Body

Professor Natan Gadoth at the Sackler Faculty of Medicine, Tel-Aviv University, Israel has written a review on the subject with a focus on the comorbidities in an attempt to present an update for researchers. "Unfortunately, published literature is mostly dedicated to the study of tics, while mentioning the comorbidities only briefly." In his review, Professor Gadoth notes that Tourette disorder is an intersection of many medical conditions which include tic disorders, obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), sleep disorders and a number of behavioral problems. Professor gadoth reckons that Tourette syndrome is a multidisciplinary disorder in nature. He concludes that "patients with Tourette disorder should be evaluated and treated by a multidisciplinary team."

On behalf of the Federal Joint Committee (G-BA), the Institute for Quality and Efficiency in Health Care (IQWiG) investigated whether it is meaningful to test newborns in Germany for spinal muscular atrophy (SMA) in combination with earlier diagnosis and treatment. The Institute's final report is now available.

After evaluating the evidence available, the IQWiG researchers see an indication of a benefit of newborn screening versus no screening: The earlier the disease is diagnosed and the earlier doctors can thus start treatment, the greater the benefit for children with an early onset of disease (infantile SMA). The advantages are mainly seen in better motor development, such as the achievement of motor milestones like "free sitting" and "walking".

Genetically related muscle atrophy is rare, but extremely serious

5q-associated SMA is a hereditary disease that leads to the progressive death of motor nerve cells (motor neurons) in the spinal cord and thus to muscle atrophy and weakness.

With about one new case per 10,000 infants, infantile SMA is very rare, but extremely serious: the muscle weakness impairs or even prevents motor development (e.g. "free sitting" and "walking") as well as lung function. If left untreated, the increasing symptoms of infantile SMA ultimately lead to the need for permanent ventilation and to death. In the equally rare forms with a later onset of disease, the course is usually milder and less predictable.

Blood sample is sufficient - effective treatment is available

The aim of newborn screening for 5q-associated SMA is the earlier identification and thus the earliest possible (ideally pre-symptomatic) start of treatment of the children affected. However, SMA is not yet one of the diseases that are examined in extended newborn screening. In this screening programme conducted in Germany in accordance with the G-BA's paediatric directive, venous or heel blood is collected in the 36th to 72nd hour of life, dripped onto filter paper cards and examined for the presence of certain diseases.

For drug therapy of SMA, a drug called nusinersen (approved since 2017) is available in Germany. Nusinersen replaces the effect of defective genes and is administered via a puncture of the spinal cord canal (lumbar puncture). Other new therapeutic approaches are currently undergoing review for approval.

Linked evidence approach used

IQWiG project manager Andrea Steinzen explains: "No direct evidence was available for this benefit assessment, i.e., there were no comparative intervention studies of the screening chain. We therefore had to compile the evidence ourselves, using various pieces of the puzzle from treatment and diagnostic studies and following the so-called "linked evidence" approach. For the final report, at our insistence the manufacturer provided a crucial piece of the puzzle to assess the effects of starting treatment earlier, which ultimately led to an indication of a benefit of newborn screening".

In order to compare an early start of treatment in symptomatic children suffering from SMA (i.e. within at most 12 weeks after symptom onset) with a later start, the IQWiG researchers evaluated a small randomized controlled trial (RCT) investigating drug therapy versus sham treatment. With regard to the combined outcome "time to death or permanent ventilation" and the outcome "achievement of motor milestones" (e.g. "free sitting" and "walking"), the children affected benefited from an early start of treatment.

In the commenting procedure, the manufacturer subsequently submitted the results of a second study comparing a start of treatment in pre-symptomatic children with an early start of treatment in symptomatic children. The study results showed a dramatic effect in favour of the former with regard to the outcome "achievement of motor milestones". Andrea Steinzen: "The earlier treatment can start, the more positively the course of the disease is influenced".

Due to the short observation period in both studies of less than or exactly one year, no conclusions can be drawn on long-term results. With regard to adverse effects, no differences were shown in either study between the different starting times of treatment. For other outcomes, there are no usable data on these comparisons.

To evaluate the diagnostic accuracy of the test procedures, the IQWiG project team was able to use four studies, the results of which indicate that the test procedures investigated are suitable for screening newborns for 5q-associated SMA.

Important ethical implications still unclear

Newborn screening also identifies newborns with a probable late onset of disease (i.e. symptoms that do not appear until years later). However, the available data on children with infantile SMA do not allow conclusions as to whether children with a late onset of disease who were identified by screening would also benefit from a pre-symptomatic start of treatment. This is because treatment data on children with infantile SMA cannot be automatically transferred to other forms of SMA. The introduction of newborn screening for SMA should therefore include consideration of appropriate management of these children and their families, including the potential option of choosing to be informed (or not) about the presence of mild forms of SMA.

Process of report production

IQWiG published the preliminary results, the preliminary report, in October 2019 for discussion. After the commenting procedure, the project team revised the preliminary report and sent it to the contracting agency, the G-BA, as a final report in February 2020. The written comments submitted are published in a separate document at the same time as the final report.

An international panel of cancer experts has recommended a one-week course of radiotherapy and delaying surgery as the best way to treat patients with bowel cancer during the COVID-19 pandemic.

