Category: Uncategorized

Paving the Way to Safer Breast Cancer Treatment With C. Diff-derived Substances

Clostridioides difficile. Credit: CDC

New experimental evidence suggests that substances known as narrow-spectrum Wnt signaling inhibitors can suppressing breast cancer tumour growth in mice. These substances, which are derived from Clostridioides difficile bacteria, could have fewer side effects than existing treatments. Aina He of Shanghai Jiaotong University Affiliated Sixth People’s Hospital, China, and colleagues published these findings in the open access journal PLOS Biology.

While certain subtypes of breast cancer can be targeted with special medications, others can only be treated with standard chemotherapy. For some patients, chemotherapy may lead to the growth of stem cell-like cancer cells that are drug resistant. Previous studies suggest that medications that inhibit a specific biological process called Wnt signaling could potentially combat these cells, but so far, the potential benefits of Wnt signaling inhibitors have been hampered by their damaging side effects, particularly on bone density.

These side effects arise from the fact that humans have ten different versions of the Wnt signaling receptor, Frizzled, with distinct functions. Researchers have therefore recently developed new Wnt signaling inhibitors that could reduce side effects by targeting just three of these receptors. However, it has been unclear how effective these narrow-spectrum Wnt signaling inhibitors might be at treating cancer.

To shed new light, He and colleagues conducted a series of experiments with a specific narrow-spectrum Wnt signaling inhibitor known as TcdBFBD, which was derived from a toxin found naturally in the bacterial species Clostridioides difficile. They tested TcdBFBD in several different mouse models that mimic different types of breast cancer – basal-like and luminal-like – found in humans.

The researchers found evidence suggesting that TcdBFBD suppressed tumour growth and reduced the activity of stem cell-like cancer cells in the mice, without side effects on bone density. They also found evidence that TcdBFBD can synergise with the standard chemotherapy drug cisplatin to inhibit both basal-like and luminal-like breast cancer tumours in mice.

These findings provide preliminary evidence for the potential therapeutic promise of narrow-spectrum Wnt signaling inhibitors like TcdBFBD. However, more research will be needed to investigate their effectiveness in humans, examine how they might synergise with other cancer treatments beyond cisplatin, and explore their effects in additional types of cancer, such as serous ovarian cancer and oral squamous cell carcinoma.

The authors add, “A bacterial toxin fragment targets and suppresses breast cancer tumour-initiating and chemo-resistant cells.”

Source: Medical Xpress

Antibodies to Cow’s Milk Linked to Increased Cardiovascular Mortality Risk

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Sensitivity to common food allergens such as cow’s milk and peanuts could be an important and previously unappreciated cause of heart disease, new research suggests – and the increased risk for cardiovascular death includes people without obvious food allergies.

In a paper published in The Journal of Allergy and Clinical Immunology the authors show that the people who produced IgE antibodies to cow’s milk and other foods were at significantly increased risk of cardiovascular mortality. This was true even when traditional risk factors for heart disease, such as smoking, high blood pressure, and diabetes were accounted for. The strongest link was for cow’s milk, but IgE to other allergens such as peanut and shrimp were also significant among those who eat the foods.

This troubling finding represents the first time that IgE antibodies to common foods have been linked to increased risk of cardiovascular mortality, the researchers report. The findings do not conclusively prove that food antibodies are causing the increased risk, but the work builds on previous studies connecting allergic inflammation and heart disease. Corinne Keet, MD, PhD, paediatric allergy and immunology professor, led the work. She said: “People who had an antibody called IgE to foods that they regularly eat seemed to be at increased risk for dying from heart disease.”

“We were surprised by these findings because it is very common to have IgE to foods (about 15% of American adults have IgE to common food allergens), and most people don’t have any symptoms when they eat the food. As allergists, our thinking has been that it is not important if people have IgE to foods, as long as they don’t have symptoms when they eat the food,” said Keet, who is the corresponding author of the paper.

