Girls exposed to certain endocrine-disrupting chemicals (EDCs) may be more likely to start puberty early, according to new research published in Endocrinology, the flagship basic science journal of the Endocrine Society. EDCs mimic, block or interfere with hormones in the body’s endocrine system.
There has been an alarming trend toward early puberty in girls, suggesting the influence of chemicals in our environment. Early puberty is associated with an increased risk of psychosocial problems, obesity, diabetes, cardiovascular disease, and breast cancer.
“We conducted a comprehensive screen of 10 000 environmental compounds with extensive follow-up studies using human brain cells that control the reproductive axis, and our team identified several substances that may contribute to early puberty in girls,” said study author Natalie Shaw, MD, MMSc, of the National Institute of Environmental Health Sciences (NIEHS).
Those substances include musk ambrette, which is a fragrance used in some detergents, perfumes, and personal care products, and a group of medications called cholinergic agonists.
“More research is needed to confirm our findings,” noted Shaw. “But the ability of these compounds to stimulate key receptors in the hypothalamus – the gonadotropin-releasing hormone receptor [GnRHR] and the kisspeptin receptor [KISS1R] – raises the possibility that exposure may prematurely activate the reproductive axis in children.”
According to the research team, musk ambrette is potentially concerning because it can be found in personal care products, and some rat studies have suggested it can cross the blood-brain barrier. Children are less likely to encounter cholinergic agonists in their daily lives.
Canadian and European regulations restrict musk ambrette use because of its potential toxicity, and the U.S. Food and Drug Administration removed the fragrance from its “generally recognized as safe” list. Yet it is still available on the market in some personal care products.
“This study suggests that, out of an abundance of caution, it is important for parents to only use personal care products for their children that are federally regulated,” Shaw said.
As part of the study, the research team screened a Tox21 10 000-compound library of licensed pharmaceuticals, environmental chemicals and dietary supplements against a human cell line overexpressing GnRHR or KISS1R. They conducted follow-up analysis using human hypothalamic neurons and zebrafish, finding that musk ambrette increased the number of GnRH neurons and GnRH expression.
“Using human hypothalamic neurons and zebrafish provides an effective model for identifying environmental substances that stimulate the KISS1R and GnRHR,” said co-author Menghang Xia, PhD, from the National Center for Advancing Translational Sciences (NCATS) “This study was a multidisciplinary team effort, and it showed that we can efficiently reduce the time and cost of assessing environmental chemicals for their potential effects on human health.”
Four behaviours explain a majority of the socioeconomic disparities observed in the disease
Source: Wikimedia CC0
Lower socioeconomic status is associated with higher rates of death from coronary artery disease compared to higher socioeconomic status, and more than half of the disparities can be explained by four unhealthy behaviours. Dr Yachen Zhu of the Alcohol Research Group, US, and Dr Charlotte Probst of the Centre for Addiction and Mental Health, Canada, report these findings in a new study published September 17th in the open-access journal PLOS Medicine.
Coronary artery disease, also known as coronary heart disease or ischaemic heart disease, occurs when the arteries supplying the heart cannot deliver enough oxygen-rich blood due to plaque buildup, and is a major cause of death in the US. The condition poses a greater risk to people with lower socioeconomic status, but previous studies have reported conflicting results on whether certain unhealthy behaviours, like smoking, are primarily responsible for the observed disparities in deaths from the disease.
In the new study, researchers used data from 524 035 people aged 25 years and older whose mortality statuses were recorded in the National Death Index and who answered the National Health Interview Survey on demographics and health behaviours. The team used education as the primary indicator for socioeconomic status, and investigated four behavioural risk factors: smoking, alcohol use, physical inactivity and BMI. The four factors together explained 74% of the differences in mortality risk from coronary artery disease in men belonging to different socioeconomic levels and 61% in women.
