New approach could overcome fungal resistance to current treatments

 

Current medications aren't particularly effective against fungi. The situation is becoming more challenging because these organisms are developing resistance to antimicrobial treatments, just as bacteria are. Now, researchers report in ACS Infectious Diseases that they have identified compounds that tackle these infections in a new way -- by interfering with fungal enzymes required for fatty acid synthesis -- potentially opening the door to better therapies.


Superficial infections by Candida or other types of fungi can cause irritating but relatively minor conditions such as oral thrush and athlete's foot, but invasive infections can result in debilitating and deadly diseases such as cryptococcal meningitis and some hospital-acquired infections. More people are getting these infections because of the growing use of invasive surgery, implanted catheters and immunosuppressive therapy. And some patients, such as those with severe COVID-19 or HIV, are especially susceptible to fungal infections. In addition, treatments can be toxic and often don't work, in part because of increasing resistance. Current targets for these compounds include molecules necessary for making fungal cell walls. As an alternative, Glen. E. Palmer and colleagues began looking for potential therapies that could work through a different mechanism and thereby avoid the drawbacks of these drugs.

The researchers zeroed in on fungal fatty acid (FA) synthase and desaturase enzymes, which are essential for the growth and virulence of human fungal pathogens. It's been difficult to devise a rapid chemical assay to find inhibitors for these enzymes, since it's hard to isolate the enzymes. So the team instead combined genetic engineering with a whole-cell assay to screen thousands of small molecules. Although none of the tested compounds blocked FA synthase activity in Candida albicans cell cultures, 16 inhibited FA desaturase activity. A core acyl hydrazide structure was found to be key to the activity of several of these molecules, which were effective even against drug-resistant strains of several infectious species of fungi, while showing little to no toxicity to mammalian cells. The researchers note that these compounds are promising leads for further development as antifungal agents.

See:

Christian DeJarnette, Chris J. Meyer, Alexander R. Jenner, Arielle Butts, Tracy Peters, Martin N. Cheramie, Gregory A. Phelps, Nicole A. Vita, Victoria C. Loudon-Hossler, Richard E. Lee, Glen E. Palmer. Identification of Inhibitors of Fungal Fatty Acid Biosynthesis. ACS Infectious Diseases, 2021; DOI: 10.1021/acsinfecdis.1c00404

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Information Systems Impacting Building Supply Chains

Image: Pexels

It’s never good news when the words “Supply Chain” are included in a headline. Something along the line has gone wrong, and it likely affects several million people. Earlier this year the Suez canal debacle grabbed headlines when a container ship beached itself. The blockage exasperated a supply chain that was already under stress from Covid-19 and cost roughly $6.7 million per minute.

 Article by Indiana Lee

In the UK, Atul Kariya, a partner at MHA, recently commented that the labour shortages wreaking havoc on UK supply chains were “not caused by Brexit but has been worsened by restrictions on movement as a result of Brexit immigration rule changes, in addition to tax measures”.

 

The Suez Canal blockage and Mr. Kariya’s comments reflect an underlying theme: supply chain issues rarely exist in isolation. Instead, supply chain problems come in clusters. In the words of Jennifer Canstenon, writing for Forbes, “it’s a messy paradigm”.

 

Trying to establish a route through the mess of supply chain management is tricky at the best of times. However, recent developments in information systems show promising signs for the future. Widespread adoption of artificial intelligence (AI) is going to take time, but business leaders are already recognizing the potential risk-reducing benefits of AI-led supply chains. Construction is one industry that may benefit greatly from the wider adoption of AI in supply chain management, as it faces unique supply chain issues in our post-pandemic reality.

Supply Chain Issue in Building and Construction

Building and construction companies currently face a number of supply chain complications. This is a serious issue as poor supply chain management will lead to delays, fines, and inefficient business practices.

 

In the UK, Darren Dodd, of the Financial Times, has warned that warehouses across the UK may run out of space within the year. Further reports have found that 8 out of 10 builders are currently facing a materials shortage.