Funded by the National Institute of Allergy and Infectious Disease and an AAAAI Faculty Development Award to her collaborator Jeff Wilson at the University of Virginia, this research used two methods to examine the association between IgE sensitisation to foods and cardiovascular mortality. Data from 4,414 adults who participated in The National Health and Examination Survey (NHANES) and 960 participants in the Wake Forest site of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort were used. Participants were enrolled in MESA from 2000–2002 and followed for up to 19 years. Participants were enrolled in NHANES from 2005 to 2006 and data on mortality up to 14 years were tracked. Total and specific IgE was measured to cow’s milk, egg, peanut, shrimp, and a panel of aeroallergens for the NHANES group. IgE to cow’s milk, alpha-gal, peanut, dust mite and timothy grass were measured in the MESA group. In NHANES, 229 cardiovascular deaths were recorded and 960 deaths from MESA were also reported. Milk sensitisation was particularly associated in both NHANES & MESA. Researchers also discovered that food sensitisation to shrimp and peanut were both additional risk factors for heart disease.

It is also important to note that associations in the findings related to food sensitisation rather than clinical allergy. Although researchers did not have access to information about clinical food allergy in either cohort, they expect that individuals who report regularly eating a food allergen on food frequency questionnaires were not showing symptoms of a food allergy. Thus, the findings that showed how associations were strengthened when researchers excluded those who avoided the food suggest that these findings were most relevant to those who have not been diagnosed with food allergy. Keet says the results raise questions about whether these apparently non-allergic individuals may have long-term consequences from consuming foods to which they are sensitised.

The study states that aside from two recent reports linking IgE to the unusual carbohydrate allergen alpha-gal to coronary artery disease, cardiovascular disease had not previously been identified as a long-term complication of food sensitisation. However, there is now substantial evidence for the importance of allergic-type immune pathways in normal cardiac physiology and heart disease. Because discovering the link between milk sensitization with cardiovascular mortality is new, Keet says there’s more to explore as far as the relevance of food sensitization and diet in cardiovascular disease development.

“More research needs to be done about how sensitisation to common food allergens is related to cardiovascular disease,” she said. “While this study provides good evidence of an association between sensitization to these allergens and death from cardiovascular disease, there is much work to be done to understand if this is a causal relationship.”

Source: University of North Carolina

In Public Places, Bystanders are Less Likely to Start CPR on a Woman

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Bystanders are less likely to give cardiopulmonary resuscitation (CPR) to women than men, particularly if the emergency takes place in a public area, according to research presented at the European Emergency Medicine Congress. The study also shows that in private locations older people, especially older men, are less likely to receive CPR.

The researchers say that CPR saves lives and urge people to learn how to perform CPR and to give it without hesitation to anyone who needs it, regardless of gender, age or location.

The research was presented by Dr Sylvie Cossette, a PhD nurse researcher at the Montreal Heart Institute research center, Canada. She conducted the research with Dr Alexis Cournoyer, an emergency medicine physician and researcher at the Hôpital du Sacré-Coeur de Montréal, Canada.

Dr Cournoyer said: “In an emergency when someone is unconscious and not breathing properly, in addition to calling an ambulance, bystanders should give CPR. This will give the patient a much better chance of survival and recovery.”

Dr Cossette added: “We carried out this study to try to uncover factors that might discourage people from delivering CPR, including any factors that might deter people from giving CPR to a woman.”

The researchers used data from records of cardiac arrests that happened outside of hospital in Canada and the US between 2005 and 2015, including a total of 39 391 patients, average age 67. They looked at whether or not a bystander performed CPR, where the emergency took place, and the age and gender of the patient.

They found that only around half of patients received CPR from a bystander (54%). Overall, women were slightly less likely to be given CPR (52% of women compared to 55% of men).

However, when the researchers looked only at cardiac arrests that happened in a public place, such as the street, the difference was greater (61% of women compared to 68% of men). These lower rates of CPR in public were found in women regardless of their age.

When the researchers looked at cardiac arrests that happened in a private setting, such as a home, the data indicated that with every ten-year increase in age, men were around 9% less likely to be given CPR during a cardiac arrest. For women having a cardiac arrest in a private setting the chances of receiving CPR were around 3% lower with every ten-year increase in age.

Dr Cournoyer said: “Our study shows that women experiencing a cardiac arrest are less likely to get the CPR they need compared to men, especially if the emergency happens in public. We don’t know why this is the case. It could be that people are worried about hurting or touching women, or that they think a woman is less likely to be having a cardiac arrest. We wondered if this imbalance would be even worse in younger women, because bystanders may worry even more about physical contact without consent, but this was not the case.”

