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System linked to operational hospitals, shorter lockdowns, lives saved

image: From June 16, Austin's Staged Alert System.

Image: 
City of Austin

A staged alert system, designed by scientists and public health officials to guide local policies, helped one city prevent hospital surges and long lockdowns, according to new research published in the journal Nature Communications.

In a new study led by The University of Texas at Austin COVID-19 Modeling Consortium in collaboration with Northwestern University, researchers describe the system that has guided COVID-19 policies in Austin, Texas, for more than a year, helping to safeguard the health care system and avoid costly measures. It tracks the number of new daily COVID-19 hospital admissions and triggers changes in guidance when admissions cross specific threshold values. While using this staged alert system, the Austin metropolitan area has sustained the lowest per capita COVID-19 death rate among all large Texas cities.

"Austin's alert system was optimized to balance the city's public health and socioeconomic goals," said Lauren Ancel Meyers, a professor of integrative biology and director of The University of Texas COVID-19 Modeling Consortium. "For over a year, it has helped our community adapt to rapidly changing risks, protected the integrity of our hospital systems, and limited the economic damage."

Throughout the COVID-19 pandemic, policymakers struggled to combat COVID-19 while minimizing social and economic consequences. Governments worldwide enacted a variety of alert systems that trigger lockdowns when cases or hospitalizations reach critical levels. According to the paper, Austin's system was better at preventing overwhelming hospital surges than the ICU-based triggers used in France and better at avoiding lockdowns than widely cited recommendations from Harvard Global Health.

"Our flexible method can design adaptive policies to combat COVID-19 worldwide and prepare for future pandemic threats," Meyers said. "When we compared Austin's optimized triggers to other similar alert systems, we found that it does a much better job of balancing competing public health and economic goals."

Northwestern University's David Morton designed the study with Meyers and Haoxiang Yang, a postdoctoral research associate at the Center for Nonlinear Studies (CNLS) at Los Alamos National Lab.

"The success of Austin's system stems partly from its reliance on hospital admission data, which provides a more reliable signal of COVID-19 transmission than reported cases, and partly from our rigorous optimization of the alert triggers," Morton said. The researchers derived thresholds that provided a 95% guarantee that hospitals would not be overrun.

The three Austin-area hospital systems, Ascension Seton, St. David's HealthCare, and Baylor Scott & White Health, provided key data that were not available in most other U.S. cities in the early months of the pandemic, including estimates for ICU and hospital capacity and daily reports of new COVID-19 hospital admissions.

"The pandemic motivated a level of cooperation among the various health players across this community in a very special and effective way," said Clay Johnston, dean of Dell Medical School at UT Austin. "Together, we created a system of triggers based on the latest local data, which was central to a coordinated response that helped prevent ICUs from exceeding capacity and ultimately saved lives."

"The staged alert system was developed by working with the hospital systems, and members of the UT COVID-19 Modeling Consortium in Austin," said Dr. Desmar Walkes of the Austin-Travis County Health Authority. "It resulted from a unique partnership between city leaders, the three hospital systems and academics. This is proof that that communicating behavioral change is most effective when it is driven by science and data."

Credit: 
University of Texas at Austin

Study examines symptoms before and after kidney transplantation

Highlights

In a study of patients waiting for a kidney transplant, those who experienced various symptoms had a higher risk of dying while on the waitlist.

Symptoms tended to increase or remain unchanged between transplant evaluation and transplantation; however, at 3 months after transplantation, 9 of 11 symptoms lessened.

Washington, DC (June 18, 2021) -- Investigators have examined how various symptoms experienced by individuals with kidney failure are impacted by kidney transplantation. The findings will appear in an upcoming issue of CJASN.

People with kidney failure must often deal with numerous symptoms, such as fatigue, cramping, muscle soreness, numbness, dizziness, and loss of appetite. Although kidney transplantation is the optimal treatment for restoring kidney function in patients with kidney failure, how it affects these symptoms is unclear.

To investigate, Mara A. McAdams-DeMarco, PhD (Johns Hopkins) and her colleagues analyzed information on 1,298 kidney transplant candidates and 521 kidney transplant recipients. "This is the first study to investigate how symptoms change before and after kidney transplantation," said Dr. McAdams-DeMarco.

Candidates reported being moderately to extremely bothered by fatigue (32%), dry skin (27%), muscle soreness (26%), and itchy skin (25%); 16% reported high and 21% reported very high symptom burden. During a median follow-up of 1.9 years, 12% of patients died on the waitlist, and those with very high symptom burden had a 67% higher risk. By the time patients were to receive transplants, 34% experienced an increased symptom burden while 42% remained unchanged.

Among kidney transplant recipients, patients experienced a lessening of symptoms following transplantation, with an overall 10% improvement in symptoms, followed by little further change from 3 months through 12 months after surgery. There were early (first 3 months) improvements in 9 of 11 symptoms, and itchy skin and fatigue had the greatest improvements.

"Our findings on the post-transplantation change in symptoms can help inform the important discussion surrounding post-transplant care, clarify the timeline for improvement, identify populations who are most likely to benefit, and promote patient-centered care," said Dr. McAdams-DeMarco.

An accompanying Patient Voice describes the perspective and experience of David Rodriguez, who was diagnosed with kidney failure in 2008 at the age of 36 and then received a kidney transplant through a paired-exchange kidney donation.

Credit: 
American Society of Nephrology

Assessing Racial, Ethnic disparities in access to COVID-19 vaccination sites

What The Study Did: Researchers reviewed access to COVID-19 vaccination sites in Brooklyn, the most populated borough in New York, to better understand disparities in vaccination.

Authors: Natasha Williams, Ed.D., M.P.H., of the New York University Grossman School of Medicine in New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.13937)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

How childhood exercise could maintain and promote cognitive function in later life

image: Box plots to show the relationship between childhood exercise and the false alarm rate in the Go/No-go task.

