Culture

There were more than 16.9 million Americans with a history of cancer on January 1, 2019, a number that is projected to reach more than 22.1 million by 2030 based on the growth and aging of the population alone, according to estimates from Cancer Treatment and Survivorship Statistics, 2019. The report is produced every three years by the American Cancer Society in collaboration with the National Cancer Institute to help the public health community better serve this growing population. It appears in CA: A Cancer Journal for Clinicians, with a companion consumer edition published as Cancer Treatment and Survivorship Facts & Figures.

The number of cancer survivors continues to increase in the United States even as incidence rates are stable in women and declining in men. This is due to a growing and aging population, as well as increases in cancer survival due to advances in treatment and early detection. The report uses the term "cancer survivor" to describe a person who has a history of cancer, from the time of diagnosis through the remainder of their life. However, it is important to note that many people with a history of cancer do not embrace this term.

The report estimates there are currently 8.1 million males and 8.8 million females in the U.S. with a history of cancer. About two out of three cancer survivors (68%) were diagnosed five or more years ago and nearly one in five (18%) was diagnosed 20 or more years ago. Nearly two-thirds (64%) are aged 65 years or older. In addition, the report estimates that in the U.S., there are 65,850 cancer survivors 14 years and under and 47,760 ages 15 to 19.

The three most prevalent cancers among men in 2019 are prostate (3,650,030), colon and rectum (776,120), and melanoma of the skin (684,470). Among women, the top three prevalent cancers are breast (3,861,520), endometrium (uterine corpus) (807,860), and colon and rectum (768,650). Cancer prevalence figures differ from those for cancer incidence because prevalence reflects not only occurrence but also survival and median age at diagnosis. For example, lung cancer is the second most commonly diagnosed cancer in men, but ranks eighth in prevalence, largely because of the disease's poor overall survival.

The authors' estimate of the number of cancer survivors in 2030 (22.1 million) is based on population projections produced by the United States Census Bureau, using current incidence, mortality, and survival rates. Changes in cancer occurrence and survival due to advances in treatment and early detection could further impact cancer prevalence.

Many survivors cope with long-term physical effects of treatment as well as psychological and socioeconomic sequelae. Challenges also remain for survivors and their caregivers with regard to navigating the health care system, including poor integration of survivorship care between oncology and primary care settings, as well as financial and other barriers to quality care, particularly among the medically underserved.

"People with a history of cancer have unique medical, psychosocial, and economic needs that require proactive assessment and management by health care providers," said Robin Yabroff, Ph.D., senior scientific director of Health Services Research and co-author of the report. "Although there are growing numbers of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care."

The report says identification of the best practices for delivering quality rehabilitation and posttreatment cancer care is needed and points to ongoing efforts by the American College of Surgeons, the Alliance for Quality Psychosocial Cancer Care, and the American Cancer Society. To this end, the American Cancer Society recently released a cancer survivorship blueprint to establish priority areas for care delivery, research, education, and policy. In addition, the American Cancer Society has produced guidelines for selected cancer types to assist primary care and other clinicians in the provision of posttreatment care for people with a history of cancer.

The national monitoring of the availability and use of information systems in healthcare in Finland revealed that the use of e-services in the exchange of health information among health service providers has increased compared to earlier studies performed since 2003.

In particular, the national health information exchange service, Kanta, enables information exchange between private and public health service providers.

"Major progress has been made in the range of e-health services available to citizens," says Professor Jarmo Reponen from the University of Oulu.

"In addition to electronic appointment bookings and advisory services, citizens can view their own data and communicate with health services more frequently than they could three years ago."

In the e-welfare sector, the supply of electronic services that are available to citizens and clients has increased, especially in the public sector. The integrating national infrastructure is actively being developed and currently several electronic document specifications and a client data repository as a part of Kanta Services in social welfare are in development.

However, there is a need for information management tools for professionals working in social services.

A drug interaction alert system is already being widely used

Clinical decision support (CDS) systems add intelligence to the healthcare systems and are both more frequently available and more likely to be integrated into the electronic patient record system compared with when the previous survey was conducted.

The most commonly integrated CDS tools are drug interaction alert systems.

"It is extremely important that we have these warning systems which improve patient safety and increase the quality of care. Moreover, in the future, we shall need even more advanced tools to support clinical workflow and the management of care on a daily basis," emphasises Professor Reponen.

Healthcare professionals are proficient users of electronic patient information systems and want to be part of their development

Nurses rate themselves as proficient users when assessing their competence in using electronic data and information systems. However, poor functionalities of information systems may jeopardise information flow and disturb nurses' work processes.

"When data cannot be accessed in a timely manner or the same data is stored in multiple systems, severe safety concerns, difficulties in decision-making, deficiencies in information exchange, and frustration in work processes may arise," highlights Professor Kaija Saranto from the University of Eastern Finland.

Healthcare professionals are keen to be involved in developing information systems. However, because of changes in the working environment, healthcare professionals need more training in the use of information systems and e-services.

Physicians' user experiences of electronic patient record systems have slightly improved compared with the results of two earlier surveys. However, there are still clear areas for improvement, for example information retrieval from other organisations is estimated to be as time consuming as it was in 2010.

The practical application of healthcare and social welfare data will be monitored and assessed regularly based on a national strategy

The Finnish Ministry of Social Affairs and Health has regularly commissioned national surveys on e-health and e-welfare to monitor the current state and trends in e-health and e-welfare in Finland to gather evidence for use in future development.

The national e-health and e-welfare strategy, 'Information to support well-being and service renewal. eHealth and eSocial Strategy 2020' set the goals for the monitoring.

The information was drawn from five nationwide e-health and e-welfare surveys. The survey aimed at citizens measures e-health and e-welfare service use and utilisation.

Two surveys were targeted at organisations (healthcare/social care), and measure the availability and use of e-health tools and services as well as the availability of e-welfare tools and services. Two surveys were targeted at professionals (physicians and nurses), and measure usability and the benefits of e-health tools and services. All the surveys were produced as part of the project on the Monitoring and assessment of social welfare and health care information system services (STePS 2.0 project).

