Palliative care services can help cancer patients

A cancer diagnosis is frightening and often impacts patients on both a physical and an emotional level. It can actually lead to symptoms such as pain, nausea, anxiety and depression. These symptoms, as well as those that are caused by the cancer and/or the cancer treatment, can be eased through the incorporation of palliative medicine into the patient’s care plan.

Palliative medicine, which is commonly referred to as palliative care, provides an extra layer of support to patients and their families throughout the cancer journey. This support can include both medical and holistic approaches to care depending on the patient’s wishes and personal circumstances.

“As a palliative care physician, I strive to get to know each patient individually by encouraging them to talk about their cancer journey and learning what is important to them. Many patients find this to be very helpful and therapeutic. By getting to know patients and finding ways to help them to manage their symptoms, I can help them live in a way in which their cancer diagnosis is not on their minds 24/7,” explains Ayelet Spitzer, D.O., Supportive Care Specialist, Valley-Mount Sinai Comprehensive Cancer Care.

Some examples of palliative care services are:Symptom management

  • Support for complex decision managing
  • Goal setting
  • Advance care planning
  • Social and caregiver assessment and support
  • Spiritual care
  • Care coordination/transition management
  • Self-management techniques

 

“Please keep in mind that palliative care should not be confused with hospice care, which is palliative care provided during the end of life. All cancer patients can benefit from palliative care services, regardless of where they are on their cancer journey. In fact, most palliative care services are offered while patients are receiving cancer treatment. Palliative care is not about dying-;it is about living life to the fullest,” adds Dr. Spitzer.

 

Metabolites significantly affected in chronic kidney disease, study finds

Chronic kidney disease (CKD) affects 1 in 7 people in the United States, according to the U.S. National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK). These individuals have a very high risk of cardiovascular disease, and some will also progress to kidney failure requiring dialysis and transplantation.

However, few options exist to treat them, and few major breakthroughs have been made during the last 30 years. More than 660,000 Americans have kidney failure, according to the NIDDK.

A new study that included researchers from Norway, the University of Washington, the University of California San Diego and The University of Texas Health Science Center at San Antonio (now called UT Health San Antonio™) found that dozens of small molecules called metabolites are altered in this disease. “We analyzed these small molecules in the blood and urine of non-diabetic patients with chronic kidney disease and compared the results to samples obtained from a group of healthy individuals,” said Stein Hallan, M.D., first author of the study published in EBioMedicine. “Importantly, our study identified that a group of molecules called tri-carboxylic acid (TCA) cycle metabolites are significantly affected in chronic kidney disease.”

Chronic kidney disease, fatigue and metabolism

The TCA cycle is a process in which fuel molecules are converted into energy. This activity occurs in mitochondria–the energy centers of all types of cells. The fact that the TCA cycle is significantly impacted in chronic kidney disease supports the view of CKD as a state of mitochondrial dysfunction, said study senior co-author Kumar Sharma, M.D., FAHA, chief of nephrology and founding director of the Center for Renal Precision Medicine at UT Health San Antonio.

“Typically, patients with more advanced stages of CKD suffer from severe fatigue, and many other organs (muscles, brain, gut and others) are also not functioning well,” Dr. Hallan said. “The clinical picture indicates that there is a general underlying defect in mitochondrial function of these patients.”

Dr. Hallan has been an active collaborator with Dr. Sharma and has done several sabbaticals with Dr. Sharma in San Antonio and San Diego.

This discovery builds on the Sharma group’s earlier work. Since 2013, when the team was based at UC San Diego, the clinical investigators published several research papers supporting that mitochondrial dysfunction is an important mechanism in diabetic and other types of kidney diseases.

The new study also found that in patients with CKD, expression of genes that regulate the TCA cycle was significantly reduced compared to healthy individuals.

Molecular clues to kidney disease therapies

Researchers hope that a new breakthrough therapy could arise from these insights.

“This is certainly our goal,” Dr. Sharma said. “Metabolomics, the analysis of small molecules in biological samples, has revealed numerous abnormalities in the blood of uremic patients, whose kidneys are unable to eliminate the body’s waste products. Further exploration of the TCA cycle, using metabolomics, may identify novel therapeutic targets for CKD and in turn may help us evaluate the effects of promising interventions.”

The Center for Renal Precision Medicine at UT Health San Antonio contributed to the work and will expand upon it in future studies. The Kidney Precision Medicine Project, which is funded by the National Institutes of Health at centers including UT Health San Antonio, and The University of Texas System STARs Program will be part of the ongoing research.

STARs awards, established by the UT System Board of Regents in 2004, are granted to UT System institutions to help attract and retain the best-qualified faculty. (STARs is short for Science and Technology Acquisition and Retention.)

Center for Renal Precision Medicine

Dr. Sharma recently was awarded a $1.4 million Translational STARs award to establish the Center for Renal Precision Medicine at UT Health San Antonio. Dr. Sharma is also the vice chair of research in the Department of Medicine of the Joe R. & Teresa Lozano Long School of Medicine, and occupies the L. David Hillis, M.D. Endowed Chair in Medicine.

Dr. Sharma has submitted an invention disclosure based on the research to the Office of Technology Commercialization at UT Health San Antonio.

 

Intrusive Thoughts and Post-Traumatic Stress Disorder (PTSD)

Intrusive thoughts are threatening thoughts that constantly occur to a person without conscious or voluntary control. These thoughts are capable of creating severe anxiety when they enter the mind. They play a vital role in Post-Traumatic Stress Disorder (PTSD), as they have a significant impact on the people affected by it.