Image: 
Ishihara et al., NeuroImage, 2021

A research group including Professor MATSUDA Tetsuya of Tamagawa University's Brain Science Institute (Machida City, Tokyo; Director: SAKAGAMI Masamichi) and Assistant Professor ISHIHARA Toru from Kobe University's Graduate School of Human Development and Environment has illuminated the changes in the brain's neural network and cortex structure that underlie the positive association between childhood exercise and the maintenance and promotion of cognitive function in later life.

These results were published in the academic journal NeuroImage on May 23, 2021.

Main Points

The researchers showed that people who are physically active during childhood (up to 12 years of age) have higher cognitive functions in later life.

However, they could not find a correlation between cognitive function and post-childhood physical activity.

The positive association between childhood exercise and cognitive function was evident in the modular (*1) segregation of brain networks, strengthened inter-hemispheric connectivity, greater cortical thickness, lower levels of dendritic arborization and decreased density.

During childhood, the formation of the brain's network is susceptible to environmental and experience-related factors. It is thought that exercise during this period optimizes brain network development and is linked to the maintenance and promotion of cognitive function in later life.

Research Background

Research over the previous decade has shown that exercise during childhood affects the development of cognitive functions. Recent findings have indicated that these benefits of childhood exercise extend to the maintenance and promotion of cognitive functions in middle age and later life. However, the changes in brain functionality and structure related to this positive association have yet to be illuminated. This research study investigated the relationship between physical activity in childhood and cognitive function in later life, using MRI (magnetic resonance imaging) to illuminate the structural and functional changes in the brain that are behind this relationship.

Experiment Method

The research group conducted a study on 214 participants ranging in age from 26 to 69 in order to investigate the relationship between childhood exercise and cognitive function, and the underlying functional and structural neural networks and cortical structure. Childhood exercise was assessed via questionnaire. One aspect of cognitive function, response inhibition (the ability to suppress inappropriate behaviors), was measured using a Go/No-go task. The image data from the MRI was analyzed and the following were calculated: structural and functional connectivity (*2), cortical thickness, myelination, the degree of neurite orientation dispersion and density index. The brain was divided into 360 areas in accordance with the Human Connectome Project (*3), and functional and structural parameters were obtained for each area. In the statistical analysis, information obtained through the questionnaire was used as confounders. This included each participant's educational background, parents' educational background, number of siblings and exercise during adulthood.

Experiment Results

Firstly, the researchers analyzed the relationship between whether participants exercised during childhood and Go/No-go task performance (false alarm rate). They found that participants who exercised during childhood (up until age 12) had a lower false alarm rate than those who didn't (Figure 1). Furthermore, this correlation was found regardless of the age of the participant. However, no such relationship was found between task performance and post-childhood exercise.

Next, the research group investigated structural and functional connectivity in the brain relating to Go/No-go task performance in participants who exercised during childhood. From these results, they confirmed that in terms of structural connectivity in the brain, there were positive associations (Figure 2A: connections indicated in red) and negative associations (Figure 2A: connections indicated in blue) between exercise during childhood and the false alarm rate in the Go/No-go task. Large-scale network connectivity was found in over half (73%) of structurally connected areas that were positively associated with the Go/No-go task false alarm rate (Figure 2B, left portion). On the other hand, inter-hemispheric connectivity was found in the majority (88%) of structurally connected areas that were negatively associated with the task's false alarm rate (Figure 2B, right portion). In terms of connections between functional areas, connections showing positive associations (Figure 3A: connections indicated in red) with the Go/No-go task false alarm rate were identified in participants who exercised during childhood but no negatively associated connections were found. Furthermore, large-scale network connectivity was found in the majority (91%) of connected areas that were positively associated with the task's false alarm rate (Figure 3B, left portion).

In those participants who did not exercise during childhood, there was no structural or functional connectivity identified in relation to the false alarm rate in the Go/No-go task. Lastly, the researchers investigated cortical structure parameters in relation to the Go/No-go false alarm rate for participants who exercised as children. They found that task performance was negatively associated with cortical density, and positively associated with the degree of neurite orientation dispersion and density.

The above results demonstrate that modular segregation and strengthened inter-hemispheric connections in the brain networks of people who exercised during childhood reduced the number of mistakes that they made in the Go/No-go task.

Credit: 
Kobe University

AI app could help diagnose HIV more accurately

image: Through this work, they built a library of images of HIV tests taken in various conditions - which was used as training data for the UCL team's machine-learning algorithm.

Image: 
Africa Health Research Institute

Pioneering technology developed by UCL (University College London) and Africa Health Research Institute (AHRI) researchers could transform the ability to accurately interpret HIV test results, particularly in low- and middle-income countries.

Academics from the London Centre for Nanotechnology at UCL and AHRI used deep learning (artificial intelligence/AI) algorithms to improve health workers' ability to diagnose HIV using lateral flow tests in rural South Africa.

Their findings, published today in Nature Medicine, involve the first and largest study of field-acquired HIV test results, which have applied machine learning (AI) to help classify them as positive or negative.

More than 100 million HIV tests are performed around the world annually, meaning even a small improvement in quality assurance could impact the lives of millions of people by reducing the risk of false positives and negatives.

By harnessing the potential of mobile phone sensors, cameras, processing power and data sharing capabilities, the team developed an app that can read test results from an image taken by end users on a mobile device. It may also be able to report results to public health systems for better data collection and ongoing care.

Lateral flow tests - or rapid diagnostic tests (RDTs) - have been used throughout the COVID-19 pandemic and play an important role in disease control and screening.

While they provide a quick and easy way of testing outside of clinical settings, including self-testing, interpretation of test results can sometimes be challenging for lay people.