The researchers conclude that their results highlight the need for effective public health policies and interventions that address each of these behaviours – both separately and together – because unhealthy behaviours often cluster among individuals from low socioeconomic backgrounds. They urge public health campaigns to raise awareness about heart health with messaging and outreach efforts customised for male and female audiences. The authors add, “These efforts are crucial to reducing the socioeconomic disparities in deaths from coronary artery disease in the US.”
The world’s first partial face and whole eye transplant has yielded important insights towards the development of functional eye transplants.
Over one year ago, a surgical team at NYU Langone Health transplanted part of a donor face onto a 46-year old power line worker who had suffered extensive facial injuries and the loss of his left eye. They also transplanted a complete eye into the patient, connecting it up to blood vessels and nerves, to see whether it was possible for an eye to survive. Now, findings on the health of the transplanted eye published in JAMA reveal that the eye is healthy but no light has been seen from it.
For the roughly 40 million people around the world without sight in either eye, stem cell research has been the most recent hope for regaining vision in many cases of trauma and disease.
In the eye transplant, the optic nerve was attached and immunosuppression used. Fluorescein angiography showed that perfusion of the globe and retinal were maintained throughout the immediate postoperative period. Optical coherence tomography revealed atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone.
Crucially, the retina of the transplanted eye responded to light as confirmed by serial electroretinography. MRI scans demonstrated the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye. However, after one year, no light in the eye was observed by the patient.
As discussed in an accompanying editorial published in JAMA Network, whole eye transplantation (WET) has been regarded as one of the most difficult yet important transplant procedures to attempt developing. In 1978, a report from the National Eye Institute advisory stated that “[a]t present, any effort to transplant a mammalian eye is doomed to failure by the ganglion cell axon’s inability to withstand cutting, by the difficulty of insuring adequate circulation of blood to the transplanted eye during or shortly after operation, and lastly by immune rejection of foreign tissue.”
With this transplant case, the issues of adequate circulation and immune rejection have now been shown to be surmountable, the authors point out. Other issues to address concern connecting the cranial nerves to enable opening of the eyelid.
Dr Salomine Theron, a radiologist at the SCP Radiology and Dr Lizanne Langenhoven, who specialises in the treatment of breast cancer, talk about breast cancer in men, how prevalent it is as well as the radiology behind the diagnosis, treatment and surveillance for recurrence.
‘It may come as a surprise that men can develop breast cancer,’ says Dr Langenhoven. ‘In fact, about 1% of all breast cancer cases are diagnosed in men. Unfortunately, men often present with more advanced disease, because they are not aware that they can develop breast cancer in the first place.’
Dr Theron says radiology plays a pivotal role in the diagnosis and treatment of breast cancer in both men and women. However, there is a difference in terms of radiology’s initial role in screening for breast cancer. ‘In women over 40, we recommend an annual mammography,’ she says. ‘In other words, looking for cancers which are asymptomatic. So even if there are no changes to your breast visibly or a lump, we still screen for anything that may develop into breast cancer or has already.
‘In men, that is not standard practice’ Here radiology is diagnostic and the referral is as a result of a lump in the breast, under the arm, there’s puckering or nipple pain. The mammogram differs too. It is a single mammogram image of each breast so that a comparison can be made. In men, it will also include breast ultrasound and evaluation of the lymph nodes under the armpit.
Dr Theron says, ‘the imaging of a lump may also be incidental. For example, when we do any form of CT imaging on the chest in a male, even when creating images of the lungs, we always look at the soft tissue in the breast area. If we see an asymmetric nodule with an irregular shape (almost like a star) we alert the patient’s healthcare provider, even though that wasn’t the reason for the CT scan’.
Is a breast lump always in men always cancer?
‘No,’ says Dr Langenhoven, ‘About 50% of males develop small lumps in each of their breasts during puberty, usually behind the nipples which can be tender. This is called gynaecomastia – colloquially a ‘stony’ and it’s perfectly normal. It usually goes away as they finish puberty.