Post-Traumatic Stress Disorder

Post-traumatic stress disorder is a type of serious anxiety disorder that develops after an intense experience of being involved in a traumatic event. For people with PTSD, the traumatic event repeatedly causes thoughts of fear, shock, anger, restlessness, and sometimes horror.

Traumatic Incident

A traumatic incident is an event that causes physical or psychological distress. Each person’s reaction to a traumatic event is different based on one’s personality, beliefs, and previous experiences. In all cases, the individual experiences a traumatic event that causes intense fear and anxiety.

Different types of traumatic incidents include:

  • witnessing or being involved in a severe road accident
  • being a victim of violent or sexual assaults
  • witnessing the violent death of loved ones, friends, or family
    war
  • witnessing terrorist attacks
  • being held as a hostage or prison stay
  • being involved in natural disasters including floods, tsunamis, or earthquakes

Intrusive Thoughts in PTSD

In addition to thoughts, images, sounds, smells, and feelings of a particular traumatic incident can also intrude severely upon a person with PTSD. People with PTSD are stuck in the memories and time during which they experienced the incident and are less attentive to their present life. Sufferers report a frequent recurrence of distressing memories. Patients also have nightmares about the event. They exhibit movements during sleep as a result of nightmares.

They feel as if the incident is taking place again and again in their life. These types of thoughts are known as flashbacks. The occurrence of flashback thoughts leads to deep distress and increases physical excitation and stress, including the heart rate. As a whole, these intrusive symptoms lead to intense stress and result in guilt, fear, anger, and grief.

Intrusive Symptoms

Recurring thoughts about the incident: Sufferers have a graphic and dramatic image of the trauma that arises in their memory frequently. For instance, if a person has been attacked physically, he might see the image of the face of the attacker again and again. In the case of a car accident, the person may relive the memories or the sound of the particular incident or the images of injury and blood.

Nightmares: PTSD sufferers often have nightmares that may be about the incident or themes that are related to the traumatic event. A person who has been involved in a car accident will have nightmares about the accident. PTSD people who have been victims of assault dream of being chased by an attacker. In several of these dreams, the pursuer might not be the assaulter in real life.

Reliving the incident: In this symptom, the affected individual is detached from the real world and is stuck in the past trauma event. This type of reliving the incident is called “dissociation.” Some people with this symptom act as if they are undergoing the traumatic situation physically. Others stare into empty space for a prolonged period, thinking of the incident.

Distress of the trauma: In this state, PTSD sufferers are frequently nervous and anxious when they are near the place where the incident occurred or while speaking to a person who is related in any way to the incident.

Body Sensations: Almost all PTSD patients suffer bodily sensations. They experience some physiological changes when they come into association with the person, situation, or conversation that reminds them of the incident. This leads to changes in physical parameters such as an increase in the body temperature, heartbeat, and blood pressure.

Impact of PTSD on the Brain

Recent studies have shown that people with PTSD have irregular or fluctuating stress hormones levels. When the human body is faced with danger, it automatically starts producing adrenal hormones that generate various stress reactions.

These reactions are called the “flight or fight” reactions that put the senses on full alert. In PTSD, victims experience a continuous production of elevated levels of flight or fight hormones, even when there is no actual present danger.

For people with PTSD, emotional processing occurs in different areas of the brain. The part of the brain which is thought to be primarily responsible for emotion and memory is known as the hippocampus. The size of the hippocampus in PTSD people seems to be smaller compared to other people.

Changes that occur in this part of the brain might be the reason for anxiety, flashbacks, and other memory problems. The smaller hippocampus may prevent memory from being properly processed and hence the anxiety that is generated from the flashbacks will not abate.

 

Alzheimer’s may spread through blood transfusions? Study shows

Can you catch Alzheimer’s disease? Fear has been growing that the illness might be capable of spreading via blood transfusions and surgical equipment, but it has been hard to find any evidence of this happening. Now a study has found that an Alzheimer’s protein can spread between mice that share a blood supply, causing brain degeneration.

We already know from prion diseases like Creutzfeldt-Jakob Disease (CJD) that misfolded proteins can spread brain diseases. Variant CJD can spread through meat products or blood transfusions infected with so-called prion proteins, for example.

Like CJD, Alzheimer’s also involves a misfolded protein called beta-amyloid. Plaques of this protein accumulate in the brains of people with the illness, although we still don’t know if the plaques cause the condition, or are merely a symptom.

There has been evidence that beta-amyloid may spread like prions. Around 50 years ago, many people with a growth disorder were treated with growth hormone taken from cadavers. Many of the recipients went on to develop CJD, as these cadavers turned out to be carrying prions. But decades later, it emerged in postmortems that some of these people had also developed Alzheimer’s plaques, despite being 51 or younger at the time.

Protein plaques

The team behind this work raised the possibility that some medical or surgical procedures may pose a risk.

Now a study has found that, when a healthy mouse is conjoined with a mouse with Alzheimer’s plaques, it will eventually start to develop plaques of beta-amyloid protein in its own brain. When the plaques form in healthy mice this way, their brain tissue then starts dying.

This suggests that Alzheimer’s can indeed spread via the beta-amyloid protein in blood. “The protein can get into the brain from a connected mouse and cause neurodegeneration,” says Weihong Song at the University of British Columbia in Vancouver, who led the work.

Song’s team conducted their study on mice with a gene that makes the human version of beta-amyloid, because mice don’t naturally develop Alzheimer’s. This gene enabled mice to develop brain plaques similar to those seen in people, and to show the same pattern of neurodegeneration.

