New survey reveals majority of European dietitians believe moderate coffee consumption has clear health benefits

Reports and Proceedings

KAIZO

 

VIDEO: A NEW REPORT BY THE EUROPEAN FEDERATION OF THE ASSOCIATIONS OF DIETITIANS (EFAD), SUPPORTED BY THE INSTITUTE FOR SCIENTIFIC INFORMATION ON COFFEE (ISIC), REVEALS MAJORITY OF EUROPEAN DIETITIANS BELIEVE MODERATE COFFEE CONSUMPTION HAS CLEAR HEALTH BENEFITS. view more 

CREDIT: EFAD, SUPPORTED BY ISIC

• 62% believe drinking coffee in moderation has clear health benefits
• 86% agreed that regular, moderate intake of coffee improves alertness and 67% agreed that coffee consumption is associated with an improvement in overall sports performance
• However, gaps in knowledge were identified regarding the associations between coffee intake and key non-communicable diseases

Tuesday 22nd November: A new report by the European Federation of the Associations of Dietitians (EFAD), supported by the Institute for Scientific Information on Coffee (ISIC), has revealed that almost two thirds (62%) of European dietitians believe drinking coffee in moderation has clear health benefits, with 86% agreeing that regular moderate intake can improve alertness and 69% agreeing that regular, moderate intake is associated with an improvement in overall sports performance.

The survey was completed by 585 dietitians from across 26 European countries who have direct contact with patients/clients, and provides new insights on current awareness and attitudes to coffee consumption from a healthcare perspective.

With over 2 billion cups of coffee being enjoyed around the world every day1, emerging research into its prospective role in health has suggested a possible ‘protective effect’ in relation to a number of non-communicable diseases, particularly those with an inflammatory component2. Whilst a detailed understanding of the exact association remains unclear, coffee continues to be an important consideration for healthcare professionals when considering aspects of a health lifestyle.  

Key insights from the survey of European dietitians include:

• The majority of dietitians (62%) believe that moderate coffee consumption has some clear health benefits, but the potential associations between coffee consumption and health are not widely known by the general public

• Coffee remains a popular beverage throughout Europe, with 43% reporting patient’s consuming up to 3 cups a day and 3-5 cups a day, respectively, intake levels that are in line with current European Food Safety Authority’s (EFSA) recommendations3
• 62% of dietitians surveyed acknowledged a positive association with aspects of mental and physical performance, including improved alertness (86%), improved mood (61%), improvement in overall sports performance (69%) and agreed that coffee may be beneficial prior to exercise (51%). These findings reflect a previous ISIC consumer survey conducted during the lockdown of 20204
• The associations between coffee intake and key non-communicable diseases are not as well known, with only 36% positively associating moderate coffee consumption with a reduced risk of cardiovascular disease (CVD), 30% with reduced risk of type 2 diabetes and 42% with a reduced risk of neurodegenerative conditions. This is in contrast to the weight of scientific evidence that suggests potential beneficial effects across all three disease areas5-9 much of which is summarised at coffeeandhealth.org
• Caution in the level of consumption was observed in some populations, including those living with GI disorders (54%). Current research in relation to GI disorders shows no association between coffee intake and a number of gastric complaints10,11. Further research also suggests the polyphenols present in coffee may induce positive changes in the composition of the ‘good bacteria’ that supports the immune system12

To read the full report, titled “European dietitians’ perspectives on coffee consumption”, click here.

-ENDS-

Notes to editors

• Of 585 recipients, 329 reported being currently employed in clinical services, including oncology, diabetes, weight management, gastroenterology, geriatrics, paediatrics, critical care, inpatient services, surgery, allergy and food intolerance. The remaining 256 reported current employment in sports, education, wellbeing, food services and/or are freelance
• Countries included, Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Luxembourg, Netherlands, North Macedonia, Poland, Portugal, Romania, Slovenia, Spain, Sweden, Switzerland, Turkey and the UK
• European Food Safety Authority’s (EFSA) Scientific Opinion on the Safety of Caffeine states that 400mg of caffeine (approximately 3-5 cups of coffee) per day can be considered safe for most adult individuals. A cup of coffee typically provides around 75mg caffeine per day
• ISIC press office team contact information: isic.kaizo@kaizo.co.uk 

About EFAD

Established in 1978. The European Federation of the Associations of Dietitians (EFAD) is a not-for-profit organisation that aims to be ‘The Voice of European Dietetics’, by supporting the leadership role of registered dietitians in positively impacting the nutritional health of their clients, patients and the wider community and ensuring every European citizen has access to safe and appropriate dietary and nutritional interventions.

EFAD members represent more than 35,000 registered dietitians, across 28 European countries. As well as a further 40 education associate members from two further EU countries.

For more information about the important work of EFAD, please visit efad.org.

