Body

COVID-19: Reduced sense of taste and smell lingers

Patients with mild Covid-19 infections experience a significantly increased longer lasting reduced sense of taste and smell. This is also the case for long-term shortness of breath, although relatively few people are affected. And women and the elderly are particularly affected. This is shown by new research findings from Aarhus University Aarhus University Hospital and Regional Hospital West Jutland

The last 14 months have taught us that there are different symptoms and outcomes of Covid-19. However, the vast majority of people who fall ill with Covid-19 experience mild symptoms and get over the disease in two to three weeks.

These are precisely some of the people who have been the subject of a new study from AUH, HEV and AU. In the study, researchers have compared symptoms on a daily basis for up to 90 days in 210 healthcare workers who had tested positive and 630 with a negative test.

Each day, the participants received a link to a questionnaire on whether they had experienced one of the following symptoms within the last 24 hours: coughing, sore throat, headaches, fever, muscle pain, shortness of breath and reduced sense of taste and smell.

"We saw that the prevalence of a longer lasting reduced taste and smell is significantly increased in patients with mild Covid-19 disease who did not require hospitalisation. This pattern is also seen for shortness of breath, but far fewer people were affected," says Henrik Kolstad, who is behind the study.

Women and the elderly experience more symptoms

Thirty per cent of those who had tested positive and almost none of the participants with a negative test reported a reduced sense of taste and smell over the full ninety days. At the beginning of the project, shortness of breath was reported by twenty per cent of those who had tested positive, with the figure falling to five per cent after thirty days, though without ever reaching the level of the participants who had tested negative.

Coughing, sore throat, headaches, muscle pain and fever were more common among those who tested positive than those who tested negative in the first few days, but after thirty days no increases were seen.

Woman with a positive test reported more symptoms compared to women with a negative test than was the case for men with a positive test when compared to men with a negative test. The same was true for older and younger participants. According to the researcher, this could indicate that women and the elderly are more susceptible to developing long-term COVID-19 symptoms.

"This study provides detailed knowledge of which symptom pathways you can expect after having tested positive for COVID-19 without requiring hospitalisation," says Henrik Kolstad.

Background for the results

The study is a cohort study

Partners: The Departments of: Occupational Medicine, Blood Bank and Immunology, Clinical Microbiology, and Infectious Diseases at Aarhus University Hospital; Occupational Medicine, at the Regional Hospitals West Jutland; Business Intelligence, at the Central Denmark Region; The Department of Public Health, Aarhus University; and Occupational and Environmental Medicine, Bispebjerg and Frederiksberg Hospital.

The study is financed by the Central Denmark Region.

The scientific article can be read in the International Journal of Infectious Diseases: https://pubmed.ncbi.nlm.nih.gov/34022336/

Credit: 
Aarhus University

83% of the Spanish population trusts in vaccination against COVID, 25 points more than in January

image: Presentation of the results of the third Social Perception Survey on scientific aspects of COVID-19. From left to right, Josep Lobera, professor of Sociology at the UAM and scientific director of the Survey, Raquel Yotti, director of the ISCIII, Pampa García Molina, editor-in-chief of the SINC Agency and Pablo Simón, professor of Political Science at the UC3M.

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FECYT

FECYT - Spanish Foundation for Science and Technology - presented today at the headquarters of the National Museum of Science and Technology, MUNCYT, IN Alcobendas, the results of the third Social Perception Survey of scientific aspects of the COVID-19 in a debate moderated by Pampa García Molina, Editor-in-Chief of the SINC Agency, in which Raquel Yotti, Director of the Carlos III Health Institute of Madrid, Josep Lobera, Professor of Sociology at the Universidad Autónoma de Madrid (UAM) and scientific director of the Social Perception Survey on the scientific aspects of COVID-19 and Pablo Simón, Professor of Political Science at the Carlos III University of Madrid, took part.

The results of this third survey correspond to interviews conducted by telephone with 2,100 individuals from 3 to 21 May 2021 and measures the evolution of vaccine reluctance and its associated social factors. The study with the results of this third survey was also presented during the event and is available on the FECYT website.

The first survey was conducted between 25 June and 15 July 2020 and the second between 4 and 22 January 2021. With the results obtained from both, the report Evolución de la percepción social de aspectos científicos de la COVID-19 (Evolution of Social Perception of Scientific Aspects of COVID-19) was produced.

This series of surveys has been conducted for the FECYT by Professor Josep Lobera (Universidad Autónoma de Madrid) with the collaboration of researcher Pablo Cabrera (Universidad de Salamanca).

Attitudes towards vaccination

Results of the study show that the uptake of covid-19 vaccines consolidates the improvement initiated in January 2021. In July 2020, only one third of the population (32%) expressed with full confidence their intention to be vaccinated as soon as a vaccine was offered by health authorities. In January, that proportion increased to 58% and, in May, it has reached 83% (adding those already vaccinated and those fully confident of doing so).

The main factors associated with reluctance to vaccinate are the belief that vaccines are unsafe, complacency (the perception that when the majority are vaccinated, vaccination is no longer necessary), individualistic values (measured as disengagement from "I would accept the coronavirus vaccine if it helps protect my elders") and the conspiracy mentality around covid-19.

Compliance with COVID-19 preventive measures

Results show a certain relaxation in compliance with prevention measures, particularly in maintaining social distance. In May, only a third of the population (32%) said that they had strictly avoided social contacts in the last month, twenty points less than in January.

On the other hand, only half of the population (49%) say that they have avoided or have been able to strictly avoid being in enclosed spaces with other people outside their living environment. The main factors associated with non-compliance with prevention measures are: 1) non-compliance with the measures by their immediate social environment, 2) lack of trust in health institutions, 3) having a low level of education, and 4) being male. The quadratic effect of educational level points to a possible effect of living/working conditions on the maintenance of prevention norms. On the other hand, conspiracy mentality adds to the list of factors associated with mask use.

COVID-19 conspiracy theories

There is a significant percentage of people who believe in some conspiracy theories. One in four Spaniards (25%) strongly believe that there are secret organisations that strongly influence political decisions and only 17% strongly believe the opposite. Almost a third of the Spanish population (31%) believe that face masks are bad for their health and only 16% firmly believe that they are not. Nearly 8% strongly believe that vaccinating children is harmful, and this fact is hidden, while 35% strongly believe that this is not the case.

58% of the population declare they have seen or heard messages, through one or more media, encouraging people not to be vaccinated against the coronavirus. Twenty-seven per cent say they have heard or seen them on television, while 34% say these messages have come to them via a social network.

The main factors associated with having conspiratorial beliefs about covid-19 are: 1) a previous conspiratorial mindset about vaccines, 2) distrust of political institutions, 3) avoidance of mask use, 4) experiencing social difficulties associated with covid-19 containment measures, 5) being female, and 6) having a low level of education.