‘Breast cancer, on the other hand, usually presents as a firm nodule in one breast that is not tender. There are some men who present with inflammatory breast cancer, where the breast is red, swollen and tender. This is however, a rare but aggressive type of invasive breast cancer in which cancer cells block lymph vessels in the skin.’
She says, ‘the first message is one of awareness. Men can develop breast cancer. And that they should see their GP if they become aware of a lump in their breasts which feels firm and asymmetrical or if the breast becomes red, swollen and tender.’
The second message is one of precaution
Women and men can inherit the harmful BRCA1 or BRCA2 gene mutation that belong to a class of genes, known as tumour suppressors and have an increased risk of breast cancer.
Dr Langenhoven says, ‘I have a patient in my practice who presented with a hard lump on his left breast. Because he was aware of his family’s history of breast cancer, he went to his GP for an examination. A mammogram and biopsy confirmed the diagnosis of breast cancer.
She says men with these genes should always be assessed by a genetic counsellor. In addition, should you have a family member diagnosed with male breast cancer, prostate cancer below the age of fifty or ovarian cancer (women), you should seek the opinion of a genetic counsellor to discuss the possible genetic risk and the option of genetic testing. Prevention is better than cure.’
The role of radiology in diagnosis
‘A suspicious lump or mass can only be definitively diagnosed by a biopsy,’ says Dr Theron. She explains that there are three biopsy options:
Ultrasound guided core biopsies, where a sample of tissue or blood is taken for testing by a pathologist and a marker is left in the lesion or lump where the sample was taken
A fine needle aspiration (FNA) is a procedure to obtain a sample of cells from your body for testing by a cytologist for cancer cells usually of a lymph node or occasionally of a breast mass
A vacuum-assisted biopsy can produce slightly larger samples of tissues which is sent to the pathology lab
If there is no lump visible on ultrasound, only suspicious calcification on the mammogram, stereotactic guided vacuum biopsy will be done. Put simply, a mammogram will help us find the abnormality to biopsy
If the lump is very small or has a cystic component, an ultrasound guided vacuum assisted biopsy will be performed
Radiology at every stage of cancer care
‘Radiology is integral to breast cancer management beyond diagnosis, providing critical information that guides clinical decisions at every stage of care,’ says Dr Theron. ‘This includes staging of the disease, it allows for precise treatment planning, guiding surgical procedures, effective monitoring of treatment responses, early detection of recurrence, all of which are essential for improving patient outcomes.’
Male breast cancer treatment
Men with breast cancer are treated exactly as their female counterparts. Based on the type of breast cancer and the extent (stage), treatment options include chemotherapy, hormone withdrawal therapy, targeted therapies, immunotherapy, surgery and radiotherapy.
‘Even though only one in a hundred diagnosed cases of breast cancer is men,’ says Dr Theron, ‘we still urge men and of course women to check themselves regularly and to see a doctor if they feel or see any changes in their breasts.’
Cognionics, founded by bioengineering alumnus Mike Yu Chi, has developed a wearable EEG headset that’s comparable to state of the art laboratory equipment. Credit: UC San Diego
Since the first recording in July 1924, human electroencephalography (EEG) has been integral to our understanding of brain function and dysfunction: most significantly in the clinical diagnosis of epilepsy, where the analysis of the EEG signal meant that a condition previously seen as a personality disorder was quickly redefined as a disorder of brain activity.
Now, a century on, more than 500 experts from around the globe have been asked to reflect on the impact of this groundbreaking methodology, as well as on the challenges and priorities for the future.
A survey led by University of Leeds academics, saw respondents – with 6685 years of collective experience – presented with possible future developments for EEG, ranging from those deemed ‘critical to progress’ to the ‘highly improbable,’ and asked to estimate how long it might be before they were achieved. The results are published in the journal Nature Human Behaviour.
