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Study presents novel therapeutic target for treatment of sepsis

A new strategy for preventing complications associated with sepsis is presented by researchers affiliated with the University of São Paulo (USP) and collaborators in an article published in the journal Blood. Credit: CRID-USP A new strategy for preventing

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A new strategy for preventing complications associated with sepsis is presented by researchers affiliated with the University of São Paulo (USP) and collaborators in an article published in the journal Blood.

Credit: CRID-USP

A new strategy for preventing complications associated with sepsis is presented by researchers affiliated with the University of São Paulo (USP) and collaborators in an article published in the journal Blood.

The proposal is to inhibit the action of a protein called gasdermin D, which the authors show is possible with disulfiram, a drug already approved for human use and originally indicated to combat alcohol dependence.

The study was conducted at the Center for Research on Inflammatory Diseases (CRID), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP. CRID is hosted by the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) in Brazil.

“We know the drug is safe because it’s been in use since the 1950s, and we propose it be repurposed to treat sepsis. We saw that it worked in animal trials in the laboratory. We now need a clinical trial to assess its effectiveness in septic patients,” Camila Meirelles Silva, a postdoctoral fellow at CRID and first author of the article, told.

Popularly known as “generalized infection”, sepsis is actually systemic inflammation, frequently triggered by a bacterial infection that has entered the bloodstream. As the immune system combats the pathogen, it ends up damaging the entire organism. Severe sepsis patients develop lesions that impair the functioning of vital organs, especially the lungs.

In previous research, the CRID group showed that an immune mechanism known as neutrophil extracellular traps (NETs) is directly involved in septic patients’ tissue lesions. As the name suggests, NETs are a defense strategy used mainly by neutrophils, a type of white blood cell that phagocytizes (kills) bacteria, fungi, and viruses. In extreme situations, these immune cells themselves may die, and the material held in their nuclei is ejected to the external medium in the form of an extracellular network toxic to both pathogens and cells of the organism.

“In our latest study we investigated the mechanism that permits the release of NETs, in which gasdermin D is directly involved,” Silva said. “We show that when we prevented neutrophils from releasing these mesh-like traps by inhibiting gasdermin D, we were able to reduce the level of tissue injury and improve the patient’s prognosis.”

Methodology

Some of the experiments involved white blood cells isolated from 24 septic patients hospitalized 24 hours previously (12 men and 12 women). Confocal microscope analysis showed NETs being released in vitro by a large proportion of the cells. The tests also pointed to a large amount of active gasdermin D in the patients’ neutrophils. This had already been observed in neutrophils isolated from septic mice.

“Gasdermin D is a pore-forming protein,” Silva said. “Previous research showed that when this molecule is activated in cells, it forms pores in the nuclear membrane that let genetic material out into the cytosol. Other pores are then opened up by gasdermin D in the plasma membrane, allowing all this content to be released into the extracellular medium. We proved that in sepsis the protein also acts in this manner.”

In vivo experiments were performed with mice submitted to a procedure designed to induce sepsis. Some expressed gasdermin D normally. The other group consisted of mice that had been genetically modified so as not to produce the protein in any cells of their bodies (gasdermin D knockout mice).

“When we induced sepsis, we found that the knockout mice produced a smaller amount of NETs, developed fewer organ lesions [with no pulmonary edema, unlike the rest], and survived more,” Silva said. 

In vitro trials involving cells from knockout mice confirmed that neutrophils did not release NETs even in the presence of LPS, a molecule in the membranes of pathogenic bacteria usually interpreted as a threat by the immune system.

Inhibition tests 

Data from the scientific literature showed that disulfiram binds to gasdermin D to prevent cell membrane pore formation by the protein. Based on this evidence, the CRID scientists decided to test the effect of the drug in the context of sepsis, for which there are no specific medications.

They found from in vitro tests that after treatment with disulfiram both human and murine neutrophils stopped releasing NETs when they were stimulated with LPS.

In another experiment, neutrophils isolated from septic patients were incubated with disulfiram. The treatment inhibited the release of NETs.

Lastly, septic mice were treated with disulfiram and their progress was compared with that of untreated mice. The treated animals had fewer tissue lesions (including less pulmonary edema), fewer NETs in the blood, and an improved prognosis: 60% survived, compared with 20% in the untreated group.
     
The results aroused interest in the scientific community and motivated a commentary, also published in Blood, by researchers Maksim Klimiankou and Julia Skokowa at University Hospital Tuebingen in Germany.

