Tag: 8/6/23

Categories : GeneticsTags : Leave a comment

The Genes that Determine the Thickness of Eyebrows

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The first gene mapping study on eyebrow thickness in Europeans discovered three previously unreported genetic loci, as reported in the Journal of Investigative Dermatology. The study conducted by the International Visible Trait Genetics (VisiGen) Consortium demonstrates that eyebrow appearance has partly the same and partly different underlying genes in people from different parts of the world.

The appearance of human eyebrows is not just a matter of grooming but is in the genes. Eyebrow thickness, as any other appearance trait, is highly heritable. Thus far, genetic knowledge on eyebrow thickness has been very limited and solely restricted to non-Europeans. This study is the first genome-wide association study (GWAS) on eyebrow thickness in Europeans. By identifying new genes and rediscovering some of the genes previously identified in non-Europeans, the study expands genetic knowledge on human eyebrow variation, which is of broad interest and has implications for dermatology and other fields.

Previous studies were performed among Latin American and Chinese individuals, establishing four eyebrow thickness -associated genetic loci. Because no European eyebrow thickness GWAS had been reported, researchers did not know whether the genetic eyebrow thickness effects described in non-Europeans persist in Europeans, or whether there are European-specific genetic loci involved in eyebrow thickness, or both.

Lead investigator Prof Dr Manfred Kayser, Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, and co-chair of the VisiGen Consortium responsible for this study, commented, “Despite the immense efforts in mapping genes underlying human complex traits, we still know much more about the genes that make us sick than about those behind our healthy looks. For the first time, we performed a gene mapping study on eyebrow thickness variation in Europeans. Previous genetic knowledge on eyebrow thickness was limited and solely restricted to non-Europeans. We discovered new genes involved in eyebrow variation in Europeans and rediscovered some of the genes previously identified in non-Europeans.”

The study among 9948 individuals from four groups of European ancestry not only discovered three previously unreported genetic loci associated with eyebrow thickness, but also rediscovered two of the four genetic loci previously found in non-Europeans. Two other genetic loci previously reported in non-Europeans had minimal effects in Europeans, due to very low allele frequencies in Europeans.

Prof Dr Kayser concluded, “Our study significantly improves the genetic knowledge of human eyebrow appearance by increasing the number of known genes from four to seven and delivers new targets for future functional studies. By having demonstrated that eyebrow variation is determined by both shared and distinct genetic factors across continental populations, our findings underline the need for studying populations of different ancestries for unveiling the genetic basis of human traits, including, but not restricted to, physical appearance.”

Source: Elsevier

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Some Antihypertensives might Boost the Effectiveness of Cancer Immunotherapy

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A study reported in the latest issue of Nature has shown that some molecules previously used to treat hypertension might also help the immune system to better target cancer cells. The researchers believe that these findings could eventually be applied to significantly improve the effectiveness and applicability of cancer immunotherapy.

“Immunotherapy today can effectively fight only 30% to 40% of cancers,” said Benoît Van den Eynde, at the Ludwig Institute for Cancer Research, co-director of the de Duve Institute and professor of Tumour Immunology at the University of Oxford. “Many cancers are resistant, largely because their T lymphocytes are not reactive enough. We discovered that drugs once used to treat hypertension could have a very interesting effect in combating these forms of immunotherapy-resistant cancers.”

T lymphocytes are active components in the immune system, recognising and destroying cells that appear foreign. Cancer cells, however, are not foreign and are therefore often not recognised and attacked by T lymphocytes. But about thirty years ago, Thierry Boon and his colleagues at the former Brussels Branch of the Ludwig Institute for Cancer Research at the de Duve Institute discovered specific markers on the surface of cancer cells – tumour antigens – that can be recognised by T cells that then destroy the cancerous cells.

This work paved the way for cancer immunotherapy, a treatment approach that helps T cells destroy cancerous cells. Thanks to T cells’ specificity and memory of tumour antigens, immunotherapy makes it possible to treat advanced cancers with some success. It is now used worldwide. However, such therapies are not equally effective in all patients or against all types of cancer.

In the current study, a team led by Jingjing Zhu in Van den Eynde’s laboratory shows that anti-hypertensive drug-molecules known as α2-adrenergic receptor (α2AR) agonists also influence the behaviour of macrophages. While doing that job, macrophages also alert T cells of any abnormalities they encounter, presenting suspicious antigens to the cells to trigger a possible immune response.

Zhu, Van den Eynde and colleagues discovered that alongside their known hypotensive and anaesthetic effects, α2AR agonists can also stimulate macrophages in their role as sentinels, making T cells more reactive and more effective at rejecting cancer cells. The effect extended, most notably, to cancer models that are resistant to standard immunotherapy. This suggests the new approach could boost the efficacy of clinical immunotherapy, even for the many types of cancer that are largely unresponsive to such interventions.