 

The stress placed on supply chains globally will invariably lead to higher costs, meaning that strategic leveraging of emerging information systems like AI will be pivotal for those looking to remain on track in construction and building.

Benefits of Information Systems

Complex information systems have been informing supply chain management decisions for a number of years. However, companies are now looking to leverage technological developments to boost supply chain resiliency and improve their bottom lines. By adopting new information systems like predictive analysis, companies can make more accurate forecasts of potential supply chain issues and can adapt their practices in response to increasing demands or potential areas of slack.

 

Information systems can also directly benefit the highly competitive building and construction industries. Knut Alicke, writing for McKinsey, found that “early adopters to [AI] improve logistics costs by 15 percent, inventory levels by 35 percent, and service levels by 65 percent, compared with slower-moving competitors”. For those in building and construction--who are often pitched directly against competitors--a reduction of logistical cost and an increase in inventory management efficiency of this level is impossible to ignore (particularly as the idea of self-building continues to grow in the UK and younger generations express significant interest in building their own homes).

Hires You Need to Make

In order to utilize information systems, companies need to hire information system specialists. Information system specialists are well-educated employees who combine various skills and approaches. They are adept computer system managers and are capable of maintaining and understanding key analytics, but they also have the ability to look beyond the program and consider the business as a whole.

 

An adept information system specialist should also be capable of managing teams, as supply chain management typically utilizes an array of employees who assert their value and specialisms along the supply chain.

Risks to Consider

The use of information systems in supply chain management is not a clearly defined science. It is impossible to predict the problems of tomorrow, and information systems must be redesigned to consider sustainability. In addition, AI relies on massive amounts of data in order to make accurate predictions.

 

Currently, there may not be enough data for AI to make accurate forecasts, and businesses that are transitioning to AI-led supply chain management may be feeling some growing pains. That said, the utilization of AI is all about patience. AI systems grow as data grows--as more data is made available, AI will have a greater tolerance and will contribute massively to the overall reduction of risk in supply chain management.

The Future of Building Supply Chains

Researchers and business leaders are always looking to align developments in information systems with current business practices. Advancements in artificial intelligence and the technology we use for shipping and handling can increase the overall efficiency of a supply chain, which ultimately improves companies’ bottom lines.

 

While there will be significant growing pains with all new technologies, the future of building and construction points towards technological development and the adoption of AI in decision making.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Physics explains the 20 second handwashing rule

 

Handwashing is of great importance in relation personal hygiene. According to the U.S. Centers for Disease Control and Protection (CDC): “Washing hands can keep you healthy and prevent the spread of respiratory and diarrheal infections from one person to the next.”

 

The agency, along with other health authorities around the world, recommends washing hands with hot soap and water for 20 seconds. Such advice has been in the public domain for the past two years in the context for the COVID-19 pandemic.

 

But where has the 20 seconds come from? While there is a biological basis and 20 seconds appears to be effective, it remains that no one – unt now – has looked in detail at the dynamics of the 20 second process.

 

Researchers from the non-biological domain have looked at the 20-second rule, drawing on the laws of physics to explore what is happening at the micro-level. The physics behind hand washing has behind has rarely been studied.

 

The new approach comes from scientists working at Hammond Consulting Limited. Here researchers have described a model that captures the key mechanics of hand-washing. This model helps to establish the optimal time – and this is confirmed as a minimum of 20 seconds - provided the washing activity is vigorous. With a gentler washing, there is insufficient physical activity with which to disassociate particles from skin. 

 

 

This was shown by simulating hand-washing through a series of experiments. In doing so, the  researchers have estimated the time scales upon which particles, including viruses and bacteria, were removed from hands.

 

The mathematical model developed acts in two dimensions. This is with one wavy surface moving past another wavy surface, where a thin film of liquid between the two. The wavy surfaces represent hands because they are rough on small spatial scales.