“Neutrophils deploy multiple defenses against pathogens, including phagocytosis, production of reactive oxygen species, secretion of bactericidal enzymes, and formation of NETs. Neutrophils pay a high price for all these defensive actions, dying during the process of digesting, neutralizing and killing invaders. However, not all is perfect in this line of defense: it is almost impossible to regulate the degree of neutrophil activation. Once activated, they frequently display hypersensitive phenotypes, causing deleterious effects both at the site of inflammation and systemically, and playing an essential role in the onset of the dysfunction process of multiple organs and the lethality of sepsis. Attacking the mechanisms responsible for the deleterious effects of neutrophils during sepsis while preserving other functions of these cells could represent a valuable therapy,” the German researchers write in the commentary.

Results of the research were also the theme of a podcast produced by the staff in Blood.

Next steps 

According to Fernando de Queiroz Cunha, a professor at FMRP-USP and CRID’s principal investigator, production of disulfiram was shut down in Brazil in 2019 and this has prevented the group from conducting a clinical trial. 

“It was such a cheap drug that the company decided to take it off the market, and psychiatrists who treat alcohol-dependent patients now have to import it,” Cunha said. “As an alternative, we’re in talks with a Brazilian pharmaceutical company to develop a slightly modified molecule that could be patented and marketed domestically.”

Cunha also disclosed CRID’s intention to test whether disulfiram can be used to prevent organ lesions in COVID-19 patients. A previous study by the group showed that NETs participate in the runaway inflammation triggered by SARS-CoV-2 (more at: agencia.fapesp.br/33523/). 

###

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.


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Economics

Peppercomm Named Public Relations Agency of Record for AgriFORCE

Peppercomm Named Public Relations Agency of Record for AgriFORCE
PR Newswire
NEW YORK, Aug. 18, 2022

AgTech innovator taps integrated communications and marketing agency to drive global growth and brand awareness
NEW YORK, Aug. 18, 2022 /PRNewswire…

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Peppercomm Named Public Relations Agency of Record for AgriFORCE

PR Newswire

AgTech innovator taps integrated communications and marketing agency to drive global growth and brand awareness

NEW YORK, Aug. 18, 2022 /PRNewswire/ -- Peppercomm, award-winning, strategic and integrated communications and marketing agency, today announced it has been named global PR agency of record for AgriFORCE Growing Systems Ltd. (NASDAQ: AGRI; AGRIW), an AgTech company dedicated to advancing sustainable cultivation and crop processing to yield more nutritious food with limited environmental impact. AgriFORCE selected Peppercomm following a competitive evaluation of several firms.

Headquartered in Vancouver, British Columbia, AgriFORCE is poised to disrupt the agriculture industry by building a portfolio of proprietary AgTech solutions to help growers achieve higher quality and more sustainably produced crops, alongside branded products and ingredients that unlock superior nutrition for consumers. With an agreement to acquire Delphy Group BV and a binding LOI to acquire Deroose Plants NV recently announced, the company's strategic and holistic approach aims to address key challenges facing the agriculture industry.

"We're pleased to work with a company that can have a real impact on our food and our planet," said Steve Cody, CEO of Peppercomm. "The global pandemic and Russian invasion of Ukraine have significantly affected the food supply chain and accelerated the need for solutions to address these extraordinary challenges. AgriFORCE's IP and expertise are coming to the marketplace at just the right time."

Peppercomm will help AgriFORCE build global brand awareness through an integrated approach that includes strategic counsel, messaging development, thought leadership, earned media and social media, and digital advertising. 

"AgriFORCE is excited to partner with Peppercomm as our agency of record," shared Mauro Pennella, President of AgriFORCE Brands and CMO of AgriFORCE Growing Systems. "Peppercomm has strong experience across agriculture, agtech, and consumer brands, including public companies with multinational operations. We are confident that their tight-knit and senior team, with existing industry and media relationships, can bring to life the vision and purpose of AgriFORCE in the months ahead."

About Peppercomm
Peppercomm is an award-winning strategic, integrated communications and marketing agency headquartered in New York City with offices in San Francisco and London. The firm, which was recently acquired by Ruder Finn, combines 27 award-winning years of expertise serving blue chip and breakout clients with forward-thinking new service offerings and the freshness of a start-up. This unique mix of experience and energy enables the firm to attract and empower teams with a creative edge, drive, and passion for promoting, protecting, and connecting clients in a fast-changing marketplace. Founded in 1995, Peppercomm has received numerous accolades, including Crain's Best Places to Work in NYC 2021, PRWeek's Best Places to Work 2020, the Agency Elite 100, SABRE Award (Integrated Campaign), PRSA Big Apple (2020, 2019 Winner Integrated Campaign), Platinum PR Awards (Media Relations), PRNews Digital Awards (CSR), the Bulldog PR Awards (Media Relations) and PR Daily's Top Agencies of 2022 among others. For more information visit peppercomm.com.

