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  • CT Nails in the coffin of ectodermalism.

    The many faces of Pluripotency: in vitro adaptations of a continuum of in vivo states

    https://bmcdevbiol.biomedcentral.com...ource=Teradata

    Abstract


    Pluripotency defines the propensity of a cell to differentiate into, and generate, all somatic, as well as germ cells. The epiblast of the early mammalian embryo is the founder population of all germ layer derivatives and thus represents the bona fide in vivo pluripotent cell population. The so-called pluripotent state spans several days of development and is lost during gastrulation as epiblast cells make fate decisions towards a mesoderm, endoderm or ectoderm identity. It is now widely recognized that the features of the pluripotent population evolve as development proceeds from the pre- to post-implantation period, marked by distinct transcriptional and epigenetic signatures. During this period of time epiblast cells mature through a continuum of pluripotent states with unique properties. Aspects of this pluripotent continuum can be captured in vitro in the form of stable pluripotent stem cell types. In this review we discuss the continuum of pluripotency existing within the mammalian embryo, using the mouse as a model, and the cognate stem cell types that can be derived and propagated in vitro. Furthermore, we speculate on embryonic stage-specific characteristics that could be utilized to identify novel, developmentally relevant, pluripotent states.
    Keywords

    Pluripotency Naïve Intermediate Formative Primed Embryonic stem cells Epiblast-like cells Epiblast stem cells Ground state Chimaera



    Background


    Pluripotency is the potential of a single cell to generate all somatic lineages of the adult organism, comprising mesoderm, endoderm and ectoderm derivatives, as well as the germ cells. During early mammalian development, cells within the epiblast (Epi) of the embryo are pluripotent and go on to form the embryo-proper. As development progresses, a combination of Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein (BMP), Wnt and Nodal signaling triggers the loss of pluripotency by driving differentiation of the Epi into specialized, developmentally-restricted fates [1]. In the mouse, pluripotent cells are present from embryonic day (E) 3.5 to 8.0, representing approximately one quarter of the gestation period (Fig. 1). During this time, the pluripotent population evolves, characterized by changes in gene expression, epigenetic profile and functional properties. While distinct “naïve” and “primed” pluripotent states have been described, that correspond to the pre and post-implantation Epi respectively [2], the progressive nature of development means that a broad continuum of pluripotency likely exists within the developing embryo (Table 1). To define additional intermediate states, a high-resolution gene expression map of these embryonic stages is required, a task made difficult by the rapid advancement of in vivo development and limited availability of material.


    12861_2017_150_Fig2_HTML.gif

    Fig. 2

    The role of signaling pathways in self-renewal and differentiation of in vitro pluripotent stem cell populations. Embryonic stem cells (ESCs) represent a naïve state of pluripotency similar to the pre-implantation epiblast (Epi). ESCs are routinely maintained in a self-renewing state in serum (a source of BMP) and LIF (SL). Under these conditions, ESC cultures are heterogeneous and contain subpopulations of lineage-primed cells (yellow and green cells) i.e. cells that coexpress germ layer markers alongside pluripotency markers, and are biased in differentiation towards particular lineages. A more homogeneous ESC state can be generated by blocking FGF signaling using a MEK inhibitor (PD0325901), and activating Wnt signaling using a GSK3 inhibitor (CHIR99021), a condition known as ‘2i’. In these conditions, self-renewal occurs in the absence of external signals, although cell propagation is enhanced in the presence of Wnt pathway activity through CHIR99021. This state is referred to as the naïve or “ground state” of pluripotency. ESCs can be pushed further along the differentiation trajectory by culturing in the presence of FGF and Activin (FA) for 48 hours to generate a cell state referred to as Epi-like cells (EpiLCs). This is a transient cell state, and it is unknown whether self-renewing EpiLCs can be captured by the addition of other factors. It is also not known whether EpiLCs are a homogeneous population of cells. Upon further differentiation in FA over multiple passages, cells resemble a primed state of pluripotency akin to the later post-implantation Epi, referred to as epiblast stem cells (EpiSCs). While FA promotes differentiation of ESCs and EpiLCs, it promotes EpiSC self-renewal. EpiSCs can be derived from ESCs in culture or directly from embryos with FA. When grown in FA, EpiSCs, like ESCs in SL, are heterogeneous and contain lineage-primed populations. While activation of Wnt signaling promotes a naïve ground state of self-renewal, inhibition of Wnt signaling promotes a more homogeneous primed ground state of self-renewal. Therefore cells in naïve and primed pluripotent states respond to signaling factors with opposite outcomes, Wnt and BMP promote self-renewal of the naïve state but differentiation of the primed state of pluripotency and conversely FA promote differentiation of the naïve state but self-renewal of the primed state of pluripotency. Addition of BMP4 and WNT3A in combination with FA stimulates further differentiation of EpiSCs into PS-derived mesoderm and endoderm, while in the absence of FA, BMP or Wnt EpiSCs differentiate to neurectoderm [127]. EpiLCs are the only pluripotent state that has been shown to efficiently generate primordial germ cell-like cells (PGCLCs). Presumably, ESCs have not yet acquired this capacity, while EpiSCs have lost it. Cells within the dashed box are within the pluripotency spectrum while cells outside have differentiated. Blue arrows indicate self-renewal. Orange arrows denote the direction of differentiation along the developmental trajectory
    Last edited by Jo Bowyer; 03-10-2017, 01:49 AM.
    Jo Bowyer
    Chartered Physiotherapist Registered Osteopath.
    "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