Induced illness

The team then surgically attached mice with this Alzheimer’s-like condition to healthy mice without the beta-amyloid gene, in a way that made them share a blood system.

At first, the healthy mice started to accumulate beta-amyloid in their brains. Within four months, the mice were also showing altered patterns of activity in brain regions key for learning and memory. It is the first time that beta-amyloid has been found to enter the blood and brain of another mouse and cause signs of Alzheimer’s disease, says Song.

“They somewhat convincingly show that it is possible to induce [the plaques] in mice just by connecting the circulation,” Gustaf Edgren at the Karolinska Institute in Stockholm, Sweden. “It strengthens the case that amyloid beta is infectious somehow – it may actually be a prion or act like a prion.”

These findings contradict a study earlier this year by Edgren and his colleagues, which tracked 2.1 million recipients of blood transfusions across Sweden and Denmark. They found that people who received blood from people with Alzheimer’s didn’t seem to be at any greater risk of developing the disease.

Infectious protein

Edgren says that although his own study was very large, there’s still a chance it did not run long enough to catch evidence that Alzheimer’s proteins might be transmissible. “We only have follow-up for 25 years,” he says. “It could take a long time [for the disease to develop], or there could not be enough data. A lot of researchers fear that it’s an infectious protein.”

Song’s team say it is too soon to draw conclusions from their findings. Stitching mice together is not a situation that applies to people, says Edgren.

Mathias Jucker at the German Center for Neurodegenerative Diseases in Tübingen doesn’t think the study shows that Alzheimer’s is a transmissible disease. And the team have not yet looked at the behaviour of the mice to see if they show signs of the cognitive decline characteristic of Alzheimer’s.

In the meantime, Song thinks researchers and doctors should pay more attention to beta-amyloid in the blood, which could potentially be used to diagnose the disease. One of the reasons it has been difficult to treat Alzheimer’s is the difficulty of designing drugs that can cross the brain’s protective barrier. It may be easier to target the protein in the bloodstream, which could have knock-on effects for the brain, says Song.

 

Breast cancer researchers track changes in normal mammary duct cells leading to disease

The findings of the multidisciplinary team of surgeons, pathologists and scientists led by principal investigator Dr. Susan Done are published online today in Nature Communications. Dr. Done, a pathologist affiliated with The Campbell Family Institute for Breast Cancer Research at Princess Margaret Cancer Centre, University Health Network, is also an associate professor in the Department of Laboratory Medicine and Pathobiology, University of Toronto.

“We have found another piece in the cancer puzzle – knowledge that could one day be used for more precision in screening and breast cancer prevention, and also help with therapeutic approaches to block some of the earliest alterations before cancer develops and starts to spread.”

Lead author Moustafa Abdalla writes: “Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells.”

Instead, this study found a way to identify early changes that preceded the tumour, enabling better understanding of cancer biology and disease development.
“Normal breast epithelium from the duct giving rise to a breast cancer has not been previously studied in this way.”

Dr. Done explains: “Most breast cancer starts in the epithelial cells lining the mammary ducts. But the breast ducts are complex structures, like the branches of a tree. Guesstimating which duct is close to the tumour is not very accurate. Thanks to our surgeons, we were able to obtain samples along normal-looking ducts close to the nipple and close to the tumour, as well as samples on the opposite side of the same breast to study and compare.”

In the operating room, surgeons inserted a fibre-optic scope through the nipple into the ducts below, and then injected dye into cancerous breasts being removed. This ductoscopy technique enabled the pathologists to identify the exact duct leading to the tumour and subsequently classify genetic alterations either increasing or decreasing as they moved nearer to the cancer.

“Cancer is not a switch that happens overnight. Once a patient notices a lump the tumour has been present for some time accumulating genetic changes. It is difficult at that point to identify the first changes that may have had a role in initiating or starting the cancer,” says Dr. Done.

The research further identified genes that seem to be acting together in groups or pathways. “Some of these genes were either increased or decreased in the area of the tumour, no matter the type of breast cancer, and this is important because within the patterns we identified were predictable alterations. This meant we could determine from the sample where it came from in the breast,” says Dr. Done.

“Our research demonstrated and supports earlier research from elsewhere that changes in cells occur before you can see them. The fact that changes are already present in different regions of the breast could be important in the delivery of radiation therapy or surgical margin assessment. We’re a long way from bringing this into clinic, but it is something we will think about as we continue our research.”

 

Can bones affect your appetite — and your metabolism?

Your skeleton is much more than the structure supporting your muscles and other tissues. It produces hormones, too. And Mathieu Ferron knows a lot about it. The researcher at the Montreal Clinical Research Institute (IRCM) and professor at Université de Montréal’s Faculty of Medicine has spent the last decade studying a hormone called osteocalcin. Produced by our bones, osteocalcin affects how we metabolize sugar and fat.

In a recent paper in The Journal of Clinical Investigation, Ferron’s team unveiled a new piece of the puzzle that explains how osteocalcin works. The discovery may someday open the door to new ways of preventing type 2 diabetes and obesity.

Bone: An endocrine organ

It has long been known that hormones can affect bones. “Just think about how women are more prone to suffer from osteoporosis when they reach menopause because their estrogen levels drop,” said Ferron, director of the IRCM’s Integrative and Molecular Physiology Research Unit.

But the idea that bone itself can affect other tissues took root only a few years ago with the discovery of osteocalcin. Thanks to this hormone, produced by bone cells, sugar is metabolized more easily.