These findings also present a rationale for the development of new molecules that might be used in combination with immunotherapy to improve its efficacy.

“One could imagine using existing blood pressure-lowering drugs,” said Van den Eynde. “But that would be quite risky, owing to the undesired effects and the toxicity of these drugs at the necessary doses. Another approach would be to develop new molecules that would act in the same way on macrophages but would not have the unwanted toxic effects. We have already made significant progress in this direction.”

Source: Ludwig Cancer Research

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SA one of Many Countries Failing to Combat Antimicrobial Resistance, International Review Finds

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Methicillin resistant Staphylococcus aureus (MRSA) bacteria, the bane of hospital infection control strategies. Image by CDC on Unsplash.

Governments around the world must do more to tackle the growing threat of antimicrobial-resistant infections, new research suggests – with South Africa falling quite short in the rankings.

The review, published in The Lancet Infectious Diseases, assessed national action plans developed by more than 100 countries to tackle the threat from antimicrobial resistance (AMR). It comprehensively graded international AMR efforts and national action plans and generate comparable quantitative results across countries and regions.

National action plans focus on designing policies to curb AMR and devising tools to implement the policies – but they do not adequately factor in monitoring and evaluation.

The new research, carried out by experts at the universities of Leeds, Edinburgh and Hamburg, is the first large-scale analysis of these plans. They were designed after encouragement from the World Health Organisation, which has declared AMR one of the top 10 public health threats facing humanity.

Lead author Jay Patel, undergraduate dental student in the University of Leeds’ School of Dentistry, said: “Our analysis showed that countries were highly focused on designing AMR policies, and thinking about what tools would be required to implement those, but they generally did not consider how they would monitor and evaluate the impact of those efforts.

“This suggests that the international response may be inadequate to meet the scale and severity of AMR. This is particularly concerning in low and middle-income countries, where action plan activities often lack sustainable funding – relying instead on funds from foreign donors and philanthropies.

“The available evidence also suggests that simply developing a national action plan may not necessarily mean a country is more prepared to respond to the threat of AMR.

“Our study shows that the global response to AMR, and preparedness for the predicted challenges of AMR, require improvement in all locations around the world.”

The research team says governments across the world must strengthen their responses to AMR.

In 2017, the World Health Organization encouraged member states to develop national action plans stipulating how countries would tackle AMR. More than 100 countries have produced action plans, with several being implemented – but there had been no global analysis of the contents of these plans.

The 114 action plans, which were created in 2020-21, were evaluated against 54 elements, such as education, stewardship, and accountability, and each awarded a score out of 100. A mean score out of 100 for each country’s plan was then taken from these results.

The findings

At 43 points for AMR governance, South Africa falls far short of the top score of 85, and rather closer to the lowest score of 29. Reproduced from The Lancet. Figure 2b, Patel et al., 2023. (Open Access)

Norway’s response was the highest scoring with 85, followed by the USA with 84 and the UK with 83. The lowest scoring countries were Ukraine and Sierra Leone with 29 points each, and Barbados and Micronesia with 28 points. With 43 points, South Africa trailed behind Brazil, Namibia, Rwanda and Egypt – and received 0 for research and development as well as the effectiveness of its monitoring and evaluation.

The study found that across all plans, there was a greater focus on policy design and implementation tools, but efforts to monitor and evaluate activities are generally poorly-considered.

Of all areas evaluated, accountability and feedback mechanisms were the joint-lowest scoring, followed by education.

Training and professional education across human health, veterinary, and agricultural sectors were insufficient in many countries, with several lacking a sustainable workforce strategy to deliver antimicrobial stewardship policies.

Countries scored well on participation, demonstrating a shared awareness that AMR can only be successfully addressed through engagement with multiple sectors spanning human, animal and environmental health. Infection prevention and control was frequently recognised as a critical objective.

Source: University of Leeds

Categories : Implants and Prostheses NeurologyTags : 2 Comments

‘Digital Bridging’ Enables Paraplegic Man to Walk Again

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Study participant Gert-Jan Oskam walking with the brain-spine interface. Credit: Swiss Federal Institute of Technology in Lausanne

A 40 year-old man, Gert-Jan Oskam, has regained the ability to walk independently after being paralysed from a spinal cord injury with the use of a new brain-spine interface. The ‘digital bridging’ technology, developed at the Swiss Federal Institute of Technology in Lausanne and described in Nature, consists of implants and a computer to translate brain signals of the intention to move into stimulations that move the legs accordingly..

This BSI system could be calibrated in minutes, and remained stable for one year, including use at home. The BSI enabled the participant to exert natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains.

