more_vertVictor Frankenstein—a student at the Royal College of Physicians, and a master natural philosopher—pores over Leonardo-esque anatomy drawings in the chiaroscuro of his laboratory. His shadowy researches into the restoration and creation of life are illuminated by lightning flashes of inspiration and accompanied by hysterical, megalomaniac laughter—in which the audience is invited to join, for if this is horror, it’s of the rocky horror variety.
Preference: Physiology and Anatomy
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[Comment] Italy, the Land of Holy Miracles—revisited
Can Italy regain its once pivotal position as a cradle of scientific innovation and advancement in Europe? During medieval times, the Renaissance, and the Enlightenment Italy was considered pre-eminent in natural science and medicine. The birthplace of modern universities and medical schools, Italy was a training ground for distinguished scholars and physicians, such as William Harvey, who came to Italy to study anatomy and medicine at the University of Padua under Hieronymus Fabricius and Giulio Cesare Casserius in the early 17th century.
Health funds spend millions on unproven treatments
There is no evidence that any of the natural therapies typically covered by private health insurance deliver clinical benefit, increasing the focus on the value for money provided by health funds.
An exhaustive review of 17 natural therapies conducted by the Office of the National Health and Medical Research Council found that while a small number may provide some short-term pain relief, most lack any scientific evidence to back their health claims.
“Overall, there was not reliable, high-quality evidence available to allow assessment of the clinical effectiveness of any of the natural therapies for any health conditions,” the review, chaired by the Chief Medical Officer Professor Chris Baggoley, said.
The report, which has been with the Government for months, looked at therapies including massage, yoga, pilates, shiatsu, homeopathy, kinesiology, reflexology, naturopathy, aromatherapy, herbalism, iridology, Bowen therapy and Alexander technique – many of which are covered by insurers under their extras cover.
Medibank Private, for instance, will provide up to $200 a year toward consultations for reflexology, kinesiology, Chinese and Western herbalism, exercise physiology, shiatsu, aromatherapy, homeopathy, Bowen therapy, Alexander technique and Feldenkrais for singles with extras cover.
The Baggoley review found there was “moderate quality evidence” that massage therapy could provide immediate-term relief for people with chronic lower back pain, but said there was only very low-quality evidence that tai chi benefited health. For therapies like kinesiology, homeopathy, reflexology and rolfing it found scientific evidence was either lacking, insufficient or uncertain.
The funds argue that natural therapy cover encourages younger, healthier people to take out private health insurance, helping offset the financial drain from older and sicker members.
But critics argue it is a misuse of resources which should only be directed to therapies of proven clinical effectiveness.
The Baggoley review was commissioned by the former Labor Government, which wanted to stop paying the Private Health Insurance Rebate for therapies not backed by scientific evidence. It estimated the cut would save $32 million a year.
The report has been released in the midst of a Government review of private health insurance.
Health Minister Sussan Ley has launched a round of consultations, including a consumer survey, and has aired a range of ideas including allowing insurers to charge higher premiums for smokers or the obese, and to reduce industry regulation.
The Minister said cover for natural therapies would be considered as part of the review, but has so far stopped short of declaring the rebate for such claims would be axed.
She told The Australian that, in theory, she supported the rebate only going toward treatments backed by evidence, but said Labor’s decision to launch the Baggoley review had been “purely about desperate budget cuts…not evidence”.
Ms Ley claimed that around 500,000 dumped or downgraded their health cover in the past 12 months in a clear demonstration that something was wrong.
But AMA President Professor Brian Owler said that although there was clearly a problem, the Minister was misreading what was going on.
Professor Owler said most people were not choosing to downgrade their cover. Instead, insurers were shifting often-unsuspecting consumers onto policies with bigger excesses and more gaps and exclusions, leaving them liable for unexpected charges.
The AMA President warned that insurers, driven more by the search for profit rather than the health of their customers, were taking the health system down a path toward US-style managed care, which would see the poorest and sickest increasingly shunted into the already-stretched public health system.
Public concern about the quality of health insurance has been fuelled by relentless above-inflation premium increases and reducing coverage.
It has been reported that the funds, which are subsidised by the $6 billion a year Private Health Insurance Rebate, are seeking an average 7 per cent premium increase next year.