“One of osteocalcin’s functions is to increase insulin production, which in turn reduces blood glucose levels,” Ferron explained. “It can also protect us from obesity by increasing energy expenditure.”

Studies have shown that, for some people, changes in blood concentrations of osteocalcin may even stave off the development of diabetes. These protective properties sparked Ferron’s interest in how this hormone actually works.

Hormone scissors

Osteocalcin is produced by osteoblasts, the same cells responsible for making our bones. The hormone builds up in bone, and then, through a series of chemical reactions, is released into the blood. The IRCM team is focusing on this key step.

“When it is first produced in osteoblasts, osteocalcin is in an inactive form,” Ferron noted. “What interested us was understanding how osteocalcin becomes active so as to be able to play its role when released into the blood.”

The IRCM lab demonstrated that an enzyme, which acts like molecular scissors, is required. Inactive osteocalcin has one more piece than active osteocalcin. The researchers examined in mice the different enzymes present in cells where osteocalcin was produced that could be responsible for snipping off the piece in question.

Ferron’s team succeeded in identifying it: it’s called furin. Furin causes osteocalcin to become active and the hormone is then released into the blood.

“We demonstrated that when there was no furin in bone cells, inactive osteocalcin built up and was still released, but this led to an increase in blood glucose levels and a reduction in energy expenditure and insulin production,” Ferron said.

Deleting these “scissors” also had an unexpected effect: it reduced the mice’s appetite. “We’re confident that the absence of furin was the cause,” Ferron said.

Indeed, his team demonstrated that osteocalcin itself has no effect on appetite. “Our results suggest the existence of a new bone hormone that controls food intake,” Ferron said.

“In future work, we hope to determine whether furin interacts with another protein involved in appetite regulation.”

 

Driving may be affected in prescription drug users

A large portion of patients taking prescription drugs that could affect driving may not be aware they could potentially be driving impaired, according to research in the November issue of the Journal of Studies on Alcohol and Drugs.

Nearly 20 percent of people in the study reported recent use of a prescription medication with the potential for impairment, but not all said they were aware that the medication could affect their driving, despite the potential for receiving warnings from their doctor, their pharmacist, or the medication label itself.

The percentages of those who said they had received a warning from one of those sources varied by type of medication: 86 percent for sedatives, 85 percent for narcotics, 58 percent for stimulants, and 63 percent for antidepressants.

In the report, researchers used data from the 2013-2014 National Roadside Survey, which asked drivers randomly selected at 60 sites across the United States questions about drug use, including prescription drugs. A total of 7,405 drivers completed the prescription drug portion of the survey.

Although it is unclear if the study participants actually received the warnings, or if they did receive the warnings but didn’t retain the information, the authors say this scenario is in need of further research.

“We were very surprised that our study was the first we could find on this topic,” says lead researcher Robin Pollini, Ph.D., M.P.H., of the Injury Control Research Center at West Virginia University. “It’s a pretty understudied area, and prescription drugs are a growing concern.”

In this study, the type of medication in question was also related to drivers’ perceptions about their impairment risk. They were most likely to think that sleep aids were the most likely to affect safe driving, followed by morphine/codeine, other amphetamines, and muscle relaxants. Attention-deficit hyperactivity disorder (ADHD) medications were viewed as least likely to affect driving risk. Sleep aids were also viewed as the most likely to cause an accident or result in criminal charges, and ADHD medications were viewed as the least likely.

Pollini says she hopes this research will lead to increased warnings provided by doctors and pharmacists, as well as improved labeling for medications that are likely to impair driving. She says it’s not yet clear what the optimum messaging would be. But she is encouraged by the fact that patients who are prescribed these medications have several points at which they could receive this important information.

“The vast majority of drivers who are recent users of prescription drugs that have the potential for impairment have come into contact with a physician, a pharmacist, and a medication label,” says Pollini. “There’s an opportunity here that’s not being leveraged: to provide people with accurate information about what risks are associated with those drugs. People can then make informed decisions about whether they’re able to drive.”

A related commentary by Benedikt Fischer, Ph.D., of the Centre for Addiction and Mental Health in Toronto, Canada, and colleagues expresses concern that increased warnings and interventions may be insufficient to reduce the chances of driving while impaired. These authors point to the issue of alcohol-impaired driving to suggest that only deterrence-based measures — such as roadside testing, license suspensions, and increased insurance premiums — have the potential to change behavior.

 

Why Afternoon Open Heart Surgery Is Better for Patient Outcomes

Open heart surgery is linked to better patient outcomes when carried out in the afternoon, rather than in the morning, according to a study published yesterday (October 26) in The Lancet. The reasons have to do with circadian rhythms, and the risk of heart damage following operation, researchers report.

“Our study found that post-surgery heart damage is more common among people who have heart surgery in the morning, compared to the afternoon,” says coauthor David Montaigne of the University of Lille, France, in a statement. “Our findings suggest this is because part of the biological mechanism behind the damage is affected by a person’s circadian clock and the underlying genes that control it.”

In an observational study of nearly 600 people receiving heart valve replacement surgery from January 2009 to December 2015, the team identified a 50 percent lower risk of heart failure or another cardiac event in people operated on in the afternoon, instead of in the morning. A one-year, randomized controlled trial of 88 patients that concluded last February also established a causal link in the same direction between time of day and surgery outcomes.

To understand the mechanisms responsible for the findings, the researchers analyzed 30 tissue samples from a subgroup of patients in the most recent trial, and found that afternoon surgery samples were quicker to regain the ability to contract when put in conditions mimicking blood filling back into the heart. These samples also revealed differential expression of 287 circadian clock-related genes between morning and afternoon samples.

