Tag: 1/7/21

Categories : Medical Research & TechnologyTags :

A Step to Towards Electrically Restoring Oral Sensation and Function

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In an effort towards restoring oral functionality lost to nerve or brain damage, researchers at Texas A&M University have determined the minimum electrical stimulation needed to provide sensation in various parts of the mouth.

Sensorimotor feedback loops involve the brain interpreting incoming signals from sensory nerves and then ordering motor nerves to execute a particular movement. Sensorimotor loops play a vital role in voluntary functions, like walking or holding an object, and involuntary movements, like sneezing or blinking.

Within the mouth, both sensory and motor nerves are richly supplied. In particular, sensorimotor nerves in the soft palate and tongue coordinate several intraoral movements related to swallowing, speech and respiration. Damage to either the sensory or motor nerve fibres due to neurotrauma or disease can therefore compromise these essential functions and worsening the quality of life for afflicted individuals.

Electrical nerve stimulation might help jumpstart the nerves into action, much like how a pacemaker can electrically stimulate nerves in the heart, causing the heart muscle to contract. Unlike a pacemaker however, the parameters of the electrical currents needed for proper stimulation of different parts of the mouth have not been investigated.

“Electrical stimulation can modulate nerve currents or action potentials, which are the mode of communication to and from the brain,” said Hangue Park, assistant professor in the Department of Electrical and Computer Engineering. “And so, electrical stimulation should be carefully applied, because if not, then it might cause undesirable effects, or it might not stimulate anything at all.”

To investigate the minimum stimulation currents needed, Park and his team place tiny metal electrodes in a standard dental retainer. These electrodes were positioned in subjects’ mouths to stimulate either their soft palate or the side and tip of the tongue, which are dense in sensory nerves. The researchers slowly changed the amplitude of the stimulation current, keeping the frequency fixed. Subjects reported when they began feeling a sensation and when the sensation was uncomfortable, and the same experiment was repeated with a higher frequency of current.

After compiling their data, the team determined the average perception and discomfort thresholds for the tongue and soft palate. In addition, they produced an equivalent circuit of the intraoral cavity to duplicate the electrical properties of that area. This circuit, the researchers said, can help to further study the effects of electrical stimulation offline without requiring human subjects.

The researchers noted that their next steps would be to electrically stimulate the intraoral region and investigate how these simulations change chewing, swallowing and other behaviours.

“Sensorimotor systems can be extremely vulnerable to damage due to neural defects, aging and neurodegenerative diseases,” Park said. “In this study, we have begun to lay the groundwork for electrically stimulating parts of the mouth that control involuntary and voluntary movements. Our work is a seminal study and it is important so that we can, in the near future, help people that face enormous challenges doing everyday tasks that we take for granted.”

Source: Texas A&M University

Journal information: Park, B., et al. (2021) Electrical Characterization of the Tongue and the Soft Palate using Lumped-Element Model for Intraoral Neuromodulation. IEEE Transactions on Biomedical Engineering. doi.org/10.1109/TBME.2021.3070867.

Categories : Cardiovascular DiseaseTags :

Cardiac Surgery Guidelines Updated with Emphasis on Patient Blood Management

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Newly updated multi-society cardiac surgery guidelines have shifted to a comprehensive blood management approach, with no longer simple recommendations on transfusion.

An update to the 2011 recommendations from the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists, now in collaboration with the American Society of ExtraCorporeal Technology, and the Society for the Advancement of Patient Blood Management (SABM), has been put out. It is available online in the Annals of Thoracic Surgery.

Since the last version, there has been so much new evidence that Pierre R. Tibi, MD, of Yavapai Regional Medical Center in Prescott, Arizona, and colleagues revised or added 23 recommendations and scrapped others.

Probably the biggest change is going from ‘blood conservation’ to the broader ‘patient blood management‘ (PBM) approach, Dr Tibi told MedPage Today.

“Basically we’re considering blood as another vital organ,” he said. “Why that is important is because now we look at a patient’s blood system as an organ that needs to be assessed and treated for the sake of that organ and not simply to decide when or when not to transfuse.”

Recommendations range from preoperative assessment of bleeding risk and anaemia to intraoperative perfusion and blood salvage practices to postoperative treatment with human albumin for volume replacement.

“Most hospitals around the U.S. are acutely aware of patient blood management and, to some degree or another, are implementing many of the things we are talking about,” noted Tibi, who is the most recent past president of SABM. Nationwide, the amount of blood transfused in cardiac surgery has dropped 45% in the past 10 to 15 years but still ranges widely across centres.

A broadly endorsed guideline like this emphasising the importance of a whole-patient strategy should hopefully standardize effective practices and move insurers to cover them, he suggested.