Technical data sheet of the survey:

Universe: individuals aged 18 and over resident in Spain for 5 or more years.

Sample size: 2,100 interviews.

Sampling: random selection of the interviewee with a sample stratified by the intersection habitat / autonomous community and distributed proportionally to the total of the region.

Method of data collection: computer-assisted telephone interview (CATI) using a structured and pre-coded questionnaire. The interviews were carried out in 75% of the cases by means of the interviewees' landline telephones and in the remaining 25% by means of their mobile telephones for people who did not have a landline telephone.

Data collection: computer-assisted telephone interview (CATI) using a structured, pre-coded questionnaire. The interviews were carried out in 75% of the cases through the landline phones of the interviewees and in the remaining 25% through their mobile phones for people who did not have a landline phone.

Sampling error: assuming the criteria and principles of simple random sampling, under the assumption of maximum sampling inefficiency due to the non-proportional distribution of the sample, for a confidence level of 95% and in the worst case scenario of maximum indeterminacy (p=q=50%), the margin of error for the total sample can be estimated at +-2.14%.

Fieldwork: between 3 and 21 May 2021.

Credit: 
Spanish Foundation for Science and Technology

New corona mass test up to 100 times more sensitive than rapid antigen tests

image: Blue-stained swab material from corona tests is prepared for analysis in a sequencing device with the help of a laboratory robot.

Image: 
Felix Heyder / University Hospital Bonn

A new corona test developed at the University Hospital Bonn can analyze a large number of swabs simultaneously using sequencing technology and has a similarly high sensitivity as the common qPCR test. The innovative method offers great potential, especially for systematic testing in daycare centers, schools or companies. Today, the results of the study on the new Corona test have been published in the renowned journal "Nature Biotechnology".

Bonn, 6/29/2021 - In addition to vaccination, systematic testing of the population remains of central importance in order to effectively monitor and contain the spread of infections during the Coronavirus pandemic. Only in this way can the spread of the virus be effectively monitored and contained through targeted measures.

The innovative corona test "LAMP-Seq", which has been developed at the University Hospital Bonn (UKB), offers the possibility to test many people regularly for the SARS-CoV-2 virus. In this way, infections can be detected at an early stage and corresponding chains of infection can be interrupted quickly. "Our corona test "LAMP-Seq" can detect about 100 times lower amounts of virus than current rapid antigen tests and is almost as sensitive and specific as the common qPCR test" describes Prof. Dr. Jonathan Schmid-Burgk from the Institute of Clinical Chemistry and Clinical Pharmacology of the UKB the characteristics of the test procedure, which was developed interdisciplinary with other researchers at the UKB.

"Added to this is the high scalability of the test. By using sequencing machines, thousands of samples can be analyzed simultaneously," said Schmid-Burgk, who was appointed to the University of Bonn from the Broad Institute of MIT and Harvard in early 2020. The LAMP-Seq method detects not only corona infections with the original SARS-CoV-2 virus, but also the novel variants of concern alpha to delta.

Members of the ImmunoSensation2 cluster of excellence, the Institute of Hygiene and Public Health, Life&Brain GmbH and Bundeswehr Central Hospital Koblenz were among those involved in the project.

For the "LAMP-Seq" test, the Bonn scientists have adapted the already established LAMP method ("Loop-mediated Isothermal Amplification" - propagation of the viral genome at a constant temperature) and made it compatible with sequencing machines used for biomedical research. As a result, many samples can be analyzed simultaneously in a high-throughput procedure. Before thousands of samples are analyzed together in a sequencing run, each individual sample is linked to a molecular barcode. This barcode ensures that each sample can be assigned without doubt, even after thousands of samples have been pooled. "Retesting of the entire pool in case of a positive test result is therefore no longer necessary" says Dr. Kerstin Ludwig, Emmy-Noether group leader at the Institute of Human Genetics. This technology significantly reduces the cost per test in comparison to the qPCR test and makes the "LAMP-Seq" procedure a scalable corona mass test.

"With its high throughput and sensitivity, the "LAMP-Seq" test can make a significant contribution to the screening of undetected infections. Especially in schools or companies, where many people regularly meet, the corona test is ideal to systematically and preventively monitor the occurrence of infections" describes Ludwig, the co-developer of the test procedure, the possible application scenarios of the "LAMP-Seq" test.

Prof. Wolfgang Holzgreve, Medical Director and CEO of the UKB, explains the benefits of the new test for corona surveillance as follows: "In order to effectively contain a pandemic, infected people must be found before they infect others. To achieve this goal, we need mass screenings with the highest sensitivity that can give us a detailed picture of existing chains of infection. This is exactly what the corona test "LAMP-Seq" developed at UKB is suited for."

Even smaller models of the sequencing machines used are capable of analyzing around 10,000 samples in a single run (duration: around ten to twelve hours). This virtually eliminates laboratory capacity as a limiting factor in testing.

In several large studies (including school and employee testing) with a total of around 20,000 tests, the Bonn scientists have extensively tested, optimized and successfully validated the entire upstream and downstream logistics, from sample collection by throat swabs to fully digital feedback of the test results. The documentation of the study results recently passed an independent peer review process and was published today in the renowned journal Nature Biotechnology.

While the Bonn scientists have currently focused their innovative method entirely on SARS-CoV-2 testing, "LAMP-Seq" can also be used in the future for differential diagnostics in testing for other viruses such as influenza A and can also be quickly adapted to other viruses.

The scientists are currently working on CE certification in order to make the "LAMP-Seq" test available internationally in the near future. Until this approval is obtained, the technically and scientifically fully validated "LAMP-Seq" method will continue to be used for pilot testing.

Credit: 
University Hospital Bonn

People living with HIV/AIDS have a significantly higher risk of suicide

HERSHEY, Pa. -- A new study by researchers at Penn State College of Medicine indicates that people living with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) -- approximately 38 million worldwide -- are more likely to have suicidal thoughts and die from suicide than members of the general population. The researchers said that despite significant medical advancements related to HIV treatment and patients' quality of life, risk of suicide in these patients is high and health care providers should prioritize mental health screenings in this population.

According to the World Health Organization, roughly 800,000 people worldwide die from suicide annually. Among members of the general population who have suicidal thoughts, one out of three will attempt suicide. Out of 286 suicide attempts, one will result in death. Results from a College of Medicine study suggest that for every two people living with HIV/AIDS who have suicidal thoughts, one person will attempt suicide. Among this population, out of 13 suicide attempts, one will result in death.

Analyzing data from more than 185,000 adults living with HIV/AIDS worldwide, the researchers examined risk factors and incidences of attempted and completed suicides among this population. They found that not only is suicidal ideation higher, but people living with HIV/AIDS were 100 times more likely to die by suicide compared to the general population.