In a subsequent mouse study, the team showed that using experimental drugs to reduce the activity of one of the genes expressed at higher levels in the morning could reduce the risk of heart damage following surgery. Study coauthor Bart Staels of the University of Lille tells STAT that “one could imagine, quite rapidly, a pharmacological approach that could basically wipe out the effects between morning and afternoon.”

From a biological point of view, the results are “not hugely surprising,” John O’Neill of the UK Medical Research Council’s Laboratory of Molecular Biology tells the BBC. “Just like every other cell in the body, heart cells have circadian rhythms that orchestrate their activity. Our cardiovascular system has the greatest output around mid/late-afternoon, which explains why professional athletes usually record their best performances around this time.”

Although hospitals can hardly eliminate morning surgery altogether, the authors suggest that patients with complicating conditions such as obesity and type 2 diabetes be prioritized for afternoon operations. “We don’t want to frighten people from having surgery—it’s life saving,” Staels tells the BBC. But “if we can identify patients at highest risk, they will definitely benefit from being pushed into the afternoon and that would be reasonable.”

 

Do bacteria have sense of touch?

Although bacteria have no sensory organs in the classical sense, they are still masters in perceiving their environment. A research group at the University of Basel’s Biozentrum has now discovered that bacteria not only respond to chemical signals, but also possess a sense of touch. In their recent publication in Science, the researchers demonstrate how bacteria recognize surfaces and respond to this mechanical stimulus within seconds. This mechanism is also used by pathogens to colonize and attack their host cells.

Be it through mucosa or the intestinal lining, different tissues and surfaces of our body are entry gates for bacterial pathogens. The first few seconds — the moment of touch — are often critical for successful infections. Some pathogens use mechanical stimulation as a trigger to induce their virulence and to acquire the ability to damage host tissue. The research group led by Prof. Urs Jenal, at the Biozentrum of the University of Basel, has recently discovered how bacteria sense that they are on a surface and what exactly happens in these crucial first few seconds.

Research focused only on chemical signals

In recent decades, research has made enormous progress in exploring how bacteria perceive and process chemical signals. “However, we have little knowledge of how bacteria read out mechanical stimuli and how they change their behavior in response to these cues,” says Jenal. “Using the non-pathogenic Caulobacter as a model, our group was able to show for the first time that bacteria have a ‘sense of touch’. This mechanism helps them to recognize surfaces and to induce the production of the cell’s own instant adhesive.”

How bacteria recognize surfaces and adhere to them

Swimming Caulobacter bacteria have a rotating motor in their cell envelope with a long protrusion, the flagellum. The rotation of the flagellum enables the bacteria to move in liquids. Much to the surprise of the researchers, the rotor is also used as a mechano-sensing organ. Motor rotation is powered by proton flow into the cell via ion channels. When swimming cells touch surfaces, the motor is disturbed and the proton flux interrupted.

The researchers assume that this is the signal that sparks off the response: The bacterial cell now boosts the synthesis of a second messenger, which in turn stimulates the production of an adhesin that firmly anchors the bacteria on the surface within a few seconds. “This is an impressive example of how rapidly and specifically bacteria can change their behavior when they encounter surfaces,” says Jenal.

Better understanding of infectious diseases

“Even though Caulobacter is a harmless environmental bacterium, our findings are highly relevant for the understanding of infectious diseases. What we discovered in Caulobacter also applies to important human pathogens,” says Jenal. In order to better control and treat infections, it is mandatory to better understand processes that occur during these very first few seconds after surface contact.

 

The brain can re-map advanced artificial limbs

Targeted motor and sensory reinnervation (TMSR) is a surgical procedure on patients with amputations that reroutes residual limb nerves towards intact muscles and skin in order to fit them with a limb prosthesis allowing unprecedented control. By its nature, TMSR changes the way the brain processes motor control and somatosensory input; however the detailed brain mechanisms have never been investigated before and the success of TMSR prostheses will depend on our ability to understand the ways the brain re-maps these pathways. Now, EPFL scientists have used ultra-high field 7 Tesla fMRI to show how TMSR affects upper-limb representations in the brains of patients with amputations, in particular in primary motor cortex and the somatosensory cortex and regions processing more complex brain functions. The findings are published in Brain.

Targeted muscle and sensory reinnervation (TMSR) is used to improve the control of upper limb prostheses. Residual nerves from the amputated limb are transferred to reinnervate and activate new muscle targets. This way, a patient fitted with a TMSR prosthetic “sends” motor commands to the re-innervated muscles, where his or her movement intentions are decoded and sent to the prosthetic limb. On the other hand, direct stimulation of the skin over the re-innervated muscles is sent back to the brain, inducing touch perception on the missing limb.

But how does the brain encode and integrate such artificial touch and movements of the prosthetic limb? How does this impact our ability to better integrate and control prosthetics? Achieving and fine-tuning such control depends on knowing how the patient’s brain re-maps various motor and somatosensory pathways in the motor cortex and the somatosensory cortex.

The lab of Olaf Blanke at EPFL, in collaboration with Andrea Serino at the University Hospital of Lausanne and teams of clinicians and researchers in Switzerland and abroad have successfully mapped out these changes in the cortices of three patients with upper-limb amputations who had undergone TMSR and were proficient users of prosthetic limbs developed by Todd Kuiken and his group at the Rehabilitation Institute of Chicago.

The scientists used ultra-high field 7T functional magnetic resonance imaging (fMRI), a technique that measures brain activity by detecting changes in blood flow across it. This gave them an unprecedented insight at great spatial resolution into the cortical organization of primary motor and somatosensory cortex of each patient.