A Swansea University study has revealed how as little as an hour a week of outdoor learning has tremendous benefits for children and also boosts teachers' job satisfaction.

Through interviews and focus groups, researchers explored the views and experiences of pupils and educators at three primary schools in south Wales that had adopted an outdoor learning programme, which entailed teaching the curriculum in the natural environment for at least an hour a week.

Interviews were held with headteachers and teachers, and focus groups were conducted with pupils aged 9-11 both before and during the implementation of an outdoor learning programme within the curriculum.

The schools in the study reported a variety of benefits of outdoor learning for both the child and the teacher and for improving health, wellbeing, education and engagement in school.

Lead author of the study Emily Marchant, a PhD researcher in Medical Studies at Swansea University, explained: "We found that the pupils felt a sense of freedom when outside the restricting walls of the classroom. They felt more able to express themselves, and enjoyed being able to move about more too. They also said they felt more engaged and were more positive about the learning experience. We also heard many say that their well-being and memory were better, and teachers told us how it helped engage all types of learners."

The benefits of outdoor education for children are well documented, but a finding of this study is the impact that the outdoor learning programme had on teachers.

Emily said: "Initially, some teachers had reservations about transferring the classroom outdoors but once outdoor learning was embedded within the curriculum, they spoke of improved job satisfaction and personal wellbeing. This is a really important finding given the current concerns around teacher retention rates. Overall, our findings highlight the potential of outdoor learning as a curriculum tool in improving school engagement and the health, wellbeing and education outcomes of children.

"The schools within our study have all continued with regular outdoor learning within the curriculum. With support and recognition from education inspectorates of the wider benefits to children's development and education, outdoor learning could be set within the primary school curriculum."

The Estée Lauder Companies Inc. (NYSE: EL) Research & Development (R&D) team will present data focused on new findings in skin metabolomics, skin defense, ingredient science, and anti-aging research at the 2019 World Congress of Dermatology (WCD) in Milan, Italy from June 10 -15.

Additionally, a sponsored symposium, "Metabolomics as a New Diagnostic to Assess Skin Health" will take place on June 12, presented by Session Chair, Leihong Xiang, M.D. Ph.D., Keynote Speaker, Paolo Sassone-Corsi, Ph.D., University of California, Kirk Beebe, Ph.D., Metabolon, Inc. and Nadine Pernodet, Ph.D., The Estée Lauder Companies. The symposium will unveil novel metabolomics research illustrating the complex relationship between genetics and the environment, unveiling the role they play in skin and how their changes reflect skin's condition.

The Estée Lauder Companies' R&D team is a global leader in understanding the factors that impact our skin and in using the data found in the skin to understand how it behaves and appears. The following summarizes the Estée Lauder Companies' R&D team's research that will be presented at the 2019 WCD meeting:

Skin metabolomics can help us better understand young and aging skin and the impact of circadian rhythm changes in the human skin metabolome.

The relationship between autophagy and inflammation in skin cells, with a look at the link between autophagy and resolution phase, a mechanism in the inflammation process that helps protect the skin against chronic inflammation.

Development of a skin model to further understand the causes of post inflammatory hyperpigmentation (PIH) and how those findings offer more options to explore the underlying biological causes.

Macrocystis pyrifera (Kelp) ferment is effective in addressing inflammation and in enhancing fibroblast migration. Together these activities may help skin maintain its natural integrity and a state of visible calm.

UP302, a plant-derived tyrosinase enzyme inhibitor, acts as a whitening agent to reduce pigmentation, outperforming the benchmark compound, Kojic Acid, at the industry-standard concentration.

There is a beneficial link between sirtuins and maintaining the integrity of natural cellular activity.

Examining changes in skin physiology induced by exposure to small particles (PM 2.5) can help inform skin protection against the detrimental effects from the environment.

A multi-prong approach to acne treatment significantly reduced facial lesions after a 12-week trial.

"The Estée Lauder Companies' R&D team is a global leader in understanding the impact of biological processes like those in the skin," said Nadine Pernodet, Ph.D., Vice President, Skin Biology and BioActives, Research and Development, The Estée Lauder Companies. "These new findings provide us with an unprecedented snapshot of skin status, enabling new precision approaches and treatments to improve skin's appearance. As the first in our industry to use metabolomics in relation to time, we have a better understanding of key factors of skin repair efficiency and damage accumulation and their relationship to skin circadian rhythm. We will continue to apply this knowledge to formulate products that can address and improve optimal skin processes, leading to younger looking skin."

The following research posters will be presented by The Estée Lauder Companies R&D at the 2019 WCD meeting, and are summarized below:

First assessment of skin circadian metabolomics on young and aging subjects, The Estée Lauder Companies and Metabolon, Inc., [Poster #5638]

Metabolomics is a comprehensive study of metabolites, which are small molecule (

Autophagy and inflammation relation in skin cells, The Estée Lauder Companies, [Poster #3897]

Autophagy, a major cellular degradative and recycling pathway, is critical for cellular longevity and has been linked to the aging process. A decrease in autophagy leads to increased cellular damage as we age. For the first time in skin cells, a relationship between autophagy and the resolution phase of inflammation has been found, showing their link in protecting the skin against long-lasting inflammation and its visible effects.

Development of a post inflammatory hyperpigmentation model in reconstructed skins, The Estée Lauder Companies [Poster #4263]

Prominently seen in people with darker skin tones, post inflammatory hyperpigmentation (PIH) occurs following an inflammatory insult, such as acne or a cutaneous injury, and results in a hyperpigmented area of the skin. Little is known about the cause of PIH, but new research using in vitro models offers the chance to screen the skin pigmentation effects of migration inhibitors on melanocytes--offering more options to explore the underlying biological causes.

