Culture

Hydroxylated polychlorinated biphenyls (OH-PCBs) are metabolites of PCBs and known endocrine disruptors in humans. Of particular concern regarding this kind of effect has been the disruption of the thyroid hormone homeostasis by OH-PCBs. Some OH-PCB congeners are involved in disrupting TH transport by competitive binding to the thyroid hormone transport protein, transthyretin (TTR) in mammalian blood. Prenatal OH-PCBs exposure may disrupt fetal brain development during the critical period of thyroid hormone action. Congenital hypothyroidism causes cretinism and mental retardation, and an insufficient thyroid hormone signaling has been suggested as one of the causes of attention deficit/hyper activity disorder (ADHD). However, there have been limited studies on the OH-PCBs transfer to the fetal brain, particularly in primates.

In this study, we selected the Japanese macaque (Macaca fuscata) as a model animal for the fetal transfer of OH-PCBs in humans, and revealed OH-PCB concentrations and their relationships in maternal and fetal blood, liver, and brain. L-thyroxine (T4)-like OH-PCBs, including 4OH-CB187 as a major congener in humans, were found in high proportions in the blood, liver, brain, and placenta of pregnant Japanese macaques. OH-PCBs were detected in the fetal brain (7.2 ~ 32 pg/g wet wt.), indicating their transfer to the brain in early pregnancy. 4OH-CB187 and 4OH-CB202 of OH-PCB congeners were the major congeners found in the fetal brain, indicating that these T4-like OH-PCBs are transported from maternal blood to the fetal brain via the placenta. These results are important as a potential model for further assessing and understanding of the ability of OH-PCBs to alter neurodevelopment in the human fetus.

In this study, OH-PCBs concentrations in the fetal brains of the Japanese macaques were comparable to the levels that suppressed the T3-induced transcriptional activation of the thyroid hormone receptor and caused neurodevelopmental abnormalities in cerebellar Purkinje cells of mice in a previous study. The brain of the human fetus may be exposed to higher PCB contamination levels than the Japanese macaque fetus; OH-PCB concentrations may thus exceed the levels that induce adverse effects on neurodevelopment. Considering the chronic exposure to PCBs in humans, further studies on the effects of their long-term exposure on fetal brain function are needed.

Colorectal cancer is the third most common cause of cancer deaths in the United States and advanced colorectal polyps are a major risk factor. These high-risk patients have a three-fold higher risk of developing colorectal cancer and therefor a three-year follow up interval of colonoscopy is generally recommended. Many clinicians rely on self-reports from their high-risk patients about their need and proper interval for repeat surveillance colonoscopy.

In a study published in the Journal of Gastroenterology and Digestive Systems, researchers from Florida Atlantic University's Schmidt College of Medicine analyzed data over a period of four years from 2013 to 2017 to explore the knowledge of these high-risk patients. They analyzed data from structured interviews on 84 subjects between ages 40 to 91 years old with biopsy proven advanced colorectal polyps.

Results showed that 28.6 percent were unaware of either the need for a repeat colonoscopy or the proper surveillance interval. Of these, 16.6 percent were unaware of the proper three-year interval to obtain a follow-up surveillance colonoscopy. In addition, 12 percent were not even aware that they required a follow-up surveillance colonoscopy.

Screening modalities for colorectal cancer include fecal immune testing, multi-targeted stool DNA testing, flexible sigmoidoscopy and colonoscopy.

"Our data demonstrate a lack of knowledge of patients with biopsy proven advanced colorectal polyps about their need for repeat colonoscopy as well as the proper surveillance interval," said Lawrence Fiedler, M.D., co-author, a gastroenterologist and an affiliate associate professor in FAU's Schmidt College of Medicine. "For patients with biopsy proven advanced colorectal polyps, the interval for colonoscopy is about three years. Our data raise a challenge for us to rely on more objective data than self-reports. Clinicians should have the ability and willingness to share their objective findings with all clinical colleagues involved in the care of the patient. These efforts should also include younger patients such as Chadwick Boseman who recently died of colon cancer at age 43."

The incidence of colorectal cancer is increasing in younger people. According to the American Cancer Society, from 2007 to 2016, incidence rates of colorectal cancer in people 55 years or older dropped by 3.6 percent each year, but increased by 2 percent each year in those younger than 55.

"Data from our study pose clinical and public health challenges to reduce the rates of recurrences of colorectal polyps as well as subsequent risks of colorectal cancer in these high-risk patients," said Charles H. Hennekens, M.D., Dr.P.H., senior author, first Sir Richard Doll Professor and senior academic advisor in FAU's Schmidt College of Medicine. "More than 90 percent of patients diagnosed with colorectal cancer are 50 years or older. The major risk factors for colorectal cancer are similar to those for heart attacks and stroke and include overweight and obesity, type 2 diabetes, as well as physical inactivity."

The researchers say that if such strategies were adopted for all patients it would have major clinical and public health implications. Specifically, it also would avoid the overutilization of colonoscopies for lower risk patients and increase both the benefit-to-risk and benefit-to-cost ratio from a public health perspective.

According to the U.S. Centers for Disease Control and Prevention, additional risk factors include inflammatory bowel disease such as Crohn's disease or ulcerative colitis; a personal or family history of colorectal cancer or colorectal polyps; and a genetic syndrome such as familial adenomatous polyposis or hereditary non-polyposis colorectal cancer (Lynch syndrome).

