Is Osteogenic Differentiation of Human Nucleus Pulposus Cells a Possibility for Biological Spinal Fusion?

Objective The purpose of this study was to investigate whether a simple, biologically robust method for inducing calcification of degenerate intervertebral discs (IVD) could be developed to provide an alternative treatment for patients requiring spinal fusion. Design Nucleus pulposus (NP) cells isolated from 14 human IVDs were cultured in monolayer and exposed to osteogenic medium, 1,25-dihydroxyvitamin D3 (VitD3), parathyroid hormone (PTH), and bone morphogenic proteins (BMPs) 2/7 to determine if they could become osteogenic. Similarly explant cultures of IVDs from 11 patients were cultured in osteogenic media with and without prior exposure to VitD3 and BMP-2. Osteogenic differentiation was assessed by alkaline phosphatase activity and areas of calcification identified by alizarin red or von Kossa staining. Expression of osteogenic genes during monolayer culture was determined using polymerase chain reaction and explant tissues assessed for BMP inhibitors. Human bone marrow-derived mesenchymal stromal cells (MSCs) were used for comparison. Results Standard osteogenic media was optimum for promoting mineralization by human NP cells in monolayer. Some osteogenic differentiation was observed with 10 nM VitD3, but none following application of PTH or BMPs. Regions of calcification were detected in 2 of the eleven IVD tissue explants, one cultured in osteogenic media and one with the addition of VitD3 and BMP-2. Conclusions Human NP cells can become osteogenic in monolayer and calcification of the extracellular matrix can also occur, although not consistently. Inhibitory factors within either the cells or the extracellular matrix may hinder osteogenesis, indicating that a robust biological fusion at this time requires further optimization

Primary angiosarcoma of the ovary with prominent fibrosis of the ovarian stroma. Case report of an 81-year old patient

Primary angiosarcoma of the ovary (AS) is a rare entity with only 31 reported cases. The majority are pure angiosarcomas, the remainder are associated either with teratomas or conventional epithelial tumors. More than 50% of ovarian AS are disseminated at the time of diagnosis, the minority is detected in stage I. The prognosis of ovarian angiosarcoma in general is poor. Most reports refer to younger individuals, aged from 7 to 46 years, and only 2 case reports could be found for patients older than 64 years. Here we present a very unusual case of angiosarcoma in a 81-year-old patient

Clinical practice: Protein-losing enteropathy in children

Protein-losing enteropathy (PLE) is a rare complication of a variety of intestinal disorders characterized by an excessive loss of proteins into the gastrointestinal tract due to impaired integrity of the mucosa. The clinical presentation of patients with PLE is highly variable, depending upon the underlying cause, but mainly consists of edema due to hypoproteinemia. While considering PLE, other causes of hypoproteinemia such as malnutrition, impaired synthesis, or protein loss through other organs like the kidney, liver, or skin, have to be excluded. The disorders causing PLE can be divided into those due to protein loss from intestinal lymphatics, like primary intestinal lymphangiectasia or congenital heart disease and those with protein loss due to an inflamed or abnormal mucosal surface. The diagnosis is confirmed by increased fecal concentrations of alpha-1-antitrypsin. After PLE is diagnosed, the underlying cause should be identified by stool cultures, serologic evaluation, cardiac screening, or radiographic imaging. Treatment of PLE consists of nutrition state maintenance by using a high protein diet with supplement of fat-soluble vitamins. In patients with lymphangiectasia, a low fat with medium chain triglycerides (MCT) diet should be prescribed. Besides dietary adjustments, appropriate treatment for the underlying etiology is necessary and supportive care to avoid complications of edema. PLE is a rare complication of various diseases, mostly gastrointestinal or cardiac conditions that result into loss of proteins in the gastrointestinal tract. Prognosis depends upon the severity and treatment options of the underlying disease

Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans

Translation of hundreds of small ORFs (smORFs) of less than 100 amino acids has recently been revealed in vertebrates and Drosophila. Some of these peptides have essential and conserved cellular functions. In Drosophila, we have predicted a particular smORF class encoding ~80 aa hydrophobic peptides, which may function in membranes and cell organelles. Here, we characterise hemotin, a gene encoding an 88aa transmembrane smORF peptide localised to early endosomes in Drosophila macrophages. hemotin regulates endosomal maturation during phagocytosis by repressing the cooperation of 14-3-3ζ with specific phosphatidylinositol (PI) enzymes. hemotin mutants accumulate undigested phagocytic material inside enlarged endo-lysosomes and as a result, hemotin mutants have reduced ability to fight bacteria, and hence, have severely reduced life span and resistance to infections. We identify Stannin, a peptide involved in organometallic toxicity, as the Hemotin functional homologue in vertebrates, showing that this novel regulator of phagocytic processing is widely conserved, emphasizing the significance of smORF peptides in cell biology and disease