"There is an urgent need to prioritize mental health screening and care into all HIV testing and treatment settings," said Dr. Paddy Ssentongo, researcher and an epidemiology doctoral student. "Suicide risk should be assessed in all HIV patients, especially in those who are newly-diagnosed and those with advanced disease."

According to the findings, people living with HIV/AIDS in North America are 50 times more likely to commit suicide compared to those living in Europe. Similarly, North America, South America and Australia have the highest rates of suicide attempts in people living with HIV/AIDS. The researchers also found that the risk of suicide was high for both newly diagnosed individuals and those whose illness progressed to AIDS.

The researchers noted that several possible factors may contribute to the increased risk of suicide among people living with HIV/AIDS, including advanced disease, neurological changes and societal stigmas. On the other hand, data from the study showed that patients being treated with antiretroviral therapy were less likely to commit suicide. The researchers said the study reveals the importance of mental health screenings and interventions for people living with HIV/AIDS.

Credit: 
Penn State

'Unlocking' the potential of viruses to fight cancer

image: Drs Amit Kulkarni (left) and Antonio Marchini (right) from LOVIT

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Drs Amit Kulkarni (left) and Antonio Marchini (right) from LOVIT

Researchers from the Laboratory of Oncolytic-Virus-Immuno-Therapeutics (LOVIT) at the LIH Department of Oncology (DONC) are working on the development of novel anticancer strategies based on oncolytic viruses, "good" viruses that can specifically infect, replicate in and kill cancer cells. In particular, the LOVIT team elucidated the mechanism through which the H-1PV cancer-destroying virus can attach to and enter cancer cells, thereby causing their lysis and death. At the heart of this process lie laminins, and specifically laminin γ1, a family of proteins on the surface of a cancer cell to which this virus binds, and which therefore act as the 'door' through which the virus enters the cells. The findings, which were published in the prestigious international journal Nature Communications, carry significant implications for the advancement of virus-based anticancer strategies and for the prediction of a patient's response to this innovative therapeutic approach.

Oncolytic viruses, such as the rat virus H-1PV, have the ability to selectively infect and kill tumour cells, inducing their lysis and stimulating an anticancer immune response, without however harming normal healthy tissues. Despite their notable clinical potential, their use as a standalone treatment does not currently result in complete tumour regression, mainly due to the varying degree of patient sensitivity and responsiveness. It is therefore important to be able to identify patients whose tumours display genetic characteristics that make them vulnerable to the virus and who are thus most likely to benefit from this novel anticancer therapy.

"In this context, we sought to elucidate the features of host cancer cells that enable oncolytic viruses to effectively infect and destroy them, focusing specifically on the factors required for cell attachment and entry", says Dr Antonio Marchini, leader of LOVIT and corresponding author of the publication.

Using a technique known as RNA interference, the research team progressively 'switched off' close to 7,000 genes of cervical carcinoma cells to detect those that negatively or positively modulate the infectious capacity of H-1PV. They thus identified 151 genes and their resulting proteins as activators and 89 as repressors of the ability of H-1PV to infect and destroy cancer cells. The team specifically looked at those genes that coded for proteins localised on the cell surface, in order to characterise their role in determining virus docking and entry. They found that a family of proteins called laminins, and particularly laminin γ1, play a crucial role in mediating cell attachment and penetration. Indeed, deactivating the corresponding LAMC1 gene in glioma, cervical, pancreatic, colorectal and lung carcinoma cells resulted in a significant reduction in virus cell binding and uptake, and in increased cancer cell resistance to virus-induced death. A similar effect was observed when switching off the LAMB1 gene encoding the laminin β1 protein.

"Essentially, laminins at the surface of the cancer cell are the 'door' that allows the virus to recognise its target, attach itself and penetrate into it, subsequently leading to its destruction. In particular, the virus interacts with a specific portion of the laminin, a sugar called sialic acid, which is essential for this binding and entry process and for infection", explains Dr Amit Kulkarni, first author of the publication.

The team went a step further and sought to assess the clinical implications of their findings for cancer patients. They found that laminins γ1 and β1 are differentially expressed across different tumours, being for instance overexpressed in pancreatic carcinoma and glioblastoma (GBM) cells compared to healthy tissues. Moreover, in brain tumours, their expression increases with tumour grade, with late-stage GBM displaying higher laminin levels than lower grade gliomas. Similarly, based on the analysis of 110 biopsies from both primary and recurrent GBM, the researchers reported significantly higher levels of laminins in recurrent GBM compared to primary tumours.

"These observations indicate that elevated laminin expression is associated with poor patient prognosis and survival in a variety of tumours, including gliomas and glioblastoma. The encouraging fact, however, is that cancers displaying high laminin levels are more susceptible to being infected and destroyed by the H-1PV virus and that patients with these tumours are therefore more likely to be responsive to this therapy", adds Dr Marchini.

These findings could lead to the classification of cancer patients according to their individual laminin expression levels, thereby acting as a biomarker that predicts their sensitivity and responsiveness to H-1PV-based anticancer therapies. This will in turn allow the design of more efficient clinical trials with reduced costs and approval times and, ultimately, the development of enhanced combinatorial treatments to tangibly improve patient outcomes.

The study was published in June 2021 in the renowned journal Nature Communications, with the full title "Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry".

Credit: 
Luxembourg Institute of Health

Strategies to speed global vaccine availability

NEW YORK (June 29, 2021)--In a new paper published in the journal Vaccine: X, public health experts from Columbia University Mailman School of Public Health, the University of Oslo, and Spark Street Advisors highlight actions to accelerate access to vaccines globally. The paper reviews the vaccine research and development process and proposes areas where reforms could increase access, speed time to market and decrease costs--from R&D to manufacturing and regulation to the management of incentives like patents and public funding.

The COVID-19 pandemic has highlighted the importance of vaccines as public health and pandemic preparedness tools and amplified the importance of issues ranging from equitable distribution to reliable supply of quality, affordable vaccines. Delays in time from the first dose in a high-income country to introduction at scale in a low-income country can take years. These delays are driven by several challenges, some of which are unique to the vaccine development ecosystem. The authors write that the patenting and overall intellectual property (IP) protection are complex, regulatory oversight is rigorous, manufacturing processes require technical support or know-how transfer from the innovator, and market dynamics create obstacles to delivering at scale. To address these challenges, the authors propose several opportunities to accelerate the availability of vaccines in low and middle-income countries:

Regulatory harmonization. Regulatory agencies around the world are increasingly recognizing the need to harmonize their approval process to enable efficiencies to save both time and money--something particularly important with regard to new technologies. For example, mRNA and DNA vaccines have the greatest potential of speeding the development processes and the recent approval of mRNA vaccine against COVID-19, brings promise for fully establishing regulatory pathways for these innovations. While mRNA vaccines do pose some challenges for low-income settings, in particular their requirement for ultra-cold storages, there are ongoing efforts to try to address this issue, including the establishment of a COVID-19 mRNA vaccine technology transfer hub.