Futuristic innovations
The list features an array of fascinating, futuristic innovations that experts believe could be achieved within a generation. This includes using EEG to enhance cognitive performance; early detection of learning disabilities; widespread use as a lie detector; and use as a primary communication tool for those with severe motor disabilities and locked-in syndrome.
Real-time, reliable diagnosis of brain abnormalities such as seizures or tumours is believed to be just 10-14 years away, while the probability of reading the content of dreams and long-term memories is judged to be more than 50 years away by some experts, but dismissed by many as closer to science fiction than reality.
It may be surprising to many that, according to the survey, within a generation we could all be carrying around our own, personal, portable EEG.
The paper’s co-author Dominik Welke, Research Fellow in Leeds’ School of Psychology, said: “They could really become something like a smartphone: where almost everybody has access to them and can use them daily – ideally improving their life by providing meaningful insight into physiological factors.”
He added: “One such positive, potential future use of EEG technology could be vigilance control for drivers or pilots. These work-safety systems could assist the user in identifying if they were falling asleep, then wake them up or tell the co-pilot they need to take over.”
They could really become something like a smartphone: where almost everybody has access to them and can use them daily
Dominik Welke, Research Fellow at the University
The hardware involved in recording EEG is relatively basic, remaining unchanged – in principle – since it was first used by psychiatrist Hans Berger in Germany on July 6, 1924. What has drastically changed since then is the analysis of – and what we can do with – the now digitally-recorded data.
Consisting of just electrodes and an amplifier, EEG systems are becoming increasingly cheap to produce, as well as more portable and user-friendly. Coupled with its non-invasive nature, there is little to prevent it from becoming more accessible to a wider audience.
Reducing health inequalities
While the prospect of EEG technology being widely used in gaming and VR – predicted to be only around 20 years away – will thrill gamers, the truly exciting possibility for scientists and clinicians is that this increasing accessibility will allow them to engage with communities traditionally excluded from EEG research, crucially, in low-income countries that cannot afford more complex imaging technology.
Advances in AI-driven automation are also expected to improve and speed up analysis of complicated data.
Dr Welke said: “Looking ahead to the future: from the hardware side, it’s comparatively cheap and easy to produce, and from the analysis and software side, with these new computing technologies, all the puzzle pieces are there to really roll out EEG to a very large user base.
“As opposed to other methods out there – such as MRI, or implanted devices – EEG has the potential to make neuroimaging available to all the people in the world.”
I think that EEG, when combined with technologies such as AI and virtual reality, could radically transform the ways in which we interact with machines, and in doing so, play an extremely important role in science and society over the next 100 years
Faisal Mushtaq, Professor of Cognitive Science and the Director of the Centre for Immersive Technologies at the University
“EEG stands out as the most cost-effective and logistically feasible neuroimaging tool for worldwide use across diverse settings. This would help build a neuroscience that is inclusive and representative of the global population.
He added: “Our partners at the Global Brain Consortium are laying the foundations for increasing reach in this way and I expect this will unlock new opportunities for groundbreaking discoveries on the mechanisms of brain function.”
Ethical questions
Alongside the optimism that emerging technologies are opening exciting new possibilities for EEG, the experts consulted also sounded a note of caution, with concerns that ranged from a lack of adherence to agreed standards and protocols to ethical questions created by novel commercial applications and the lure of ‘neuroenhancement’.
Dr Welke said: “I’m sure some of the multi-national tech companies might be very interested in rolling out EEG or other neuroimaging technology, just to get more information on their users that hints at their preferences and emotions 24 hours a day. But should it be used in this way?
“There are obvious concerns around cognitive freedom and mental privacy. This feeds back into the importance of ‘responsibility’ – the fact that new ways of using a technology are also likely to raise new ethical questions.”
Another objective of the survey was to identify the priorities of the EEG community for guiding future efforts. Participants rated how important major developments and advancements in various domains of EEG research would be to their work.
Professor Mushtaq said: “I think that EEG, when combined with technologies such as AI and virtual reality, could radically transform the ways in which we interact with machines, and in doing so, play an extremely important role in science and society over the next 100 years.