About ISIC

The Institute for Scientific Information on Coffee (ISIC) is a not-for-profit organisation founded in 1990. ISIC is devoted to the study and disclosure of science related to coffee and health, including:

• Study of scientific matters related to coffee and health
• Evaluation of studies and scientific information about coffee and health
• Support of independent scientific research on coffee and health
• Dissemination of balanced coffee and health scientific evidence and knowledge to a broad range of stakeholders

ISIC respects scientific research ethics in all its activities and all of ISIC’s communications are based on sound science and rely on scientific studies derived from peer-reviewed scientific journals and other publications.

ISIC members are six of the major European coffee companies: illycaffè, Jacobs Douwe Egberts, Lavazza, Nestlé, Paulig, and Tchibo.

For more information about ISIC and to view the latest research into coffee, caffeine and health, please visit our new website www.coffeeandhealth.org.

Follow us on twitter: @coffeeandhealth.

References    

1. British Coffee Association (BCA). (2022). Coffee is the most popular drink worldwide with around two billion cups consumed every day. Available at: https://britishcoffeeassociation. org/coffee-consumption/.
2. Ribeiro M, et al. (2022). The magical smell and taste: Can coffee be good to patients with cardiometabolic disease? Critical Reviews in Food Science and Nutrition. DOI: 10.1080/ 10408398.2022.2106938.
3. European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition and Allergies (NDA). (2015). Scientific Opinion on the safety of caffeine. EFSA Journal. 13(5):4102.
4. Institute for Scientific Information on Coffee (ISIC). (2022). Legacy of lockdown on mental wellbeing and the role of coffee to support mood. Available at: https://www. coffeeandhealth.org/information-campaign/legacy-of-lockdown-on-mental-wellbeing-and-the-role-of-coffee-to-support-mood.
5. Crippa A, et al. (2014). Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol. 180(8):763-75.
6. Carlstrom M & Larsson SC. (2018). Coffee consumption and reduced risk of developing type 2 diabetes: a systematic review with meta-analysis. Nutr Revs. 76(6):395-417
7. Rodriguez Artalejo F & Lopez Garcia E. (2017). Coffee consumption and cardiovascular  disease: a condensed review of epidemiological evidence and mechanisms. J Agric Fd Chem. 66(21):5257-63.
8. O’Keefe JH, et al. (2018). Coffee for cardioprotection and longevity. Prog Cardiovasc Dis. 61(1):38-42
9. Nehlig A. (2016). Effects of coffee/caffeine on brain health and disease: What should I tell my patients? Pract Neurol. 16(2):89-95.
10. Boekema PJ. (1999). Coffee and gastrointestinal function: facts and fiction. A review. Scand J Gastroenterol. 230:35-9.
11. Shimamoto T, et al. (2013). No association of coffee consumption with gastric ulcer, duodenal ulcer, reflux esophagitis, and non-erosive reflux disease: a cross-sectional study of 8,013 healthy subjects in Japan. PLoS One. 8(6):e65996.
12. Nehlig A. (2022) Effects of coffee on the gastro-intestinal tract: a narrative review and literature update. Nutrients.14(2):399.

New insight into how long-banned chemicals (PCBs) unleash their toxicity inside the body

Peer-Reviewed Publication

KOBE UNIVERSITY

 

IMAGE: THE BASIC STRUCTURE OF A POLYCHLORINATED BIPHENYL (PCB) view more 

CREDIT: HIDEYUKI INUI

Polychlorinated biphenyls (PCBs) (*1) were widely used in industrial and commercial products including plastics, paints, electronic equipment and insulating fluids. Their manufacture was extensively banned from the late 70s onwards due to their toxicity, however large amounts still remain in our environment and accumulate inside animals’ bodies.

Chiral PCBs (*2) are PCBs that have two mirror-image isomers (*3); these isomers are identical reflections of each other with the same composition. Chiral PCBs are particularly dangerous because they have more chlorine atoms, which are hard for the body to break down, so they can accumulate in the body easily and their isomers are metabolized differently, causing isomer-specific toxicity (particularly neurodevelopmental issues). However, the process behind this selective metabolism was not known. To address this, a research group has illuminated how enzymes produced by the body unevenly metabolize the mirror-image isomers. These results will make it possible to estimate PCB metabolism and detoxification pathways in animals. They will also contribute towards the development of technology to make predictions about chiral PCBs’ mirror isomers, so that we can obtain a better understanding of potential toxicity in humans and other mammals.

These findings were made by a multi-institutional research collaboration, which included Associate Professor INUI Hideyuki (Kobe University Biosignal Research Center), Lead Researcher MATSUMURA Chisato (Hyogo Prefectural Institute of Environmental Sciences), Professor YAMAMOTO Keiko and Professor ITOH Toshimasa (Showa Pharmaceutical University), Associate Professor MORI Tadashi (Osaka University Graduate School of Engineering), and Visiting Professor NAKANO Takeshi (Osaka University Research Center for Environmental Preservation).

These research results were published online in the international academic journals Environmental Science & Technology on July 8, and Chemosphere on September 6, 2022.