Lugano, Switzerland, 14 September 2020 - Delays and cancellation of cancer treatments and other safety measures undertaken to minimise the risk of exposure to the coronavirus (COVID-19) have generated a huge backlog in oncology care and research. The threat of delayed diagnoses looms while oncology professionals face burnout, according to new studies discussed at the ESMO Virtual Congress 2020.

But is only COVID-19 to blame?

"Whether the risk for dark statistics is real or not will only become evident in the future when more robust results from real-world studies and registries are available," said Dr Stefan Zimmermann, ESMO Press Officer, at the congress opening press conference. "For now, it is legitimate to ask ourselves if there are other factors beyond COVID-19 that currently put strain on oncology as the pandemic has also revealed some weaknesses in how cancer care is resourced and organised," he added.

Prior to the pandemic, Europe's cancer burden was estimated by the ECIS - European Cancer Information System (1) to reach 2.7 million new cases and 1.3 million deaths in 2020. However, the COVID-19 outbreak has placed unprecedented pressures on healthcare systems around the world.

A study (2) to be presented at the ESMO Virtual Congress 2020 highlights the extent to which COVID-19 has challenged the organisation and delivery of cancer care. Responses were obtained from oncology centres in 18 countries. Overall, 60.9% reported that clinical activity was reduced at the peak of the pandemic, while nearly two-thirds (64.2%) cited under-treatment as a major concern and 37% expected to see significant reductions in clinical trials this year.

Study author Dr Guy Jerusalem, Centre Hospitalier Universitaire Sart Tilman, Belgium, said: "COVID-19 has had a major impact on the organisation of patient care, on the wellbeing of caregivers and clinical trial activities. There is a risk that the diagnosis of new cancer cases will be delayed and that more patients will be diagnosed at a later stage of their disease."

The data also revealed that the cancer treatments most likely to have been cancelled or delayed were surgery (in 44.1% of centres), chemotherapy (25.7%) and radiotherapy (13.7%), while an earlier end to palliative care was observed in 32.1% of centres.

The impact of COVID-19 on patient care worldwide is also highlighted in another study (3) which gathered data from 356 cancer centres across 54 countries during April 2020. The vast majority (88%) reported facing challenges in providing care during the pandemic, with 54% and 45% reporting cases of coronavirus among their patients and staff, respectively. And while half (55%) reduced services pre-emptively, others were forced to do so after being overwhelmed by the situation (20%) or following a shortage of personal protective equipment (19%), staff (18%) and medicines (9.8%).

As a result, 46% of centres reported that more than one in 10 patients missed at least one cycle of treatment, with some estimating that up to 80% of patients were exposed to some harm.

To continue providing treatment to patients throughout the pandemic, most centres (83.6%) adapted, by implementing virtual clinics and virtual tumour boards (93%), with more than half of respondents suggesting that both will continue beyond the pandemic (55.5% and 60%, respectively). Centres also performed routine tests in laboratories close to patients' homes (76%) and shipped medication to patients (68%) so that treatment could continue.

Study author Dr Abdul-Rahman Jazieh, King Abdulaziz Medical City in Riyadh, Saudi Arabia, said: "The detrimental impact of COVID-19 on cancer care is widespread, with varying magnitude among centres worldwide. The pandemic has impacted healthcare systems globally, interrupting care and exposing cancer patients to significant risks of being harmed."

"Even before the pandemic, pressure on healthcare professionals and systems was mounting as a result of the growing cancer burden in Europe and globally," said Dr Rosa Giuliani, ESMO Director of Public Policy. "A harmonised EU action that provides comparable cancer burden indicators across European countries is extremely important. In this context, the JRC-IARC scientific collaboration has resulted in the computation of up-to-date figures for 2020 new cancer occurrences and cancer deaths. These numbers help to support the development of national policies, tackling the rising burden of cancer with prevention measures as well as with the provision of the necessary resources."

Cancer patients are not the only ones at risk. The results of two online surveys undertaken by the ESMO Resilience Task Force in May 2020 (4) - the largest ever COVID-19 survey of the oncology workforce - reveals the impact of the pandemic on oncology professionals. The first survey showed that more than one-third (38%) experienced feelings of burnout and 25% were at risk of distress, while two-thirds (66%) said they were unable to perform their duties as well as they could prior to the pandemic.

This survey, involving 1,520 participants from 101 countries, also found that levels of wellbeing and job performance declined as national COVID-19 mortality rates rose. A follow-up online survey undertaken in July-August 2020 showed that while job performance had improved compared to the first study, indicating early signals of taking control of the emergency, both wellbeing and burnout rates had worsened.

The main factors associated with distress and burnout were increased working hours, feeling worried about wellbeing, less resilience and oncologists' concerns about training and career.

"The ESMO Resilience Task Force surveys indicate that COVID-19 is having an impact on wellbeing, burnout and job performance," said Dr Susana Banerjee, ESMO Director of Membership, lead author of the surveys. "As an oncology community, we must work collaboratively, individuals and organisations, to ensure that resources are used in the best way possible to support oncology professionals and make sure that ?distress and burnout do not increase. The ESMO Resilience Task Force will look into developing more specific interventions so that we can further help and support oncology professionals during and beyond the pandemic."

Dr Giuseppe Curigliano, ESMO Guidelines Committee Chair, added: "ESMO has responded quickly to the crisis brought by the pandemic, developing a series of specific recommendations across different diseases, to guide oncologists in providing cancer care under unprecedented circumstances. (5) It is now crucial to avoid delays to any treatment which could impact survival by re-allocating resources to cancer patients and continuing to deliver the best possible treatment."

A drug used to treat cirrhosis of the liver may be an effective treatment for a form of Dementia and motorneuron disease, scientists have discovered.

