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For people who suffer from various psychiatric and neurological conditions, brain stimulation has become an increasingly important treatment option in the recent decades.

Deep Brain Stimulation

Deep Brain Stimulation

Brain simulation techniques can be divided into two broad categories, invasive and noninvasive. Both of them work by targeting specific sites in the brain to adjust the overall brain activity. Among the most well-known invasive techniques is the deep brain stimulation (DBS) which requires a brain surgery and is approved by the U.S. Food and Drug Administration (FDA). This process is typically used for treated Parkinson's disease and this process requires an electrode to be inserted in the brain. Among the noninvasive techniques is the transcranial magnetic stimulation (TMS) which can be administered from outside the head. This treatment is currently approved for treating depression.

Brain stimulation has resulted in dramatic benefits to patients with such disorders, which has motivated researchers to test if it can be useful in treated patients suffering from other diseases. The problem is that doctors have been unable to pinpoint which are the ideal sites to administer simulation in a given patient for a given condition.

A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) in the Proceedings of the National Academy of Sciences (PNAS) suggest that brain networks which consists of the interconnected pathways that link brain circuits to one another can assist in selection of ideal spot for brain stimulation therapies.

Michael D. Fox, MD, PhD, First author of the study, an investigator in the Berenson-Allen Center for Noninvasive Brain Stimulation and in the Parkinson’s Disease and Movement Disorders Center at BIDMC remarked that although different types of brain stimulation are currently applied in different locations, it has been found that the targets used to treat the same disease are nodes in the same connected brain network. This can have a direct implication on how brain stimulations are administered to treat diseases.

For example, in order use brain stimulation to treat Parkinson’s disease or tremor an electrode need to be inserted deep in the brain. Getting the same effect with noninvasive stimulation is difficult, as the spot is deep in the brain. However, by looking at the brain’s network connectivity, sites can be identified on the surface of the brain that is connected with the deep spot site. Hence, that deep spot can also be stimulated noninvasively.

For this study Fox's team conducted a large-scale literature search to find out all neurological and psychiatric diseases where brain stimulation via both invasive and non-invasive techniques had shown improvement. The search found 14 such conditions namely addiction, Alzheimer’s disease, anorexia, depression, dystonia, epilepsy, essential tremor, gait dysfunction, Huntington’s disease, minimally conscious state, obsessive compulsive disorder, pain, Parkinson disease and Tourette syndrome. In the next step, they listed the stimulation sites, both deep in the brain or on the surface of the brain that was found to have been effective for the treatment of each of the 14 diseases.

In order to test the hypothesis that the various stimulation sites in the brain are different spots within the same brain network, Fox's team used a data base of functional MRI images and a technique that enabled them to see correlations in spontaneous brain activity. These correlations helped the investigators in creating a map of connections from deep brain stimulation sites to the surface of the brain. When this map was compared to sites for noninvasive brain stimulation on the brain surface, the two matched.

The study suggest that understanding the brain networks can help in understanding why brain stimulation works and how these therapies can be improved by identifying the best place to stimulate the brain for a given patient suffering from a given disease. These findings also suggest that resting-state functional connectivity can be useful for translating therapy between treatment modalities, optimizing treatment and identifying new stimulation targets.




Complementary Reading

Cimaglermin Facilitates Heart RepairAccording to a recent study, Cimaglermin, a novel experimental drug, can be helpful in restoring cardiac function after heart failure.

Heart failure, due to the loss of cardiac function, is one of the major causes of death across the globe. A significant portion of heart failure patients, particularly those with severe left ventricular systolic dysfunction, do not sufficiently respond to current medical therapy.

Efficiency ofcimaglermin

Researchers evaluated the safety and efficiency of a single combination of cimaglermin, which plays the role of a growth factor for the heart, facilitating the structural, metabolic and contractile elements of the heart to repair itself after the injury. The study was conducted among 40 heart failure patients who were undergoing best medical therapy for at least three months earlier to the trial. When compared with patients who received a placebo, patients who given a high dose of cimaglermin had a prolonged increase in left ventricular ejection fraction, or pumping capacity, through 90 days after dosage, with the highest increase reached at day 28.