Main points

• In the past, PCBs were utilized in a vast range of industrial and commercial products. These highly carcinogenic chemical compounds remain in our environment and accumulate inside organisms.
• PCBs have a dioxin-like toxicity and research into PCB metabolism is advancing.
• However, research had yet to uncover how chiral PCBs’ mirror-image isomers are metabolized.
• The researchers split the two atropisomers (mirror-image isomers) found in each type of chiral PCB and used them as substrates for CYP enzymes (*4).
• Even though a pair of atropisomers are physically and chemically identical, there was a big difference in the extent to which they were metabolized.
• Differences in CYP’s amino acids’ binding inhibition of each atropisomer cause the atropisomers to be metabolized differently.
• These findings will be useful for measuring the atropisomers of chiral PCBs, which accumulate easily inside animals’ bodies.

Research Background
Even though the manufacture and use of PCBs was banned around 50 years ago, they still remain in the environment. It has been discovered that PCBs accumulate inside the bodies of humans and other animals through food consumption. In particular, PCBs with many chlorine bonds are water resistant and do not break down easily. This enables high concentrations of these PCBs to accumulate inside animals’ bodies, which adversely affects their health. PCBs’ toxicity is induced by the aryl hydrocarbon receptor (AhR) (*5), causing similar adverse effects to dioxin (*6) poisoning such as cancer, teratogenesis and immune system damage. Research is being conducted on the particular types of PCB widely known to cause these effects, which are dioxin-like PCBs with one ortho chlorine substitution in the biphenyl ring of their chemical structure, or PCBs with no substitutions (Figure 1). However, if a PCB has more than 3 chlorine substitutions at the ortho position of the biphenyl ring, it becomes a mirror-image isomer called chiral PCB (Figure 2). These chiral PCBs do not demonstrate dioxin-like toxicity but are far more dangerous, binding with the ryanodine receptors (RyR) in organisms to become neurotoxic. The two mirror-image isomers (called atropisomers) in chiral PCB have identical physical and chemical properties and exist at a 1:1 ratio in commercial chiral PCB. However, biased ratios are often observed in the environment and in animals such as earthworms and whales, as well as humans. It is believed that this unbalanced ratio is mainly caused by metabolism and that one of chiral PCB’s atropisomers is more effected by the metabolic reaction thus reducing its concentration.

However, very little research has been carried out into differences in how these atropisomers are metabolized nor the structural arrangement of the metabolic enzymes.

Research Methodology
To address this knowledge gap, the team conducted research focusing on the metabolic enzyme cytochrome P450 (CYP enzyme). The CYP enzyme reacts with foreign compounds that enter an animal’s body (for example, chemicals or pollutants in food, or medicines). CYP can convert them into water-soluble compounds and promote their expulsion from the body. Previous research by this group has shown that CYP enzymes hydroxylate and dechlorinate dioxin-like PCBs. This decreases PCB’s binding with AhR and increases its water solubility, promoting expulsion from the body and therefore counteracting its toxicity. In other words, CYP is an important enzyme that determines whether or not PCBs are treated as toxic compounds by the body. To measure the metabolic action of CYP on chiral PCB, the researchers set up a CYP enzyme and PCB docking model. They used this to estimate the structure of PCB metabolites and the structure of the CYP that decides to metabolize each of the PCB atropisomers differently.

For the experiment, the group selected three types of chiral PCB, each with a different number of substituted chlorine atoms; CB45 (4 chlorine substitutions), CB91 (5 chlorine substitutions) and CB183 (7 chlorine substitutions) (Figure 2). They separated the atropisomers for each type of chiral PCB using chromatography and let them react with a human CYP enzyme. It is thought that research on separating the atropisomers and letting them react has not been done before now. The results revealed big differences in how each atropisomer is metabolized (Figure 3). This revealed that even though the two atropisomers in one PCB have the same physical and chemical composition, they are biologically different. The researchers found that one of the chiral PCB atropisomers was metabolized more than the other one, disrupting the 1:1 ratio. In addition, it is thought that the amount of (aS)-CB183 atropisomer decreases because it is metabolized more than the other atropisomer, and this is supported by the reports of low accumulation of (aS)-CB183 in humans.

But why are these physically and chemically identical atropisomers metabolized differently by the CYP enzyme? To solve this mystery, the researchers used a computer model to investigate how easily each chiral PCB atropisomer binds to the chemical structure of CYP. They found that when an atropisomer fills up the substrate-binding cavity inside the CYP enzyme, CYP’s amino acids (that form the cavity) interfere with the binding between CYP and the atropisomer (see Figures 4 and 5).

Therefore, the atropisomer that isn’t interfered with by CYP’s amino acids becomes easy to metabolize (atropisomer (aR)-CB45 in CB45, and (aS)-CB183 in CB183), resulting in alterations to the original 1:1 ratio of atropisomers found in chiral PCB.

Further Research
The results of this research will be useful for making predictions about the atropisomers of chiral PCBs, which accumulate easily inside animals’ bodies. In other words, it will be possible to work out which atropisomer is reduced by the metabolic reaction with CYP enzymes and which atropisomer remains inside the body. Chiral PCB’s toxicity is activated by binding with RyR, however the ability to bind with RyR differs between the atropisomers. Therefore, this research will make it possible to estimate the toxicity of chiral PCBs.