Manufacturing capacity building. In order for vaccines to be deployed quickly and at scale, manufacturing capacity must be in place to allow for sufficient scale up when demand is high. Given the substantial know-how required, access to facilities is not enough; low-income countries and regions must also have sufficient know-how about manufacturing processes. This will require freedom to operate around patents and investment in technology transfer. To face the unprecedented need and opportunity for rapid and massive worldwide availability of COVID-19 vaccines, new business models have emerged with agreements between originator companies and manufacturing companies operating in different geographical and market environments.

Streamlined IP arrangements. With regard to IP arrangements, biopharmaceutical manufacturers and governments have made use of governmental compulsory licensing, patent oppositions, IP pools and voluntary IP licenses and technology transfer to advance access to new technologies. Although this has been limited in the field of vaccines, improving transparency and creating more streamlined IP arrangements, could contribute to increased diversity of supplier which will also help alleviate supply constraints.

"The COVID-19 outbreak and steps that have been taken to speed time to market could act as a catalyst for other vaccines," says senior author Nina Schwalbe, MPH, adjunct assistant professor of Population and Family Health. "While still very much a work in progress, the advancements demonstrated through the R&D of COVID-19 vaccines, give promise that many of the challenges to efficient and equitable vaccine development can be successfully addressed with adequate financing and political will."

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Columbia University's Mailman School of Public Health

More efficient tests may one day replace endoscopy

In two journal articles, a University of Houston biomedical researcher reports a step forward in diagnosing intestinal diseases, including colorectal cancer, ulcerative colitis and Crohn's disease using stool proteins. The current gold standard for colon cancer testing measures blood (hemoglobin) present in stool, and tests for inflammatory bowel disease (IBD) measure levels of calprotectin, a protein that detects inflammation in the intestines.

"The unique aspect of both research reports is that we are looking at stool samples comprehensively, and not just at one or two favorite molecules," said Chandra Mohan, Hugh Roy and Lillie Cranz Cullen Endowed Professor of biomedical engineering in the UH Cullen College of Engineering. "We are casting a wide net, and this has never been done before."

With colon cancer, typical fecal blood tests look for hemoglobin in stool samples. In Mohan's work, hemoglobin is just one of more than a thousand proteins being hunted.

"By the time you see blood, it might be too late, and there are other proteins that appear in the stool if someone has colon cancer, and they may appear much earlier than when the blood appears," reports Mohan in Nature Communications.

Using aptamer-based screening, Mohan and team screened 1,317 proteins searching for precursor biomarkers of colon cancer and found five elevated. Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising stool biomarkers of colorectal cancer, outperforming stool hemoglobin.

Aptamers are pieces of DNA that can be selected to bind to other molecules. They serve as bait, carefully selected for each protein they will try to detect. If the protein is present in the stool, it will bind to the aptamer in the library. If the protein is not present, it will be washed away.

"Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of colorectal cancer," said Mohan.

Mohan's research team includes Robert S. Bresalier, University of Texas MD Anderson Cancer Center; Nicholas Chia, Mayo Clinic; Hao Li and Kamala Vanarsa, University of Houston.

Predicting the Future with Markers for IBD

In the Journal of Gastroenterology, Mohan is reporting similar findings in early diagnosis of ulcerative colitis and Crohn's disease, finding several proteins elevated in pediatric patients with the disease after screening for 1300 proteins. Those proteins are stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1, all significantly elevated in both ulcerative colitis and Crohn's disease.

The team took samples from patients at four different time periods, allowing the researchers a rare window into disease progression.

"Using the new biomarkers, we can predict if the disease will become worse or if the intestines will become more inflamed. Stool proteins assayed at baseline can predict how the disease might progress in the weeks and months ahead," reports Mohan.

The IBD study represents the first use of the aptamer-based screen of stool samples in IBD, representing the largest-ever targeted stool proteomic study in IBD.

"We demonstrate the utility of comprehensive aptamer-based proteomic screens in identifying novel disease biomarkers for IBD that outperform the current gold standard, fecal calprotectin," said Mohan.

Mohan's hope is to replace the invasive endoscopy test by finding stool markers that can predict what is happening in the intestine without having to do endoscopy. Stool test for proteins can be done at home and through the mail.

On this paper, Mohan was joined by Subra Kugathasan from Emory University whose lab supplied the stool samples; Suresh Venkateswaran, Emory University; Sanam Soomro and Kamala Vanarsa, University of Houston.

Credit: 
University of Houston

IU researchers discover promising new way to prevent, treat kidney infections

INDIANAPOLIS - Ten IU School of Medicine researchers out of a team of 11 scientists, are responsible for the findings of a new study they conducted to investigate alternative ways to treat kidney infections. Their work, which is published in the high-quality research journal Nature Communications, examined how to utilize the kidneys' own internal infection fighting capabilities to treat and even prevent kidney infections, with the knowledge that eventually antibiotics won't work.

According to statistics, urinary tract infections or UTIs are one of the most frequent bacteria-causing infections affecting people of all ages. UTIs become more severe kidney infections, when the bacteria ascend from the bladder to the kidney. Kidney infections are common, occurring in 13 out of 10,000 females and 4 of 10,000 males every year. Kidney infections may cause high fevers, permanent kidney damage or even sepsis. Additional data suggests that cases of antibiotic resistant UTIs are surging, making the way for more UTIs to become the more serious kidney infections.

Specifically, the research team discovered that a type of cells within the kidney called "intercalated cells" both consume bacteria and secrete acid, which is a process - known as phagocytosis - and has historically been a capability only associated with white blood cells.

"If you were to increase white blood cell activity to treat an infection, you would affect a person's whole body. However, since we found these cells work the same way but are only present in the kidney, the long-term potential would be the ability to activate these cells to prevent or clear an infection from the kidney," said Andrew Schwaderer, MD, professor of pediatrics at IU School of Medicine, and one of the study's senior authors. "The idea is that with this approach we will eventually be able to replace or complement antibiotic therapy."

Intercalated cells exist at the exit to the kidney and can act as its guardians; the first to encounter and consume the bacteria as they invade the kidney from the bladder and then secrete the acid to neutralize it.

The researchers initially predicted this pathway using single-cell RNA sequencing available through the IU School of Medicine's Medical Genomics Core. Utilizing normal human kidney tissue, they were able to sequence each intercalated cell individually, allowing them to tell exactly what's going on in one cell type versus the other. When an advanced software analyzed the cells, phagocytosis capabilities of these cell was predicted as a leading function.