 

The study showed that particles are trapped on the rough surfaces of each hand in potential wells (this is described by the research team as a little like lying at the bottom of a valley). In order for particles to escape, the energy from the water flow must be high enough to get them up and out of the valley.

 

Furthermore, the strength of the flowing liquid depends on the speed of the moving hands. In contrast, a stronger flow removes particles more easily. In other words, the faster the motion, then the more likely particles are to be released).

 

This means if a person moves their hands too gently, or too slowly, relative to one another, the forces created by the flowing fluid are not big enough to overcome the force holding the particle down.

 

It also stands that even when particles are removed, that process is not fast. Typical hand-washing guidelines suggest at least 20 seconds under the tap (faucet). It follows that it takes about 20 seconds of vigorous movement to dislodge potential viruses and bacteria, using soap.

 

The research appears in the journal Physics of Fluids, where the research paper is titled “Will we ever wash our hands of lubrication theory?”

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Shape-morphing microrobots deliver drugs to cancer cells

Chemotherapy successfully treats many forms of cancer, but the side effects can wreak havoc on the rest of the body. Delivering drugs directly to cancer cells could help reduce these unpleasant symptoms. Now, in a proof-of-concept study, researchers reporting in ACS Nano made fish-shaped microrobots that are guided with magnets to cancer cells, where a pH change triggers them to open their mouths and release their chemotherapy cargo.

Scientists have previously made microscale (smaller than 100 µm) robots that can manipulate tiny objects, but most can't change their shapes to perform complex tasks, such as releasing drugs. Some groups have made 4D-printed objects (3D-printed devices that change shape in response to certain stimuli), but they typically perform only simple actions, and their motion can't be controlled remotely. In a step toward biomedical applications for these devices, Jiawen Li, Li Zhang, Dong Wu and colleagues wanted to develop shape-morphing microrobots that could be guided by magnets to specific sites to deliver treatments. Because tumors exist in acidic microenvironments, the team decided to make the microrobots change shape in response to lowered pH.

So the researchers 4D printed microrobots in the shape of a crab, butterfly or fish using a pH-responsive hydrogel. By adjusting the printing density at certain areas of the shape, such as the edges of the crab's claws or the butterfly's wings, the team encoded pH-responsive shape morphing. Then, they made the microrobots magnetic by placing them in a suspension of iron oxide nanoparticles.

The researchers demonstrated various capabilities of the microrobots in several tests. For example, a fish-shaped microrobot had an adjustable "mouth" that opened and closed. The team showed that they could steer the fish through simulated blood vessels to reach cancer cells at a specific region of a petri dish. When they lowered the pH of the surrounding solution, the fish opened its mouth to release a chemotherapy drug, which killed nearby cells. Although this study is a promising proof of concept, the microrobots need to be made even smaller to navigate actual blood vessels, and a suitable imaging method needs to be identified to track their movements in the body, the researchers say.

The authors acknowledge funding from the National Natural Science Foundation of China, the National Key R&D Program of China, Major Scientific and Technological Projects in Anhui Province, the Fundamental Research Funds for the Central Universities, the Youth Innovation Promotion Association of the Chinese Academy of Sciences, the Hong Kong Research Grants Council, CAS-Croucher Funding Scheme for Joint Laboratories, the Hong Kong Special Administrative Region of the People's Republic of China Innovation and Technology Commission and the Multi-scale Medical Robotics Center.
Chen Xin, Dongdong Jin, Yanlei Hu, Liang Yang, Rui Li, Li Wang, Zhongguo Ren, Dawei Wang, Shengyun Ji, Kai Hu, Deng Pan, Hao Wu, Wulin Zhu, Zuojun Shen, Yucai Wang, Jiawen Li, Li Zhang, Dong Wu, Jiaru Chu. Environmentally Adaptive Shape-Morphing Microrobots for Localized Cancer Cell Treatment. ACS Nano, 2021; DOI: 10.1021/acsnano.1c0665

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)