“These results support continued clinical development of the experimental drug cimaglermin, including further safety assessments and detailing the potential advancement on clinical heart failure outcome measures,” mentioned Daniel J. Lenihan MD, the lead author of the study who works with the division of cardiovascular medicine at Vanderbilt University. “Along with all investigational therapeutics, further studies will be needed and are subject to regulatory review to conclude if the relative risks and benefits of cimaglermin confirm approval.”

The most general side effects were headache and nausea, which were, in the short term, related to drug exposure. One patient who received the maximum planned dosage of cimaglermin had an adverse reaction that met the stopping criteria of Federal Drug Administration guidance for drug induced liver injury.

Limitations of this study include the smaller sample size and that the patients only received a single dose rather than multiple infusions.

“Even though the results of the study must be considered as provisional because of the small numbers of patients, the results of this study are however very exciting,” noted Douglas L. Mann, MD, FACC, editor-in-chief of JACC: Basic to Translational Science. “Rather than blocking the basic mechanisms that lead to cardiac injury, the early results with cimaglermin propose that it can also be possible to administer therapeutics that permit the failing heart to repair itself with the help of its own repair mechanisms. If the findings of this study can be replicated and translated into advancements in clinical results in larger numbers of patients in phase II and III clinical trials, it will symbolize a paradigm shift in the way in which clinicians treat patients with heart failure.”

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Protein Nrf2 May Facilitate Neurodegenerative Diseases TreatmentA recent study offers new information regarding an important cellular protein (Nrf2) which could facilitate the treatment of neurodegenerative diseases like Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS) and Huntington’s disease.

As to their origin, these diseases are caused by proteins which misbehave in the brain. The proteins misfold and build up in neurons, causing damage and finally destroying the cells. In the study, researchers at the Gladstone Institutes used another protein, Nrf2, to reinstate the disease-causing proteins levels within the healthy range, thus avoiding cell death.

The researchers used two models of Parkinson’s disease to test Nrf2. One model had cells with mutations in the LRRK2 protein and the other model had cells with mutant alpha-synuclein protein. By triggering Nrf2, the researchers enabled various “house-cleaning” processes in the cell to eliminate excess LRRK2 and alpha-synuclein.

How Nrf2 works?

“Nrf2 organizes a whole series of gene expression, however we didn’t know how significant it was for managing protein levels till now,” described first author Gaia Skibinski, PhD, who serves as a staff research scientist at Gladstone. “Nrf2 overexpression in cellular models of Parkinson’s disease showed a massive effect. Actually, it saves cells from the disease in a better way than all others we’ve found.”

The scientists made use of both neurons of rat neurons and human neurons developed from stimulated pluripotent stem cells. Then neurons were programmed for Nrf2 expression along with mutant LRRK2 oralpha-synuclein. With the help of a unique robotic microscope crafted by the Finkbeiner laboratory, the researchers labeled and observed individual neurons eventually to examine their overall health and protein levels. They took multiple images of the cells for more than a week, determining the progress and death of each one.

The scientists found that Nrf2 functioned in various ways to facilitate elimination of mutant alpha-synuclein or LRRK2 from the cells. For mutant LRRK2, Nrf2 made the protein assemble into incidental clumps that can stay in the cell without destroying it. For alpha-synuclein, Nrf2 intensified the clearance and breakdown of the protein, decreasing its levels in the cell.

“I am highly interested about this approach for neurodegenerative diseases treatment,” mentioned Finkbeiner, a senior investigator at Gladstone and senior author on the study. “We’ve examined Nrf2 in models of Parkinson’s disease, Huntington’s disease and ALS, and it is the major protective thing we’ve ever known. As per the level and the extent of the effect, we in fact want to study Nrf2 and its function in protein regulation as well.”

The scientists note that Nrf2 itself can be hard to target with a drug since it is associated with so many cellular processes, so they are currently concentrating on a few of its downstream effects. They anticipate to find other players in the regulating protein pathway that communicate with Nrf2 to enhance cell health and that can be simpler to treat.

Fenofibrate May Reduce Heart Disease Risk in Type 2 DiabetesAccording to a recent study, the drug fenofibrate could decrease the risk of cardiovascular diseases in patients with type 2 diabetes who have high triglycerides levels and low good cholesterol levels, despite being treated with statins. The study, supported by the National Heart, Lung, and Blood Institute (NHLBI), published in JAMA Cardiology journal.