"It was also interesting that we started with human tissue as opposed to mouse models and then went back to the mouse, said Vijay Saxena, PhD and lead author of this study. "It's a very nonbiased way to study a cellular function and a very translational approach."

Utilizing IU School of Medicine's O'Brien Imaging Center, one of only three available in the world, allowed researchers the ability to image mice in real time, delivering live results. This approach is preferable to a cell culture system which may or may not reflect what happens in the human body.

Credit: 
Indiana University School of Medicine

A promising two-punch therapy for Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a rare cancer involving dendritic cells, a type of white blood cell that usually helps defend against infections. The current standard of care for LCH, chemotherapy, cures fewer than half of patients.

"Our research team focuses on identifying the causes of LCH so that we can develop better therapies for patients," said Dr. Rikhia Chakraborty, assistant professor of pediatrics - hematology and oncology at Baylor College of Medicine.

Most cells in LCH lesions are not abnormal dendritic cells but other invading immune cells, such as T cells, that are recruited to sites of disease. The contribution of T cells and other immune cells to LCH disease is not known. Chakraborty and her team at the Texas Children's Cancer Center Histiocytosis Program characterized the types of immune cells in LCH lesions and the activity of those cells.

"We wanted to understand the composition of the immune microenvironment in LCH and why the accessory immune cells are present," Chakraborty said. "Are they trying to help and can't? Or are they influenced by diseased dendritic cells to aggravate the situation?"

Understanding the immune microenvironment in LCH

There are two broad categories of T cells: one that battles and kills, called the cytotoxic T cells, and another that assists in keeping the immune system in check, called regulatory T cells. In a study published in the journal Blood, Chakraborty's team found that both cytotoxic and regulatory T cells are present in increased numbers in LCH lesions. However, the cytotoxic T cells are paralyzed -- a state called "exhaustion" -- and are ineffective in preventing LCH lesion formation.

Exhausted T cells are usually associated with a viral infection. After the infection is cleared, the immune system tells the T cells to stop fighting and retreat. As if raising a white flag of surrender, the T cells show a protein on their surface signaling that they are done fighting and are exhausted. In LCH, the diseased cells trick the T cells into entering the exhausted state by triggering programmed cell death protein 1 (PD-1) receptors, an immune checkpoint protein that turns the T cells off, preventing an attack on the cancer cells.

"These exhausted T cells are not permanently damaged," Chakraborty said. "If we can use therapies to turn off the PD-1 receptor, these T cells can overcome the exhaustion and the associated functional incapacitation."

Combining therapies shows promising results

Early studies treating LCH patients with drugs that block a growth pathway in LCH (MAPK pathway) have demonstrated rapid improvement of LCH lesions. However, responses may be incomplete, and lesions almost always grow back when treatment is stopped.

In the current study, Chakraborty and her team described a new therapeutic option for LCH directed at the inflammatory immune compartment. The new approach uses immunotherapy to target the PD-1 receptors that incapacitate T cells in combination with MAPK inhibition to target the dendritic cells that cause the disease. They hypothesized that this therapeutic combination would be more effective than either therapy on its own.

Using murine models of LCH developed in collaboration with Dr. Miriam Merad and her team at Icahn School of Medicine at Mount Sinai, the researchers measured the response to MAPK inhibitor treatment alone, anti-PD-1 treatment alone and the combination of the two treatments.

In models with the MAPK inhibitor treatment, the team observed a reduction in diseased LCH cells but not infiltrating T cells. In models with the anti-PD-1 treatment, the team observed the opposite--a reduction in infiltrating T cells but not the diseased LCH cells. But in the model using a combined therapy, Chakraborty's group saw a significant decrease in both diseased LCH cells and infiltrating T cells.

"We demonstrated that the combination therapy resulted in synergistic response with a significant decrease of disease burden when compared to either monotherapy," Chakraborty said. "The results are very encouraging and highlight combined MAPK and checkpoint inhibitors as a potential therapeutic strategy in future pre-clinical and clinical trials for LCH."

According to Chakraborty, clinical trials testing combination therapy could offer hope to patients whose disease has relapsed. The combination therapy could also help reduce toxicity seen with the current standard of care, she said.

Credit: 
Baylor College of Medicine

Gene therapy breakthrough offers hope to children with rare and fatal brain disease

Scientists and doctors at University College London Great Ormond Street Institute of Child Health (UCL GOS ICH) and Great Ormond Street Hospital (GOSH) have given hope of a gene therapy cure to children with a rare degenerative brain disorder called Dopamine Transporter Deficiency Syndrome (DTDS).

The team have recreated and cured the disease using state-of-the-art laboratory and mouse models of the disease and will soon apply for a clinical trial of the therapy. Their breakthrough comes just a decade after the faulty gene causing the disease was first discovered by the lead scientist of this work.

The results, published in Science Translational Medicine, are so promising that the UK regulatory agency MHRA has advised the researchers that they can now proceed to prepare for a clinical trial. DTDS is a rare, progressive and life-limiting neurological condition caused by a faulty gene that affects brain cells. Infants with DTDS are rarely able to learn to walk or speak and as they grow they develop 'parkinsonism', so called because of similarities to Parkinson's Disease.

This includes slow movements, involuntary twisting postures of their arms and legs and whole-body stiffness.

There are no effective treatments or a cure and most children with DTDS sadly die before reaching adulthood, often from respiratory infections or other complications. Although the condition is rare, with around 50 children worldwide currently known to doctors, it has previously been mistaken for cerebral palsy and may continue to be undiagnosed.

Professor Manju Kurian discovered the faulty gene causing DTDS in 2009 and was subsequently granted seed funding worth just over £86,500 from Great Ormond Street Hospital Children's Charity (GOSH Charity) to begin developing the treatment. Professor Kurian's team and her collaborators at UCL have also spent the last decade working to better understand the mechanisms that underpin this disease, and this has enabled them to develop a new, precision gene therapy with the potential to treat this devastating disorder.

How the precision gene therapy works

Scientists took skin cells from children with DTDS and turned them into stem cells, which can grow into any type of cell to build or repair different parts of the body. Professor Kurian's team, with work led by Dr Serena Barral, converted these stem cells into the exact brain cells (dopaminergic neurons) that carry the genetic 'fault' responsible for DTDS.

Using this laboratory model - or 'disease in a dish' - made directly from the cells of children with this rare condition, scientists were able to test the experimental gene therapy for DTDS and show that it could relieve the disease-related defects in DTDS brain cells.

The team used fluorescence microscopy to see what was happening in their 'disease in a dish'. The seemingly random pattern of colours in the untreated cells (left) shows how the neurons and their communicating 'arms' - called neurites - had not formed properly in cells with DTDS. The gene therapy treated cells form a much more obvious cluster pattern for the neuron - seen in white - with its red neurites, essentially showing the DTDS is cured in a laboratory model.

