Medical & Health Sciences

Most human diseases are localised in terms of their location but currently, injected or orally administered drugs are evenly distributed all over the body and thus, act indiscriminately. The targeted delivery of medication to the exact site where it is needed is a common theme in science fiction but thanks to Professor Richard Klemke and his team at the University of California San Diego’s Moores Cancer Center, this fantasy may soon become a reality.

Hypertension (high blood pressure) is a common health issue in adults that can lead to numerous co-morbidities. For hypertension to develop, a pathway called the renin-angiotensin-aldosterone system needs to be activated, and a vital part of this system involves the angiotensin 1 receptor. Dr Sudhir Jain from New York Medical College studies this receptor and how specific groups of genetic mutations, known as haplotypes, promote hypertension under different conditions.

The relatively new field of paediatric pharmacovigilance aims to improve the clinical care of children by understanding and appropriately managing the risks of medicines administered to this group of patients. Dr Beate Aurich is an established expert in this field, and with colleagues, has published an article on the practical aspects of paediatric pharmacovigilance. She notes that the assessment of the benefit-risk balance of available treatment options should be based on multidisciplinary efforts and include both children and their families.

As the strains of bacteria that are not killed by antibiotics proliferate, increasing numbers of people are at risk of severe illness and even death. Dr Rogier Hopstaken from Star-shl Diagnostic Centres in the Netherlands has shown that a simple, yet effective technique may be the answer to antibiotic over-prescription. A C-reactive protein test at primary points of care can indicate whether a patient with a respiratory tract infection has a severe (bacterial) infection and thus, whether antibiotics are required. This test may be our best tool yet to help combat antibiotic resistance in primary care.

The pH inside our cells is constantly changing, but also carefully controlled within certain limits. Dynamic intracellular pH (pHi) is essential for normal cell behaviours, but when it becomes dysregulated, it can enable an array of diseases from cancer to Alzheimer’s. Dr Diane Barber from the University of California San Francisco has carried out extensive research into how normal pHi dynamics regulate cell behaviours and the impact that dysregulated pHi can have in different diseases.

N-nitrosodimethylamine (NDMA for short) is a worryingly prevalent, potentially potent carcinogen found in food, water, cigarettes and medical drugs. Researchers at the Massachusetts Institute of Technology, USA, are working to better understand what NDMA does and how cells can defend themselves from its effects, with important implications for public health.

On the surface of many of our cells, intriguing receptors called cannabinoid receptors reach out into their environment. The CB2 subtype of this receptor family is expressed largely on our immune cells and plays an important role in inflammatory responses, making it a promising target for anti-inflammatory therapeutics. To produce effective drugs, the molecules that bind to the CB2 receptor, known as ligands, need to be characterised. Dr Uwe Grether from F. Hoffmann-La Roche Ltd has dedicated his research to discovering useful CB2 receptor ligands and utilising them in the development of novel anti-inflammatory therapeutics.

Worldwide, an estimated 38 million people are living with HIV. Many are still unaware of their status and so are not linked to care and treatment which can prevent them from passing HIV onto their partners and infants and keep them healthy. Dr Richard Hayes from the London School of Hygiene and Tropical Medicine in the UK has led the HIV Prevention Trials Network’s 071 (PopART) trial over the past ten years. This dedicated international collaboration of experts has successfully demonstrated how universal testing and treatment can reduce new HIV infections in Zambia, South Africa and beyond.

Scoliosis, the curving of the spine, is a relatively common condition that develops in early adolescence. Whilst there are surgical options to neutralise the curve, there is no solid evidence for its long-term impact. Dr Hans-Rudolf Weiss is an expert in scoliosis treatments and has dedicated his research to improving the care of scoliosis patients. Through his back brace innovations and novel exercise therapies, he has developed ground-breaking new standards of care for patients. Additionally, through his Schroth Best Practice program, he is educating a new generation of doctors and physiotherapists on his non-surgical methods.

This is a recounting of a scientific investigation into a mysterious but potentially deadly disease that first came to light principally in the Balkan states, and then several Asian countries. It manifests itself first as a nephropathy resulting in the destruction of kidney tissue often followed by a cancer of the upper urothelial tract. Professors Arthur Grollman and Francis Johnson at Stony Brook University have achieved a revolutionary understanding of the molecular biology, epidemiology and root cause of both diseases. Their findings have critical implications for medical and scientific communities, as well as the general public.