“But to ensure this, the neuroscience community—from academic, clinical and industry settings—must commit to promoting robust, ethical, inclusive, and sustainable practices that will help realise its enormous potential.”
The work was conducted by more than 90 authors, ranging from early career researchers to eminent figures in the field, collectively known as the EEG100 consortium.
It started out as a partnership between #EEGManyLabs – an international network of researchers from more than 30 countries assessing the replicability of the results of some of the most important and influential EEG experiments of psychological phenomena – and the Global Brain Consortium, a diverse network of brain researchers, clinicians and institutions committed to achieving improved and more equitable health outcomes worldwide.
“There are hurdles to overcome to employ EEG at a global scale, but by doing so, we can hopefully improve millions more lives.”
Dr Sadhana Sharma, Head of Bioscience for Health Strategy at the Biotechnology and Biological Sciences Research Council (BBSRC) – which funded the paper’s lead authors – said: “EEG technology has the potential to transform our day-to-day activities and how we diagnose and treat neurological conditions in the future, ensuring that insights into brain health are accessible to diverse populations worldwide.
“As we embrace developments in bioscience, our focus remains on fostering interdisciplinary collaborations that drive ethical, equitable and impactful advancements in brain science on a global scale.”
Without immediate action, humanity will potentially face further escalation in resistance in fungal disease, a renowned group of scientists from the across the world has warned. The commentary – published in ‘The Lancet’ this week – was coordinated by scientists at The University of Manchester, the Westerdijk Institute and the University of Amsterdam. According to the scientists most fungal pathogens identified by the World Health Organization – accounting for around 3.8 million deaths a year – are either already resistant or rapidly acquiring resistance to antifungal drugs.
The authors argue that the currently narrow focus on bacteria will not fully combat antimicrobial resistance (AMR). September’s United Nations meeting on antimicrobial resistance (AMR) must, they demand, include resistance developed in many fungal pathogens.
Devastating health impacts
Resistance is nowadays the rule rather than the exception for the four currently available antifungal classes, making it difficult – if not impossible – to treat many invasive fungal infections. Fungicide resistant infections include Aspergillus, Candida, Nakaseomyces glabratus, and Trichophyton indotineae, all of which can have devastating health impacts on older or immunocompromised people.
Dr Norman van Rhijn from The University of Manchester coordinated the comment with Professor Ferry Hagen from the University of Amsterdam and the Westerdijk Institute in the Netherlands.
Dr van Rhijn said: “Most people agree that resistant bacterial infections constitute a significant part of the AMR problem. However many drug resistance problems over the past decades have also been the result of invasive fungal diseases largely underrecognized by scientists, governments, clinicians and pharmaceutical companies. The threat of fungal pathogens and antifungal resistance, even though it is a growing global issue, is being left out of the debate.”
Unlike bacteria, the close similarities between fungal and human cells which, say the experts, means it is hard to find treatments that selectively inhibit fungi with minimal toxicity to patients.
Back to square one
Professor Ferry Hagen added: “Despite the huge difficulties in developing them, several promising new agents including entirely new classes of molecules, have entered clinical trials in recent years. But even before they reach the market after years of development, fungicides with similar modes of action are developed by the agrochemical industry resulting in cross-resistance. That sets us back to square one again. It is true many essential crops are affected by fungi, so antifungal protection is required for food security. But the question is, at what price?”
The scientists recommend:
Worldwide agreement on restricting the use of certain classes of antifungal molecules for specific applications.
Collaboration on solutions and regulations that ensure food security and universal health for animals, plants, and humans.
Adding priority to AMR to fungal infections at the UN’s meeting in September.
Study’s findings reveal increased risks, indicating the need for interventions to reduce stress for patients and their relatives.