Macrocystis pyrifera ferment: Anti-inflammatory and pro-resolution properties, The Estée Lauder Companies and Max Huber Research Laboratories [Poster #2331]

Research has shown that inflammation, especially chronic inflammation, is a potential cause of accelerated skin aging. The resolution of inflammation is an actively coordinated and dynamic process that attenuates inflammation and enables skin's natural repair and helps skin maintain its natural integrity. In this study, the anti-inflammatory and pro-resolution activities of the Macrocystis pyrifera (kelp) ferment were assessed. Results show that the use of the kelp ferment is effective in addressing all three phases of inflammation and in enhancing fibroblast migration. Together these activities may help skin maintain a state of visible calm and its natural integrity.

Evaluation of a potent skin whitening agent, The Estée Lauder Companies [Poster #4255]

UP302, a plant-derived tyrosinase enzyme inhibitor, acts as a whitening agent by preventing melanin synthesis through the conversion of tyrosinase in human skin. Using a clinical whitening test measuring Skin Lightening Factor, both in vitro and in vivo, against Kojic acid (the industry standard), the UP302 treatments demonstrated a more-significant decrease in melanin, indicating a decrease in tyrosinase activity and pigmentation.

Sirtuins and their importance in skin, The Estée Lauder Companies [Poster #3893]

Increasing evidence has demonstrated the importance of Sirtuins, also known as longevity proteins, in maintaining optimal skin cell processes such as metabolism, genomic stability, inflammation, energy, environmental stress response and aging. The effects of environmental stressors were examined through the response of skin cells to UVB and ozone (measured by the effect on energy (ATP) production and oxidative damage (ROS), along with the effect on mechanical properties). This research demonstrates a beneficial link between sirtuins and cellular integrity and activity, and for the first time, introduces the role of Sirtuin-2 in supporting skin cells' natural mechanical properties.

The effect of exposure to PM 2.5 on skin physiological function, The Estée Lauder Companies [Poster #4260]

Using an in vitro model, changes in skin physiology induced by exposure to fine particles (PM 2.5) were observed. Results suggested that these particles may be damaging to the epidermis and compromise skin barrier function, as well as impact morphology, physiology, and inflammatory response in cells. Findings showed that skins treated with PM 2.5 had compromised skin barrier integrity and an increase in cellular proteins indicating a possible inflammatory response.

A multi-prong approach to acne significantly reduced facial lesions after a 12-week treatment, The Estée Lauder Companies [Poster #4194]

The pathogenesis of acne is complex, with strong evidence supporting the involvement of sebaceous hyperplasia, follicular hyperkeratinization, bacterial hypercolonization, and inflammation. In order to combat acne and address these components, researchers used a multi-prong formulation to assess its effect on the overall lesion count in a population with acne. Findings showed treatments significantly reduced the total lesion count after 12 weeks.

"As science and technology enable more a more holistic and in-depth look at skin over time, The Estée Lauder Companies can continue to better understand the biological mechanisms that drive how skin behaves and how to combat environmental stressors and insults to skin. We will continue to apply our research findings to help define and advance the future of beauty for our global consumers." said Tom Mammone, Ph.D., Vice President, Skin Physiology and Pharmacology, Research & Development, The Estée Lauder Companies.

An analysis of U.S. intelligence programs aimed at collaborating with academic and industry partners finds that these collaborations are valuable for addressing complex intelligence challenges. The study also notes that institutional silos, lack of information sharing and lack of trust are obstacles to getting the most out of these collaborative efforts.

The researchers point to the Laboratory for Analytic Sciences (LAS) as the first long-term, collocated attempt at collaboration between the intelligence community, academia and industry. As such, the study authors report that the LAS holds promise as a laboratory that can be used by the intelligence community and its partners to develop effective approaches to cooperation and collaboration.

The LAS is a research partnership between North Carolina State University and the National Security Agency, based on NC State's campus.

"We looked at five collaborative intelligence programs," says Beverly Tyler, a professor of management, innovation and entrepreneurship at NC State who is co-author of a paper on the work. "Do any of the five provide an ideal model for how cross-sector, interdisciplinary collaborations on intelligence should work? No. But they do offer useful lessons about what can and should be considered to develop successful collaborations: time, effort, leadership, strong communication and dedicated resources."

"And the payoff for such collaborations can be invaluable," Tyler says. "For example, the LAS was created in 2013, and it has received a number of awards for its work - including two National Intelligence Awards for mission contributions."

"Given today's fiscal realities and intelligence challenges, the need for cross-sector collaboration is only going to increase," says Kathleen Vogel, an associate professor of public policy at the University of Maryland and lead author of the paper.

For this study, the researchers drew on interviews with members of the intelligence and academic communities, as well as reports and journal articles related to LAS and four other collaborative intelligence programs. Their analysis led them to identify certain key themes related to intelligence collaborative efforts, as well as factors that they identified as being essential to success.

One of the key themes was that the hybrid organizations used by the intelligence community for cross-sector, interdisciplinary collaborations are particularly vulnerable to budget cuts. They also found that these collaborations can vary widely in terms of how interdisciplinary they are - and that the broader the interdisciplinary focus, the less likely they are to survive.

However, the researchers say that the LAS gives the intelligence community an opportunity to learn more about how it can design and maintain a more complex program that incorporates a broader interdisciplinary collaboration over a longer period of time.

The study also identified a number of factors that are key to the success of collaborative intelligence programs. Four of those factors are:

High-level support within the collaborating organizations;

Long-term commitment by collaborating organizations to accomplish the program's intended goals;

Internal communications mechanisms to evaluate how ongoing research efforts are going; and

Open lines of communication with the relevant intelligence organizations to ensure that research remains mission-focused, relevant and meaningful.

"We want to be clear that we found all collaborative efforts by the intelligence community to be valuable," Tyler says. "Our goal here is not to nitpick what has been done. It's simply to identify ways to make these programs even better moving forward."