  • #2
    Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI

    https://elifesciences.org/articles/29738

    Abstract


    Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.


    https://doi.org/10.7554/eLife.29738.001eLife digest


    How does the brain rid itself of waste products? Other organs in the body achieve this via a system called the lymphatic system. A network of lymphatic vessels extends throughout the body in a pattern similar to that of blood vessels. Waste products from cells, plus bacteria, viruses and excess fluids drain out of the body’s tissues into lymphatic vessels, which transfer them to the bloodstream. Blood vessels then carry the waste products to the kidneys, which filter them out for excretion. Lymphatic vessels are also a highway for circulation of white blood cells, which fight infections, and are therefore an important part of the immune system.

    Unlike other organs, the brain does not contain lymphatic vessels. So how does it remove waste? Some of the brain’s waste products enter the fluid that bathes and protects the brain – the cerebrospinal fluid – before being disposed of via the bloodstream. However, recent studies in rodents have also shown the presence of lymphatic vessels inside the outer membrane surrounding the brain, the dura mater.

    Absinta, Ha et al. now show that the dura mater of people and marmoset monkeys contains lymphatic vessels too. Spotting lymphatic vessels is challenging because they resemble blood vessels, which are much more numerous. In addition, Absinta, Ha et al. found a way to visualize the lymphatic vessels in the dura mater using brain magnetic resonance imaging, and could confirm that lymphatic vessels are present in autopsy tissue using special staining methods.

    For magnetic resonance imaging, monkeys and human volunteers received an injection of a dye-like substance called gadolinium, which travels via the bloodstream to the brain. In the dura mater, gadolinium leaks out of blood vessels and collects inside lymphatic vessels, which show up as bright white areas on brain scans. To confirm that the white areas were lymphatic vessels, the experiment was repeated using a different dye that does not leak out of blood vessels. As expected, the signals observed in the previous brain scans did not appear.

    By visualizing the lymphatic system, this technique makes it possible to study how the brain removes waste products and circulates white blood cells, and to examine whether this process is impaired in aging or disease.

    ‘Drain Pipes’ in the Brain: Lymphatic Vessels Act As Pipeline Between Brain and Immune System

    http://neurosciencenews.com/lymphati...ls-brain-7646/

    By scanning the brains of healthy volunteers, researchers at the National Institutes of Health saw the first, long-sought evidence that our brains may drain some waste out through lymphatic vessels, the body’s sewer system. The results further suggest the vessels could act as a pipeline between the brain and the immune system.

    Last edited by Jo Bowyer; 04-10-2017, 03:04 AM.
    Jo Bowyer
    Chartered Physiotherapist Registered Osteopath.
    "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

    Comment


    • #3
      There is a tendency amongst some specialist pain manual therapists to be reductionist in their search for evidence which supports their preferred methods. My own bias is towards generalism, because that is how I was trained. I say trained, because although we spent time in the lecture halls, classrooms, practical rooms and gymnasia, we spent a great deal more time on the wards, in theatres and in clinic. In later years, when I was looking after juniors who didn't "get it", didn't see the connection between who the patient is and what had happened to them, I sent them to theatres and outpatient clinics despite the fact that I was going to have to cover their work. Courses weren't going to cut it if they couldn't reconcile what they had seen from the comfort of a chair to the reality of a live patient who wanted answers. Ours is a hands on profession, much can be achieved during examination, even if we choose not to follow this up with the use of a much hyped method.