A further collaboration with UCL's Professor Simon Waddington and Dr Joanne Ng enabled the researchers to build on their 'disease in a dish' results, studying DTDS in mice and testing gene therapy as a cure. The gene therapy injects a modified, harmless virus containing the healthy gene into the area of the brain where this gene is missing. The mice were successfully cured of their symptoms including involuntary and disordered movements, progressive parkinsonism and weightloss. Based on the promising results of the laboratory tests, the next phase is to develop a clinicaltrial which would involve children diagnosed with DTDS.

22-year-old Shannon from Cornwall was one of the first patients diagnosed with DTDS after Professor Kurian discovered the faulty gene in 2009. Her mum, Judith said: "Shannon is a happy, bubbly girl and finds everything hilarious. DTDS meant Shannon suffered badly from shakes - she couldn't control her legs. She shakes very slightly now, but it's very mild."

On Shannon being one of the first patients in whom the faulty gene was discovered, Judith said, "It's amazing. The last time we saw Professor Kurian she said there had been a breakthrough with the research, but it hadn't been tried on anyone yet.

"GOSH is a brilliant hospital and I donate to the charity every month to help keep the extra support at the hospital going."

Professor Manju Kurian, Consultant Paediatric Neurologist at GOSH and NIHR Research Professor at UCL Great Ormond Street Hospital Institute of Child Health, co-lead author on this study and the scientist behind the discovery of this disease: "Our study provides real hope of an effective treatment for children who are living with this devastating, life-limiting brain disease, and it is hugely exciting to be at the stage of planning a clinical trial just ten years after discovering the gene that causes the condition.

"We hope this pioneering gene therapy will prevent the progression of this rare but cruel disease with a single procedure, giving children the improved quality and length of life that they deserve. If we can use gene therapy to treat children with this condition early enough, there is great potential for improvement in their health.

"We're hugely grateful to our funders including GOSH Charity who supported our research at the very beginning, as well as the Wellcome Trust, MRC, John Black Charitable Foundation, Robert Luff Foundation and Rosetrees for their investment; without their support we wouldn't be within touching distance of delivering a breakthrough cure that these children so desperately need."

Professor Simon Waddington, Professor of Gene Therapy at UCL, co-lead author on this study:

"Our whole working process has been guided by one principle: we want to find the answers for these children and how we can treat them. "The mice received the same carefully selected vector and delivery route that we plan to use in
treating the children. This careful selection has allowed us to progress rapidly to design a protocol so we can start the clinical trial next year.

"While DTDS is rare, we know that there are many other conditions we can model in this way, opening the door for a standardised approach to finding cures for these rare conditions."

Dr Kiki Syrad, Director of Grants and Impact at GOSH Charity, which provided funding early in the development of this treatment said: "At GOSH Charity we fund paediatric research to aid the discovery of desperately needed new treatments and cures for children living with rare diseases.

"We are absolutely delighted to see the progress that this study publication points to. It offers the hope of an effective treatment which could be nothing short of lifechanging for children and families living this with this rare, devastating condition. This is the hope that paediatric rare disease research can offer, and that's why we will continue to invest in trail-blazing projects such as this."

Credit: 
University College London

Young adult cancer survivors reluctant to get COVID vaccines

A new paper in JNCI Cancer Spectrum, published by Oxford University Press, indicates that many survivors of adolescent and young adult cancers hesitate to obtain COVID-19 vaccinations.

As of March 2021, there were over 33 million cases and 580,000 deaths from COVID in the United States. Vaccines offer the best hope to control the spread of COVID-19. Some 20%-40% of the US population, however, is hesitant to obtain COVID-19 vaccination. Cancer survivors often have weakened immune systems and are more likely to develop severe respiratory infections, making them particularly vulnerable to the threat of COVID-19.

National organizations recommend strongly that cancer survivors receive the COVID-19 vaccine. Cancer survivors are a priority vaccination group.

Researchers involved in the study aimed to identify sociodemographic factors associated with COVID-19 vaccine hesitancy among adolescent and young adult cancer survivors. Eligible participants were 18 years or older, diagnosed with cancer between the ages of 15 and 39, and received services through an adolescent and young adult cancer care program run by Huntsman Cancer Institute at the University of Utah and Intermountain Healthcare.

A total of 342 participants completed a cross-sectional survey. While 62.9% intended to get the COVID-19 vaccine, over one-third (37.1%) expressed COVID-19 vaccine hesitancy. Female survivors and survivors with a high school education or less reported greater vaccine hesitancy compared to their male or college graduate counterparts.

Some 42% of female young adult cancer survivors in the study indicated vaccine hesitancy (vs. 30.1% of males). Survivors with high school education or less had 3.15 times higher odds of reporting COVID-19 vaccine hesitancy compared to college graduates. Of Hispanic participants, 52.9% exhibited vaccine hesitancy, while 31.6% of White participants reported such hesitancy.

"As life returns to some resemblance of normal, receiving the COVID-19 vaccine is as important as ever," said Austin Waters, who led the study with a research team. "Cancer survivors should not wait to get the COVID-19 vaccine. Oncology care providers and cancer centers should play an important role in encouraging young survivors to receive the vaccine. To ensure equitable protection of vulnerable populations, special attention should be paid to vaccine hesitancy among at risk groups such as young adult cancer survivors and groups that may have higher vaccine hesitancy such as female survivors or those with a high school education or less."

The paper "COVID-19 Vaccine Hesitancy Among Adolescent and Young Adult Cancer Survivors" is available (at midnight on June 29th) at: https://doi.org/10.1093/jncics/pkab049

Credit: 
Oxford University Press USA

Worse outcomes observed after heart attacks during pandemic compared to previous year

Sophia Antipolis - 29 June 2021: Heart attacks during the COVID-19 pandemic were more likely to result in heart failure compared with heart attacks one year earlier, according to research presented today at Heart Failure 2021, an online scientific congress of the European Society of Cardiology (ESC).1

"Heart attack patients waited an average of 14 hours to get help during the pandemic, with some delaying for nearly two days. That compares to a delay of six hours in the previous year," said study author Dr. Ali Aldujeli of the Hospital of Lithuanian University of Health Sciences, Kaunas, Lithuania. "This gap may have been one contributor to the higher incidence of subsequent heart failure."

Urgent treatment for heart attacks is essential to restore the flow of oxygen-rich blood to the heart muscle. A longer duration of oxygen deprivation is associated with a greater area of damaged muscle and reduced pump function (called ejection fraction), which is a type of heart failure.

This study compared treatment delays, post-treatment ejection fraction, and decompensated heart failure hospitalisation rate in heart attack patients before versus during the COVID-19 pandemic.