Smalleye stingrays are the largest marine stingrays on record, reaching disc widths of up to 222 cm, and yet almost nothing is known about them. Scientists from the Marine Megafauna Foundation have for the first time used photo IDs to study this elusive animal in southern Mozambique, one of the only locations where it is regularly seen in the wild. Their findings are published today in the journal PeerJ.

"We reported the first sightings of smalleye stingray in 2004 and have since been racing against the clock to learn more about their ecology before it is too late", said Dr Andrea Marshall, co-founder and principal scientist of the Marine Megafauna Foundation. 31% percent of the world's sharks and rays are threatened with extinction according to the IUCN Red List of Threatened Species ? due to lack of scientific effort and information, it has not been possible to evaluable the conservation status of smalleye stingrays to date. "This species of ray is likely in trouble too but we can't protect what we don't know much about. Our study is an important first step in understanding more about the animal's ecology and behaviour", she added.

"These mysterious giants are thought to be patchily distributed across the Indian Ocean and Western Pacific, but southern Mozambique is probably the best location to encounter them on inshore reefs", Marshall added.

The marine biologists tested whether photographs of the stingrays' (Megatrygon microps) white dorsal spots could be used to distinguish and track individuals over long periods of time.

"Through local dive centers, we called on tourists to help us collect images of this solitary stingray. Fortunately for us, southern Mozambique and its rich marine life attract many passionate scuba divers, most of which own GoPros or other lightweight cameras and will happily make their images and footage available for research", said Atlantine Boggio-Pasqua who volunteered with the Tofo-based foundation.

She added: "Their contributions proved immensely valuable, we managed to gather more than 140 photographs suitable for comparison and identification, with some images dating as far back as 2003."

The team was able to visually identify 70 different individuals, including 15 that had been seen on several occasions in the area. The dorsal spot patterns looked unchanged over the years indicating they may be permanent markings like in manta rays.

Boggio-Pasqua said: "Smalleye stingrays may look intimidating at first glance with their large, razor-sharp tail spines, but they're actually really charismatic and easy to approach. We hope to receive many photo and video contributions from citizen scientists in future. They could tell us more about the species' habitat preference as well as feeding and cleaning behavior."

The encountered stingrays were often spotted at cleaning stations where reef bannerfish and other small fish appeared to be removing parasites from the rays' skin.

The photographic study also provided a glimpse into the migratory behaviour of Megatrygon microps. Some individuals traveled hundreds of kilometers along the coastline, including a near-term pregnant female which traveled from Tofo to the Bazaruto Archipelago and back (200km in a minimum of 102 days and a total 400km return trip). She returned to Tofo, no longer visibly pregnant, suggesting this individual had pupped during her journey.

This proved to be the longest straight-line distance ever recorded for any species of whiptail stingrays (Dasyatidae family). Unlike other stingrays, smalleye stingrays are rarely seen resting on the seabed and are thought to be semi-pelagic.

Smalleye stingrays are likely under threat from increasing fishing pressures. Targeted and incidental catch in coastal gillnets and industrial purse seiners operating offshore are an ongoing issue in Mozambique.

"There are so many questions that remain unanswered about this rare species. Where do they live, how fast do they mature and how do they reproduce? Filling these knowledge gaps is crucial to figuring out how to protect them properly in Mozambique and other parts of the Indian Ocean", concluded Dr Marshall.

Addressing the lack of available data will eventually allow scientists to formally assess the species' conservation status in the IUCN Red List and inform management practices.

The ability to hear depends on proteins to reach the outer membrane of sensory cells in the inner ear. But in certain types of hereditary hearing loss, mutations in the protein prevent it from reaching these membranes. Using a zebrafish model, researchers at Case Western Reserve University School of Medicine have found that an anti-malarial drug called artemisinin may help prevent hearing loss associated with this genetic disorder.

In a recent study, published in the Proceedings of the National Academy of Sciences (PNAS), researchers found the classic anti-malarial drug can help sensory cells of the inner ear recognize and transport an essential protein to specialized membranes using established pathways within the cell.

The sensory cells of the inner ear are marked by hair-like projections on the surface, earning them the nickname “hair cells.” Hair cells convert sound and movement-induced vibrations into electrical signals that are conveyed through nerves and translated in the brain as information used for hearing and balance.

The mutant form of the protein–clarin1–render hair cells unable to recognize and transport them to membranes essential for hearing using typical pathways within the cell. Instead, most mutant clarin1 proteins gets trapped inside hair cells, where they are ineffective and detrimental to cell survival. Faulty clarin1 secretion can occur in people with Usher syndrome, a common genetic cause of hearing and vision loss.

The study found artemisinin restores inner ear sensory cell function—and thus hearing and balance—in zebrafish genetically engineered to have human versions of an essential hearing protein.

Senior author on the study, Kumar N. Alagramam, PhD, The Anthony J. Maniglia Chair for Research and Education, and associate professor at Case Western Reserve University School of Medicine Department of Otolaryngology at University Hospitals Cleveland Medical Center, has been studying ways to get mutant clarin1 protein to reach cell membranes to improve hearing in people with Usher syndrome.

“We knew mutant protein largely fails to reach the cell membrane, except patients with this mutation are born hearing,” Alagramam said. “This suggested to us that, somehow, at least a fraction of the mutant protein must get to cell membranes in the inner ear.”

Alagramam’s team searched for any unusual secretion pathways mutant clarin1 could take to get to hair cell membranes. “If we can understand how the human clarin1 mutant protein is transported to the membrane, then we can exploit that mechanism therapeutically,” Alagramam said.

For the PNAS study, Alagramam’s team created several new zebrafish models. They swapped the genes encoding zebrafish clarin1 with human versions—either normal clarin1, or clarin1 containing mutations found in humans with a type of Usher syndrome, which can lead to profound hearing loss.

“Using these ‘humanized’ fish models,” Alagramam said, “we were able to study the function of normal clarin1 and, more importantly, the functional consequences of its mutant counterpart. To our knowledge, this is the first time a human protein involved in hearing loss has been examined in this manner.”