The short course of treatment involves higher-intensity radiation rather than five weeks of radiotherapy coupled with chemotherapy. Surgery, which normally happens one to two weeks after radiotherapy, can be safely delayed by up to 12 weeks, say the expert panel.

This approach, based on the latest research evidence, will maintain the best chance of successfully treating the disease while at the same time reducing the side effects of treatment and the risks of COVID-19 infection.

People with bowel cancer are more susceptible to severe complications from COVID-19 because their immune system is weakened. Shorter-course radiotherapy avoids the need for chemotherapy, which further suppresses the immune system. It also means significantly fewer hospital appointments, allowing patients to maintain social distancing rules.

David Sebag-Montefiore, Professor of Clinical Oncology at the University of Leeds and Honorary Clinical Oncologist with the Leeds Teaching Hospitals NHS Trust, who led the expert panel, said: "The COVID-19 pandemic is a global emergency and we needed to work very quickly to identify changes that would benefit patients. Our recommendations were published 20 days after our first meeting.

"This process normally takes many months, if not years."

Writing in the journal Radiotherapy and Oncology, the panel, made up of cancer experts from across Europe, say it is also possible that hospitals may struggle to offer the current treatment approaches as COVID-19 impacts on hospital staffing levels.

The expert panel's recommendations can be found here: https://www.thegreenjournal.com/article/S0167-8140(20)30173-0/pdf

The 15- strong panel comprised researchers who led the defining studies. Their research shows that surgery can be safely delayed by 12 weeks. The chances of successful treatment are maintained and post-operative side effects are reduced. This allows surgery to be scheduled after the peak of the pandemic.

The recommendation to use shorter-course radiotherapy follows a major study, funded by the UK Medical Research Council and led by Professor Sebag-Montefiore, which demonstrated the benefit of the one-week course of radiotherapy.

Professor Sebag-Montefiore added: "Our guidelines will result in a very substantial change in treatment across the globe. During the COVID-19 pandemic, our patients will benefit from the use of an effective, shorter and safer radiotherapy treatment."

A Lancaster University statistician who worked on the first published large randomised clinical trial for a potential treatment for the COVID-19 virus said the scientific community was coming together to combat the coronavirus.

There are currently no specific treatments for COVID-19. However, it is possible that some existing drugs, usually used for other conditions, may have some benefits.

Professor Thomas Jaki, from the Medical and Pharmaceutical Statistics Research Unit in the Department of Mathematics and Statistics at Lancaster University, said the initial trial investigated whether anti-viral drugs used to treat HIV would relieve the symptoms of COVID-19 - and started when there were less than 500 confirmed cases worldwide.

The trial saw 199 COVID-19 patients at Jin Yin-Tan Hospital treated either using standard of care or being given lopinavir-ritonavir. The results were published recently and showed enough promise that further, larger trials of the lopinavir-ritonavir treatment have now been established.

Specifically, the trial showed that patients who were randomly chosen to receive lopinavir-ritonavir appeared to improve faster. Meanwhile, among those patients who actually received lopinavir-ritonavir, the time to clinical improvement was significantly shorter than in patients receiving standard of care alone. At the same time acceptable safety levels were observed.

Professor Jaki said: "The results were quite encouraging, which has led to further studies taking place and I would expect to see these treatments to be introduced into routine care, in some cases, in the coming weeks."

The findings from this study will also be considered as part of the forthcoming Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial. This will provide a trial platform to evaluate some of the approximately 30 treatments which are currently believed to have potential for treatment of COVID-19. The chief investigator for that trial is Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine at the University of Oxford - who was also part of the initial study in Wuhan.

Professor Jaki said the fact these studies were taking place during a medical emergency had seen a determination to move things forward at pace.

He added: "The astonishing thing about the RECOVERY trial is the speed with which it got off the ground, from the initial agreement being received from the Department of Health and Social Care it was just nine days before the first patient was recruited. That process would usually take between six and nine months.

"We have benefitted by learning from trials in China - keep it simple. RECOVERY uses a very short protocol and attempts to minimise burden on staff in hospitals which are overwhelmed, so we have tried to ensure data collection is simple. It is an important study and one which needs to be done quickly.

"This is one of the largest trials into treatments for COVID-19. There is a second large trial that is currently recruiting in the UK - REMAP-CAP - which is looking at impacts of treatments on severely ill patients, but both teams have worked together to ensure they will be able to learn as much as they can from both trials.

"This is unusual but a lot of the competitive nature of these things isn't there at the moment. We all have the same goal."

The RECOVERY trial has been classed as an Urgent Public Health Research Study. It is one of a round of projects to receive £10.5m as part of the £20m rapid research response funded by UK Research and Innovation, and by the Department of Health and Social Care through the National Institute for Health Research (NIHR).

Chief Medical Officer Professor Chris Whitty and NHS England Medical Director Professor Stephen Powis have written to NHS trusts in England asking them to fully support the new trial.

Professor Jaki is also one of the authors of an opinion piece published in the New England Journal of Medicine last week on an approach to clinical trials around large epidemics.