Adrian Rollins
[Comment] A novel total artificial heart: search for haemocompatibility
During the past four decades several groups in the USA and Europe have developed and clinically implemented different cardiac prostheses or total artificial hearts (TAH)—the Cooley/Liotta TAH, Jarvik7 TAH, Bücherl Heart TAH, AbioCor TAH, and CardioWest TAH (TAH-t), which is currently in use. The aim of TAHs is to mimic native heart anatomy and function, fitting into the pericardial cavity and providing pulsatile unidirectional blood flow from the atria to the great arteries in patients with end-stage biventricular heart failure.
Bad times for good bacteria: how modern life has damaged our internal ecosystems
Human actions damage ecosystems on a global scale. Our influence is so great we’ve triggered a new geological epoch, called the Anthropocene, simply because of the changes we’ve brought about. But it’s not just the outside environment we’ve changed, we’ve also damaged the ecosystems inside us.
Our activities alter natural processes, such as weather patterns, and the way nutrients, such as nitrogen and phosphorus, move within ecosystems. We cause declines in species diversity, trigger extinctions and introduce weeds and pests.
All this comes with costs, caused by the increasing unpredictability of both physical and biological systems. Our infrastructure and agriculture rely on a consistent climate, but that’s now becoming increasingly unreliable. And it’s not just the outside world that’s unpredictable; it may come as a surprise to some that we have internal ecosystems, and that these have also been damaged.
Shrinking population
Every adult is made up of 100 million, million human cells (that’s a one followed by 14 zeroes). But the human body is also home to ten times this number of bacterial cells, which, collectively, are called the microbiota. Biologists have only been exploring this internal ecosystem for a decade or so, but surprising and important results are already emerging.
Humans damage ecosystems on an epic scale. Global Water Forum/Flickr, CC BY
Because the laboratory where I work is interested in how humans affect evolutionary processes, it was natural for us to ask how much humans might affect microbial ecosystems. The answer turns out to be quite a lot.
Possibly the most direct and personal effects are on our own microbiota. And these changes come with consequences for health and well-being. Exactly the same processes we see in external ecosystems – loss of diversity, extinction, and introduction of invasive species – are happening to our own microbiota. And damaged ecosystems don’t function as well as they should.
Scientists have tried to “go back in time” and ask what the original human microbiota might have looked like. There are three ways of doing this: biologists can look at the microbiota of our nearest relatives, the great apes; we can examine DNA from fossils; or we can look at the microbiota of modern-day humans who still have a hunter-gatherer lifestyle.
All these approaches tell the same story. Modern humans have a lower diversity of microbiota than our ancestors, and there’s been a consistent decline in this diversity across ancient and recent human history.
There are a number of reasons for the decline. The widespread use of fire from 350,000 years ago increased the calories we could obtain from food. This probably decreased our need for a big gut, and a smaller gut means less room for microbes.
The invention of agriculture between 8,000 and 10,000 years ago changed our diet, and with it, our microbiota. The end result was the extinction of some components of the microbiota in farming populations. Even today, hunter-gatherers and subsistence societies have many bacterial species in their gut that are never found in the guts of people from westernised societies.
One of the last hunter-gatherer societies in the world, the Yanomami people of South America, have a highly diverse and stable microbiota, and don’t suffer from diseases common in the developed world. christian caron/Flickr, CC BY-ND
Modern onslaught
Changes in microbiota have been tracked using bacteria preserved on the teeth of skeletons, and this showed falls in diversity linked to dietary changes, as well as a shift to microbial species associated with disease.
The changes are particularly apparent after the Industrial Revolution, when processed flour and sugar became widely available. And diet continues to have a major influence on our microbiota.
But the greatest disruption probably happened after the 1950s. This time period corresponds to a number of changes that directly affect the composition of the human microbiota. One involves the opportunity for microbiota to colonise newborns and infants. Normally, babies obtain some microbiota from their mother during childbirth, but caesarean births interrupt this opportunity. Bottle feeding, increased sanitation, and eating processed, sterile foods also limit opportunities to acquire microbiota.
Modern medicine has been very successful at controlling bacterial diseases with antibiotics. Unfortunately, antibiotics cause considerable collateral damage to innocent and beneficial bacteria. After antibiotic therapy, the microbiota may never return to their original abundance, and genetic diversity is reduced in those bacteria that remain.