Zebrafish offer several advantages to study hearing. Their larvae are transparent, making it easy to monitor inner ear cell shape and function. Their genes are also nearly identical to humans—particularly when it comes to genes that underlie hearing. Replacing zebrafish clarin1 with human clarin1 made an even more precise model.

The researchers found the unconventional cellular secretion pathway they were looking for by using florescent labels to track human clarin1 moving through zebrafish hair cells. The mutated clarin1 gets to the cell membrane using proteins and trafficking mechanisms within the cell, normally reserved for misfolded proteins “stuck” in certain cellular compartments.

“As far as we know, this is the first time a human mutant protein associated with hearing loss has been shown to be ‘escorted’ by the unconventional cellular secretion pathway,” Alagramam said. “This mechanism may shed light on the process underlying hearing loss associated with other mutant membrane proteins.”

The study showed the majority of mutant clarin1 gets trapped inside a network of tubules within the cell analogous to stairs and hallways helping proteins, including clarin1, get from place to place. Alagramam’s team surmised that liberating the mutant protein from this tubular network would be therapeutic and tested two drugs that target it: thapsigargin (an anti-cancer drug) and artemisinin (an anti-malarial drug).

The drugs did enable zebrafish larvae to liberate the trapped proteins and have higher clarin1 levels in the membrane; but artemisinin was the more effective of the two. Not only did the drug help mutant clarin1 to reach the membrane, hearing and balance functions were better preserved in zebrafish treated with the anti-malarial drug than untreated fish.

In zebrafish, survival depends on normal swim behavior, which in turn depends on balance and the ability to detect water movement, both of which are tied to hair cell function. Survival rates in zebrafish expressing the mutant clarin1 jumped from 5% to 45% after artemisinin treatment.

“Our report highlights the potential of artemisinin to mitigate both hearing and vision loss caused by clarin1 mutations,” Alagramam said. “This could be a re-purposable drug, with a safe profile, to treat Usher syndrome patients.”

Alagramam added that the unconventional secretion mechanism and the activation of that mechanism using artemisinin or similar drugs may also be relevant to other genetic disorders that involve mutant membrane proteins aggregating in the cell’s tubular network, including sensory and non-sensory disorders.

A group of researchers from Japan has discovered a novel enzyme from a soil fungus. In their study published in the Journal of Biological Chemistry, they speculate that this enzyme plays important roles in the soil ecosystem, and then describe its structure and action. Once the usefulness of the main product of this enzyme is better understood in the future, this enzyme could also be exploited for industrial purposes. The researchers state, "Our study sheds light on the fact that new enzymes are still being discovered. It possibly lays the foundation for further research to identify new enzymes that yield carbohydrates that were once thought to be extremely difficult to prepare."

Carbohydrates are probably the most versatile organic molecules on the planet, as they play various roles in organisms. Accordingly, the functions and structures of enzymes related to carbohydrate are just as diverse. Glycoside hydrolases (GHs) are enzymes that break "glycosidic bonds" in carbohydrates or sugars. GHs are the largest known group of carbohydrate-related enzymes, and the group keeps expanding. A novel family, GH144, was identified by the same research group in the past from a soil bacterium Chitinophaga pinensis and called CpSGL.

The enzyme endo-β-1,2-glucanase (SGL), a member of the GH family, is involved in the metabolism of β-1,2-glucan, which is a polysaccharide (sugar chain) composed of β-1,2-linked glucose units. β-1,2-glucan serves as an extracellular carbohydrate that plays important roles in the symbiosis or infectivity of some bacteria. However, the role of SGLs in eukaryotic cells and their relationship with bacterial SGLs are not well understood.

This group of Japanese scientists from different universities and a research institute, working on a collaborative project led by Masahiro Nakajima, has discovered a novel SGL enzyme from a soil fungus, Talaromyces funiculosus. The enzyme, hereafter called TfSGL, showed no significant sequence similarity to other known GH families. However, it showed significant similarities to other eukaryotic proteins with unknown functions. The researchers thus propose that TfSGL and these related GH enzymes be classified into a new family, which they call GH162.

Usually when scientists find a novel protein--in this case, an enzyme--they further clone the gene containing the sequence that encodes it to better understand its functionality. This clone is called a "recombinant" sequence. The recombinant TfSGL protein (TfSGLr) was found to break down both linear and cyclic β-1,2-glucans to sophorose, a simpler and smaller carbohydrate.

Stereochemical analysis done by these researchers revealed that it is an inverting enzyme, a characteristic that is associated with its mechanism of action. They found that TfSGL breaks down sophorooligosaccharides (β-1,2-glucooligosaccharides), with degree of polymerization of 5 or more, to the disaccharide sophorose as the main product.

X-ray crystal structure analysis revealed that the overall structure of TfSGLr is similar to that of members of the GH144 family mentioned earlier, notably CpSGL. However, the two enzymes are very different in amino acid sequences, as well as substrate recognition sites and the positions of the base catalyst. This difference indicates that TfSGL and its homologs probably make up a novel family, and that there could be a molecular evolutionary relationship between GH144 and GH162.

In fact, most TfSGL homologs are found in eukaryotic organisms, particularly fungi (Basidiomycota and Ascomycota), and slime molds (Mycetozoa). Some of these species are associated with the rhizosphere, which is the ecosystem around the root and the soil, where the metabolism of cyclic β-1,2-glucan might occur as part of this symbiotic relationship with plants. Other species are parasitic, and thus, it is believed that the cyclic β-1,2-glucan might be used to reduce immune responses in hosts. TfSGL homologs are also speculated to be involved in interactions with other organisms.

This novel enzyme, TfSGL, breaks down β-1,2-glucan into sophorose. According to Nakajima, "As the functions and applications of sophorose become more apparent in the future, the enzyme could potentially be used for sophorose production. β-Glucanases already play an important role in our lives, as they are widely used in biofuel production.

