Monthly Archives: January 2020

Neuroscience

Using the logic of neuroscience to heal from a breakup – Big Think

While the feeling of being in love is seemingly magical, there are scientific reasons why being in love feels so good. And as such, there are scientific reasons why falling out of love or going through the heartache of a breakup feels so awful.

Biological anthropologist and well-respected human behavior researcher Dr. Helen Fisher published a groundbreaking study in 2005 that included the very first functional MRI images of the brains of people who were in the midst of "romantic love".

The team of researchers, led by Dr. Fisher, analyzed 2500 brain scans of students who viewed photos of someone special to them (in a romantic capacity) and compared those with scans taken of students who viewed photos of acquaintances.

In the instances where people were shown photos of individuals that they were romantically involved with, the brain would show activity in regions such as the caudate nucleus, which is a region of the brain associated with reward detection and the ventral tegmental area of the brain, which is associated with pleasure and motivation.

These are also areas of the brain that are rich with dopamine, which is a type of neurotransmitter that plays a big role in feeling pleasure. The role of dopamine in our system is to activate the reward circuit, which makes whatever we're doing at the time a more pleasurable experience that can be equated to the type of euphoria associated with the use of addictive substances such as cocaine or alcohol.

Not only does the human brain work to amplify positive emotions when it experiences love, but the neural pathways that are responsible for negative emotions such as fear are deactivated. When we are engaged in what is considered "romantic love," the neural mechanism that is responsible for making assessments of other people and formulating fear-based thoughts shuts down.

A 2011 study conducted at Stony Brook University in New York (which also included Dr. Fisher) concluded that it's possible to feel these effects with someone even after decades of marriage.

The study looked at MRI scans of couples who had been married an average of 21 years, and while the euphoria that comes with falling in love may have changed, the same heightened levels of activity in dopamine-rich areas of the brain that were found in new couples were also seen on these MRI scans.

When we are in love, our bodies are actively producing feel-good hormones and denying the release of negative hormones - and when this process suddenly stops, the "withdrawal" we feel can be extremely difficult to process both on an emotional and physiological level.

A study performed by researchers Lucy Brown, Xiomeng Xu, and Dr. Fisher scanned the activity in the brains of 15 young adults who had all experienced unwanted breakups yet still reported feeling "in love" with the person.

All of these individuals were in various stages of break up. Some still sent messages to their loved ones that went unanswered, and some simply feeling depressed that the relationship was over.

The individuals were shown photos of their former partners, and the scans taken during this time showed activity in several different areas of the brain, including the ventral tegmental, the ventral striatum, and the nucleus accumbens. All three areas are a part of our reward/motivation system, which communicates through the release of dopamine.

There is a direct link between those who have experienced rejection from someone they love (an ex-partner, for example) and those who have experienced withdrawal from addictive substances.

"Romantic love can be a perfectly wonderful addiction when it's going well...and a perfectly horrible addiction when it's going poorly."

- Helen Fisher

According to Dr. Guy Winch, psychologist and author of "How to Fix a Broken Heart," heartbreak is a form of grief and loss that can cause serious issues with insomnia, anxiety and even depression or suicidal thoughts. According to Winch, who is known to specialize in "emotional first aid," heartbreak should be taken very seriously, as should our efforts to recover from it.

Columbia University cognitive neuroscientist Edward Smith completed a series of studies and tests in 2011 that proved the pain we feel during heartbreak is similar to physical pain we might feel due to a severe burn or broken arm.

In these studies, the goal was to see what happens in the brains of people who have recently been through a breakup with a long-term partner.

In the MRI images of these people struggling with recent heartbreak, the parts of the brain that lit up were the same parts of the brain that are active when you experience physical pain.

Dr. Winch, in an interview with Blinkist Magazine, explained a similar study that he was a part of where physical pain that was rated as level 8 (on a scale of 1-10, with 10 being almost intolerable pain) showed similar results to an MRI taken by someone who had just talked about and relived their breakup.

The physical pain, which only lasted 7 seconds, registered the same in the patient's brain as the emotional pain of the breakup, which for some can last for days, weeks, or even months.

Understanding this link between heartbreak and physical pain should allow us to take a more all-encompassing approach to heal from the pain of a breakup.

"It's not just about time and waiting it out - it's about taking steps." - Dr. Guy Winch

Photo by Tero Vesalainen on Shutterstock

There are a few things we can do that are essential to surviving and healing from heartbreak, based on what we know from these studies.

Avoiding visual reminders of your ex-partner may seem like an obvious answer to help you recover, but sentimental reminders such as pictures or revisiting places you used to spend time with them are very likely to create dopamine surges in your brain that relate to feelings of craving and withdrawal.

Replacing those surges of dopamine is the next positive step: taking up a fitness class or joining a gym is something many people do to "power through" a breakup, but exercise can also lead to the release of endorphins that trigger a positive feeling throughout the body and brain.

Finding a "new normal" after a heartbreak can seem impossible - but one of the first things you need to do is to recalibrate your mind. Making a list of reasons your ex-partner wasn't perfect or being honest with yourself about parts of that relationship that were negative or unhealthy can be the beginning of resetting your system to see things in a more true light.

According to Dr. Winch, one of the biggest hurdles to recalibrating your mind and adapting to life without your ex-partner is that we don't find closure.

Winch suggests that we try to accept the reason for the breakup or even find another reason. Maybe the relationship would not have worked out because you wanted different things in life or because they were not emotionally available for you. Finding logic in heartbreak can be a good start to the healing process.

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Using the logic of neuroscience to heal from a breakup - Big Think

Neuroscience

Decoding the Brain Goes Global With the International Brain Initiative – Singularity Hub

Few times in history has mankind ever united to solve a single goal. Even the ultimate moonshot in historyputting a man on the moonwas driven by international competition rather than unification.

