Drug to stop sepsis reaching major organs!

Sepsis arises when the body’s response to an infection injures its own tissues and organs, potentially leading to death or significant morbidity.

Researchers discover a drug that has the potential to stop sepsis before the condition reaches major organs and becomes fatal.

  • It is estimated that sepsis affects more than 30 million people worldwide every year, potentially leading to 6 million deaths. The burden of sepsis is most likely highest in low- and middle-income countries.

sepsis-1

Researchers at the Royal College of Surgeons in Ireland (RCSI) — which is located in Dublin — have tested a compound called cilengitide in a preclinical trial. The drug goes by the brand name InnovoSep.

The drug acts by preventing the bacteria from getting into the bloodstream from the site of infection by stabilising the blood vessels so that they cannot leak bacteria and infect the major organs

“Sepsis occurs when an infection gets into the bloodstream and our own body’s defence system spins out of control trying to fight the infection, which results in multiple organ failure, if untreated. There is only a short window of opportunity for treatment of sepsis, with the early administration of antibiotics and fluid. However, in many cases, antibiotics are not effective, due to drug resistance or delays in identifying the type of bacteria that has caused the infection. Therefore, there is a need for a non-antibiotic therapy that can be used at all stages of infection against all bacterial causes of sepsis,” –Prof. Kerrigan

Sepsis can be the clinical manifestation of infections acquired both in the community setting or in health care facilities. Health care-associated infections are one of, if not the most frequent type of adverse event to occur during care delivery and affect hundreds of millions of patients worldwide every year. Since these infections are often resistant to antibiotics, they can rapidly lead to deteriorating clinical conditions. The promising results of the InnovoSep preclinical trial gives hope for a new, nonantibiotic treatment of this condition that could be effective in both the early and more advanced stages of sepsis

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ADDICTION

Addiction is a psychological and physical inability to stop consuming a chemical, drug, activity, or substance, even though it is causing psychological and physical harm.

New research has found that the cerebellum, a large part of the human brain that scientists thought was primarily involved in motor control, may play a key role in reward-seeking and social behaviours such as addiction.

The scientists conducted a study on mice using optogenetics to test their hypothesis. By genetically inducing photosensitivity, the researchers could selectively activate the axons of the neurons in the cerebellum, to see how the neurons in the VTA would be affected.

In the first experiment, rodents were free to explore all four corners of a room, but when they reached one specific corner, the researchers stimulated the rodents’ cerebellar neurons using optogenetics.

The scientists hypothesized that, if the stimulation were pleasurable, the rodents would continue to seek the rewarding behavior — that is, they would repeatedly go back to the corner where they received the pleasurable stimulation.

As the team expected, the stimulated rodents opted to return to that same corner more often than the control mice.

Next, to confirm that stimulating the axons of the cerebellar neurons played a role in addiction, the researchers conditioned the mice to receive pleasurable stimulation of these axons in a brightly lit area.

Typically, mice avoid bright lights and tend to feel more comfortable in the dark, where they can avoid predators. But in this final experiment, they chose to go against their usual preference, for the sake of the pleasurable stimulation.

Current treatments of addiction include…..

  • behavioral therapy and counseling
  • medication and drug-based treatment
  • medical devices to treat withdrawal
  • treating related psychological factors, such as depression
  • ongoing care to reduce the risk of relapse

However addiction treatment is highly personalised and can take a long time. Addiction is a chronic condition with a range of psychological and physical effects. Each substance or behaviour may require different management. This new research provides more knowledge about addiction which could potentially have a beneficial impact on the way in which it is treated

Young homeless adult male sitting and begging in subway tunnel

“We propose that this […] pathway may explain, at least in part, the association between the cerebellum and addictive behaviors, and provides a basis for a role for the cerebellum in other motivated and social behaviors.”

2018 NOBEL PRIZE in Physiology or Medicine

The Nobel Prize in Physiology or Medicine 2018 was awarded to James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation.  Cancer is the second leading cause of death globally, and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer. This discovery by Allison and Honjo has provided a revolutionary principle for research into cancer therapy.

James P. Allison

Allison studied a known protein, CTLA-4, that functions as a brake on the immune system, specifically, T cells. He realised the potential of releasing the brake and unleashing immune cells to attack tumours. Having already developed an antibody that is able to bind to CTLA-4 and block its function, he continued to research if the CTLA-4 blockade could disengage the T-cell brake and allow our immune cells to attack tumours.

