhanced an immunotherapy targeting a virus in the tumour.
Glioblastoma tumours carry a strain of cytomegalovirus not seen in surrounding brain tissue, earlier research had found. This virus acts as a natural target for immunotherapy, a procedure that turns the power of a patient`s own immune system against the cancer cells.
"Because the average survival is 12 to 15 months in patients diagnosed with this tumour, we were quite surprised when three patients had much longer survival times," said Kristen Batich, a medical student at the Duke University and study author. In the study conducted by Batich and her colleagues, 12 glioblastoma patients were divided into two groups: six were given a tetanus booster and the other six received a placebo (dummy) shot. The following day, all of them took dendritic cell immunotherapy, a treatment that uses dendritic cells to "train" the immune system to respond to a specific infectious agent.
Three of the patients who had received a dose of tetanus in addition to the immunotherapy lived much longer than the average of 12-15 months. One of them is still alive 9 years after she received the tetanus shot.
C. A Novel Way to Improve Vaccine Efficacy in Brain Tumors
For years scientists have tried to beat back glioblastoma using immunotherapy, a process that turns the body’s own immune system against the deadly cancer but with very little success. Finally, however, a new study published in Nature, researchers claim to have discovered a way to improve the outcome of immunotherapy among glioblastoma patients.
“For a while immunotherapies including dendritic cell-based therapy have been considered promising for combating brain cancer. However, our study shows that it is possible to significantly improve their clinical impact among patients with this terrible disease,” said Duane A. Mitchell, M.D., Ph.D., director of the Brain Tumor Immunotherapy Program at the University of Florida in Gainesville and co-lead author of the study.
Normally specialized immune cells called dendritic cells capture microorganisms and migrate to the lymph nodes where they prepare immune weapons like T cells, to fight off the invaders. They have, therefore, been used for immunotherapy against a variety of tumor types, including brain tumours. These cells are drawn from patients and then injected back into them after they have been ‘doctored’ to express antigens from the tumor to create a vaccine. Inside the patient, the injected dendritic cells activate T cells, which are not only capable of battling the tumor buts also can prevent it from returning via an immune memory response.
Would increasing dendritic cell migration to lymph nodes improve the efficacy of the vaccine? To find out Dr. Mitchell and his team administered a tetanus booster shot on a random group of glioblastoma patients before injecting them with the dendritic cell vaccine. The purpose of the booster was to set off an inflammatory response at the vaccination site and thereby prep the immune system for a larger battle. Another group of patients received their own native dendritic cells instead of a tetanus shot before being treated with the dendritic cell vaccine.
The results showed that a shot of tetanus booster prior to the injection of the vaccine not only increased the migration of dendritic cells to lymph nodes but also had a significant effect on clinical outcomes. The booster patients lived more than 36.6 months after diagnosis compared to an average of 18.5 months in those who received dendritic cells alone.
D. Genes responsible for brain tumour growth identified
A family of genes thought to be behind the growth of a wide range of difficult-to-treat tumours has been identified by scientists.
Joshua Breunig, the lead author of the study and a research scientist in the Brain Programme at the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the US said that these new genetic findings have opened a way for us to work towards developing targeted therapeutics, which hopefully could be used in the future to treat patients with high grade brain tumours".
Known as gliomas high-grade brain tumours are difficult to treat and patients rarely survive more than five years. Invariably, lethal secondary gliomas develop among patients treated for primary gliomas and that is nearly always fatal.
Moise Danielpour, director, Pediatric Neurosurgery Programme and the Center for Pediatric Neurosciences in the Maxine Dunitz Children's Health Center said that "any tumour can breed a range of several combinations of mutations". And despite major progress achieved in radiation and chemotherapy, a cure remains elusive.
Using cutting edge methods that can model up to five distinct tumour types within 45 minutes, researchers identified that the Ets family of genes were contributors to glioma brain tumours. These factors regulate the behaviour of tumour cells by controlling the expression of genes that are required for the growth of tumour and cell fate. Stopping the expression of Ets genes would help researchers identify and strategize novel treatment therapies.
E. Researchers find drug that could check spread of glioblastoma
A drug that targets a protein called TROY thereby limiting the spread of glioblastoma, the most common and aggressive brain tumour has been developed by researchers in Phoenix, US. Called propentofylline or PPF, the drug helps in increasing the potency of temozolomide (TMZ), and radiation, which are standard response to the deadly cancer. The researchers have claimed that PPF decreases the expression and curbs the invasion of glioblastoma cells and alongside increases their vulnerability to TMZ and radiation.