About AgriFORCE
AgriFORCE Growing Systems Ltd. (NASDAQ: AGRI; AGRIW) is an AgTech company focused on the development and acquisition of crop production know-how and intellectual property augmented by advanced AgTech facilities and solutions. Looking to serve the global market, the Company's current focus is on North America, Europe, and Asia. The AgriFORCE vision is to be a leader in delivering plant-based foods and products through advanced and sustainable AgTech solution platforms that make positive change in the world—from seed to table. The AgriFORCE goal: Clean. Green. Better. Additional information about AgriFORCE is available at: agriforcegs.com.

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Economics

NEARLY HALF OF AMERICANS FEEL THEY CAN’T AFFORD THEIR FORMER LIFESTYLE; THREE-FOURTHS ARE SHIFTING GROCERY PURCHASING BEHAVIORS, FINDS NCSOLUTIONS

NEARLY HALF OF AMERICANS FEEL THEY CAN’T AFFORD THEIR FORMER LIFESTYLE; THREE-FOURTHS ARE SHIFTING GROCERY PURCHASING BEHAVIORS, FINDS NCSOLUTIONS
PR Newswire
NEW YORK, Aug. 18, 2022

66% of consumers are more mindful of spending on groceries85% of …

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NEARLY HALF OF AMERICANS FEEL THEY CAN'T AFFORD THEIR FORMER LIFESTYLE; THREE-FOURTHS ARE SHIFTING GROCERY PURCHASING BEHAVIORS, FINDS NCSOLUTIONS

PR Newswire

  • 66% of consumers are more mindful of spending on groceries
  • 85% of Americans are concerned or very concerned about inflation
  • 58%  believe the cost of living will be more expensive in the coming year
  • 46% of consumers say they're buying fewer non-essentials
  • 43% seek out sales and promotions to afford their favorite brands 

NEW YORK, Aug. 18, 2022 /PRNewswire/ -- Nearly half of Americans (45%) feel like they can't afford their previous lifestyle and 76% of American consumers say their family has changed how they buy food with prices on the rise. In addition, two-thirds (66%) are more mindful of how they are spending their money. These findings are part of a new consumer sentiment survey on inflation commissioned by NCSolutions (NCS), the leading company for improving advertising effectiveness.

Eighty-five percent of Americans are very concerned or extremely concerned about inflation and almost unanimously (93%) they said we're in an inflationary time. On the same economic theme, over half (57%) are concerned about the country's financial situation, while 47% say they're concerned about their family's financial situation. Eight out of 10 or 83% of Americans expect the cost of living will become somewhat more or much more expensive in the coming year. Sixty-five percent of Americans agree with the statement 'my income has not increased as fast at the cost of food, beverage and personal care products.'

"For the second time in a little over two years, consumers are pivoting to new purchasing behaviors at the grocery store," commented Alan Miles, CEO, NCSolutions. "Since the start of the pandemic, they've been swapping their favorite brands for what's available. Today, though, value is the centerpiece more often than availability, consumers are selecting brands and products to stretch their budgets as far as possible. CPG brands that meet customers where they are both in this inflationary moment and as prices ease have the best shot at keeping them for the long-term."

SIX YEARS OF PRICE TRENDS
NCSolutions' proprietary purchase data, which reflects the buying trends of consumers for CPG products, shows an almost 13% price increase on average. In a six-year price trend analysis, we see that price increases in 2022 are pacing at an accelerated rate compared to other years.  The survey findings bear this out with 58% of consumers believing the cost of living will be much more expensive in the coming year and 71% feeling the U.S. economy is declining. 

Six-year Inflation Trend

 

Percentage Inflation Change Year-Over-Year

On a consumer packaged goods category level, there are wide variations in percentage increases.

CONSUMERS REACT TO THE PINCH
Compared to one year ago, six in 10 Americans believe CPG product packaging has gotten smaller but costs the same. Consumers still feel the strain of supply chain issues as 69% say there are fewer items of the same product on the shelves. Thirty-six percent of Americans said there is less variety of  brands available on the shelf today compared with one year ago.

Over half (53%) of American consumers say they find basic food staples more expensive; 40% believe a recession will occur in 2023. For almost half of consumers (46%), this means buying fewer non-essential items on the food aisle, or for 43%, it means buying only the essentials.  Seventy-one percent of Americans say the increased price of groceries is straining their savings. For other American consumers, increased prices on the grocery aisle mean seeking out less expensive brands (45%).  Other ways consumers are coping with the increased price of groceries are loading up the pantry (27%) or freezer (26%) or shopping closer to home (24%).

When it comes to consumers' preferred brands, they have to make tough choices. Sixty percent of consumers seek less expensive alternatives when their favorite brands reach a price beyond their budget. Forty-six percent of consumers plan to go without their favorite brands, and 43% of consumers look for sales to offset the cost. In the survey, respondents could select multiple ways they react.