Surprisingly, the study showed that motor cortex maps of the amputated limb were similar in terms of extent, strength, and topography to individuals without limb amputation, but they were different from patients with amputations that did not receive TMSR, but were using standard prostheses. This shows the unique impact of the surgical TMSR procedure on the brain’s motor map.

The approach was even able to identify maps of missing (phantom) fingers in the somatosensory cortex of the TMSR patients that were activated through the reinnervated skin regions from the chest or residual limb.

The somatosensory maps showed that the brain had preserved its original topographical organization, although to a lesser degree than in healthy subjects. Moreover, when investigating the connections between upper-limb maps in both cortices, the researchers found normal connections in the TMSR patients, which were comparable with healthy controls. However, preservation of original mapping was again reduced in non-TMSR patients, showing that the TMSR procedure preserves strong functional connections between primary sensory and motor cortex.

The study also showed that TMSR is still in need of improvement: the connections between the primary sensory and motor cortex with the higher-level embodiment regions in fronto-parietal cortex were as weak in the TMSR patients as in the non-TMSR patients, and differed with respect to healthy subjects.

This suggests that, despite enabling good motor performance, TMSR-empowered artificial limbs still do not move and feel like a real limb and are still not encoded by the patient’s brain as a real limb. The scientists conclude that future TMSR prosthetics should implement systematic somatosensory feedback linked to the robotic hand movements, enabling patients to feel the sensory consequences of the movements of their artificial limb.

The findings provide the first detailed neuroimaging investigation in patients with bionic limbs based on the TMSR prosthesis, and show that ultra-high field 7 Tesla fMRI is an exceptional tool for studying the upper-limb maps of the motor and somatosensory cortex following amputation.

In addition, the findings suggest that TMSR may counteract poorly adapted plasticity in the cortex after losing a limb. According to the authors, this may provide new insights into the nature and the reversibility of cortical plasticity in patients with amputations and its link to phantom limb syndrome and pain.

Finally, the study also shows that there is a need of further engineering advances such as the integration of somatosensory feedback into current prosthetics that can enable them to move and feel as real limbs.

Story Source:

Materials provided by Ecole Polytechnique Fédérale de Lausanne.

 

Adderall Misuse May Be Hidden Part of Teen Amphetamine Abuse

American teens underestimate their use of amphetamines, likely because many don’t know that the attention-deficit/hyperactivity disorder (ADHD) drug Adderall is an amphetamine, a new study suggests.

High school and college students sometimes use Adderall, a type of stimulant medication, without a doctor’s order because they believe it will boost their mental function and school performance.

Use of amphetamines without a doctor’s order, known as nonmedical use, carries a high risk of abuse and dependency, as well as potential harmful side effects such as heart problems and seizures. People who use prescription stimulants like amphetamines without a doctor’s order also are more likely to engage in other drug use and risky behaviors, the researchers said.

The researchers examined the responses of more than 24,000 high school seniors who took part in a national survey between 2010 and 2015. Though nearly 8 percent of the students reported nonmedical amphetamine use and about 7 percent reported nonmedical Adderall use in the past year, about 29 percent of nonmedical Adderall users reported no nonmedical amphetamine use.

Students aged 18 and older, black students, and students with parents with lower education levels were more likely than others to report no nonmedical amphetamine use, despite reporting nonmedical Adderall use, the study found. It was conducted by the Center for Drug Use and HIV/HCV Research at New York University’s Meyers College of Nursing in New York City.

“Over a quarter of teens who reported using Adderall without a doctor telling them to take it contradicted themselves by saying they do not use amphetamine,” senior author Joseph Palamar, an associate professor of population health, said in a university news release.

“As a result, the estimated prevalence of nonmedical amphetamine use of 7.9 percent may be an underestimate,” he said. “It may be as high as 9.8 percent, or one out of 10 high school seniors, when considering the discordant reporting we found.”

“Our findings suggest that many young people are unaware that Adderall is amphetamine,” Palamar said. “In addition, such conflicting reports mean that prescription stimulant misuse may be underestimated.”

The study was published Oct. 23 in the journal Drug and Alcohol Dependence.

“Alarmingly, we had similar findings regarding opioids in another study, with many teens appearing unaware that the Vicodin and OxyContin they took are opioids,” Palamar added. “Better drug education is needed to inform the public about common drugs like amphetamines and opioids.”

He and his colleagues also said their study shows the need to improve how drug use surveys are conducted. For example, surveys could provide images of specific substances to help respondents recognize specific pills.

SOURCE: New York University, news release, Oct. 23, 2017

 

A healthy heart may protect older adults from disability

 

A healthy heart is important to the well-being of older adults. The American Heart Association (AHA) defines “ideal cardiovascular health” based on four health behaviors (current smoking, body mass index, physical activity, and healthy diet and three health factors (total cholesterol, blood pressure), and fasting blood glucose level).

Recently, a team of researchers studied older Latin Americans to examine the relationship between the AHA guidelines and disability. Their study was published in the Journal of the American Geriatrics Association.

The relationship is an important one to consider, since heart disease (also known as “cardiovascular disease”) can lead to several disabling problems for older adults. In fact, heart attacks and strokes are the first and third most common causes of disability in the US. The effect of a stroke on the brain is a leading cause of disability. Cardiovascular disease is the second leading cause of dementia and, for older adults, the disease also can make it difficult to function in daily life.

In their study, the researchers used information from the Chilean National Health Survey conducted between 2009-2010. 460 Chilean adults all over age 65 participated in the study.

