Another year of growth for the Healthinnovations, many great breakthroughs, with previously immature technologies and disciplines coming into their own, as crucial parts of global innovation. For instance, biomarkers have now become a must in all disciplines, particularly in neuroscience, where they have become prerequisite, with mazes and tick boxes no longer enough for the highly evolved world of medicalised neuropsychiatry. This also includes the now obligatory neuroimaging, as imaging-sensitivity in the brain becomes single-cellular and delves deeper into topography; with these psychological behaviours now used as symptomatic-based questions to ask before using medical diagnostics to diagnose and treat with medically based treatments. This has also led to neurogenetics being blown wide-open, as researchers begin to genotype single neurons in the newly proven neural network theory, where ‘communities’ or groups of interconnected neurons activate or work in unison, in some cases forming a linear pathway. This year saw the neurogenetics discipline hone in on the gene-based circuitry and genomic analysis of many neuropsychiatric disorders, even proffering the ability to link the neurogenomic source to the rest of the body.
This pinpointing of genetic causation, has in part, been due to precision medicine, which has changed the gene-based landscape forever and for the better. This discipline has given the field, via epigenetics, the sum of the once impossible, promiscuous equation. Moving on from master gene regulators, precision medicine hones in on exact causal loci upstream, and the resultant epigenetic tags and marks downstream; the result of a milieu of genetic interactions. Will the global medical community, see the intricate and copious upstream parts of the equation mapped and made finite by the other side of the equation, the epigenetic mark?
Healthinnovations has also witnessed a rise in neurotransmitter precursor and ‘natural compound’ white papers, with a big push in prevention and many recent studies showing the effect of these naturally occurring chemical entities at a molecular-level. The progressive work being performed in epigenetics could also account for this, as more environmental and controllable origin-based pathologies are brought to light.
Immunology has become a big player in the research field with studies paying particular attention to neuroinflammation and microglia with the brain’s immune system implicated in a multitude of neurological disorders. The long forgotten spinal cord is now being researched as an integral part of the brain, with view to extending mapped circuitry, as well as investigating paralysis. Logically, the spinal cord is the intersection between the central and peripheral nerve system, and integral to many of the neural networks currently being mapped in the upper brain.
Mitochondria has been causing a lot of debate in 2015, with some school of thoughts associating this once symbiotic entity to all disease, with many concurring that this is the best of both worlds, the link between metabolism and genetics. Another hypothesis is that this ATP machine is metabolizing everything with mtDNA spewing forth gene mutation-after-mutation. Logically, these cell-powerhouses are thought to be responsible for helping to fuel all changes within the cell, including inheritable gene expression, as well as being attributed to many aspects of aging along with telomere activity and mechanism.
Metabolics has gained ground, particularly in the many interactions involved in ‘onconutrients’, the fuel used by mutated cells in cancer proliferation and, of course, being instrumental in type 2 diabetes. Lipidomics, the quantification of the thousands of cellular lipid molecular species and their interactions with other lipids, proteins, and other metabolites; has also begun to take shape as a diagnostic for diabetes and obesity. Analysing lipids or the ‘lipidome’ in the same way in which a study would for genomics has blown the barn doors off of many metabolic disorders, not only the case with brown and beige fat. The lipodome has also started the deliberation for the use of high fat diets for certain heart diseases as well as brain health. Definitely a key area, pertinent to many different disciplines as we see many organs, many disorders, many cells as bridges or links to other disorders, biological systems within the body or causative factors; this would make sense, would it not, for a body that has many parts, none of which can be autonomous. Yet, none of which can be healed or controlled by one single, magical pill; quite the dichotomy.