While the piece was predominantly written months before the coronavirus outbreak, it encourages greater collaboration between scientists and much of the advice is already being reflected in the World Health Organisation's developing strategy.

Professor Jaki added: "This is the culmination of a conversation which started several years ago where the WHO recognised the necessity of pre-planning in the event of a disease outbreak.

"While it may sometimes feel like we are unprepared for incidents like the COVID-19 outbreak there is actually a co-ordinated global effort among scientists, and Lancaster plays its part in that."

BOSTON - (March 31, 2020) - People with type 1 diabetes, particularly those with poor glycemic control, are at markedly increased risk for cardiovascular disease than the general population. Even more puzzling, in individuals with type 1 diabetes, many of the risk factors for cardiovascular disease do not line up with the known risk factors associated with type 2 diabetes.

Dr. Myra Lipes, Investigator in the Section on Immunobiology at Joslin Diabetes Center at Harvard Medical School, has been working for more than a decade to understand exactly what leads to such increase risk of cardiovascular disease in patients with type 1 diabetes and what can be done about it.

"Heart failure in particular has recently been recognized as an important complication of type 1 with national register-based studies showing tenfold increased risk of heart failure in individuals with poor glycemic control," says Dr. Lipes. "In addition, there's a higher case fatality rate in type 1 than type 2 diabetes, which suggests different mechanisms for heart failure might be involved in type 1 diabetes." Given the burden of heart failure in type 1 diabetes, the early identification of patients at particular risk is of importance.

New research from Dr. Lipes's lab at Joslin shows that in people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies against heart muscle proteins was associated with cardiac magnetic resonance (CMR) imaging evidence of increased volume of the left ventricle (the heart's main pumping chamber), increased muscle mass, and reduced pumping function (ejection fraction), features that are associated with higher risk of failure in the general population. This new study was published in Circulation.

Antibodies are normally produced by the immune system and circulate in the blood, playing in important role in the body's defense against infection. In autoimmune-prone people, the body misidentifies its own proteins as threats and attacks. This is what happens in type 1 diabetes--the immune system thinks pancreatic beta cells are invaders and destroys them. In these situations, antibodies are called autoantibodies. So, perhaps it's not too surprising that this complication of type 1 diabetes also involves a faulty immune response against the heart muscle cells.

Previous studies run by Dr. Lipes' group have shown that mouse models of type 1 diabetes developed dilated cardiomyopathy (weakened heart muscle) and early heart failure associated with the presence of autoantibodies directed against heart muscle proteins. Her group has also shown that poor glycemic control in patients with type 1 diabetes - but not in those with type 2 diabetes - was associated with cardiac autoimmunity. An unexpected finding was the similar cardiac autoantibody levels in the patients with type 1 diabetes, who were young adult and without diabetes complications, and a heart failure cohort with Chagas' cardiomyopathy, which is thought to be caused by chronic inflammation of the heart muscle ("myocarditis"), raising the possibility of a subclinical autoimmune-associated myocardial dysfunction in type 1 diabetes " says Dr. Lipes.

In this study, Lipes wanted to determine whether the dilated heart phenotype seen in mouse models and Chagas' patients was also present in people with type 1 diabetes who had these circulating autoantibodies. She and her team used data gathered from a participants involved in the post-Diabetes Control and Complications Trial (DCCT) Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study, and consisted of people who had type 1 diabetes for an average of 28 years. As part of this study, the participants had their heart imaged using CMR, the gold-standard noninvasive imaging technique for assessing heart structure and function.

"In the study, we measured autoantibodies to heart muscle proteins in blood samples taken from the time of CMR imaging in 892 EDIC participants without any known cardiovascular disease," says Lipes. "And then we examined where the presence of cardiac antibodies was associated with CMR evidence of myocardial dysfunction."

They found that although the recent A1c levels were similar in participants with and without cardiac autoantibodies, presence of cardiac autoantibodies identified patients with worse glycemic control in the past, suggesting that cardiac autoantibodies are markers of long-term glycemic exposure. In addition, they found that the CMR scans from people with two or more of these autoantibodies showed dilated hearts. They sorted patients into categories based on numbers of circulating autoantibodies, which indicated that people with more of these specific autoantibodies had more pronounced changes to the heart. These findings were not weakened after adjusting for traditional cardiovascular risk factors, suggesting these changes were primarily due to cardiac autoimmunity.

They knew from previous research that the heart can have structural and functional changes related to the metabolic problems of diabetes itself; however, these relationships were relatively modest. For example, higher A1C levels were associated with slightly smaller left ventricle volumes that were not clinically significant. But this study suggests that higher A1C levels can trigger an additional autoimmune response that damages the heart in a different and more pronounced way that leads to enlargement and worse function, features that are known to be associated with a high risk of heart failure.

"This points to a novel process involving the heart and linked to poor glycemic control in type 1 diabetes," says Lipes.

Because cardiac autoantibodies can be detected in simple blood test, this research opens a new avenue for detecting the potential for heart failure in patients with type 1 diabetes.

"Given the high burden of heart failure in type 1 diabetes, cardiac antibodies may enable the early identification of people at higher risk of developing heart failure," says Lipes. "And, of course, understanding the underlying cause of heart failure is important since it could lead to targeted therapeutic approaches to improve outcomes in these patients."