Self-testing relies on people self-reporting results for clinical support and surveillance purposes. Evidence suggests that some lay caregivers can struggle to interpret RDTs because of colour blindness or short-sightedness.

The new study examined whether an AI app could support HIV testing decisions made by fieldworkers, nurses and community health workers.

A team of more than 60 trained field workers at AHRI first helped build a library of more than 11,000 images of HIV tests taken in various conditions in the field in KwaZulu-Natal, South Africa, using a mobile health tool and image capture protocol developed by UCL.

The UCL team then used these images as training data for their machine-learning algorithm. They compared how accurately the algorithm classified images as either negative or positive, versus users interpreting test results by eye.

Lead author and Director of i-sense Professor Rachel McKendry (UCL London Centre for Nanotechnology and UCL Division of Medicine) said: "This study is a really strong partnership with AHRI that demonstrates the power of using deep learning to successfully classify 'real-world' field-acquired rapid test images, and reduce the number of errors that may happen when reading test results by eye. This research shows the positive impact the mobile health tools can have in low- and middle-income countries, and paves the way for a larger study in the future."

A pilot field study of five users of varying experience (ranging from nurses to newly trained community health workers) involved them using the mobile app to record their interpretation of 40 HIV test results, as well as capture a picture of the tests to automatically be read by the machine learning classifier. All participants were able to use the app without training.

The machine learning classifier was able to reduce errors in reading RDTs, correctly classifying RDT images with 98.9% accuracy overall, compared to traditional interpretation of the tests by eye (92.1%).

A previous study of users of varying experience in interpreting HIV RDTs showed the accuracy varied between 80% and 97%.

Other diseases that RDTs could support include malaria, syphilis, tuberculosis, influenza and non-communicable diseases.

First author Dr Valérian Turbé (UCL London Centre for Nanotechnology) and i-sense researcher in the McKendry group said: "Having spent some time in KwaZulu-Natal with fieldworkers organising the collection of data, I've seen how difficult it is for people to access basic healthcare services. If these tools can help train people to interpret the images, you can make a big difference in detecting very early-stage HIV, meaning better access to healthcare or avoiding an incorrect diagnosis. This could have massive implications on people's lives, especially as HIV is transmissible."

The team now plan a larger evaluation study to assess the performance of the system, with users of differing ages, gender and levels of digital literacy.

A digital system has also been designed to connect to laboratory and healthcare management systems, where RDT deployment and supply can be better monitored and managed.

AHRI Clinical Research Faculty Lead, Professor Maryam Shahmanesh (UCL Institute for Global Health), said: "Trials we have conducted in the area have found that HIV self-testing is effective in reaching large numbers of adolescents and young men. However, HIV self-testing has been less successful in linking people to biomedical prevention and treatment. A digital system that connects a test result and the person to healthcare, including linkage to antiretroviral therapy and pre-exposure prophylaxis, has the potential to decentralise HIV prevention and deliver on UNAIDS goals to eliminate HIV."

Dr Kobus Herbst, AHRI's Population Science Faculty lead, added: "This study shows how machine learning approaches can benefit from large and diverse datasets available from the global South, but at the same time be responsive to local health priorities and needs."

The researchers also suggest that real-time reporting of RDT results through a connected device could help in workforce training and outbreak management, for example by highlighting 'hotspots' where positive test numbers are high. They are currently extending the approach to other infections including COVID-19, and non-communicable disease.

Former AHRI Director Professor Deenan Pillay (UCL Infection & Immunity), said: "As digital health research moves into the mainstream, there remain serious concerns that those populations most at need around the world will not benefit as much as those in high income settings. Our work demonstrates how, with appropriate partnerships and engagement, we can demonstrate utility and benefit for those in low- and middle-income settings."

Credit: 
University College London

First trial of faecal microbiota transplantation for people with active peripheral psoriatic arthritis shows no advantage

In this proof-of-concept study, Maja Skov Kragsnaes and colleagues evaluated efficacy and safety of FMT in people with psoriatic arthritis (PsA). PsA is an inflammatory arthritis that causes a person's joints to become stiff and painful. It is often found people with the skin condition psoriasis, and there is also a link between PsA and inflammatory bowel disease or gastrointestinal symptoms.

This double-blind, parallel-group, sham-controlled, superiority trial randomly allocated31adults with active peripheral PsAd espite ongoing treatment with methotrexate to one gastroscopic-guided FMT procedure, or sham transplantation into the duodenum. The transplants (50 g faeces) came from one of four healthy, anonymous stool donors. The primary efficacy endpoint was the proportion of participants experiencing treatment failure, defined as needing treatment intensification through 26 weeks, and safety was monitored throughout.

The results showed that treatment failure occurred more frequently in the FMT group than in the sham group (60%versus19%, and improvement in function was also in favour of sham. No serious adverse events were observed.

Credit: 
European Alliance of Associations for Rheumatology (EULAR)

There is an unacceptable delay to diagnosis in axial spondyloarthritis

The Axial Spondyloarthritis International Federation (ASIF) set out to coordinate a comprehensive evidence-based global review of the factors influencing the current diagnosis delay in axSpA, and to produce a definitive report that shines a light on these barriers, as well as providing a resource that can ultimately empower a range of international stakeholders to reduce this delay.

At the 2021 EULAR congress, Wendy Gerhart and colleagues report the results of a full literature review and two virtual global forum events, involving patients and patient group representatives, researchers, rheumatologists, and other healthcare professionals. The aim was to explore key diagnosis challenges across different healthcare systems and identify opportunities for addressing these. Break-out discussions were held, and participants were asked to identify the personal and societal effects of the diagnostic delay, the reasons it occurs, and initiatives to tackle the challenge. Alongside key stakeholder testimonies, best practices from around the world were also identified. In total,92 stakeholders participated in the events, representing patients and healthcare professionals from 23 countries across five continents.