So its perhaps fitting that mankind is now uniting to understand the organ that fundamentally makes us human: our brain. First envisioned in 2016 through a series of discussions on the grand challenges in neuroscience at Johns Hopkins University, the International Brain Initiative (IBI) came out this week in a forward-looking paper in Neuron.

Rather than each country formulating their own brain projects independently, the project argues, its high time for the world to come together and share their findings, resources, and expertise across borders. By uniting efforts, the IBI can help shape the future of neuroscience research at a global scalefor promoting brain and mental health, for stimulating international collaboration, for ethical neuroscience practices, and for crafting future generations of scientists.

It takes a world to understand the brain, said Caroline Montojo of the Kavli Foundation, which offered support to the project. When we have the best brains and the best minds working together, sharing information and research that could benefit us all.

The initiative, at the time of writing, includes Japans Brain/Minds, Australian Brain Alliance, the EUs Human Brain Project (HBP), Canadian Brain Research Strategy, the US BRAIN Initiative (BRAINI), the Korea Brain Initiative, and the China Brain Project.

The IBI comes at a time when global research divisions are prominent. Established national projects, such as the BRAINI and the HBP, have notably different goals at the operational level. The BRAINI, for example, prominently champions developing new tools to study brain functions, whereas the HBPs ultimate goal is to recreate the function of a human brain inside machines.

Even within single countries, divisions in practical paths forward have been, mildly put, chaotic. Chinas Brain Project, announced officially in 2016 and kicked off two years later, was plagued by different opinions on focus: should it be on solving brain disorders, or understanding the neurobiology behind cognition, or focused on engineering problems that more intimately link human brains with AI?

Then theres the underlying political milieu, where certain countries are cracking down on international researchers for fear that they may be stealing or selling trade secrets. To all these divisions, the IBI took a stance and said noits time to work together.

The biggest challenge that were facing is to really understand how the brain works, the mystery of the brain, to crack the code, said Dr. Yves De Koninck of the Canadian Brain Research Strategy. If were going to make the really big leap changes in the level of understanding of how the brain works in health and disease, we need to have global collaboration, I mean thats just absolutely vital, added Dr. Linda Lanyon at the IBI Data Standards and Sharing Working Group.

The IBI is best viewed as a grassroots organization driven by the views of neuroscientists across the globe, rather than a bureaucratic entity following the views of a select few. In a way, the IBI organizes itself similar to the United Nations, with a five-year strategic plan, multiple working groups, and a governance structure.

Its clear that the IBI benefited from a global recognition, and subsequent establishment, of large-scale neuroscience projects to understand the brain. Yet any single initiative is like the blind men and the elephant parabledespite millions (or even billions) of dollars in investment, due to the brains complexity each can only probe a small part of human brain function.

However, even with different end goals, findings from each project will likely benefit each otherif properly shared in an easily-interpretable manner (the Kavli Foundation also backs a standardized format for neuroscience data called Neurodata Without Borders 2.0). Tools developed from BRAINI, for example, will likely benefit brain mapping initiatives around the world, and neural simulations can inspire insights into brain disorders or better paths towards brain-machine interfaces. A synergistic international effort could provide greater overall impact and better utilization of precious research funding, the authors argued.

Working across political aisles is already tough; now imagine sharing terabytes of data across international borders to someone you hardly know. The IBI aims to provide a platform that explores new models of collaboration among scientists so that, to put it bluntly, no one gets screwed out of their recognition. In addition, the IBI also works outside the ivory tower with private and public funding bodies, industry partners, and government-related agencies on the social, economic, and ethical impacts of neuroscientific discoveries and their translation.

Thats huge. The initiative comes at a time when technological advances are increasingly making it easier to skirt ethical considerations and move forward with iffy research projects. Making human-animal hybrid embryos to understand the roots of intelligence? Conducting brain stimulation trials that may slowly change a persons personality? Linking multiple human minds into computers by probing their brain waves? These futuristic projects abound and will only grow in number as our ability to crack the neural code improves.

The IBI argues that neuroscientists across the globe need to take a moral stancesimilar to emerging projects for ethical AIto guide research in an ethical manner. With several countries infamous for pushing moral boundaries also joining the alliance, the IBI may put an international leash on less-savory projects going forward, while respecting diverse cultural frameworks.

IBI group members stressed that the initiative isnt meant to be bureaucratic. Rather, its adaptive and allows the organization to be shaped by the scientific community over time, the authors said. Integrating multiple goals of various brain projects together, the IBI serves as meta-middleman to promote coordination, share resources, and help unite different ideas on the future of neuroscience.

This IBI is quite unique in trying to go from the very microscopic scale of the synapses that encode information within the brain, all the way up to how the information manifests itself in human cognition and animal behavior, said Dr. Linda Richards of the Australian Brain Alliance.

Despite being years in the making, the initiative is just crossing the starting line. With a solid infrastructure now in place and enthusiasm amassed, an immediate focus for the IBI is to establish and develop the core working groups that are making progress toward short-term deliverables, the authors said. The execution of a five-year plan to propel neuroscience research forward will need considerable debates on specific aims, approaches, and technologies, but will also add to a foundation for collaboration and priority-setting across the world, they added.

This is a new era of neuroscience, where neuroscientists will have access to large datasets and new ways of sharing in a collaborative manner internationally, said Richards.

Is IBIs vision nave? Maybe. The most impactful technological advancements of our ageflight, nuclear weapons, conquering space, the Internethave all stemmed from the minds of a relatively small group of people working under duress from other people. But when it comes to truly understanding the brain, the basis of who we are and what we believe, the root cause of divided opinions and worldviews, the organ that could one day be directly manipulated and fundamentally alter humanity as a speciesfighting for a global consortium is the least we can do.

Image Credit: adike/Shutterstock.com

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Decoding the Brain Goes Global With the International Brain Initiative - Singularity Hub

Neuroscience

How the Striatum’s Cell Types Work Together To Keep Us Moving – Technology Networks

Researchers at Karolinska Institutet have mapped how different nerve cells in the brain's striatum process information to plan and execute our movements at just the right time and with the right vigour. The results, presented in the journal Cell Reports, show that different cell types in the striatum receive signals from completely different parts of the cerebral cortex and thus respond to different types of information.