Diabetes and cardiovascular diseases

Diabetes is a metabolic disorder which can affect many parts of the body and is associated with serious complications, such as heart disease, stroke, erectile dysfunction, blindness, kidney failure and lower-limb amputation. Diabetes management and prevention is the need of the hour, because 29.1 million people in the United States are reported to have diabetes in 2014. This means that 9.3 percent of the population has diabetes.

Type 2 diabetes is the most common type, and about 90 to 95 percent of diabetic people have type 2 diabetes. Though this type is associated with older age, it can develop even during childhood. People with excess weight, physical inactivity, family history of diabetes, and previous history of gestational diabetes are at risk for type 2 diabetes. Unmanaged diabetes may lead to severe complications like stroke, amputations, etc. So there is a need for new drugs to manage diabetes effectively and prevent complications like cardiovascular diseases.

Efficiency of Fenofibrate

Fenofibrate is mainly used to help decrease elevated triglycerides levels in the blood. But the researchers needed to know if the drug, when associated with statin treatment, could also decrease the risk of heart disease in people with type 2 diabetes. People with type 2 diabetes are at high risk of cardiovascular-related issues, such as heart attacks, stroke, and even death, frequently since their levels of triglycerides are very high, and their high-density lipoprotein (HDL) cholesterol levels are low.

To find the efficiency of the combination of Fenofibrate with statins, the researchers analyzed 4,640 participants from the NHLBI-funded Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study for five years after the wrapping up of the trial in 2009. The findings propose that fenofibrate therapy may be helpful in the way the researchers expected: by decreasing cardiovascular diseases in patients with type 2 diabetes who take statins but still have particularly high triglycerides levels and low HDL cholesterol levels. Yet, a randomized study is required to verify these findings, as per the authors.

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It’s difficult to talk about cancer. Many Canadians are affected by, or are close to someone that has, this disease. Last year the Canadian Cancer Society estimated that:

  • More than 100,000 men would be diagnosed with cancer
  • More than 40,000 men would pass away from cancer
  • Over 90,000 women would be diagnosed with cancer
  • Over 37,000 women would pass away from cancer
  • An average of 555 Canadians would be diagnosed every day and an average of 216 would be claimed by the disease daily

With statistics like that, it’s clear that Canadians need to be having conversations about cancer, and one of those conversations should be about the relationship between cancer and life insurance.

Did you know that cancer patients and cancer survivors can get life insurance? Over the past few years, underwriters across Canada have revamped polices and added no medical insurance (more on that below) to ensure that everyone can get coverage! This is a great relief to those facing funeral costs within the next 3-5 years, or to those that were not insured prior to diagnosis.

Life Insurance for Cancer Patients Varies Because Not all Cancers are the Same

Women are more prone to breast and thyroid cancer than men, and men are more prone to prostate and bladder cancer than women. Both sexes are equally affected by lung/bronchus and colorectal cancers. Cancer may go into remission, or shorten a life span. Some cancers are quickly treated, and others require long, aggressive interventions.

Underwriters providing life insurance for cancer patients consider the type of cancer, its survival rate, the method of treatment, if the cancer is in remission, how long the cancer has been in remission, etc. If the patient has been cancer-free for a number of years, the underwriter may offer a rated or excluded policy. This means the insurer charges a little more to cover their risk, or offers a standard life insurance policy but excludes cancer-related death from the benefit.

Life Insurance for the Most Serious Cancer Cases

Those that do not qualify for a form of standard insurance can still qualify for no medical life insurance. There are two types of no medical life insurance: simplified issue and guaranteed issue.

Simplified Issue

  • The application process does not include a medical exam
  • The application has a series of medical questions (you must be able to answer no to all of them)
  • Different underwriters have different question lists a broker will guide you to the company that is the most likely to insure you
  • If the applicant passes away within two years of the policy being in force, the benefit is not paid, but the premiums are returned to the beneficiaries
  • Lower premiums than guaranteed issue, but higher than a standard policy
  • Less maximum coverage available than for a standard policy

Guaranteed Issue

  • The application process does not include a medical exam
  • The application does not have any medical questions
  • If the applicant passes away within two years of the policy being in force, the benefit is not paid, but the premiums are returned to the beneficiaries
  • More expensive than simplified issue or a standard policy, but guaranteed acceptance
  • Less maximum coverage available than for a simplified issue policy

Where to get life insurance for cancer cases

Both agents and brokers can offer life insurance to those with cancer, but there is a very important distinction: an agent works for one company and can only sell the products of that company. A broker is independent and can sell the products of any Canadian insurer.