The research, led by the University of York in collaboration with the University of Sheffield, used brain cells from fruit flies and rats to model the neurodegeneration process which occurs in patients with Frontotemporal Dementia (FTD).

The researchers identified new proteins involved in protecting neurons and discovered that Ursodeoxycholic Acid - an already approved drug, with very low toxicity - increases these proteins and protects neurons from death.

The authors of the study will now embark on further research to discover exactly how the drug works to protect neurons and whether more targeted drugs to treat FTD and a range of other neurodegenerative conditions could be developed.

FTD impacts the frontal and temporal lobes of the brain. Unlike other forms of dementia which primarily affect people over 65, FTD tends to start at a younger age with most cases diagnosed in people aged 45-65.

Senior author of the study, Dr Sean Sweeney, from the Department of Biology at the University of York, said: "We are on the cusp of being able to 'repurpose' a drug used for a liver complaint, that has very little toxicity in humans".

"The mechanism of action for this drug is currently unknown and the work we will now do to increase our understanding of how it works may help us lengthen and improve the lives of patients with FTD and potentially other neurodegenerative conditions too."

Up to 50% of cases of FTD have a genetic history of the disease in the family and previous research has identified nine genes that may have a role in its development.

Lead authors of the study, Dr. Ryan West and Dr. Chris Ugbode, used one of these genes to develop their unique genetic models of the disease in fruit flies and rat neurons. In these models, they found Ursodeoxycholic Acid keeps neurons in better health, but the drug is not a potential cure for the disease.

Dr West from the University of Sheffield, said: "In our lab models the drug was effective for treating Frontotemporal Dementia and motorneuron disease, but it does not rectify the underlying deficits, suggesting that the drug is neuroprotective but not a cure."

Fiona Carragher, Director of Research and Influencing at Alzheimer's Society added: "Currently, there's no way to slow down or cure frontotemporal dementia, one of the most common forms of dementia in people under 65, so we're excited to see an existing drug stopping brain cells from dying. While this is in the early stages, it's a valuable first step on the road to finding a way to improve the lives of people with FTD and help them live longer. We need help to continue funding studies like this, so we're asking the Government to honour their commitment to double dementia research funds - while finding new drugs from scratch costs billions and takes decades, we must make every penny count by grasping opportunities to repurpose drugs already approved for other conditions."

Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition. It is especially important now when multiple vaccines against COVID-19 are being developed. The top immunologists analyse types of immune response to predict what kind of vaccine would be the best.

The COVID-19 pandemic is still ongoing, and it is a major challenge for healthcare professionals worldwide. Currently, there are several strategies of preventing the spread of the disease caused by the SARS-CoV-2 virus, including confinement or quarantine measures, social distancing, use of face masks, and good hygiene -- with frequent hand washing and application of antiseptics. However, it is clear that such restrictions affect our personal and professional lives. This is why vaccines against SARS-CoV-2 are being developed across the globe, as vaccination could help stop the pandemic. But these vaccines can be designed in a number of ways, and immune responses may be different. The recent keynote paper by Sechenov University scientists and their Swiss colleagues analyses which type of immune reaction would be more favourable so the vaccine could be effective. The study has been published in International Archives of Allergy and Immunology.

The vaccine, as expected, should efficiently induce high-affinity neutralising antibodies which would target SARS-CoV-2. At the same time, there are concerns that infection after vaccination might lead to eosinophilic lung disease and eosinophil associated Th2 immunopotentiation. Eosinophils are white blood cells involved in conditions such as bronchial asthma, eosinophilic oesophagitis, and hypereosinophilic syndromes. Currently, despite the limited available data, there is no indication that eosinophils play a protective or pathogenic role in COVID-19 infection.

However, eosinophils might still get involved when a person is vaccinated. For example, the research on potential vaccines against SARS-CoV-1, a closely related virus which caused an epidemic in 2002-2004, showed that pulmonary eosinophilia was induced in ferrets, monkeys, and mice after viral challenge. This fact suggests that vaccines against SARS-CoV-2 could also cause a similar immunopathology. Another source of complications might be the induced antibodies that promote viral uptake via Fc receptors.

According to the authors of the study, the most advantageous strategy should focus on vaccines that would induce the production of high-affinity virus-neutralising antibodies. These antibodies should block the interaction of SARS-CoV-2 with its cellular receptor -- angiotensin-converting enzyme 2 (ACE2). Successful vaccines are expected to polarise the T-cell response towards type 1 immunity and prevent the stimulation of cytokines which induce T-helper 2 immunity.

'From our experience with the SARS-1 vaccine, we know that mice which received the whole spike protein (responsible for ACE2 binding) exhibited some eosinophilic complications due to the Th-2 polarisation of the immune response', says Alexander Karaulov, Head of the Department of Clinical Immunology and Allergology at Sechenov University and one of the authors of the paper. 'At the same time, if the injected vaccine contained not the whole spike protein, but rather its receptor-binding domain which is directly involved in interactions with ACE2, immune-mediated pathologies (hypereosinophilic syndrome) could be avoided because of the high immunogenicity and high antibody titre. I believe this to be an important aspect, which remains poorly investigated'.

Visuospatial training exercises can train the brain to reduce motion sickness, providing a potential remedy for future passengers riding in autonomous vehicles. Researchers at WMG, University of Warwick reduced motion sickness by over 50% using the training tool and it was found to be effective in both a driving simulator and on-road experimentation.WMG's 3xD simulator at the University of Warwick

Everyone can experience motion sickness, with 1 in 3 of us being highly susceptible to motion sickness. Motion sickness, sometimes referred to as travel sickness usually can occur during travel in cars and boats, but also when using virtual reality headsets or in a simulator.