Many behaviours occur in response to sensory input from our environment. For example, when playing a new piece on the piano, we adjust our finger movements according to the sound we hear and the sensory feedback from the keys. Researchers at Karolinska Institutet in Sweden aimed to increase our understanding of how this works by studying the neuronal network that allows us to align our planned movements to sensory information such as touch. The nerve cells (neurons) that underlie this function are in the striatum, which is part of a larger structure in the brain called the basal ganglia.

While playing piano, sensory feedback from our fingertips is processed in the somatosensory cortex, the brain area specialised for touch. Movements are planned in a separate part of the brain called motor cortex. Information from the somatosensory cortex, the motor cortex and other brain areas such as thalamus are sent to the striatum, which is the first instance where movement plans and sensory information are combined. Based on the broad information delivered by these inputs, the striatum is able to generate a precisely timed output signal that is sent back to the muscles and allows us to press the next keys correctly on the piano.

"Although it has long been known that the striatum is composed of different types of nerve cells, it is unclear how striatal cells achieve this complex function," says Yvonne Johansson, PhD student at the Department of Neuroscience, Karolinska Institutet. "To address this question, we asked which striatal cell populations process which incoming information."

The researchers have used optogenetics, among other technologies, to analyse which of five important cell types in the striatum are responsible for the communication from the motor cortex, the somatosensory cortex and the thalamus.

Studies on mice revealed that striatal medium spiny neurons strongly respond to sensory inputs representing a sensation of touch. Another class of striatal neurons, the low-threshold spiking interneurons, hardly respond to inputs carrying sensory information but are strongly activated by inputs from motor cortex. In sharp contrast, cholinergic interneurons respond most strongly to thalamic inputs which are thought to notify us that something important is happening in our environment.

The researchers also found that the responses of the different neuron classes are mediated by different receptor compositions. As some receptors open faster than others, the receptors strongly shape the timing of the response.

The findings shed new light on how the striatum is systematically processing the vast amount of information that it receives.

"Our work shows that the flow of information into the striatal network is highly organised and that the properties of the numerous inputs targeting different striatal neuron populations are pathway-specific," says Gilad Silberberg, professor at the Department of Neuroscience, Karolinska Institutet.

Reference: Johansson, Y., & Silberberg, G. (2020). The Functional Organization of Cortical and Thalamic Inputs onto Five Types of Striatal Neurons Is Determined by Source and Target Cell Identities. Cell Reports, 30(4), 1178-1194.e3. https://doi.org/10.1016/j.celrep.2019.12.095

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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How the Striatum's Cell Types Work Together To Keep Us Moving - Technology Networks

Neuroscience

Decibel Therapeutics Announces Strategic Research Focus on Regenerative Medicine for the Inner Ear – Yahoo Finance

Company signs option agreement with The Rockefeller University to access intellectual property covering compounds targeting key regeneration pathway

Decibel Therapeutics, a development-stage biotechnology company developing novel therapeutics for hearing loss and balance disorders, today announced a new strategic research focus on regenerative medicine approaches for the inner ear. The company is also announcing a collaboration and option agreement that gives Decibel exclusive access to novel compounds targeting proteins in a critical regenerative pathway.

Decibels research focus on regeneration will be powered by the companys research and translation platform. The company has built one of the most sophisticated single cell genomics and bioinformatics platforms in the industry to identify and validate targets. Decibel has also developed unique insights into regulatory pathways and inner ear delivery mechanisms that together enable precise control over gene expression in the inner ear and differentiate its AAV-based gene therapy programs.

"Our deep understanding of the biology of the inner ear and our advanced technological capabilities come together to create a powerful platform for regenerative medicine therapies for hearing and balance disorders," said Laurence Reid, Ph.D., acting CEO of Decibel. "We see an exciting opportunity to leverage this platform to address a broad range of hearing and balance disorders that severely compromise quality of life for hundreds of millions of people around the world."

The first program in Decibels regeneration portfolio aims to restore balance function using an AAV-based gene therapy (DB-201), which utilizes a cell-specific promoter to selectively deliver a regeneration-promoting gene to target cells. In collaboration with Regeneron Pharmaceuticals, Decibel will initially evaluate DB-201 as a treatment for bilateral vestibulopathy, a debilitating condition that significantly impairs balance, mobility, and stability of vision. Ultimately, this program may have applicability in a broad range of age-related balance disorders. There are currently no approved medicines to restore balance. Decibel expects to initiate IND-enabling experiments for this program in the first half of 2020.

Decibel is also pursuing novel targets for the regeneration of critical cells in both the vestibule and cochlea of the inner ear; these targets may be addressable by gene therapy or other therapeutic modalities. As a key component of that program, Decibel today announced an exclusive worldwide option agreement with The Rockefeller University, which has discovered a novel series of small-molecule LATS inhibitors. LATS kinases are a core component of the Hippo signaling pathway, which plays a key role in regulating both tissue regeneration and the proliferation of cells in the inner ear that are crucial to hearing and balance. The agreement gives Decibel an exclusive option to license this series of compounds across all therapeutic areas.

The agreement also establishes a research collaboration between Decibel and A. James Hudspeth, M.D., Ph.D., the F.M. Kirby Professor at The Rockefeller University and the director of the F.M. Kirby Center for Sensory Neuroscience. Dr. Hudspeth is a world-renowned neuroscientist, a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and a Howard Hughes Medical Institute investigator. Dr. Hudspeth has been the recipient of numerous prestigious awards, including the 2018 Kavli Prize in Neuroscience.

"Rockefeller scientists are at the leading edge of discovery, and we are excited to see the work of Dr. Hudspeth move forward in partnership with Decibel," said Jeanne Farrell, Ph.D., associate vice president for technology advancement at The Rockefeller University. "The ambitious pursuit of harnessing the power of regenerative medicine to create a new option for patients with hearing loss could transform how we address this unmet medical need in the future."