Nakajima concludes by surmising, "The structures of sugar chains are complex and diverse, and sugar chains are also involved in various life phenomena. Synthesis and degradation of such diverse sugar chain structures are performed by enzymes, but only one end of the diversity seems to have been understood. With our research, we hope to identify genes encoding novel enzymes that break down sugar chains and yield carbohydrates that were once considered extremely difficult to prepare."

A study from Massachusetts General Hospital (MGH) researchers finds that electronic consultations (e-consults) in allergy and immunology can simplify the process of providing the most appropriate care, often reducing the need for in-person specialist visits. The paper, which has been published online in the Journal of Allergy and Clinical Immunology: In Practice, reports on the first two years of the MGH program and finds a significant reduction in the time needed to access specialist guidance.

"We found that e-consults expedite care for all patients with allergy/immunology conditions," says senior author Kimberly Blumenthal, MD, MSc, MGH Division of Rheumatology, Allergy and Immunology. "Whereas wait times for an in-person patient visit with an allergist often exceed three weeks, e-consults can provide allergist guidance to referring physicians within 72 business hours. For many patients, e-consults avert the need for an in-person visit entirely; and even when an in-person consult is required, the initial e-consult provides valuable information - including additional patient history, previous diagnostic testing and treatment trials - that can make the in-person consult more productive and valuable for the allergist, the referring provider and the patient."

Electronic, clinician-to-clinician consultations based on data in the electronic health record do not require real-time communication and are designed to address non-urgent questions specific to the care of an individual patient. The MGH began offering e-consults in Cardiology and Dermatology in late 2013 and extended the program to Allergy/Immunology in August 2016. As of January 2019, the MGH e-consult program involves 47 specialty areas, and almost 10,000 e-consults were provided during 2018.

The current study, led by first author Neelam Phadke, MD, MGH Division of Rheumatology, Allergy and Immunology, looked at data regarding allergy/immunology e-consults provided from August 2016 through July 2018, as well as in-person consults beginning in August 2014. Of approximately 300 e-consults completed during the study period, around 60 percent led to recommendations for in-person specialty visits, while 27 percent provided only advice and education to the referring practitioner. When the e-consult led to a recommendation for an in-person specialty visit, information from the e-consult made visits more productive by allowing the allergist to be better prepared. Educational information provided via e-consults benefited both referring physicians and the patients, often providing reassurance on the appropriateness of a planned course of action.

Two-thirds of e-consults related to patients with histories of potentially allergic reactions to drugs, primarily antibiotics like penicillin, many in conjunction with a program to evaluate pregnant patients with a history of penicillin allergy. Immunology e-consults could result from patient or provider concerns about frequent infections or abnormal antibody levels. While the average wait time for an in-person allergist visit before institution of the e-consult program was 22.5 days, the wait time reduced to 21.0 days after the program began. Allergists completed e-consults in an average of 11 minutes, and the average turnaround time for the referring provider to receive allergy specialist guidance was less than 24 hours.

Study co-author Jason H. Wasfy, MD, MPhil, MGH Cardiology - who founded the MGH e-consult program in 2013 and now directs population health management at MGH - says, "E-consults have become a critical tool in our efforts to innovate in outpatient care delivery. We believe they can increase patient satisfaction, since we always give patients the choice between e-consults and regular in-person consults, and they reduce the burden for primary care providers. We also believe they can improve the quality of care and reduce costs, since electronic consults can substitute for in-person consults that are billed to insurance companies and to patients themselves."

Lead author Phadke notes that a key limitation to broader use of e-consults is the reliance on electronic medical records systems that may not be shared between specialists and referring physicians, a problem that could disproportionately affect smaller hospitals that already lack access to subspecialists like allergists. But when the required systems are in place, she says, "E-consults can allow primary care physicians to receive guidance from one or more subspecialists, synthesize messages that may have been conveyed from multiple providers, and delivery neatly packaged recommendations to the patient."

ST. LOUIS, MO, June 11, 2019 - Overdose from opiates has skyrocketed. According to the National Center for Health Statistics, on average, 130 Americans die every day from an opioid overdose.1 The high cost of antidotes such as NARCAN® prevents many first responders from having access to lifesaving antidotes when they need it most.2 Researchers at the Donald Danforth Plant Science Center have identified a new method of producing these compounds using a microorganism discovered in a waste stream associated with the processing of opium poppy. This green chemistry process has the potential to greatly reduce the cost of the antidote drugs as well as decrease chemicals currently used that result in large amounts of harmful waste. Details of the discovery were published as the cover story in the journal Nature Sustainability: "Enzyme morphinan N-demethylase for more sustainable opiate processing".

"Enzymes perform reactions at efficiencies that surpass synthetic chemistry, thereby reducing the cost and impact of drug production on the environment. We work now to optimize production levels of the enzyme to a scale sufficient for industrial processes. Greener manufacturing would make a difference in people's lives," said Megan Augustin, lead author and research associate in the Kutchan lab at the Danforth Center.

Naturally occurring opiates, such as morphine and thebaine, are produced in poppy species. Thebaine is converted into painkillers and opiate addiction treatments, the latter requiring a chemical reaction called N-demethylation. Current opiate N-demethylation utilizes noxious reagents, resulting in harmful waste. One way to make opiate production more sustainable is to use enzymes rather than chemicals. Microorganisms provide a rich source of enzymes useful for metabolizing unique compounds in their environment. Augustin and her colleagues probed an opium processing waste stream sample to identify an organism capable of catalyzing opiate N-demethylation. To identify a biocatalyst, a sludge sample was subjected to minimal medium containing thebaine as the sole carbon source. This led to the discovery of Thebainfresser, a Methylobacterium that metabolizes opiates by removing the N-methyl group. N-demethylation was induced following growth in minimal medium, a characteristic that led to discovery of the underlying gene MND (morphinan N-demethylase). The enzyme MND was found to be robust and versatile, N-demethylating structurally diverse substrates at varying temperatures and pH levels. In addition, MND tolerated selected organic solvents and maintained activity when immobilized. These properties make it an attractive candidate for further development for pharmaceutical manufacture.

