A Primeview on Sickle Cell Disease !

Primeview:

Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system. SCD is characterized by a remarkable phenotypic complexity. Common acute complications are acute pain events, acute chest syndrome and stroke; chronic complications (including chronic kidney disease) can damage all organs. Hydroxycarbamide, blood transfusions and haematopoietic stem cell transplantation can reduce the severity of the disease. Early diagnosis is crucial to improve survival, and universal newborn screening programmes have been implemented in some countries but are challenging in low-income, high-burden settings.

Sickle cell disease (SCD) is an umbrella term that defines a group of inherited diseases (including sickle cell anaemia (SCA), HbSC and HbSβ-thalassaemia) characterized by mutations in the gene encoding the haemoglobin subunit β (HBB). Haemoglobin (Hb) is a tetrameric protein composed of different combinations of globin subunits; each globin subunit is associated with the cofactor haem, which can carry a molecule of oxygen. Hb is expressed by red blood cells, both reticulocytes (immature red blood cells) and erythrocytes (mature red blood cells). Several genes encode different types of globin proteins, and their various tetrameric combinations generate multiple types of Hb, which are normally expressed at different stages of life — embryonic, fetal and adult. Hb A (HbA), the most abundant (>90%) form of adult Hb, comprises two α-globin subunits (encoded by the duplicated HBA1 and HBA2 genes) and two β-globin subunits.

A single nucleotide substitution in HBB results in the sickle Hb (HbS) allele βS; the mutant protein generated from the βS allele is the sickle β-globin subunit and has an amino acid substitution. Under conditions of deoxygenation (that is, when the Hb is not bound to oxygen), Hb tetramers that include two of these mutant sickle β-globin subunits (that is, HbS) can polymerize and cause the erythrocytes to assume a crescent or sickled shape from which the disease takes its name. Hb tetramers with one sickle β-globin subunit can also polymerize, albeit not as efficiently as HbS. Sickle erythrocytes can lead to recurrent vaso-occlusive episodes that are the hallmark of SCD. SCD is inherited as an autosomal codominant trait; individuals who are heterozygous for the βS allele carry the sickle cell trait (HbAS) but do not have SCD, whereas individuals who are homozygous for the βS allele have SCA. SCA, the most common form of SCD, is a lifelong disease characterized by chronic haemolytic anaemia, unpredictable episodes of pain and widespread organ damage.

This primeview focuses on SCA and aims to balance such remarkable advances with the key major challenges remaining worldwide to improve the prevention and management of this chronic disease and ultimately to discover an affordable cure.

Read More »

         

DOWNLOAD BOOKS

      

DOWNLOAD PRIME REVIEWS

Nipah Virus -Infection, Symptoms, Diagnosis & Treatment !

Viruses

Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus. NiV was initially isolated and identified in 1999 during an outbreak of encephalitis and respiratory illness among pig farmers and people with close contact with pigs in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis. Given the relatedness of NiV to Hendra virus, bat species were quickly singled out for investigation and flying foxes of the genus Pteropus were subsequently identified as the reservoir for NiV (Distribution Map).

In the 1999 outbreak, Nipah virus caused a relatively mild disease in pigs, but nearly 300 human cases with over 100 deaths were reported. In order to stop the outbreak, more than a million pigs were euthanized, causing tremendous trade loss for Malaysia. Since this outbreak, no subsequent cases (in neither swine nor human) have been reported in either Malaysia or Singapore.

Read More »

Download Recent Review Articles »

Genetics of Coronary Artery Disease: Discovery, Biology and Clinical Translation !

Genetics

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked approximately 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forwards, genetic testing could enable precision medicine approaches by identifying subgroups of patients at increased risk of coronary artery disease or those with a specific driving pathophysiology in whom a therapeutic or preventive approach would be most useful.