Dr Cossette said: “We would like to study this issue in greater detail to understand what lies behind the difference. This could help us make sure that anyone who needs CPR gets it, regardless of gender, age or location.”

Source: EurekAlert!

Antioxidants Boost Tumour Growth by Stimulating Blood Vessel Formation

In this image from a genetically engineered mouse model, lung cancer driven by the Kras oncogene shows up in purple. As a key driver in many types of cancer, the Kras gene makes a promising target for new cancer therapies. Credit: National Cancer Institute, National Institutes of Health

A new study from Karolinska Institutet shows that vitamin C and other antioxidants stimulate the formation of new blood vessels in lung cancer tumours. Published in The Journal of Clinical Investigation, this discovery corroborates the idea that dietary supplements containing antioxidants can accelerate tumour growth and metastasis.

“We’ve found that antioxidants activate a mechanism that causes cancer tumours to form new blood vessels, which is surprising, since it was previously thought that antioxidants have a protective effect,” says study leader Martin Bergö, professor and vice president of Karolinska Institutet in Sweden. “The new blood vessels nourish the tumours and can help them grow and spread.”

Antioxidants neutralise free oxygen radicals, which can damage the body, and are therefore commonly found in dietary supplements. But overly high doses can be harmful.

“There’s no need to fear antioxidants in normal food but most people don’t need additional amounts of them,” says Professor Bergö. “In fact, it can be harmful for cancer patients and people with an elevated cancer risk.”

Previously unknown mechanism

Professor Bergö’s research group has previously shown that antioxidants like vitamin C and E accelerate the growth and spread of lung cancer by stabilising a protein called BACH1. BACH1 is activated when the level of free oxygen radicals drops, which happens, for example, when extra antioxidants are introduced via the diet or when spontaneous mutations in the tumour cells activate endogenous antioxidants. Now the researchers have been able to show that the activation of BACH1 induces angiogenesis, the formation of new blood vessels .

While hypoxia is known to be required for angiogenesis to occur in cancer tumours, the new mechanism identified by the researchers demonstrates that tumours can form new blood vessels in the presence of normal oxygen levels as well. The study also shows that BACH1 is regulated in a similar way as the HIF-1α protein – a mechanism that was awarded the 2019 Nobel Prize in Physiology or Medicine and that allows cells to adapt to changes in oxygen levels. HIF-1α and BACH1 work together in the tumours, the new research shows.

Hoping for more effective drugs

“Many clinical trials have evaluated the efficacy of angiogenesis inhibitors, but the results have not been as successful as anticipated,” says Ting Wang, doctoral student in Professor Bergö’s group at Karolinska Institutet. “Our study opens the door to more effective ways of preventing angiogenesis in tumours; for example, patients whose tumours exhibit high levels of BACH1 might benefit more from anti-angiogensis therapy than patients with low BACH1 levels.”

The researchers used a range of cell-biological methods and concentrated most of their work on lung cancer tumours by studying organoids, as well as mice and samples of human breast and kidney tumours. Tumours in which BACH1 was activated, either via ingested antioxidants or by overexpression of the BACH1 gene, produced more new blood vessels and were highly sensitive to angiogenesis inhibitors.

“The next step is to examine in detail how levels of oxygen and free radicals can regulate the BACH1 protein, and we will continue to determine the clinical relevance of our results,” says Ting Wang. “We’ll also be doing similar studies in other cancer forms such as breast, kidney and skin cancer.”

Source: Karolinska Institute

Ciprofloxacin-resistant E. coli Incidence Grows Despite Slashed Prescriptions

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A US study found that, despite prescriptions for the antibiotic ciprofloxacin dropping by two-thirds between 2015 and 2021, the rates of ciprofloxacin-resistant E. coli bacteria circulating in the community did not decline.

In fact, a study of women over age 50 who had not taken any antibiotics for at least a year discovered that the incidence of gut-colonising ciprofloxacin-resistant E. coli actually increased. About 1 in 5 women in the study were affected.

Scientists at the University of Washington School of Medicine, Kaiser Permanente Washington Health Research Institute and Seattle Children’s Hospital conducted the study. Their findings appear in Communications Medicine.

Their results are consistent with theoretical models indicating that, once a drug-resistant form of E.coli emerges, it will continue to spread by taking up long-term residence in individuals’ gut microbiomes. E. coli is among an alarming number of disease-causing bacteria that have become resistant to several types of antibiotics. Resistance means that the antibiotics can’t kill the bacteria.