In parallel with its new research focus on regenerative strategies, Decibel will continue to advance key priority preclinical and clinical programs. DB-020, the companys clinical-stage candidate designed to prevent hearing damage in people receiving cisplatin chemotherapy, is in an ongoing Phase 1b trial. Decibel will also continue to progress DB-OTO, a gene therapy for the treatment of genetic congenital deafness, which is being developed in partnership with Regeneron Pharmaceuticals. The DB-OTO program aims to restore hearing to people born with profound hearing loss due to a mutation in the otoferlin gene and is expected to progress to clinical trials in 2021.

Story continues

To support the new research focus, Decibel is restructuring its employee base and discontinuing some early-stage discovery programs.

About Decibel Therapeutics, Inc.Decibel Therapeutics, a development-stage biotechnology company, has established the worlds first comprehensive drug discovery, development, and translational research platform for hearing loss and balance disorders. Decibel is advancing a portfolio of discovery-stage programs aimed at restoring hearing and balance function to further our vision of a world in which the benefits and joys of hearing are available to all. Decibels lead therapeutic candidate, DB-020, is being investigated for the prevention of ototoxicity associated with cisplatin chemotherapy. For more information about Decibel Therapeutics, please visit decibeltx.com or follow @DecibelTx.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200129005162/en/

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Decibel Therapeutics Announces Strategic Research Focus on Regenerative Medicine for the Inner Ear - Yahoo Finance

Neuroscience

Bio professor, Tudor, shares her passion for memory research – The Hawk

Jennifer Tudor, Ph.D., assistant professor of biology, gave a talk titled Nosh and Neuro, addressing a room filled with students on the second floor of Post Hall on Jan. 23. She spoke on the subject of translating sleep and memory.

Tudor began by informing students that her initial interest in neuroscience was a result of wanting to understand her own personal experience. She was born with neurodevelopmental disorder, a disorder that disturbs the development of the nervous system.

I got interested in neuroscience through a personal experience, Tudor said. I wanted to try to figure out what was wrong with me.

Tudor focuses her research on how sleep and disease affect the pathways that are significant for learning, memory and behavior. However, toward the beginning of Tudors research career, she wasnt interested in studying sleep at all.

Thats a little bit about how the process came from: a college student studying psych to now being a single cell transduction biologist in terms of memory, Tudor said.

While still in school, Tudors research adviser assigned her to study sleep.As a result, Tudor became more interested in the topic of study, especially as research and experimenting continued.

I tell people that I am a memory researcher who happens to study sleep, Tudor said. I find studying sleep more fascinating, interesting and dynamic than I did before.

Rebecca Roque 20, a psychology major with minors in behavioral neuroscience and English, said she believes that Tudors lecture about her experience is helpful.

Coming to the Nosh and Neuro talks affords me the ability to connect with other neuroscientists, Roque said. I learn about potential job opportunities in their labs and hear about studies that otherwise I may not have been exposed to.

Hailey Abati 23, a psychology major, said she attended this event because of its relevance to her line of study.

It is important to know how sleep affects memory, Abati said. Memory is a very important part of our everyday lives and the long-run of our lives, and knowing how to better your memory by properly getting sleep is very important.

Even though Abati is a psychology major, she thought this lecture was interesting because of Tudors change of study.

I found it interesting that she originally did not want to study sleep, she thought it was very boring, Abati said. But now looking at her, she has made amazing discoveries and done incredible research on the topic and is now fascinated by it.

Tudors research and work has been featured in publications such as Science Signaling, Journal of Neuroscience and Elife. Roque believes these lectures are very beneficial not only to her, but to the other students and professors studying similar fields at St. Joes.

I find this especially important as a young scientist to learn about new materials in the field so I can better do my job as a researcher, Roque said. Additionally, I think its important to support members at Saint Josephs by making time to hear about the research conducted on our own campus. In doing so, I think we can build a stronger community for students who are interested in pursuing a career in science.

At the end of the lecture, Tudor encouraged students to widen their knowledge using other fields of study and by connecting to the students in the classroom.

My learning curve was so steep; it was so hard, Tudor said. My encouragement for undergraduates in the room is to learn as much as you can about almost anything that mightpotentially relate to what you have to learn.

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Bio professor, Tudor, shares her passion for memory research - The Hawk

Neuroscience

Putting the ‘lazy eye’ to work – University of California

When University of California, Irvine neurobiologist Carey Y.L. Huh, Ph.D., set her sights on discovering more about amblyopia, she brought personal insight to her quest. As a child, Huh was diagnosed with the condition, which is often called lazy eye.

Huh is a researcher in the lab of UC Irvine associate professor of neurobiology & behavior Sunil Gandhi. She and her colleagues have just found that amblyopia originates in an earlier stage of the visual pathway than was previously thought. Their research, which raises the possibility of new treatment approaches, appears in the Journal of Neuroscience.

For those with amblyopia, vision in one eye is much poorer than the other, interfering with how their brains and eyes work together to produce what they see. One of amblyopias hallmarks is difficulty with three-dimension perception, which necessitates use of both eyes. Many of the estimated two to five percent of people globally with amblyopia lack this ability known as binocular vision. Amblyopia begins in childhood and accounts for most visits by youngsters to vision professionals.

Traditionally, scientists have thought amblyopia starts in the brains visual cortex. Using two-photon calcium imaging, an advanced technique that displays cerebral activity in real time, Huh and her colleagues investigated this accepted belief in rodent models. Their research revealed amblyopias impact on binocular vision actually originates in the thalamus, which serves as the information relay station between the eyes and the visual cortex. They did, however, find that the visual cortex does serve a role in amblyopia by affecting the ability to see fine detail.