• Coronary artery disease is a heritable disorder that remains the leading cause of global mortality despite advances in treatment and prevention strategies. Human genetics studies have started to unravel the genetic underpinnings of this disorder.
• Gene discovery efforts have rapidly transitioned from family-based studies (for example, those that led to the discovery of familial hypercholesterolaemia) to large cohorts that facilitate both common and rare variant association studies.
• Common variant association studies have confirmed ∼60 genetic loci with a robust association with coronary disease, the majority of which are of modest effect size and in non-coding regions. Rare variant association studies have linked inactivating mutations in at least nine genes with risk of coronary artery disease.
• Human genetics and large-scale biobanks can facilitate drug development for coronary artery disease by highlighting causal biology and helping to understand the phenotypic consequences of lifelong deficiency of a given protein.
• Genomic medicine may provide patients and their health care providers with genetic data that will aid in coronary artery disease prevention and treatment.
• Genome editing to introduce mutations that are protective against coronary artery disease into the population could prove curative with a one-time injection, although substantial additional work is needed to confirm efficacy and safety, and to address the underlying ethics.

Observational epidemiology and translational research efforts have led to significant progress in improving the understanding of the pathophysiology underlying coronary artery disease (CAD). Prevention and treatment strategies developed on the basis of this knowledge led to a >50% decrease in age-adjusted CAD mortality rate in the United States between 1980 and 2000. However, despite these advances, CAD remains the leading global cause of mortality. Current predictions estimate that more than 900,000 individuals in the United States will suffer a myocardial infarction (heart attack) or die of CAD this year.

This review outlines research efforts to understand the genetic drivers of CAD, the role of human genetics in catalysing CAD drug discovery efforts and the promises and challenges of integrating genetic information into routine clinical practice.

Read More »

Can Vitamin D Really Stop You Getting Cold And Flu?

Have you had a cold, flu or even pneumonia in the last year? You're not alone - in fact you're among 70% of the UK population.

But a new study claims that three million people could be spared the sniffles if they took vitamin D pills.

That's more than the number of people who are stopped from getting the flu after having the vaccine.

The people behind the new study want vitamin D to be added to food so that everyone gets enough.

Read more: Can Vitamin D Really Stop You Getting Cold And Flu?

Source: bbc.co.uk/newsbeat

Male Birth Control Shot Shows Promise

When it comes to birth control methods, women have more options than ever before. However, for men, the choice is limited to condoms, withdrawal, and vasectomy. A new study - published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism - has established that a male birth control shot is effective at preventing pregnancy.

In the last 40 years, studies have demonstrated that reversible hormonal suppression of spermatogenesis - the process of sperm cell development - in men can prevent pregnancies in their female partners, although the commercial development of the product has been stalled.

In previous studies, testosterone management in men demonstrated birth control efficacy comparable with female methods. However, participants had to be given much greater doses than are typically found in the body and the method caused long-term adverse effects in healthy men.

While giving progesterone alongside can reduce the dose of testosterone, there have been few studies that have evaluated the efficacy and safety of such a combination. With 40 percent of all pregnancies worldwide unintended in 2012, better birth control options are required for men.

Read more: Male Birth Control Shot Shows Promise

The male birth control shot may provide more choice for controlling male fertility in the future.

Source: MedicalNewsToday

Cancer: Four-Stranded DNA Could Help Develop Targeted Treatments

By taking a closer look at four-stranded versions of DNA inside the genome of human cells, scientists have discovered some potential new avenues for targeted cancer treatments. They found that the quadruple helix structures occur in DNA regions that control genes, especially cancer genes.

The researchers, from the University of Cambridge in the United Kingdom, report their findings in the journal Nature Genetics.

Targeted cancer therapies are currently the focus of much research and development into new anticancer treatments.

They are an important area of precision medicine - where information about an individual patient's genes and proteins are used to prevent, diagnose, and treat disease.

Read more: Cancer: Four-Stranded DNA Could Help Develop Targeted Treatments

The aim of targeted therapy is to attack cancer cells without affecting healthy cells.

Source: MedicalNewsToday

How To Prevent and Treat Fatty Liver

I have a Fatty Liver- Now what?

Many of my clients have digestive issues and think it is to do with a food they are eating. Sometimes they opt for allergy testing, others get blood work or an ultrasound done to see if there are any serious problems.

More and more clients are been diagnosed with a fatty liver and ask me now what do I do?

What is a fatty liver?

A fatty liver is the result of excess fat in the liver. This fat builds up when a person’s diet exceeds the amount of fat their body can handle. Having a fatty liver can lead to fatty liver disease, which then leads to chronic illnesses. Many who are overweight, have belly fat, are insulin resistant, pre- diabetic and who crave sugars and starches are likely have a fatty liver. Yet many who are ultimately healthy and not overweight are finding they to, have a fatty liver.