Photo by Alex Green on Pexels
New research suggests that a family member’s cancer diagnosis may increase first-degree relatives’ and spouses’ risks of developing psychological and cardiovascular illnesses. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
Having a family member diagnosed with cancer can be a stressful and traumatic experience for the entire family. Because stress influences not only mental health but also cardiovascular health, investigators explored whether a cancer diagnosis contributes to negative psychological and cardiovascular outcomes in family members.
Using data from the Utah Population Database, the researchers identified 77 938 first-degree relatives and spouses of 49 284 individuals diagnosed with genitourinary cancer between 1990 and 2015, and they compared them with 81 022 relatives and spouses of 246 775 individuals not diagnosed with cancer.
The team found that 7.1% of relatives and spouses were diagnosed with a psychological illness within 5 years of a family member’s cancer diagnosis, and 7.6% were diagnosed with a cardiovascular illness. Compared with controls, they had 10%, 5%, and 4% higher risks of developing a psychological condition at 1, 3, and 5 years after a family member’s cancer diagnosis. They also had 28%, 16%, and 14% higher risks of developing cardiovascular disease at 1, 3, and 5 years.
Parents of children with cancer experienced the highest risks of developing negative health outcomes – a nearly 4-times increased risk at 1-year compared with other relatives. Also, a diagnosis of kidney or bladder cancer appeared to be the most stressful among genitourinary cancer types, while testis cancer was the least.
“A diagnosis of cancer is a life-changing event for patients and their families. With our group’s unique access to the Utah Population Database, we were able to create multi-generational networks highlighting the impact of a cancer diagnosis on families,” said lead author Mouneeb Choudry, MD, of the Mayo Clinic, in Phoenix, Arizona. “As health care professionals, we should take a multidisciplinary approach to addressing the stress of a cancer diagnosis by helping mitigate financial toxicity, treatment burden, and emotional impact on both the patient and their family.”
Researchers at the University of Pittsburgh are pioneering a new approach to blood pressure monitoring, using the devices we carry with us every day. Ramakrishna Mukkamala, professor of bioengineering at Pitt’s Swanson School of Engineering, is passionate about developing accessible blood pressure (BP) detection tools. Instead of designing a new medical device to monitor BP, Mukkamala decided to take advantage of the sensors readily available in smartphones and figure out how to detect blood pressure with them.
“The most significant thing you can do to reduce your risk of cardiovascular disease is to lower high blood pressure through lifestyle changes, but in underserved populations, many people don’t have access to blood pressure cuffs, regular doctor’s appointments, or even know it’s a problem,” Mukkamala said. “But they do have smartphones.”
Mukkamala’s team harnessed tools already built into most smartphones, like motion-sensing accelerometers, front cameras, and touch sensors to build an Android smartphone application that can measure an individual’s pulse pressure.The user performs a hand-raising motion while holding the smartphone to make a measurement. The results of the project, published in Scientific Reports, demonstrate a promising new technology that could uniquely help reduce the burden of systolic hypertension globally, particularly in underserved populations.
Designing blood pressure technology for a touchscreen
Turning a smartphone into a monitoring device is no easy task, as Vishaal Dhamotharan, graduate student in the Cardiovascular Health Tech Laboratory, found out through multiple iterations of app development. Because smartphones don’t have force sensing tools, a crucial element of the project was figuring out how to replicate the effects of a traditional blood pressure exam using only a cell phone, which the team solved by using a familiar force – gravity.
“Because of gravity, there’s a hydrostatic pressure change in your thumb when you raise your hands up above your heart, and using the phone’s accelerometer, you’re able to convert that into the relative change in pressure.” Dhamotharan said.
By pairing this hand-raising motion with guided thumb maneuvers on the smartphone, the team was able to calculate each participant’s pulse pressure, the difference between systolic and diastolic numbers. For example, an individual with a BP measurement of 120/80 has a pulse pressure of 40. For Sanjeev Shroff, collaborator and bioengineering department chair, this publication is a promising advancement for blood pressure measurement devices.
