Culture

Some doctors fear litigation and professional ruin if they are seen to have overprescribed opioids to terminally ill patients, according to a University of Queensland researcher.

Palliative care expert Professor Geoffrey Mitchell said opioid overuse and some states' new assisted dying legislation had put end-of-life care clinicians created a "perfect storm" of fear for clinicians involved in end-of-life care.

"Some are choosing to abandon end-of-life care altogether rather than risk professional ruin should they persist in the use of any opioid therapy," Professor Mitchell said.

"The fear is that the use of medicines to minimise suffering and distress at the very end of life may hasten death and be construed by critics as euthanasia by stealth.

"The reality is that the person is dying.

"While treatments such as opioids may theoretically shorten life marginally, it is the disease that causes death, not the treatment."

Professor Mitchell said a study he co-authored should alleviate doctors' fears and help ensure patients received proper medical care.

"The research indicates regulatory bodies are not seeking to blame practitioners when a patient dies in the presence of opioid administration," he said.

"In fact the researchers found no such criminal proceedings had been brought in Australia against doctors.

"It is reassuring that doctors' intentions to alleviate suffering and adhere to good clinical practice has been respected."

Professor Mitchell said an overcautious attitude could result in people suffering needlessly at the end of their lives.

"The study identified 12 cases in publicly available electronic databases across all Australian jurisdictions, and of those, only two had adverse findings recorded, and neither led to criminal proceedings," he said.

"This indicates regulatory bodies are not seeking to blame practitioners when death occurs in the presence of opioid administration.

"Practitioners should use treatments and doses that are clinically indicated to alleviate the person's suffering.

"Opioids should not be avoided, and the minimum dose that achieves pain relief or reduction of chronic breathlessness should be prescribed.

"Clinical practice that seeks to alleviate suffering will be respected by the law and not punished.

"Practitioners can be assured that the law does not constitute a hazard to safe practice, but an ally to be valued."

More than 15 years after scientists first mapped the human genome, most diseases still cannot be predicted based on one's genes, leading researchers to explore epigenetic causes of disease. But the study of epigenetics cannot be approached the same way as genetics, so progress has been slow. Now, researchers at the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital have determined a unique fraction of the genome that scientists should focus on. Their report, which provides a "treasure map" to accelerate research in epigenetics and human disease, was published today in Genome Biology.

Epigenetics is a system for molecular marking of DNA - it tells the different cells in the body which genes to turn on or off in that cell type. But the cell-specific nature of epigenetics makes it challenging to study. Whereas a blood sample can be used to 'genotype' an individual, most epigenetic marks in blood DNA provide no clues about epigenetic dysregulation in other parts of the body, such as the brain or heart.

Dr. Robert A. Waterland, professor of pediatrics - nutrition and of molecular and human genetics at Baylor, and his team identified special regions of the genome where a blood sample can be used to infer epigenetic regulation throughout the body, allowing scientists to test for epigenetic causes of disease.

To do this, they focused on the most stable form of epigenetic regulation - DNA methylation. This addition of methyl groups to the DNA molecule occurs in the embryonic state and can impact health for your entire life.

To identify genomic regions in which DNA methylation differs between people but is consistent across different tissues, they profiled DNA methylation throughout the genome in three tissues (thyroid, heart and brain) from each of 10 cadavers.

"Since these tissues each represent a different layer of the early embryo, we're essentially going back in time to events that occurred during early embryonic development," Waterland said. "To map DNA methylation we converted methylation information into a genetic signal, then sequenced the genomes. Our atlas required massive amounts of sequencing data - 370 times more than were used for the first map of the human genome in 2001."

The nearly 10,000 regions the researchers mapped out, called correlated regions of systemic interindividual variation (CoRSIVs), comprise a previously unrecognized level of molecular individuality in humans.

"Recent studies are already showing that methylation at these regions is associated with a range of human diseases including obesity, cancer, autism, Alzheimer's disease and cleft palate," said Dr. Cristian Coarfa, associate professor of molecular and cell biology at Baylor and co-leader of the project

Waterland believes these findings will transform the study of epigenetics and disease, as researchers will now know where in the genome to look.

"Because epigenetic marking has the power to stably silence or stably activate genes, any disease that has a genetic basis could equally likely have an epigenetic basis," Waterland said. "There is incredible potential for us to understand disease processes from an epigenetic perspective. CoRSIVs are the entryway to that."

