Relationship Between the Development of the Spinal Canal and the Etiopathogenesis of Lumbar Spinal Stenosis

INTRODUCTION: The presence of a pre-existing narrow spinal canal may have an important place in the ethiopathogenesis of lumbar spinal stenosis. By consequence the study of the development of the spinal canal is crucial. The first goal of this work is to do a comprehensive literature search and to give an essential view on the development of spinal canal and its depending factors studied until now. The second goal is to give some considerations and hypothesize new leads for clinically useful researches. MATERIALS AND METHODS: A bibliographical research was executed using different search engines: PubMed, Google Schoolar ©, Ovid ® and Web Of Science ©. Free sources and avaible from the University of Lausanne (UNIL) and Centre Hospitalier Universitaire Vaudois (CHUV) were used. At the end of the bibliographic researches 114 references were found, 85 were free access and just 41 were cited in this work. Most of the found references are in English or in French. RESULTS AND DISCUSSION: The spinal canal is principally limited by the vertebrae which have a mesodermal origin. The nervous (ectodermal) tissue significantly influences the growth of the canal. The most important structure participating in the spinal canal growth is the neurocentral synchondrosis in almost the entire vertebral column. The fusion of the half posterior arches seems to have less importance for the canal size. The growth is not homogeneous but, depends on the vertebral level. Timing, rate and growth potentials differ by regions. Especially in the case of the lumbar segment, there is a craniocaudal tendency which entails a greater post-natal catch-up growth for distal vertebrae. Trefoil-shape of the L5 canal is the consequence of a sagittal growth deficiency. The spinal canal shares some developmental characteristics with different structures and systems, especially with the central nervous system. It may be the consequence of the embryological origin. It is supposed that not all the related structures would be affected by a growth impairment because of the different catch-up potentials. Studies found that narrower spinal canals might be related with cardiovascular and gastrointestinal symptoms, lower thymic function, bone mineral content, dental hypoplasia and Harris' lines. Anthropometric correlations found at birth disappear during the pediatric age. All factors which can affect bone and nervous growth might be relevant. Genetic predispositions are the only factors that can never be changed but the real impact is to ascertain. During the antenatal period, all the elements determining a good supply of blood and oxygen may influence the vertebral canal development, for example smoking during pregnancy. Diet is a crucial factor having an impact on both antenatal and postnatal growth. Proteins intake is the only proved dietetic relationship found in the bibliographic research of this work. The mechanical effects due to locomotion changes are unknown. Socioeconomic situation has an impact on several influencing factors and it is difficult to study it owing to numerous bias. CONCLUSIONS: A correct growth of spinal canal is evidently relevant to prevent not-degenerative stenotic conditions. But a "congenital" narrower canal may aggravate degenerative stenosis. This concerns specific groups of patient. If the size of the canal is highly involved in the pathogenesis of common back pains, a hypothetical measure to prevent developmental impairments could have a not- negligible impact on the society. It would be interesting to study more about dietetic necessities for a good spinal canal development. Understanding the relationship between nervous tissues and vertebra it might be useful in identifying what is needed for the ideal development. Genetic importance and the post-natal influences of upright standing on the canal growth remain unsolved questions. All these tracks may have a double purpose: knowing if it is possible to decrease the incidence of narrower spinal canal and consequently finding possible preventive measures. The development of vertebral canal is a complex subject which ranges over a wide variety of fields. The knowledge of this subject is an indispensable tool to understand and hypothesize the influencing factors that might lead to stenotic conditions. Unfortunately, a lack of information makes difficult to have a complete and satisfactory interdisciplinary vision.

The international development of the RGHQoL: a quality of life measure for recurrent genital herpes.

This paper describes the international development and psychometric testing of the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL), a condition-specific quality of life (QoL) instrument. The theoretical foundation for the measure is the needs-based model of QoL and the content of the instrument was derived from in-depth qualitative interviews with relevant patients in the UK. Versions of the RGHQoL were required for the UK, USA, Italy, Germany, France and Denmark for use in international clinical trials. The results indicate that the final 20 item measure has good reliability, internal consistency and validity for all language versions. A small responsiveness study in Denmark suggested that the measure is sensitive to changes in QoL associated with the initiation of suppression treatment for recurrent genital herpes (RGH). It is concluded that the RGHQoL is a valuable instrument for inclusion in clinical trials. The psychometric properties of the instrument are such that it may also be used to monitor the progress of individual patients.