To treat amblyopia, a patch, either in physical form or pharmaceutically, is placed over the better eye to force the brain to learn how to use the weaker one. Without this process, the brain could lose its ability to utilize the latter.

However, our findings indicate amblyopia treatment may need to be revised, said Huh, the articles first author. The traditional treatment of patching the good eye may need to be supplemented with newer methods such as binocular training, to preserve and improve 3-Dvision as much as possible.

Amblyopia can result from childhood strabismus, a condition in which the eyes are misaligned. Other principal causes of amblyopia include childhood cataracts and severe refraction differences between eyes that are left uncorrected in youngsters. It is important to have childrens eyes examined early so the underlying problems can be properly treated.

With the colloquial name lazy eye, it may be easy to overlook the impact of amblyopia, Huh said. It is a significant condition that prevents people from enjoying full visual capacity and can keep them from entering certain professions, she said. And the vision degeneration that can come with aging could raise special concerns for those with amblyopia.

Funding for the research was provided by the National Institutes of Health, the Canadian Institutes of Health Research and Knights Templar Eye Foundation Grants.

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Neuroscience

Neuroscience Market Global and Regional Analysis by Top Key Market Players, Key Regions, Product Segments, and Applications by 2512 – The Industry…

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Biochemistry

No more weight loss resolutions this is the last program youll ever need – KSTU FOX 13 Salt Lake City

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Dr. Kristen Kells, DC, BSc, a Chiropractic Physician, is the founder of Dr. Kells Weight Loss.

She says the components of her program are simple. It's an all-natural, whole body approach that uses real food, pharmaceutical grade supplements, mineralized water and red light therapy.

Dr. Kells Weight Loss addresses the biochemistry and broken metabolism and even promises to eliminate those sugar cravings!

Dr. Kells isn't just the founder of the program, she's been through it. At her highest weight she was 200lbs, and she's a tiny little thing, just 5'1"! Now she's 80 pounds down and helping others do the same, including her client Roxanne Swift.

After just eight months on the program, Roxanne is down 48 pounds. She says before her weight loss she was sick and even had a hard time walking. Now she goes to the gym and walks on the treadmill! She says she feels great and feels she can keep it up for the rest of her life.

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No more weight loss resolutions this is the last program youll ever need - KSTU FOX 13 Salt Lake City

Biochemistry

‘People take on more debt to make ends meet’: the cost of postgrad study – The Guardian

Growing up in Redcar on the north-east coast of Yorkshire, Kerry-Anne Revie, who is from a low-income background, thought that people like me dont belong at Oxford. The elite university wants to change this perception: in July 2019 it launched UNIQ+ a summer school designed to widen minority groups access to postgraduate education, such as those who have been in care or received free school meals.

Revie spent six weeks at Oxfords biochemistry department, assisting an academics research into DNA transcription. The 22-year-old is doing an integrated masters in biological sciences at University of Leeds, and says UNIQ+ put her on a par with peers who could afford to do voluntary work.

Its one of a flurry of recent schemes, from mentoring to financial aid, designed to boost postgrad diversity in response to concerns that undergrad debt is deterring people from staying on at university. A 2016 study found that 2.4% of white students had started a PhD within five years of graduating, compared with just 1.3% of black, Asian or minority ethnic (BAME) students. A key factor is the financial barrier: only 1.2% of PhD studentships from UK Research and Innovation research councils have been awarded to black or black-mixed students in the past three years.

Prof Paul Wakeling at the University of Yorks department of education says universities focused on the bottom line by prioritising the recruitment of a more diverse range of undergrad students rather than postgrads a move driven in part by financial necessity. In order to charge the max 9,250 undergrad fees, a universitys fair access plan must be approved by the Office for Students, but only for undergrad degrees and postgrad initial teacher training, because there is no cap on postgrad tuition fees, other than for initial teacher training.

We need more regulatory oomph, says Wakeling.

For its part, the government introduced loans of up to 25,000 (now 25,700) for doctoral students in 2018/19, and in 2016/17 loans for masters degrees worth 10,000 (now 10,906) were launched. The latter widened access to postgrad study: enrolment on loan-eligible masters courses increased by 74% among black students, and by 59% among those from low undergrad participation areas a proxy for disadvantage between 2015/16 and 2016/17. Both groups had previously cited finance as a major barrier to a postgrad degree.

But the loans could subsidise the wealthy as they are not based on students financial need, says Wakeling you can get one no matter how much money you have in the bank. And they rarely cover all tuition and living costs, which can be up to 30,000 a year in London, says Catherine Baldwin, director of recruitment and admissions at London School of Economics.

LSE fills this gap in finance by awarding more than 13m of scholarships annually, including needs-based awards such as the Graduate Support Scheme, worth between 5,000 and 15,000. Baldwin says this helps LSE attract a broad range of nationalities, as well as students from across the UK, not just south-east England.

However, Ginevra House, a freelance researcher at the Higher Education Policy Institute (HEPI), says that recent gains made in fair access will be eroded if tuition fees continue to increase: People will rely on part-time work or bank loans that add more debt to make ends meet.

Since the introduction of masters loans, universities have been hiking postgrad tuition fees to cover the cost of running courses; research programmes overall make a substantial loss, she says.

Revie is searching for funding to potentially do a PhD in immunology at Oxford, but she remains undecided. While she was on the UNIQ+ scheme last year, university admissions staff pointed out sources of funding and shared potential admissions interview questions so she could prepare. Oxford will also waive her 75 application fee.

In addition, UNIQ+ pays a 2,500 stipend, and Oxford put Revie up in halls in Jericho, an Oxford city suburb. Some students in the halls were snobby she says. When she complained that bars shut relatively early at the weekend, one quipped: Thats because everyone works harder in Oxford and does better.

But the experience has not deterred her from staying on and indeed, most UNIQ+ students are considering a postgrad at Oxford or another Russell Group university, says Nadia Pollini, director of graduate admissions. She adds: We were amazed by the response in four weeks we had 200 applications for 33 places. Theres a real need for this. We are looking to expand it.

