Culture

INDIANAPOLIS -The majority of people visiting preoperative testing clinics before an elective surgery do not have an advance directive (AD) in case of surgical complications. This can lead to situations where patients' families are forced to make tough decisions about their loved one's care.

A study from researchers at the Regenstrief Institute, Indiana University Health and Indiana University School of Medicine found that only 30% of the patients in the study reported having some form of AD documenting their wishes regarding emergency medical care. However, only 16% had one on file in their electronic medical record (EMR) where a clinician could access it at the time of surgery. When there is no record of care preferences, families must decide what kind of emergency care their loved one receives.

An advance directive is a legal document stating the patient's wishes for care if he or she is incapacitated. These preferences can include whether or not the person wants to receive CPR or intubation or who is in charge of making care decisions on their behalf. If there is no AD, doctors turn to a priority list of people, reaching out to them, in order of priority, to make the decision.

The lead author of the study, Shilpee Sinha, M.D., is the service line lead for the Adult Academic Health Center for Palliative Care at IU Health in Indianapolis. She sees patients every day who are at an increased risk of surgical complications. "When a crisis does occur," Dr. Sinha said, "family members tend to project their own emotions into what they think is best for the patient, but their choices may not be what the patient actually wants."

Dr. Sinha and her colleagues looked at EMRs of 400 patients who underwent preoperative evaluation. They found only 16% of those people had some form of AD on file.

Dr. Sinha performed this research as part of The Advanced Scholars Program for Internists in Research and Education (ASPIRE). ASPIRE is a one-year program through the Division of General Internal Medicine and Geriatrics at IU School of Medicine and the Regenstrief Institute that provides physicians in clinical practice with a chance to hone their skills in research.

"One of my goals for doing this study is to drive clinical change," said Dr. Sinha. "The discussion of advance care planning is not part of the established routine. I think we've achieved buy-in on the idea of having these conversations. Now we need actual logistical application."

Regenstrief researcher Alexia Torke, M.D., M.S., was Dr. Sinha's mentor through the ASPIRE program, and senior author of this paper. She has conducted extensive research in surrogate decision making.

"When an AD is not available in cases of emergency, it creates a complex situation for the care providers and surrogate decision makers. Emotions are often high, and family members may have difficulty navigating those emotions to make the best decision for their loved ones," said Dr. Torke. "Work like Dr. Sinha's is very important. These findings suggest there is a significant opportunity for improvement in advanced care planning in the clinical setting."

"Advance Care Planning in A Preoperative Clinic: A Retrospective Chart Review" was published in the Journal of General Internal Medicine. The study was funded through the ASPIRE program. Dr. Torke was supported by a Midcareer Investigator Award in Patient-Oriented Research (K24 AG053794) from the National Institute on Aging.

Aggressive behaviour in pet dogs is a serious problem for dog owners across the world, with bite injuries representing a serious risk to both people and other dogs. New research by the University of Bristol has explored the factors that in?uence how owners manage aggressive behaviour in their dogs. The study found that clinical animal behaviourists should focus on helping dog owners to feel confident in the effectiveness of the behaviour modification techniques that they recommend and, in their ability, to actually use them successfully.

Dogs are the most popular pet in the UK, with 31 per cent of households owning one or more dogs. However, the majority of dog owners ?nd some aspect of their pet's behaviour problematic and behavioural disorders are often mentioned as the main reason dogs are given to rehoming organisations.

The aim of the study was to find out what influences an owner's decision to use outdated punishment-based methods and what the barriers and drivers were to dog owners using positive reinforcement-based solutions. In particular, the researchers wanted to explore whether theoretical models and psychological concepts used in other contexts could help them to understand this issue.

Current evidence suggests that positive reinforcement-based behaviour modification techniques are both humane and effective in the treatment of aggressive behaviour in dogs and that the use of punishment-based techniques are likely to be detrimental to the welfare of the dog and can lead to an increase in aggression. However, many dog owners continue to use punishment-based techniques in an attempt to inhibit this problematic behaviour.

The research found owners' perceptions of how effective the behaviour modification techniques are and how effectively they feel they can apply them are key factors predicting their current and future use.

Although a lot of attention has been focussed on the consequences to the dog of using certain training techniques, this is the first-time research has systematically examined the factors influencing an owner's choice of training technique, as well as the impact of this behaviour upon the owners of these dogs.

Dr Emily Blackwell, Director of Companion Animal Population Health at the Bristol Veterinary School, said: "Our findings highlight the need for behaviourists to offer practical support to owners, to demonstrate the effectiveness of reward-based training and to provide them with an opportunity to practice under expert guidance, so that they feel confident in their ability to use the techniques before attempting to apply them independently.

"The study also shows the emotional impact that attempting to manage a reactive dog can have, with its associated ups and downs. It is therefore important for practitioners to consider the wellbeing of the owner as well as the dog, including the potential implications of this, when helping them along their journey."

Dr Emma Williams, VC Fellow in Digital Innovation and Wellbeing in the School of Psychological Science, added: "The majority of research on companion animal behaviour has focused on the behaviour of the animal itself, rather than the behaviour of the owner. We believe this is the first time that psychological theories exploring how people respond to threatening situations, such as Protection Motivation Theory, have been applied to understand people's interactions with their pets."