With the concept of autonomous vehicles coming closer to our roads, the need to reduce motion sickness is more apparent than ever. It is expected that due to potential vehicle designs and people's desire to engage in non-driving related tasks such as reading or watching films, motion sickness will be a significant factor for vehicle occupants.

In fact, if we were able to reduce motion sickness so much that people could read and work in future cars, it's predicted that this productivity boost could be worth as much as US$508billion per year according to Morgan Stanley.

Considering the number of people affected, relatively little research has been done into motion sickness, especially not into motion sickness and autonomous vehicles.

However, in the paper 'A Novel Method for Reducing Motion Sickness Susceptibility through Training Visuospatial Ability - A Two-Part Study', published in the journal Applied Ergonomics, researchers from WMG, University of Warwick have been successful in reducing motion sickness.

In the project, researchers have found by using visuospatial training you can essentially train the brain to reduce motion sickness by over 50%.

Participants in the study went in either the WMG 3xD simulator for a driving simulator trial, or on an on-road trial where they were driven around as passengers, imitating what it would be like to be in an autonomous vehicle.

Baseline motion sickness was first measured during their initial ride, using a verity of pre-validated questionnaires, to report severity of the symptoms. A 'fast motion sickness scale', was also used to capture 'real-time' symptoms as participants were asked to rate their sickness every minute on a scale of 0-20 considering nausea, discomfort, and stomach problems.Example of a visuospatial exercise part of the Vandenberg and Kuse mental rotations test

After their first run, participants completed various pen-and-paper visuospatial training tasks, once per day for 15 minutes per day, for 2 weeks. This included exercises such as a looking at a pattern of boxes that and having to identify which image out of three is the original just rotated, paper folding tasks and understand spatial patterns.

After the training period, participants took part in another motion sickness assessment and it was recorded that motion sickness reduced by 51% in the driving simulator, and 58% in the on-road trial.On-road experimentation

Dr Joseph Smyth, from WMG, University of Warwick comments:

"Being able to reduce an individual's personal susceptibility to motion-sickness using simple 'brain training style' tasks training is a massive step-forward in the development of future transport systems, including autonomous vehicles. Human factors research is all about how we can design products and services that are pleasurable. Motion sickness has, for a long time, been a significant limitation to many peoples transport options and this research has shown a new method for how we can address this.

"I hope that in the future we can optimise the training into a short, highly impactful method. Imagine if when someone is waiting for a test-drive in a new autonomous vehicle they could sit in the showroom and do some 'brain training puzzles' on a tablet before going out in the car, therefore reducing their risk of sickness. It's also very likely this method can be used in other domains such as sea-sickness for navy staff or cruise passengers. We are particularly excited about applying this new finding to Virtual Reality headset use."

Pete Bennett, from Jaguar Land Rover comments:

"Making our future autonomous vehicles as user friendly as possible is key, and motion sickness is something we knew we needed to research as so many people experience it even now as a passenger.

"The research done by WMG has shown that motion sickness can be reduced, and we can incorporate the research into our future vehicle design process."

Have you ever wondered whether the brains of right-handed people work differently from those of left-handers? Is it possible to distinguish between them by observing their brain activity in response to stimuli or tasks? These are important questions from the perspectives of both basic sciences and application-based fields such as brain-computer interfaces, rehabilitation robotics, and augmented reality.

Since the past few years, a team of scientists at Daegu Gyeongbuk Institute of Science and Technology (DGIST), Korea, has been actively conducting fundamental research to answer these questions. Led by Principal Scientist Dr Jinung An, their initial focus was on finding a method to objectively evaluate haptic devices, which provide tactile feedback simulating textures and surfaces, based on user responses at the brain level.

In a previous study, they had found that the brains of right-handers responded differently from those of left-handers when performing complicated manipulation tasks. In short, when a right-hander uses their preferred hand, specific areas within the left-brain hemisphere are activated. In contrast, when they use their left hand, a much larger area spanning both brain hemispheres is used. Surprisingly, this asymmetry was significantly more pronounced in right-handers than in left-handers.

In their latest study published in Scientific Reports, Dr An and his colleagues show that this asymmetry in right-handers was also evident during passive tactile stimulation of the fingers. They used a technique called functional near-infrared spectroscopy to noninvasively monitor changes in the oxygenation of red blood cells in the brain, which reflect its local activation patterns. Excited about the results, Dr An remarks, "We present the possibility of distinguishing left-handed and right-handed people using passive touch alone, which reveals functional cortical differences. Our outcomes can be immediately used to quantitatively evaluate hand preference and may also be useful for brain-computer interfaces that connect tactile displays to brain signals in augmented reality."

These findings are also relevant for developing cognitive enhancement treatments for autism and brain-mimicking artificial intelligence. Additionally, this approach could be a turning point in haptics--the study of sensing through touch. "Although existing haptic research has mainly focused on the peripheral nervous system, I hope that our study will serve as the starting point for a paradigm shift involving central nervous system-oriented research," concludes Dr An.

The outcomes of this study may truly have consequences left and right!

According to existing estimates, migraine is a highly prevalent ailment, with about 15 percent of global population suffering from it at one time or another. In Russia, the ratio is as high as 20 percent. The current diagnostics and treatment methods are strictly clinical, i. e. they are based on a patient's complaints.