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'People take on more debt to make ends meet': the cost of postgrad study - The Guardian

Physiology

Skeletal system 1: the anatomy and physiology of bones – Nursing Times

Bones are an important part of the musculoskeletal system. This article, the first in a two-part series on the skeletal system, reviews the anatomy and physiology of bone

The skeletal system is formed of bones and cartilage, which are connected by ligaments to form a framework for the remainder of the body tissues. This article, the first in a two-part series on the structure and function of the skeletal system, reviews the anatomy and physiology of bone. Understanding the structure and purpose of the bone allows nurses to understand common pathophysiology and consider the most-appropriate steps to improve musculoskeletal health.

Citation: Walker J (2020) Skeletal system 1: the anatomy and physiology of bones. Nursing Times [online]; 116: 2, 38-42.

Author: Jennie Walker is principal lecturer, Nottingham Trent University.

The skeletal system is composed of bones and cartilage connected by ligaments to form a framework for the rest of the body tissues. There are two parts to the skeleton:

As well as contributing to the bodys overall shape, the skeletal system has several key functions, including:

Bones are a site of attachment for ligaments and tendons, providing a skeletal framework that can produce movement through the coordinated use of levers, muscles, tendons and ligaments. The bones act as levers, while the muscles generate the forces responsible for moving the bones.

Bones provide protective boundaries for soft organs: the cranium around the brain, the vertebral column surrounding the spinal cord, the ribcage containing the heart and lungs, and the pelvis protecting the urogenital organs.

As the main reservoirs for minerals in the body, bones contain approximately 99% of the bodys calcium, 85% of its phosphate and 50% of its magnesium (Bartl and Bartl, 2017). They are essential in maintaining homoeostasis of minerals in the blood with minerals stored in the bone are released in response to the bodys demands, with levels maintained and regulated by hormones, such as parathyroid hormone.

Blood cells are formed from haemopoietic stem cells present in red bone marrow. Babies are born with only red bone marrow; over time this is replaced by yellow marrow due to a decrease in erythropoietin, the hormone responsible for stimulating the production of erythrocytes (red blood cells) in the bone marrow. By adulthood, the amount of red marrow has halved, and this reduces further to around 30% in older age (Robson and Syndercombe Court, 2018).

Yellow bone marrow (Fig 1) acts as a potential energy reserve for the body; it consists largely of adipose cells, which store triglycerides (a type of lipid that occurs naturally in the blood) (Tortora and Derrickson, 2009).

Bone matrix has three main components:

Organic matrix (osteoid) is made up of approximately 90% type-I collagen fibres and 10% other proteins, such as glycoprotein, osteocalcin, and proteoglycans (Bartl and Bartl, 2017). It forms the framework for bones, which are hardened through the deposit of the calcium and other minerals around the fibres (Robson and Syndercombe Court, 2018).

Mineral salts are first deposited between the gaps in the collagen layers with once these spaces are filled, minerals accumulate around the collagen fibres, crystallising and causing the tissue to harden; this process is called ossification (Tortora and Derrickson, 2009). The hardness of the bone depends on the type and quantity of the minerals available for the body to use; hydroxyapatite is one of the main minerals present in bones.

While bones need sufficient minerals to strengthen them, they also need to prevent being broken by maintaining sufficient flexibility to withstand the daily forces exerted on them. This flexibility and tensile strength of bone is derived from the collagen fibres. Over-mineralisation of the fibres or impaired collagen production can increase the brittleness of bones as with the genetic disorder osteogenesis imperfecta and increase bone fragility (Ralston and McInnes, 2014).

Bone architecture is made up of two types of bone tissue:

Also known as compact bone, this dense outer layer provides support and protection for the inner cancellous structure. Cortical bone comprises three elements:

The periosteum is a tough, fibrous outer membrane. It is highly vascular and almost completely covers the bone, except for the surfaces that form joints; these are covered by hyaline cartilage. Tendons and ligaments attach to the outer layer of the periosteum, whereas the inner layer contains osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) responsible for bone remodelling.

The function of the periosteum is to:

It also contains Volkmanns canals, small channels running perpendicular to the diaphysis of the bone (Fig 1); these convey blood vessels, lymph vessels and nerves from the periosteal surface through to the intracortical layer. The periosteum has numerous sensory fibres, so bone injuries (such as fractures or tumours) can be extremely painful (Drake et al, 2019).

The intracortical bone is organised into structural units, referred to as osteons or Haversian systems (Fig 2). These are cylindrical structures, composed of concentric layers of bone called lamellae, whose structure contributes to the strength of the cortical bone. Osteocytes (mature bone cells) sit in the small spaces between the concentric layers of lamellae, which are known as lacunae. Canaliculi are microscopic canals between the lacunae, in which the osteocytes are networked to each other by filamentous extensions. In the centre of each osteon is a central (Haversian) canal through which the blood vessels, lymph vessels and nerves pass. These central canals tend to run parallel to the axis of the bone; Volkmanns canals connect adjacent osteons and the blood vessels of the central canals with the periosteum.

The endosteum consists of a thin layer of connective tissue that lines the inside of the cortical surface (Bartl and Bartl, 2017) (Fig1).

Also known as spongy bone, cancellous bone is found in the outer cortical layer. It is formed of lamellae arranged in an irregular lattice structure of trabeculae, which gives a honeycomb appearance. The large gaps between the trabeculae help make the bones lighter, and so easier to mobilise.

Trabeculae are characteristically oriented along the lines of stress to help resist forces and reduce the risk of fracture (Tortora and Derrickson, 2009). The closer the trabecular structures are spaced, the greater the stability and structure of the bone (Bartl and Bartl, 2017). Red or yellow bone marrow exists in these spaces (Robson and Syndercombe Court, 2018). Red bone marrow in adults is found in the ribs, sternum, vertebrae and ends of long bones (Tortora and Derrickson, 2009); it is haemopoietic tissue, which produces erythrocytes, leucocytes (white blood cells) and platelets.