June 2021 vs. June 2022: Inflation Increases by category

"Though it may be tempting to pull back on advertising, a more effective strategy is to recognize and respond to consumer 'stress-flation.' Brands have an opportunity now to build loyalty and attract new customers with empathetic marketing," said Leslie Wood, Chief Research Officer, NCSolutions. "We're heading into a period of heavy CPG purchasing moments, such as back to school and the approaching holidays. Compelling, well-targeted advertising is a proven strategy for increasing brand equity and sales both in the short- and long-term."

CONSUMER PRIORITIES
Respondents were asked, "When shopping for groceries, which products are most important." The majority ranked:

  1. Affordable products that provide a clear value for my money 
  2. Finding food products that feed their families for several meals
  3. Products they know their families will enjoy eating

ABOUT THE CONSUMER SURVEY: The online survey of 2,141 respondents was fielded from June 17- 20, 2022.  Responses presented in this survey were weighted by location, education, income and other demographics to be representative of the overall population. To read more about the findings, you can download the full report

ABOUT NCS
NCSolutions makes advertising work better. Our unrivaled data resources powered by leading providers combine with scientific rigor and leading-edge technology to empower the CPG ecosystem to create and deliver more effective advertising. With NCS's proven approach, brands achieve continuous optimization everywhere ads appear through purchase-based audience targeting and sales measurement solutions that have impacted billions in media spend for our customers. NCS is a joint venture company with  Nielsen as the majority owner. 

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SOURCE NCSolutions

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Economics

Legal Services Sourcing and Procurement Market by 2025| COVID-19 Impact & Recovery Analysis | SpendEdge

Legal Services Sourcing and Procurement Market by 2025| COVID-19 Impact & Recovery Analysis | SpendEdge
PR Newswire
NEW YORK, Aug. 18, 2022

NEW YORK, Aug. 18, 2022 /PRNewswire/ — The “Legal Services Market” report has been added to SpendEdge’s…

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Legal Services Sourcing and Procurement Market by 2025| COVID-19 Impact & Recovery Analysis | SpendEdge

PR Newswire

NEW YORK, Aug. 18, 2022 /PRNewswire/ -- The "Legal Services Market" report has been added to SpendEdge's library which is trusted by more than 100 CPOs and 500 category managers who use our insights daily.

The Legal Services market is poised to grow by USD 187.38 Billion, progressing at a CAGR of almost 3.64% during the forecast period

https://spendedge.com/sample-report/process-instrumentation-sourcing-and-procurement-intelligence-report

Key Highlights Offered in the Report:

  • Information on how to identify strategic and tactical negotiation levels that will help achieve the best prices.
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Fetch actionable market insights on the post-COVID-19 impact on each product and service segment.

Some of the Top Legal Services suppliers listed in this report:

This Legal Services procurement intelligence report has enlisted the top suppliers and their cost structures, SLA terms, best selection criteria, and negotiation strategies.

  • Latham and Watkins
  • Allen and Overy
  • Hogan Lovells

Fetch actionable market insights on the post-COVID-19 impact on each product and service segment:

https://spendedge.com/sample-report/process-instrumentation-sourcing-and-procurement-intelligence-report

Top Selling Report:

  1. Asset Recovery Services - Forecast and AnalysisThe asset recovery services will grow at a CAGR of 9.49% during 2021-2025. Asia Asset Recovery Pte Ltd., TES-Amm Singapore Pte Ltd., and Iron Mountain Inc. are among the prominent suppliers in the asset recovery services market. Click the above link to download the free sample of this report.
  2. Vulnerability Management Sourcing and Procurement ReportVulnerability Management Procurement Market, prices will increase by 4%-6% during the forecast period and suppliers will have moderate bargaining power in this market. Click the above link to download the free sample of this report.
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To access the definite purchasing guide on the Legal Services that answers all your key questions on price trends and analysis:

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Table of Content

  • Executive Summary
  • Market Insights
  • Category Pricing Insights
  • Cost-saving Opportunities
  • Best Practices
  • Category Ecosystem
  • Category Management Strategy
  • Category Management Enablers
  • Suppliers Selection
  • Suppliers under Coverage
  • US Market Insights
  • Category scope
  • Appendix

About SpendEdge:

SpendEdge shares your passion for driving sourcing and procurement excellence. We are the preferred procurement market intelligence partner for 120+ Fortune 500 firms and other leading companies across numerous industries. Our strength lies in delivering robust, real-time procurement market intelligence reports and solutions.

Contacts:

SpendEdge
Anirban Choudhury
Marketing Manager
Ph No:
+1 (872) 206-9340
https://www.spendedge.com/contact-us

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