The senior author of the study Mr Nhan Tran at the Phoenix-based Translational Genomics Research Institute (Tgen), in Phoenix, US said that in combination with TMZ and radiation PPF could improve the clinical outcome for patients of brain tumour. Know More
F. Research points link between Glioblastoma & dopamine
Glioblastoma to date remains the deadliest and most aggressive cancerous brain tumour resisting all currently available treatments. A study by Canadian team of scientists has spearheaded brain cancer research into the field of neuro degenerative medicine and neuro-chemical signalling. New connects between glioblastoma and dopamine have been explored. It is a well established fact that a severe neurodegenerative condition known as Parkinson's disease occurs if the levels of dopamine dip in the brain or if dopamine signalling is interrupted. In the new study this process has been worked upon by identifying chemicals that block dopamine function in glioblastoma tumours in the lab. as A result the glioblastoma stem cells undergo neurodegenerative process which kills glioblastoma stem cells instead of causing Parkinson's. Know More
Seizures, Endocrine Problems (diabetes and/or hormone regulation), Visual changes or double vision, Headaches, Paralysis of nerves/muscles of the face or half of the body, Respiratory changes, Clumsy, Uncoordinated walk, Hearing loss, Personality changes.
A. A diamond edged weapon against cancer
By attaching the chemotherapy drug Epirubicin to nanodiamonds it may be possible to effectively destroy chemoresistant cancer stem cells says a study led by the National University of Singapore (NUS). Led by Assistant Professor Edward Chow, Junior Principal Investigator at the Cancer Science Institute of Singapore (CSI Singapore) at NUS, the study shows that repurposing prevalent chemotherapy drugs with the help of nanotechnology is an effective method for defeating cancer stem cells that are chemoresistant.
The ability of cancer cells to defy chemotherapy (chemo-resistance) is the main reason for the failure of treatment in cancer. The formation of tumour is initiated by cancer stem cells and these are commonly found to be more resistant to chemotherapy than the rest of the bulk tumour. This leads to the recurrence of the disease following chemotherapy.
The NUS researchers attached nanodiamonds to the widely-used chemotherapy drug Epirubicin and evolved a nanodiamond-Epirubicin drug delivery complex (EPND), which they found was capable of killing chemoresistant cancer stem cells and preventing secondary tumour formation.
The nanodiamonds provided a broader range of protection and more safely than any of the current approaches to overcome chemo-resistance with combination drugs. The delivery of Epirubicin by nanodiamonds rendered a normally lethal dosage of Epirubicin safe thereby enhancing its effectiveness.
The versatility of the nanodiamond-based drug delivery platform opens up the possibility of future applications of nanodiamonds such as the addition of other similar drugs as well as active targeting components such as antibodies or peptides against tumour cell surface proteins for targeted drug release.
B. Genes behind growth of brain tumour revealed!
A family of genes instrumental in the growth of a wide range of tough to treat brain tumours has been unmasked by a team of scientists at the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the US. The lead author Dr Joshua Breunig said that “following these fresh genetic findings, we propose to evolve targeted therapeutics that in the future may be effective against high-grade brain tumours and increase the survival of patients." It is extremely difficult as of now to treat high grade brain tumours or gliomas and the survival rate of patients is very low and almost never exceeds five years. Invariably, deadly secondary gliomas develop among patients treated for primary gliomas. This is a surefire killer. Tumours typically breed multiple different groupings of mutations, which defy even the latest in in radiation and chemotherapy and eventually kill patients. After modeling high grade brain tumours from stem cells that reside within the brain with the help of a leading edge method called rapid modeling, which is capable of creating as many as five distinct tumour models within 45 minutes, the scientists traced the gliomas to the Ets family of genes, which determine the behaviour of tumour cells by controlling the generation of genes required for tumour growth and the fate of a cell. By blocking the expression of the Ets genes, the researchers were able to identify and deploy novel treatment therapies. The researchers said that the immediate next steps would be to test the function of every individual Ets factor to understand their particular role in the progression and recurrence of tumour.
Severe pain in back of the nose and throat (nasopharynx), Pain in the back of the tongue/ear/throat/tonsil area/voice box (larynx), Pain usually on one side, Pain triggered by chewing/coughing/laughing/speaking/swallowing
Twitching of the muscles on one side of the face,Involuntary blinking of the eyes,Involuntary smacking/twitching of the lips, Hemi facial pain-sharp and shooting type for brief periods
Back pain/neck pain, Pain radiating to the hand from the neck,Shooting pain along the back of the leg, Burning sensation along the back of the leg, Numbness of feet, Muscle weakness, Bladder or bowel disturbance.
Involuntary dancing movements of limbs, Involuntary of facial muscles, Slowness of movements, Stiffness of muscles, Imbalance, Difficulty in talking and swallowing, Forgetfulness, Behavioral disturbances, Depression, Sleep disturbances, Personality change.