Mirror-image isomers for 3 different types of chiral PCB.

Of the two atropisomers in each chiral PCB, (aR)-CB45 in CB45 and (aS)-CB183 in CB183 are metabolized into hydroxylated metabolites more. In CB91, each atropisomer is metabolized at a similar rate.

Light blue indicates the substrate-binding cavity inside the CYP enzyme. The CYP enzyme is unable to form a stable interaction with the atropisomer (aS)-CB45 because (aS)-CB45 collides (indicated by the red lines) with leucine 363, therefore CYP produces fewer metabolites (see Figure 3).

Light blue indicates substrate-binding cavity inside the CYP enzyme. It is thought that metabolite formation activity is the same for both atropisomers (see Figure 3) because (aR)-CB91 collides with leucine 363 and (aS)-CB91 collides with phenylalanine 206 (collisions indicated by red lines).

CREDIT

Modified from Inui et al. Environmental Science & Technology, 2022

Glossary
1. Polychlorinated biphenyl (PCB): A chemical compound with between 1 to 8 chlorine atoms bound to its biphenyl ring. There are 209 types of PCB, each with different structures. Until the late 1970s, PCBs were manufactured for use as insulating oil and were also found in a variety of products, however their manufacture and use were banned worldwide after it was discovered that they are highly toxic. PCBs with many chlorine bonds do not break down easily so large quantities remain in the environment and inside organisms even almost 50 years after they were banned.
2. Chiral PCB: This is a PCB that has 3 or more chlorine substitutions at the ortho position. This structure inhibits the rotation of the bond connecting the 2 benzene rings. It also has 2 mirror isomers (a pair of atropisomers). There are 19 types of chiral PCB and according to the Cahn-Ingold-Prelog priority rules, their atropisomers are referred to as ‘aS’ and ‘aR’.
3. Mirror-image isomer (enantiomer): A pair of isomers that are non-superimposable mirror-images of each other, slightly similar to your left and right hands. Asymmetrical carbon compounds have mirror-image isomers. These isomers have the same physical and chemical properties. In chemical synthesis, a racemic mixture consists of an equal amount of each isomer in a 1:1 ratio.
4. Cytochrome P450 monooxygenase (CYP enzyme): This metabolic enzyme is found in most organisms- it is responsible for the oxygenation reaction in the biosynthesis pathway for various chemical compounds in the body. In addition to this it has a detoxifying function; it oxygenates foreign compounds in the body, which makes them water soluble and easier to excrete.
5. Receptor: These are proteins found in organism cells that bind to chemical substances and promote or control the expression of the gene required for the organism to respond to the chemical substance. Aside from the estrogen receptor (ER) that binds to the female hormone and the aryl hydrocarbon receptor (AhR) that binds to dioxins, there are many other known receptors for various hormones.
6. Dioxin: Dioxins are generated by incinerating trash at low temperatures. They are difficult to break down and persist in the environment and inside organisms for a long period of time. When dioxins enter an animal’s body via food, they bind to AhR (aryl hydrocarbon receptors) inside the cells and the gene transcription for the enzyme that detoxifies dioxins is activated.

Acknowledgements
This study was supported by a Grant-in-Aid for Challenging Exploratory Research (grant number 25550064) from the Japan Society for the Promotion of Science and the Japan Science and Technology Agency’s CREST program (grant number JPMJCR2001).

Journal Information

Title: “Differences in Enantioselective Hydroxylation of 2,2′,3,6-Tetrachlorobiphenyl (CB45) and 2,2′,3,4′,6-Pentachlorobiphenyl (CB91) by Human and Rat CYP2B Subfamilies”
DOI: https://doi.org/10.1021/acs.est.2c01155
Authors: Hideyuki Inui1,2, Terushi Ito2, Chiharu Miwa3, Yuki Haga4, Makoto Kubo5, Toshimasa Itoh5, Keiko Yamamoto5, Masayuki Miyaoka6, Tadashi Mori6, Harunobu Tsuzuki2, Shintaro Mise2, Erika Goto2, Chisato Matsumura4, and Takeshi Nakano7

1. Biosignal Research Center, Kobe University.
2. Graduate School of Agricultural Science, Kobe University.
3. Faculty of Agriculture, Kobe University.
4. Hyogo Prefectural Institute of Environmental Sciences, Hyogo Environmental Advancement Association.
5. Showa Pharmaceutical University.
6. Graduate School of Engineering, Osaka University.
7. Research Center for Environmental Preservation, Osaka University.

Journal
Environmental Science & Technology

Title: “Enantioselective metabolism of chiral polychlorinated biphenyl 2,2′,3,4,4′,5′,6-heptachlorobiphenyl (CB183) by human and rat CYP2B subfamilies”

DOI: https://doi.org/10.1016/j.chemosphere.2022.136349

Authors: Terushi Ito1, Chiharu Miwa2, Yuki Haga3, Makoto Kubo4, Toshimasa Itoh4, Keiko Yamamoto4, Shintaro Mise1, Erika Goto1, Harunobu Tsuzuki1, Chisato Matsumura3, Takeshi Nakano5, Hideyuki Inui1,6

1. Graduate School of Agricultural Science, Kobe University.
2. Faculty of Agriculture, Kobe University.
3. Hyogo Prefectural Institute of Environmental Sciences, Hyogo Environmental Advancement Association.
4. Showa Pharmaceutical University.
5. Research Center for Environmental Preservation, Osaka University.
6. Biosignal Research Center, Kobe University.