The researchers measured AHA-identified heart-healthy behaviors:

  • Maintain a Body Mass Index (BMI) of less than 25. (BMI is a ratio between your weight and height.)
  • Be physically active for at least 30 minutes a day, 5 or more days a week.
  • Don’t smoke tobacco.
  • Eat a healthy diet with plenty of fruits and vegetables and few to no processed or fast foods.

The researchers also measured these risk factor measurements of “ideal cardiovascular health”:

  • Blood pressure of 120/80
  • Total cholesterol under 200 mg/dL
  • Fasting blood sugar under 100 mg/dL

In their study, the researchers created three different levels of health based on the participants’ cardiovascular-healthy behaviors and heart health factors:

  • People in the healthiest level had 5 to 7 of the behaviors/measurements.
  • People in the middle level had 3 to 4 healthy behaviors/measurements.
  • People in the lowest (most unhealthy) level had 0 to 2 behaviors/measurements.

The researchers compared the behaviors/measurements with disability among the participants. They learned that having an ideal level of physical activity reduced the chances for being disabled for older adults, even for those who had a history of heart disease or arthritis.

The researchers also found that Chilean women tended to be less active and more disabled than Chilean men.

Compared to people with an unhealthy level of behaviors/measurements, people in the two healthier groups had a lower risk for disability.

Finally, people who had an ideal BMI had lower disability. The researchers noted that obesity may quicken age-related declines in functional ability, and poses a threat to independence as we age. The authors suggest that public policies might promote ideal health behaviors early in life, helping people maintain their health into older adulthood.

 

Does smell sensitivity change everyday?

It has always been apparent that some individuals have a better sense of smell than others, but a new study of 37 teens provides the first direct evidence that within each person, smell sensitivity varies over the course of each day. The pattern, according to the data, tracks with the body’s internal day-night cycle, or circadian rhythm.

“This finding is very important for olfactory perception science,” said Rachel Herz, lead author of the study in Chemical Senses and an adjunct assistant professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University. “This hadn’t been known before and this is the first clear, direct evidence.”

As one of the five senses, smell is an important ability, Herz noted, not only for experiencing and enjoying the world, but also for receiving information about danger, such as nearby fire or spoiled food, and for basic functions like eating. Changes in the sense during the day can affect all these capabilities.

Indeed Herz, an expert in the sense of smell, made the findings in collaboration with sleep expert Mary Carskadon, a Brown professor of psychiatry and human behavior. Carskadon is conducting a larger study with a hypothesis that circadian timing and sleep habits may affect the eating habits of teens, potentially contributing to obesity. Smell is associated with food consumption, notes Herz — who has authored the upcoming book “Why You Eat What You Eat” — so the researchers devised an experiment to determine whether smell varies with circadian rhythm.

28-hour ‘days’

To conduct the study, the researchers asked the 21 boys and 16 girls, all between ages 12 and 15, to sleep on a fixed schedule for two weeks before reporting to the Bradley Hospital sleep lab. After an adaptation night in the lab, the teens began a week of 28-hour days where their sleep was shifted four hours later each “night.”

All along, they lived indoors in dim light, socializing and participating in fun activities with each other and staff members. The goal was to separate them temporarily from typical sleep disruptions and from external cues of circadian timing. In this way, Carskadon said, their inherent, internal circadian rhythms could be measured, as could the sensitivity of their sense of smell at all times throughout their rhythms (in addition to other measures, such as food intake).

The team measured circadian rhythm by detecting levels of the sleep-cueing hormone melatonin in their saliva. Melatonin secretion begins about an hour before the urge to sleep hits. They assessed smell sensitivity using “Sniffin’ Sticks,” a common test for measuring odor detection thresholds. Each time they used the sticks, the researchers could determine the threshold concentration of the odor that the teens could detect. Smell was assessed every three hours while teens were awake.

The rhythm of smell

Individuals varied substantially in how much their smell sensitivity varied over a circadian cycle and in when it peaked. But there were clear patterns individually and overall. One was that the variance showed a circadian rhythm, and the other was that smell sensitivity was never strongest well into the “biological night,” or the period well after melatonin onset when people are most likely to be asleep and least likely to be eating. In clock terms, it’s from about 3 to 9 a.m.

“So we have 84 tests done on each child, and each one has a circadian phase associated with it,” Carskadon said. “There is a rhythm here, and it’s not flat or that you smell the same all the time. Your sense of smell changes in a predictable manner, though it’s not the same for every child.”

Carskadon said the findings should be of note to clinicians and researchers who seek to assess a patient’s sense of smell. The study suggests that sensitivity might be inherently higher at an afternoon appointment than in the early morning.

Herz noted that there could be implications for fire safety as well. A decade ago she and Carskadon had found that the sense of smell all but shuts down during sleep. Now there is evidence that the sense of smell is relatively weak during a quarter of the circadian cycle. This emphasizes, Herz said, the value of audible smoke alarms, since smell may be a poor indicator of that danger at least in the early morning hours.

On average, the peak of smell sensitivity was at the beginning of biological night, or about 9 p.m. for the teens.

Herz said she can only speculate about why smell sensitivity might peak, on average, in the late evening. From an evolutionary standpoint, it might be to ensure the greatest sense of satiety during the important end of day meal, it might be a way of increasing mating desire, or perhaps a way of scanning for nearby threats before bedding down for the evening.

For each individual, she said, knowing when during the day smell their sensitivity might peak could be a way of identifying the time when sensory experiences could be most pleasant.