This research was conducted by KFU's Neurobiology Lab and Gene and Cell Technologies Lab. The team looked for genetic markers of migraine for about two years. Colleagues from Saint-Petersburg and Kazan State Medical University also contributed.

"Chronic migraine is a much more serious disease than episodic migraine. Migraine is prone to becoming a chronic syndrome, so it's important to detect those who may become afflicted in the risk groups with episodic migraines. Such patients may be assigned prevention medications to avoid chronic migraine. Thanks to this particular research, we found genetic factors protecting from the chronification of migraines," says neurologist, Junior Research Associate Aliya Yakubova.

For the testing, 46 patients with migraine and 50 patients without the disease were selected. They donated blood for DNA sequencing. In the sequencing process, the scientists determined polymorphisms in the pain receptor TRPV1. In this case, the replacement of nucleotide A by nucleotide G leads to the change in amino acids.

At this stage, the pilot studies have been completed. The selection process will continue, and patients with chronic or episodic migraine can partake.

"We will test the results on a larger selection of individuals. If our takeaways stand ground, we'd like to introduce them into clinical practice. If a patient has genotypes AA or AG, which don't prevent migraine chronicity, they can receive long-term prevention therapies. If they have the GG genotype, chronicity is unlikely, and only symptomatic therapy can be prescribed," continues Yakubova.

The work helped find significant differences in polymorphisms in patients with chronic versus episodic migraine. This means that some degree of genetic predisposition exists, and there are risk factors and prevention factors of chronicity for all the three genotypes. The patenting process for the technique is currently underway.

Singapore, 14 September 2020 - Researchers from Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have discovered a new way to manufacture human red blood cells (RBCs) that cuts the culture time by half compared to existing methods and uses novel sorting and purification methods that are faster, more precise and less costly.

Blood transfusions save millions of lives every year, but over half the world's countries do not have sufficient blood supply to meet their needs. The ability to manufacture RBCs on demand, especially the universal donor blood (O+), would significantly benefit those in need of transfusion for conditions like leukemia by circumventing the need for large volume blood draws and difficult cell isolation processes.

Easier and faster manufacturing of RBCs would also have a significant impact on blood banks worldwide and reduce dependence on donor blood which has a higher risk of infection. It is also critical for disease research such as malaria which affects over 220 million people annually, and can even enable new and improved cell therapies.

However, manufacturing RBCs is time-consuming and creates undesirable by-products, with current purification methods being costly and not optimal for large scale therapeutic applications. SMART's researchers have thus designed an optimised intermediary cryogenic storage protocol that reduces the cell culture time to 11 days post-thaw, eliminating the need for continuous 23-day blood manufacturing. This is aided by complementary technologies the team developed for highly efficient, low-cost RBC purification and more targeted sorting.

In a paper titled "Microfluidic label-free bioprocessing of human reticulocytes from erythroid culture" recently published in the prestigious journal Lab on a Chip, the researchers explain the huge technical advancements they have made towards improving RBC manufacturing. The study was carried out by researchers from two of SMART's Interdisciplinary Research Groups (IRGs) - Antimicrobial Resistance (AMR) and Critical Analytics for Manufacturing Personalised-Medicine (CAMP) - co-led by Principal Investigators Jongyoon Han, a Professor at MIT, and Peter Preiser, a Professor at NTU. The team also included AMR and CAMP IRG faculty appointed at the National University of Singapore (NUS) and Nanyang Technological University (NTU).

"Traditional methods for producing human RBCs usually require 23 days for the cells to grow, expand exponentially and finally mature into RBCs," says Dr Kerwin Kwek, lead author of the paper and Senior Postdoctoral Associate at SMART CAMP. "Our optimised protocol stores the cultured cells in liquid nitrogen on what would normally be Day 12 in the typical process, and upon demand thaws the cells and produces the RBCs within 11 days."

The researchers also developed novel purification and sorting methods by modifying existing Dean Flow Fractionation (DFF) and Deterministic Lateral Displacement (DLD); developing a trapezoidal cross-section design and microfluidic chip for DFF sorting, and a unique sorting system achieved with an inverse L-shape pillar structure for DLD sorting.

SMART's new sorting and purification techniques using the modified DFF and DLD methods leverage the RBC's size and deformability for purification instead of spherical size. As most human cells are deformable, this technique can have wide biological and clinical applications such as cancer cell and immune cell sorting and diagnostics.

On testing the purified RBCs, they were found to retain their cellular functionality, as demonstrated by high malaria parasite infectivity which requires highly pure and healthy cells for infection. This confirms SMART's new RBC sorting and purifying technologies are ideal for investigating malaria pathology.

Compared with conventional cell purification by fluorescence-activated cell sorting (FACS), SMART's enhanced DFF and DLD methods offer comparable purity while processing at least twice as many cells per second at less than a third of the cost. In scale-up manufacturing processes, DFF is more optimal for its high volumetric throughput, whereas in cases where cell purity is pivotal, DLD's high precision feature is most advantageous.

"Our novel sorting and purification methods result in significantly faster cell processing time and can be easily integrated into current cell manufacturing processes. The process also does not require a trained technician to perform sample handling procedures and is scalable for industrial production," Dr Kwek continues.

The results of their research would give scientists faster access to final cell products that are fully functional with high purity at a reduced cost of production.

September 14, 2020 - Some critically ill patients with septic shock need medications called vasopressors to correct dangerously low blood pressure. When high doses of vasopressors are needed or blood pressure isn't responding well, the steroid hydrocortisone is often used. In this situation, earlier treatment with hydrocortisone reduces the risk of death and other adverse outcomes, reports a study in SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches, Official Journal of the Shock Society. The journal is published in the Lippincott portfolio by Wolters Kluwer.