The hotel industry and its importance in the technical and economic development of a region : the Lake Geneva case (1852-1914)

The historiography dedicated to tourism has emphasised how some socio-economic evolutions such as urbanisation, mechanisation of transport or the advent of leisure time in society have supported pleasure trips and therefore the development of the hotel industry. On the contrary, the research has too often neglected or at least minimised the impact of the hotel sector on a region's development. This contribution seeks to fill this gap by analysing the Geneva Lake region, one of the most important birthplaces of the European tourism. In this space not much touched by the first industrial revolution, the hotel business has in fact played the role of an economic motor, stimulating investment and employment. This dynamism provoked a domino effect on several other sectors of the economy (industry, bulding sector, banking). To please their customers, the hoteliers have not only given impulses on housing modernisation, but also to the revitalisation of transport, energy and communication networks. The necessity to remain on the state-of-the-art of technical issues, with the concern of competitiveness, has called forth an acceleration of the technology transfer and stimulated the constitution of technical know-how.

Role of the NALP3 Inflammasome in the Development of Two-Kidney, One Clip Hypertension in Mice

Objective: The NALP3 inflammasome functions as a sensor of danger signals and triggers processing and release of IL-1b. Mutations of NALP3 are responsible for the cryopyrin associated periodic syndromes, a group of autoinflammatory disorders that respond to IL1 inhibition. Genetic studies have also linked NALP3 to hypertension in man, but the mechanism is not understood. The aim of this study is to investigate the role of NAPL3 inflammasome in the development of hypertension in an animal model. Design and Method: Six-week old male WT and NALP3 KO mice were used for generating a two-kidney, one clip (2K1C) renovascular hypertension. A U-shaped stainless steel clip (O^ ¼0.12mm) was placed on left renal artery under anaesthesia. The same surgery without clipping was performed in sham mice. At week 6 and 12 after the clipping, intra-arterial blood pressure (BP) was measured in conscious mice. Blood was collected for plasma renin analysis. Heart and kidney were excised and stored for molecular and morphological examinations. n¼5-6 mice per group. Data are mean_SEM. Results: Mean BP was significantly increased at week 6 and 12 in WT-2K1C mice compared to WT-sham group (MBPweek6: 138_2 vs.124_3 mmHg, p<0.01 and MBPweek12: 141_5 vs.122_3 mmHg, p<0.01) followed with an significant increase in heart weight (HW) and a decrease in clipped kidney weight indices in WT-2K1C mice compared to the WT-sham (HW/ BWweek6: 4.65_0.04 vs. 3.99_0.12 mg/g, p<0.001 and HW/BWweek12: 4.94_0.15 vs. 4.22_0.12 mg/g, p<0.001). Interestingly, NALP3 KO-2K1C mice did not develop hypertension. The MBP of KO-2K1C mice was comparable to the KO-sham (MBPweek6: 122_3 vs. 119_3 mmHg, p>0.05 and MBPweek6: 128_5 vs.122_4 mmHg, p>0.05). There was also no significant change in heart and kidney weight indices between KO- 2K1C and KO-sham mice. Conclusion: The preliminary results suggest that absence of NALP3 protects mice from the development of renin-dependent hypertension. Further molecular and morphological examinations are ongoing for the confirmation and mechanism explanation.

Development of a system for 3D high-resolution seismic reflection profiling on lakes

A high-resolution three-dimensional (3D) seismic reflection system for small-scale targets in lacustrine settings has been developed. Its main characteristics include navigation and shot-triggering software that fires the seismic source at regular distance intervals (max. error of 0.25 m) with real-time control on navigation using differential GPS (Global Positioning System). Receiver positions are accurately calculated (error < 0.20 m) with the aid of GPS antennas attached to the end of each of three 24-channel streamers. Two telescopic booms hold the streamers at a distance of 7.5 m from each other. With a receiver spacing of 2.5 m, the bin dimension is 1.25 m in inline and 3.75 m in crossline direction. To test the system, we conducted a 3D survey of about 1 km(2) in Lake Geneva, Switzerland, over a complex fault zone. A 5-m shot spacing resulted in a nominal fold of 6. A double-chamber bubble-cancelling 15/15 in(3) air gun (40-650 Hz) operated at 80 bars and 1 m depth gave a signal penetration of 300 m below water bottom and a best vertical resolution of 1.1 m. Processing followed a conventional scheme, but had to be adapted to the high sampling rates, and our unconventional navigation data needed conversion to industry standards. The high-quality data enabled us to construct maps of seismic horizons and fault surfaces in three dimensions. The system proves to be well adapted to investigate complex structures by providing non-aliased images of reflectors with dips up to 30 degrees.