Physiological responses to inflammation and pain are complex and varied, depending on which cellular structure you focus on. Planted within our cell membranes is a channel that facilitates the transport of ions in response to perceived dangers. Named P2X7 receptor, this channel subtype is activated by adenosine triphosphate (ATP) to open the gate for ions, and is of particular interest to Dr Fritz Markwardt at Martin-Luther-University Halle-Wittenberg in Germany. Dr Markwardt studies P2X7 to elucidate its structure, function and ATP activation mechanisms to provide novel avenues for drug development.

Throughout the world, especially in low-income countries, environmental contaminants such as fluoride have huge health consequences. While some countries add fluoride to their drinking water, others have little control over its concentration, resulting in dangerously high fluoride concentrations. Excess fluoride exposure is known to cause the bone disease skeletal fluorosis, but Dr Tewodros Rango Godebo from Tulane University in Louisiana, USA, believes that current diagnosis techniques are incomplete. Using ultrasound technology, he has determined for the first time how fluoride exposure leads to reduced bone quality, and how this diagnosis can be used in fluoride-exposed populations.

Cancer comes with many symptoms, but its life-saving treatments also cause negative side effects. One of these is radiation-induced fatigue, a clinical subtype of cancer-related fatigue and a debilitating issue that causes extreme lack of energy in those receiving radiation therapy. While this is a well-known effect of the treatment, exactly why it happens is unclear. Dr Chao-Pin Hsiao at Frances Payne Bolton School of Nursing in Case Western Reserve University, Ohio, is studying the molecular and genetic-level mechanisms that drive fatigue induced by cancer/cancer treatments. Her work on finding fatigue biomarkers provides promise for future combative therapies.

The Association of Medical Research Charities (AMRC) is dedicated to supporting medical research charities in saving and improving lives through research and innovation. Founded over 30 years ago, the AMRC has united more than 150 medical research charities in all areas of health and disease throughout the UK and overseas. In this exclusive interview, we follow up our 2019 interview with the new Chief Executive, Nicola Perrin, to hear their latest news.

Rheumatoid arthritis is an autoimmune disease that results in painful and swollen joints, among other complications. Although treatment can alleviate the symptoms, more research is needed to understand the underlying causal mechanisms that could be exploited to prevent it. Dr Mario Zaiss the University of Erlangen-Nürnberg has carried out extensive research in this field and focuses on the impact of diet. He has made the exciting and important discovery that a high-fibre diet produces metabolites that play a vital role in preventing the onset of rheumatoid arthritis.

Bacteriophages are tiny viruses that infect and kill bacteria but are harmless to humans. With the world facing devastating antibiotic resistance in the coming years, they may be our best hope for treating bacterial disease. There are believed to be 10^31 bacteriophages in the world, and most of them have not yet been identified. Dr Kristin Parent from Michigan State University is working on exciting, collaborative projects hunting for bacteriophages in their natural environment. She has made huge strides in elucidating the mysterious and important world of bacteriophages.

The design of effective antivirals is a key priority in the global effort to curb the pandemic caused by the novel coronavirus SARS-CoV-2. The FDA-approved drug Remdesivir (RDV) acts by interfering with the SARS-CoV-2 viral replication mechanism. Dr Jin Yu and her team from the University of California, Irvine, conducted a computational study to elucidate how the RNA-dependent RNA polymerase (RdRp), responsible for SARS-CoV-2 genomic replication, is inhibited by RDV. Excitingly, they showed that RDV binds tightly to RdRp, stabilising a closed conformation of the active site for successful incorporation to effectively halt viral replication.

Dr Anne Hansen is the Medical Director of the Neonatal Intensive Care Unit and Associate Chief of the Division of Newborn Medicine at Boston Children’s Hospital. With her colleagues, Dr Hansen has developed and tested a low cost, non-electrical warming mattress called the ‘Dream Warmer’ to help prevent and treat neonatal hypothermia in countries with limited medical resources. Her team has conducted extensive testing in Rwanda with results demonstrating that this medical device is safe, effective and ready for use on a wider scale.

Dr Arpan Ashok Patel of the University of Rochester School of Medicine and Dentistry is dedicated to better understanding the prevalence and impact of financial toxicity amongst older, more advanced cancer patients. His recent work in this field is the first to analyse real conversations between patients and oncologists in this high-risk group. His findings show that those struggling with financial stability following cancer treatment are more likely to have a lower health-related quality of life, highlighting the need for better screening tools to identify at-risk patients to allow appropriate signposting to support.