Genetic defect may cause rare movement disorders

A Massachusetts General Hospital (MGH)-led research team has found that a defect in transcription of the TAF1 gene may be the cause of X-linked dystonia parkinsonism (XDP), a rare and severe neurodegenerative disease. Symptoms begin around age 40 with dystonia-involuntary muscle contractions that can force the body into abnormal, sometimes twisted positions and eventually proceed to Parkinson's-like symptoms, such as slowness of movement and a shuffling gait. Patients become progressively more disabled as the disease progresses and often die from complications such as infections or pneumonia.

Individuals with XDP share seven DNA sequence changes, which cluster within a region of the X-chromosome that includes the TAF1 gene. These sequence changes have always appeared to be inherited together. The largest genomics study ever performed for XDP, analyzing a total of 792 DNA samples from individuals with XDP and their unaffected relatives, as well as historical samples from studies dating back to the initial descriptions of the disease.

The analysis of these samples revealed a far greater genetic diversity among XDP patients than was previously known. While most shared a total of 54 unique sequence changes in a collection of variants known as a haplotype, in some individuals the haplotype had been broken apart due to genetic recombination. By comparing these recombination events, it was possible to narrow the disease-causing genomic segment to a smaller region that contained only the TAF1 gene.

Researchers reprogramed skin cells from patients with XDP and their healthy relatives back into stem cells, which differentiated into neural progenitor cells and then mature neurons. The team used RNA sequencing to characterize TAF1 expression patterns and found a defect in how the DNA sequence is transcribed into RNA in neural cells from XDP patients. In those cells, a portion of the TAF1 RNA appeared to terminate prematurely, which reduced expression of the full-length RNA. The truncated TAF1 RNA ended close to a known XDP-specific sequence variants - a large DNA insertion known as a retrotransposon.

 To determine whether the retrotransposon caused the transcriptional defect, t used genome they used editing tools to remove the sequence, which restored RNA transcription and normalized TAF1 expression. In a separate study, they analyzed the sequence of the retrotransposon in patients with XDP and found that it contained a segment of repetitive DNA that was longer in patients who developed symptoms at an earlier age and shorter in those whose symptoms appeared later.
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Vapers are vulnerable to pneumonia

The vapor from e-cigarettes seems to help pneumonia-causing bacteria stick to the cells that line the airways. The study included experiments with cells mice and humans. It showed that e-cigarette vapor had an effect similar to the reported effects of traditional cigarette smoke or particulate matter from fossil-fuel pollution, both of which are known to increase susceptibility to lung infection with pneumococcal bacteria.

Lead researcher, Jonathan Grigg, Professor of Paediatric Respiratory and Environmental Medicine at Queen Mary University of London, said the study indicates that vaping, especially in the long term, could raise the risk of bacterial lung infection. Pneumococcal bacteria can exist in human airways without causing illness. However, in some cases, they can invade the lining cells causing pneumonia or septicaemia. Exposure to traditional cigarette smoke helps these bacteria stick to airway lining cells, increasing the risk of infection.

The research examined the effects of e-cigarette vapor on a molecule produced by the cells that line the airways, called platelet-activating factor receptor (PAFR). Previous research by Professor Grigg's group has shown that pneumococcal bacteria use PAFR to help them stick to airway cells, which in turn increases the ability of bacteria to invade body tissues and cause disease. Research has also shown that PAFR levels increase in response to smoking, passive smoking, pollution and welding fumes.

Researchers examined human nose lining cells in the lab. They exposed some cells to e-cigarette vapor, some containing nicotine and some without, while other cells were not exposed. Cells exposed to either nicotine-containing or nicotine-free vapor produced levels of PAFR that were three times higher. When researchers introduced pneumococcal bacteria to these cells, they found that exposure to either nicotine-containing or nicotine-free vapor doubled the amount of bacteria that stuck to airway cells.

They tested the effect of e-cigarette vapor in mice and found that inhaled exposure to e-cigarette vapor also increased levels of PAFR on airway lining cells and increased the number of pneumococcal bacteria in the respiratory tract after infection, making mice more susceptible to disease. The team studied PAFR levels in cells lining the nose of 17 people. Of these, ten were regular users of nicotine-containing e-cigarettes, one used nicotine-free e-cigarettes, and six were not vapers.