At this year's Euroanaesthesia Congress (the annual meeting of the European Society of Anaesthesiology) in Vienna, Austria (1-3 June), doctors present the unique case of a man who suffered a flash fire in his chest cavity during emergency heart surgery caused by supplemental oxygen leaking from a ruptured lung.

Dr Ruth Shaylor and colleagues from Austin Health in Melbourne, Australia, where the incident took place, warn that the case highlights the potential dangers of dry surgical packs in the oxygen-enrich environment of the operating theatre where electrocautery devices (using heat to stop vessels from bleeding) are used.

In August 2018, a 60-year-old man presented for emergency repair of an ascending aortic dissection--a tear in the inner layer of the aorta wall in the chest. The patient had a history of chronic obstructive pulmonary disease (COPD) and had undergone coronary artery bypass grafting one year previously.

As surgeons began to operate, they noted that the man's right lung was stuck to the overlying sternum with areas of overinflated and destroyed lung (bullae; often caused by COPD). Despite careful dissection, one of these bullae was punctured causing a substantial air leak. To prevent respiratory distress, the flows of anaesthetic gases were increased to 10 litres per minute and the proportion of oxygen to 100%.

Soon after, a spark from the electrocautery device ignited a dry surgical pack. The fire was immediately extinguished without any injury to the patient. The rest of the operation proceeded uneventfully and the repair was a success.

"While there are only a few documented cases of chest cavity fires--three involving thoracic surgery and three involving coronary bypass grafting--all have involved the presence of dry surgical packs, electrocautery, increased inspired oxygen concentrations, and patients with COPD or pre-existing lung disease", explains Dr Shaylor.

"This case highlights the continued need for fire training and prevention strategies and quick intervention to prevent injury whenever electrocautery is used in oxygen-enriched environments. In particular surgeons and anaesthetists need to be aware that fires can occur in the chest cavity if a lung is damaged or there is an air leak for any reason, and that patients with COPD are at increased risk."

Giving patients virtual reality sessions before and during locoregional anaesthesia for orthopaedic procedures substantially reduces pain and the need for intravenous sedation, according to new research being presented at this year's Euroanaesthesia congress (the annual meeting of the European Society of Anaesthesiology) in Vienna, Austria (1-3 June).

The randomised trial suggests that virtual reality hypnosis distraction (VRHD) could be a valuable drug-free alternative for reducing anxiety and procedure-related pain without the side effects and longer recovery time associated with traditional intravenous sedation.

"Given the immersive and distracting nature of the virtual reality experience, this technology has the ability to act as a preventive intervention transforming local anaesthesia into a less distressing and potentially pain-free medical procedure", says Dr Dragos Chirnoaga from CUB Erasmus Hospital, Brussels, Belgium who co-led the research.
Along with many other procedures, having a local anaesthetic injection can be a stressful and painful experience, and it is often combined with intravenous sedation to help patients relax. However, the use of intravenous sedation is not without adverse effects such as headache, nausea, and drowsiness.

In this randomised trial, researchers tested the hypothesis that VRHD could reduce the requirement for intravenous sedation by at least 50% during local anaesthesia at CUB Erasmus Hospital.

They randomised 60 adults scheduled for orthopaedic surgery (shoulder, hand or knee surgeries) with locoregional anaesthesia into three groups. In the control group (20 patients), standard intravenous sedation during locoregional procedure was administered without VHRD; in the second group (20), VRHD was used during locoregional anaesthesia, and intravenous sedation was given if patients reported pain scores of greater than 3 out of 10; in the third group (20), VRHD before and during locoregional anaesthesia was used, and intravenous sedation given if patients reported pain scores greater than 3.

VRHD therapy consisted of wearing virtual reality goggles and headphones to watch relaxing video content of a submarine ride and life under the sea, with a calming voice guiding the journey and focused on slowing the patient's breathing rhythm.

Analyses showed that just 25% (5/20) of patients receiving VRHD during local anaesthesia required intravenous sedation, whilst only 10% (2/20) patients given VRHD both before and during locoregional anaesthesia needed further sedation.

Additionally, patients receiving VRHD showed similar comfort and satisfaction before and during the procedure as those given intravenous sedation (see table in link to abstract below).