Radiolabeled molecules, so-called radiotracers, help nuclear physicians to detect and precisely target tumors, which are often developing due to pathological changes in metabolic processes. Using positron emission tomography, a team of scientists at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) has now developed the first radiotracer labelled with the fluorine isotope 18F, which can visualize special transport proteins often found in the cell membranes of cancer cells. The researchers opted for an unusual radiochemical synthesis approach, as they describe in the journal Scientific Reports (DOI: 10.1038/s41598-019-55354-w).

During metabolism, malignant tumors generate increased amounts of a certain type of transport protein, which, for example, transports the intermediate metabolic product, lactate, into certain tumor cells while simultaneously exporting it away from others - a strategy to prevent apoptosis, a form of programmed cell death that would kill the tumor in a healthy metabolism.

"This correlation has been observed in a variety of tumor types. For this reason, so-called monocarboxylate transporters are considered as key proteins for treating a broad spectrum of different kinds of cancer. Manipulating them can lead to a successful therapy," explains Prof. Peter Brust. He is the head of the Department of Neuroradiopharmaceuticals at the HZDR research site in Leipzig and works on current radiopharmaceutical topics with a focus on brain research. "This includes the synthetic development of modern radiotracers, which play a special role in battling cancer and, in particular, aggressive brain tumors," says Peter Brust, outlining his team's mission.

In molecular-biological and preclinical studies, scientists had already tried to block the activity of monocarboxylate transporters (MCT) by using certain small organic molecules with a pronounced inhibitory effect (for example, α-CHC). Initial results showed that interrupting lactate flow can be a highly effective therapeutic strategy to stunt the growth of malignant tumors.

Radiopharmaceuticals for non-invasive imaging

In addition to its therapeutic interest, the metabolic function of MCT also opens up new diagnostic possibilities: They can be used as valuable biomarkers in many types of cancer, for example by using positron emission tomography (PET). This method uses radionuclides emitting positively charged elementary particles, called positrons. The patient is first given a radiopharmaceutical, a molecule coupled with a radioactive atom such as 18F, which emits positrons. As a positron interacts with an electron in the body, radiation is emitted in diametrically opposed directions in the form of two high-energy photons, which are recorded by detectors arranged in a ring around the patient. This image of the metabolic processes allows physicians to draw conclusions about the spatial distribution of the radiopharmaceutical inside the body, and thus, about any pathological changes.

Objective: Rapid, automated radiopharmaceutical synthesis for everyday clinical use

Despite their potential as therapeutic target structures in the fight against cancer, hardly any radiolabeled MCT inhibitors have recently been studied to gauge their suitability in diagnostic imaging procedures such as PET. "We have now developed a structural analog of the known MCT inhibitor α-CHC and successfully coupled it with the PET radionuclide 18F in a complex procedure. Its relatively short half-life of 110 minutes ensures that the patient can tolerate the radiation exposure," says Dr. Masoud Sadeghzadeh, who coordinated the experiments, describing the approach used by the Leipzig chemists.

After conducting the first promising preclinical studies of their new compound [18F]FACH, the scientists revised their synthetic pathway. "The challenge is to produce the radiotracer fast enough so we can harness the radiating properties of 18F in practical applications," radiochemist Dr. Barbara Wenzel explains. The timespan during which the radiotracer is usable is determined by the half-life of the radionuclide. While the chemists initially needed 160 minutes to manually produce the new radiotracer, they were now able to reduce the synthesis time by half by modifying their approach..

"The key feature of our synthesis is that it does not require the addition of a protective group. This now obsolete intermediate step used to be necessary to protect the reactive parts of a molecule from unintended side reactions," Barbara Wenzel adds. The scientists have thus considerably simplified the procedure and adapted it for the transfer to an automated synthesis module - an indispensable prerequisite for the tumor examinations that are now planned as well as for possible future use in nuclear medicine.

It is clear that we must prioritize identifying and alleviating the conditions that made the Covid-19 pandemic possible. Even as it rages, scientists are already asking if it is more than just a virus, but rather a symptom emerging from something much deeper, a nonlinear dynamical system of coupled pathologies underlying a veneer of "progress" in an increasingly fragile, volatile, hyperconnected world.

A new article by Kang Hao Cheong and Michael C. Jones published in BioEssays describes the convergence of four broad, but easily identifiable systemic, pathologically networked conditions, or "four Horsemen", that are hurtling civilization towards potential self-destruction in which a pandemic is only one of many possible triggers. The "four Horsemen" of overpopulation, globalization, hyperconnectivity and increasingly limited and centralized supply chains are the broad parameters underlying the probability space of catastrophe.

"The Covid-19 pandemic has exposed critical pathologies lurking within the dynamical global system of commerce, governance, and public health," said Cheong, from the Singapore University of Technology and Design.

From this heuristic framework a pandemic can metastasize into other vital domains, such as economic and geopolitical stability and other 2nd and 3rd order, multiplicative effects that could snowball into unprecedented catastrophe.

