Difficulties, Challenges, and the Learning Curve of Avoiding Complications in Lumbar Endoscopic Spine Surgery.

Spinal endoscopy has the stigma of being reserved for only a few surgeons who can figure out how to master the steep learning curve and develop clinical practice settings where endoscopic spine surgery can thrive. In essence, endoscopic treatment of herniated discs specifically and nerve root compression in the lumbar spine in general amounts to replacing traditional open spine surgery protocols with spinal endoscopic surgery techniques. In doing so, the endoscopic spine surgeon must be confident that the degenerative spine's common painful problems can be handled with endoscopic spinal surgery techniques with at least comparable clinical results and complication rates. In this review article, the authors illustrate the difficulties and challenges of the endoscopic lumbar decompression procedure. In addition, they shed light on how to master the learning curve by systematically looking at all sides of the problem, ranging from the ergonomic aspects of the endoscopic platform and its instruments, surgical access planning, challenging clinical scenarios, complications, and sequelae, as well as the training gaps after postgraduate residency and fellowship programs.

The in vitro functional analysis of single-nucleotide polymorphisms associated with growth hormone (GH) response in children with GH deficiency.

Response to recombinant human growth hormone (r-hGH) in the first year of therapy has been associated with single-nucleotide polymorphisms (SNPs) in children with GH deficiency (GHD). Associated SNPs were screened for regulatory function using a combination of in silico techniques. Four SNPs in regulatory sequences were selected for the analysis of in vitro transcriptional activity (TA). There was an additive effect of the alleles in the four genes associated with good growth response. For rs3110697 within IGFBP3, rs1045992 in CYP19A1 and rs2888586 in SOS1, the variant associated with better growth response showed higher TA with r-hGH treatment. For rs1024531 in GRB10, a negative regulator of IGF-I signalling and growth, the variant associated with better growth response had a significantly lower TA on r-hGH stimulation. These results indicate that specific SNP variants have effects on TA that provide a rationale for their clinical impact on growth response to r-hGH therapy.

Characterization and thermogravimetric analysis of lanthanide hexafluoroacetylacetone chelates.

This work reports the thermodynamic characterizations of organometallic species as a vehicle for the rapid separation of volatile nuclear fission products via gas chromatography due to differences in adsorption enthalpy. Because adsorption and sublimation thermodynamics are linearly correlated, there is considerable motivation to determine sublimation enthalpies. A method of isothermal thermogravimetric analysis, TGA-MS and melting point analysis are employed on thirteen lanthanide 1,1,1,5,5,5-hexafluoroacetylacetone complexes to determine sublimation enthalpies. An empirical correlation is used to estimate adsorption enthalpies of lanthanide complexes on a quartz column from the sublimation data. Additionally, four chelates are characterized by SC-XRD, elemental analysis, FTIR and NMR.

Metabolites involved in glycolysis and amino acid metabolism are altered in short children born small for gestational age.

BACKGROUND: Later life metabolic dysfunction is a well-recognized consequence of being born small for gestational age (SGA). This study has applied metabolomics to identify whether there are changes in these pathways in prepubertal short SGA children and aimed to compare the intracellular and extracellular metabolome in fibroblasts derived from healthy children and SGA children with postnatal growth impairment. METHODS: Skin fibroblast cell lines were established from eight SGA children (age 1.8-10.3 y) with failure of catch-up growth and from three healthy control children. Confluent cells were incubated in serum-free media and the spent growth medium (metabolic footprint), and intracellular metabolome (metabolic fingerprint) were analyzed by gas-chromatography mass spectrometry. RESULTS: Nineteen metabolites were significantly altered between SGA and control cell lines. The greatest fold difference (FD) was seen for alanine (fingerprint FD, SGA: control 0.3, P = 0.01 and footprint FD = 0.19, P = 0.01), aspartic acid (fingerprint FD = 5.21, P = 0.01), and cystine (footprint FD = 1.66, P = 0.02). Network analysis of the differentially expressed metabolites predicted inhibition of insulin as well as growth (ERK) signaling in SGA cells. CONCLUSION: This study indicates that changes in cellular metabolism associated with both growth failure and insulin insensitivity are present in prepubertal short children born SGA.

Thermodynamic analysis of volatile organometallic fission products.