The study has identified the potential for extreme negative emotional responses and feelings of failure experienced by owners when their dog reacts badly towards another person or dog. This provides a foundation from which, in the future, research can further explore the influence of different psychological factors on an owner's decision to use positive reinforcement techniques to manage their dog's aggressive behaviour.

This research will be built on by designing and testing improved communications-based interventions that encourage engagement with positive reinforcement-based techniques across different groups of dog owners and the various practitioners who work with them.

BETHESDA, M.D. (June 17, 2019) - Nearly three-quarters (74%) of Americans are concerned about burnout among healthcare professionals, according to new survey data released today by ASHP (American Society of Health-System Pharmacists). The results follow a 2018 study in the American Journal of Health-System Pharmacy (AJHP) that found 53 percent of pharmacists self-reported a high degree of burnout caused by increasing stresses and demands.

"Pharmacists, as patient care providers and members of the healthcare team, strive to provide the best quality of care to their patients. But with chronic job stressors many clinicians are experiencing symptoms of burnout," said ASHP CEO Paul W. Abramowitz, Pharm.D.,Sc.D. (Hon.), FASHP. "We believe that fostering and sustaining the well-being and resiliency of the pharmacy workforce is in the best interest of patients and the healthcare system as a whole. ASHP has had a longstanding commitment to working with our members and their patients and colleagues to raise awareness and advance solutions to help prevent burnout in healthcare."

The survey, conducted online in May 2019 by The Harris Poll on behalf of ASHP, drew on the opinions of more than 2,000 U.S. adults ages 18 and up and demonstrated a high degree of public awareness that burnout among pharmacists, physicians, nurses, and other professionals can lead to impaired attention and decreased functioning that threatens to cause medical errors and reduce safety. Another recent study conducted by the Mayo Clinic in Rochester, Minn., found that burnout costs the U.S. healthcare system an estimated $4.6 billion a year.

One in four Americans in the new survey said they believe hospital pharmacists (26%) and retail pharmacists (25%) are often burnt out. The National Academy of Medicine's definition of clinician burnout includes clinicians feeling emotionally exhausted, unsatisfied and detached from one's work, and a low sense of personal accomplishment. According to the study in AJHP, pharmacists list increased workloads, periodic drug shortages, and heavy demands from electronic health records, insurance, and regulatory requirements as drivers of burnout.

A majority of Americans encourage healthcare professionals to take care of themselves. In The Harris Poll, 9 out of 10 (91%) said it is important that their doctor, pharmacist, nurse, or other healthcare professional do whatever they can to avoid burnout; and 77 percent said that when they see their clinician is feeling burnt out, they become concerned about their own care and safety.

The survey showed high levels of awareness of burnout, nearly half of U.S. adults (47%) said they would avoid asking questions if they thought their healthcare professional appeared burnt out because they would not want to add to their stress. The survey also suggests that healthcare professionals may be conveying signs of burnout without knowing it. U.S. adults said they can tell when healthcare providers feel burnt out if they seem tired (60%) or rushed (56%).

"A healthy and thriving clinician workforce is essential to ensure optimal patient health outcomes and safety," said Abramowitz. "Within the healthcare industry, we are working to help build a culture of resilience and well-being to ensure that no patient or clinician is harmed due to burnout; but it takes a concerted effort from all entities involved - providers and healthcare organizations."

ASHP has, for nearly 40 years, provided resources, tools, and community connections to help its members develop solutions to combat burnout in the workplace. The organization's 2018 professional policy emphasizes the shared responsibility among members of the healthcare team and between individuals and organizations to take action to boost resilience. ASHP is a sponsoring member of the National Academy of Medicine's Action Collaborative on Clinician Well-Being and Resilience, which seeks to understand the underlying causes of clinician stress, burnout and suicide, and to advance evidence-based solutions.

ASHP recently launched an online portal - Wellbeing & You - which serves as both a resource center and a place for pharmacists, student pharmacists, and pharmacy technicians to share their experiences with burnout and take a pledge to show their personal commitment to strengthening resilience.

To build a resilient workforce, ASHP recommends that clinicians monitor their stress levels, find a mentor, develop meaningful social connections, embrace change, and start a daily gratitude practice.

ASHP encourages healthcare organizations to boost resilience by:

Recognizing the presence and risk of burnout in the workplace

Identifying burnout risk factors

Forming a committee to explore burnout causes and resilience solutions

Evaluating changes to confirm an increase in employee resilience

Celebrating and sharing positive improvements

A first-of-its-kind survey of American neurologists reveals that more than half carry the mistaken belief that a patient's sexual orientation and gender identity have no bearing on treatment of neurologic illness.

That belief can have damaging repercussions for patients seeking care, according to a study published today in the journal Neurology.

"Many neurologists are not aware that gender-affirming care can directly impact neurologic health," said Holly Hinson, M.D., M.C.R., an associate professor of neurology in the OHSU School of Medicine.

Hinson, who is leading the American Academy of Neurology initiatives to improve medical care for LGBTQI patients, co-authored the research paper that accompanied the survey results. The survey was distributed to a random, representative sample of 1,000 U.S.-based members of the AAN, resulting in a total of 135 responses.

Sexual and gender minority, or SGM, individuals have been shown to have persistent disparities in health care, researchers write, including twice the mortality rate compared to heterosexuals.