Antibiotics can also damage beneficial bacteria. Photo: Shutterstock
Collectively, these changes mean that our microbial ecosystems have become degraded, much like natural ecosystems globally. The microbiota are less functional and resilient than they should be. And it turns out they have essential roles in developing our immune systems, and in regulating metabolism. So it shouldn’t be surprising that altered microbiota are now being associated with many diseases of the modern world.
These diseases include obesity, allergic reactions, chronic inflammatory conditions and autoimmune disorders. More recently, it’s also been suggested that psychological conditions, such as depression and anxiety, are linked to the bacteria that live inside us.
In some cases, the parallels with more conventional ecosystems are clear. Clostridium difficile is a bacterium that can grow out of control in our gut, like an invasive weed. And, like a weed invading degraded land, it often spreads rapidly after other bacteria have been eliminated from the gut by antibiotics. The most effective cure is similar to bush regeneration; donating microbiota from healthy volunteers (a “poo transplant”) helps restore a healthy ecosystem.
But, for many diseases associated with our microbiota, there are no immediate cures. Like most ecosystems, our gut bacteria are complex and dynamic. The challenge now is to understand this system and how to acquire and maintain a healthy microbiota, so that in the future, a microbiota check-up might be a routine part of a visit to the doctor.
In such a future, hunter-gatherers such as the Yanomami of the Amazon may turn out to be the custodians of valuable species that are extinct in the microbiota of the developed world.
This article was originally published on The Conversation. Read the original article.
[Series] Targeting the interleukin pathway in the treatment of asthma
Asthma is a common heterogeneous disease with a complex pathophysiology. Current therapies based on inhaled corticosteroids and longacting β2 agonists are effective in controlling asthma in most, but not all patients, with a few patients falling into the severe asthma category. Severe asthma is characterised by poor asthma control, recurrent exacerbations, and chronic airflow obstruction despite adequate and, in many cases, high-dose treatments. There is strong evidence supporting the role for interleukins derived from T-helper-2 (Th2) cells and innate lymphoid cells, such as interleukins 4, 5, and 13, as underlying the eosinophilic and allergic inflammatory processes in nearly half of these patients.
[Comment] Type 2 diabetes: multimodal treatment of a complex disease
Type 2 diabetes is becoming the plague of the 21st century. With the so-called diabesity epidemic the disease threatens to reduce life expectancy for future generations globally. Surgery for diabetes has been marketed as an effective treatment option for patients with obesity and type 2 diabetes. Different surgical procedures have been used successfully, with some changing the anatomy of the stomach, bypassing parts of the gut, or using devices. These trials have provided an intriguing model to study the role of the gut in maintaining glucose homoeostasis.
Cancer nanomedicine: challenges and opportunities
Nanotechnology holds enormous promise for personalised cancer medicine — translation is the key
Medicine is on the cusp of a revolution. Personalised, precision medicine — designed and tailored at a molecular level for an individual’s own physiological make-up — will become an inevitable reality in the 21st century. As with all paradigm shifts in medicine, this will be driven by new science and technology, and the technology of the 21st century is nanotechnology.