The ability to perform rapid separations in a post nuclear weapon detonation scenario is an important aspect of national security. In the past, separations of fission products have been performed using solvent extraction, precipitation, etc. The focus of this work is to explore the feasibility of using thermochromatography, a technique largely employed in superheavy element chemistry, to expedite the separation of fission products from fuel components. A series of fission product complexes were synthesized and the thermodynamic parameters were measured using TGA/DSC methods. Once measured, these parameters were used to predict their retention times using thermochromatography.

Network analysis identifies protein clusters of functional importance in juvenile idiopathic arthritis.

INTRODUCTION: Our objective was to utilise network analysis to identify protein clusters of greatest potential functional relevance in the pathogenesis of oligoarticular and rheumatoid factor negative (RF-ve) polyarticular juvenile idiopathic arthritis (JIA). METHODS: JIA genetic association data were used to build an interactome network model in BioGRID 3.2.99. The top 10% of this protein:protein JIA Interactome was used to generate a minimal essential network (MEN). Reactome FI Cytoscape 2.83 Plugin and the Disease Association Protein-Protein Link Evaluator (Dapple) algorithm were used to assess the functionality of the biological pathways within the MEN and to statistically rank the proteins. JIA gene expression data were integrated with the MEN and clusters of functionally important proteins derived using MCODE. RESULTS: A JIA interactome of 2,479 proteins was built from 348 JIA associated genes. The MEN, representing the most functionally related components of the network, comprised of seven clusters, with distinct functional characteristics. Four gene expression datasets from peripheral blood mononuclear cells (PBMC), neutrophils and synovial fluid monocytes, were mapped onto the MEN and a list of genes enriched for functional significance identified. This analysis revealed the genes of greatest potential functional importance to be PTPN2 and STAT1 for oligoarticular JIA and KSR1 for RF-ve polyarticular JIA. Clusters of 23 and 14 related proteins were derived for oligoarticular and RF-ve polyarticular JIA respectively. CONCLUSIONS: This first report of the application of network biology to JIA, integrating genetic association findings and gene expression data, has prioritised protein clusters for functional validation and identified new pathways for targeted pharmacological intervention.

Pediatric perspective on pharmacogenomics.

The advances in high-throughput genomic technologies have improved the understanding of disease pathophysiology and have allowed a better characterization of drug response and toxicity based on individual genetic make up. Pharmacogenomics is being recognized as a valid approach used to identify patients who are more likely to respond to medication, or those in whom there is a high probability of developing severe adverse drug reactions. An increasing number of pharmacogenomic studies are being published, most include only adults. A few studies have shown the impact of pharmacogenomics in pediatrics, highlighting a key difference between children and adults, which is the contribution of developmental changes to therapeutic responses across different age groups. This review focuses on pharmacogenomic research in pediatrics, providing examples from common pediatric conditions and emphasizing their developmental context.

Human growth is associated with distinct patterns of gene expression in evolutionarily conserved networks.

BACKGROUND: A co-ordinated tissue-independent gene expression profile associated with growth is present in rodent models and this is hypothesised to extend to all mammals. Growth in humans has similarities to other mammals but the return to active long bone growth in the pubertal growth spurt is a distinctly human growth event. The aim of this study was to describe gene expression and biological pathways associated with stages of growth in children and to assess tissue-independent expression patterns in relation to human growth. RESULTS: We conducted gene expression analysis on a library of datasets from normal children with age annotation, collated from the NCBI Gene Expression Omnibus (GEO) and EBI Arrayexpress databases. A primary data set was generated using cells of lymphoid origin from normal children; the expression of 688 genes (ANOVA false discovery rate modified p-value, q < 0.1) was associated with age, and subsets of these genes formed clusters that correlated with the phases of growth--infancy, childhood, puberty and final height. Network analysis on these clusters identified evolutionarily conserved growth pathways (NOTCH, VEGF, TGFB, WNT and glucocorticoid receptor--Hyper-geometric test, q < 0.05). The greatest degree of network 'connectivity' and hence functional significance was present in infancy (Wilcoxon test, p < 0.05), which then decreased through to adulthood. These observations were confirmed in a separate validation data set from lymphoid tissue. Similar biological pathways were observed to be associated with development-related gene expression in other tissues (conjunctival epithelia, temporal lobe brain tissue and bone marrow) suggesting the existence of a tissue-independent genetic program for human growth and maturation. CONCLUSIONS: Similar evolutionarily conserved pathways have been associated with gene expression and child growth in multiple tissues. These expression profiles associate with the developmental phases of growth including the return to active long bone growth in puberty, a distinctly human event. These observations also have direct medical relevance to pathological changes that induce disease in children. Taking into account development-dependent gene expression profiles for normal children will be key to the appropriate selection of genes and pathways as potential biomarkers of disease or as drug targets.