"SGM status can have a direct bearing on diagnosis and treatment, even within a non-primary care specialty like neurology," the authors wrote. "Unfortunately, many medical professionals receive little to no training in SGM health, which could lead to substandard care due to lack of knowledge."

About 36% of survey respondents agreed that they would tailor their neurologic care based on a patient's sexual orientation or gender identity. More than half the respondents were interested in receiving further training in culturally appropriate care.

A lack of awareness can be problematic for neurologic patients in a variety of ways, with the study citing several examples:

Antiretroviral medications such as preexposure prophylaxis (PrEP), increasingly prescribed to gay men, can be associated with neuropathy.

Poor understanding of SGM identity can lead to discrimination within long-term care facilities during neurorehabilitation.

Gender-affirming hormones can interact with other important medications, for example, anti-epileptic therapy used to seizures.

Notably, it is the first survey of any physician group to ask the sexual and gender identity of the physicians themselves: about 88% identified as heterosexual or straight. Some of the providers who identify as sexual or gender minorities reported their own fear of discrimination in the workplace.

"Providers themselves are not immune to stigma and burnout," Hinson said.

Some dinoflagellate plankton species are bioluminescent, with a remarkable ability to produce light to make themselves and the water they swim in glow. Now, researchers reporting in Current Biology on June 17 have found that for one dinoflagellate species (Lingulodinium polyedra), this bioluminescence is also a defense mechanism that helps them ward off the copepod grazers that would like to eat them.

"That bioluminescence, in addition to being a beautiful light phenomenon in the sea, is a defensive mechanism that some species of plankton use to ward off their enemies," said Andrew Prevett of the University of Gothenburg, Sweden. "The bioluminescent cells sense very low concentrations of their grazers and turn up the light when needed, which is rather impressive for a unicellular organism. This in turn helps to better protect them from their grazers, letting them survive longer to reproduce and therefore compete better within the plankton."

Through a combination of high-speed and low-light sensitive videos, the researchers, including Prevett, Erik Selander, and their collaborators at the Technical University of Denmark, revealed that the bioluminescent cells flash upon contact with the copepod grazer. The copepod reacts by rapidly rejecting the flashing cell, seemingly unharmed.

They note that observational data from the west coast of Sweden support their study's prediction that the presence of copepod grazers would have a positive effect on the abundance of bioluminescent L. polyedra. The single-celled, bioluminescent dinoflagellates are usually poor competitors, because they grow at about a third of the rate of other plankton. But copepods reject them in favor of grazing on more poorly defended but otherwise faster-growing plankton species.

The researchers had expected increased bioluminescence to result in reduced grazing by copepods. But they were surprised by just how great the reduction was.

"Earlier studies had shown that dinoflagellates with naturally brighter bioluminescence than L. polyedra were grazed less but still required cell concentrations to be relatively high before all grazing on the bioluminescent cells ceased," Prevett said. "L. polyedra abundance in our study is low by comparison, and we were surprised at how effective the bioluminescence defence became despite this."

It's still not clear exactly how the glow protects L. polyedra, however.

"There are three popular theories as to how bioluminescence protects dinoflagellates," Prevett said. "The first is that it acts as aposematic colouration, a warning to potential grazers that the cell is toxic or harmful to the grazer in some way. The second is that the flash of bioluminescence behaves like a flash-bang and startles the copepod, provoking a copepod escape response or disorienting it long enough for the dinoflagellate to escape. The third theory suggests that the flash acts as a form of burglar alarm, attracting the attention of a larger visual predator, like a fish, which could track and consume the copepod. There is evidence to support each of these theories and bioluminescence protection could be combinations of some or all of the above."

No matter how it works, it appears their ability to ward off predators with bioluminescence serves as a key mechanism behind the success of an otherwise poor competitor such as L. polyedra, the researchers say.

They say that they plan to pursue more studies in the system exploring the ways that the "fear" of being eaten drives the structure of ecosystems. They plan to study compounds produced by copepods as general alarm signals and their influence on complex plankton assemblages.

"These indirect effects of consumers are understudied in unicellular dominated food webs such as marine plankton," Prevett said. "This paper and other similar results suggest that indirect predator effects are strong drivers in the microscopic food web of the oceans too."

An international research team has investigated the transport mechanism of a bacterial membrane protein using an artificially produced antibody fragment. The transport proteins, called ABC exporters, are present, for instance, in the cell membranes of bacteria and in large quantities in cancer cells and are responsible for transporting small molecules out of the cells. Some transporters can pump antibiotics or chemotherapy agents out of the cells, thus rendering therapies ineffective. In the current study, researchers worked with isolated ABC exporters and showed how substrate transport is related to the energy drive of the protein and how both can be modified by an antibody fragment or by mutations. The results were published in the journal Nature Communications on 21st May 2019.

For the study, Professor Enrica Bordignon and Professor Lars Schäfer from Ruhr-Universität Bochum, both members of the Cluster of Excellence Resolv, cooperated with Professor Markus Seeger from the University of Zurich and Professor Mikko Karttunen from the University of Western Ontario.

Multi-stage transport process

ABC exporters consume energy when transporting molecules out of the cells. They obtain this from the splitting of the energy storage molecule ATP on the inside of the membrane. Broadly speaking, the ABC exporter is comprised of three areas: the energy-providing motor inside the cell, a connector that extends through the cell membrane, and a gate on the outside of the membrane.