The guideline, for example, gives preoperative assessment of anaemia and its treatment with IV iron and erythropoietin-stimulating agents, if there is time, a class IIA endorsement. Anaemia is widespread, with possibly as many as 40% of patients having it, with one in 10 being under the 8 mg/dL haemoglobin threshold.

“There is a distinct correlation between preoperative anemia and worse clinical outcomes in most studies,” the guidelines note. “Usually, the greater the anemia, the more severe the complications.”

However, preoperative anaemia is “very, very underrecognised and undertested,” Dr Tibi said. While there isn’t always time to reverse anaemia that is found before cardiac surgery, he pointed out that “most of the factors in elective heart surgery have to do with insurance and Medicare. … Oftentimes the treatment for anaemia is not covered by various entities and is too expensive for patients to cover themselves.”

Other notable updates included a class IA recommendation for red blood cell salvage with centrifugation when patients are on cardiopulmonary bypass and the addition of recommendations for the assessment and treatment of patients on anticoagulants.

The guideline, for example, says to withdraw ticagrelor (Brilinta) at least 3 days, clopidogrel (Plavix) 5 days, and prasugrel (Effient) 7 days prior to elective cardiac surgery, while other non-vitamin K oral anticoagulants (NOACs) should be stopped at least 2 days in advance.

“Despite their advantages, NOACs present some periprocedural challenges for operations with a high-risk bleeding profile,” the document says. “Available measurement assays to assess anticoagulation for NOACs are imprecise, and the availability of reversal agents is limited.”

If point-of-care testing with thrombin clotting time is available for dabigatran (Pradaxa), or anti-factor Xa assays for apixaban (Eliquis) and rivaroxaban (Xarelto), in the case of emergent surgery, the guidelines recommend their use.

Source: MedPage Today

Journal information: Tibi P, et al “STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management” Ann Thor Surg 2021; DOI: 10.1016/j.athoracsur.2021.03.033.

Categories : Mental Health Substance UseTags :

The Delicate Balance of the Endocannibinoid Pathway

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Scientists have uncovered an unexpected link between a synapse protein that has been implicated in neuropsychiatric disorders and the endocannabinoid pathway.

These findings suggest a role for the endocannabinoid system in conditions including bipolar disorder, according to Peter Penzes, PhD, the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Sciences, professor of Physiology and Pharmacology, and senior author of the study.

“The endocannabinoid system could be disrupted in patients with bipolar disease, or it could be the opposite: medical marijuana could have therapeutic potential for these patients,” said Prof Penzes, who is also director of the Center for Autism and Neurodevelopment. “These are the questions that need to be answered.”

Cannabis mimics naturally occurring endocannabinoids in the brain, which is how it produces its effect in humans. Since the specific function of endocannabinoids is still not fully understood, the legalisation of marijuana in many US states has prompted more investigation into its biological pathways, Prof Penzes said. The endocannabinoid system is a widespread neuromodulatory system that plays important roles in central nervous system (CNS) development, synaptic plasticity, and the response to endogenous and environmental insults.

Endocannabinoids are produced by an enzyme known as diacylglycerol lipase alpha (DAGLA), which is concentrated in synapses. Endocannabinoids dampen synaptic strength, which is why marijuana has calming effects.

Prof Penzes and colleagues have previously studied ankyrin-G, another synapse protein which regulates transmission speed across synapses. Aberrant over- or under-expression of ankyrin-G has been associated with disorders such as bipolar disorder, schizophrenia and autism.

Studying mice with ankyrin-G genetically deleted, they made a surprising discovery: Ankyrin-G seemed to stabilise DAGLA at synapses, increasing the efficiency of DAGLA.

“It’s a delicate mechanism that regulates dendritic spine morphology,” said lead author Sehyoun Yoon, PhD, research assistant professor of Physiology.

These findings comport with another recent study, led by investigators at Icahn School of Medicine at Mount Sinai and published in Nature Genetics. The study showed that both DAGLA and ankyrin-G (ANK3) are risk genes for bipolar disorder in a genome analysis of over 40,000 patients.

“It’s almost like somebody who is leading a double life, Dr. Jekyll and Mr. Hyde,” Prof Penzes said. “Ankyrin-G has this entire separate function.”

The convergence of ankyrin-G with the endocannabinoid pathway opens up an entire new world of possibilities, both for investigating disease risk and possible therapies.

“Cannabis may contribute to increased risk for mental disorders, which has actually been shown in schizophrenia,” Prof Penzes said. “Conversely, cannabis could be beneficial in some brain disorders, which prompted trials of medical marijuana in patients with autism.”