Pathogenic E. coli from the gut occasionally enters the urinary tract opening and causes infections. The female pelvic anatomy makes women more vulnerable to these mobile bacteria. Postmenopausal women are especially susceptible to severe, drug-resistant infection. Some drug-resistant E. coli infections are associated with considerable risk of hospitalization and death from sepsis.

Urinary tract infections from antibiotic-resistant E. coli can be frustrating to treat, even with third-generation cephalosporins, the newer types of antibiotics that are being prescribed more frequently for some populations of patients. Resistance to cephalosporins among ciprofloxacin-resistant E. coli also rose between 2015 and 2021.

Ciprofloxacin and similar drugs in its class were once the most prescribed antibiotic for urinary tract infections. In 2015, recommendations from the Centers for Disease Control and Prevention, Food and Drug Administration and Infectious Disease Society of America discouraged broad use of this class of drugs for uncomplicated urinary tract infections, partly due to rising resistance.

“However, it appears to be questionable whether a reduction in antibiotic use can be effective in reducing the rates of resistance in E. coli infections,” the research paper’s authors noted.

“Evidence from studies such as this one may be changing lots of paradigms on how to fight the rise in antibiotic resistance,” said physician scientist Dr. Evgeni V. Sokurenko, professor of microbiology at the University of Washington School of Medicine, who headed this latest research.

In the study, the scientists examined participants’ positive samples to determine which antibiotic-resistant strains of E. coli were present.

They found that the rate of a particularly virulent strain, ST1193, rose during the study period. Together with E. coli strain ST131-H30, these strains are the major causes of a global pandemic of multi-drug-resistant urinary tract infections among all women.

If ST1193 makes its home in more people’s guts, the situation could lead to more urinary tract infections with this more virulent strain, regardless of the curbing of fluoroquinolones prescriptions.

Another strain with a troubling increase in the participant samples was ST69, known to more frequently cause urinary tract infections in children.

tize discovering better ways to control drug-resistant E. coli’s ability to colonize the gut before it causes these infections, the authors wrote. They mentioned potential strategies of deploying probiotic bacteria and anti-bacterial viruses (bacteriophages).

The researchers added that these approaches might be offered to high-risk patients or deployed against the most clinically relevant strains. More investigation is needed on the epidemiology and ecology of antibiotic-resistant gut E. coli, they said, to help determine how these bacteria skillfully colonize human guts and how to target them most effectively to reduce antibiotic-resistant infections.

Source: University of Washington School of Medicine/UW Medicine

Cluster of Slightly High Traits Linked to Cardiovascular Risk

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Middle-aged adults with three or more unhealthy traits including slightly high waist circumference, blood pressure, cholesterol and glucose have heart attacks and strokes two years earlier than their peers, according to research presented at ESC Congress 2023.1

“Many people in their 40s and 50s have a bit of fat around the middle and marginally elevated blood pressure, cholesterol or glucose but feel generally well, are unaware of the risks and do not seek medical advice,” said study author Dr Lena Lönnberg. “This scenario, called metabolic syndrome, is a growing problem in Western populations where people are unknowingly storing up problems for later in life. This is a huge missed opportunity to intervene before heart attacks and strokes that could have been avoided occur.”

It is estimated that up to 31% of the global population has metabolic syndrome.2 Previous studies have shown that people with metabolic syndrome are at higher risk of diabetes, heart disease, stroke and premature death.3-5 This study investigated the link between asymptomatic metabolic syndrome in midlife and cardiovascular disease and death up to three decades later.

The study enrolled 34 269 adults in their 40s and 50s who attended a cardiovascular screening programme in 1990 to 1999, where participants underwent clinical examination. They also completed a questionnaire about lifestyle habits, previous history of cardiovascular disease and diabetes, and socioeconomic factors such as education.

Individuals were classified as having metabolic syndrome if they had three or more of the following: 1) waist circumference of 102cm+ for men and 88cm+ for women, 2) total cholesterol 6.1mmol/L or above, 3) 130mmHg or higher systolic blood pressure and/or 85mmHg or higher diastolic blood pressure, 4) fasting plasma glucose 5.6mmol/L or higher.