For the transport process, the ABC exporter opens inside the cell, takes in a molecule from the cytoplasm, and transports it to the other side of the membrane. There, the outer gate opens and the molecule is excreted - but only if the protein motor splits ATP inside. Only once the outer gate is closed again can the next transport process begin.

Motor switched off

The researchers developed an artificial antibody fragment, also known as a sybody, that docked at the isolated ABC exporter in the test tube. Using X-ray crystallography and electron spin resonance, the team showed that the sybody binds to the open outer gate. As a result of this, the gate was no longer able to close and thus no new transport process could be initiated. Consequently, the motor inside remained switched off; no more ATP was split.

The group confirmed the results in further experiments without the sybody. In these, they specifically replaced certain amino acids of the protein using genetic mutation; this also blocked the closing mechanism of the outer gate and ATP splitting.

"Our analyses have shown that the mechanism to open and close the outer gate is structurally related to the splitting of the energy supplier ATP on the inside," describes Enrica Bordignon. "Our results are fundamental research," says the head of the Bocum-based EPR Spectroscopy Research Group. "We hope to use this information to open up new approaches to combat drug resistance."

Cardiogenic shock is a possible complication of serious heart attack involving an associated mortality rate of approximately 50% of all cases

The combination of this new tool with existing methods renders precise and patient-specific decision-making possible

The research is being led by Dr. Antoni Bayés at Germans Trias and the Proteomics Unit of the CRG and UPF, under Dr. Eduard Sabidó

A joint research effort by the Hospital and the Instituto de Investigación Germans Trias i Pujol (IGTP) is characterising and studying a new cohort of cardiogenic shock patients to predict the risk of having this heart attack-derived complication which, while infrequent, sometimes presents a fatal outcome. It is the first molecular study for risk prediction described for this disease and is based on a proteomic meta-analysis that has made it possible to discover biomarkers and validate their use in decision-making. The new method, combined with existing techniques, will help to implement more precise treatments. Moreover, the know-how has been patented and work is under way to transfer it to the immunological techniques widely used in clinical diagnosis, such as ELISA.

The objective of the study was to obtain a reliable method to predict which post-heart attack cardiogenic shock patients have a greater risk of not surviving. Cardiogenic shock is a possible complication of severe infarction in which the heart is suddenly unable to maintain the required blood flow. It does not occur in all heart attack cases, although it is fatal if it goes undetected and is not treated promptly. In this case, the discovery of four proteins that can be used as biomarkers is a new tool which, in conjunction with existing ones, makes it possible to pre-empt this complication more precisely.

The group led by Dr. Antoni Bayés-Genís at the Hospital e Instituto de Investigación Germans Trias i Pujol (CIBER Cardiovascular investigators) and Dr. Eduard Sabidó of the Proteomics Unit (a node of the ICTS OmicsTech and a member of the ProteoRed-ISCIII network) of the Centre for Genomic Regulation (CRG) and the Pompeu Fabra University (UPF), has identified 4 proteins (from more than 2600 analysed) that identify patients with cardiogenic shock and a poor vital prognosis. The work has been published in the European Heart Journal, the leading publication in the cardiovascular field.

"The article demonstrates the complex work of sample collection we conducted for the Barcelona Discovery cohort, following strict and standard criteria that enabled us to use them to perform an in vitro trial in liquid biopsies to prevent death in patients with cardiogenic shock", Dr. Bayés explains. "This type of complication, if detected in time, can be treated specifically in order to restore blood flow. The know-how provided by this new tool will help us to decide the best treatment option on a by-case basis", he continues.

The title of the trial is CS4P, and it is comprised of these 4 proteins, which were discovered with the help of mass spectrometry. "We used a combination of liquid chromatography and mass spectrometry to quantify the proteins present in the cohort samples. It is the first risk-prediction molecular study described for this disease, and the trial has been transferred to ELISA and validated in a European reference cohort", Sabidó adds.

For the first time ever, an integrated quantitative approach combined with proteomics has been used to discover biomarkers and to be validated as a risk assessment tool in patients with this condition, and in which the level of the four proteins involved was compared to two current evaluation methods. "We have discovered that the new method complements existing ones, making them much more reliable," Bayés concludes.

The proteomics aspect of the work also furnished valuable information about the mechanisms that trigger cardiogenic shock, as well as the failure of other organs in critical patients. In other words, they could be valid biomarkers for other types of failure. There are a great many possibilities for extending the use of protein biomarkers in serious patients by means of similar techniques.

One of the next steps will be to fine-tune the ELISA assays for clinical use. A patent application has also been submitted for the use of the CS4P cardiovascular shock risk stratification model for the IGTP, the CRG and the UPF.

BINGHAMTON, N.Y. - Nurse practitioners are more likely to conduct HIV screenings if they feel that their colleagues support routine screenings, according to new research from Binghamton University, State University of New York. This comes in advance of National HIV Testing Day, taking place June 27.

Despite 40 years of efforts to end the throes of the HIV crisis and now the epidemic, the infection continues to affect gay, bisexual, and other men who have sex with men of all races and ethnicities; Black and Latino men and women; people who inject drugs; youth ages 25 - 34; and people in the Southern U.S. disproportionately.

"Research data suggests that the social norm expectation in practice settings where many nurse practitioners work do not support routine HIV screening," said Jodi Sutherland, clinical assistant professor at Binghamton University's Decker School of Nursing. "This is a disappointing finding given that patients often trust and look to providers to make clinical decisions and judgments that best support their health according to recommendations and practice guidelines."