Tasuku Honjo

Additionally, Tasuku Honjo discovered a protein expressed on the T-cells, PD-1, which also operates as a brake, but with a different mechanism of action. He discovered that PD-1 blockade was also a promising strategy in the fight against cancer. When a study was conducted in the treatment of patients with different types of cancer, using his discovery, results showed long-term remission and a possible cure in several patients with metastatic cancer, previously thought to be untreatable.

Of both Honjo and Allison’s strategies, checkpoint therapy against PD-1 has proven more effective and has shown positive results in cancers including lung cancer, renal cancer, lymphoma and melanoma. However a combining therapy which targets both CTLA-4 and PD-1 is thought to be even more effective and has inspired efforts to combine these strategies to eliminate tumour cells even more efficiently. Both these discoveries will be revolutionary to the lives of many in the treatment opportunities that future research may lead to and constitute a landmark in our fight against cancer.

 

Breakthrough discovery for IBD?!

Scientists have discovered what drives inflammation in IBD

Reachers have now found a mechanism which regulates gut inflammation in inflammatory bowel disorders and this may lead to improvements in treatment and diagnosis of some IBD such as Crohn’s disease and ulcerative colitis.
IBD can reduce quality of life, so finding new treatments for it is vital.

Researchers at Sanford Burnham Prebys (SBP) Medical Discovery Institute in La Jolla, CA, and Technion-Israel Institute of Technology in Haifa have identified a role for a protein called RNF5, which is abundant in cells that line the gut.

  • What they found is that the protein RNF5 controls the activity of S100A8, a protein already known to be a promoter of inflammation.
  • The scientists found that RNF5 keeps S100A8 stable in cells of the gut lining, and that its absence unleashes the pro-inflammatory power of S100A8.
  • IBD can cause symptoms that, in turn, cause discomfort, pain, and distress. These include: diarrhoea, constipation, rectal bleeding, abdominal pain and cramp, and a sudden and urgent need to go to the bathroom.
  • According to the Centres for Disease Control and Prevention (CDC), around 3 million adults in the United States report having received a diagnosis of IBD showing how much of a pressing issue this is.
  • Treatments currently do not work in all cases, and they can also become less effective over time.

 

Our findings,” says Prof. Ronai, “indicate that RNF5 is the lock that keeps a key inflammatory protein under control.”

Breaking the lock is like opening Pandora’s box, he adds, and the result is that S100A8 is released to cause inflammation.

 Although it is already known that inflammatory proteins are involved in IBD, the underlying driving mechanism has remained a mystery until now. Recent findings will now allow for more targeted treatments which will hopefully aid in diagnosis as well as managing peoples pain and ultimately aiding in the process to find a long term cure. 

ARTIFICIAL INTELLIGENCE

Artificial Intelligence in Radiology is a hot topic at the moment! So what is Artificial Intelligence?….

Artificial Intelligence– The theory and development of computer systems able to perform tasks normally requiring human intelligence, such as visual perception, speech recognition, decision-making, and translation between languages.

Deep learning– Deep learning is part of a broader family of machine learning methods based on learning data representations, as opposed to task-specific algorithms. Learning can be supervised, semi-supervised or unsupervised.

A huge step forward for radiology is Computer Aided Diagnosis– through image processing, image feature analysis, data classification in deep learning, the possible ability for computers to use images in radiology in order to come to a diagnosis would have a huge effect. It will have the ability to filer out normal plain films and flag abnormal films for review. As well as this it could be used in CTIMRI for example identifying malignancy. A key benefit being, with an increase in the reporting workload of radiologists with hospitals increasingly relying on imaging, artificial intelligence would be a great way to help reduce this.  

However developing artificial intelligence requires access to large volumes of data which may be challenging in the UK particularly in the NHS. It also poses a threat to jobs as artificial imaging is likely to be largely driven by computer scientists which will restrict the input of radiologists. 

In the UK surrounded already by artificial intelligence in our day to day life we are already ready for it. Now for the next step, we need to promote artificial intelligence amongst the radiology community, including technicians and undergraduates.