      Complex pain patients sometimes get irritated with me when they have booked an appointment to get their right sided neck pain fixed and I want to know about what is happening in the left side of the neck, the knees, the gut and why their GP has referred them to a cardiologist. They understand the need for neurological testing, but wonder why, in some cases, I want to do a vestibular exam.

      Patients are not machines and we are not mechanics. Our function is to see them for who they are, where they came from and how they can be cued to move and load.
      Last edited by Jo Bowyer; 04-10-2017, 12:53 PM.
      Jo Bowyer
      Chartered Physiotherapist Registered Osteopath.
      "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

      Comment


      • #4
        Ectodermalism along with any reductionist mind set is pernicious. Occasionally I get a call from a patient in the wounded healer category, asking me very nicely, if they can pay for more of my time in order to learn how to do what I do. They are asking me to teach them hands on technique.
        Last edited by Jo Bowyer; 04-10-2017, 01:19 PM.
        Jo Bowyer
        Chartered Physiotherapist Registered Osteopath.
        "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

        Comment


        • #5
          I am approaching the twilight years of my career and I am beginning to wind down. Decades ago I was fielding phone calls from those who wanted me to cross continents to set up clinics and rehab facilities abroad. Fully staffed houses and a choice of chauffeur driven cars were proffered. I didn't go, I was romantically involved and I had sporting ambitions.

          Were I to go now, I would be looking to recruit those with a voracious appetite for reading, good with children and farm animals, and outside interests which include arts, craft, and playing a musical instrument. One of my best juniors was a former carpenter.
          Last edited by Jo Bowyer; 04-10-2017, 05:52 PM.
          Jo Bowyer
          Chartered Physiotherapist Registered Osteopath.
          "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

          Comment


          • #6
            The Law of Attraction, the Placebo Effect, and the Immune-Brain Connection

            https://knowingneurons.com/2018/03/0...EMAIL_CAMPAIGN)
            Jo Bowyer
            Chartered Physiotherapist Registered Osteopath.
            "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

            Comment


            • #7
              The healing power of painful memories

              http://science.sciencemag.org/conten...et_cid=1895792
              Summary

              Our body's epithelia are barriers that interface with the terrestrial environment and routinely experience inflammation. Although a vast majority of these inflammatory reactions resolve, they imprint the tissue with a memory. Cells of the immune system are traditionally thought to be the bearers of this memory, allowing them to react faster to subsequent inflammatory pressures (1, 2). Yet, barrier tissues are composites of epithelial, mesenchymal, nervous, vascular, and immunological networks working in unison to sustain optimal function in health and disease. The question of whether tissue-resident cells, distinct from the immune system, are entrained in response to a perturbation remains to be addressed.
              http://science.sciencemag.org/conten...113.1.full.pdf

              I attend monthly neuroscience lectures at The Crick, much of the material presented is way beyond my limited capabilities as these lectures are for post docs. A couple of days ago Prof Bill Harris of Cambridge University was presenting on "Stochastic fates and nuclear movements" (with reference to cell development in the retina). Coding and proteins are still outwith my limited capabilities, but movement in all it's manifestations is what drives me as a physiotherapist and as a learner, and I got a huge amount out of this one.


              I have a thread here headed Gene genie

              https://www.somasimple.com/forums/fo...021-gene-genie

              I have a passionate interest in gene expression as it drives who we are and what we do,


              I have another thread headed Human Evolution,

              https://www.somasimple.com/forums/fo...uman-evolution


              I realise that these are somewhat niche, unless you practice as a generalist. Once upon a time all physiotherapists were generalists, medicine hasn't abandoned generalism and I wonder if physiotherapists would be happier if they re engaged.

              Yesterday, I saw an expectant mother, a few coping with failed surgery, a casualty of the music business lifestyle whose immune system has been trashed, and several pain patients. "Ectodermalism" as prescribed and fiercely defended by the North Americans who moderate SomaSimple, would barely have touched the surface, if you'll pardon the expression.