Sutherland, along with the Decker School's Gale A. Spencer, asked 141 nurse practitioners about their attitudinal, social normative and perceived behavioral control beliefs toward HIV screening and their HIV screening behaviors. The researchers found that the strongest predictor of nurse practitioner HIV screening behavior was social normative expectations, followed by their attitudinal beliefs toward routine HIV screening. The findings revealed that the belief that "my office staff supports routine HIV screening with my patients" predicted HIV screening, whereas the belief that "consent from a parent/guardian should be obtained before screening for HIV in a person younger than 18 years" predicted less HIV screening.

"Nurses provide the essential link between the people of the community and the complex healthcare system," said Sutherland. "Nurse practitioners have an important role to increase HIV screening rates and could help put an end to HIV. This would require the support of the office staff even when HIV testing requires additional time."

Sutherland said that health care organizations and leaders of organizations need to advocate translation of HIV screening recommendations into practice to meet the needs of the individuals, families and communities served. She also stressed a need for research efforts and practice recommendations to address screening in a person younger than 18 years. Recommendations that address procedures for health care providers to perform HIV screening for this age group are also needed.

Schizophrenia causes hallucinations and memory or cognition problems inter alia. This psychiatric illness affects 0.5% of the general population, and it may be related to genetic abnormalities of chromosome 22, known as 22q11 deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms. So, what triggers the illness? Researchers at the University of Geneva (UNIGE), Switzerland, have provided an initial answer after observing and analysing several years of patients with deletion syndrome. The scientists found that the size of the hippocampus, the area of the brain responsible for memory and emotions, was smaller than normal but followed the same developmental curve as in healthy subjects. Yet, when the first psychotic symptoms appear - generally in adolescence - the hippocampus atrophies dramatically. The results, which you can read all about in the journal Molecular Psychiatry, open up new avenues for understanding the causes of schizophrenia.

22q11 deletion syndrome is a neurogenetic disorder that targets chromosome 22. Thirty percent of people affected by the syndrome end up developing psychotic symptoms specific to schizophrenia, such as auditory hallucinations, memory problems, disorders affecting their perception of reality, and difficulties in social interactions characterised by strong paranoia. "It's now known that schizophrenia is linked to the hippocampus, a complex area of the brain that carries out a vast amount of processes simultaneously linked to memory, imagination and the emotions," explains Stephan Eliez, professor in the Department of Psychiatry in UNIGE's Faculty of Medicine. Recent studies have shown that also people suffering from deletion syndrome have a smaller than average hippocampus. "That's why we studied the development of this structure in detail," continues the UNIGE researcher, "so we could understand why some people affected by deletion syndrome eventually develop psychotic symptoms, while others don't."

18-year study investigating the development of the hippocampus

The Geneva team has been following 275 patients aged 6 to 35 years for 18 years: a control groups of 135 individuals - i.e. individuals without genetic problems - and 140 people with deletion syndrome, including 53 with moderate to severe psychotic symptoms. "They underwent an MRI every three years so that we could observe their brain development," says Valentina Mancini, a researcher in UNIGE's Department of Psychiatry. "This has helped us create a statistical model that measures and compares the development of the hippocampus in both groups of patients." It was discovered that the hippocampus of the group affected by deletion syndrome, although smaller from the beginning, followed a growth curve identical to that of the control group. "This meant that we could hypothesise that the smaller size of the hippocampus originates in utero during its development in the womb." The UNIGE scientists also observed the subfields of the hippocampus in detail, discovering that one of them - called CA3 - was not affected by the decrease in size. "This subfield plays a crucial role in the work of memorisation and seems stronger than the other sub-parts," adds professor Eliez.

Adolescence: the period that counts the most

The researchers then compared the developmental curves of the hippocampus in people with deletion syndrome but no psychotic symptoms with those who developed psychotic symptoms. "There's no doubt about our results: around the age of 17 or 18, people with schizophrenic symptoms experience a drastic atrophy in the size of their hippocampus, and especially in the CA3 area, despite CA3 had initially managed to develop normally, unlike the other subfields," says Mancini. But why?

The researchers don't have yet a precise answer that could explain the drastic drop in the development of this vital brain structure. But their hypotheses are geared towards environmental factors, such as stress or neuronal inflammation. "The hippocampus of individuals with deletion syndrome is smaller; this means it has to compensate for its size through hyperactivity. In the event of a huge stress factor, especially during the critical period of adolescence, this hyperactivity might lead to a significant rise in glutamate that 'poisons' the hippocampus and causes its atrophy," explains Mancini. The psychotic symptoms may result from this hyper-compensation, which ends up destroying the hippocampus.

Act before the critical period

The study suggests the following hypothesis: the small size of the hippocampus in patients with 22q11 deletion syndrome is defined in the mother's womb, probably due to poor vascularisation. However, a "second hit" later in development might determine the further hippocampal atrophy and the emergence of psychotic symptoms. As the critical period for schizophrenia is adolescence, the Genevan team is now working on the possibility of preventing the atrophy of the hippocampus in order to preserve its functions.

Human exposure to unnecessary and potentially harmful chemicals could be greatly reduced if manufacturers add chemicals only when they are truly essential in terms of health, safety and functioning of society. That's the conclusion of a study published today in Environmental Science: Processes & Impacts, a peer-reviewed journal published by the Royal Society of Chemistry.