Biologically flavored perspectives on Garmezian resilience.

Norman Garmezy devoted the better part of four decades developing and promoting the construct of resilience for developmental psychopathology. He proposed resilience as a paradigm to guide the understanding of how people can transcend adversity and go on to live healthy, productive lives. This tribute to Norman starts with a look at the early context for his work during his distinguished tenure in the Department of Psychology at the University of Minnesota. Resilience constructs are then compared from interdisciplinary perspectives across a variety of biological and physical sciences. All of these perspectives lead to similar conclusions: resilience is not a thing but a process. Furthermore, the processes are the product of energy-hungry systems. Finally, these insights are applied to difficult to modify maladaptive behaviors raising the question of a dark side to resilience.

Unstable thoracolumbar burst fractures: anterior-only versus short-segment posterior fixation.

Operative management of a thoracolumbar burst fracture varies according to many factors. Fracture morphology, neurologic status, and surgeon preference play major roles in deciding upon anterior, posterior, or combined approaches. Optimizing neural decompression while providing stable internal fixation over the least number of spinal segments is the goal. Short-segment constructs via a single-stage approach (anterior versus posterior) have become viable options with advances in instrumentation and techniques. This study compares anterior-only fixation utilizing a corpectomy strut graft and a modern thoracolumbar plating system with a posterior-only construct using pedicle screws and load sharing hooks for the treatment of unstable burst fractures. Functional outcome and sagittal plane restoration and maintenance of sagittal plane alignment were evaluated. Fifty-three patients with unstable burst fractures were assessed with 40 undergoing an anterior-only construct and 13 having a short-segment posterior-only construct. The posterior-only group had no hardware failures; however, the loss of sagittal plane correction averaged 8.1 degrees, whereas the anterior-only group averaged only a 1.8-degree increase in sagittal plane kyphosis. Both techniques resulted in statistically significant initial improvement in sagittal alignment; however, the posterior short-segment group lost this statistical significance at follow-up whereas the anterior-only group continued to demonstrate statistically significant improvement in sagittal alignment at follow-up compared to preoperative measurements.

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis.

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons.

Human development: biological and genetic processes.

Adaptation is a central organizing principle throughout biology, whether we are studying species, populations, or individuals. Adaptation in biological systems occurs in response to molar and molecular environments. Thus, we would predict that genetic systems and nervous systems would be dynamic (cybernetic) in contrast to previous conceptualizations with genes and brains fixed in form and function. Questions of nature versus nurture are meaningless, and we must turn to epigenetics--the way in which biology and experience work together to enhance adaptation throughout thick and thin. Defining endophenotypes--road markers that bring us closer to the biological origins of the developmental journey--facilitates our understanding of adaptive or maladaptive processes. For human behavioral disorders such as schizophrenia and autism, the inherent plasticity of the nervous system requires a systems approach to incorporate all of the myriad epigenetic factors that can influence such outcomes.

Focal adhesion kinase: in command and control of cell motility.

A central question in cell biology is how membrane-spanning receptors transmit extracellular signals inside cells to modulate cell adhesion and motility. Focal adhesion kinase (FAK) is a crucial signalling component that is activated by numerous stimuli and functions as a biosensor or integrator to control cell motility. Through multifaceted and diverse molecular connections, FAK can influence the cytoskeleton, structures of cell adhesion sites and membrane protrusions to regulate cell movement.

Molluscum contagiosum.

Molluscum contagiosum is a disease caused by a poxvirus of the Molluscipox virus genus that produces a benign self-limited papular eruption of multiple umbilicated cutaneous tumors. This common viral disease is confined to the skin and mucous membranes. Transmission requires direct contact with infected hosts or contaminated fomites. It is generally thought to infect humans exclusively, but there are a few isolated reports of Molluscum contagiosum occurring in chickens, sparrows, pigeons, chimpanzees, kangaroos, a dog, and a horse. The infection is found worldwide and has a higher incidence in children, sexually active adults, and those who are immunodeficient.