Participants with metabolic syndrome were matched for age, sex and date of health examination to two individuals without metabolic syndrome who served as controls. Data on cardiovascular events (myocardial infarction and stroke) and death were collected from national and local registers. The researchers analysed the associations between midlife metabolic syndrome and nonfatal cardiovascular events and all-cause mortality after adjusting for age, sex, smoking, physical inactivity, education level, body mass index, hip circumference and living alone or with family.

A total of 5084 individuals (15%) met the criteria for metabolic syndrome and a control group of 10 168 individuals without metabolic syndrome was identified. Some 47% of participants were women. During a median follow-up of 27 years, 1317 (26%) participants with metabolic syndrome died compared with 1904 (19%) controls – meaning that those with metabolic syndrome were 30% more likely to die during follow-up than their counterparts without metabolic syndrome.

Non-fatal cardiovascular events (myocardial infarction and/or stroke) occurred in 1645 (32%) participants with metabolic syndrome and 2321 (22%) controls, corresponding to a 35% greater risk of heart attack and stroke in the metabolic syndrome group. The median time to the first non-fatal heart attack or stroke was 16.8 years in the metabolic syndrome group and 19.1 years in the control group, a 2.3 year difference.

Dr. Lönnberg said: “As metabolic syndrome is a cluster of risk factors, the level of each individual component does not have to be severely raised. In fact, most people live with slightly raised levels for many years before having symptoms that lead them to seek health care. In our study, middle-aged adults with metabolic syndrome had a heart attack or stroke 2.3 years earlier than those without the collection of unhealthy traits. Blood pressure was the riskiest component, particularly for women in their 40s, highlighting the value of keeping it under control.”

She concluded: “The results underline the importance of early detection of risk factors through health screening programmes so that preventive actions can be taken to prevent heart attack, stroke and premature death. As a general rule of thumb, even if you feel well, check your blood pressure every year, avoid smoking, keep an eye on your waist circumference and last, but definitely not least, be physically active every day.”

Source: European Society of Cardiology


1The abstract “Early screening for metabolic syndrome opens a window of opportunity learnings from a long-term, population-based study” will be presented during the session Risk factors and prevention: epidemiology (2) which takes place on Friday 25 August from 09:15 to 10:00 CEST at Station 10.

2Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, et al. Geographic distribution of metabolic syndrome and its components in the general adult population: A meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022;188:109924.

3Lind L, Sundström J, Ärnlöv J, et al. A longitudinal study over 40 years to study the metabolic syndrome as a risk factor for cardiovascular diseases. Sci Rep. 2021;11:2978.

4Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288:2709-2716.

5Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care. 2005;28:1769-1778.

Deadline for Public Comments on NHI Bill Pushed Back

The Select Committee on Health and Social Services has extended the deadline for public comments on the contentious National Health Insurance (NHI) Bill by two weeks, according to a report from Business Insider. In its announcement, the Committee said that it had received numerous requests from stakeholders to extend the date on written submissions for the act.

The committee has therefore extended the deadline from Friday, 1 September 2023 to Friday, 15 September 2023. The Bill is already before the National Council of Provinces (NCOP) after being passed by Parliament in June, in spite of vehement opposition. Once past the NCOP, which seems all but assured given its stubborn progress, it will then be sent to President Cyril Ramaphosa to be signed into law.

Contact details to submit enquiries or written submissions are at the end of the article.

Controversy continues unabated

An unrelenting barrage of criticism has been directed at the Bill, which so far has shown little change in response and according to many its constitutionality is questionable. While stakeholders are generally for universal healthcare and the idea of an NHI, the current public healthcare system is already under dire pressure, being underfunded, under-resourced in terms of skilled professionals and equipment, and riddled with corruption.

Indeed, South Africa would be the first country in the world to completely bring all healthcare. The fact that other countries with better governance track records and more resources have not done so has been brought up as a red flag.

Another is the vague notion that the government will pay for the scheme somehow – which inevitably means reaching into taxpayers’ wallets. The estimated cost of R300 billion and R660 billion a year will be by far the largest single government expense in a time of shrinking funds.

“Looking at 2026 – the year in which the NHI is supposed to be implemented – an enormous extra R296 billion will be required in order to balance the books,” the Solidarity Research Institute (SRI) said.