              Treatment methods, in and of themselves are not the answer and should never underpin cults, catechism, and punishment of dissidents. The skin and this board's obsession with it, is in my opinion more than a barrier, it's a road block.
              Jo Bowyer
              Chartered Physiotherapist Registered Osteopath.
              "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

              Comment


              • #8
                How biology breaks the ‘cerebral mystique’

                https://www.sciencenews.org/article/...-newsletter-v2



                In The Biological Mind, Jasanoff, now a neuroscientist at MIT, refers to the romanticized view of the brain — its separateness and superiority to the body and its depiction as almost supernatural — as the “cerebral mystique.” Such an attitude has been fueled, in part, by images that depict the brain without any connection to the body or by analogies that compare the brain to a computer. Admittedly, the brain does have tremendous computing power. But Jasanoff’s goal is to show that the brain doesn’t work as a distinct, mystical entity, but as a ball of flesh awash with fluids and innately in tune with the rest of the body and the environment. “Self” doesn’t just come from the brain, he explains, but also from the interactions of chemicals from our bodies with everything else around us.

                To make his case, Jasanoff offers an extensive yet entertaining review of the schools of thought and representations of the brain in the media that led to the rise of the cerebral mystique, especially during the last few decades. He then tears down those ideas using contrary examples from recent research, along with engaging anecdotes. For instance, his clear, lively writing reveals how our emotions, such as the fight-or-flight response and the suite of thoughts and actions associated with stress, provide strong evidence for a brain-body connection. Exercise’s effect on the brain also supports this notion. Even creativity isn’t sacred, often stemming from repeated interactions with those around us.

                Jasanoff is critical of how the cerebral mystique reduces problems of human behavior, such as drug addiction or eating disorders, to problems of the brain. Such problems are no longer viewed as “moral failings” but as a result of “broken brains.” This shifting view, its advocates argue, reduces the stigma associated with psychiatric disorders. But it also leads to other problems, Jasanoff notes: Society views broken brains as harder to fix than moral flaws, making life even more challenging for individuals already struggling with mental illness. People could benefit from a more comprehensive view of the brain, one that includes how biology, environment and culture shape behavior.

                When mental processes are seen as transcending the body, society perceives people as “more independent and self-motivated than they truly are,” and that minimizes “the connections that bind us to each other and to the environment around us,” Jasanoff writes. As a result, he argues, we’re living in an age of self-absorption and self-centeredness, driven in part by our fascination with the brain.

                In reality, the brain isn’t a miraculous machine, but instead a prism refracting countless internal and external influences. A few more specifics on how this prism works — details of what is going on at the cellular or molecular level, for instance — might have helped support Jasanoff’s arguments.

                But he does leave readers with a thought-provoking idea: “You are not only your brain.” Grapple with that, he contends, and we could move toward communities that are much more socially minded and accepting of our interconnectedness.
                Jo Bowyer
                Chartered Physiotherapist Registered Osteopath.
                "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                Comment


              • #9
                Parkinson’s Gene Initiates Disease Outside of the Brain

                http://neurosciencenews.com/parkinsons-genetics-8686/

                Until very recently, Parkinson’s had been thought a disease that starts in the brain, destroying motion centers and resulting in the tremors and loss of movement. New research published this week in the journal Brain, shows the most common Parkinson’s gene mutation may change how immune cells react to generic infections like colds, which in turn trigger the inflammatory reaction in the brain that causes Parkinson’s. The research offers a new understanding of Parkinson’s disease.
                gene genie
                Jo Bowyer
                Chartered Physiotherapist Registered Osteopath.
                "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                Comment


                • #10
                  Neuronal–immune system cross-talk in homeostasis

                  http://science.sciencemag.org/conten...6383/1465.full



                  Maintenance of mammalian tissue homeostasis and function requires coordinated actions of multiple cellular and molecular networks. This complexity is reflected in the immune system, which is composed of a plethora of cells that constitute the innate and adaptive immune system and which can sense multiple endogenous and exogenous factors. Similarly, the nervous system includes a myriad of distinct neurons that perceive, integrate, and respond to ever-changing environmental conditions. Functional interactions between the neuronal and immune systems have been reported in health and disease, such as in multiple sclerosis, autism, cancer, and chronic inflammatory disorders (1). More recently, a number of studies have revealed that discrete neuronal and immune cells share anatomical localization and interact functionally, forming neuroimmune cell units (NICUs) that orchestrate tissue homeostasis and integrity (2). These findings are provoking a fundamental paradigm shift in our understanding of neuronal–immune cell interactions. A recent noteworthy example is the finding that the nervous system can have a major regulatory effect on multiple innate immune cells with functional impact in several physiological processes (38).