The retrospective, multicentre study covered six out of ten administrative regions in Lithuania. The study included consecutive patients with acute myocardial infarction who received a negative test result for COVID-19 infection between 11 March and 20 April 2020 and underwent invasive treatment. The data were compared to patients admitted with the same diagnosis during the same period in 2019. Patients were followed up for six months following hospital discharge.

A total of 269 heart attack patients were evaluated in the study. There was a 34.0% decline in heart attack admissions during the early phase of the pandemic compared to the same period in 2019. Patients waited significantly longer before presenting to hospital during the pandemic compared to 2019 (a median of 858 versus 386 minutes, respectively).

Admission rates and delays were less pronounced for heart attacks with complete blockage of the heart arteries (ST-elevation myocardial infarction; STEMI) compared to non-STEMI. Admission rates fell by 22.1% for STEMI and 47.4% for non-STEMI. Patient delays more than doubled for STEMI patients during the pandemic and increased by more than fourfold for non-STEMI patients.

Dr. Aldujeli said: "Declines in admissions and delays in seeking treatment may be partly attributed to the extensive media coverage which amplified patients' fear of contracting COVID-19 and precluded them from seeking timely medical care. A possible explanation for the differences according to type of heart attack could be because STEMI patients tend to have more acute and intense symptoms compared to those with non-STEMI."

Post-treatment pump function was significantly lower during the pandemic compared to 2019. At six months, 22% of patients who had a heart attack during the pandemic were admitted to the hospital with decompensated heart failure compared to 2.5% in 2019.

When the authors examined the results by type of heart attack, they found that at six months, nearly one-third of patients (30%) who had non-STEMI during the pandemic were admitted to the hospital for decompensated heart failure compared to 1.3% in 2019. For STEMI, the corresponding proportions of admissions were 16.4% during the pandemic versus 3.5% in 2019.

Dr. Aldujeli said the outcomes according to type of heart attack may have been influenced by new pandemic-specific protocols implemented to prevent spread of the virus. Patients diagnosed with STEMI according to an electrocardiogram (ECG) were prioritised for urgent treatment (i.e. without waiting for a COVID-19 test result) and staff used personal protective equipment (PPE) during the procedure. Patients with non-STEMI were deemed less urgent and were isolated for around 24 hours while waiting for COVID-19 test results, which dictated whether staff needed PPE during the procedure or not.

Dr. Aldujeli said: "Our findings suggest that all heart attacks during a pandemic should be treated urgently with staff using PPE. More balanced media coverage is also needed so that patients do not wait to seek help in medical emergencies."

Credit: 
European Society of Cardiology

Study identifies biomarker that could help to diagnose pancreatic cancer

Researchers from Queen Mary University of London have identified a protein that could be used to aid in the diagnosis of pancreatic cancer.

Findings from the new study suggest that a protein called pentraxin 3 (PTX3) may be a specific diagnostic biomarker - or biological measure - for pancreatic cancer, with the ability to differentiate pancreatic cancer from other non-cancerous conditions of the pancreas.

The research was published today in npj Precision Oncology, and primarily funded by the Pancreatic Cancer Research Fund, Barts Charity and Cancer Research UK.

PTX3 levels elevated in patients with pancreatic cancer

In the study, researchers measured PTX3 levels in serum blood samples from patients with pancreatic ductal adenocarcinoma (PDAC) - the most common type of pancreatic cancer - and from healthy volunteers or patients with other non-cancerous conditions of the pancreas, and found levels of the protein to be significantly higher in the serum samples of those with PDAC.

Patients with PDAC had notably higher serum PTX3 levels than those with intra-ductal papillary mucinous neoplasm or chronic pancreatitis - two non-cancerous conditions that often present with similar symptoms to PDAC, making a definitive diagnosis more difficult.

Hemant Kocher, Professor of Liver and Pancreas surgery at Queen Mary University of London and consultant at Barts Health NHS Trust, who led the study, said: "In the clinic, computerised tomography (CT) scanning is usually used in the diagnosis of pancreatic cancer. Although CT can detect the presence of a pancreatic mass, it cannot distinguish pancreatic cancer from other non-cancerous pancreatic diseases. This poses frequent diagnostic dilemmas in clinical practice, and there are currently no clinically applicable biomarkers for the early detection of PDAC."

"The findings from our study suggest that PTX3 could be used as a biomarker to improve PDAC diagnosis, and warrants further testing to determine whether it could aid early detection of PDAC in the clinic."

"Thanks to the generous donation of samples from patients in London, Verona and Milan, our study represents a clinically relevant cohort with translational significance. This research has been made possible by an international collaboration of cancer biologists, surgeons, oncologists, clinical triallists, statisticians and bio-banking specialists, with funding from a number of sources."

Blood samples from 267 donors were analysed, including 140 samples from patients with PDAC, which had been donated to tissue banks in London, Verona and Milan. Samples in London were from the Pancreatic Cancer Research Fund Tissue Bank - the national tissue bank for pancreatic cancer.

The research was performed in collaboration with researchers from Humanitas Research Hospital and Humanitas University (Milan, Italy), including Dr Paola Allavena and Professor Alberto Mantovani (who also holds the Chair of Inflammation and Therapeutic Innovation at Queen Mary's William Harvey Research Institute), and ARC-NET Research Centre for Applied Research on Cancer (Verona, Italy), including Dr Aldo Scarpa. The Humanitas team is supported by the Italian Association for Cancer Research (AIRC).

A cancer biomarker released from non-cancerous cells

Most cancer biomarkers used in clinical practice are proteins released from the cancer cells themselves. One of the defining features of PDAC is that there are very few cancer cells; pancreatic cancer is surprisingly made up of mostly non-cancer cells, which have been co-opted by cancer to build a huge amount of scar tissue or stroma around the cancer, providing a strong defence for the cancer cells.

The unique feature of PTX3 is that this biomarker is released from non-cancerous cells such as stellate cells (star shaped cells) that surround the pancreatic tumour. Further analyses conducted by the team in human PDAC samples, pancreatic cancer cell lines and a mouse model of pancreatic cancer confirmed that PTX3 is, indeed, released predominantly from pancreatic stellate cells when they have been activated in response to signals from cancer cells.

By looking at data from clinical trials, the team found that when pancreatic cancer alone is targeted, PTX3 does not seem to change upon administration of chemotherapy; however, when medications targeting both cancer and stroma are administered, changes are seen in PTX3 levels. This change in PTX3 can be easily measured in blood to monitor how the drug is working. Thus, PTX3 may help in monitoring the effectiveness of treatment much earlier than scans may be able to indicate treatment response.

Stellate cells have an important role in normal tissue formation, and normal stellate cells do not seem to release PTX3. Stellate cells release PTX3 when they are 'activated,' which can occur in cancer or in response to other conditions. Therefore, further investigations are necessary to determine whether the PTX3 levels detected in this study are specific to stellate cell activation in PDAC.