For critical care specialists, the study provides new evidence on the optimal timing of steroid treatment for patients with vasopressor-dependent septic shock. "If hydrocortisone is to be initiated in patients with septic shock, it should be initiated within at least the first 24 hour after shock onset, and ideally within the first 12 hours," according to the new research by Gretchen L. Sacha, PharmD, and colleagues of the Cleveland Clinic.

New Evidence on Timing of Hydrocortisone for Septic Shock
The study included 1,470 patients with septic shock treated with hydrocortisone at Cleveland Clinic ICUs between 2011 and 2017. All patients required vasopressors to maintain near-normal blood pressure after fluid resuscitation.

Based on the timing of hydrocortisone therapy, patients were divided into five groups. About 39 percent started hydrocortisone within 0 to 6 hours after shock onset. Other groups started hydrocortisone at 6 to 12 hours (about 16 percent of patients), 12 to 24 hours (18 percent), 24 to 48 hours (13 percent), or after 48 hours (15 percent).

Toward determining the optimal timing of hydrocortisone initiation, time alive and off vasopressors - that is, with blood pressure within the target range - was compared among groups, along with other key outcomes. Patient characteristics varied between groups, including higher sepsis severity scores in patients who started hydrocortisone earlier.

"Despite being more critically ill at baseline, patients who received hydrocortisone earlier had better clinical outcomes when compared to patients who received hydrocortisone later after shock onset," Dr. Sacha and coauthors write. Patients starting steroids earlier not only had more days alive and off vasopressors but also had lower mortality rates. For example, risk of in-hospital death was 48.5 percent for patients initiating hydrocortisone at 0 to 6 hours versus 59.0 percent for those who started treatment after 48 hours.

After adjustment for severity of illness and other factors, earlier hydrocortisone therapy was still associated with increased vasopressor-free days. In this analysis, the odds of death in the ICU were 40 percent lower in patients receiving hydrocortisone within 0 to 6 hours, compared to those who started treatment beyond 48 hours.

Sepsis occurs when the immune system mounts an overwhelming inflammatory response to infection in the blood or elsewhere in the body. Septic shock is present in patients who develop a sharp drop in blood pressure and other metabolic abnormalities, with a risk of progression to organ failure.

Hydrocortisone is recommended for some patients with vasopressor-dependent septic shock, but there is ongoing debate over how and when it should be used. Some smaller studies have suggested hydrocortisone is more likely to be beneficial when started earlier after shock onset.

The new study, in a relatively large sample of patients, highlights the importance of early hydrocortisone therapy. "Timing of hydrocortisone initiation in patients with septic shock appears to be crucial and hydrocortisone should be started within the first 12 h after shock onset," Dr. Sacha and coauthors write.

In contrast, starting hydrocortisone after 24 hours does not appear to have any benefit. The researchers conclude, "Future randomized studies should focus on the timing of hydrocortisone initiation, ensuring initiation within the first 12 hours from shock onset."

Relationship between obstructive sleep apnoea and poorer outcomes from COVID-19 identified in systematic review of studies by University of Warwick

Researchers advise that people with obstructive sleep apnoea should take the necessary precautions to reduce their exposure and follow their treatment plan diligently

1.5 million people in the UK currently diagnosed with the condition, but up to 85% of people could be undiagnosed

Researchers call for better recording and more data on the condition

People who have been diagnosed with obstructive sleep apnoea could be at increased risk of adverse outcomes from COVID-19 according to a new study from the University of Warwick.

The conclusion is drawn from a systematic review of studies that reported outcomes for COVID-19 patients that were also diagnosed with obstructive sleep apnoea. Published in the journal Sleep Medicine Reviews, the review highlights the need to further investigate the impact of the virus on those with the sleep condition and to better identify those currently undiagnosed with it.

Obstructive sleep apnoea is a condition characterised by complete or partial blockage of the airways during sleep when the muscles there become weaker. It is commonly diagnosed in people who snore or appear to stop breathing or make choking sounds during sleep, and those who are obese in particular are more likely to experience it. If you are told that you make strange noises when you sleep or seem to stop breathing during sleep, you should speak to their GP about being referred to a sleep service to be checked for the condition. You can also find more information about the condition here: http://www.sleep-apnoea-trust.org and https://www.hope2sleep.co.uk

Many of the risk factors and comorbidities associated with sleep apnoea, such as diabetes, obesity and hypertension, are similar to those associated with poor COVID-19 outcomes. However, the researchers wanted to investigate whether being diagnosed with obstructive sleep apnoea conferred an additional risk on top of those factors.

The systematic review looked at eighteen studies up to June 2020 with regards to obstructive sleep apnoea and COVID-19, of these eight were mainly related to the risk of death from COVID-19 and ten were related to diagnosis, treatment and management of sleep apnoea. Although few studies of obstructive sleep apnoea in COVID-19 had been performed at the time, there is evidence to suggest that many patients who presented to intensive care had obstructive sleep apnoea and in diabetic patients it may confer an increased risk that is independent of other risk factors. In one large study in patients that had diabetes, who were hospitalised for COVID-19, those being treated for obstructive sleep apnoea were at 2.8 times greater risk of dying on the seventh day after hospital admission.

Researchers believe that in the UK up to 85% of obstructive sleep apnoea disorders are undetected, suggesting that the 1.5 million people in the UK currently diagnosed with the condition may be just the tip of the iceberg. With obesity rates and other related risk factors on the increase, the researchers also believe that rates of obstructive sleep apnoea are also increasing. The review highlights that the pandemic has also had worldwide effects on the ongoing diagnosis, management and treatment of patients with this and other sleep conditions. Moving forward it may be necessary to explore new diagnosis and treatment pathways for these individuals.