The findings from these activities were incorporated within a new 'Delay to Diagnosis' report, which for the first time definitively sets out the lived realities from a global perspective of the axSpA diagnosis delay. The report identified important commonalities across different countries and healthcare systems contributing to the current average global 7-year diagnosis delay. These include: 1) poor awareness of axSpA, particularly in primary-care services; 2) complexities in diagnosing the disease; 3) poorly defined referral pathways; and 4) insufficient patient access to rheumatologists and appropriate diagnostics.

The report also highlights the significant impact this delay has on individuals and wider society, providing a foundation for future advocacy work. A series of recommendations has been identified, the implementation of which will help make tangible progress in reducing the delay.

Despite longstanding challenges, there are now clear opportunities for transforming how axSpA is diagnosed around the world. This message needs to be heard and acted upon urgently by all those involved in the management and delivery of axSpA care. The future programme of work for ASIF's Delay to Diagnosis project will respond to these findings and be centred around supporting axSpA patient associations globally to take this call to action forward throughout 2021 and beyond.

Credit: 
European Alliance of Associations for Rheumatology (EULAR)

The true spread of SARS-CoV-2 infection is much greater than that observed by capturing only swab-diagnosed COVID-19 cases

As part of the MAINSTREAM project, Favalli and colleagues conducted a seroprevalence cross-sectional study between 4th May and 16th June 2020toestimate the prevalence of anti-SARS-CoV-2 antibodies in a large cohort of people with rheumatoid arthritis (RA) or spondyloarthritis (SpA) treated with biologic or targeted synthetic disease modifying anti rheumatic drugs (b/tsDMARDs) in a COVID-19 high-endemic area (Lombardy, Italy). Over this time, 300 people were tested for IgG, IgM and IgA antibodies against three viral antigens-nucleoprotein, spike protein, and the receptor-binding domain. These data were compared with those observed in the healthy population in the same period and region. Everyone taking part also completed a questionnaire to collect information about symptoms consistent with COVID-19, risk factors, and comorbidities.

Overall, 65% of people taking part had RA, 23% had psoriatic arthritis, and 21% had ankylosing spondylitis. Most people were being treated with tumour necrosis factor inhibitors (TNFi;57%), and the remainder were receiving abatacept (20%), interleukin-6 inhibitors (IL-6i;11%), or januskinase inhibitors (JAKi;5%).Of the 300 people, 4 had a prior diagnosis of COVID-19 defined by nasopharyngeal swab.

Immunoglobulin titres were evaluated resulting in 9%, 13.6%, and 13.3% positive patients for IgG, IgM and IgA, respectively, and there was no significant difference to the healthy population. Among seropositive patients, 55.3% were asymptomatic, 16% had minor and 19.6% major symptoms, 7.1% were hospitalized. No deaths or admission to intensive care occurred. IgM, IgG and IgA titres to the receptor binding domain of the virus were higher in patients with both minor and major symptoms compared with asymptomatic ones. No differences were found between seronegative and seropositive patients in relation to age, sex, rheumatic diagnosis, and treatment with cs- and b/tsDMARDs or corticosteroids. A relative increased risk was associated with obesity and presence of at least two comorbidities.

This study confirms that, even in a cohort of rheumatic patients, the spread of SARS-CoV-2 infection is much greater than that observed by capturing only swab-diagnosed COVID-19 cases. The underlying rheumatic disease and ongoing therapy with b/tsDMARD does not seem to impact SARS-CoV-2 antibody positivity, which conversely seems to be associated to symptomaticCOVID-19 and presence of comorbidities.

Credit: 
European Alliance of Associations for Rheumatology (EULAR)

Foresight diagnostics to show vision of the new standard of lymphoma MRD detection at ICML

AURORA, COLORADO, June 16, 2021 -- Foresight Diagnostics, the emerging leader in blood-based lymphoma disease monitoring, announced today that clinical performance of its minimal residual disease (MRD) detection platform in diffuse large B-cell lymphoma (DLBCL) will be presented at the 16th International Conference on Malignant Lymphoma (ICML) on June 18-22, 2021. The oral presentation demonstrates the utility of Foresight Diagnostics' proprietary PhasED-Seq technology to improve MRD detection rates in DLBCL patients in low-disease burden settings.

"Foresight's MRD testing platform can detect relapsing disease 200 days earlier than current methods in DLBCL patients receiving first-line therapy," says David Kurtz, MD, PhD, a Stanford University professor and a co-founder of Foresight Diagnostics who will present the talk at ICML. "We believe that such early detection constitutes the future standard for ctDNA-guided patient monitoring and treatment in the clinic and for drug development applications. We're proud that our abstract was selected for oral presentation at this year's ICML meeting and are excited to share this impactful data."

The presentation, titled "Phased variants improve DLBCL minimal residual disease detection at the end of therapy" will be presented during Session 3: Aggressive Lymphomas (Channel 3) on Sunday, June 20 at 17:45-19:15 (CEST).

Circulating tumor DNA (ctDNA) detection has prognostic value in DLBCL and has the potential to change the management of lymphoma in the clinic. But detection is still challenging in low-disease burden states with existing methods, such as MRD detection at the end of therapy.

Foresight's talk at ICML will introduce Phased Variant Enrichment & Detection Sequencing (PhasED-Seq), Foresight's proprietary ctDNA technology that leverages a novel class of somatic alteration called "phased variants" (PVs). By identifying and tracking PVs, PhasED-Seq enables ctDNA MRD detection down to parts-per-million levels, providing levels of sensitivity that are significantly better than SNV-based methods. The talk will also demonstrate that PVs are common in B-cell lymphomas and occur in stereotyped locations, enabling an "off-the-shelf" approach to variant monitoring that does not require tumor tissue or patient-specific customization.