Prof Penzes said in future he plans to examine the downstream effects of this biological pathway, both in normal subjects and in disease.

Source: Northwestern University

Journal information: Sehyoun Yoon et al, cAMP Signaling–Mediated Phosphorylation of Diacylglycerol Lipase α Regulates Interaction With Ankyrin-G and Dendritic Spine Morphology, Biological Psychiatry (2021). DOI: 10.1016/j.biopsych.2021.03.023

Categories : AddictionTags :

New Insights into Genetic Risk for Nicotine Dependence

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A new study has developed a new model for examining the genetic risk for nicotine dependence. 

Tobacco smoking carries undeniable health risks, and being unable to quit or moderate smoking draws out the problem. While some people may be casual smokers and can easily quit, others become heavy smokers who struggle to quit. This risk for nicotine dependence comes from a complex mix of environmental, behavioural, and genetic factors.

Twins studies indicate that 40 to 70 percent of the risk factors are heritable. Until recently, however, studies have only explained about 1 percent of the observed variation in liability to nicotine dependence, using a genetic score based on how many cigarettes a person smokes per day.

The new study led by psychologists at Emory University leveraged genome-wide association studies for a range of different traits and disorders correlated with nicotine dependence and explained 3.6 percent of the variation in nicotine dependence. The findings were reported in the journal Nicotine & Tobacco Research.

Higher polygenetic scores for a risk for schizophrenia, depression, neuroticism, self-reported risk-taking, a high body mass index, alcohol use disorder, along with more cigarettes smoked a day were all indicators of a higher risk for nicotine dependence, the researchers found. Meanwhile, the results showed that polygenetic scores associated with higher education attainment lowered the risk for nicotine dependence.

Senior author Rohan Palmer, assistant professor, Behavioral Genetics of Addiction Laboratory, Emory University explained: “If you look at the joint effect of all of these characteristics, our model accounts for nearly 4 percent of the variation in nicotine dependence, or nearly four times as much as what we learn when relying solely on a genetic index for the number of cigarettes someone smokes daily,”

“What we’re finding,” Prof Palmer added, “is that to better leverage genetic information, we need to go beyond individual human traits and disorders and think about how risk for different behaviors and traits are interrelated. This broader approach can give us a much better measure for whether someone is at risk for a mental disorder, such as nicotine dependence.”

“All of the traits and diseases we looked at are polygenic, involving multiple genes,” added first author Victoria Risner, who did the work as an Emory undergraduate majoring in neuroscience and behavioural biology. “That means that millions of genetic variants likely go into a complete picture for all of the heritable risks for nicotine dependence.”

The researchers hope that others will build on their multi-trait, polygenetic model and continue to boost the understanding of the risk for such complex disorders. “The more we learn, the closer we can get to one day having a genetic test that clinicians can use to inform their assessment of someone’s risk for nicotine dependence,” Prof Palmer said.

Though smoking hazards are well known, about 14 percent of Americans use tobacco daily. Around half a million people die each year in the US from smoking or exposure to smoke, and another 16 million have serious illnesses caused by tobacco use, including cancer, cardiovascular disease, and pulmonary disease. While chemicals produced during smoking and vaping cause the health impacts, nicotine hooks people on these habits.

Risner worked on this paper for her Honours thesis. “Nicotine dependence was interesting to me because the vaping scene was just arriving while I was an undergraduate,” she says. “I saw some of my own friends who were into vaping quickly becoming dependent on it, while some others who were using the same products didn’t. I was curious about the genetic underpinnings of this difference.” Risner is now in medical school at University of North Carolina.

The work made use of genome-wide association studies for a range of traits and disorders. The researchers then sought matching variants in genetic data from a nationally representative sample of Americans with nicotine dependence. Polygenetic scores for the different traits and disorders either raised or lowered the risk for that dependence. The strongest predictors were number of cigarettes smoked per day, self-perceived risk-taking, and educational attainment.

The multi-variant, polygenetic model offers a path forward. For instance, a clearer picture of heritability for nicotine dependence, may be gained by adding more risk associations to the model (such as nicotine metabolism) and clusters of polygenic traits (such as anxiety along with neuroticism).

“As we continue to zero in on who is most at risk for becoming nicotine dependent, and what inter-related factors, whether genetic or environmental, may raise their risk, that could help determine what intervention might work best for an individual,” Prof Palmer said.

“Just a few decades ago, it was not well understood that nicotine dependence could have a genetic component,” Risner said. “Genetic studies may help reduce some of the stigma society has against substance use disorders, while also making treatment more accessible.”