Journal:
Chemosphere

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JOURNAL

Chemosphere

DOI

10.1016/j.chemosphere.2022.136349 

METHOD OF RESEARCH

Experimental study

ARTICLE TITLE

“Enantioselective metabolism of chiral polychlorinated biphenyl 2,2′,3,4,4′,5′,6-heptachlorobiphenyl (CB183) by human and rat CYP2B subfamilies”

Cultural differences affect how we support close friends and family

Japanese university students tend to be hesitant in providing social support when help is not clearly requested

Peer-Reviewed Publication

OSAKA METROPOLITAN UNIVERSITY

 

IMAGE: AN OSAKA METROPOLITAN UNIVERSITY STUDY FINDS THAT CULTURAL DIFFERENCES BETWEEN JAPANESE AND AMERICAN UNIVERSITY STUDENTS CONTRIBUTE TO HESITANCY IN PROVIDING SOCIAL SUPPORT TO CLOSE FRIENDS OR FAMILY MEMBERS. view more 

CREDIT: OSAKA METROPOLITAN UNIVERSITY

A research team led by Associate Professor Hirofumi Hashimoto, from the Graduate School of Literature and Human Sciences, Osaka Metropolitan University, analyzed the perspectives of providers of social support to examine differences in the attitudes of Japanese and American university students toward providing social support to close friends or family members.

Initially, a questionnaire based on previous research was administered that surveyed 183 Japanese university students, indicated that the Japanese students were hesitant to provide social support unless the person they were close to explicitly asked for help. To confirm the robustness of these results a second questionnaire was administered to an additional 118 Japanese and 52 American university students, using a scenario-based method to gauge their willingness to support close friends or family members in need.

The results of the second survey confirmed that even when Japanese university students were aware that someone close to them was in need, they tended to be hesitant in offering assistance unless that person had explicitly asked for their help. In contrast, U.S. university students were often willing to offer assistance when they recognized that someone close to them was in need, even when they had not been asked for help. Nevertheless, when requests for assistance were clear, both Japanese and American university students were equally likely to offer assistance.

“The results of our study indicate that the reason Japanese people feel hesitation towards helping others is not because they are unsympathetic but because these situations—where a request for help is not clear—create hesitation,” said Professor Hashimoto. “Based on these findings, we need to consider ways to encourage Japanese people to provide assistance when they recognize it is needed.”

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About OMU

Osaka Metropolitan University is a new public university established by a merger between Osaka City University and Osaka Prefecture University in April 2022. For more science news, see https://www.upc-osaka.ac.jp/new-univ/en-research/, and follow @OsakaMetUniv_en, or search #OMUScience.

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JOURNAL

Frontiers in Psychology

DOI

10.3389/fpsyg.2022.953260 

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Solicitation Matters: Cultural Differences in Solicited and Unsolicited Support Provision

Warmer brain-irrigation fluid in surgery more efficacious

Peer-Reviewed Publication

UNIVERSITY OF GOTHENBURG

 

IMAGE: ANDREAS BARTLEY AND MAGNUS TISELL, SAHLGRENSKA ACADEMY AT THE UNIVERSITY OF GOTHENBURG. view more 

CREDIT: PHOTO BY JOSEFIN BERGENHOLTZ AND UNIVERSITY OF GOTHENBURG.

A simple method can halve the number of repeat operations to remedy bleeding under the cranium, a study at the University of Gothenburg shows. The method is based on replacing irrigation fluid at room temperature with fluid at body temperature.

Bleeding between the cranium and the brain (subdural hemorrhage or hematoma) mainly affects older people and arises most often after a relatively light blow to the head. The condition can cause accumulation of inflammatory fluid mixed with blood, resulting in swelling and pressure on the brain.

This fluid sometimes continues to accumulate for weeks and months, with increasingly severe symptoms ranging from persistent headache to confusion, weakness on one side of the body, balance problems, and reduced awareness.

Surgical treatment is necessary. After the fluid is drained out through a drill hole in the skull, the surface of the brain is rinsed clean with irrigation fluid to ensure that no residues from the hemorrhage remain and grow, causing recurrence. In Sweden today, this is the most common brain operation.

Historically, fluid at various temperatures has been used for brain irrigation. Just as with other forms of irrigation, there is reason to assume that temperature may play a part in how effectively the bleeding residues can be flushed away. The temperature of the fluid can also affect how rapidly new minor bleeding is stopped.

Warmer liquid — fewer interventions

The current study, published in the journal JAMA Neurology, comprised a total of 541 patients at Uppsala University Hospital, Karolinska University Hospital in Solna, and Sahlgrenska University Hospital in Gothenburg. The participants’ average age was 76 years.