"While many patients with diffuse large B-cell lymphoma are cured using standard therapies, there remains a great need to accurately identify those who are not cured and would benefit from new therapeutic strategies," states Foresight Board Member Mark Lee, MD, PhD, a founding executive at GRAIL and most recently SVP and Global Head of Personalized Healthcare at Genentech. "The improved sensitivity for ctDNA-based MRD detection during and after treatment showcases the potential for PhasED-Seq as the new standard for lymphoma MRD applications, such as MRD-adapted clinical trials."

Foresight Diagnostics recently announced a $12.5M Series A financing to accelerate the commercialization of the PhasED-Seq technology and also presented clinical performance data on PhasED-Seq at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Foresight's first commercially available test offering will be a CLIA-validated B-cell lymphoma MRD assay, and the company is initiating retrospective and prospective clinical studies with multiple partners to evaluate the utility of the assay in patients with a variety of B-cell malignancies.

Credit: 
Samba Scientific

Exposure to nature during COVID-19 lockdown was beneficial for mental health

A study carried out by the Institute of Environmental Science and Technology of the Universitat Autònoma de Barcelona (ICTA-UAB) and the Instituto de Saúde Pública of the University of Porto (ISPUP), concludes that exposure to natural spaces during the first COVID-19 lockdown in 2020 was beneficial for the mental health of Spanish and Portuguese citizens.

The research shows that, in Portugal, during the first confinement, people who maintained or increased contact with natural public spaces, such as parks and coastal areas, or who could contemplate these spaces from their homes, presented lower levels of stress, psychological distress and psychosomatic symptoms.

In Spain, those who maintained or increased contact with private natural spaces, such as indoor plants or community green areas, presented lower levels of stress and psychosomatic symptoms. This could be due to the fact that Spain adopted more restrictive measures for foreign circulation during the period analysed.

The research Exposure to nature and mental health outcomes during COVID-19 lockdown. A comparison between Portugal and Spain, published in the journal Environment International, was conducted between March and May 2020.

Dr Ana Isabel Ribeiro, researcher at the ISPUP and first author of the work together with Margarita Triguero-Mas from the ICTA-UAB says that "we decided to study whether natural, public and private spaces had a beneficial effect on the mental health of Portuguese and Spanish citizens, helping them to better cope with the negative effects of lockdown". For her part, Margarita Triguero-Mas adds that "people around us and ourselves talked about how we missed the park we crossed when we went to the office or the walk on the beach with our dogs, so we wanted to check to what extent contact with natural spaces was an important factor during confinement".

Several previous articles have also shown the positive impact of exposure to natural spaces on mental health, that is, in reducing stress, anxiety and improving psychological well-being as a whole. "Taking into account what is described in the literature, we wanted to evaluate whether people who enjoyed greater exposure to natural spaces during the first COVID-19 lockdown had better mental health indicators than those who had no contact with natural areas", explains Dr Ribeiro. At the same time, they wanted to investigate whether exposure to private natural spaces, such as gardens, orchards or plants, was more beneficial among Spanish citizens than among Portuguese, given that Spain applied stricter measures to restrict mobility than Portugal.

To carry out the research, the authors applied an online questionnaire, between March 27 and May 6, 2020, aimed at all citizens aged 18 years old or older, residing in Spain or Portugal. The survey covered aspects related to the frequency and type of exposure people had to natural spaces (public and private), before and during the first confinement; mental health questions to assess levels of stress, mental disorders and somatization symptoms, and sociodemographic issues. Of the more than 3,000 citizens (n = 3,157) who answered the questionnaire, 1,638 were Portuguese and 1,519 Spanish.

In both countries, during the confinement, there was a significant reduction in the use of public natural spaces, such as beaches, parks and gardens, and an increase in contact with private natural spaces, such as community gardens, urban gardens and plants, especially in Spain. People living in single-family houses (detached house) and flats located in cities were the ones who least maintained or increased their exposure to public natural spaces in both countries.

In Spain, where the measures during the period analysed were much more restrictive and it was forbidden to leave the house and public outdoor spaces were closed, the benefits of exposure to public natural spaces were not as relevant as in Portugal, but it was clear the importance of private natural elements. Among the Spanish citizens who participated in the study, 66% decreased the frequency of exposure to public natural spaces (compared to 54% in Portugal).

In Spain, it is remarkable that the people who least maintained or increased the care of indoor plants were people over 65 years of age, those who lived with several people at home or those who were in a second residence during confinement. In contrast, the people who maintained or increased the care of indoor plants the most were those with children, but without dependent adults.

In Portugal, those who were confined the longest and those who commuted to work were those who least maintained or increased their contact with the natural public spaces. In turn, those who practiced physical exercise indicated greater exposure to these places. Portuguese citizens who managed to maintain or increase their exposure to natural public spaces showed lower levels of stress compared to those who did not. Likewise, those who contemplated natural spaces from their homes obtained improvements in all the mental health outcomes analysed: stress, mental disorders and somatization.

"This study clearly demonstrates the benefit of natural spaces for the mental health of the population in a context of public health crisis," says Ana Isabel Ribeiro.

"Public authorities and decision-makers could implement measures that facilitate access to natural public spaces, in a safe and controlled manner, in the context of a pandemic. This is particularly important for the most socially and economically vulnerable population groups, and for those who have little access to these spaces in their private context", she emphasizes.

In addition, Dr Triguero-Mas adds that "our study is especially important for cities like Barcelona, where new buildings rarely have balconies or community spaces with vegetation. It is important to revalue how building remodelling or new homes can be healthier spaces that promote and prevent deterioration in the health of the people who inhabit them".