Source: Emory Health Sciences

Journal information: Risner, V A., et al. (2021) Multi-Polygenic Analysis of Nicotine Dependence in Individuals of European Ancestry. Nicotine & Tobacco Research. doi.org/10.1093/ntr/ntab105.

Categories : Mental HealthTags :

Half of GP Staff Face Abuse as a Result of Vaccinations

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A survey published in The BMJ has found that in UK practices, over half (52%) of GP staff face abuse while working on the COVID vaccination programme.

The Medical Protection Society (MPS) survey of 222 GP practice staff , which included GPs, nurses, and practice managers, also found that over half (53%) of staff said that their surgery or vaccination centre had been defaced by anti-vaccination material. GP practices in the UK had been offering COVID vaccinations since December 2020.

One respondent said, “Staff of all disciplines are leaving the profession in droves because of the behaviour of the public creating unbearable working situations. Morale is the lowest I have ever known, anyone near retirement is retiring early.” Another said, “Abuse—especially written and posted in the prescription box on the gate—has resulted in staff being very concerned for their safety at the surgery.”

About two-thirds of respondents (60%) said that abuse and complaints relating to the UK’s COVID vaccination programme had affected their own or their team’s mental wellbeing. A further 71% said that the increased workload resulting from the programme has impacted their wellbeing.

Pallavi Bradshaw, medicolegal lead for risk prevention at MPS, said that GP practices were in the firing line over patient frustrations with the vaccination programme. “GPs are mentally and physically exhausted, with the risk of disillusionment and burnout higher than ever,” Bradshaw said. “Wellbeing support must be provided to all GP surgery staff who are feeling overwhelmed and demoralised, and a zero tolerance policy of abuse must be enforced across the NHS so healthcare workers feel their safety is a priority.”

Source: The BMJ

Categories : COVID General InterestTags :

Month-long COVID Coma Left Ambulance Worker ‘Scarred’

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A UK ambulance worker who contracted COVID and was in an induced coma for over a month says his family is psychologically scarred by what happened.

Paul Clements, 59, had major organ failure as well as several infections, leaving him in intensive care at Bristol Royal Infirmary. Doctors told him he was lucky to survive the 33-day induced coma. Speaking to the BBC, Mr Clements said that the time passed “in the blink of an eye”.

“The last thing I remember is being handed a cup of tea by my daughter,” said Mr Clements. He was agitated, complaining that the tea tasted awful, prompting concern from his family.

“I put it down, and then I blinked. I then found myself lying on a bed looking at a nurse,” he recalled. “I told her that I’d put my tea down somewhere.”

He said the nurse laughed in response, and then explained to him that he “had been unconscious for 33 days.”

On 19 March 2020, Mr Celements began to have COVID symptoms. Five days later, he was rushed into hospital.

“They tried three times to wake me up. The doctors told me I had pneumonia, a chest infection, an abdominal infection, kidney failure and liver failure – all wrapped up in COVID.” Up to a third of hospitalised COVID patients in the UK’s first wave had ‘do not resuscitate’ orders, recorded on or just before their admission.

He says that “Trying to get my head around that was almost impossible. Even now they have no idea why I survived.”

At the time, his family weren’t allowed to visit the Bristol Royal Infirmary where he was due to COVID restrictions.

“It was hell, absolute hell,” said Paul’s wife, Kerri. “Every time the phone rings you’re on edge thinking this is a call we don’t want. Listening out for his breathing every night, if he coughs I’m on edge, if he says he doesn’t feel well we’re back on edge.”

Mr Clements spent a total of three months in hospital before being leaving the ward to applause by the staff.

He returned to his work as an emergency care assistant six months later, with South Western Ambulance Service where has been for the past 38 years. He acknowledges the close call he had. “Unfortunately in my job I’ve put people in body bags and taken them to the mortuary,” he said.

“I spent some time in hospital trying to get my head around it and realised that could’ve been me, and the reality of it is so scary.”

Source: BBC News

Categories : Diseases, Syndromes and Conditions T-cellsTags :

Ginger Promising in Countering Autoimmune Diseases

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A pre-clinical study has shown that the common herbal remedy and condiment, ginger, may be effective in countering some autoimmune disease mechanisms.

It is already known that ginger has some anti-inflammatory and anti-oxidative properties, making it a popular herbal remedy for inflammatory conditions.Out of at least 14 bioactive compounds, 6-gingerol, which also gives it its distinctive aroma and taste, is reported by a news study to be therapeutic in countering certain autoimmune disease mechanisms in mice.
In mice with antiphospholipid syndrome or lupus, 6-gingerol inhibited the release of neutrophil extracellular traps, which is triggered in response to the autoantibodies produced by these diseases. 

“Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils,” said lead author Ramadan Ali, PhD. “These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil’s surface.”

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The premise of the study was: “Will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?”
“This pre-clinical study in mice offers a surprising and exciting, ‘yes’,” Ali said.

The researchers discovered that after giving 6-gingerol, the mice had lower levels of NETs. Clot formation tendency was drastically reduced and 6-gingerol seemed to inhibit neutrophil enzymes called phosphodiesterases, in turn lowering neutrophil activation.

All of the mice had reduced autoantibodies, suggesting a disruption of the inflammatory cycle of autoantibodies stimulating NETs which stimulate more autoantibodies.

Study author and rheumatologist Jason Knight, MD, noted that patients often asked about herbal supplements, about which he had not been taught much. However, the pre-clinical trial results show that 6-gingerol has anti-neutrophil properties that may be protective against autoimmune disease progression.

“As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol,” said Knight. “It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit.”
For a patient with active antiphospholipid syndrome or lupus, the bioactive compound cannot be the primary therapy, but the natural supplement may help those at high risk for disease development.

“Those that have autoantibodies, but don’t have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice,” Ali said.

“Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?”

Source: Medical Xpress

Journal Information: Ramadan A. Ali et al, Anti-neutrophil properties of natural gingerols in models of lupus, JCI Insight (2020). DOI: 10.1172/jci.insight.138385

Categories : COVIDTags :

COVID Cases Surge in Africa

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Over the past month, Africa has recorded the highest growth in new infections, with a 13% growth over the last week. With only two million cases and 45 000 deaths, Sub-Saharan Africa still only has a small part of the caseload of other regions. 

Dr John Nkengasong, who heads the African Centres for Disease Control (CDC), said: “I think this is serious, the second wave is extremely aggressive.”  The latest surge is thought to be driven by the more transmissible South African variant, known as 501Y.V2. President Cyril Ramaphosa said this variant, found in 90% of new cases, was likely responsible for the country’s latest surge, which has caused morgues to fill up and hospitals to run short of staff and critical resources such as oxygen.  North of the border, Zimbabwe this week started a month-long lockdown to curb a rise in new cases and protect its own overburdened health care system. Nearly two million Zimbabweans live in SA and regularly travel and forth, potentially spreading the virus.

Rashida Ferrand, a London School of Hygiene and Tropical Medicine professor working at the Parirenyatwa Group of Hospitals in the Zimbabwean capital Harare told Reuters that there was “a pretty high likelihood” that the new SA strain of the virus identified could be circulating in Zimbabwe.

Lockdowns may now not be enough to control the spread of the new variant – certain studies of the similar, highly transmissible UK variant suggests that it may now spread too fast for its R (reproduction) value to be brought below 1, or otherwise cause a much slower decline in infections. Fortunately, it seems that lockdown measures in the UK are having some effect. 
Meanwhile, there are concerns that the SA variant may also be able to evade the protection of current vaccines, according to new research – but that has not been peer reviewed yet. Research in SA on the question is expected to provide answers. Meanwhile, 12 gene sequencing laboratories are being geared up around Africa to track the spread of the virus variants, and some genome sequencing work has been done since December, but not enough to paint a clear picture.

Source: The Telegraph

Categories : COVID UncategorizedTags :

Medical Aid Schemes to Share Cost of Nationwide Vaccination

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As arrangements are being made to pay for the COVID vaccination programme for South Africa, medical aid schemes are expected to contribute to the cost towards ensuring at least 67% of the population receives a vaccine, which is the minimum number to establish herd immunity.

Across South Africa, there are some 9 million medical aid beneficiaries, making up some 16% of the population and who collectively spent R186 billion last year on healthcare. The total cost of providing sufficient vaccines for the South African population is thought to range from R5 billion to R20 billion, depending on whether the vaccine is simply bought for the commercial price or whether the distribution and administration costs are factored in as well.

Discussions into paying for the mass vaccinations have suggested that mass-employers, such as mines, ought to contribute  This week, the Council for Medical Schemes (CMS) confirmed that vaccination would be a minimum prescribed benefit, so this will not be paid for out of medical savings.”The CMS acknowledges that there may be an additional cost burden to medical schemes for the provision of the vaccine, but this is not expected to be prohibitively high,” the body said. “In addition, industry associations have assured the CMS that vaccine costs can be absorbed by most medical schemes.”

South Africa’s vaccine source is not yet clear, although President Cyril Ramaphosa has hinted that Canada may share its excess vaccine stock. Canada currently has enough vaccine pre-purchase agreements to vaccinate its population five times over.

Source: Business Insider