In this study, researchers propose a framework based on the concept of "essential use" to determine whether a chemical is really needed in a particular application. They demonstrate the concept on a class of synthetic chemicals known as PFAS (per- and polyfluoroalkyl substances).

PFAS are used in many consumer goods because of their unique properties such as water and stain repellency. However, a growing number of scientists and health professionals express concern about these chemicals since they persist for a very long time, seep into our water and soil, and may adversely impact people's health and wildlife. Human health problems linked to certain PFAS exposure include kidney and testicular cancer, liver malfunction, hypothyroidism, high cholesterol, ulcerative colitis, lower birth weight and size, obesity, and decreased immune response to vaccines.

The study classifies many uses of PFAS as "non-essential". For example, the study points out that it may be nice to have water-repelling surfer shorts, but in this instance water repellency is not essential. Other products analyzed with the Essential Use Framework include personal care products and cosmetics, durable water repellency and stain resistance in textiles, food contact materials, medical devices, pharmaceuticals, laboratory supplies and ski waxes. Some uses may be regarded as essential in terms of health and safety, e.g., fire-fighting foams, but functional alternatives have been developed that can be substituted instead.

"Our hope is the approach can inform and encourage manufacturers, retailers and end users to consider phasing out and substituting uses of PFASs." said Ian Cousins of Stockholm University, lead author of the study and a world-leading researcher specializing in understanding the sources and exposure pathways of highly fluorinated chemicals. "A starting point would be the phase-out of the multiple non-essential uses of PFASs, which are driven primarily by market opportunity."

The article notes that some retailers and manufacturers are already taking voluntary measures to phase out the use of PFAS in their products. It suggests that the Essential Use Framework can be applied to other chemicals of concern.

It's a feat three decades in the making: Harvard University chemists have achieved what a new paper calls a "landmark in drug discovery" with the total synthesis of halichondrin. Known to be a potent anti-cancer agent in mouse studies, and found naturally in sea sponges -- though only ever in minuscule quantities -- the halichondrin class of molecule is so fiendishly complex that it had never been synthesized on a meaningful scale in the lab.

Researchers led by Yoshito Kishi, Morris Loeb Professor of Chemistry, Emeritus, in Harvard's Department of Chemistry and Chemical Biology, have now synthesized sufficient quantities of E7130, a drug candidate from the halichondrin class, to enable for the first time rigorous studies of its biological activity, pharmacological properties, and efficacy, all conducted in collaboration with researchers at Japanese pharmaceutical company Eisai.

The molecule has undergone unusually rapid development and is already being tested in a Phase I clinical trial in Japan, under a license from Harvard's Office of Technology Development (OTD) to Eisai. The company hopes to begin a second clinical trial in the United States in due course.

The Kishi Lab's results, driven to completion through an intense, three-year research collaboration with Eisai, are published today in Scientific Reports, an open-access Nature journal. The paper reports the total synthesis of the highly potent halichondrin molecule E7130 -- 11.5 grams of it, with 99.81% purity -- and characterizes its mode of action. In preclinical studies, the research team has identified it not only as a microtubule dynamics inhibitor, as was previously recognized, but also as a novel agent to target the tumor microenvironment.

"We spent decades on basic research and made very dramatic progress," says Kishi, whose laboratory has, since 1978, received significant and sustaining support from the National Cancer Institute (NCI) of the National Institutes of Health to study the synthesis of natural products.

The structure of the complete E7130 molecule derived by total synthesis is particularly challenging to replicate because it has 31 chiral centers, asymmetrical points that must each be correctly oriented. In other words, there are roughly 4 billion ways to get it wrong.

When the natural product was first identified 33 years ago by Japanese researchers, it sparked immediate interest. "At that time, they realized the halichondrins looked exceedingly potent," recalls Takashi Owa, PhD, Chief Medicine Creation Officer and Chief Discovery Officer for Eisai's oncology business group, and a coauthor of the paper. Over time, NCI investigators testing tiny amounts of it recognized that it was affecting the formation of microtubules, which are essential to cell division. "Due to the very unique structure of the natural product, many people were interested in the mode of action, and the investigators wanted to do a clinical study," Owa explains, "but a lack of drug supply prevented them from doing it. So 30 years have passed, very unfortunately, but Prof. Kishi is a pioneer in this field."

Over the years, the Kishi Lab advanced methods of convergent synthesis, which enables complex molecules to be assembled from subunits, rather than constructed linearly. Another innovation, now known as the Nozaki-Hiyama-Kishi reaction, protected the highly reactive functional groups while they were being assembled. And in 1992, Kishi and colleagues achieved the first total synthesis of a halichondrin molecule (halichondrin B). The process required a sequence of more than 100 chemical reactions and produced less than a 1% overall yield. It was a major achievement, however, and a simplified version of that molecule, eribulin, became a drug to treat metastatic breast cancer and liposarcoma, now marketed by Eisai. Since then, Kishi's lab has been engaged in basic research on organic synthesis, including discovery and development of new reactions usable at a late stage of synthesis.

"In 1992, it was unthinkable to synthesize a gram-quantity of a halichondrin," Kishi says, "but three years ago we proposed it to Eisai. Organic synthesis has advanced to that level, even with molecular complexity that was untouchable several years ago. We are very delighted to see our basic chemistry discoveries have now made it possible to synthesize this compound at large scale."