Nanomedicine is a rapidly evolving paradigm where nanoscience and nanotechnology are applied to medicine. The science underpinning nanotechnology is that some materials, when reduced from everyday, bulk scales down to nanoscales (billionths of a metre; smaller than the size of a typical virus), exhibit dramatically different physical properties. Harnessing and customising these unique nanoscale properties offer unique advantages to health and medicine for two reasons. First, many key molecules involved in biochemical processes responsible for regulating biological function have nanometre (nm) sizes (eg, a glucose molecule is about 1 nm), so nanoscale probes offer a means for molecular-based interrogation and intervention strategies. Second, because of their size, nanoprobes offer a relatively discreet, non-invasive strategy for disease detection and targeted therapy (although the immune system inevitably catches up).1
An important example of how nanoscale properties can be harnessed for medical applications is magnetic resonance imaging. Here, image contrast is enhanced using magnetic nanoparticles, usually based on gadolinium or iron oxide, which exhibit strong magnetism only when reduced to scales of 20 nm or less.2
Nanoparticles: size matters when it comes to targeting tumours
In cancer nanomedicine, a wide range of nanoparticles continue to be developed for better tumour-targeted delivery of therapeutics (chemotherapy and radiotherapy). These include liposome-, polymer- and micelle-based nanoparticles for encapsulated delivery, and metallic nanoparticles (eg, gold), which have been investigated for targeted radiotherapy.1–3 There are two types of tumour-targeting approaches with nanoparticles: passive and active. Passive targeting relies on tumour vasculature, which has larger endothelial gap junctions compared with healthy tissue. Nanoparticles greater than 8 nm can pass through these gaps to reach tumour cells. An enhanced permeability and retention effect results from the combination of larger gap junctions and defective lymphatic drainage, particularly around fast-growing tumours, facilitating preferential accumulation and prolonged retention in the tumour tissue.1 In active targeting, however, nanoparticles are conjugated with targeting agents, such as antibodies, that are specific to proteins highly expressed by certain tumours (eg, human epidermal growth factor receptor 1 in non-small cell lung cancer).3
Challenges: clinical translation
Despite ongoing progress in basic and preclinical cancer nanomedicine research, arguably the single most important challenge is clinical translation.4 However, most of the many different nanoplatforms developed for cancer therapy have not progressed past Phase II clinical trials.1 Very few have achieved United States Food and Drug Administration approval (eg, liposome-encapsulated doxorubicin and daunorubicin for breast and ovarian cancers, and Kaposi sarcoma). New efforts are focusing on the potential to extend the capabilities of other therapeutic and imaging nanoplatforms developed and approved for non-cancer indications. For example, ferumoxytol is an iron oxide nanoparticle used for treating anaemia and it is also a magnetic resonance imaging contrast-enhancing agent.5 Nanotheranostics — the use of nanoplatforms combining targeted therapy and diagnostic imaging functionality — is a rapidly growing trend.
Why is bench-to-bedside so challenging for cancer nanomedicine? The problems are many. Key difficulties include controlling nanoparticle size and preventing nanoparticle aggregation in vivo, which are critical for clearance by the kidney or liver. Biocompatibility, blood circulation time and the ability to elude the immune system long enough to release a therapeutic cargo, are similarly difficult to clinically validate. Additional practical challenges that need to be overcome for clinical translation include tumour cell specificity, cellular uptake and localisation, and controlled release and functionality of the cancer therapeutic.3
Opportunities: clinical translation
The challenges presented by clinical translation could equally be viewed as opportunities. This is the approach taken by the European Foundation for Clinical Nanomedicine (https://www.clinam.org). Similarly, the US National Cancer Institute (NCI) integrates translational and basic science research in its Alliance for Nanotechnology in Cancer (http://nano.cancer.gov). Launched in 2004, the Alliance held a strategic workshop in 2013, the outcomes of which highlighted several recommendations for future opportunities in cancer nanotechnology.6 These include supporting the development of new techniques and clinical translation in parallel; supporting a stronger focus on developing active targeting strategies; and giving a high priority to imaging probes and lower priority to developing in-vitro nano-enabled techniques. The NCI report also highlighted the importance of interdisciplinary collaboration — bringing together clinical and basic science researchers from diverse backgrounds is the key to creating unique opportunities for genuine breakthrough discoveries in cancer nanomedicine.
[Seminar] Acute pancreatitis
Acute pancreatitis, an inflammatory disorder of the pancreas, is the leading cause of admission to hospital for gastrointestinal disorders in the USA and many other countries. Gallstones and alcohol misuse are long-established risk factors, but several new causes have emerged that, together with new aspects of pathophysiology, improve understanding of the disorder. As incidence (and admission rates) of acute pancreatitis increase, so does the demand for effective management. We review how to manage patients with acute pancreatitis, paying attention to diagnosis, differential diagnosis, complications, prognostic factors, treatment, and prevention of second attacks, and the possible transition from acute to chronic pancreatitis.
[Comment] Rethinking and reframing obesity
In 2011, we published The Lancet’s first Series on obesity, which summarised the then available knowledge about its origins, economic and health burden (with projections for the future), and the physiology of weight control and maintenance. The Series concluded with science-based recommendations for action.1–4 In an accompanying Editorial, we called for a concerted response with five urgent messages (panel).5