We all say we don't like liars. But when it comes time to negotiating a big sale, it turns out we tolerate people stretching the truth, and even expect it.

New research from the University of Chicago Booth School of Business finds that the ability to deceive is viewed as a sign of competence in jobs that require selling.

In the study, Deception as Competence: The Effect of Occupational Stereotypes on the Perception and Proliferation of Deception, Chicago Booth Assistant Professor of Behavioral Science Emma Levine and Johns Hopkins University's Brian Gunia find that people don't always disapprove of deception. In fact, they perceive the ability to deceive as an asset in occupations that are stereotyped as high in "selling orientation."

"Deception, in the form of fraud, embezzling, and corruption, costs the economy a great deal of money and undermines the economy's underlying moral fabric," Gunia and Levine explain. "Companies expose themselves to greater risk by hiring deceivers."

In two pilot studies, the researchers asked participants to rate 32 occupations as "high" or "low" in selling orientation, reflecting the degree to which occupational members persuade others to make immediate purchases as part of their jobs. In four subsequent studies, the researchers honed in on three occupations that are stereotyped as particularly high in selling orientation--sales, investment banking, advertising--and three occupations that participants viewed as relatively low in selling orientation--consulting, nonprofit management, accounting.

The researchers then ran experiments in which participants observed individuals lying or acting honestly in a variety of circumstances (for example, when reporting their expenses after a business trip or when completing an economic game in the laboratory). Finally, participants judged how successful and competent a liar or honest individual would be in occupations that were high or low in selling orientation--and, in two of the studies, whether to hire them into those occupations.

Among the key findings: Participants believed that liars would be more successful in high-selling orientation occupations (such as banking, advertising, and sales) than low selling-orientation occupations (such as nonprofit management and accounting). Furthermore, participants believed that liars would be more successful than honest people in high-selling orientation occupations.

Indeed, when participants had the opportunity to hire individuals to complete selling-oriented tasks, they were more likely to hire deceivers for these tasks, even when their own money was on the line.

"We found that people don't always disapprove of liars," Levine says. "Instead, they think liars are likely to be successful in certain occupations--those that do a lot of high-pressure selling."

The paper is published in the journal, Organizational Behavior and Human Decision Processes.

The findings may help to explain why deception persists in certain occupations: because hiring managers and other organizational actors see deceivers as more competent for high-pressure sales roles, and hire them at an elevated rate, the researchers find.

High-pressure selling occupations, which include investment bankers and advertisers, are some of society's highest-status and highest-paid occupations, so prospective employees and employers should worry "if deception is a prerequisite for employees to get hired and rewarded," Levine says.

Organizations intent on reducing deception should avoid framing occupational tasks as requiring high-pressure sales tactics to succeed, the study says. Instead, they would do well to align their job requirements with a customer-oriented approach to selling that emphasizes how the employee can help fulfill a client's long-term interests. Such a shift could reduce hiring managers' tendencies to see deceivers as competent and reduce the temptation to recruit deceivers into key roles.

"Armed with the knowledge that deception is perceived to signal competence in high-pressure sales occupations," the researchers write, "companies may want to explicitly deem deception as incompetent."

A finding from University of Alberta researchers is shining new light on the role fibrinogen has in regulating a natural defence mechanism in the body. The discovery is hoped to contribute to improved diagnosis and treatments for patients in a variety of diseases ranging from inflammation, to heart failure, to cancer.

Fibrinogen is a well-known protein that is essential for wound healing and blood clotting in the body. But a study published in Scientific Reports shows it is also a natural inhibitor of an enzyme named MMP2 that is important for normal organ development and repair.

MMP2 is typically found in increased levels in the blood in disease conditions. The researchers believe a vital function of fibrinogen is to allow or disallow the enzyme to carry out its normal functions. However, high levels of fibrinogen may excessively inhibit MMP2, which could result in arthritic and cardiac disorders similar to those seen in patients with MMP2 gene deficiency.

"Whenever there's an infection or there's an injury, fibrinogen can go up by tenfold in the blood. So at that concentration it would excessively inhibit MMP2," said Hassan Sarker, a PhD candidate at the U of A and study lead author.

"Binding of fibrinogen in the circulation to MMP2 enzymes prevents them from docking to target tissues," added Carlos Fernandez-Patron, a professor of biochemistry at the U of A, who directed this research. "It affects their activity and we don't know exactly whether that results in a beneficial or deleterious effect. It's something we need to investigate."

The finding opens a new window into the inner workings of the MMP family of enzymes. The researchers say having a greater understanding of how MMPs are regulated creates opportunities for future treatments. They also suspect that abnormal MMP2 activity could be an undesirable side effect of important common medications such as the cholesterol-lowering drug known as statins and the antibiotic doxycycline, both of which are known to inhibit MMPs.

The researchers emphasize that future therapeutic developments must strike a balance between the levels of MMPs and their inhibitors, such as fibrinogen, so that net MMP activity in the body remains at nearly normal levels. "We don't want to inhibit them more than needed and we don't want to cause their expression to be higher than it should," said Fernandez-Patron. "Knowing how those enzymes are regulated is key to improving diagnosis, prognosis and treatment of patients experiencing abnormal levels of either MMP2 or fibrinogen."

Bottom Line: In a new recommendation, the U.S. Preventive Services Task Force (USPSTF) recommends clinicians offer preexposure prophylaxis (PrEP) with effective antiretroviral therapy to people at high risk of acquiring HIV to decrease their risk of infection with the virus that causes AIDS. The USPSTF routinely makes recommendations about the effectiveness of preventive care services. This recommendation statement comes after a review of the evidence on the benefits of PrEP to prevent HIV infection. There were more than 38,000 new diagnoses of HIV infection reported in the United States in 2017. HIV is now treatable but there is no cure and the virus can have significant health consequences.