Well, now the creative, scientific juices are flowing, so here we go. Here are the peerless, most superlative studies currently in the world; The Top Ten Healthinnovations of 2015:
1. At the top spot and the best of the best is Massachusetts General Hospital: As with last year a glial cell study tops the list. This great study began to investigate previously unmapped chronic pain at its source, the brain; the end, or rather, start of the line for innervation. As of 2012, chronic pain was costing the USA $635 billion alone, with over 16,000 people dying of opiate related overdose in 2013, according to the CDC. With many chronic pain patients, desolate, ignored and in many cases, unbelieved; this study helped, in part, to explain unseen chronic pain, identifying a glia-linked biomarker protein in regions such as the thalamus. The translocator protein (TSPO) identified is highly expressed in microglia when they are activated in response to some pathologic event; which could also explain why, after the initial healing of a peripheral injury, patients are still experiencing long-term acute pain. This strong human study measured levels of TSPO in the brain and provided quantitive PET neuroimaging of glial activation. The findings ultimately show that this protein actually limits the magnitude of glial response after its initiation and promotes the return to a pain-free, pre-injury status. The researchers address the ‘run-away train’ problem that is chronic pain, and hit back with a new target, a new imaging marker and a new protein biomarker. The fact neuroinflammation is addressed in a very real and tangible way makes this study the world’s number one Healthinnovations for 2015, causing the most excitement.
2. Following [very] closely at number two is Northwestern University: They say that the greatest discoveries are made by accident and this certainly rings true for number two on our list. Following the blueprint for accidental discoveries such as penicillin and Viagra, this investigation made a sex bias-based breakthrough in Multiple Sclerosis (MS) unintentionally. It is known that male mice either get no disease or very little in MS experiments, so researchers typically use females in their studies. The team accidentally used male mice instead of female mice to show why women are more likely than men to develop autoimmune diseases such as MS. The results identified a c-kit mutation in male mice that knocks out type 2 innate lymphoid cells. The team realised that the mutation was behaving differently in males and hypothesize that these type 2 innate lymphoid cells produce a protein in males that may help to protect from the disease by interfering with the damaging immune response. This is the first study to show that type 2 innate lymphoid cells exhibit sex differences in their activity and can protect in autoimmune disease. The findings should now enable researchers to target these cells in a sex-specific way and provide a therapy with fewer side effects. This early research may also have implications for understanding other diseases which also show a female bias.
3. Coming in third is Tulane National Primate Research Center: Neuroinflammation, paired with the elusive and impossible Lyme disease made this study popular. This team began the gargantuan task of mapping the neuroinflammation and nervous system manifestations associated with Lyme disease. Most importantly, this extensive study identified multiple cytokine biomarkers to indicate that neuroinflammation actually plays a causal role in the vast array of neurologic changes associated with Lyme disease. From interleukin markers, to demyelination of neurons in both the brain and spinal cord, these findings blew the disease wide open; with the guts and targets of the matter in plain view. Necrotizing myelitis and degeneration in the spinal cord, neurodegeneration in the dorsal root ganglia, and demyelination in the nerve roots were all identified when lymphocytic inflammatory lesions were also observed in both the central and peripheral nervous system. The results also proffer an explanation for the persistent symptoms of fatigue, pain, and cognitive dysfunction that patients sometimes experience despite having been treated. The data shows the potential therapeutic impact of simplistic anti-inflammatory or immune-modulatory agents, with most of the neuropathological changes prevented by a broad-spectrum steroidal anti-inflammatory drug.
4. In fourth place we have the University of California, Berkeley: This study identified a mitochondria-dependent pathway critical to aging, which was then manipulated to help make ‘old blood’, new again. Amongst its many new implications, mitochondria is also crucial to protein folding via the mitochondrial unfolded-protein response, also known as UPRmt, which kicks in to boost the production of specific proteins to fix or remove the misfolded protein. The study identified the importance of UPRmt in blood stem cell aging while studying a class of proteins known as sirtuins. The team noticed that levels of one particular sirtuin, SIRT7, increases as a way to help cells cope with stress from misfolded proteins in the mitochondria; notably, SIRT7 levels decline with age. Therefore, the lab isolated blood stem cells from aged mice and increased the levels of SIRT7 to reduce mitochondrial protein-folding stress. They then transplanted the blood stem cells back into mice, and identified improved regenerative capacity. Thus, a new potential regenerative medicine for controlling the aging process has been provided.