"Even if Covid-19 is not the proximal cause of global catastrophe this time, like the rogue iceberg that slashed the Titanic, it is a blow sufficiently unsettling to awaken us to the fact that we are sailing into a dangerous sea that is increasingly crowded with icebergs," said Jones, a co-author of the article.

In this increasingly complex and chaotic landscape, manoeuvres such as colossal financial bailouts to avoid ruin by the Covid-19 iceberg can turn the ship straight into a bigger "iceberg", or, more likely, into a chain of collisions to the point that catastrophic failure is virtually inevitable. From the standpoint of decision making, as long as these conditions are not resolved, catastrophe should be considered an inevitable endpoint from the nonlinear dynamics.

"A proper understanding of this explosive risk landscape points towards a solution: a massive change of global course based on the precautionary principle and informed by biological principals," observed Cheong.

"Biological theory and complexity science will play a major role in guiding the paradigmatic transformations required to defuse the time bomb. We will have to construct sustainable social institutions and behaviors that imitate life, rather than systems that defy the principles of the living state, in which living things both anticipate and avoid ruin to achieve persistence," said Jones.

Hospitals can prepare for a surge of patients critically ill with COVID-19, but it will require hospital leaders, practitioners and regional officials to adopt drastic measures that challenge the standard way of providing care, according to a new RAND Corporation report.

The analysis summarizes a range of evidence-based and promising strategies for creating critical care capacity in the nation's hospitals. It includes a simple-to-use online tool that allows decision-makers at all levels -- hospitals, health care systems, states, regions -- to estimate current critical care capacity and rapidly explore strategies for increasing it.

"Because the crisis falls upon a system that already is stretched thin, creating the critical care capacity needed for the surge in COVID-19 patients will require creative thinking about the allocation and use of space, staff and the stuff needed to provide critical care," said Dr. Mahshid Abir, co-author of the report and a senior physician researcher at RAND, a nonprofit research organization. She also is an emergency medicine physician at the University of Michigan and director of the university's Acute Care Research Unit.

The RAND report is based upon a review of research about experiences during past outbreaks (including SARS, MERS and others), a survey of front-line clinicians conducted in collaboration with the American College of Emergency Physicians, and two roundtables conducted by conference call with leading emergency and critical care physicians and public health and preparedness experts from around the country.

The research identified two tiers of activities that hospitals can take to expand critical care capacity.

The first tier includes strategies to expand critical care capacity without significantly impacting the ability to provide other medical care. Those approaches include things such as acquiring additional ventilators from stockpiles and converting some operating rooms to critical care units.

The second tier focuses on crisis capacity strategies that are likely to significantly impact routine care delivery and operations. This might include turning regular hospital beds into critical care beds and re-opening shuttered hospitals. It also includes items such as changing staffing and supervisory ratios, altering standards of care.

To illustrate the possible impact of the strategies on capacity, researchers used publicly available data on the 10 Federal Emergency Management Agency Regions to estimate the number of patients that could be accommodated, given the number of available critical care doctors and nurses, respiratory therapists, ventilators, and beds.

The analysis found the number of ventilators is the most common limiting factor, followed by the number of critical care doctors. The number of nurses, respiratory therapists, or beds were not the limiting factor in any FEMA region.

As expected, the capability to move to higher tiers increases capacity. But the degree of increase in critical care surge depends on both the amount of resources available and the specific combinations. In most situations, the Tier 2 options produce considerably more capacity than Tier 1 options, but in some cases, there is little additional gain.

In the survey of 343 physicians conducted nationally on March 13, the most-cited concerns were shortages in diagnostic kits, a shortage of negative pressure room capacity, and a shortage of N95 masks.

Roundtable participants emphasized the need for real-time information sharing to increase situational awareness of critical care surge capacity among hospitals and across regions.

"When Italy began to appreciate the community spread of COVID-19, it began using an ICU network to increase capacity to care for and to distribute infected patients and non-COVID-19 patients with critical care needs," said Christopher Nelson, co-author of the study and a senior political scientist at RAND. "Regionalization of critical care should be considered as the United States prepares for a surge in critical care needs with COVID-19."

This release has been removed upon further editorial review.

Experts writing in the Journal of Parkinson's Disease discuss potentially grave consequences for Parkinson's disease patients related to social distancing, but also opportunities like new avenues for research and initiatives that may offer positive help and support

Amsterdam, April 3, 2020 - While much attention has focused on the potential for severe respiratory complications and unfavorable outcomes from the COVID-19 pandemic among patients with Parkinson's disease (PD), the impact extends beyond these threats. Social distancing requires flexible adaptation to new circumstances, resilience, and a reduction in physical activities, which may be more difficult for patients with PD.

Writing in the Journal of Parkinson's Disease, Rick C. Helmich, MD, PhD, and Bastiaan R. Bloem, MD, PhD, both of the Radboud University Medical Centre; Donders Institute for Brain, Cognition and Behavior; Department of Neurology; Centre of Expertise for Parkinson & Movement Disorders; Nijmegen, The Netherlands, say, "The pathophysiology of PD puts patients at an increased risk of chronic stress, and a further worsening of this may well be one of the 'hidden sorrows' of the COVID-19 pandemic. Increased psychological stress can worsen motor symptoms, while reducing the efficacy of dopaminergic medication." They also note that there is some evidence that stress can trigger latent PD.