 

What surprised me about my work experience at a Hospital…

During my work experience at St George’s Hospital I learnt a lot which maybe I didn’t quite expect but nevertheless widened my knowledge of the healthcare profession. Here are 3 things that particularly stood out to me…

On the first day I was sitting in the outpatients clinic of the cardiothoracic unit in the Hospital and I realised through many of the consultations the importance of following up with the patients and keeping them informed about the outcome of their treatment. One man, although well informed before hand, was very upset at the time taken for recovery. He had 3 coronary artery bypasses and after 3 months was experiencing pain in his chest and trouble with breathing and walking as well as suffering from depression. After many scans it was established he was on a healthy route to recovery however he was still disappointed . The doctor then de-esculated the situation by remaining calm and communicating. He emphasised and listened to the patient, comforting him and he displayed excellent qualities which are important in a doctor. I found the way in which he handled the situation a great learning experience for me truly inspiring.

Something that particularly stood out to me throughout my whole placement was the importance of teamwork skills used in working in a multidisciplinary team. It had become second nature to these doctors and throughout the operation it really highlighted the importance of communication between all teams for example between the anaesthetist and the surgeon or between the nurses and the doctors, every member of the team played a vital role in ensuring patient safety.

I watched OPEN HEART surgery!!

WORK EXPERIENCE.

DAY 12e254eb36cec8e95e0c3181ea808e835--heart-painting-folk-art-paintings

St George’s Hospital

This week I have the amazing opportunity to shadow a cardiothoracic consultant and so I will document all of the exciting things I see! Day 1 was spent at St George’s Hospital, and after seeing outpatients in the morning, I had the amazing opportunity to witness a Coronary artery bypass surgery! The coronary artery bypass surgery I witnessed was performed on someone who suffered from Coronary artery disease , which is a condition involving the clogging of arteries that bring blood to the heart muscle caused by fatty deposits on the inner walls of the arteries. The main factors which contribute to coronary artery disease are:

(CAUSES)

  1. Smoking
  2. High blood pressure
  3. High cholesterol
  4. Diabetes or insulin resistance
  5. Sedentary lifestyle

(RISK FACTORS)

  1. Age
  2. Sex
  3. Family history
  4. Smoking
  5. High blood pressure
  6. High blood cholesterol levels
  7. Diabetes
  8. Overweight or obesity
  9. Physical inactivity
  10. High stress
  11. Unhealthy diet

A doctor will diagnose coronary artery disease from symptoms and tests such as performing a physical examination, blood tests, an exercise stress test, a cardiac nuclear scan, and cardiac catheterization. Any of these tests will play an important part in deciding whether or not bypass surgery will be needed. It is a fairly low-risk procedure. For someone who has a normal functioning heart, non-emergency bypass surgery carries a risk of death of 1% or less. There is a 5% chance of a heart attack during surgery. The risk from surgery is a bit higher if someone has had other cardiovascular problems. About 90% of people who undergo the surgery experience complete or dramatic relief of their symptoms.

THE PROCEDURE

  • Coronary artery bypass surgery is an open-heart procedure. The patient was placed under general anesthetic and the surgeon began the operation by making an incision down the centre of the chest, then dividing and separating the sternum. Tubes were then attached to the heart and connected to a heart-lung machine that keeps the blood supplied with oxygen, and the blood was pumped from the heart to the machine and back to the body to be circulated again. Blood pressure, temperature, and breathing were all able to be regulated throughout the whole procedure.
  • The surgeon then clamped the aorta, and he then sewed 4 veins taken from the legs to join the aorta to the coronary artery, bypassing the blocked part of the coronary artery to allow blood carrying oxygen to reach the heart.
  • When the grafting finished, the patient was taken off the heart-lung machine, and the surgeon rejoined the breastbone with stainless steel wires.

The operation I saw lasted 4 hours, and an average operation lasts from 3 to 6 hours. After surgery, all patients will need to continue taking medications that decrease the work of the heart and reduce the risk of future heart attacks. More than 80% still work 10 years after the surgery. Vein grafts more often become obstructed. After 5 years, one-quarter of any vein grafts may be clogged. New techniques of bypass surgery may be used in some cases, such as  the “beating-heart” technique which does not use the heart-lung machine setup but still needs to be done through the incision in the middle of the chest. Bypasses are sewn directly onto the heart without stopping the heart which means that the risk of complications from the heart-lung machine is lower.