"Virtual reality hypnosis distraction is feasible, well tolerated, and liked by patients", says Dr Delphine Van Hecke from CUB Erasmus Hospital, Brussels who co-led the study. "While it is not clear exactly how virtual reality works to reduce anxiety and pain, it's thought that it creates a distraction that stops the mind feeling pain. Further studies should focus on other procedures suited for the use of VRHD, particularly its potential benefit in children as premedication or during low pain procedures."

Tokyo, Japan - Researchers from Tokyo Metropolitan University have successfully determined the high-resolution three-dimensional structure of proteins inside living eukaryotic cells. They combined "in-cell" nuclear magnetic resonance (NMR) spectroscopy, a bioreactor system and cutting-edge computational algorithms to determine protein structures in crowded intracellular environments for the first time. The technique promises insight into the intracellular behavior of disease-causing proteins and novel drug screening applications, allowing in-situ visualization of how proteins respond to biochemical stimuli.

Eukaryotic cells are the building blocks of a vast range of organisms, including all fungi, plants and animals. Their internal structure is extremely complex and varied, with an intricate structural hierarchy and a vast range of biomacromolecules distributed around a cytoskeletal network. This has made it difficult to see what each protein inside the cells does in its natural environment, despite the obvious biomedical benefits of knowing e.g. how a particular protein reacts when cells are subjected to chemical stimuli, like pharmaceutical drugs.

To tackle this challenge, a team from Tokyo Metropolitan University led by Assistant Professor Teppei Ikeya and Professor Yutaka Ito applied nuclear magnetic resonance (NMR) spectroscopy measurements to specific proteins expressed inside sf9 cultured insect cells, a strain of cells originally derived from a type of moth larva widely used for protein production. The team's pioneering NMR work had already succeeded in elucidating high-resolution protein structures inside bacteria (non-eukaryotes). The problem with simply applying the same techniques to proteins in sf9 cells was the significantly lower concentration of target proteins and short lifetime of cells, making it difficult to collect high quality multi-dimensional NMR spectra for nuclear Overhauser effect spectroscopy (NOESY) which would give precise information about how different atoms are spaced inside individual molecules. Thus, they combined a sparse sampling-based rapid NMR measurement scheme with state-of-the-art computational methods employing statistical techniques like Bayesian inference, methods tailored to elucidate protein structures efficiently based on a limited amount of structural information from in-cell NMR spectra with inherently low-sensitivity. A bioreactor system was also equipped inside the NMR apparatus which kept the cells in a healthy state during the measurements.

With this new data, the team were able to elucidate the 3D structure of three model proteins with unprecedentedly high resolution, with a precision of 0.5 Angstroms (0.05 nanometers) for the position of the protein's main chain atoms. In particular, they identified a significantly different conformation in a localized region of one of the proteins compared to its reference structure in dilute solution. The conformational difference between proteins "in cells" and "in test tubes" was presumably caused by non-specific interactions with other molecules inside the cells. It is becoming clear that these interactions contribute to the proteins' biological functions: the ability to locate and quantify structural changes of proteins in an intracellular environment is expected to have a significant impact on biomedical research, making it possible to see how different conditions e.g. neurodegenerative diseases affect protein conformations in-situ, and quantitatively gauge how treatments impact structural anomalies.

With flattened bodies, grabbing forelegs and deciduous wings, deer keds do not look like your typical fly. These parasites of deer -- which occasionally bite humans -- are more widely distributed across the U.S. than previously thought, according to Penn State entomologists, who caution that deer keds may transmit disease-causing bacteria.

"It was more or less known where deer keds are found, but very broadly," said Michael Skvarla, extension educator and director of the Insect Identification Lab in the Department of Entomology at Penn State. "We don't know if deer keds transmit pathogens (disease-causing microorganisms), but if they do, then knowing where they are at more precisely could be important in terms of telling people to watch out for them."

The researchers collated records of the four North American deer ked species and produced the most detailed locality map of these flies to date, documenting ten new state and 122 new county records. The researchers published their results in a recent issue of the Journal of Medical Entomology. They also provided an illustrated species-identification key.