Resilience, or the ability to maintain or quickly recover mental health during and after times of adversity, can protect against the detrimental effects of stress. Dr. Helmich and Dr. Bloem note that the current crisis offers opportunities to see who copes best under the current circumstances, in order to understand the factors that contribute to resilience in PD patients. Mindfulness-based interventions can reduce stress, and they see opportunities for web-based solutions to help reduce anxiety and depression, and also reduce social isolation.

Another hidden consequence of the pandemic is a marked reduction in physical activities. Recent evidence has shown that physical exercise may reduce symptom progression in PD. Loss of aerobic exercise may lead to a worsening of motor symptoms in PD and may contribute further to psychological stress. "A hopeful consequence of the current crisis has been the emergence of web-based exercise initiatives such as online singing, exercise, or dance classes for PD patients," note the authors. "Self-management strategies that reduce stress, increase coping, or increase physical exercise will play an increasing role in the treatment of PD."

The crisis offers emerging opportunities for PD research, as well. The authors observe that the COVID-19 pandemic is an external stressor that is aligned in time for large groups of people. This provides a unique opportunity for researchers to test how the pandemic influences the course of PD in existing groups of patients enrolled in research studies. It also allows researchers to study what factors increase resilience in PD. "Deleterious as the current crisis may be, it will hopefully also bring about some long-term positive outcomes for the many people living with PD worldwide," observe Dr. Helmich and Dr. Bloem.

PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

Deaths of children and adolescents in China due to infectious diseases were becoming rare prior to the covid-19 pandemic, according to a new study.

Quarantinable conditions with high death rates such as cholera and plague had effectively disappeared and many traditional and vaccine-preventable infectious diseases of childhood including diarrhoea, measles and rubella became uncommon.

The research, led by the Murdoch Children's Research Institute (MCRI) and Peking University and published in the British Medical Journal, found the leading causes of death from infectious diseases in China had shifted markedly over a 10 year period from rabies and tuberculosis to HIV/AIDS.

But overall deaths from infectious diseases decreased steadily between 2008-2018 from 0.21 per 100 000 population in 2008 to 0.07 per 100 000 in 2017.

MCRI Professor George Patton said until now no study had reported on recent trends in infectious diseases among children and adolescents in China.

The new research analysed national surveillance data across 31 mainland Chinese provinces. It involved 5 million students aged six to 22 years, and involved 44 notifiable infectious diseases.

Study author Yanhui Dong, from Peking University, said China had made 'remarkable progress' in infectious disease control in this age group.

But Dr Dong said while animal-to-human infections like bird flu remained low, the potential for major outbreaks like SARS-CoV-2 remained a very real possibility.

After the SARS outbreak in 2003, China made substantial investments in laboratory testing, surveillance system enhancement, national intervention programs for specific diseases, and collaboration with international partners.

Professor Patton said despite the progress, China faced new challenges in responding to seasonal and unpredictable new infectious diseases in children and adolescents.

Comprehensive national surveillance systems and rapid proactive government responses would be an integral part of future infectious disease control in China and around the world, he said.

"China will need to continue its successful efforts against older infectious diseases of children and adolescents, including measles, tuberculosis, rabies, and scarlet fever and now scale-up vaccination for mumps, seasonal influenza, and hepatitis B," Professor Patton said.

"Along with the rest of the world, China will also need greater vigilance around the highly transmissible seasonal and unpredictable diseases that we have seen in the past two decades including SARS, MERS, novel influenzas, Zika, Ebola and now the new SARS-CoV-2 virus."

Despite expanding the national childhood immunisation program in 2008, the most common infections in early childhood in China were still vaccine preventable diseases and gastrointestinal and enterovirus diseases, such as hand, foot and mouth disease.

Sexually transmitted diseases and bloodborne infections largely affected older adolescents.

Dr Dong said the significant increase of HIV/AIDs and STI's among 15-24 year olds seemed related to high risk sexual behaviours and poor awareness of infection risks.

"There is a pressing need for more school and university-based sex education programs as well as peer education, and access to rapid testing for sexually transmitted infections," Dr Dong said.

Dr Dong said the data especially highlighted the need for prevention programs to pivot towards a different set of risks, which would also require different interventions.

Researchers from the Chinese Centre for Disease Control and Prevention, the University of Melbourne and The Royal Children's Hospital also contributed to the study.