Read more: How To Prevent and Treat Fatty Liver

Source: justnaturallyhealthy

HIV: Newly Discovered Component Could Lead to More Effective Drugs

Scientists from the Medical Research Council Laboratory of Molecular Biology in Cambridge and University College London - both in the United Kingdom - have uncovered key components of HIV, which they believe could lead to new approaches for drugs to fight the infection.

HIV weakens a person's immune system by destroying important cells that fight disease and infection. Only certain body fluids - blood, semen, rectal fluids, vaginal fluids, and breast milk - from a person who has HIV can transmit HIV.

According to the Centers for Disease Control and Prevention (CDC), an estimated 1.2 million people are living with HIV in the United States. Although there is no cure for HIV infection, improved treatments allow people living with HIV to slow the virus' progression and stay relatively healthy for several years.

HIV is a part of a subtype of viruses called retroviruses, which means that the virus is composed of RNA - instead of normal DNA - and has the unique property of transcribing RNA into DNA after entering a cell.

Read more: HIV: Newly Discovered Component Could Lead to More Effective Drugs

Findings from the research could lead to future drugs that can enter human cells and block the pores
from within.

Source: medicalnewstoday

Amazing Foods That Help Prevent Fatty Liver

Have you been suffering from abdominal pain, nausea, vomiting, fatigue and loss of appetite quite often?

Then, you need to watch out, as these could be the symptoms of a fatty liver disease. In case of fatty liver disease, one tends to develop excess fats within the liver.

Liver is one of the most important vital organs of our body. A certain amount of fat in the liver is normal, but when it increases above the normal (above 5 per cent of the organ's weight), then the person could be at the risk of developing fatty liver disease.

Read more: Amazing Foods That Help Prevent Fatty Liver

Source: boldsky

Heart Disease Seen as a Man's Issue by Many Male Doctors

Male family physicians, or general practitioners, may be overlooking the risk of cardiovascular disease in female patient because they more often see it as a man's issue, according to new research published in the European Journal of Preventive Cardiology.

Heart disease is a leading cause of death in the United States.

Since the 1980s, developed countries have seen a fall in the number of deaths from cardiovascular disease (CVD). Around 50 percent of this improvement is thought to be because of preventive action.

In men, the rates of mortality from CVD have dropped more than they have in women. There is also evidence that men receive better cardiovascular care after experiencing a cardiovascular problem, as well as better secondary prevention.

Read more: Heart Disease Seen as a Man's Issue by Many Male Doctors

Women, too, may be at risk of heart disease.

Source: medicalnewstoday

Lowering LDL Cholesterol: When Numbers are Not Enough

Clinicians worldwide continue to be challenged by cholesterol management for their patients; specifically, whether to attempt low-density lipoprotein (LDL-C) reduction to previously described targets, or to specific percent reductions (e.g., ≥ 50% or < 50%) based on an individual's risk assessment as advocated by the US Guidelines. Indeed, Canadian and European Guidelines suggest using both strategies. Data addressing whether the high-intensity statin strategy (to achieve ≥ 50% LDL-C reduction) correlates with improved cardiovascular outcomes is limited.

In addition, it is known that LDL-C reduction to the same strength of statin can vary widely in the population4 resulting in a significant number of patients who may continue to be at increased, potentially modifiable risk, for future events. Recently, the Treating to New Targets (TNT) investigators reported in their known coronary artery disease patient population that visit-to-visit variability in LDL-C levels correlated with increased cardiovascular risk, suggesting yet another possible contributor to residual risk, reportedly independent of LDL-C levels.

Read more: Lowering LDL Cholesterol: When Numbers are Not Enough

Source: acc

Vitamin D and cardiovascular disease prevention

Vitamin D is a precursor of the steroid hormone calcitriol that is crucial for bone and mineral metabolism. Both the high prevalence of vitamin D deficiency in the general population and the identification of the vitamin D receptor in the heart and blood vessels raised interest in the potential cardiovascular effects of vitamin D. Experimental studies have demonstrated various cardiovascular protective actions of vitamin D, but vitamin D intoxication in animals is known to induce vascular calcification. In meta-analyses of epidemiological studies, vitamin D deficiency is associated with an increased cardiovascular risk. Findings from Mendelian randomization studies and randomized, controlled trials (RCTs) do not indicate significant effects of a general vitamin D supplementation on cardiovascular outcomes. Previous RCTs, however, were not adequately designed to address extra skeletal events, and did not focus on vitamin D-deficient individuals. Therefore, currently available evidence does not support cardiovascular benefits or harms of vitamin D supplementation with the commonly used doses, and whether vitamin D has cardiovascular effects in individuals with overt vitamin D deficiency remains to be evaluated. Here, we provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from a cardiovascular health perspective.

Key points

• The vitamin D receptor (VDR) and enzymes for vitamin D metabolism are expressed throughout the cardiovascular system
• VDR and 1α-hydroxylase knockout mice have hypertension with myocardial hypertrophy and increased activity of the renin–angiotensin–aldosterone system
• The molecular effects of VDR activation indicate various anti-atherosclerotic and protective effects on the heart and on common cardiovascular risk factors
• Observational studies have shown that low 25-hydroxyvitamin D levels are associated with an adverse cardiovascular risk profile and significantly increased risk of cardiovascular events
• Mendelian randomization studies and randomized clinical trials have not shown significant effects of vitamin D on cardiovascular events, but these trials were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals
• Vitamin D supplementation is currently not indicated for the purpose of cardiovascular disease prevention, but treatment of vitamin D deficiency is critical for skeletal health

Introduction

The critical involvement of vitamin D in bone and mineral metabolism is historically known. The identification of the vitamin D receptor (VDR) in almost all human organs including the heart and the blood vessels, and observations that individuals deficient in vitamin D are at increased risk of various extraskeletal diseases, stimulated research on the role of vitamin D for overall and cardiovascular health. In this Review, we summarize the existing knowledge on the effects of vitamin D on cardiovascular diseases and associated risk factors, with a particular focus on meta-analyses of large, epidemiological studies and randomized, controlled trials (RCTs). First, we provide a short summary of vitamin D metabolism and current vitamin D guidelines, a historical perspective on vitamin D and cardiovascular diseases, and a brief overview on the mechanistic effects of VDR activation on cardiovascular risk factors, the blood vessels, and the heart. The principal aspect of this Review is an update on observational studies, Mendelian randomization studies, and RCTs on vitamin D and cardiovascular risk. Finally, we outline and discuss ongoing vitamin D research, including large RCTs, and present our conclusions on how to deal with the management of vitamin D deficiency from a public health and cardiovascular health perspective.

Read more: Vitamin D and cardiovascular disease prevention

Figure 1: Human metabolism of vitamin D.

Download in PDF

Source: NatureReviewsCardiology

Vitamin D and cardiovascular disease prevention

Combined HIV-Hepatitis C Vaccine Soon Preventing Co-Infection

Some 2.3 million people around the world are infected with both HIV and the hepatitis C virus (HCV) at the same time. The two are often intertwined, with HCV being the top cause of death aside from AIDS for co-infected patients. While there are currently vaccines for both hepatitis A and hepatitis B, there is no vaccine for hepatitis C. Likewise, HIV/AIDS treatment has improved significantly in recent decades, but there is still no vaccine.

In a new study, researchers note that a combined HIV and hepatitis C vaccine may soon be on the horizon. The study, which was presented at The International Liver Congress in Barcelona, describes how a combined vaccine would involve two main steps: first, exposing the immune system to adenoviral vectors that contain fragments of both HCV and HIV viruses, which would trigger antigens; and afterwards, administering booster vaccinations in an MVA vector containing the same HCV and HIV virus fragments.

“Finding effective vaccinations against the world’s biggest killers is a huge and pressing problem,” said Laurent Castera, Secretary General of the European Association for the Study of the Liver, in a statement. “This study shows for the first time that it is possible to generate simultaneous immune response against diseases HCV and HIV, raising the possibility of a combined vaccination.”

HIV, or the human immunodeficiency virus, causes HIV infection and over time, acquired immunodeficiency syndrome (AIDS). HCV is also a viral infection that mostly targets the liver, resulting in symptoms of fever, dark urine, stomach pain, and eventually liver disease, cirrhosis (scarring of the liver), or liver failure.

Read more: Combined HIV-Hepatitis C Vaccine Soon Preventing Co-Infection

While HIV and hepatitis C vaccines are still in experimental stages, researchers may have paved

the way for a combined vaccine in which they're administered at the same time.

Source: Josep Lago / Getty