5. At number five, and the midway mark is University of Iowa: This study identified the first example of a protein which causes muscle weakness and loss during aging. The protein identified, known as ATF4, is a transcription factor that alters gene expression in skeletal muscle, causing reduction of muscle protein synthesis, strength, and mass. What also caused a frenzy was the fact the researchers identified the environmental factors or precursors that affect this protein, and thus, aging of muscle. The two natural compounds, ursolic acid, which is found in apple peel, and tomatidine, which comes from green tomatoes, were found to prevent acute muscle wasting caused by starvation and inactivity. The team also showed that by reducing ATF4 activity, ursolic acid and tomatidine as small molecules can then assist skeletal muscle to recover from effects of aging. When reviewing the numerous conditions, diseases, mental disorders, cancers, bacteria and millions of other environmental/epigenetic factors the human body staves off every day, logic would dictate that the intake of natural, protective and beneficial compounds or precursors is just as important as the cure. A premise now being mirrored in many new, medically-sound whitepapers, supplying preventative countermeasures.
6. Number six in the list is the University of North Carolina at Chapel Hill School of Medicine: At number six we have a strong neurogenetics study which encompasses both epigenetics and the resulting denditric spine formation in autism. The study brought to light the quandary of many thousands of loci identified for autism with no way of knowing how these many genes cause the disorder at a cellular level, with epigenetic marks not yet identified. So, geneticists have this big, unbalanced molecular equation with no way of knowing how removing even one part of this equation would effect the other thousands of genes; this study provides the epigenetic total, the sum of this unbalanced equation. The findings in essence moves the genetic timeline downstream to the outcome of many different possibilities, many different gene interactions and couplings, rocking back and forth between causal environmental switches and resultant proteins. Here, the researchers simply and quietly supply us with the cause of overproduction of dendritic spines, a long known pathology in autism. The phosphorylated epigenetic reaction mapped is at the UBE3A gene, the cellular changes it causes are the UBE3A enzyme becoming hyperactive and driving abnormal brain development and autism. Amazingly, this epigenetic reaction allows the team to travel backwards, upstream to identify the molecular reaction; the duplication of the 15q chromosome region, which accomodates UBE3A, one of the most commonly seen genetic alterations in people with autism. Travelling back downstream they then show that protein kinase A (PKA) is the enzyme that tacks the bulky phosphate group onto UBE3A, leading to therapeutic implications as drugs exist to control PKA. A great experience which allows readers to travel along the genetic causal timeline, molecular to cellular, upstream and downstream and back again.
7. A respectable number seven globally is Georgia Regents University: As neuroinflammation is being implicated in many mental disorders, and Alzheimer’s studies flitting between many schools of thought. When following the doctrine of immunology, Alzheimer’s studies either use the approach of a sole astrocytic role, treating a head injury, implicating the shared blood system of the brain and heart, cardiac blood plaques reaching the brain, and/or a neuroinflammatory reaction causing the initial damage. And so a common thread begins to take shape, with this study firing off on all cylinders to investigate where the source autoimmune reaction is originating from. It has been previously shown that the brain is the ‘fattest’ organ in the body, which would make the right types of fat important for its running, just like any other body part or organ. Here the researchers show that ceramide levels are elevated well before Alzheimer’s mouse models show signs of substantial plaque formation.
Ceramide is needed for a variety of physiological functions including apoptosis, cell growth arrest, differentiation, cell senescence, cell migration and adhesion. Ceramide and its downstream metabolites have been implicated in a number of pathological states including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation. Here the researchers show excess ceramide in the brain results in the production of vesicles, called exosomes, that start piling up around brain cells. When ceramide exosomes get taken up by other cells, they of course trigger cell death with the clearance system stopping to work after a time. Toxic levels of amyloid and ceramide pile up, with excessive ceramide working its way into the bloodstream, generating antibodies that support disease progression, most markedly in female mice. Data findings show that when more ceramide was introduced, it not only increased antibody levels, it also increased levels of plaque and exosomes to fulfill the Alzheimer’s cycle. Currently, the researchers are circling back to a previous approach of more directly blocking ceramide, theorising that the mice genetically programmed to get Alzheimer’s will produce less ceramide, less exosomes, and therefore, less plaques.