Key findings for the six to 22 year age group in China included:

Deaths from infectious diseases has decreased between 2008-2018 from 0.21 per 100 000 population in 2008 to 0.07 per 100 000 in 2017

Quarantinable conditions with high death rates have effectively disappeared

Zoonotic infections like bird flu remained low but there is potential for major outbreaks

Notifiable infectious diseases decreased from 280 per 100 000 in 2008 to 162 per 100 000 in 2015, but rose again to 242 per 100 000 in 2017, largely related to mumps and seasonal influenza

Most vaccine preventable diseases were at low levels, but seasonal variation in mumps, rubella, measles, and influenza suggested these diseases should remain a priority for public policy

Vectorborne diseases, such as those transmitted by mosquitoes and fleas, have declined

Gastrointestinal and enterovirus diseases remained constant, but typhoid, paratyphoid, and dysentery continued to decline

Tuberculosis remained the most common bacterial infection, although cases of scarlet fever doubled between 2008 and 2017

Sexually transmitted diseases and bloodborne infections increased significantly. By the end of 2018, 149 000 people with newly diagnosed HIV/AIDS had been reported, 95 per cent of which were sexually transmitted. Of these, 16 000 new HIV/AIDS cases were reported among 15-24 year olds

Children and adolescents in western China continued to carry a disproportionate burden from infectious diseases

Nagano prefecture is home to a group of people effected with a rare genetic neurodegenerative disorder called familial amyloid polyneuropathies (FAP). This disease impacts the gene encoding protein transthyretin (TTR) which is produced in the liver and also eyes. Liver transplants are often a treatment for this disease, but severe eyesight problems such as cloudiness and glaucoma remains, despite such procedures. This research is a retrospective observational study of what ophthalmologists have experienced in their practice over the years.

A group of doctors at Shinshu University Hospital decided to put together this study with the hope that sharing information with other researchers and doctors around the world might help further and bolster understanding and treatment for this eye disease, TTR-related FAP, which is referred to as hereditary ATTR amyloidosis, an autosomal dominant disorder.

The team led by Shinji Kakihara strived to articulate how doctors have cared for patients who have this disease and share issues that need addressing as well as positive outcomes from their care, on account that many ophthalmologists remain unaware of TTR-related FAP.

Patients are usually diagnosed with hereditary transthyretin amyloidosis by age 50 and have an overall survival rate of less than 10 years. Through accurate diagnosis by the Third Department of Internal Medicine (Neurology), patients were referred to the ophthalmology medical team of Shinshu University. Doctor Teruyoshi Miyahara examined many of the patients over the years.

Small gauge vitrectomy, or surgery on the eyes improved eyesight which was maintained until the last visit with the ophthalmologist when intraocular pressure control was adequate. However, subsequent glaucoma surgeries were needed if the intraocular pressure was not controlled, because pressure rapidly increases after vitrectomy and advanced the progression of glaucoma.

This is a very rare disease, but there are patients around the world who suffer from hereditary transthyretin amyloidosis. Doctors at Shinshu University are hopeful that their experience can be utilized to help protect the eyesight of people around the world.

They hope to continue research to see how they can further improve the eyes of people with familial amyloid polyneuropathy. This research is about a very rare disease, but many people suffer from glaucoma. The doctors hope to employ their understanding by continuing research of FAP as well as glaucoma.

Researchers from the Center for Precision Disease Modeling at the University of Maryland School of Medicine (UMSOM) have uncovered a mechanism that appears to explain how certain genetic mutations give rise to a rare genetic kidney disorder called nephrotic syndrome. Using a drosophila (fruit fly) model, they found mutations in genes that code for certain proteins lead to a disruption of the recycling of the cell membrane. This disruption leads to an abnormal kidney cell structure and function, according to the study published this week in the Journal of the American Society of Nephrology.

Disruption of kidney cell function leads to nephrotic syndrome, a kidney disease that causes an abnormal amount of protein leaking into the urine due to a problem with the kidney's filters. It occurs in about 7 in 100,000 Americans, and though rare, it is considered one of the most common kidney diseases in children. Nephrotic syndrome caused by genetic mutations often does not respond to the standard steroid treatment, so treatment depends on the identification of the genetic mutation that causes the disease, followed by targeted therapeutic development based on the disease mechanism. There are, however, no known treatments for the condition when it is caused by mutations in the genes examined in this study.

"Researchers have recently identified a mutation in one of the genes that codes for these proteins, called the exocyst complex, that has been linked to kidney disease," says Zhe Han, Ph.D., Associate Professor at the Department of Medicine and Director of the Center for Precision Disease Modeling at UMSOM. "However, the underlying mechanism by which the exocyst complex contributes to kidney disease had long been a mystery."

Dr. Han's team used Drosophila as a model to better understand the mechanism by which these gene mutations potentially give rise to kidney disease. Drosophila have specialized filtration cells (nephrocytes) that closely resemble human podocytes, a type of kidney cell associated with nephrotic syndrome, both in structure and function. Using the power of fly genetics, the research team carried out a genetic screen with Drosophila and identified each of the eight exocyst genes that are required for nephrocytes to function properly.

Silencing the Drosophila exocyst genes in nephrocytes led to a disruption of a structure essential for filtering called the nephrocyte slit diaphragm. The researchers then used a transmission electron microscope to take a closer look at the ultrastructural changes, which revealed the appearance of unique electron-dense tubular structures which they named "exocyst rods".

"Therefore, the formation of the exocyst rods can be used as a new biomarker for diseases caused by genetic mutations in exocyst genes," Dr. Han said.

The finding, if replicated, also has important clinical implications for patients who are screened for genetic kidney diseases. "Our study suggests that mutations in all eight exocyst genes could lead to nephrotic syndrome and thus should be included in the sequencing panel for genetic kidney diseases," Dr. Han said.