Neutrality and Robustness in Evo-Devo: Emergence of Lateral Inhibition

Embryonic development is defined by the hierarchical dynamical process that translates genetic information (genotype) into a spatial gene expression pattern (phenotype) providing the positional information for the correct unfolding of the organism. The nature and evolutionary implications of genotype–phenotype mapping still remain key topics in evolutionary developmental biology (evo-devo). We have explored here issues of neutrality, robustness, and diversity in evo-devo by means of a simple model of gene regulatory networks. The small size of the system allowed an exhaustive analysis of the entire fitness landscape and the extent of its neutrality. This analysis shows that evolution leads to a class of robust genetic networks with an expression pattern characteristic of lateral inhibition. This class is a repertoire of distinct implementations of this key developmental process, the diversity of which provides valuable clues about its underlying causal principles

A randomized controlled pilot study of a brief web-based mindfulness training

Background: Mindfulness has been shown to be effective in treating various medical and mental problems. Especially its incorporation in cognitive-behavioural interventions has improved long-term outcomes of those treatments. It has also been shown, that brief mindfulness-based trainings are effective in reducing distress. There have been few web-based interventions incorporating mindfulness techniques in their manual and it remains unclear whether a brief web-based mindfulness intervention is feasible. Methods: Out of 50 adults (different distress levels; exclusion criteria: < 18 years, indication of psychotic or suicidal ideation in screening) who were recruited via e-mail and screened online, 49 were randomized into an immediate 2-weeks-treatment group (N = 28) or a waitlist-control group (N = 21), starting with a 2-week delay. Distress (BSI), perceived stress (PSQ), mindfulness (FMI), as well as mood and emotion regulation (PANAS/SEK-27) were measured at pre-, post- and 3-month follow-up (3MFU). Intention-to-treat analyses using MI for missing data and per-protocol analyses (≥ 50% attendance) were performed. Results: 26 participants of the treatment group completed post-measures. Most measures under ITT-analysis revealed no significant improvement for the treatment group, but trends with medium effect sizes for PSQ (d = 0.46) and PANASneg (d = 0.50) and a small, non-significant effect for FMI (d = 0.29). Per-protocol analyses for persons who participated over 50% of the time revealed significant treatment effects for PSQ (d = 0.72) and PANASneg (d = 0.77). Comparing higher distressed participants with lower distressed participants, highly distressed participants seemed to profit more of the training in terms of distress reduction (GSI, d = 0.85). Real change (RCI) occurred for PSQ in the treatment condition (OR = 9). Results also suggest that participants continued to benefit from the training at 3MFU. Conclusion: This study of a brief web-based mindfulness training indicates that mindfulness can be taught online and may improve distress, perceived stress and negative affect for regular users. Although there were no significant improvements, but trends, for most measures under ITT, feasibility of such a program was demonstrated and also that persons continued to use techniques of the training in daily life

The lived experiences of experienced Vipassana Mahasi meditators: an interpretative phenomenological analysis.

Research into the effects and mechanisms of mindfulness training draws predominantly on quantitative research. There is a lack of understanding about the subjective experiences of experienced mindfulness meditators, which may provide additional insights into the effects, processes and context of mindfulness training. This qualitative study explored the lived experiences of a novel group of experienced mindfulness meditators who practise Vipassana Mahasi (VM) meditation. The study aimed to understand how experienced VM practitioners make sense of the effects of practice and what processes they ascribe to it. Participants attended semistructured interviews, and their responses were analysed using interpretative phenomenological analysis. Results yielded overarching themes including (a) improvements in hedonic and eudaimonic well-being; (b) insights into self, others and perception of reality; (c) attaining equanimity; and (d) physical and interpersonal difficulties. Participants perceived VM as a ‘cleansing’ process whereby maladaptive responses were eliminated through mindfulness, other supportive mental qualities, decentering and nonattachment. The findings revealed a complex and dynamic set of interdependent outcomes and processes, which are reinforced by Buddhist teachings and ethical practices. This study highlights the need for additional interdisciplinary research into topics such as insight generation and supportive mental qualities cultivated during VM, novel states of well-being informed by Buddhist constructs and interpersonal difficulties related to long-term practice. Findings also suggest that incorporating Buddhist teachings and ethics into mindfulness-based interventions may enhance practitioner understanding and implementation of meditation techniques.N/

Specialization Can Drive the Evolution of Modularity

Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations