Gene expression may determine time of death

International team of scientists led by Roderic Guigó at the Centre for Genomic Regulation in Barcelona showed that changes in gene expression in different tissues triggered by death can be used to predict the time of death of an individual. Analyzing a few available tissues for example lung or skin tissue, the post-mortem interval-time elapsed since death can be determined with considerable accuracy and may have implications for forensic analyses.

It all started with the GTEx project, which aimed at creating a reference database and tissue bank for scientists to study how genomic variants affect gene activity and disease susceptibility. GTEx was designed to sample as many tissues as possible from a large number of individuals in order to understand the causal effects of genes and variants, and which tissues contribute to predisposition to disease.

To understand the tissue-specific changes to gene expression following the death of a person, Roderic Guigó and his colleagues studied RNA-sequencing data of over 7,000 samples from 36 different tissues obtained from 540 donor. They show that the time since death has an effect on gene expression and that this effect varies from tissue to tissue. Models for the prediction of the post-mortem interval based on these tissue-specific gene expression changes using high-throughput sequencing of the cell.
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Water could be deadly for an infant

Drinking too much water can be deadly for an infant, and even small amounts offer little benefit to babies. Water is key to adult health, but babies get fully hydrated from drinking breast milk. When an infants drink too much water, the sodium levels drop too lo, this hinders the process of nutrients, which can cause seizures, coma and death.

According to pediatric nurse Danielle Stringer, for the first six months of  infants lives, they are better off getting all of their calories and water from breast milk or baby formula. Drinking water can deprive babies of calories that they need in the first six months of their lives, leading to malnutrition and death.

The American Academy of Pediatrics advises that infants should consume exclusively breast milk - if at all possible - for the first six months of their lives, and continuing with supplemented soft foods and drinks through their first year. When babies drink too much water, it knocks their sodium to fluid ratio out of balance, and they can die of water intoxication.

Their bodies will try to overcompensate by having the cells take on more water, which will result in swelling all over the body, including the brain, which can result in seizures, coma or brain death. In rare cases when a baby is given an inordinate amount of water, this can happen suddenly, it's more likely to occur with small doses of water, over time.

Long before they seize, a lot of babies will just start to show signs of malnutrition, such as losing weight and swelling. Their tiny, rapidly growing bodies need about all the calories they can get, meaning they need nourishment - in the form of breast milk or baby formula - about every two to four hours. Breast milk is about 88 percent water, so new mothers that can breastfeed need not worry that their infants could get dehydrated.

At six months old, you can offer water to your baby in a sippy cup, but they don't typically need it because they are still getting breast milk or formula. Between six and 12 months old, it is safe for infants to have two to four ounces of water, but even then, interestingly, babies are smart enough that they're mainly not interested in water at that age, and parents need to know that that's totally okay for them.
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Kymriah for treating acute lymphoblastic leukemia

Kymriah (tisagenlecleucel) suspension for intravenous infusion, it is a prescription cancer treatment used in patients up to 25 years old who have acute lymphoblastic leukemia (ALL) that is either relapsing or refractory.

 Kymriah is made from your white blood cells, your healthcare provider has to take some of your blood called leukapheresis. Your blood cells are frozen and sent to the manufacturing site to make Kymriah.

 Your healthcare provider may give you chemotherapy for a few days to prepare your body. When your body is ready, your healthcare provider will give you Kymriah. The drug can increase the risk of life-threatening infections that may lead to death.

Having Kymriah in your blood may cause a false-positive HIV test result by some commercial tests. Kymriah may cause side effects that are life-threatening like: difficulty breathing, fever, shaking chills, confusion, severe nausea, vomiting, diarrhea, severe muscle or joint pain, very low blood pressure and dizziness.
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Cyltezo for chronic inflammatory diseases

Cyltezo is for the treatment of multiple chronic inflammatory diseases, including: moderate to severe active rheumatoid arthritis, moderate to severe polyarticular juvenile idiopathic arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active adult Crohn’s disease,
moderate to severe active ulcerative colitis and moderate to severe plaque psoriasis

Patients treated with adalimumab products, including Cyltezo, are at increased risk for developing serious infections that may lead to hospitalization or death.

Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease.

Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.

Do not start Cyltezo during an active infection, including localized infections.
Patients older than 65 years, patients with co-morbid conditions and patients taking concomitant immunosuppressants may be at greater risk of infection.

Cyltezo for patients with these disorders; discontinuation of Cyltezo should be considered if any of these disorders develop.
Hematological Reactions
Congestive Heart Failure
Autoimmunity
Patients on Cyltezo should not receive live vaccines.
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Targeted cell metabolism can improve immune system

Immune system can become so over-activated when fighting infections that the resulting inflammatory response can lead to death. Excessive response by the immune system can be modulated by targeted manipulation of the sugar metabolism to produce an immune response that eliminates the pathogens without causing any harmful to the immune system.

Using 2-Deoxy-D-glucose 2-DG during the infection make this possible, adding 2-DG, that prevents glycolysis, causes increased production of interleukin-12 IL-12, a pro-inflammatory cytokine, while suppressing the production of interleukin-10, an anti-inflammatory cytokine.

IL-12 triggers a specific T-cell immune response, which is part of the cellular immune response, to specifically boost the defence mechanisms that serve to eliminate intracellular pathogens like listeria. Addition of 2-DG changes the nature of the immune response and the intensity of the inflammatory process, inflammation is controlled so that the immune system is able to manage the situation without allowing the infection to leads to a deadly outcome.

This prevents excessive inflammatory responses, following addition of of 2-DG, only p40 is upregulated, while no p35 is produced. This modified cytokine profile, there is also a simultaneous increase in IL-23 expression which could subsequently bring about modified recruitment of immune cells and hence have a decisive influence on the intensity of the immune response.

The metabolic increased production of activating mediators with simultaneous inhibition of immunosuppressive mediators. Manipulation of the sugar metabolism and associated modulation of the immune system could open up new options for treating specific infectious and autoimmune diseases
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Mavyret for treating chronic hepatitis C

Mavyret is a prescription medicine used to treat adults with chronic hepatitis C virus HCV genotypes 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis. It contains two medicines: glecaprevir and pibrentasvir.

If you have ever had hepatitis B virus infection, the hepatitis B virus could become active again during or after treatment of hepatitis C virus with Mavyret. Hepatitis B virus becoming active again may cause serious liver problems including liver failure and death.

The common side effects are headache and tiredness.

The active ngredients in Mavyret are: glecaprevir and pibrentasvir

Inactive ingredients: colloidal silicon dioxide, copovidone (type K 28), croscarmellose sodium, hypromellose 2910, iron oxide red, lactose monohydrate, polyethylene glycol 3350, propylene glycol monocaprylate (type II), sodium stearyl fumarate, titanium dioxide, and vitamin E (tocopherol) polyethylene glycol succinate.
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The 16 genetic markers associated with short lifespan

How long we will live is encoded in our genome. Researchers have identified 16 genetic markers associated with a short lifespan. This reveals computational framework to uncover the genetics of our time of death and disease. It explained why some people live longer than others. 

 About 30 percent of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could be responsible for some of the reasons for our longevity.

Changes in the DNA is linked to age-related diseases. About 1 in 10 people carry some configurations of these markers that shorten their life by over a year compared with the population average. Those who inherited a lifespan-shortening version of one of these SNPs may die earlier than their mate. 

The researchers explore how the DNA changes affected lifespan in a holistic way. They discovered that most SNPs had an effect on lifespan by impacting more than a single disease or risk factor, for example through being more addicted to smoking as well as through being predisposed to schizophrenia.

The discovered SNPs and gene expression data, allowed the researchers to identify that lower brain expression of three genes neighbouring the SNPs- RBM6, SULT1A1 and CHRNA5, involved in nicotine dependence was linked to increased lifespan. These three genes could therefore act as biomarkers for surviving beyond 100 years. 

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Neuroticism may postpone death

Having higher levels of trait of the neuroticism may reduce the risk of death for those that hav poor health. An aspect of neuroticism related to worry and feelings of vulnerability was associated with lower mortality, irrespective of state of health.

Being high in neuroticism may sometimes have a protective effect, perhaps by making people more vigilant about their health. People with high levels of neuroticism may experience negative emotions like irritability, frustration, nervousness, worry, and guilt compared with those who have lower levels of neuroticism.

 The link between neuroticism and risk of death may depend on how people rate their health. The protective effect was present in people who rated their health very low or does not really care about what will happen to their health.

Behaviors like smoking, exercise, diet and alcohol consumption did not have any link with vulnerability and mortality risk. Worry and vulnerability to sicknesses and diseases might encourage people to behave in a healthier way and hence lower their risk of sudden death.
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Heartburn drugs increases untimely death

Proton pump inhibitors (PPIs), a heartburn drug is linked to different health problems like kidney damage, bone fractures and dementia.

Researchers examined medical records of users of PPIs and people who took another class of drugs for treatment of stomach acid. They discovered that there is an increased risk of death among PPI users.

Researchers compared patients taking H2 blockers with those taking PPIs for one to two years and discovered that patients taking  PPIs had a 50 percent increased risk of dying over the next five years.

PPIs and H2 blockers are used for treating serious medical conditions like upper gastrointestinal tract bleeding, gastroesophageal reflux disease, heartburn and esophageal cancer.
Long-term use of PPIs increased risk of death.
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HPV vaccine can reduce cervical cancer

Cervical cancer affects more than half a million women and causes more than a quarter of a million deaths globally.
Cervical cancers result from a human papillomavirus, or HPV infection.

HPV infections can cause cancers in other parts of the body, the latest HPV vaccine could prevent infections and many cancers.

The HPV vaccine could prevent up to 90 percent of HPV-related cancers, the vaccine can prevent HPV infection if the vaccine is given before exposure to any of the HPV types that the vaccine protects against.

 Different formulas of the HPV vaccine protect against different types of HPV. Only two types, HPV16 and HPV18, cause 70 percent or more of all invasive cervical cancers and all HPV vaccine formulas protect against these two.

 The nonavalent formula of the HPV vaccine is the most protective: it protects against HPV16, HPV18 and five other cancer-causing HPV types.

Experts estimate that the nonavalent HPV vaccine could reduce HPV-related cancers worldwide by 90 percent or more if the entire global population received it.
     


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Malaria can cause bone loss

Malaria caused by Plasmodium parasites is a life-threatening infectious disease that kills at least half a million people annually while causing over 200 million new infections.

Common complications are: cerebral malaria, respiratory distress and severe anemia, often leading to death. The majority of patients recover from disease, however, there is increasing evidence to suggest that survivors experience long-term 'hidden' pathologies due to infection.

Now, the Laboratory of Malaria Immunology Team at the Immunology Frontier Research Center (IFReC), Osaka University, headed by Professor Cevayir COBAN, have used mouse malaria models to show that robust immune activation and invasion of parasite by-products into the bone marrow during and after malaria infection leads to an adverse balance in bone homeostasis.

Researchers discovered that Plasmodium products continuously accumulate in the bone marrow niche which turns the bone noticeably black in color, and results in it being "eaten-up" by bone resorbing cells known as osteoclasts, eventually disrupting bone homeostasis.

 Side effects of malaria infection on bone can be reversed by taking oral supplementation with alfacalcidol, a vitamin D3 analog, could completely prevent bone loss. Anti-malarial drugs combined with bone therapy may be beneficial in improving bone health in malaria-infected individuals.

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Amazing facts about tobacco

•According to the World Health Organisation, tobacco is the world's
largest cause of preventable death.

•The total tax revenue from tobacco in the UK in 2015-16 was £12billion.

•Estimates of the direct annual cost to the NHS of tobacco-related diseases range from £3-6bn.

•King James IV in 1604 described smoking as a “custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous to the lungs.

•The average adult in China smokes 4,124 cigarettes a year, the world’s highest figure.

•There are about a billion smokers in the world of whom 80 per cent are male.

•The word tabacco in Spanish was originally used for the pipe or tube through which native Americans inhaled tobacco smoke.

•Tobago took its name from tobacco, possible because of its cigar or pipe-like shape.

•The word tobacco was first seen in English in 1577. Tobacconist, in 1600, meant a heavy smoker.

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Increase in weight increases death risk

A new study suggests increase in death risk for overweight and obese people. Being overweight or obese attract many diseases like: cancer, diabetes, high blood pressure, stroke, and heart disease.

Scientists examined data from 225,000 people, after checking their weight history, the results shows that becoming overweight at any stage in life could have negative impact on health.

The overall risk of dying increased based on their maximum Body Mass Index BMI, 10 percent increased risk for the overweight, 34 percent for obese, and 98 percent for the morbidly obese.

Being underweight does not have advantage, underweight people have increase overall risk of death by 46 percent and 77 percent for heart disease.

Antidepressants and prostrate cancer

Prostate cancer is the growth of cancer in the prostate, it may grow slowly or very fast and it can spread to other parts of the body particularly the bones and lymph.

These factors increase the risk of prostate cancer:
• Family history of the disease
• Old age
• Diet high in processed meat and milk

Prostate cancer is common among men and it's the third leading cause of cancer death.

Antidepressants are drugs used for the treatment of major depressive disorder and other conditions.

Scientists believe antidepressants could prevent spreading of cancer to the bone based on latest research.