Bone and marrow are highly vascularised and account for approximately 10-20% of cardiac output (Bartl and Bartl, 2017). Blood vessels in bone are necessary for nearly all skeletal functions, including the delivery of oxygen and nutrients, homoeostasis and repair (Tomlinson and Silva, 2013). The blood supply in long bones is derived from the nutrient artery and the periosteal, epiphyseal and metaphyseal arteries (Iyer, 2019).

Each artery is also accompanied by nerve fibres, which branch into the marrow cavities. Arteries are the main source of blood and nutrients for long bones, entering through the nutrient foramen, then dividing into ascending and descending branches. The ends of long bones are supplied by the metaphyseal and epiphyseal arteries, which arise from the arteries from the associated joint (Bartl and Bartl, 2017).

If the blood supply to bone is disrupted, it can result in the death of bone tissue (osteonecrosis). A common example is following a fracture to the femoral neck, which disrupts the blood supply to the femoral head and causes the bone tissue to become necrotic. The femoral head structure then collapses, causing pain and dysfunction.

Bones begin to form in utero in the first eight weeks following fertilisation (Moini, 2019). The embryonic skeleton is first formed of mesenchyme (connective tissue) structures; this primitive skeleton is referred to as the skeletal template. These structures are then developed into bone, either through intramembranous ossification or endochondral ossification (replacing cartilage with bone).

Bones are classified according to their shape (Box1). Flat bones develop from membrane (membrane models) and sesamoid bones from tendon (tendon models) (Waugh and Grant, 2018). The term intra-membranous ossification describes the direct conversion of mesenchyme structures to bone, in which the fibrous tissues become ossified as the mesenchymal stem cells differentiate into osteoblasts. The osteoblasts then start to lay down bone matrix, which becomes ossified to form new bone.

Box 1. Types of bones

Long bones typically longer than they are wide (such as humerus, radius, tibia, femur), they comprise a diaphysis (shaft) and epiphyses at the distal and proximal ends, joining at the metaphysis. In growing bone, this is the site where growth occurs and is known as the epiphyseal growth plate. Most long bones are located in the appendicular skeleton and function as levers to produce movement

Short bones small and roughly cube-shaped, these contain mainly cancellous bone, with a thin outer layer of cortical bone (such as the bones in the hands and tarsal bones in the feet)

Flat bones thin and usually slightly curved, typically containing a thin layer of cancellous bone surrounded by cortical bone (examples include the skull, ribs and scapula). Most are located in the axial skeleton and offer protection to underlying structures

Irregular bones bones that do not fit in other categories because they have a range of different characteristics. They are formed of cancellous bone, with an outer layer of cortical bone (for example, the vertebrae and the pelvis)

Sesamoid bones round or oval bones (such as the patella), which develop in tendons

Long, short and irregular bones develop from an initial model of hyaline cartilage (cartilage models). Once the cartilage model has been formed, the osteoblasts gradually replace the cartilage with bone matrix through endochondral ossification (Robson and Syndercombe Court, 2018). Mineralisation starts at the centre of the cartilage structure, which is known as the primary ossification centre. Secondary ossification centres also form at the epiphyses (epiphyseal growth plates) (Danning, 2019). The epiphyseal growth plate is composed of hyaline cartilage and has four regions (Fig3):

Resting or quiescent zone situated closest to the epiphysis, this is composed of small scattered chondrocytes with a low proliferation rate and anchors the growth plate to the epiphysis;

Growth or proliferation zone this area has larger chondrocytes, arranged like stacks of coins, which divide and are responsible for the longitudinal growth of the bone;

Hypertrophic zone this consists of large maturing chondrocytes, which migrate towards the metaphysis. There is no new growth at this layer;

Calcification zone this final zone of the growth plate is only a few cells thick. Through the process of endochondral ossification, the cells in this zone become ossified and form part of the new diaphysis (Tortora and Derrickson, 2009).

Bones are not fully developed at birth, and continue to form until skeletal maturity is reached. By the end of adolescence around 90% of adult bone is formed and skeletal maturity occurs at around 20-25 years, although this can vary depending on geographical location and socio-economic conditions; for example, malnutrition may delay bone maturity (Drake et al, 2019; Bartl and Bartl, 2017). In rare cases, a genetic mutation can disrupt cartilage development, and therefore the development of bone. This can result in reduced growth and short stature and is known as achondroplasia.

The human growth hormone (somatotropin) is the main stimulus for growth at the epiphyseal growth plates. During puberty, levels of sex hormones (oestrogen and testosterone) increase, which stops cell division within the growth plate. As the chondrocytes in the proliferation zone stop dividing, the growth plate thins and eventually calcifies, and longitudinal bone growth stops (Ralston and McInnes, 2014). Males are on average taller than females because male puberty tends to occur later, so male bones have more time to grow (Waugh and Grant, 2018). Over-secretion of human growth hormone during childhood can produce gigantism, whereby the person is taller and heavier than usually expected, while over-secretion in adults results in a condition called acromegaly.

If there is a fracture in the epiphyseal growth plate while bones are still growing, this can subsequently inhibit bone growth, resulting in reduced bone formation and the bone being shorter. It may also cause misalignment of the joint surfaces and cause a predisposition to developing secondary arthritis later in life. A discrepancy in leg length can lead to pelvic obliquity, with subsequent scoliosis caused by trying to compensate for the difference.

Once bone has formed and matured, it undergoes constant remodelling by osteoclasts and osteoblasts, whereby old bone tissue is replaced by new bone tissue (Fig4). Bone remodelling has several functions, including mobilisation of calcium and other minerals from the skeletal tissue to maintain serum homoeostasis, replacing old tissue and repairing damaged bone, as well as helping the body adapt to different forces, loads and stress applied to the skeleton.