The team harnessed citizen science -- collection of data by the public -- to gather deer ked records from the U.S. and Canada. In addition to scouring museum databases and community websites like BugGuide and iNaturalist, the team distributed deer ked collection kits to hunters as part of the Pennsylvania Parasite Hunters community project. The researchers also collected flies directly from carcasses at Pennsylvanian deer butcheries.

"I really like using citizen science information," said Skvarla. "It often fills in a lot of gaps because people are taking photographs in places that entomologists may not be going. Deer keds are the perfect candidate for citizen science. They're easy to identify because there's only four species in the country and because they're mostly geographically separated. And as flat, parasitic flies, they're really distinctive. You couldn't do this with a lot of insect groups because they'd be too difficult to identify from photographs."

The European deer ked, Lipoptena cervi, thought to have been introduced from Europe, previously was reported to occur throughout the Northeast region. The researchers newly report this species from Connecticut, Rhode Island, Vermont, and as far south as Virginia. In Pennsylvania, it occurs throughout the state, with 26 new county records.

The researchers also describe new records of the neotropical deer ked, L. mazamae, from North Carolina, Tennessee and Missouri -- increasing its range further north and east than had previously been reported.

In western North America, two deer ked species, L. depressa and Neolipoptena ferrisi, are found from British Columbia through the U.S. and into Mexico -- and as far east as South Dakota. The researchers newly report these species from Nevada and Idaho.

Deer keds are usually found on deer, elk and moose, but occasionally bite humans and domestic mammals. Although several tick-borne pathogens -- including bacteria that cause Lyme disease, cat scratch fever and anaplasmosis -- have been detected in deer keds, it is unknown whether they can be transmitted through bites.

"In Pennsylvania you have a lot of hunters," said Skvarla. "Deer keds can run up your arm while you're field dressing a deer and bite you. If these insects are picking up pathogens from deer, they could transmit them to hunters. With two million hunters in the state, that's not an insignificant portion of the population. We don't want to scare people, but people should be aware there is the potential for deer keds to transmit pathogens that can cause disease."

The researchers will next screen hundreds of deer keds for pathogens. They will also dissect some insects to screen the salivary glands and guts separately. According to Skvarla, this approach will give a good indication of whether deer keds could transmit pathogens through bites, or whether the bacteria are merely passed through the gut after a blood meal.

In Pennsylvania, after deer keds emerge from the soil each fall, they fly to a host and immediately shed their wings, usually remaining on the same host for life. Females produce just one egg at a time -- it hatches inside her, and she feeds the growing larva with a milk-like substance. When the larva is almost fully developed, it drops to the soil and forms a pupa, eventually emerging as a winged adult. If disease-causing bacteria are transmitted from mother to offspring, newly emerged flies could pass on pathogens to hosts. Pathogens could also be spread when bacteria-harboring flies jump between animals in close contact.

For the first time, researchers have observed a break in a single quantum system. The observation--and how they made the observation--has potential implications for physics beyond the standard understanding of how quantum particles interact to produce matter and allow the world to function as we know it.

The researchers published their results on May 31st, in the journal Science.

Called Parity-Time (PT) Symmetry, the mathematical term describes the properties of a quantum system--the evolution of time for a quantum particle, as well as if the particle is even or odd. Whether the particle moves forward or backward in time, the state of oddness or evenness remains the same in the balanced system. When the parity changes, the balance of system -- the symmetry of the system -- breaks.

In order to better understand quantum interactions and develop next-generation devices, researchers must be able to control the symmetry of systems. If they can break the symmetry, they could manipulate the spin state of the quantum particles as they interact, resulting in controlled and predicted outcomes.

"Our work is about that quantum control," said Yang Wu, an author on the paper and a PhD student in the Hefei National Laboratory for Physical Sciences at the Microscale and Department of Modern Physics at the University of Science and Technology of China. Wu is also a member of the Chinese Academy of Sciences Key Laboratory of Microscale Magnetic Resonance.

Wu, his PhD supervisor Rong and colleagues used a nitrogen-vacancy center in a diamond as their platform. The nitrogen atom with an extra electron, surrounded by carbon atoms, creates the perfect capsule to further investigate the PT symmetry of the electron. The electron is a single-spin system, meaning the researchers can manipulate the entire system just by changing the evolution of the electron spin state.