“This is unheard of for a middle-income country, where spending on education usually enjoys the highest priority. While more affluent countries spend more on healthcare, social grants usually receive the highest priority, never health,” said the SRI.

Options to foot the bill range from a staggering 40% surcharge on income tax to a payroll tax of 13.4%, which Professor Alex van den Heever criticised as being “incredibly naïve set of fiscal proposals that you cannot even consider implementing.” Discovery Health CEO Ryan Noach warned of a tax revolt if the government attempts to pay for this.

Practical allternatives on offer include a public-private partnership as envisaged by Business Leadership South Africa CEO Busi Mavuso.

Enquiries, as well as written submissions, can be directed to Ms M Williams, Select Committee on Health and Social Services, e-mail

Measuring Heart Rate from Facial Colour Changes

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Scientists have for a long time tried to develop contactless heart rate monitoring, such as using cameras to measure subtle colour changes in the face from blood flow, but have been hampered by noise artefacts. Now, Japanese researchers have developed a way to pick up a clean signal by taking advantage of the pulse’s characteristic rhythm.

In the past decade or so, researchers tried to develop contactless heart rate (HR) measuring which avoids the discomfort and dermatitis risk of physical contact. An example is cameras that focus on the blood volume pulse (BVP), that causes slight temporal changes in facial skin colour captured in videos and which can be used for HR estimation. However, due to the small magnitude of these colour changes, the accuracy of HR estimation is adversely affected by facial movements, ambient lighting variations, and noise.

To address these challenges, a team of researchers from Japan have now developed a novel method that leverages the temporal characteristics of the blood pulse. Importantly, it builds on the ability of the pulse to exhibit quasi-periodic behaviour, which distinguishes it from noise artefacts. The study was led by Dr Yoshihiro Maeda, Junior Associate Professor, from the Department of Electrical Engineering at the Tokyo University of Science and is published in the journal IEEE Access.

The proposed method uses dynamic mode decomposition (DMD), a technique that analyses spatio-temporal structures in multi-dimensional time-series signals. It also employs adaptive selection of the optimal spatio-temporal structure based on medical knowledge of HR frequencies. “Our method, unlike previous applications of DMD, effectively models and extracts the BVP signal by incorporating physics-informed DMD in a time-delay coordinate system, taking into account the nonlinearity and quasi-periodicity of the BVP dynamics,” explains PhD student Kosuke Kurihara.

The proposed method relies solely on tracking time-series data from videos of a person’s face, eliminating the need for any attached detectors on the person’s body. In this method, the video time-series of the face, monitoring continuous changes, are converted into RGB time-series signals, which helps in extracting information of blood volume changes occurring beneath the skin. After effectively dealing with noise or misinformation that might creep into the data, the observed RGB signals are then converted to pulse wave information data.

Using the DMD method in a time-delayed coordinate system with conservative dynamics modeling, pulse waves containing major and accurate information can be extracted to estimate HR.

To demonstrate the efficacy of this method, the researchers used 67 facial videos from three publicly available datasets. The results of this method were then compared with other non-contact HR estimation methods. Interestingly, the proposed method adaptively selects the dynamic mode that contains the most pulse wave components, based on the knowledge of the typical range of pulse wave components. As a result, the method showed a 36.5% improvement in estimation accuracy compared to conventional methods, especially in scenes with ambient light fluctuations.

“This achievement is expected to play a significant role as a fundamental technology for vital monitoring systems in the medical and fitness fields. The breakthrough contactless method holds great potential for non-contact heart rate estimation in various applications, such as remote health monitoring and physiological assessments,” concludes Dr Maeda. Further research will be needed to explore techniques that incorporate multispectral information, which can contribute to reducing noise and improving the accuracy of the method.

Source: Tokyo University of Science

US Officials Discover Illegal Biological Laboratory inside Warehouse

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Authorities in the US have shut down what seems to be an illegal biological lab in California. Hidden inside a warehouse, the lab held nearly 1000 lab mice, around 800 unidentified chemicals, refrigerators and freezers, thousands of vials of biohazardous materials such as blood, incubators, and at least 20 infectious agents, including SARS-CoV-2, HIV, and a herpes virus. The lab’s owners claim they were developing COVID testing kits.

NBC News affiliate KSEE of Fresno reported that the authorities first cottoned on to the lab when a local official noticed an illegal hosepipe connection, prompting a warrant to search the building, which was only supposed to be used for storage.