The patients were randomly assigned to receive irrigation at either body or room temperature during their operations, while the rest of the treatment proceeded in the same way for both groups. Among those who were given room-temperature irrigation fluid, 14 percent (39 of 277 patients) needed a repeat operation within six months. In the group receiving body-temperature fluid, the corresponding proportion was 6 percent (16 of 264 patients).

The study’s first author is Andreas Bartley, a PhD student in clinical neuroscience at Sahlgrenska Academy, University of Gothenburg, and neurosurgeon at Sahlgrenska University Hospital.

“The fact that we can reduce the number of recurrences, and hence repeat operations, with such a simple measure is of great importance —above all for reducing unnecessary suffering in this group of older patients, but also for lessening pressure on the healthcare services,” Bartley says.

Patient group expected to grow

The researchers involved in the study describe the operating environment as highly complex and say it is rare for systematic studies of such simple physical properties as fluid temperature to be conducted.

The study’s last author is Magnus Tisell, Associate Professor (docent) of Neurosurgery at Sahlgrenska Academy, University of Gothenburg, and neurosurgeon at Sahlgrenska University Hospital.

“The total number of operations for subdural hemorrhage is expected to rise sharply with the growing proportion of older people in the population. What’s more, raising the irrigation-fluid temperature is a measure that can be easily applied in resource-poor, low-income countries as well,” Tisell concludes.

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JOURNAL

JAMA Neurology

DOI

10.1001/jamaneurol.2022.4133 

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Effect of Irrigation Fluid Temperature on Recurrnce in the Evacuation of Chronic Subdural Hematoma, A Randomized Clinical Trial

ARTICLE PUBLICATION DATE

21-Nov-2022

Key to chemical industries’ sustainable future? The world’s first industrial model of a flow photo-on-demand synthesis system

Continuous production of useful chemical products using chloroform as a precursor

Peer-Reviewed Publication

KOBE UNIVERSITY

 

IMAGE: THE FLOW PHOTO-ON-DEMAND CHEMICAL SYNTHESIS SYSTEM DEVELOPED IN THIS STUDY view more 

CREDIT: AKIHIKO TSUDA

Various chemical products, such as polymers and pharmaceutical intermediates, are currently synthesized with phosgene as their precursor or raw material. However, phosgene is highly toxic and this usage poses safety risks. Thus, there is demand for the development of new methods and substitutes to replace phosgene. In collaboration with industry, Associate Professor TSUDA Akihiko’s research group at Kobe University Graduate School of Science has become the first in the world to successfully develop a new flow photo-on-demand synthesis system that uses chloroform as the precursor. Using this system, they were able to synthesize phosgene-derived chemical products. Furthermore they achieved a high conversion rate (over 96%), synthesizing these useful compounds in a short period of time (a minute or less of light exposure). The system has multiple advantages; it is safe, inexpensive and simple with a low impact on the environment. It can be used to synthesize various chemical products, which it can produce continuously in large quantities. The researchers expect that this system can be scaled up into a model system of industrial production in the near future.

Patents for this system were filed in Japan in February 2021 and internationally in January 2022. Following the patent announcement in August 2022, the related academic paper was published online in Organic Process Research & Development (OPR&D) on November 11, 2022.

Main Points

• From the common organic solvent chloroform and commercially available alcohol, the researchers successfully synthesized pharmaceutical intermediates and polymers at a highly efficient rate (over 96%) and in a short amount of time (a minute or less of light exposure).
• They showed that continuous production is possible, which cannot be done with conventional batch systems.
• In 2 hours, they successfully synthesized up to ten grams of chemical products (and this can be scaled up)
• They synthesized 10 types of functional carbonates and 3 types of polycarbonates as examples.
• Improved safety compared to the standard method of producing phosgene (a strong exothermic reaction of carbon monoxide and chlorine gas that uses a carbon catalyst). The chloroform used as a precursor in the new method is easy to store safely and the chemical reaction can be controlled by exposure to light.
• The byproduct of this new method is mostly hydrogen chloride (neutralized by alkali), therefore dirt does not build up inside the system apparatus. The reduced need to clean the inside lessens the environmental impact and lowers costs.
• The system achieves continuous production without the additional use of organic solvents.
• This new chemical reaction system is expected to make a significant contribution in the move towards carbon neutral and sustainable societies.

(a) A conventional reaction with phosgene, (b) the photo-on-demand phosgenation reaction developed at Kobe Univ., and (c) a batch-type reaction system for the photo-on-demand chemical synthesis developed at Kobe Univ.

System overview of the flow photo-on-demand chemical synthesis method developed in this study.

Research Background
Phosgene (COCl2) is used as precursor for polymers and as a pharmaceutical intermediate. The global phosgene market continues to grow by several percent each year, with around 8 to 9 million tonnes produced annually. However, phosgene is extremely toxic. For safety reasons, research and development is being conducted to find alternatives. In a world-first discovery, Associate Professor Tsuda’s research group irradiated chloroform with ultraviolet light, which caused it to react with oxygen and generate high yields of phosgene (patent no. 5900920). In order to do this in an even saferand easier manner, the research group found a way that the phosgene-generating reactions could be instantly performed. They first dissolved the reactants and catalysts in chloroform, and generated phosgene by irradiating the solution with light (patent no. 6057449). In this way, phosgene-based organic synthesis can be carried out as if phosgene wasn’t used.

The research group has named their discovery ‘photo on demand organic synthesis method’ and have successfully used it to synthesize numerous useful organic chemicals and polymers (list of patents (in Japanese): Patents of Tsuda Laboratory). For example, they successfully synthesized large quantities of chloroformate and carbonate in a safe, inexpensive and simple manner merely by irradiating a mixed solution of chloroform and alcohol (with a base added as needed) with light (Figure 2, for more information see press release (Japanese) and journal paper (English)).

These highly original reactions developed at Kobe University have been improved through cooperation with domestic chemical companies, and the eventual aim of this research is practical implementation. With the addition of funding from JST A-STEP, further applied research is being conducted, as well the development of functional polyurethane using this synthesis method.

The photo-on-demand organic synthesis method is highly safe and economical, in addition to having a low impact on the environment. Consequently, it has garnered attention from both industry and academia as a sustainable chemical synthesis method (Highlights of Tsuda Laboratory (in Japanese)).

Research Methodology
In this research, a flow photo-on-demand system was redesigned for the photo-oxidation reaction of chloroform. Through experimenting with various flow channel arrangements, materials and light sources, the following system was created as shown in Figures 1 and 3. In the batch photo-on-demand method developed by this research group previously, the photoreaction between the chloroform and oxygen occurs in heterogeneous phases where the chloroform is a liquid and the oxygen is a gas (Figure 2c). However, in experiments using the new system the authors found that the reaction dramatically increased when both were in a gaseous state. By irradiating this gaseous mixture of vaporized chloroform and oxygen under ultraviolet light, the majority (over 96%) was converted into phosgene. Furthermore, the phosgene continuously reacted with the alcohol inside the system (with a base catalyst added as required), which meant that the system could be used to continuously synthesize high yields of chloroformate, carbonates and polycarbonates on a gram scale (Figure 4). These reactions are completed inside the system so the highly toxic phosgene gas does not escape. N-methylimidazole (NMI), which becomes an ionic liquid when it reacts with hydrogen chloride, was used as the base catalyst, so carbonates could be synthesized without using additional solvents. This system can be scaled up further, which will enable it to be used in a wide range of fields from academia to chemical industries.

Mechanism: It is thought that the chloroform photo-oxidation reaction is promoted by a radical chain mechanism. The ultraviolet light cleaves the C-Cl bond, which produces chlorine radicals and these radicals become primers that instigate the mechanism.

The researchers confirmed that the chloroform photo-oxidation reaction is extremely energy efficient even when a low-power light source is used. This is due to the oxidation part of the reaction whereby chlorine radicals are repeatedly consumed and regenerated.

Further Developments
The photo-on-demand synthesis method is expected to spark new innovation in how various chemical products are synthesized with phosgene as a precursor. With this new flow photo-on-demand system, it is possible to avoid the dangers of directly using phosgene produced from carbon monoxide and chlorine because the phosgene reaction occurs within the closed environment inside the system. In addition, the system only uses chloroform and oxygen as precursors, meaning that expensive phosgene substitutes are not required. This safe and simple versatile system can be used for the small to large-scale synthesis of various chemical products and the apparatus of this basic model can be customized to suit specific chemical reactions. It is hoped that this system can be used for industrial production by refining the process according to the scale of production. However, this system is not only for large scale chemical production; it will also be of great benefit to chemical manufacturers who need to produce various products on a small to medium scale. It is hoped that it can be used in new ventures, as well as to replace existing set-ups that are wearing out.

Acknowledgements
This research was supported by the Adaptable and Seamless Technology Transfer Program through Target-driven R&D (A-STEP) (seeds development type) from the Japan Science and Technology Agency (JST). ‘Developing highly functional and high added value polyurethane-materials through safe production processes using fluoroalkyl carbonates as key intermediates’ (Principle Researcher: Akihiko Tsuda).

Patent Information
Presentation Title: Method for Producing Halogenated Carbonyls
Patent application no. : 2021-21001 (Date of application: February 12, 2021).
Priority application no.: PCT/JP2022/2661 (Date of application: January 25, 2022).
Patent publication no.: WO2022172744 A1 (Date of publication: August 18, 2022).
Presenters: Akihiko Tsuda, and 2 others.
Applicants: Kobe University, and 2 others.

Journal Information
Title:
“Flow Photo-on-Demand Phosgenation Reactions with Chloroform”
DOI: doi.org/10.1021/acs.oprd.2c00322
Authors:
Yue Liu, Itsuumi Okada, Akihiko Tsuda*
* Corresponding author
Kobe University Graduate School of Science
Journal:
Organic Process Research & Development (OPR&D)

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JOURNAL

Organic Process Research & Development

DOI

10.1021/acs.oprd.2c00322 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Flow Photo-On-Demand Phosgenation Reactions with Chloroform

ARTICLE PUBLICATION DATE

11-Nov-2022

COI STATEMENT

The authors declare no competing financial interest.