Through what Wu and Rong call a dilation method, the researchers applied a magnetic field to the axis of the nitrogen-vacancy center, pulling the electron into a state of excitability. They then applied oscillating microwave pulses, changing the parity and time direction of the system and causing it to break and decay with time.

"Due to the universality of our dilation method and the highly controllability of our platform, this work paves the way to study experimentally some new physical phenomena related to PT symmetry," Wu said.

Corresponding authors Jiangfeng Du and Xing Rong, professors with the Hefei National Laboratory for Physical Sciences at the Microscale and Department of Modern Physics at the University of Science and Technology of China, were in agreement.

"The information extracted from such dynamics extends and deepens the understanding of quantum physics," said Du, who is also an academician of the Chinese Academy of Sciences. "The work opens the door to the study of exotic physics with non-classical quantum systems."

The other authors include Wenquan Liu, Jianpei Geng, Xingrui Song, Xiangyu Ye, Chang-Kui Duan and Xing Rong. All of the authors are affiliated with the Hefei National Laboratory for Physical Sciences at the Microscale and Department of Modern Physics at the University of Science and Technology of China. Liu, Ye, Duan, Rong and Du are also affiliated with both the University's CAS Key Laboratory of Microscale Magnetic Resonance, and the University's Synergetic Innovation Center of Quantum Information and Quantum Physics.

In an effort to better protect the world's last ecologically intact ecosystems, researchers developed a new metric called "The Last of the Wild in Each Ecoregion" (LWE), which aimed to quantify the most intact parts of each ecoregion.

They tested whether LWE against intact forest landscapes (IFL) - another technique to map ecological integrity at the global scale - to see which could adequately capture the abundance of a set of large mammal species sensitive to human disturbance, by mapping the abundance of nine large mammal species from Africa, Asia and the Americas and comparing them to the areas identified by the LWE and IFL approaches.

The results show that neither IFL nor LWE identifies areas of ecologically intact fauna well enough, underscoring a strong need to obtain additional site-level survey data to confirm faunal intactness.

In a new study published today in the Journal of Allergy and Clinical Immunology, scientists from King's College London have found that young children with severe eczema infected with Staphylococcus aureus (SA) bacterium, are at a higher risk of developing a food allergy.

Staphylococcus aureus (SA) is a bacterium that can be found in the nose and the skin of healthy individuals.

However, SA is more common in sufferers of eczema, especially severe eczema.

When someone has an allergy, their immune system mistakes a harmless substance (such as eggs or peanuts) as an intruder and overreacts in response. Their body produces a molecule or else antibody known as Immunoglobin E (IgE).

When IgE encounters the intruder on the skin or within the body it releases chemicals, such as histamine that cause the allergic reaction.

The team of scientists found that young children with severe eczema who are infected with SA produce more IgE against peanut, egg and milk indicating they have a food allergy to each of these.

These children were also more likely to have their egg allergy persist at the age of 5 or 6 years in comparison to children that did not have SA present.

Lead author Dr Olympia Tsilochristou from King's College London said: "This is significant as most children with egg allergy usually outgrow this at an earlier age.

"We do not know yet the exact mechanisms that lead from eczema to food allergy however our results suggest that the bacteria Staphylococcus aureus could be an important factor contributing to this outcome."

These results build on the earlier ones from the Learning Early About Peanut Allergy (LEAP) study which demonstrated that infants who were at a high-risk of developing peanut allergy but consumed a peanut?containing snack throughout the study were prevented from later developing a peanut allergy.

In this current study, scientists found that children with SA on their skin and/or nose were more likely to develop peanut allergy despite them being fed with peanut from early ages as part of the LEAP study protocol.

Co-author Professor du Toit said: "These findings indicate that SA may have reduced the chance of young infants gaining tolerance to peanut, even if peanut was eaten in early childhood."

Professor Lack, who conceived and led the LEAP study, said that "SA could be considered as an additional risk factor for the development of food allergy."

Children exposed to paternal tobacco smoking before birth are more likely to develop asthma - and associated changes to immune genes predict the level of risk.

These are the findings of a new study of Taiwanese families, whose lifestyle and genetic make-up were analyzed to determine how fathers' tobacco smoking during pregnancy relates to asthma risk in their children.

Published in Frontiers in Genetics, the study reinforces the risks of either parent smoking - and according to the authors, could provide DNA targets for the early prediction and reversal of tobacco smoking-associated childhood asthma.