If you have cancer and need life insurance, strongly consider speaking with a broker. Upon doing a full needs assessment, the broker can match you with a policy from a top insurance brand, or a company that is known to frequently insure those with cases similar to yours. You do not want to get denied for a policy because a denial makes it much harder to get any type of policy in the future. A broker has more options to get you the policy that best suits your needs.

NoMedicalLifeInsurance.ca will help you to connect with the best life insurance brokers who are experienced in various types of health pre-conditions, including different types of cancer. Contact us for free and confidential advice, quotes and information.

New Drug Combos Work Better Against Breast CancerResearchers identified ten potential new and experimental combinations for treating breast cancer, using in-silico analysis. A team of researchers at the Institute for Research in Biomedicine (IRB Barcelona) studied the pairing of 64 drugs used for treating breast cancer, where half of them already existed and the remaining half were investigational drugs.

Among the 10 combinations, 7 were tested in breast cancer cells in-vitro analysis and the results demonstrated synergy among the drugs; the effect was higher when used with combinations. One of these combinations was confirmed to be effective in mice. The findings in mouse models denote that the combination of two drugs namely raloxifene and cabozantinib, which were prescribed by oncologists, “significantly” enhance the anti-tumour potential of the two drugs.

Breast Cancer Treatment With Combined Drugs

According to Patrick Aloy, who serves as ICREA researcher and also as the head of the Structural Bioinformatics And Network Biology Lab at IRB Barcelona, “We find many more synergistic combinations in-silico than combinatorial assays till date with high-performance lab techniques, and we can offer experimental information. This denotes that earlier computational analyses provide better results and are more consistent.” The researchers noted that in 70% of the combinations tested, the synergic effect of the two drugs is “much higher” than the effect of each drug alone and hence, the similar effect could be obtained even by a smaller dose.

For this study, when scientists tested the combination of raloxifene and cabozantinib as treatment in mice, they noticed that the tumor got reduced in size by 60%, whereas individually the effect of each drug only prohibited tumour growth. Additionally, with the combination, the dosage of raloxifene can be three times smaller and the dose of cabozantinib can be 25 times smaller when compared to the treatments now. “This smaller dosage itself is highly significant since drugs are toxic in nature and are meant to kill cells. When a smaller dose has the same or greater therapeutic effect, it is an important benefit for the patients, since side effects could be reduced. In addition resistance would be delayed or avoided explains Aloy.

One of the challenges of cancer treatment that oncologists and patients have to deal with is treatment resistance. Cancer cells turn out to be “resistant” to drugs that should destroy them. Resistance occurs since the cancer cell, by means of random mutations, begins to escape from the effect of the drug. Among 15% of cases, different molecular signaling pathways are triggered to permit tumour cells to divide again or to avoid programmed cell death. Combination therapy by two or more drugs appears as a promising strategy to handle this type of treatment resistance.

“Our studies have facilitated us to identify the signalling pathways that are triggered by the combined action of two drugs,” says Samira Jaeger, who is the first author of this study. The scientists confirmed at the molecular level that the molecules predicted in the in-silico models were really suppressed. “By combination of drugs, we intend to attack the cancerous cell from various sides at the same time, therefore it will be hard for the cell to resist against the treatment, since the pathways that permit it to live and multiply will be affected simultaneously,” she clarifies.

Having confirmed the computational network model, the scientists have three lines of study currently. First, with the objective of focusing on clinical applications, they will test combination therapy raloxifene and cabozantinib in cancerous cells obtained from patients and transferred in mice. Second, with the same objective of discovering more efficient treatments for breast cancer, the lab will work on combining an anti-tumour agent with a drug used to treat other conditions like high blood pressure and diabetes. Lastly, Aloy’s lab is enhancing an experimental method which will facilitate them to confirm the combination therapies that have the highest enduring effectiveness in fighting against resistance.

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