                  Earlier studies established that signals from the parasympathetic vagus nerve, which connects the brainstem with peripheral organs, can have an anti-inflammatory effect via tuning the activity of macrophages, innate immune cells that engulf pathogens and cell debris, leading to the production of macrophage-derived immunomodulatory molecules (9). Bidirectional neuronal-macrophage interactions were also shown to regulate important aspects of intestinal physiology. Notably, intestinal macrophages control myenteric neuron activity and small intestine peristalsis (muscular contractions that move food down the intestine) in response to microbial signals in the intestines (3), whereas intestinal pathogenic bacterial infections activate neurons to produce norepinephrine that induces a tissue-protective program in enteric macrophages (4). Notably, neuron-associated macrophages are also present in adipose tissue and were shown to buffer sympathetic neuronal activity and fat tissue physiology, thus controlling obesity and organismal metabolism (10). Dendritic cells and mast cells (both components of the innate immune system) also interact with peripheral neurons (1). For example, upon chemical irritation or infection with fungi, sensory neurons in the skin instruct dermal dendritic cells to produce the cytokine interleukin-23 (IL-23), which activates adaptive T lymphocytes to produce proinflammatory cytokines (11). Reciprocally, lymphocyte-derived type 2 cytokines—such as IL-4, IL-5, and IL-13—were also shown to induce chronic itch via sensory neuron activation (12). Together, these findings demonstrate that neurons can trigger functional molecular cascades that lead to the activation of innate and adaptive immune cells, influencing immunity to infection, chronic inflammation, and restoration of tissue homeostasis. Nevertheless, defining additional pathways that operate in the opposing direction, whereby immune cells can modulate neuronal activity, requires further study.

                  But how widespread and biologically important is this neuronal-immune interaction? Over the past decade, we have witnessed the formal discovery of innate lymphoid cells (ILCs) and their roles in development, infection, inflammation, metabolic disease, and cancer (13). ILCs are a relatively rare cell type, but they are particularly abundant at barrier surfaces that are exposed to the external environment, which are also densely populated with neuronal cells. Group 2 ILCs (ILC2s) are associated with allergy and parasitic worm infections and were reported to respond to vasoactive intestinal peptide signals that were presumably derived from neuronal cells (14), suggesting that neuronal-ILC interactions could also occur at mucosal barriers. Consistent with this concept, group 3 ILCs (ILC3s) were shown to control intestinal health as part of a glial cell-ILC3 unit orchestrated by neurotrophic factors (5). Glial cells, considered to provide support and protection to neurons, are adjacent to ILC3s and integrate microbial-derived and host alarmin (danger molecules that are released upon tissue damage)-derived signals to control neurotrophic factor production (5). In turn, these neuroregulatory molecules activate RET-expressing ILC3s that produce the tissue-protective cytokine IL-22 (5). Thus, glial cells translate microbial and host cues into neurotrophic factor production, which target coordinated neuronal and ILC3 functions to promote intestinal tissue repair after exposure to infectious and inflammatory stimuli (see the figure).

                  Adding to the growing understanding of NICUs, other recent studies revealed that mucosal neurons regulate the production of ILC-derived type 2 cytokines via the production of the neuropeptide neuromedin U (NMU) (68). NMU-producing cholinergic neurons are adjacent to intestinal and pulmonary ILC2s, whereas NMU receptor 1 (NMUR1) is selectively expressed by ILC2s (68). Notably, activation of ILC2s with this neuropeptide leads to a rapid and potent production of type 2 inflammatory and tissue-protective cytokines (6, 7). Consistent with this, activation of this signaling axis in ILC2s in vivo leads to rapid type 2 cytokine responses after exposure to parasite infections or allergens (68). The capacity of neuronal-derived signals to rapidly trigger ILC2 responses may also explain in part why, despite their relatively low numbers, ILC2s can be rapidly activated and have profound effects across large barrier surfaces.

                  In addition to the activating functions of cholinergic nerve-derived NMU, catecholaminergic neurons—a component of the sympathetic nervous system that is a potent source of molecules such as norepinephrine that binds the β2-adrenergic receptor (β2AR)—were shown to act as a potent “off switch” that dampens ILC2 responses (15). β2AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues, whereas β2AR agonist treatment, a frontline therapy for asthma patients, was associated with impaired ILC2 responses and reduced inflammation in vivo (15). Together, these new findings demonstrate that neuronal-ILC units are poised to trigger immediate barrier tissue protection programs through a neuronal-immune “fast track” response that can both switch on and switch off ILC2 responses, whereas activation by cytokines and alarmins appears to follow a “regular track,” inducing and sustaining ILC2 function with comparatively delayed kinetics.