A perfect storm

"We found that prenatal exposure to paternal tobacco smoking is associated with increased methylation of certain immune genes, which alters how the genetic code is read," says lead author Dr. Chih Chiang Wu of Po-Zen Hospital, Taiwan. "This smoking-associated DNA methylation is significantly retained from birth to 6 years of age, and correlates with development of childhood asthma."

Exposure to tobacco smoke during development is already known to harm children in a variety of ways, and non-coding 'epigenetic' changes to DNA (such as methylation) have been repeatedly implicated.

However, this study is the first to show that just like maternal smoking or air pollution, paternal smoking during pregnancy can program epigenetic modifications in important immune system genes - and that these modifications are associated with an increased risk of childhood asthma.

"Twenty-three percent of the fathers [367 in a cohort of 1629 couples with newborns] were smokers, compared to just 3 of the mothers [0.2%]. This unique disparity provided the perfect opportunity to study the effects of paternal tobacco smoking (PTS) exposure," says co-author Dr. Ho Chang Kuo of Kaohsiung Chang Gung Memorial Hospital.

The study

The researchers followed 1629 children from birth to 18 months (1348) to 6 years of age (756), with medical assessment and DNA analysis at each time point.

Infants with prenatal PTS exposure had a significantly higher risk of asthma by age of 6 than those without.

"Children with prenatal PTS exposure corresponding to more than 20 cigarettes per day had a significantly higher risk of developing asthma than those with less than 20 cigarettes per day and those without prenatal PTS exposure: 35%, 25% and 22.7%, respectively," reports senior author Dr. Kuender Yang of Mackay Children's Hospital, Taipei.

More striking, however, were the results of the DNA analysis.

The higher the PTS exposure dose, the higher the level of methylation of LMO2, IL10 and GSTM1 - genes known to have key roles in immune function, which could provide a mechanistic link to asthma risk.

"The combination of higher methylation levels of all three genes corresponded to the highest risk of asthma: 43.48%, compared to 16.67%-23.08% with any other combination," adds Dr. Yang.

Conclusions

Based on these results, the authors postulate that prenatal PTS exposure might program epigenetic modifications of immune genes, that are retained into childhood and so contribute to the development of childhood asthma.

They emphasize though that their study can only show associations between these factors.

"It remains to be determined whether the DNA methylation associated with PTS originated from tobacco smoke exposure in utero, from preconception changes to the father's sperm, or if there is an alternative explanation," explains Dr. Wu. "Preconception paternal smoking has been shown previously to alter sperm DNA methylation, with associated increased asthma risk in offspring."

Nevertheless, secondary outcomes from the study suggest an important mechanistic insight.

"While prenatal PTS exposure was associated with childhood asthma development at 6 years of age, it did not correlate with allergen sensitization or total levels of IgE - an allergy-associated antibody implicated in asthma. Against expectations, this implies that prenatal PTS-associated asthma is mediated by an IgE-independent mechanism," concludes Dr. Yang.

It is hoped that further work to clarify the pattern of epigenetic changes to immune genes such as LMO2 and IL10 and detoxification gene such as GSTM1 in PTS-associated asthma development can provide strategies for prediction and even reversal.

Children with autism spectrum disorder (ASD) are often affected by co-occurring conditions, such as epilepsy, immune disorders, gastrointestinal problems, and developmental delays. According to research published today in Autism Research, creating a classification system for ASD based on co-occurring conditions could provide useful insights into the underlying mechanics of ASD and these conditions.

The study was produced by a Rensselaer Polytechnic Institute team, led by Juergen Hahn, a professor of biomedical engineering, which analyzed de-identified administrative claims data from the OptumLabs Data Warehouse for thousands of children with and without ASD over five years. What the team found, Hahn said, were three subgroups within the cohort of 3,278 children with autism.

The first group, about a quarter of the children, had high rates of co-occurring condition diagnoses. The second cluster, also about a quarter of the children, had high rates of developmental delays, specifically. The third group, which encompassed the remaining 50%, had the lowest rates of co-occurring condition diagnoses - only slightly higher than the group of 279,693 children without ASD.

These findings, Hahn said, lay the groundwork for creating a sub-classification system within ASD.