Reduced development of CD4-8-B220+ T cells but normal autoantibody production in lpr/lpr mice lacking major histocompatibility complex class I molecules.

The lpr gene has recently been shown to encode a functional mutation in the Fas receptor, a molecule involved in transducing apoptotic signals. Mice homozygous for the lpr gene develop an autoimmune syndrome accompanied by massive accumulation of double-negative (DN) CD4-8-B220+ T cell receptor-alpha/beta+ cells. In order to investigate the origin of these DN T cells, we derived lpr/lpr mice lacking major histocompatibility complex (MHC) class I molecules by intercrossing them with beta 2-microglobulin (beta 2m)-deficient mice. Interestingly, these lpr beta 2m-/- mice develop 13-fold fewer DNT cells in lymph nodes as compared to lpr/lpr wild-type (lprWT) mice. Analysis of anti-DNA antibodies and rheumatoid factor in serum demonstrates that lpr beta 2m-/- mice produce comparable levels of autoantibodies to lprWT mice. Collectively our data indicate that MHC class I molecules control the development of DN T cells but not autoantibody production in lpr/lpr mice and support the hypothesis that the majority of DN T cells may be derived from cells of the CD8 lineage.

The efficiency of a novel delivery system (PEI600-Tat) in development of potent DNA vaccine using HPV16 E7 as a model antigen.

DNA vaccination is a promising approach for inducing both humoral and cellular immune responses. The mode of plasmid DNA delivery is critical to make progress in DNA vaccination. Using human papillomavirus type 16 E7 as a model antigen, this study evaluated the effect of peptide-polymer hybrid including PEI600-Tat conjugate as a novel gene delivery system on the potency of antigen-specific immunity in mice model. At ratio of 10:50 PEI-Tat/E7DNA (w/w), both humoral and cellular immune responses were significantly enhanced as compared with E7DNA construct and induced Th1 response. Therefore, this new delivery system could have promising applications in gene therapy.

The development of a stable oral solution of captopril for paediatric patients

Study objectives: Many major drugs are not available in paediatric form. The aim of this study was to develop a stable liquid solution of captopril for oral paediatric use allowing individualised dosage and easy administration to newborn and young patients. Methods: A specific HPLC-UV method was developed. In a pilot study, a number of formulations described in the literature as affording one-month stability were examined. In the proper long-term study, the formulation that gave the best results was then prepared in large batches and its stability monitored for two years at 5°C and room temperature, and for one year at 40°C. Results: Most formulations described in the literature were found wanting in our pilot study. A simple solution of the drug (1 mg/mL) in purified water (European Pharmacopeia) containing 0.1% disodium edetate (EDTA-Na) as preservative proved chemically and microbiologically stable at 5°C and room temperature for two years. Conclusion: The proposed in-house formulation fulfils stringent criteria of purity and stability and is fully acceptable for oral administration to newborn and young patients.

Development of an enzyme-linked immunosorbent assay for serodiagnosis of ringworm infection in cattle.

The aim of this study was to develop an in-house enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of ringworm infection in cattle. We used available recombinant forms of Trichophyton rubrum dipeptidyl peptidase V (TruDppV) and T. rubrum leucin aminopeptidase 2 (TruLap2), which are 98% identical to Trichophyton verrucosum orthologues. Field serum samples from 135 cattle with ringworm infection, as confirmed by direct microscopy, fluorescence microscopy, and PCR, and from 55 cattle without any apparent skin lesions or history of ringworm infection that served as negative controls were used. Sensitivities, specificities, and positive and negative predictive values were determined to evaluate the diagnostic value of our ELISA. Overall, the ELISAs based on recombinant TruDppV and TruLap2 discriminated well between infected animals and healthy controls. Highly significant differences (P < 0.0001, Mann-Whitney U test) were noted between optical density values obtained when sera from infected versus control cattle were tested. The ELISA developed for the detection of specific antibodies against DppV gave 89.6% sensitivity, 92.7% specificity, a 96.8% positive predictive value, and a 78.4% negative predictive value. The recombinant TruLap2-based ELISA displayed 88.1% sensitivity, 90.9% specificity, a 95.9% positive predictive value, and a 75.7% negative predictive value. To the best of our knowledge, this is the first ELISA based on recombinant antigens for assessing immune responses to ringworm infection in cattle; it is particularly suitable for epidemiological studies and also for the evaluation of vaccines and/or vaccination procedures.