                  How do neuronal cells sense environmental perturbations to instruct immune responses? Enteric neurons and glial cells can sense microbial products, parasites, and host alarmins through myeloid differentiation primary response 88 (MYD88) signaling in the neuronal cells to produce ILC-activating neuroregulators (5, 6). Although this local neuronal-innate immune cell interaction is critical during pathogen insults (5, 6), the nature of the efferent nervous signals (impulses emerging from the central nervous system) that may also regulate peripheral immune cells remain elusive. Nevertheless, perhaps local neural networks function as relay stations of environmental stimuli, amplifying these local insults through the increased expression of neuroregulators that maximize rapid tissue-protective responses of immune cells.

                  Understanding the broader roles of NICUs in the regulation of tissue homeostasis in the context of health and disease is certainly a major challenge ahead. Notably, clarifying cellular and molecular players of NICUs could identify new putative therapeutic targets in the context of chronic inflammation, cancer, metabolic health, and beyond. Because pathogens and other environmental triggers have been major drivers of mammalian evolution, connecting immune and neuronal responses may therefore be considered a paradigm of coordinated multi-tissue physiology, suggesting that throughout evolution, neuroimmune networks may have also been selected at an organismal level. The neuroimmune system is out there to be explored.
                  I am passionate about this. I'm a generalist which in practice means that I have had to up my game to approaching specialist level in order to deal with complex cases who have been discharged from specialist care. I am seeing far too many cases in which the primary complaint is pain, because manual therapists have taken a reductionist approach and then dumped the patient when they have failed explain pain and manual therapies.

                  Patients who have failed physiotherapy will try anything and often end up with alternative therapists, who after months of slow or no progress will refer to another alternative therapist. This afternoon, I was told that a massage therapist was looking to refer someone for "craniosacral therapy" and would this be something I would be interested in taking on!!!!!!!!! If someone had told me thirty years ago when I was running an outpatient department, that decades into the future. I would be considered as someone supplementary to massage therapy, I would have thought that I had entered a parallel universe.........perhaps I have.

                  CauseHealth is working along the right lines in consideration of the patient and their environment, and I recommend that anyone who is prepared to put the work in, attend Dr Thacker's courses and do the follow up reading,
                  Jo Bowyer
                  Chartered Physiotherapist Registered Osteopath.
                  "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                  Comment


                  • #11
                    Structure and Distribution of an Unrecognized Interstitium in Human Tissues

                    https://www.nature.com/articles/s41598-018-23062-6

                    The interstitial space is the primary source of lymph and is a major fluid compartment in the body. While the anatomy and composition of the interstitial space between cells is increasingly understood, the existence, location, and structure of larger inter- and intra-tissue spaces is described only vaguely in the literature. This is particularly important in reference to “third spacing” (interstitial fluid build-up) and when considering overall interstitial fluid flow and volume, which have not been well studied1.

                    Advances in in vivo microscopy offer the potential to identify new, functionally-relevant anatomical structures in humans. Lymphatic vessels in the brain, for example, were recently identified for the first time using in vivo multiphoton microscopy imaging through a thinned skull preparation2. Probe-based Confocal Laser Endomicroscopy (pCLE) is an in vivo imaging technology that provides real-time histologic assessment of tissue structures during endoscopy, generally after intravenous injection of fluorescein. We and others have observed that, in the extrahepatic bile ducts and pancreatic ducts, pCLE at the fixed focal length of 60–70 μm shows a submucosal “reticular pattern” (Fig. 1A,B) consisting of 20 μm wide dark branching bands surrounding large, fluorescein-filled polygonal spaces3. These have no obvious correlate to known structures. Although endoscopists have suggested that this network represents capillaries or lymphangioles3, neither structure can explain the reticular pattern of dark bands and bright, fluid-filled spaces.
                    We hypothesized that this pattern reflects an extension of the intercellular interstitial space. We carried out an in-depth study using pCLE and histology of the human extrahepatic bile duct in order to identify the microanatomic correlates of the reticular pattern. We report here the existence of a novel interstitial (i.e. pre-lymphatic) space defined by a complex lattice of thick collagen bundles. We observed similar structures when we extended our study to include the dermis, peri-arterial stroma, submucosa of the viscera (gastrointestinal tract, urinary bladder), bronchial tree of the lungs, and fascial planes of the musculoskeletal system and adipose tissue, and as a result propose a large-scale revision of the macro- and microanatomy of the human interstitium.
                    Jo Bowyer
                    Chartered Physiotherapist Registered Osteopath.
                    "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                    Comment


                    • #12
                      How one cell gives rise to an entire body

                      http://www.sciencemag.org/news/2018/...et_cid=1998037

                      Watch the clip, it's all about gene expression.