"This could potentially be a blueprint for looking at the subtypes of autism. I'm not saying it's the only way to do it but I think it's an important step in that direction," he said.

The analysis also showed that certain conditions like gastrointestinal and immune disorders, and seizure and sleep disorders often co-occurred at similar points in time in children with autism. Hahn said those findings could prompt further exploration by other research teams.

"Once you know which conditions happen together, then you can look at if there is some commonality among the underlying mechanisms. Maybe you find that if there's intersection of the mechanism that causes one problem or the other," Hahn said.

This study built upon earlier research published in Journal of Autism and Developmental Disorders, where the Rensselaer researchers looked at gastrointestinal problems and antibiotic use in both children with autism and without.

The data showed that gastrointestinal symptoms are twice as common in children with autism, but that antibiotics don't increase those symptoms in children with ASD any more than they do in children without.

"I think that's important because it's basically a question a lot of parents have when they go to the doctor," Hahn said.

Answering these big medical questions is a hallmark of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer, of which Hahn is a part.

"At Rensselaer, using an interdisciplinary approach at the intersection of the physical, computational, and life sciences and engineering, we seek to provide a new angle to human health for complex disorders and diseases such as ASD, Alzheimer's, and Parkinson," said Deepak Vashishth, director of CBIS.

The dedication to collaborative work at the center has enabled Hahn's previous discoveries, including his finding that patterns with certain metabolites in the blood can accurately predict if a child has an ASD diagnosis.

In both of these most recent studies, the team was able to map over time when children were diagnosed with co-occurring conditions. Those timelines show that, at certain ages, diagnosis rates diverge between children with autism and children without.

These maps may help doctors better determine at what age they should start screening children with autism for various co-occurring conditions.

Larger than that, Hahn said, these findings raise more questions to be explored.

"That tells you that something must be causing this and so we have to figure out what's going on in the body at this point in time that might either cause or contribute to these divergences somehow," he said.

Performing a procedure on the wrong side of a patient's body, although rare, may be more common than generally thought. More than 80 wrong side error (WSE) incidents were reported across 100 hospitals in Spain over the past decade, according to new research being presented at this year's Euroanaesthesia Congress (the annual meeting of the European Society of Anaesthesiology) in Vienna, Austria (1-3 June).

While this might be just the tip of the iceberg, the authors stress the opportunity for improvement. "The stark reality is that due to the lack of reporting to incident databases, these figures most likely represent an underestimate of the true situation", says Dr Daniel Arnal from the Hospital Universitario Fundación Alcorcón, Madrid, Spain who led the research. "However, the reporting of wrong side errors have led to substantial corrective measures to prevent their repetition in our hospitals."

Further prevention of wrong side errors requires the correct implementation of surgical safety checklists (with every team member present), and the creation of a standardised surgical site marking protocol, while increasing reporting of case occurrence and reducing the shame felt by medical teams associated with these events, researchers say.

Although wrong side errors seem preventable, they continue to occur. Previous studies have estimated 1 wrong side surgery per 100,000 procedures and 1.3 wrong-side nerve blocks per 10,000 procedures [1].

To provide more information on how often and why they occur, and on the safety mechanisms needed to prevent them, Arnal and colleagues analysed WSE incidents reported to SENSAR (Spanish Safety Reporting System in Anaesthesia and Resuscitation), which covers 100 predominantly large hospitals across Spain between 2007 and 2018.

Overall, 81 incidents were reported in 11 years, with high numbers of WSEs noted in orthopaedic (48%) and ophthalmology (28%) surgery.

36 (44%) of these WSEs were related to the surgical procedure, and the surgery was actually performed in half of these cases. The remaining 45 (56%) WSEs involved the anaesthetic technique (the wrong side of the the body given anaesthesia), with an incorrect nerve block performed in 91% of cases. Severe harm was caused on three occasions.

Analysis of WSEs suggests several common causes and systemic failures. In two-thirds of cases, the absence or incorrect use of the surgical checklist was reported. Other factors included rushing and poor communication amongst the medical team.

"Our findings highlight the need for adequate training and appropriate use of surgical check-lists, as well the creation of a standardised surgical site marking protocol, the correct revision of clinical history and imaging tests, and involving patients in their own safety", says Dr Arnal. "While these serious wrong side events are extremely rare, our mission should be to drive them down to zero."