Le développement des interactions triadiques mère-père-enfant = The development of mother-father-child triadic interactions

Cet article présente un état des lieux des recherches menées selon le paradigme de « l'alliance familiale » sur le développement des interactions triadiques mère-père-enfant lors de la transition à la parentalité. Ces recherches ont montré tout d'abord que la qualité des interactions triadiques tend à être stable au cours des deux premières années de vie de l'enfant, et qu'elle peut être anticipée durant la grossesse par l'observation d'interactions dans une simulation de jeu triadique. Ensuite, elles ont montré qu'une altération de ces interactions a une influence sur le développement de l'enfant qui se manifeste tout au long des cinq premières années, tant au niveau affectif que cognitif (par exemple : la capacité d'attention triangulaire lors des premiers mois, ou le développement de la théorie de l'esprit et les difficultés de comportements à cinq ans). Cette influence s'exerce en plus de celle d'autres variables comme la relation d'attachement mère-enfant, ou la personnalité de l'enfant lui-même évaluée selon son tempérament. La triade constitue donc un contexte de développement en soi qui doit être pris en compte dans la prise en charge et l'intervention auprès de jeunes enfants.This paper presents the main results of researches on the development of mother-father-child triadic interactions during the transition to parenthood, according to the « family alliance » model. First, these researches have shown that the quality of triadic interactions tends to be stable through the first two years, and that it can be predicted during pregnancy by observation of a simulated triadic play. Then, they have shown that disturbances in triadic interactions have an impact on several affective and cognitive developmental outcomes for the child throughout the first five years (for example, the triangular attention capacity during the first months, or the development of theory of mind and externalized behaviors at age five). This impact is specific, and triadic interactions exert an influence on the development of the child over and above other variables like the mother-child attachment relationship, or the personality of the child assessed in terms of temperament. The triad constitutes then a context of development per se which has to be taken into account when working clinically with young children.

Development of the Crohn's disease digestive damage score, the Lémann score.

Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage. (Inflamm Bowel Dis 2011).

Difference in distribution of microtubule-associated proteins 5a and 5b during the development of cerebral cortex and corpus callosum in cats: dependence on phosphorylation.

MAP5, a microtubule-associated protein characteristic of differentiating neurons, was studied in the developing visual cortex and corpus callosum of the cat. In juvenile cortical tissue, during the first month after birth, MAP5 is present as a protein doublet of molecular weights of 320 and 300 kDa, defined as MAP5a and MAP5b, respectively. MAP5a is the phosphorylated form. MAP5a decreases two weeks after birth and is no longer detectable at the beginning of the second postnatal month; MAP5b also decreases after the second postnatal week but more slowly and it is still present in the adult. In the corpus callosum only MAP5a is present between birth and the end of the first postnatal month. Afterwards only MAP5b is present but decreases in concentration more than 3-fold towards adulthood. Our immunocytochemical studies show MAP5 in somata, dendrites and axonal processes of cortical neurons. In adult tissue it is very prominent in pyramidal cells of layer V. In the corpus callosum MAP5 is present in axons at all ages. There is strong evidence that MAP5a is located in axons while MAP5b seems restricted to somata and dendrites until P28, but is found in callosal axons from P39 onwards. Biochemical experiments indicate that the state of phosphorylation of MAP5 influences its association with structural components. After high speed centrifugation of early postnatal brain tissue, MAP5a remains with pellet fractions while most MAP5b is soluble. In conclusion, phosphorylation of MAP5 may regulate (1) its intracellular distribution within axons and dendrites, and (2) its ability to interact with other subcellular components.

Development of a control banding tool for nanomaterials

Control banding (CB) can be a useful tool for managing the potential risks of nanomaterials. The here proposed CB, which should be part of an overall risk control strategy, groups materials by hazard and emission potential. The resulting decision matrix proposes control bands adapted to the risk potential levels and helps define an action plan. If this plan is not practical and financially feasible, a full risk assessment is launched. The hazard banding combines key concepts of nanomaterial toxicology: translocation across biological barriers, fibrous nature, solubility, and reactivity. Already existing classifications specific to the nanomaterial can be used "as is." Otherwise, the toxicity of bulk or analogous substances gives an initial hazard band, which is increased if the substance is not easily soluble or if it has a higher reactivity than the substance. The emission potential bands are defined by the nanomaterials' physical form and process characteristics. Quantities, frequencies, and existing control measures are taken into account during the definition of the action plan. Control strategies range from room ventilation to full containment with expert advice. This CB approach, once validated, can be easily embedded in risk management systems. It allows integrating new toxicity data and needs no exposure data. [Authors]