Credit: 
Universitat Autonoma de Barcelona

'Mosquito smoothie' innovation boosts future malaria vaccine potential

image: The mosquito 'smoothie' and the purified parasites after the team's process.

Image: 
Joshua Blight/Imperial College London

A faster method for collecting pure malaria parasites from infected mosquitos could accelerate the development of new, more potent malaria vaccines.

The new method, developed by a team of researchers led by Imperial College London, enables more parasites to be isolated rapidly with fewer contaminants, which could simultaneously increase both the scalability and efficacy of malaria vaccines.

The parasite that causes malaria is becoming increasingly resistant to antimalarial drugs, with the mosquitoes that transmit the disease also increasingly resistant to pesticides. This has created an urgent need for new ways to fight malaria, which is the world's third-most deadly disease in under-fives, with a child dying from malaria every two minutes.

Existing malaria vaccines that use whole parasites provide moderate protection against the disease. In these vaccines, the parasites are 'attenuated' - just like some flu vaccines and the MMR vaccine - so they infect people and raise a strong immune response that protects against malaria, but don't cause disease themselves.

However, these vaccines require several doses, with each dose requiring potentially tens of thousands of parasites at an early stage of their development, known as sporozoites. Sporozoites are normally found in the salivary glands of mosquitoes, and in a natural infection are passed to humans when the mosquito bites. They then travel to the human liver, where they prepare to cause infection in the body.

Extracting sporozoites for use in a live vaccine currently requires manual dissection of the mosquito salivary glands - miniscule structures behind the mosquito head - by a skilled technician, which is a time-consuming and costly process.

The new method, described today in Life Science Alliance, vastly speeds up this process by effectively creating a 'mosquito smoothie' and then filtering the resulting liquid by size, density and electrical charge, leaving a pure sporozoite product suitable for vaccination. Importantly, no dissection is required.

Lead researcher Professor Jake Baum, from the Department of Life Sciences at Imperial, said: "Creating whole-parasites vaccines in large enough volumes and in a timely and cost-effective way has been a major roadblock for advancing malaria vaccinology, unless you can employ an army of skilled mosquito dissectors. Our new method presents a way to radically cheapen, speed up and improve vaccine production."

But it's not just about speed and cost. Traditional dissection methods struggle to remove all contaminants, such as proteins from the salivary glands, which are often extracted with sporozoites. The extra debris is likely to affect the infectivity of the sporozoites once they are inside the body, and could even affect how the immune system responds, impacting the efficacy of any whole parasite vaccine.

The new method also tackles this problem, resulting in pure uncontaminated sporozoite samples. The team discovered that, as well as being purer, sporozoites produced were surprisingly more infectious, hinting that vaccines produced using their method may require a much lower dose of sporozoites.

First author of the study Dr Joshua Blight, from the Department of Life Sciences at Imperial, said: "With this new approach we not only improve the scalability of vaccine production, but our isolated sporozoites may actually prove to be more potent as a vaccine, giving us additional bang per mosquito buck."

The team developed and tested their method with both human and rodent malaria parasites. They then tested the rodent version as a vaccine in mice, and found that when exposed to an infected mosquito bite, vaccinated mice showed 60-70 per cent protection when immunisations were given into muscle. When the same sporozoites were given directly into the blood stream (intravenously) protection was 100 per cent, known as 'sterile' protection.

The researchers are now developing the method further in readiness for mass manufacture of sporozoites under good manufacturing practice (GMP) conditions in order to produce a vaccine ready for human challenge trials. The plan is that participants would be given vaccine-grade sporozoites produced using this method and then purposefully bitten by an infected mosquito.

Looking beyond vaccines the researchers also say their method should help accelerate studies of sporozoite biology in general, which could in turn lead to fresh insights into the liver stage of malaria and new drug and vaccine regimes.

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Imperial College London

RUDN University biologists develop a rapid test for detecting the fire blight in plants

image: RUDN University biotechnologists have created a method for detection of bacterial infection in apple, pear, hawthorn and other plants of the Rosaceae family. The test does not require laboratory equipment, the result is ready in 10 minutes. This will allow detecting the disease quickly and prevent the spread of infection.

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RUDN Unviersity

RUDN University biotechnologists have created a method for detection of bacterial infection in apple, pear, hawthorn and other plants of the Rosaceae family. The test does not require laboratory equipment, the result is ready in 10 minutes. This will allow detecting the disease quickly and prevent the spread of infection. The results are published in Physiological and Molecular Pathology of Plants.

Erwinia amylovora bacteria causes a dangerous infectious disease in plants -- a fire blight. Most plants of the Rosaceae family are vulnerable to it, for example, hawthorn, apple, pear. The bacteria causes the blossom to wither, the leaves dry up and curl, the bark develop necrotic lesions. The disease can spread through infected plants, garden tools, and with the wind, which carries the exudate produced by lesions. To stop the spread of infection in time, we need ways to diagnose it quickly and effectively. Existing testing methods require laboratory equipment. This slows down diagnostics. RUDN University biotechnologists have developed a method that gives the results in 10 minutes right "on the spot".

"To control E. amylovora, disease diagnosis right in the orchard or nursery is important, especially for monitoring disease outbreaks or independent control of farm and private orchards. Thus our main objective was to develop an express-test to detect E. amylovora and compare different organs of infected plants for optimization", Shyatesa Razo, PhD student at RUDN University

The new test is based on immunochromatographic analysis. This is one of the most universal diagnostic methods -- this is how most modern express tests works (for example, a pregnancy test or SARS-CoV-2 test) are arranged. A test strip is placed in a biological liquid - for example, a leaf extract. Specific antibodies are applied to the strip, which "bind" to the desired substance and color certain areas forming the stripes. By their number, it can be concluded that a particular substance is present in the biological fluid. The aim of the RUDN University biotechnologists was to select such antibodies that would allow to determine the presence of Erwinia amylovora in the plant liquids.