“Development of a cuffless blood pressure measurement device that does not require any external calibration is the holy grail – such a device currently does not exist,” Shroff said. “The research work reported in this publication is an important step in the right direction, and is also encouraging for additional work aimed at obtaining systolic, diastolic, and mean pressures.”
Although pulse pressure isn’t typically used in cardiovascular disease monitoring, the study revealed its significance as a metric for detecting hypertension, according to Céderick Landry, assistant professor at the University of Sherbrooke and former postdoctoral researcher in the lab.
“Guidelines typically require doctors to measure both systolic and diastolic blood pressure, and pulse pressure is just the difference between the two.” Landry said. “We showed that if you only have access to pulse pressure, it’s still very correlated with hypertension, so part of our challenge now is changing the mentality on how to best measure things.”
Hypertension management within reach
This app could bring blood pressure monitoring software to any smartphone owner, enabling consistent self-monitoring and easy sharing of results with healthcare providers. This innovation is especially promising for managing hypertension, which can often be lowered through lifestyle changes such as reducing salt intake, quitting smoking and exercising regularly.
“This app would be really useful in low-income settings where people may not even have existing access to blood pressure tools.” Dhamotharan said. “Being able to measure blood pressure more frequently would allow an individual to track any significant changes in blood pressure, monitor for hypertension, and be able to manage their conditions with that knowledge.”
“The research is here – we just need some help making the technology better.” Landry said. “This is the first method of its kind, and even better, it’s something that we can start implementing right now.”
For decades, one of the most fundamental and vexing questions in neuroscience has been: what is the physical basis of consciousness in the brain? Most researchers favour classical models, based on classical physics, while a minority have argued that consciousness must be quantum in nature, and that its brain basis is a collective quantum vibration of ‘microtubule’ proteins inside neurons.
New research from Wellesley College published in eNeuro has yielded important experimental results relevant to this debate, by examining how anaesthesia affects the brain of rat models. Volatile anaesthetics are currently believed to cause unconsciousness by acting on one or more molecular targets including neural ion channels, receptors, mitochondria, synaptic proteins, and cytoskeletal proteins.
Anaesthetic gases including isoflurane bind to cytoskeletal microtubules (MTs) and dampen their quantum optical effects, potentially contributing to causing unconsciousness. This idea is supported by the observation that taxane chemotherapy, consisting of MT-stabilising drugs, reduces anaesthesia effectiveness during surgery in human cancer patients.
Lead researcher professor Mike Wiest and his research team found that when they gave rats the brain-penetrant MT–stabilising drug epothilone B (epoB), it took the rats significantly longer (69s) to fall unconscious under 4% isoflurane, as measured by loss of righting reflex (LORR).
The effect could not be accounted for by tolerance from repeated exposure to isoflurane.
Their results suggest that binding of the anesthetic gas isoflurane to MTs causes unconsciousness and loss of purposeful behaviour in rats (and presumably humans and other animals). This supports the idea that consciousness is a quantum state tied to MTs.
“Since we don’t know of another (ie, classical) way that anesthetic binding to microtubules would generally reduce brain activity and cause unconsciousness,” Wiest says, “this finding supports the quantum model of consciousness.”
It’s hard to overstate the significance of the classical/quantum debate about consciousness, says Wiest, an associate professor of neuroscience at Wellesley. “When it becomes accepted that the mind is a quantum phenomenon, we will have entered a new era in our understanding of what we are,” he says. The new approach “would lead to improved understanding of how anaesthesia works, and it would shape our thinking about a wide variety of related questions, such as whether coma patients or non-human animals are conscious, how mysterious drugs like lithium modulate conscious experience to stabilize mood, how diseases like Alzheimer’s or schizophrenia affect perception and memory, and so on.”
More broadly, a quantum understanding of consciousness “gives us a world picture in which we can be connected to the universe in a more natural and holistic way,” Wiest says. Wiest plans to pursue future research in this field, and hopes to explain and explore the quantum consciousness theory in a book for a general audience.