8. Number eight is The Institute of Bioengineering and Nanotechnology (IBN) of A*STAR: The much-loved discipline of field medicine is never left out in the cold by health innovators across the globe, no matter the budget or location. Not necessarily costly or cumbersome, intricate or modern, the optimum residuum is to provide the best possible solution on and off the field at a fraction of the price; the study at number eight on this best of list certainly delivers. Melding nanotechnology with the ever-popular MEMs, this study delivered the testing solution for the most prevalent mosquito-borne disease in the world, dengue fever. Currently, dengue infection is diagnosed in the laboratory by testing the patient’s blood sample for the presence of dengue antigens or antibodies. The new device, on the other hand, is capable of detecting IgG, a dengue-specific antibody found at the onset of secondary infections, directly from saliva in one step. Unlike blood samples, saliva can be collected quickly and painlessly, with the easily transported lab-on-a-chip relying on particles meaning the sample can be greatly reduced in size due to higher sensitivity; the uniform system also creates a standardised flow. The new diagnostic device can also be adapted to detect other infectious diseases such as HIV and Syphilis; a great all-rounder from IBN.
9. Coming in at number nine of The Top 10 Healthinnovations of 2015 is the Salk Institute for Biological Studies: Here the team explains ever evolving and degrading brain circuitry via epigenetics. This logical study tackled brain plasticity and showed that the malfunction of a single molecule can prompt a neuron to make an ‘early-career’ switch, changing from a neuron originally destined to process sound or touch, for example, to a neuron that processes vision. The researchers identified a mechanism that provides brain plasticity to maturing sensory neurons. The mechanism, a transcription factor called Lhx2, can be used to switch genes on or off to change the function of sensory neurons in mice. The team actually controlled Lhx2 in mice to instruct neurons situated in one sensory area to process a different sense, thus enlarging one region at the expense of the other. Before this study it was unclear how relatively mature neurons could be reprogrammed in this way. The results show that the brain is very plastic and responds to both genetic and epigenetic influences well after birth.
10. And at number ten of this outstanding list is the UI Carver College of Medicine: This study not only identified areas of the human brain in which breathing is controlled; it also controlled the said area, the amygdala, via neurostimulation to investigate Sudden unexpected death in epilepsy (SUDEP). It has long been suspected that in SUDEP the patient’s breathing is impaired during and after seizures, without their knowledge. The researchers finally verified this hypothesis, proving once and for all that when seizures spread to the amygdala, the participants with medically intractable epilepsy stopped breathing. The team also reproduced this effect by electrically stimulating the amygdala to show that the patients were unaware they weren’t breathing. Therefore, they provided an explanation for why SUDEP occurs after seizures, whilst identifying brain areas where seizure spread interferes with breathing to help identify patients at risk for SUDEP, all of which may lead to preventive strategies.
A fantastic line-up, decided by the global community for the global community and really encompassing the main interests in medical research to-date. Newer studies that didn’t make this list as they were towards the end of the year were obesity being mapped as an autoimmune disease, tying in with diabetes and brown fat. This is also the case for the rare herpes study, which tends to viral throughout the healthinnovations digital channels, with the public quick to read and share information on the disease. It should also be noted that any and all immunology news tends to be picked up with view to virology. Whilst datamining Healthinnovations has recorded channels full of miracle cures and misinformation on the herpes simplex virus with only a minute amount of actual verified news for 90% of the world to read. Presently, this is one of the worst gaps in health information ever witnessed.
In contrast, great strides are also being made in traversing the blood-brain barrier, with nanobots being pushed out of proof-of-concept to successfully lever open BBB tight junctions in animal models. These biological and synthetic submicron helpers have also been utilised as controllable nanoparticles for highly targeted treatment delivery. This is also indicative of the strong nanotechnology industry which is now being applied in ways only imagined, with fail-safes and removal systems now in place.