For less ancient health concerns, however, Carskadon says more data from the experiments is coming to help the team determine whether the circadian fluctuations of smell sensitivity helps determine food choices and eating behaviors among teens.

“The sense of smell changes across the 24 hours of the day,” Carskadon said. “We don’t know if that difference will affect what or how people eat. There is more to come.”

 

Eating more fruits, vegetables boosts psychological well-being

Fruits and vegetables are a pivotal part of a healthful diet, but their benefits are not limited to physical health. New research finds that increasing fruit and vegetable consumption may improve psychological well-being in as little as 2 weeks.

Study leader Dr. Tamlin Conner, of the Department of Psychology at the University of Otago in New Zealand, and colleagues found that young adults who were given extra fruits and vegetables each day for 14 days ate more of the produce and experienced a boost in motivation and vitality.

The researchers recently reported their findings in the journal PLOS One.

According to the United States Department of Agriculture, adults should aim to consume around two cups of fruits and around two to three cups of vegetables daily.

One cup of fruits is the equivalent to half a grapefruit or a large orange, and one cup of vegetables is proportionate to one large red pepper or a large, baked sweet potato.

As part of a healthful diet, fruits and vegetables can help reduce the risk of obesity, type 2 diabetes, heart disease, stroke, and some types of cancer.

In recent years, studies have suggested that fruit and vegetable intake may also improve mental health. For their study, Dr. Conner and team set out to investigate this association further.

Increased motivation, vitality with higher intake of fruits and vegetables

The researchers enrolled 171 students aged between 18 and 25 to their study, and they were divided into three groups for 2 weeks.

One group continued with their normal eating pattern, one group was personally handed two additional servings of fresh fruits and vegetables (including carrots, kiwi fruit, apples, and oranges) each day, while the remaining group was given prepaid produce vouchers and received text reminders to consume more fruits and vegetables.

At the beginning and end of the study, participants were subjected to psychological assessments that evaluated mood, vitality, motivation, symptoms of depression and anxiety, and other determinants of mental health and well-being.

The researchers found that participants who personally received extra fruits and vegetables consumed the most of these products over the 2 weeks, at 3.7 servings daily, and it was this group that experienced improvements in psychological well-being. In particular, these participants demonstrated improvements in vitality, motivation, and flourishing.

The other two groups showed no improvements in psychological well-being over the 2-week period.

Furthermore, no improvements were seen in symptoms of depression and anxiety in any of the groups. “The majority of research linking depression to dietary patterns has been longitudinal, meaning that possible differences in ill-being may be established over a much longer period of time rather than our brief 2-week period,” note the authors.

Still, the researchers say that their findings indicate that increasing the intake of fruits and vegetables through personal delivery may lead to rapid benefits for psychological well-being.

The team concludes that:

“Providing young adults with high-quality FV [fruits and vegetables], not texting them reminders to eat more FV and giving them a voucher, resulted in improvements to their psychological well-being over a 2-week period.

This is the first study to show that providing high-quality FV to young adults can result in short-term improvements in vitality, flourishing, and motivation. Findings provide initial validation of a causal relationship between FV and well-being, suggesting that large-scale intervention studies are warranted.”

 

Insulin Use During, After Meals Raises Risk Of Non-Adherence

Individuals with type 2 diabetes who use bolus insulin during or after meals have a greater risk of non-adherence and poorer glycemic control than those who use insulin prior to meals, according to a recent analysis.

For their analysis, the researchers evaluated 1483 adult participants with type 2 diabetes from 12 countries in a web-based, self-reported, patient-preference survey. All patients included in the study had reported bolus insulin use.
____________________________________________________________________________________________

RELATED CONTENT
Diabetes Worsens CV Outcomes in HF, Severity Depends on Microvascular Complications
Post-Operative Cognitive Dysfunction Significantly More Likely With Diabetes
____________________________________________________________________________________________

The Morisky Medication Adherence Scale questionnaire was used to measure adherence.

A total of 864 (58%) participants had reported dosing bolus insulin before meals (pre-meal group), 354 (24%) during or after meals (post-meal group), and 265 (18%) before, during, or after meals (mixed group). Only participants in the pre-meal and post-meal groups (n = 1218) were included in the present analysis.

Results indicated that hemoglobin A1c (HbA1c) levels varied significantly based on the timing of insulin doses. In the post-meal group, 40% of participants had an HbA1c of 9% of higher, compared with 29% of participants in the pre-meal group.

Ultimately, the researchers found that participants who used bolus insulin during or after meals were significantly more likely to report non-adherence vs those who used insulin before meals. Furthermore, participants who used insulin during or after meals more often reported participating in diabetes education programs.

The researchers also noted that 78% of all participants had reported preferring bolus insulin “administrable whenever convenient.”

“Approximately 24% of respondents never comply with guidelines for insulin dose timing, with higher risk of non-adherence and increased participation in diabetes care programs,” the researchers concluded.

“Respondents dosing insulin post-meal are more likely to have poor glycemic control (HbA1c [of 9% or more], 74.9 mmol/mol). Given that many respondents had high HbA1c and were non-adherent, a treatment [that] satisfies patient preference for bolus insulin with flexible dose timing could be considered.”

—Christina Vogt

Reference:

Schaper NC, Nikolajsen A, Sandberg A, Buchs S, Bøgelund M. Timing of insulin injections, adherence, and glycemic control in a multinational sample of people with type 2 diabetes: a cross-sectional analysis [Published online October 23, 2017]. Diabetes Ther. https://doi.org/10.1007/s13300-017-0317-9.