People with a rare genetic mutation that causes significant vision loss early in childhood experienced a 100-fold improvement in vision after receiving a corrective gene therapy. Some patients even experienced a 10 000-fold improvement in their vision after receiving the highest dose of the therapy, according to researchers from the Perelman School of Medicine at the University of Pennsylvania who co-led the clinical trial published in The Lancet.
“That 10 000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors as opposed to requiring bright indoor lighting before treatment,” said the study’s lead author, Artur Cideciyan, PhD, a research professor of Ophthalmology and co-director of the Center for Hereditary Retinal Degenerations. “One patient reported for the first time being able to navigate at midnight outdoors only with the light of a bonfire.”
A total of 15 people participated in the Phase 1/2 trial, including three paediatric patients. Each patient had Leber congenital amaurosis as the result of mutations in the GUCY2D gene, which is essential to producing proteins critical for vision. This specific condition, which affects less than 100 000 people worldwideand is abbreviated as LCA1, causes significant amount of vision loss as early as infancy.
All subjects had severe vision loss with their best measure of vision being equal or worse than 20/80 – meaning if a typically-sighted person could see an object clearly at 80 feet (24m), these patients would have to move up to at least 20 feet (6m) to see it. Glasses provide limited benefit to these patients because they correct abnormalities in the optical focusing ability of the eye, and are unable to address medical causes of vision loss, such as genetic retinal diseases like LCA1.
The trial tested different dosage levels of the gene therapy, ATSN-101, which was adapted from the AAV5 microorganism and was surgically injected under the retina. For the first part of the study, cohorts of three adults each received either a low, mid, ore high dose. Evaluations were held between each level of dosage to ensure that they were safe before upping the dosage for the next cohort. A second phase of the study involved only administering the high dosage levels to both an adult cohort of three and a paediatric cohort of three, again after safety reviews of the previous cohorts.
Improvements were noticed quickly, often within the first month, after the therapy was applied and lasted for at least 12 months. Observations of participating patients are also ongoing. Three of six high-dosage patients who were tested to navigate a mobility course in varying levels of light achieved the maximum-possible score. Other tests used eye charts or measured the dimmest flashes of light patients perceived in a dark environment.
Of the nine patients who received the maximum dosage, two had the 10 000-fold improvement in vision.
“Even though we previously predicted a large vision improvement potential in LCA1, we did not know how receptive patients’ photoreceptors would be to treatment after decades of blindness,” said Cideciyan. “It is very satisfying to see a successful multi-center trial that shows gene therapy can be dramatically efficacious.”
Primarily, the study sought to determine the safety of the gene therapy and its varying dosage levels. Researchers did find some patients had side effects, but the overwhelming majority were related to the surgical procedure itself. The most common side effect was conjunctival haemorrhage, the breakage of small blood vessels underneath the clear surface of the eye, which healed. Two patients had eye inflammation that was reversed with a course of steroids. No serious side effects were related to the study drug.
This work comes on the heels of another successful ophthalmological trial at Penn restoring sight in patients with a different form of LCA. Earlier in 2024, CRISPR-Cas9 gene editing was used to improve the sight of many patients with a form of LCA tied to mutations in the CEP290 gene. Co-led by one of the new paper’s co-authors, Tomas S. Aleman, MD, professor in ophthalmology and co-director with Cideciyan of the Center for Hereditary Retinal Degenerations, the study used similar tests and was the first time children were involved in any gene editing work.
“The treatment success in our most recent clinical trials together with our earlier experience brings hope for a viable treatment for about 20 percent of infantile blindness caused by inherited retinal degenerations,” Aleman said. “The focus now is on perfecting the treatments and treating earlier manifestations of these conditions once safety is confirmed. We hope similar approaches will lead to equally positive outcomes in other forms of congenital retinal blindness.”
Moving forward, approval of this experimental medicine for clinical use requires a randomised controlled trial.