Nicotine and caffeine withdrawal can cause unnecessary suffering to patients in intensive care units (ICUs), and could be leading to unneeded laboratory testing and diagnostic imaging such as X-rays and MRIs, according to a systematic review of clinical and observational studies involving 483 adults.

The findings are being presented at this year's Euroanaesthesia congress (the annual meeting of the European Society of Anaesthesiology) in Vienna, Austria (1-3 June).

"Nicotine and caffeine are some of the most commonly used and highly addictive substances in modern society, but they are often overlooked as a potential source of significant withdrawal symptoms when abruptly discontinued in ICU", explains Associate Professor Maya Belitova from University Hospital "Tsaritsa Yoanna" - ISUL, Sofia, Bulgaria who led the research.

"Withdrawal symptoms including nausea, vomiting, headaches, and delirium can last for up to 2 weeks. These symptoms resemble conditions such as meningitis, encephalitis, and intracranial haemorrhage--this may confuse clinical diagnosis and result in unnecessary tests which can cause patient harm, cost a lot of money, and waste time."

In Europe, up to 27% of the population smokes, and more than half drink coffee. The systematic review, synthesising all the available evidence from the scientific literature, included 12 studies investigating withdrawal symptoms and treatment in ICUs between 2000 and 2018, involving 483 adults (aged 18-93).

Results showed that acute nicotine withdrawal substantially increases agitation (64% smokers vs 32% non-smokers) and the number of tracheal tube and intravenous line displacements caused by agitation in ICU patients (14% smokers vs 3% non-smokers).

However, nicotine substitution therapy was shown to contribute to the development of ICU delirium (severe confusion and disorientation)--which is associated with prolonged intubation, increased length of stay, and greater risk of dying.

Abrupt caffeine withdrawal leads to drowsiness, nausea, vomiting, headaches, and can increase rates of ICU delirium. Caffeine benzoate has been successfully used to treat headaches but substitution in the ICU has a limited evidence base.

"ICU patients may benefit from nicotine substitution or caffeine supplementation, but with little evidence for their effectiveness, this should be left up to the judgement of treating physicians", says Professor Belitova. "There is lack of evidence on abrupt caffeine withdrawal, its complications and therapeutic options. Future research should focus on acute caffeine withdrawal as an independent risk factor for agitation and delirium in ICU and on available treatment options."

Astrocytes are overtaxed neurons' pit crew.

The brain cells collect damaged lipids secreted by hyperactive neurons, then recycle those toxic molecules into energy, researchers at the Howard Hughes Medical Institute's Janelia Research Campus report May 23, 2019, in the journal Cell. It's a mechanism to protect neurons from the damaging side effects of overactivity. And it's another important role for astrocytes, which support neurons in various ways.

When a neuron fires fast and furious, lipid molecules in the cell get damaged and can become toxic. While most kinds of cells sequester excess fatty acids away or feed them to mitochondria to prevent buildup, neurons don't seem to rely on those tricks.

Instead, "neurons unload some of the burden to astrocytes," says study coauthor and Janelia Group Leader Zhe Liu, who worked closely with Maria Ioannou and Jennifer Lippincott-Schwartz, a senior group leader at Janelia. "For a long time, people have suspected there was some mechanism like this. The new work shows how this process actually happens."

The finding arose from a curious observation: Overactive neurons release damaged fatty acids bundled up in lipid particles. "People didn't think that neurons could secrete those lipid particles," Liu says.

But stimulating mouse neurons in a dish led to the buildup of fatty acids and, eventually, lipid particle release, the team showed. Then, nearby astrocytes engulfed the particles and amped up the activity of genes involved in energy production and detoxification.

Astrocytes feed neurons' off-loaded damaged lipids to their own mitochondria, converting waste into energy, Liu concluded. Tests in mice showed a similar response. After a lesion to the brain that mimics a stroke - a huge stress to neurons - neurons increased production of proteins involved in transporting fatty acids out of the cell, and fatty acids built up in astrocytes.

This pathway for clearing toxic molecules from neurons might be damaged in Alzheimer's patients, Liu proposes, though that hasn't been thoroughly investigated. A next step, led by Maria Ioannou in her new lab at the University of Alberta, is to examine what's different about this mechanism in cell culture and rodent models of Alzheimer's disease.