Lead author of the study Dr Michelle Miller of Warwick Medical School said: "Without a clear picture of how many people have obstructive sleep apnoea it is difficult to determine exactly how many people with the condition may have experienced worse outcomes due to COVID-19.

"This condition is greatly underdiagnosed, and we don't know whether undiagnosed sleep apnoea confers an even greater risk or not.

"It is likely that COVID-19 increases oxidative stress and inflammation and has effects on the bradykinin pathways, all of which are also affected in obstructive sleep apnoea patients. When you have individuals in which these mechanisms are already affected, it wouldn't be surprising that COVID-19 affects them more strongly."

Treatment for obstructive sleep apnoea with continuous positive airway pressure (CPAP) has been shown to have some beneficial effects on these mechanisms and it is important that treatment is optimised for these individuals. In the UK, the British Sleep Society with the OSA alliance has released guidelines with regards to the use of CPAP during the pandemic.

The researchers feel it is important that those diagnosed with obstructive sleep apnoea are aware of the potential additional risk and are taking appropriate precautions to reduce their exposure to the virus. Further research is required to determine whether these individuals need to be added to the list of vulnerable groups that may need to shield if transmission of virus increases.

Dr Miller adds: "This is a group of patients that should be more aware that obstructive sleep apnoea could be an additional risk if they get COVID-19. Make sure you are compliant with your treatment and take as many precautions as you can to reduce your risk, such as wearing a mask, social distancing and getting tested as soon as you notice any symptoms. Now more than ever is the time to follow your treatment plan as diligently as possible.

"Hospitals and doctors should also be recording whether their patients have obstructive sleep apnoea as a potential risk factor, and it should be included in studies and outcomes data for COVID-19. We need more data to determine whether this is something we should be more concerned about."

More than one quarter of asthma patients have been prescribed potentially dangerous amounts of steroid tablets, with researchers warning this puts them at greater risk of serious side-effects.

Researchers, led by University of Queensland Professor John Upham, analysed data from the Pharmaceutical Benefits Scheme (PBS) to find out how often Australians with asthma were taking repeated courses of steroid tablets.

Professor Upham said the study looked at more than 120,000 cases where asthma patients were given one or more prescriptions for steroid tablets by their doctor between 2014 and 2018.

"Researchers found more than 25 per cent of those patients were more likely to have a chronic condition," Professor Upham said.

"Short courses of steroid tablets can be effective at treating asthma attacks in the short term, but it's becoming clear that repeated use may cause significant long term side-effects like diabetes, osteoporosis and cataracts.

Around 2.5 million Australians have asthma, with the condition affecting more women than men.

Professor Upham said the best way to prevent asthma attacks was by regularly using preventer inhalers.

"Unfortunately, our study found half of asthma patients given repeated scripts for steroid tablets were not using inhalers as often as they should," he said.

"Better approaches are needed to educate and support asthma patients, and encourage them use preventer inhalers regularly.

"This is the best way to avoid or minimise the need for steroid tablets, and the side effects they can produce."

Some microorganisms, the so-called methanotrophs, make a living by oxidizing methane (CH4) to carbon dioxide (CO2). Ammonia (NH3) is structurally very similar to methane, thus methanotrophs also co-metabolize ammonia and produce nitrite. While this process was observed in cell cultures, the underlying biochemical mechanism was not understood. Boran Kartal, head of the Microbial Physiology Group at the Max Planck Institute for Marine Microbiology in Bremen, Germany, and a group of scientists from Radboud University in Nijmegen, The Netherlands, now shed light on an exciting missing link in the process: the production of nitric oxide (NO).

Nitric oxide is a highly reactive and toxic molecule with fascinating and versatile roles in biology and atmospheric chemistry. It is a signaling molecule, the precursor of the potent greenhouse gas nitrous oxide (N2O), depletes the ozone layer in our atmosphere, and a key intermediate in the global nitrogen cycle. It now turns out that NO is also the key for the survival of methanotrophs that face ammonia in the environment - which they do more and more as fertilizer input into nature increases. When methanotrophs co-metabolize ammonia they initially produce hydroxylamine, which inhibits other important metabolic processes, resulting in cell death. Thus, methanotrophs need to get rid of hydroxylamine as fast as possible. "Carrying a hydroxylamine-converting enzyme is a matter of life or death for methane-eating microbes", Kartal says.

For their study, Kartal and his colleagues used a methanotrophic bacterium named Methylacidiphilum fumariolicum, which originates from a volcanic mud pot, characterized by high temperatures and low pH, in the vicinity of Mount Vesuvius in Italy. "From this microbe, we purified a hydroxylamine oxidoreductase (mHAO) enzyme," reports Kartal. "Previously it was believed that mHAO enzyme would oxidize hydroxylamine to nitrite in methanotrophs. We now showed that it actually rapidly produces NO." The mHAO enzyme is very similar to the one used by "actual" ammonia oxidizers, which is quite astonishing, as Kartal explains: "It is now clear that enzymatically there is not much difference between aerobic ammonia- and methane-oxidizing bacteria. Using essentially the same set of enzymes, methanotrophs can act as de facto ammonia oxidizers in the environment. Still, how these microbes oxidize NO further to nitrite remains unknown."