                      Jo Bowyer
                      Chartered Physiotherapist Registered Osteopath.
                      "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                      Comment


                      • #13
                        Leg exercise is critical to brain and nervous system health

                        In a new take on the exercise truism 'use it, or lose it,' researchers show neurological health is an interactive relationship with our muscles and our world

                        https://www.sciencedaily.com/release...0523080214.htm

                        "Our study supports the notion that people who are unable to do load-bearing exercises -- such as patients who are bed-ridden, or even astronauts on extended travel -- not only lose muscle mass, but their body chemistry is altered at the cellular level and even their nervous system is adversely impacted," says Dr. Raffaella Adami from the Università degli Studi di Milano, Italy.

                        The study involved restricting mice from using their hind legs, but not their front legs, over a period of 28 days. The mice continued to eat and groom normally and did not exhibit stress. At the end of the trial, the researchers examined an area of the brain called the sub-ventricular zone, which in many mammals has the role of maintaining nerve cell health. It is also the area where neural stem cells produce new neurons.

                        Limiting physical activity decreased the number of neural stem cells by 70 percent compared to a control group of mice, which were allowed to roam. Furthermore, both neurons and oligodendrocytes -- specialized cells that support and insulate nerve cells -- didn't fully mature when exercise was severely reduced.

                        The research shows that using the legs, particularly in weight-bearing exercise, sends signals to the brain that are vital for the production of healthy neural cells, essential for the brain and nervous system. Cutting back on exercise makes it difficult for the body to produce new nerve cells -- some of the very building blocks that allow us to handle stress and adapt to challenge in our lives.

                        "It is no accident that we are meant to be active: to walk, run, crouch to sit, and use our leg muscles to lift things," says Adami. "Neurological health is not a one-way street with the brain telling the muscles 'lift,' 'walk,' and so on."

                        The researchers gained more insight by analyzing individual cells. They found that restricting exercise lowers the amount of oxygen in the body, which creates an anaerobic environment and alters metabolism. Reducing exercise also seems to impact two genes, one of which, CDK5Rap1, is very important for the health of mitochondria -- the cellular powerhouse that releases energy the body can then use. This represents another feedback loop.

                        These results shed light on several important health issues, ranging from concerns about cardio-vascular impacts as a result of sedentary lifestyles to insight into devastating diseases, such as spinal muscular atrophy (SMA), multiple sclerosis, and motor neuron disease, among others.

                        "I have been interested in neurological diseases since 2004," says co-author Dr. Daniele Bottai, also from the Università degli Studi di Milano. "The question I asked myself was: is the outcome of these diseases due exclusively to the lesions that form on the spinal cord in the case of spinal cord injury and genetic mutation in the case of SMA, or is the lower capacity for movement the critical factor that exacerbates the disease?"

                        This research demonstrates the critical role of movement and has a range of potential implications. For example, missions to send astronauts into space for months or even years should keep in mind that gravity and load-bearing exercise play an important role in maintaining human health, say the researchers.

                        "One could say our health is grounded on Earth in ways we are just beginning to understand," concludes Bottai.
                        Jo Bowyer
                        Chartered Physiotherapist Registered Osteopath.
                        "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                        Comment


                        • #14
                          Magnifying the Brain in Motion with Every Heartbeat

                          https://neurosciencenews.com/brain-m...eartbeat-9168/
                          Jo Bowyer
                          Chartered Physiotherapist Registered Osteopath.
                          "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

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                          • #15
                            The danger of absolute thinking is absolutely clear

                            https://aeon.co/ideas/the-danger-of-...d57ae-69418129
                            Jo Bowyer
                            Chartered Physiotherapist Registered Osteopath.
                            "Out beyond ideas of wrongdoing and rightdoing,there is a field. I'll meet you there." Rumi

                            Comment

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