Officials first inspected the warehouse in Reedley City, Fresno County on March 3, court documents reveal. It was only on March 16 when local health officials conducted their own inspection – and they were shocked to discover the true nature of the warehouse’s contents and operations.

Reedley City Manager Nicole Zieba told KSEE, “This is an unusual situation. I’ve been in government for 25 years. I’ve never seen anything like this.”

“Certain rooms of the warehouse were found to contain several vessels of liquid and various apparatus,” court documents read. “Fresno County Public Health staff also observed blood, tissue and other bodily fluid samples and serums; and thousands of vials of unlabeled fluids and suspected biological material.”

Chemicals and equipment were also haphazardly stored with furniture. They also discovered nearly a thousand mice; more than 175 were already dead and 773 were euthanised.

The tenant was found Prestige BioTech, which was not licensed for business in California. The company president was identified as Xiuquin Yao, whom officials questioned via email. Prestige BioTech had moved assets from a now-defunct medical technology company which had owed it money.

Prestige Biotech is accused of not having the proper permits and disposal plans for the equipment and substances, and would not explain the laboratory activity at the warehouse.

“I’ve never seen this in my 26-year career with the County of Fresno,” said Assistant Director of the Fresno County Department of Public Health Joe Prado.

“Through their statements that they were doing some testing on laboratory mice that would help them support, developing the COVID test kits that they had on-site,” Prado said.

Zieba also commented that this was only part of the investigation. “Some of our federal partners still have active investigations going. I can only speak to the building side of it,” Zieba said.

Further attempts to contact Yao for comment have been unsuccessful.

Antipsychotic Drugs Work Differently than Previously Believed, Study Finds

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Antipsychotic drugs, used to treat schizophrenia, have many unpleasant side effects and are also ineffective for many patients, so new drugs are needed. New research published in Nature Neuroscience has discovered that antipsychotic drugs, which inhibit the overactive dopamine causing the symptoms of schizophrenia, interact with a completely different neuron than originally believed.

This new finding from Northwestern Medicine scientists provides a new avenue to develop more effective drugs to treat the debilitating symptoms of schizophrenia. Traditionally, researchers have screened antipsychotic drug candidates by evaluating their effects on mouse behaviour, but the approach used by a Northwestern lab outperformed these traditional approaches in terms of predicting efficacy in patients.

“This is a landmark finding that completely revises our understanding of the neural basis for psychosis and charts a new path for developing new treatments for it,” said lead investigator Jones Parker, assistant professor of neuroscience at Northwestern University Feinberg School of Medicine. “It opens new options to develop drugs that have fewer adverse side effects than the current ones.”

Individuals with schizophrenia have increased levels of dopamine in a region of the brain called the striatum. This region has two primary types of neurons: those with either D1 or D2 dopamine receptors.

Dopamine is a key for both receptors, but antipsychotics only block the D2 receptor locks. Therefore, experts have assumed these drugs preferentially act on neurons that express the D2 receptor locks. But, in fact, it was the other brain cells – the neighbouring ones in the striatum with D1 receptors – that responded to antipsychotic drugs in a manner that predicted clinical effect.

“The dogma has been that antipsychotic drugs preferentially affect striatal neurons that express D2 dopamine receptors,” Parker said. “However, when our team tested this idea, we found that how a drug affects the activity of D2 receptor-expressing striatal neurons has little bearing on whether it is antipsychotic in humans. Instead, a drug’s effect on the other striatal neuron type, the one that expresses D1 dopamine receptors, is more predictive of whether they actually work.”

Schizophrenia is a debilitating brain disorder that affects approximately 1 in 100 people. While existing antipsychotics are effective for the hallmark symptoms of schizophrenia such as hallucinations and delusions, they are ineffective for the other symptoms of schizophrenia such as deficits in cognitive and social function.

Moreover, current antipsychotics are completely ineffective in more than 30% of patients with treatment-resistant schizophrenia. The use of these drugs also is limited by their adverse effects, including tardive dyskinesia and parkinsonism.

The new study for the first time determined how antipsychotic drugs modulate the region of the brain thought to cause psychosis in living animals.

“Our study exposed our lack of understanding for how these drugs work and uncovered new therapeutic strategies for developing more effective antipsychotics,” Parker said.

Source: EurekAlert!