The adaptation of the mHAO enzyme to the hot volcanic mud pots is also intriguing, Kartal believes: "At the amino acid level, the mHAO and its counterpart from ammonia oxidizers are very similar, but the protein we isolated from M. fumariolicum thrives at temperatures up to 80 °C, almost 30 °C above the temperature optimum of their "actual" ammonia-oxidizing relatives. Understanding how so similar enzymes have such different temperature optima and range will be very interesting to investigate."

According to Kartal, production of NO from ammonia has further implications for methane-eating microbes: "Currently there are no known methanotrophs that can make a living out of ammonia oxidation to nitrite via NO, but there could be methanotrophs out there that found a way to connect ammonia conversion to cell growth."

A new study from the Prevention Research Center of the Pacific Institute for Research and Evaluation of DUI arrests in California shows that arrests increase as distance to the southern border decrease, and that this may be due to greater availability of alcohol in the border area.

The article examines trends and population-level correlates of drinking driving arrests from 2005 to 2017 in California. Relying on arrest data from the California Department of Justice, and demographic and community data form the U.S. Census, measures of alcohol outlet density, and distance to the U.S./Mexico border, the authors found that:

Arrest rates among women and men showed an upward trend until 2008 and decreases after that year

DUI arrest rates were greater among Hispanics than Whites for younger age groups: 18-29 and 30-39

DUI arrest rates were positively related to proximity to the California/Mexico border and:

a higher percent of bar/pub outlets;

a higher percent of Hispanic population;

a higher percent of population 18-29, 30-39, and 40-49 years of age;

a higher percent of US-born population;

a higher percent of population with annual income of $100,000 or more;

a higher percent of population 150% below the federal poverty line; and

a higher level of law enforcement activities.

Lead author, Raul Caetano notes that: "These analyses were based on 2.3 million arrest records for 18 years, providing very stable results. Although DUI arrest rates increased as distance to the border decreased, in communities with larger percentages of Hispanics, DUI rates increased as distance to the border increased. This shows that effect of the increased alcohol and drug availability at the border are complex and influenced by community factors".

Scientists have discovered that measuring brainwaves produced during REM sleep can predict whether a patient will respond to treatment from depression. This enables patients to switch to a new treatment rather than continue the ineffective treatment (and the depression) for weeks without knowing the outcome.

As study leader, Dr Thorsten Mikoteit said, "In real terms it means that patients, often in the depths of despair, might not need to wait weeks to see if their therapy is working before modifying their treatment". This work is presented at the ECNP Congress.

Around 7% of adults suffer depression (also known as MDD, Major Depression Disorder) in any one year. It's a huge health burden, costing economies hundreds of billions of Euros/dollars each year. Around 27m European and 17m Americans suffer from MDD every year.

The standard treatment is antidepressants, normally Selective Serotonin Reuptake Inhibitors (SSRI's), such as Prozac and Fluoxetine. However, these can take weeks or months to show an effect, meaning that patients often have to face the depth of their depression for several weeks before even knowing if the treatment they are taking will work. Around 50% of sufferers don't respond to initial antidepressant treatment, which means that after four weeks of ineffective treatment, doctors have to change treatment strategy, and again have to wait for response for another four weeks. Being able to predict the response as early as after one week of treatment would be of huge benefit to depressed patients, and would shorten the treatment response time.

A team led by Dr Thorsten Mikoteit, of the University of Basel, has conducted a randomised controlled trial on 37 patients with Major Depression. All were treated with antidepressants, but 15 were assigned to the control group, while the remaining 22 had their details given to the psychiatrist in charge of treatment. All then had their brainwaves monitored during REM* sleep (technically, this was a measurement of prefrontal theta cordance in REM sleep). The psychiatrists in charge of the treatment group patients were under instructions to interpret the brainwaves to see if the treatment was working, and if not to change the treatment. The overall aim was to see a 50% reduction in symptoms of depression, measured by the standard Hamilton Depression Rating Scale.

Doctors tested patients as early as one week after starting treatment, to see if the brainwaves indicated that the antidepressant treatment was likely to work. Those patients who were unlikely to have successful treatment were immediately switched to a different treatment. After 5 weeks it was found that 87.5% of these patients had an improved response, as opposed to just 20% in the control group.

Thorsten Mikoteit said:

"This is a pilot study, but nevertheless it shows fairly significant improvements. We have been able to show that by predicting the non-response to antidepressants we were able to adapt the treatment strategy more or less immediately: this enables us to significantly shorten the average duration between start of antidepressant treatment and response, which is vital especially for seriously depressed patients.

It needs to be repeated with a larger group of patients to make sure that the results are consistent. Patients need to be in a situation where their REM sleep can be monitored, so this requires more care than just giving the pill and waiting to see what happens. This means that the treatment monitoring will be more expensive, although we anticipate that will be offset by being able to give the right treatment much earlier. We are working on ways of streamlining this.

What it does mean is that we may be able to treat the most at-risk patients, for example those at risk of suicide, much quicker than we can currently do. If this is confirmed to be effective, it will save lives"

Commenting, Professor Catherine Harmer, University of Oxford and ECNP Executive Committee member, said:

"Most of the time, patients need to wait for around 4 weeks before they can tell if they are responding to a particular antidepressant or not. This is a hugely disabling and lengthy process and often a different treatment then needs to be started. The study results presented by Mikoteit are interesting and suggest that it may be possible to tell if a treatment is working much more quickly - even after a week of treatment - by using a physiological measure of response (REM sleeping pattern). If this is replicated in larger, blinded study then it would have enormous implications for the future treatment of individuals with depression".

Professor Harmer was not involved in this work, it is an independent comment.