"It's a really unprecedented achievement of total synthesis, a special one," says Owa. "No one has been able to produce halichondrins on a 10-gram scale -- one milligram, that's it. They have completed a remarkable total synthesis, enabling us to initiate a clinical trial of E7130."

The team's Scientific Reports paper describes the results of studies conducted in vitro and in vivo, in animal models, that shed light on the molecule's complex mode of action. The team showed that E7130 can increase intratumoral CD31-positive endothelial cells and reduce alpha-SMA-positive cancer-associated fibroblasts, components of the tumor microenvironment that may be involved in the transformation to malignancy.

"Prof. Kishi's expertise provided us with such an exciting and unique opportunity to test the molecule in our systems," says Owa. "I have never experienced this kind of very efficient and rapid, successful collaboration. Just a three-year collaboration took this from the discovery stage to the clinical development of such a complex molecule, having a very unique mechanism and mode of action. To me this is a kind of track record in drug development."

"The collaboration between scientists at Eisai and Harvard is an example of academia and industry working together successfully to accelerate the development of a new class of therapeutics that may address important unmet medical needs," says Vivian Berlin, Managing Director of Strategic Partnerships in Harvard OTD. "The collaborative spirit and transparency of the relationship contributed enormously to the success of the project."

"Without OTD," Owa adds, "this collaboration could never have happened. Harvard OTD has been a core for bridging industry and Harvard researchers, and facilitating discussions about how to build a win-win relationship."

LEXINGTON, Ky. (June 17, 2019) - Discipline and how it is administered in schools across the U.S. continues to be a hotly debated topic. Now a University of Kentucky doctoral graduate's expansive research on the subject has been published in the Journal of School Psychology and is gaining widespread attention from teachers, administrators, and researchers.

Albert Ksinan, who earned his Ph.D. from the Department of Family Sciences in the UK College of Agriculture, Food and Environment last year, is principal investigator on the study and completed the most comprehensive analysis of the topic to date while still at UK. Currently a postdoctoral fellow in the Department of Psychology at Virginia Commonwealth University (VCU) in Richmond, Ksinan is lead author on the paper, "National Ethnic and Racial Disparities in Disciplinary Practices: A Contextual Analysis in American Secondary Schools." Co-authors are Alexander T. Vazsonyi, John I. & Patricia J. Buster Endowed Professor of Family Sciences (UK); Gabriela Ksinan Jiskrova, also a UK Ph.D. graduate in Family Sciences and now a postdoctoral fellow at VCU's School of Social Work; and James L. Peugh, associate professor of Pediatrics, University of Cincinnati.

The project analyzed how ethnicity and race are associated with school exclusionary discipline practices, which refer to students being removed from school as a form of punishment. Previous studies have found ethnic and racial disparities in the rates of school discipline actions, where ethnic and racial minority students (particularly African American youth) were found to be overrepresented among students that are disciplined.

"Exclusionary discipline can be particularly harmful during adolescence, because in many cases, it leaves adolescents without any real possibility to finish high school," said Ksinan. "Given that adolescence is the developmental period associated with the highest rate of delinquent behaviors, it is can be argued that school expulsion during this 'window of vulnerability' leads to an increased risk of engaging in substance abuse and violent crime, and an associated increased likelihood of contact with the juvenile justice system."

The data for the project included the universe of all U.S. public middle and high schools collected in 2013-14 by the U.S. Department of Education's Civil Rights Data Collection (CRDC). It is the most comprehensive study thus far to provide estimates of ethnic/racial discrepancies in who gets disciplined for 7 ethnic/racial groups (African American, Asian, Native American, Hawaiian, Hispanic, Two or more races, or White), with a dataset including almost 16,000 middle schools and more than 18,000 high schools, representing more than 22 million adolescents. Furthermore, the study assessed whether certain school characteristics (school size, percentage of students receiving free or reduced lunch, ethnic/racial diversity of the student body, whether the school is urban/suburban/rural, the U.S. region in which the school is located) affect the rates of exclusionary discipline practices as well as the ethnic/racial discrepancy.

"The results showed robust evidence of persistent discrepancies in disciplinary practices across ethnic/racial groups, with African American students and students indicating two or more races found to be at increased risk for being suspended/expelled compared to White students in both middle and high schools," said Ksinan. "Further, the risk for African American students and students indicating two or more races were higher in schools with higher poverty rates and a greater ethnic/racial diversity of the student population. Schools with students characterized by higher poverty and ones smaller in size reported higher rates of school discipline actions."

There was a result which surprised the researchers, according to Ksinan.

"Schools in the Midwest had significantly higher rates for most disciplinary measures as compared to Southern schools," he said.

With a focus on ethnic/racial discrepancies, the study provides evidence of systematic differences in how school disciplinary actions are applied, with African American youth and students indicating two or more races at increased risk for being disciplined; in turn, this can lead to a variety of problematic consequences. Thus, this research is instrumental in providing renewed impetus to the broader discussion on disciplinary actions and practices in America's middle and high schools.

New Rochelle, NY, June 14, 2019-The loss of complete segments of the esophagus often results from treatments for esophageal cancer or congenital abnormalities, and current methods to re-establish continuity are inadequate. Now, working with a rat model, researchers have developed a promising reconstruction method based on the use of 3D-printed esophageal grafts. Their work is published in Tissue Engineering, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the article for free through July 14, 2019.