Direction for future clinical trials

Pancreatic cancer is the deadliest of the common cancers and claims the lives of approximately 9,400 people each year in the UK. The majority of pancreatic cancer cases are diagnosed when the cancer is at an advanced stage due to a lack of specific symptoms at the early stages of the disease and the absence of specific biomarkers that can aid early detection.

This study suggests that PTX3 may be a sensitive and specific biomarker able to distinguish cancerous from non-cancerous conditions of the pancreas. The team hope the findings will provide direction for future prospective clinical trials to determine whether PTX3 could be effective in the clinic as a biomarker for early detection and, perhaps, used in conjunction with other biomarkers to monitor response to treatment of pancreatic cancer.

Maggie Blanks, CEO of Pancreatic Cancer Research Fund, said: "We're extremely pleased that the Pancreatic Cancer Research Fund Tissue Bank has been a valuable resource for this research. It's also exciting to learn that the project has found a new potential biomarker for both earlier detection and treatment monitoring and we look forward to hearing more about the team's progress."

Credit: 
Queen Mary University of London

Sunflower peptide as 'template' for potential analgesic

A naturally occurring peptide in sunflower seeds was synthetically optimised and has now been identified as a potential drug for treating abdominal pain or inflammation (in the gastrointestinal tract, abdominal area and/or internal organs). That is the finding of an international study led by Christian Gruber from MedUni Vienna's Institute of Pharmacology (Center for Physiology and Pharmacology), which was conducted jointly with the University of Queensland and Flinders University in Australia and has now been published.

The scientific aim of the study is to find analgesics that are only active in the periphery and do not cross the blood-brain barrier, as an alternative to commonly used synthetic opioids. Gruber explains the background: "Morphine was one of the first plant-based medicines and was isolated from the dried latex of poppies more than 200 years ago. It binds to opioid receptors in the brain and is still regarded as the main pillar of pain therapy. However, there is a high risk of opioid addiction, and an overdose - as a result of this strong dependency - inhibits the breathing centre in the brain, which can result in respiratory depression and, in the worst case, in death." For this reason, researchers throughout the world are trying to make analgesics safer and to find active drug molecules that do not have the typical opioid side-effects.

Sunflower extracts were to some extent used in traditional medicine for their anti-inflammatory and analgesic properties. In the current study, the scientists from Austria and Australia, primarily PhD student Edin Muratspahi?, isolated the plant molecule that may be responsible for this effect. Medicinal chemistry methods were then used to optimise the so-called sunflower trypsin inhibitor-1 (SFTI-1), one of the smallest naturally occurring cyclic peptides, by 'grafting' an endogenous opioid peptide into its scaffold.

A total of 19 peptides were chemically synthesized based on the original SFTI-1 blueprint and pharmacologically tested. "One of these variants turned out to be our lead candidate for as potential innovative analgesic molecule, especially for pain in the gastrointestinal tract or in the peripheral organs. This peptide is extremely stable, highly potent and its action is restricted to the body's periphery. Its use is therefore expected to produce fewer of the typical side-effects associated with opioids," point out Gruber and Muratspahi?.

The mode-of-action of the peptide is via the so-called kappa opioid receptor; this cellular protein is a drug target for pain relief, but is often associated with mood disorders and depression. The sunflower peptide does not act in the brain, hence there is much less risk of dependency or addiction. Furthermore, it selectively activates only the molecular signalling pathway that influences pain transmission but does not cause the typical opioid side-effects. The data of the animal model in the current study are very promising: the scientists see great potential for using this peptide in the future to develop a safe medication - which could be administered orally in tablet form - to treat pain in the gastrointestinal tract, and this drug could potentially also be used for related painful conditions, e.g. for inflammatory bowel disease.

Using Nature's blueprint

The research of this MedUni Vienna laboratory led by Christian Gruber exploits the concept of using Nature's blueprint to develop optimised drugs. "We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, with a view to testing them pharmacologically on enzymes or membrane receptors and ultimately utilizing them in the disease model," explains Gruber. Finally, potential drug candidates are chemically synthesised in a slightly modified form based on the natural blueprint, to obtain optimised pharmacological properties.

Credit: 
Medical University of Vienna

HKUST scientists develop simple blood test for early detection of Alzheimer's disease

image: HKUST's Vice-President (Research and Development) Prof. Nancy IP (Middle) and her research team members - including doctoral student Mr. Jason JIANG Yuanbing (second left) who is the first author of this research paper.

Image: 
HKUST

An international research team led by HKUST has developed a simple but robust blood test from Chinese patient data for early detection and screening of Alzheimer's disease (AD) for the first time, with an accuracy level of over 96%.

Currently, doctors mainly rely on cognitive tests to diagnose a person with AD. Besides clinical assessment, brain imaging and lumbar puncture are the two most commonly used medical procedures to detect changes in the brain caused by AD. However, these methods are expensive, invasive, and frequently unavailable in many countries.

Now, a team led by Prof. Nancy IP, Vice-President for Research and Development at HKUST, has identified 19 out of the 429 plasma proteins associated with AD to form a biomarker panel representative of an "AD signature" in the blood. Based on this panel, the team has developed a scoring system that distinguishes AD patients from healthy people with more than 96% accuracy. This system can also differentiate among the early, intermediate, and late stages of AD, and can be used to monitor the progression of the disease over time. These exciting findings have led to the development of a high-performance, blood-based test for AD, and may also pave the way to novel therapeutic treatments for the disease.

"With the advancement of ultrasensitive blood-based protein detection technology, we have developed a simple, noninvasive, and accurate diagnostic solution for AD, which will greatly facilitate population-scale screening and staging of the disease," said Prof. Nancy Ip, Morningside Professor of Life Science and the Director of the State Key Laboratory of Molecular Neuroscience at HKUST.

The work was conducted in collaboration with researchers at University College London and clinicians in local hospitals including the Prince of Wales Hospital and Queen Elizabeth Hospital. The discovery was made using the proximity extension assay (PEA) - a cutting-edge ultrasensitive and high-throughput protein measurement technology, to examine the levels of over 1,000 proteins in the plasma of AD patients in Hong Kong.

As the most comprehensive study of blood proteins in AD patients to date, the work has recently been published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, and has also been featured and actively discussed on different scholarly exchange platforms on AD research such as Alzforum.

AD, which affects over 50 million people worldwide, involves the dysfunction and loss of brain cells. Its symptoms include progressive memory loss as well as impaired movement, reasoning, and judgment. While patients often only seek medical attention and are diagnosed when they have memory problems, AD affects the brain at least 10-20 years before symptoms appear.

Credit: 
Hong Kong University of Science and Technology