(doi:10.1001/jama.2019.6390)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

In a search for clues to what may delay or prevent Alzheimer's disease, Johns Hopkins Medicine scientists report that smarter, more educated people aren't protected from the disease, but do get a cognitive "head start" that may keep their minds functioning better temporarily.

Put another way, the investigators say, those who start out with greater cognitive reserve -- a baseline of higher mental functioning -- may have more they can afford to lose before Alzheimer's disease symptoms begin to interfere with their daily lives compared with those who don't have as much schooling or participate regularly in mentally challenging tasks.

The findings, published in the April issue of the Journal of Alzheimer's Disease, suggest -- but don't prove -- that exercising your brain might help keep people cognitively functional longer, but won't ward off the inevitable decline of Alzheimer's disease.

"Our study was designed to look for trends, not prove cause and effect, but the major implication of our study is that exposure to education and better cognitive performance when you're younger can help preserve cognitive function for a while even if it's unlikely to change the course of the disease," says Rebecca Gottesman, M.D., Ph.D., professor of neurology at the Johns Hopkins University School of Medicine and of epidemiology at the Johns Hopkins Bloomberg School of Public Health.

About 5 million people in the U.S. live with Alzheimer's disease, a number expected to triple by 2060, according to the U.S. Centers for Disease Control and Prevention.

Because effective treatment options aren't available for Alzheimer's disease or other forms of dementia, researchers are interested in identifying ways to prevent or delay disease. Earlier studies suggested that people with higher intelligence or more education might have lower rates of these diseases, and Gottesman's team designed a study to test the idea.

For the study, the researchers used data from the federally funded Atherosclerosis Risk in Communities (ARIC) study, in which nearly 16,000 healthy participants in midlife from Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota, were enrolled from 1987 to 1989 and followed over the next decades. Twenty years into the study, participants were an average of 76 years old. About 57% were women, and 43% were African American, with the remaining participants white.

The investigators focused on a group of 331 participants without dementia who were part of an additional study, the ARIC-PET study, in which participants underwent specialized brain imaging. Some 54 had less than a high school education, 144 had completed high school or earned their GED diploma, and 133 had some college or more formal education.

Twenty years in, all participants underwent MRIs and positron emission tomography (PET) scans of their brains to measure levels of amyloid beta protein accumulated in the brain, a standard marker of Alzheimer's disease. The average PET scan score indicating the amount of amyloid beta protein in the brain after being compared with a part of the brain where amyloid beta doesn't accumulate was 1.2. Some 171 participants were categorized as having elevated values greater than this standard, and the remaining participants were assigned to the nonelevated amyloid beta values category.

In late life (ages 65-84), each participant's cognition was assessed with 10 standard tests of memory, language and other intellectual function. Three of these tests were administered at about the 10-year timepoint as well. The average score indicating normal cognition was set to zero for statistical purposes, with a value of 1 indicating an above-average score, and -1 indicating a below average score.

Participants with any level of amyloid beta and with college, postgraduate or professional schooling had average cognitive scores of about one or more standard units higher than those who had less than a high school education, regardless of beta amyloid levels in the brain. Gottesman says these data suggest that education seems to help preserve cognition, since those with education scored higher.

Gottesman noted that cognition scores in midlife weren't associated with elevated levels of amyloid beta protein in the brain in late life. White participants with higher late-life cognition scores had a 40% lower risk of having elevated amyloid beta protein in the brain. This general trend was observed in African American participants too, but to a lesser degree (around 30% lower risk).

"Our data suggest that more education seems to play a role as a form of cognitive reserve that helps people do better at baseline, but it doesn't affect one's actual level of decline," says Gottesman. "This makes studies tricky because someone who has good education may be less likely to show a benefit of an experimental treatment because they are already doing well."

What this means for future research into developing therapies for Alzheimer's disease, Gottesman says, is that it's important to focus on some sort of independent and specific biomarker to show actual treatment benefit. She also says studies must look at trends in performance over time rather than at one timepoint.

Myocardial infarction (MI) results in the localized death of the muscle cells that are essential for the heart's pumping function. Depending on the extent of the damage, MI may initiate a progressive deterioration of cardiac function that ultimately leads to heart failure. Following an acute infarction, cells of the immune system induce an inflammatory reaction in the heart muscle, which promotes clearance of the damaged tissue. "Many novel post-infarct therapies are designed to inhibit the inflammation," says Professor Oliver Söhnlein of the Institute for Cardiovascular Prevention at LMU. "However, inflammatory reactions everywhere in the body are normally self-limiting. So we set out to develop a therapeutic approach which makes use of the endogenous processes that enable the inflammation to be turned off," he explains. A new study, which appears in the Journal of the American College of Cardiology, reports how much progress Söhnlein and his team have made so far.

At the core of their strategy is the protein annexin A1 (AnxA1), which plays an important role in the regulation of the innate immune response - in particular in the switch from the damage-disposal phase of inflammation to the restorative processes that lead to its resolution and healing. In the new study, the authors used two strains of mice. One lacked the ability to synthesize AnxA1, while the other served as the positive control. In mice that were unable to produce AnxA1, the inflammatory reaction induced by MI was more widespread and persistent, and the degree of impairment of cardiac function was greater, than in the control mice. Furthermore, therapeutic administration of AnxA1 following heart damage was found to promote myocardial repair in wild type mice.

The protein causes immune cells called macrophages to secrete the signal protein VEGF-A, which stimulates the formation of new blood vessels. "This in turn helps to increase blood flow, which is a crucial factor in the healing process after myocardial infarction," says Söhnlein. He and his colleagues have observed similar positive effects of AnxA1 on the repair of heart damage in pigs. "So the annexin A1-based therapy looks like a promising approach to mitigating the effects of acute heart attacks."