Dr. Han and his team are currently using their Drosophila model to gain additional insight into the mechanisms regulating slit diaphragm proteins and how their disruption might contribute to the podocyte pathogenesis seen in kidney disease patients.

"This is an important finding that demonstrates the important mission of the Center for Precision Disease Modeling at the University of Maryland School of Medicine," said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. "Further studies to understand this molecular mechanism could lead to a new targeted therapeutic approach that could eventually benefit patients with this devastating kidney disease."

Using a modified natural substance along with current approaches could improve colon cancer treatment, according to findings by University of California, Irvine biologists. The discovery comes from their research into the role of an amino acid in tumor development and a potential method for reversing the process. Their paper appears in Nature Cancer. The disease is the second-leading cause of cancer-related deaths in the United States.

Eighty-percent of colon cancers stem from a genetic mutation of the protein adenomatous polyposis coli, or APC. While the majority of people with that mutation will develop polyps, only some of the polyps will become cancerous, a phenomenon that is not fully understood. The research team decided to investigate non-genetic factors that could propel the disease, focusing their inquiry on the role of the amino acid glutamine.

"Cancer cells consume a great amount of glutamine to proliferate," said Molecular Biology and Biochemistry Associate Professor Mei Kong. "But we found that depriving them of glutamine doesn't kill all the tumor cells. Some tumor cells are able to adapt and in fact, when their glutamine supply runs low, they turn into a more invasive form of cancer."

The researchers found that a drop in cellular levels of the metabolite alpha-ketoglutarate after glutamine starvation accompanied the transition from benign to cancerous cells. This finding led them to conduct further investigation into the metabolite's role. When they provided a modified version of alpha-ketoglutarate to animal models with APC mutations, the results were significant. Just 23% of those given the modified metabolite developed rectal bleeding, an indication of intestinal tumors, compared to 90% of the animal models who did not receive it. It also curbed tumor growth and protected against disease-associated conditions such as weight loss.

"Supplementation of the modified alpha-ketoglutarate inhibits a key cancer-development signaling pathway in colon cancer cells, turning them into more normal cells," said researcher Thai Q. Tran, the paper's first author. "What's also notable is that we administered it by mixing it into drinking water, so it was easy to take and it did not affect overall health."

The research team would like to investigate further modification of the metabolite to specifically target colon cancer cells.

"We believe this new knowledge shows great potential for using less-toxic and natural approaches in combination with current therapies to more successfully treat colon cancer while better protecting patients' overall wellbeing," said Professor Kong.

A larger thigh circumference may be associated with lower blood pressure and a reduced risk of heart disease in people with obesity, according to a study published in Endocrine Connections. In overweight and obese Chinese men and women, larger thigh circumferences were associated with lower blood pressure. These findings suggest that carrying more weight on the thighs may be a marker of better heart health in Chinese obese and overweight people, who are at a greater risk of heart disease. Thigh circumference may be useful for targeting obese and overweight people for earlier detection high blood pressure.

High blood pressure is a major public health problem affecting more than 1 billion people worldwide and is the leading cause of mortality and disability globally. A number of factors can increase risk of high blood pressure, such as being overweight, lack of exercise, smoking, or a high amount of salt in the diet. Elevated blood pressure causes excess strain on the heart and arteries and can lead to build-up of fat in blood vessels, limiting blood flow. This increases the risk of serious health conditions such as heart disease and stroke.

Many people are unaware they have high blood pressure as it rarely has noticeable symptoms. Therefore, identifying high risk individuals early and employing intervention strategies such as monitoring diet or increasing exercise may help prevent further damage to blood vessels and the heart.

Circumference measurements are easy, low cost and previously effective at evaluating risk of certain diseases - a large waist circumference is well known to be associated with elevated blood pressure and a small thigh circumference is associated with diabetes. However, there are currently no studies that examine the potential of thigh circumference as an indicator of high blood pressure in people with obesity.

Dr Zhen Yang from Shanghai Jiao Tong University School of Medicine investigated the association between thigh circumference and blood pressure in a population of 9,250 Chinese men and women aged 40 or older, of which 5,348 were overweight and obese, and 4,172 were normal weight.

A significant link between larger thigh circumference (more than 55cm in men and 54cm in women) and lower prevalence of high blood pressure was observed consistently in both men and women, independently of age, body mass index, and waist circumference. Whereas those with a small thigh circumference (less than 50cm for women and 51cm for men) were more likely to have elevated blood pressure.

"In contrast to stomach fat, leg fat may be beneficial for metabolism. The most likely cause of this association is that there is more thigh muscle and/or fat deposited under the skin which secretes various beneficial substances that help keep blood pressure in a relatively stable range." Dr Yang explains.

These findings suggest that thigh circumference could potentially be used as a convenient and inexpensive indicator for earlier detection and prevention of high blood pressure and other related complications, such as heart disease, in obese or overweight people. However, due to large differences in thigh circumferences among different races and different physical activity groups, the thigh circumference sizes in this study may not be a reference for other populations.

Dr Yang now plans to further investigate this association by measuring body composition including thigh fat mass, thigh muscle mass, thigh bone mass and thigh proteins. Different proportions of these components may provide clues to the association between thigh circumference and blood pressure and may help us develop future treatments.