In addition to the digital bridging, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis.

The system consists of a pair cortical of sensors, each an array with 64 electrodes housed in 5cm-diameter titanium discs. These discs are implanted snugly in the skull to pick up brain activity. They transmit the data wirelessly to a personalised headset, which also provides power for the sensors. The headset then sends the data to a portable processing unit (which may be carried in a backpack). Using specialised software, it uses this brain signal data to generates real-time predictions of motor intentions. These decoded intentions are translated into stimulation commands and sent on to another implant, a paddle array of 16 electrodes implanted next to the spinal cord, delivering current to the targeted dorsal root entry zones.

Neurosurgical implantation procedure

Oskam had sustained an incomplete cervical (C5/C6) spinal cord injury during a biking accident 10 years previously. He had already participated in a neurological recovery programme, the STIMO trial, which had used neurostimulation to get him to the stage where he could walk with the aid of a front-wheel walker. The neurorehabilitation from the trial also enabled him to use his hip flexors and lift his legs against gravity, but recovery had plateaued for the three years prior to his participation in the present study.

For the BSI to function, the researchers needed to locate neural features related to the intention to move the legs. To pinpoint the cortical regions associated with the intention to move, they used CT scans and magnetoencephalography. Taking into account anatomical restraints, they then decided on the positions of the implants.

Under general anaesthesia, surgeons performed a bicoronal incision of the scalp to allow two circular-shaped craniotomies over the planned locations of the left and right hemispheres. They then replaced the bone flaps with the two implantable recording devices, before closing the scalp.

The paddle lead had already been emplaced over the dorsal root entry zones of the lumbar spinal cord during the STIMO clinical trial. Its optimal positioning was identified using high-resolution structural imaging of the spine, and its final position was decided during the surgery based on electrophysiological recordings. The implantable pulse generator was inserted subcutaneously in the abdomen. Oskam was able to return home 24 hours after each procedure.

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Long COVID’s Fatigue Impacts can be Worse than Some Cancers

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A new UK study has found that fatigue is the most significant symptom for long COVID patients, and can affect quality of life more than some cancers. The research, published in BMJ Open, examines the impact of long COVID on the lives of over 3750 patients who were referred to a long COVID clinic and used a digital app as part of their NHS treatment for the condition.

Patients were asked to complete questionnaires on the app about how long COVID was affecting them – considering the impact of long COVID on their day-to-day activities, levels of fatigue, depression, anxiety, breathlessness, brain fog, and their quality of life.

The researchers, from UCL and the University of Exeter, found that many long COVID patients were seriously ill and on average had fatigue scores worse or similar to people with cancer-related anaemia or severe kidney disease. Their health-related quality of life scores were also lower than those of people with advanced metastatic cancers, like stage IV lung cancer.

Overall, the team found that the impact of long COVID on the daily activities of patients was worse than that of stroke patients and was comparable to that of patients with Parkinson’s disease.

Dr Henry Goodfellow, who co-led the study alongside the late Professor Elizabeth Murray (both UCL Institute of Epidemiology & Health), said: “Up to around 17% of people who get COVID go on to develop long COVID *. However, the impact of the condition on patients’ day-to-day lives isn’t fully understood.

“Our results have found that long COVID can have a devastating effect on the lives of patients – with fatigue having the biggest impact on everything from social activities to work, chores and maintaining close relationships.”

Not only does long COVID negatively impact the lives of patients on an individual level, the researchers also believe that it could have a significant economic and social impact on the country.

In order to be referred to a long COVID clinic, a patient must have had symptoms in keeping with long COVID for at least 12 weeks after an acute infection.

Over 90% of long COVID patients using the app were of working age (18-65) and 51% said they had been unable to work for at least one day in the previous month, with 20% unable to work at all.

Meanwhile, 71% of patients were female. As working-age women make up a majority of the health and social care workforce, the impact of long COVID on their ability to function may add additional pressures to already stretched services.

Dr Goodfellow said: “We hope that a greater understanding of the symptoms and impact of long COVID in these patients will help the NHS and policymakers to target limited resources by adapting existing services and designing new ones to better meet the needs of patients with long COVID .”

Alongside fatigue, long COVID patients typically experience breathlessness, anxiety, depression and brain fog. This is the first study to report on the impact of the condition on day-to-day functioning and health-related quality of life in patients who have been referred for specialist rehabilitation in long COVID clinics across England.

Dr Goodfellow said: “Our findings show that fatigue should be an important focus for clinical care and the design of rehabilitation services.

“Post-COVID assessment services should consider focusing on assessing and treating fatigue to maximise the recovery and return to work for sufferers of long COVID .”

Source: University College London