Calcium plays a significant role in the body and is required for muscle contraction, nerve conduction, cell division and blood coagulation. As only 1% of the bodys calcium is in the blood, the skeleton acts as storage facility, releasing calcium in response to the bodys demands. Serum calcium levels are tightly regulated by two hormones, which work antagonistically to maintain homoeostasis. Calcitonin facilitates the deposition of calcium to bone, lowering the serum levels, whereas the parathyroid hormone stimulates the release of calcium from bone, raising the serum calcium levels.

Osteoclasts are large multinucleated cells typically found at sites where there is active bone growth, repair or remodelling, such as around the periosteum, within the endosteum and in the removal of calluses formed during fracture healing (Waugh and Grant, 2018). The osteoclast cell membrane has numerous folds that face the surface of the bone and osteoclasts break down bone tissue by secreting lysosomal enzymes and acids into the space between the ruffled membrane (Robson and Syndercombe Court, 2018). These enzymes dissolve the minerals and some of the bone matrix. The minerals are released from the bone matrix into the extracellular space and the rest of the matrix is phagocytosed and metabolised in the cytoplasm of the osteoclasts (Bartl and Bartl, 2017). Once the area of bone has been resorbed, the osteoclasts move on, while the osteoblasts move in to rebuild the bone matrix.

Osteoblasts synthesise collagen fibres and other organic components that make up the bone matrix. They also secrete alkaline phosphatase, which initiates calcification through the deposit of calcium and other minerals around the matrix (Robson and Syndercombe Court, 2018). As the osteoblasts deposit new bone tissue around themselves, they become trapped in pockets of bone called lacunae. Once this happens, the cells differentiate into osteocytes, which are mature bone cells that no longer secrete bone matrix.

The remodelling process is achieved through the balanced activity of osteoclasts and osteoblasts. If bone is built without the appropriate balance of osteocytes, it results in abnormally thick bone or bony spurs. Conversely, too much tissue loss or calcium depletion can lead to fragile bone that is more susceptible to fracture. The larger surface area of cancellous bones is associated with a higher remodelling rate than cortical bone (Bartl and Bartl, 2017), which means osteoporosis is more evident in bones with a high proportion of cancellous bone, such as the head/neck of femur or vertebral bones (Robson and Syndercombe Court, 2018). Changes in the remodelling balance may also occur due to pathological conditions, such as Pagets disease of bone, a condition characterised by focal areas of increased and disorganised bone remodelling affecting one or more bones. Typical features on X-ray include focal patches of lysis or sclerosis, cortical thickening, disorganised trabeculae and trabecular thickening.

As the body ages, bone may lose some of its strength and elasticity, making it more susceptible to fracture. This is due to the loss of mineral in the matrix and a reduction in the flexibility of the collagen.

Adequate intake of vitamins and minerals is essential for optimum bone formation and ongoing bone health. Two of the most important are calcium and vitamin D, but many others are needed to keep bones strong and healthy (Box2).

Box 2. Vitamins and minerals needed for bone health

Key nutritional requirements for bone health include minerals such as calcium and phosphorus, as well as smaller qualities of fluoride, manganese, and iron (Robson and Syndercombe Court, 2018). Calcium, phosphorus and vitamin D are essential for effective bone mineralisation. Vitamin D promotes calcium absorption in the intestines, and deficiency in calcium or vitamin D can predispose an individual to ineffective mineralisation and increased risk of developing conditions such as osteoporosis and osteomalacia.

Other key vitamins for healthy bones include vitamin A for osteoblast function and vitamin C for collagen synthesis (Waugh and Grant, 2018).

Physical exercise, in particular weight-bearing exercise, is important in maintaining or increasing bone mineral density and the overall quality and strength of the bone. This is because osteoblasts are stimulated by load-bearing exercise and so bones subjected to mechanical stresses undergo a higher rate of bone remodelling. Reduced skeletal loading is associated with an increased risk of developing osteoporosis (Robson and Syndercombe Court, 2018).

Bones are an important part of the musculoskeletal system and serve many core functions, as well as supporting the bodys structure and facilitating movement. Bone is a dynamic structure, which is continually remodelled in response to stresses placed on the body. Changes to this remodelling process, or inadequate intake of nutrients, can result in changes to bone structure that may predispose the body to increased risk of fracture. Part2 of this series will review the structure and function of the skeletal system.

Bartl R, Bartl C (2017) Structure and architecture of bone. In: Bone Disorder: Biology, Diagnosis, Prevention, Therapy.

Danning CL (2019) Structure and function of the musculoskeletal system. In: Banasik JL, Copstead L-EC (eds) Pathophysiology. St Louis, MO: Elsevier.

Drake RL et al (eds) (2019) Grays Anatomy for Students. London: Elsevier.

Iyer KM (2019) Anatomy of bone, fracture, and fracture healing. In: Iyer KM, Khan WS (eds) General Principles of Orthopedics and Trauma. London: Springer.

Moini J (2019) Bone tissues and the skeletal system. In: Anatomy and Physiology for Health Professionals. Burlington, MA: Jones and Bartlett.

Ralston SH, McInnes IB (2014) Rheumatology and bone disease. In: Walker BR et al (eds) Davidsons Principles and Practice of Medicine. Edinburgh: Churchill Livingstone.

Robson L, Syndercombe Court D (2018) Bone, muscle, skin and connective tissue. In: Naish J, Syndercombe Court D (eds) Medical Sciences. London: Elsevier

Tomlinson RE, Silva MJ (2013) Skeletal blood flow in bone repair and maintenance. Bone Research; 1: 4, 311-322.

Tortora GJ, Derrickson B (2009) The skeletal system: bone tissue. In: Principles of Anatomy and Physiology. Chichester: John Wiley & Sons.

Waugh A, Grant A (2018) The musculoskeletal system. In: Ross & Wilson Anatomy and Physiology in Health and Illness. London: Elsevier.

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Skeletal system 1: the anatomy and physiology of bones - Nursing Times