Covid-19: the Spike protein is no longer the only target

A research team led by the UNIGE reveals a hidden cavity on a key SARS-CoV-2 protein to which drugs could bind

Peer-Reviewed Publication

UNIVERSITÉ DE GENÈVE

 

IMAGE: POSSIBLE MECHANISM OF ACTION OF A DRUG TARGETING THE SARS-COV-2 NSP1. IN INFECTED CELLS, NSP1 BLOCKS THE RIBOSOME’S MRNA CHANNEL BY ACTING AS A «CORK» THAT PREVENTS THE EXPRESSION OF THE HOST’S MRNA. THE BINDING OF A LIGAND TO THE PROPOSED CRYPTIC POCKET HIGHLIGHTED IN PURPLE COULD PREVENT THE NSP1-MEDIATED BLOCKAGE AND, ULTIMATELY, RECOVER THE RIBOSOME’S ABILITY TO INITIATE THE MRNA TRANSLATION. view more 

CREDIT: © CREATIVE COMMONS

With the continuous emergence of new variants and the risk of new strains of the virus, the development of innovative therapies against SARS-CoV-2 remains a major public health challenge. Currently, the proteins that are on the surface of the virus and/or are involved in its replication are the preferred therapeutic targets, like the Spike protein targeted by vaccines. One of them, the non-structural protein Nsp1, had been little studied until now. A team from the University of Geneva (UNIGE), in collaboration with University College London (UCL) and the University of Barcelona, has now revealed the existence of a hidden ''pocket’ on its surface. A potential drug target, this cavity opens the way to the development of new treatments against Covid-19 and other coronaviruses. These results can be found in the journal eLife.

The fast rollout of new vaccines and antiviral drugs has helped to contain the Covid-19 pandemic, caused by the SARS-CoV-2 virus. Despite the progress made, the development of new therapies is still an urgent priority: the continuous emergence of new variants - some of which are resistant to current treatments - and the possible appearance of new strains of the virus represent a risk of new pandemics. Proteins are at the forefront of therapeutic targets to combat the virus. The best known is the Spike protein, which is located on the surface of SARS-CoV-2 and gives it its ‘‘spiky’’ appearance. It is the key to the virus entering our cells. It is the target of Messenger RNA vaccines.

A little-studied key protein

SARS-CoV-2 also makes other proteins - the «non-structural» proteins - using the resources of our cells after entering them. There are sixteen of them. They are essential for the replication of the virus. Some have been studied in the context of the development of new drugs. Others have received less attention. This is the case of the Nsp1 protein. Without obvious cavities on its surface to anchor a potential drug, researchers felt that it could not be a target for treatment.

‘‘Nsp1 is, however, an important infectious agent of SARS-CoV-2,’’ explains Francesco Luigi Gervasio, full professor at the Section of Pharmaceutical Sciences and the Institute of Pharmaceutical Sciences of Western Switzerland of the UNIGE Faculty of Science, and at the Department of Chemistry and the Institute of Structural and Molecular Biology at UCL. ‘‘This small viral protein selectively blocks ribosomes - the protein factories of our cells - making them unusable by our cells and thus preventing the immune response. At the same time, via ribosomes, Nsp1 stimulates the production of viral proteins.’’

Revealed by algorithms

Professor Gervasio’s team, in collaboration with UCL and the University of Barcelona, revealed the existence of a ‘‘hidden’’ cavity on the surface of Nsp1, which could be the target of future drugs against SARS-CoV-2. ‘‘To uncover this cryptic, partially hidden pocket, we carried out simulations using algorithms that we developed,’’ explains Alberto Borsatto, research and teaching assistant at the Section of Pharmaceutical Sciences and the Institute of Pharmaceutical Sciences of Western Switzerland of the Faculty of Sciences of the UNIGE, first author of the study. ‘‘Then, in order to confirm that this pocket could be used as a drug target, we used experimental screening and X-ray crystallography techniques.’’

The research team tested many small molecules that could potentially bind to the Nsp1 cavity (experimental screening). It identified one in particular  – 5 acetylaminoindane or 2E10 -  that also allowed the determination of the spatial arrangement of the atoms making up the cavity (by crystallography). These are essential data that form the basis for the development of new drugs.

‘‘These results pave the way for the development of new treatments targeting the Nsp1 protein, not only against SARS-CoV-2 and its variants but also against other coronaviruses in which Nsp1 is present,’’ says Francesco Luigi Gervasio, the study’s last author. As for the method developed to reveal the hidden pocket of Nsp1, it could be used to discover, on the surface of other proteins, new cavities still unknown to scientists.

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JOURNAL

eLife

DOI

10.7554/eLife.81167 

METHOD OF RESEARCH

News article

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Revealing druggable cryptic pockets in the Nsp1 of SARS-CoV-2 and other β-coronaviruses by simulations and crystallography

ARTICLE PUBLICATION DATE

22-Nov-2022