Overall I found today VERY interesting and learnt a lot! Stay tuned to hear about Day 2 tomorrow!…

A new potential target for cancer therapy has been found!

A new discovery about how cancer cells prepare the way for tumor growth and spread may lead to new treatments that stop it.

Cancer cells are known to release tiny exosomes which are packed with proteins and other molecules that make the tissue conditions more favorable for tutor progressions in many different ways. The molecules are able to remodel the environment of the cancer cells and are able to insert cancer genes into other cells and signal the immune system not to attack them, all making it easier for tumors to grow and for the cancer to spread to other parts of the body and invade nearby tissue. The spread of cancer is a complex process called metastasis. Researchers now have discovered a protein that controls the release of exosomes from cancer cells to promote tumor progression and metastasis.

This protein is Munc13-4 and it is often largely found in lung, breast, and pancreatic tumors and it is activated by binding to calcium. The researchers found that calcium triggered exosome secretion in aggressive breast cancer cells however when they removed Munc13-4 in the breast cancer cells, calcium no longer caused the cells to secrete exosomes. This was also the case when they replaced Munc13-4 with a mutant form that cannot bind to calcium.

Having greater knowledge about this protein will allow us to produce drugs which are more focused to be able to prevent cancer growth in future and provide a target for cancer therapy.

Overall, we think that increased expression of Munc13-4, combined with elevated calcium levels, drives enhanced exosome release by highly aggressive cancer cells, and that Munc13-4 is a potential target for therapeutic intervention.” -Prof. Thomas F. J. Martin

Is nutrition science unreliable?

Is nutrition science methodologically inferior to other fields? Is nutrition knowledge insufficiently stable to be useful? Is it even causing harm?

  • Quite often nutrition science has been criticised as being unreliable yet some argue that it has made vital contributions to human health. There are continuously shifts in medicine some of which focusing on single nutrient deficiencies and some focusing on overall diets and chronic diseases from various studies leading to a greater knowledge, however these advances have also brought with them new questions and uncertainties. These include the relevance of unsaturated fats and its diverse food sources, the effects of fish oil or vitamin D supplements and the relevance or calorie counting versus diet quality for long term weight control to name a few. What really adds to the controversy surrounding this topic however is the time lag between the generation of new knowledge and its implementation.
  • It is important to remember that uncertainty exists in all scientific fields. Nutrition science is evolving but this does not necessarily mean that we should be sceptical of current conclusions.
  • Is there a potential vested interest within the nutrition industry? Their optimal role is unclear. Government and on-profic organisational support is limited so the food industry has a key role in funding studies. This has however raised concerns that bias exists in their work spewing the findings towards industry benefit. It is vital that all parts of the food system globally contributes towards the solution weather it is through voluntary action of legalisation.
  • With all of this research, it needs to be conveyed to the public in order to take substantial effect. Enhancing the quality of dietary guidelines is one important strategy. standardisation of methods and criteria is also recommended.

 

Are people with diabetes and obesity predisposed to stress?

Individuals with obesity and type 2 diabetes or prediabetes have insulin resistance so their bodies are unable to regulate blood sugar levels, but research suggests that these imbalances also mean that their emotional responses to negative stimuli are increased.

Previous studies have shown that people who live with type 2 diabetes and obesity are more predisposed to depression however it is now suggested that this is due to their insulin resistance.

A study was done in which they studied participants in different scenarios. In the first scenario, they studied the participants ‘startle response’ which is as an involuntary defensive reaction to a stimulus that is automatically perceived as potentially dangerous. The people with a more intense startle response than others tended to have diabetes.

The study next showed each participant a series of images with negative, positive, or neutral content, with the aim of triggering an emotional response. At the same time, they tested the subjects’ involuntary responses using an electroencephalogram (EEG), a test in which tiny electrical sensors are placed in key areas over the head and face to measure activity in the central nervous system. In doing so, the researchers evaluated how often each individual blinked or flinched when shown negative imagery.

“People with higher levels of insulin resistance were more startled by negative pictures,” says Willette, adding, “By extension, they may be more reactive to negative things in life.”

If people with prediabetes and diabetes are trying to reverse or treat the disease, stressful events may hinder their goals. Frequent negative reactions to stressful events can lead to a lower quality of life and create a vicious cycle that makes it difficult to be healthy, which is why it is extremely important that we fully understand the causes in order to minimise them.