To obtain specific antibodies, biologists immunized chinchilla rabbits with Erwinia amylovora. 7-10 days after the last injections, biologists took blood samples from the animals and isolated the necessary immunoglobulin IgG (protein cells that neutralize the pathogen).

The resulting test was verified on infected plants from the Voronezh region -- 121 samples of apple, pear, hawthorn, quince, blackthorn and cherry. The test fluid was isolated from leaves, twigs, flowers, fruits, and bacterial mucus. As a result, in 93.5% of cases, the results of the rapid test coincided with the results of the PCR test, which requires more time and special laboratory equipment. RUDN University biotechnologists also determined that it is best to use the vascular tissues of the plant.

"Today, the diagnosis of plant pathogens is on the rise; the number of rapid and sensitive methods of analysis, both laboratory and non-laboratory, is increasing. However, the distribution of the pathogen in the plant determines the appropriate sampling for any assay. We determined which plant parts are more accurate for fire blight detection using LFIA. In this aspect, our study will be helpful for more effective and thoughtful diagnosis of fire blight in non-laboratory conditions", Shyatesa Razo, PhD student at RUDN University.

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RUDN University

People with back pain miss far fewer workdays when they receive recommended treatments

Medical guidelines help doctors understand the best way to treat health conditions. Surprisingly, many doctors do not adhere to them, and this is a problem, according to a new study by scientists at University of Utah Health and MDGuidelines. People with lower back pain injury miss 11 more days of work in a year when they only receive treatments for lower back pain that are not recommended by medical guidelines compared to people treated according to guidelines. The findings publish in PLOS ONE on June 17.

"The closer people's care follows evidence-based guidelines, the faster their back pain resolves, by quite a bit," says the study's senior author Kurt Hegmann, M.D., director of the University of Utah Rocky Mountain Center for Occupational and Environmental Health.

That may be so, but 65% of the people included in the study received at least some non-recommended treatments for lower back pain. Among the nearly 60,000 people whose medical claims were analyzed:

14% received non-recommended treatments only,

51% received a mix of non-recommended and recommended treatments,

14% received recommended treatments only,

and 21% did not receive any medical intervention.

People who received recommended treatments combined with non-recommended treatments saw an intermediate benefit, missing a median of eight workdays within the year as compared to those who exclusively received recommended treatments.

The most common non-recommended treatments were prescriptions for opioids, which are discouraged because they reinforce debility instead of exercise and can be addictive, and X-rays, which can lead to inaccurate diagnoses. The most common recommended treatments were nonsteroidal anti-inflammatory drugs and muscle relaxants.

The data came from California workers' compensation claims between 2009 to 2018 from employees who had uncomplicated, acute lower back pain or strain, the most prevalent injury in the workplace. The researchers tracked whether treatments prescribed in clinic visits within the first week after injury were categorized as recommended or non-recommended in the peer-reviewed American College of Occupational and Environmental Medicine (ACOEM) guidelines, with the assumption that similar treatment patterns would continue in any subsequent clinic visits. The scientists then calculated the number of lost workdays within the first year after injury.

While a large proportion of workers received non-recommended treatments, health care providers improved adherence to medical guidelines over time. In 2009, 10% were treated according to guidelines, but that rose to 18% by 2018. The treatment practice that changed most drastically was opioid prescriptions, which fell by 86% over those nine years.

"The reduction in opioids prescription is particularly impressive," Hegmann says. "In this case, the insurer is likely to not pay for opioids even if they are prescribed. It suggests what's possible when the 'carrot' of good health care is missed and instead the 'stick' of compliance with a guideline is in place."

Clinical practice guidelines are based on systematic reviews of scientific evidence and are designed to guide health care providers as they decide how to treat their patients' health conditions. Typically, guidelines are updated every few years, which can make it difficult for health care providers to keep up. Doctors may not adhere to guidelines because they aren't aware of them, don't know how to implement the recommended treatments, prefer to continue practices they've used in the past, or for other reasons.

Regardless, the large reductions in opioid prescriptions for lower back pain suggest that added incentives, such as insurance refusing to pay for non-recommended treatments, increases adherence to guidelines. Hegmann and the study's first author, Fraser Gaspar, Ph.D., say that implementing decision support tools and other ways to promote adherence to guidelines will be better for patients.

"Being out of work impacts many facets of your life," says Gaspar, who carried out the research when he was a scientist at MDGuidelines. "In addition to the physical disability that's causing the person to miss work, the worker is making less money, while they often incur additional costs and experience mental strain. Getting people back to their normal lives is really important, and our research shows that following guidelines makes that happen faster."

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University of Utah Health

Online coaching improves choices of women experiencing pregnancy difficulties

Personalised coaching through a smartphone platform can help women improve their lifestyle behaviours in the period before and shortly after they become pregnant, a new study has shown. The biggest reduction in behaviours that pose risks to pregnancy were seen in overweight women.

The findings, published in the journal Reproductive Biomedicine Online, show that digital healthcare could be a cost-effective way to deliver tailored advice to women who experience difficulties in pregnancy, which the NHS does not have the resources to provide.

In this study, led by the University of Southampton, 262 women who were planning pregnancies and had either experienced difficulties in conceiving or recurrent miscarriages signed up to the online lifestyle coaching programme Smarter Pregnancy. All participants completed questionnaires through the app at the beginning and at six-week intervals over the four-month trial. The questionnaires covered subjects such as their diet, folic acid intake, smoking and consumption of alcohol.

After each questionnaire, half of the participants (the intervention group) were sent automated advice and recommendations through the coaching platform, based on their responses. The other half (the control group) were referred to standard guidance for periconceptional care on the NHS website.