Missing from research all together this year, was that strong HIV study, with a lack of studies coming out of the simian stage, bar two strong structural studies in the last weeks of this year. This current situation could denote the success of the great ARV regime. Not to detract from this, however, more work needs to be done to fill the gap in vaccines and curative studies. There is still so much to map in this disease, deciphering between immune-privileged sites and reservoirs within the immune-system, for instance. Providing a definitive model of reservoirs to control and flush out the HIV virus. A long way to go to, with a disease kept prevalent and awaiting the next mutated version, due to the out-of-control sex trafficking industry.
This leads to another missing class of studies from this years’ Top Healthinnovations, the definitive, main-streamed conditioning and suggestibility neuroimaging study, with view to schizophrenia and borderline personality disorder. This state, known historically, as hypnosis, is where a person takes cues or communications such as noises, clicks, mouthing, motions and believes they are being controlled by the ‘hypnotist’. As time went on notable psychiatrists and physicians recorded a ‘susceptibility’ in suggestibility, and linked neurological disorders such as dissociative identity disorder and schizophrenia to ‘hypnotic susceptibility‘. As research moved on it became clear that the deeper the hypnotic conditioning went or was used, and believed, led to dissociation or the start of psychosis. The situation where these acts of conditioning on an untreated schizoid is not controlling, or indeed helping the person, it’s actually more damaging; which is logical with an untreated disorder or a refusal to take medication. This research has been ongoing since the 1700’s, that’s over 300-years of sturdy research, so it is not to be taken lightly or simply buried. It would probably solve a multitude of social, grooming, conditioning, trafficking, terrorist, and brainwashing-based problems, not caused purely by physical coercion, overnight if more money was thrown at it.
Differentiation therapy for cancer has been showing promise and, therefore, deserves a mention. These exciting and evolved stem cell therapies, take out the bad and replace it with the good. Things to be addressed, however, are the replenishment of healthy cells and whether these therapies have the potential to permanently replace diseased cells with healthy ones. An interesting premise, it is hoped to stabilise these ‘corrective’ therapies for longetivity. Perhaps modelling the ‘cleaned’ or corrected cells on a virus to ‘infect’ diseased cells with a virion like capsoid and unmutated DNA could be the answer here.
Major progression is also being made in mapping the linked heart and brain circulatory system and the effect heart disease may have on the brain. There have many studies making the association between Alzheimer’s and cholesterol plaques. So far, Alzheimer’s has been linked to heart disease proper with no defining study to show the mechanism by which cardiac plaques, travel and seed in the brain to cause Alzheimer’s. However, there has been a study which identifies the link between early stage heart and brain disease that caused a stir as it was a large-scale human study. As many researchers hold the belief that the heart and brain are inextricably linked, forever balancing health between each other, it would make sense to perform more large-scale biomarker studies in the vein of this dogma.
So, it is the end of this year’s masterclass and analysis of the Top Healthinnovations of 2015. A massive well done to all who made the list, it’s no easy task as shown by the amazing number of shares and stats garnered by these amazing teams. They have set the pace and laid down the gauntlet for all those who follow around the world. Truly pioneering, and innovating their field with strong, sound studies; some answer the question, finally, whilst others have provided the foundation to work from. Here are the building blocks for 2016. These studies turn science to art with the inspiration and thought-processes forced into motion; and with inspiration comes emotion, comes heated discussion, comes passion, which all the studies above have caused.
And Healthinnovations has made sure every country was reached to cause the thinking and planning to gain as many different inputs as possible. Over the past six-months the reach for retweets hit 94 million impressions on the Healthinnovations Twitter account alone, new channels on tumblr and Pinterest have opened up a whole new audience; the ever-growing Neuroinnovations and Healthinnovations facebook pages now have a total of over 24,000 fans between them; and the Healthinnovations Google plus channel has seen a rebirth of sorts, with a rise in stats.
And, finally let’s not forget to congratulate all the teams who were reported on the Healthinnovations digital channel, achieved through sheer excellence and consistently presenting strong studies. Well done!
Looking forward to the new discoveries in 2016 everyone! See you all then!