Eun-Jae Chung, MD, PhD, Seoul National University Hospital, Korea, Jung-Woog Shin, PhD, Inje University, Korea, and colleagues present their research in an article titled "Tissue-Engineered Esophagus via Bioreactor Cultivation for Circumferential Esophageal Reconstruction". The authors created a two-layered tubular scaffold with an electrospun nanofiber inner layer and 3D-printed strands in the outer layer. After seeding human mesenchymal stem cells on the inner layer, constructs were cultured in a bioreactor, and a new surgical technique was used for implantation, including the placement of a thyroid gland flap over the scaffold. Efficacy was compared with omentum-cultured scaffolding technology, and successful implantation and esophageal reconstruction were achieved based on several metrics.

"Dr. Chung and colleagues from Korea present an exciting approach for esophageal repair using a combined 3D printing and bioreactor cultivation strategy," says Tissue Engineering Co-Editor-in-Chief John P. Fisher, PhD, Fischell Family Distinguished Professor & Department Chair, and Director of the NIH Center for Engineering Complex Tissues at the University of Maryland. "Critically, their work shows integration of the engineered esophageal tissue with host tissue, indicating a clinically viable strategy for circumferential esophageal reconstruction."

EVANSTON, Ill. --- A new meta-analysis on hiring discrimination by Northwestern University sociologist Lincoln Quillian and his colleagues finds evidence of pervasive hiring discrimination against all nonwhite groups in all nine countries they examined. Yet some countries discriminate more than others -- and certain laws and institutional practices might explain why. The study published in Sociological Science today (June 17).

The researchers examined more than 200,000 job applications in nine different countries: Belgium, Canada, France, Germany, Great Britain, Netherlands, Norway, Sweden and the United States.

Quillian and his colleagues measured the level of discrimination by calculating the percentage of interview callbacks a white native person received compared to a person who is not white. France and Sweden had the highest levels of hiring discrimination, while the U.S., the Netherlands and Germany had relatively lower levels.

"Clearly, there is a lot of discrimination against nonwhites in hiring in Western countries with a variety of negative effects," said Quillian, professor of sociology in the Weinberg College of Arts and Sciences and a faculty fellow with the Institute for Policy Research at Northwestern.

In France and Sweden, minority applicants would need to send out 70 to 94 percent more resumes than white applicants to receive the same number of responses as white applicants. In Germany and the U.S., minority applicants would need to send out 25 to 40 percent more.

The levels of discriminations were fairly similar among other nonwhite groups, including those applicants with backgrounds from Africa, the Middle East and Asia. The researchers also found low levels of discrimination against white immigrants, who are only "mildly disadvantaged" when compared to white natives of a country.

Certain laws and institutional practices explain why the U.S. had lower levels of discrimination than most of the other eight countries. More discussions about race and ethnicity take place in U.S. workplaces than in European ones, Quillian said.

"No other countries require monitoring of the racial and ethnic makeup of ranks of employees as is required for large employers in the U.S.," Quillian said. "For instance, large employers in the U.S. are required to report race and ethnicity of employees at different ranks to the Equal Employment Opportunity Commission."

Nevertheless, Quillian found in a previous study he conducted no change in rates of discrimination against African-Americans in field experiments of hiring from 1990 to 2015 in the U.S.

In Germany, the country with the lowest level of racial discrimination in hiring among the nine studied, job applicants submit several documents in their applications, including high school grades and apprenticeship reports.

"We suspect that this is why we find low discrimination in Germany -- that having a lot of information at first application reduces the tendency to view minority applicants as less good or unqualified," Quillian said.

But in some countries with higher levels of hiring discrimination, like France, employers are forbidden from asking about an applicant's race.

"The French do not measure race or ethnicity in any official -- or most unofficial capacities, which makes knowledge of racial and ethnic inequality in France very limited and makes it difficult to monitor hiring or promotion for discrimination," Quillian said.

The more information employers have about applicants, Quillian offers, the less room employers have to project their own views and stereotypes onto minority applicants.

New Rochelle, NY, June 17, 2019--A new study has shown that patients are significantly more likely to correctly identify male physicians and female nurses, demonstrating continuing gender bias in the health care environment. These lingering perceptions may slowly be changing, though, as younger patients were more likely to correctly identify female physicians and male nurses, according to the study published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article on the Journal of Women's Health website through July 17, 2019.

"The Relationship between Physician/Nurse Gender and Patients' Correct Identification of Health Care Professional Roles in the Emergency Department" was coauthored by Laurie Boge, Carlos Dos Santos, and David Farcy, Mount Sinai Medical Center (New York, NY), Lisa Moreno-Walton, Louisiana State University Health Sciences Center (New Orleans), and Luigi Cubeddu, Nova Southeastern University (Davie, FL). The researchers explored gender awareness of healthcare providers in the emergency department and suggest that better recognition of physicians, whether male or female, could improve work satisfaction by female physicians, patient satisfaction, and patient adherence to medical treatments.

Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, and President of the Academy of Women's Health, states: "Although Boge and colleagues have shown the persistence of gender bias by patients toward healthcare professionals, it is encouraging that there is a trend toward less gender bias among younger generations, even if the change is occurring slowly."