Analysis of the responses to the questionnaires showed that the group receiving advice through the Smarter Pregnancy platform were more likely to make positive changes to their lifestyle over the course of the trial than participants in the control group. The most significant change was in the reduction in smoking and drinking alcohol for those with a Body Mass Index above 25 (overweight). The findings also showed that the odds of becoming pregnant after 24 weeks were increased for the participants using the app, although the study team note that more research would be needed to validate this connection as this study was targeted on improving lifestyle choices rather than assessing pregnancy rates.

Dr Bonnie Ng, MRC Fellow in Clinical and Experimental Sciences at the University of Southampton said, "Our trial shows that digital healthcare tools can help women improve their lifestyle and the health of their babies.

"Using this tool, women can take control of their own body, and it also removes the impression that they are being 'told off' when they see their doctor.

"I truly hope that we can use this e-health platform in the future to offer women tailored advice."

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University of Southampton

Exposure to nature during COVID-19 lockdown was beneficial for mental health

A study carried out by the Institute of Environmental Science and Technology of the Universitat Autònoma de Barcelona (ICTA-UAB) and the Instituto de Saúde Pública of the University of Porto (ISPUP), concludes that exposure to natural spaces during the first COVID-19 lockdown in 2020 was beneficial for the mental health of Spanish and Portuguese citizens.

The research shows that, in Portugal, during the first confinement, people who maintained or increased contact with natural public spaces, such as parks and coastal areas, or who could contemplate these spaces from their homes, presented lower levels of stress, psychological distress and psychosomatic symptoms.

In Spain, those who maintained or increased contact with private natural spaces, such as indoor plants or community green areas, presented lower levels of stress and psychosomatic symptoms. This could be due to the fact that Spain adopted more restrictive measures for foreign circulation during the period analysed.

The research Exposure to nature and mental health outcomes during COVID-19 lockdown. A comparison between Portugal and Spain, published in the journal Environment International, was conducted between March and May 2020.

Dr Ana Isabel Ribeiro, researcher at the ISPUP and first author of the work together with Margarita Triguero-Mas from the ICTA-UAB says that "we decided to study whether natural, public and private spaces had a beneficial effect on the mental health of Portuguese and Spanish citizens, helping them to better cope with the negative effects of lockdown". For her part, Margarita Triguero-Mas adds that "people around us and ourselves talked about how we missed the park we crossed when we went to the office or the walk on the beach with our dogs, so we wanted to check to what extent contact with natural spaces was an important factor during confinement".

Several previous articles have also shown the positive impact of exposure to natural spaces on mental health, that is, in reducing stress, anxiety and improving psychological well-being as a whole. "Taking into account what is described in the literature, we wanted to evaluate whether people who enjoyed greater exposure to natural spaces during the first COVID-19 lockdown had better mental health indicators than those who had no contact with natural areas", explains Dr Ribeiro. At the same time, they wanted to investigate whether exposure to private natural spaces, such as gardens, orchards or plants, was more beneficial among Spanish citizens than among Portuguese, given that Spain applied stricter measures to restrict mobility than Portugal.

To carry out the research, the authors applied an online questionnaire, between March 27 and May 6, 2020, aimed at all citizens aged 18 years old or older, residing in Spain or Portugal. The survey covered aspects related to the frequency and type of exposure people had to natural spaces (public and private), before and during the first confinement; mental health questions to assess levels of stress, mental disorders and somatization symptoms, and sociodemographic issues. Of the more than 3,000 citizens (n = 3,157) who answered the questionnaire, 1,638 were Portuguese and 1,519 Spanish.

In both countries, during the confinement, there was a significant reduction in the use of public natural spaces, such as beaches, parks and gardens, and an increase in contact with private natural spaces, such as community gardens, urban gardens and plants, especially in Spain. People living in single-family houses (detached house) and flats located in cities were the ones who least maintained or increased their exposure to public natural spaces in both countries.

In Spain, where the measures during the period analysed were much more restrictive and it was forbidden to leave the house and public outdoor spaces were closed, the benefits of exposure to public natural spaces were not as relevant as in Portugal, but it was clear the importance of private natural elements. Among the Spanish citizens who participated in the study, 66% decreased the frequency of exposure to public natural spaces (compared to 54% in Portugal).

In Spain, people who had the opportunity to continue dedicating or increasing the time dedicated to caring for their plants had lower stress levels, while those who were able to continue enjoying or increasing the time of use of community green spaces had lower rates of somatization.

In Spain, it is remarkable that the people who least maintained or increased the care of indoor plants were people over 65 years of age, those who lived with several people at home or those who were in a second residence during confinement. In contrast, the people who maintained or increased the care of indoor plants the most were those with children, but without dependent adults.

In Portugal, those who were confined the longest and those who commuted to work were those who least maintained or increased their contact with the natural public spaces. In turn, those who practiced physical exercise indicated greater exposure to these places. Portuguese citizens who managed to maintain or increase their exposure to natural public spaces showed lower levels of stress compared to those who did not. Likewise, those who contemplated natural spaces from their homes obtained improvements in all the mental health outcomes analysed: stress, mental disorders and somatization.

"This study clearly demonstrates the benefit of natural spaces for the mental health of the population in a context of public health crisis," says Ana Isabel Ribeiro. "Public authorities and decision-makers could implement measures that facilitate access to natural public spaces, in a safe and controlled manner, in the context of a pandemic. This is particularly important for the most socially and economically vulnerable population groups, and for those who have little access to these spaces in their private context", she emphasizes.

In addition, Dr Triguero-Mas adds that "our study is especially important for cities like Barcelona, where new buildings rarely have balconies or community spaces with vegetation. It is important to revalue how building remodelling or new homes can be healthier spaces that promote and prevent deterioration in the health of the people who inhabit them".

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Universitat Autonoma de Barcelona