First, PAFR levels in the airways of all 17 volunteers were measured. Then, vapers were asked to take at least ten puffs on their e-cigarettes over five minutes. One hour after vaping, PAFR levels on airway cells increased three-fold. The result shows that vaping makes the airways more vulnerable to bacteria sticking to airway lining cells. If this occurs when a vaper gets exposed to the pneumococcal bacterium, this could increase the risk of infection.
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Immune system may prevents MRSA infection

Researchers at Johns Hopkins, the University of California, Davis, and the National Institute of Allergy and Infectious Diseases have discovered how the immune system might protect a person from recurrent bacterial skin infections caused by Staphylococcus aureus (staph). "There's a huge, unmet clinical need for new approaches against staph skin infections because of declining antibiotic development and rising drug resistance," says Lloyd Miller, M.D., Ph.D., associate professor of dermatology at the Johns Hopkins University School of Medicine.

Staph is a common bacterium and the most common cause of skin infections in people. Additionally, multidrug resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), are causing severe skin infections in healthy people outside of hospitals. And once you've had an infection, the recurrence rate is 50 percent within six months. Staph can also spread from the skin and cause invasive and life-threatening infections such as sepsis, osteomyelitis and pneumonia.

Using mice with defective immune systems, research team found that after an initial exposure of the skin to staph, they were surprisingly protected against a second skin exposure with the same bacteria. After testing for antibodies and other usual suspects of the immune system against this infection, it was not clear what immune response was protecting the mice. The researchers then tested a drug FDA-approved for treatment of multiple sclerosis, which acts by preventing certain immune cells from leaving lymph nodes for sites of inflammation.

That genetic sequencing data revealed that specific cells substantially multiplied after the initial infection, then moved to the infection site and provided protection against the second infection. These so-called gamma delta T cells account for less than 1 percent of all the cells in the lymph node prior to infection. After infection, they accounted for more than 20 percent.

Working with collaborators from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, the researchers tested blood from healthy individuals and people with a rare immune disorder that makes them highly susceptible to staph skin infections. Half of people with the disorder die by age 10, but if they survive to adulthood they somehow overcome their susceptibility to staph infections.

In blood samples from these patients, the researchers found an increase in the percentage of gamma delta T cells, similar to what they observed in mice, which remained stable over years. The findings and especially gamma delta T cells may be targeted for developing new therapies or a vaccine against staph skin infections.

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Respiratory tract infections linked to asthma

Respiratory tract infections in young children are linked to an increased risk of asthma and worse lung function in children who had upper respiratory infections like colds, sinusitis, laryngitis, tonsillitis, pharyngitis and otitis.

Children with respiratory tract infections have increased risk of developing asthma. Children who had suffered from lower respiratory tract infections, such as bronchitis, bronchiolitis, pneumonia and general chest infections can develop asthma.

Lung function is an objective measure of the function of the lungs and airways. Lung function could be affected without leading to symptoms, or it could lead to asthma or wheezing.

A child could be diagnosed with lung function unaffected, upper respiratory tract infections were not associated with worse lung function in children. However, lower respiratory tract infections at any age are link with worse lung. Lung function in childhood is related with lung function in adulthood.
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Dangers of sleeping pills

Sleeping pills pose the same threat as smoking a packet of cigarettes a day, it's linked to cancer and heart attack.

They cause infections, falling and dementia in the elderly, and they lose their effectiveness after a few weeks.

 The drugs block acetylcholine - which patients with Alzheimer's disease are believed to lack, causing them drowsiness.

 Researchers found the common pills may also increase the risk of contracting pneumonia.

Adults are advised to complete 150 minutes of such physical activity each week, with most choosing a brisk walk or gentle cycle.

Doing natural exercise, without the need to visit the gym, may provide the biggest benefits.

He added: 'I think trying to do it outside is also helpful, because bright light can help promote sleep.

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How HIV affects the immune system

Human Immunodeficiency virus (HIV) is a lentivirus that causes HIV and later AIDS. Early signs of HIV are: fever, joint pain, sore throat and skin rashes.

A T-cell is a type of lymphocyte - white blood cell that defend the body against disease, HIV infects a cell by attaching itself to T-cell, multiplies its virus and destroy the T-cell.

CD4 count shows the strength of one's immune system which is between 500 1500 for healthy people, being infected with HIV without treatment will reduce the count below 200.

 HIV  exposes the infected person to opportunistic  infections like: pneumonia, toxoplasmosis, thrush, and tuberculosis.

Presently, there is no cure for HIV. Antiretroviral therapy is recommended for people living with HIV virus.

Common side effects of Antiretroviral drugs are: glucose intolerance, kidney failure, hepatitis of the liver, insulin resistance, osteoporosis, anemia and inflamed pancreas.