Wegener's granulomatosis in Finland in 1981-2000

Objectives: Wegener s granulomatosis (WG) is a vasculitis with a predilection for the airways and kidneys. An increasing incidence and improved prognosis of WG has been shown. The aim of this study was to evaluate the incidence, clinical presentation, diagnostic delay, risk of dialysis-dependent renal insufficiency and mortality of WG in 1981-2000. Patients and methods: Data was retrieved from the Finnish hospital discharge register and hospital case reports. Patients diagnosed with WG in 1981-2000 were included, and their demographic and clinical data recorded. The patients were crossed with the national kidney dialysis register and the national mortality statistics. Results: A total of 492 patients (243 ♂ , 249 ♀) were diagnosed at a mean age of 54 years (SD 18). The incidence increased from 1.9 to 9.3/ million/ year. The median diagnostic delay decreased from 17 to 4 months. Patients presented most often with symptoms of the ear, nose and throat (ENT) (45%), lung (36%), musculoskeletal system (22%) and kidney (11%). Initial lung involvement, constitutional symptoms, high erythrocyte sedimentation rate (ESR) and high ELK scores [(number of simultaneously involved organ groups (ENT, Lung, Kidney)] were associated with a shorter diagnostic delay. Medical treatment of WG patients remained similar in the 1980s and 1990s. Almost 90% of patients received cyclophosphamide (CYC) and more than 90% glucocorticoid medication at some point during the course of the disease. Eighty-four patients (17%) needed dialysis. Initial renal involvement and elevated serum creatinine values were related to an increased risk of dialysis-dependent kidney disease. In two-thirds of the patients, renal impairment was reversible. Dialysis became chronic (>3 months) in 32 patients (6.5%). Nineteen patients (3.9%) received a kidney transplant. Altogether 203 patients (99 men, 104 women) died before 30 June 2005. WG was the underlying cause of death in 37%. The crude one-year and five-year survival rates were 83.3% and 74.2%, respectively. The standardized mortality ratio was 3.43 (95% CI = 2.98 to 3.94). Older age and elevated creatinine level at diagnosis predicted shorter survival. ENT symptoms at presentation and treatment with CYC were associated with better outcome. There was no additional risk associated with male gender or with either of the decades (1981-1990 and 1991-2000) Conclusions: In 1981-2000, the incidence of WG increased ca. 4.5-fold and diagnostic delay decreased to ca. one-fourth, reflecting increased recognition of the disease and improved diagnostic means. WG patients are at great risk of developing dialysis-dependent renal insufficiency and an increased risk of dying. During the study period the treatment of WG did not change markedly, nor did the prognosis improve.

Snoring and sleep apnea in children

Snoring is a primary and major clinical symptom of upper airway obstruction during sleep. Sleep-disordered breathing ranges from primary snoring to significant partial upper airway obstruction, and obstructive sleep apnea. Adult snoring and obstructive sleep apnea have been extensively studied, whereas less is known about these disorders in children. Snoring and more severe obstructive sleep apnea have been shown to have a harmful effect on the neurobehavioral development of children, but the mechanisms of this effect remains unknown. Furthermore, the correlation of this effect to objective sleep study parameters remains poor. This study evaluated the prevalence of snoring in preschool-aged children in Finland. Host and environmental risk factors, and neurobehavioral and neurocognitive symptoms of children suffering from snoring or obstructive sleep apnea were also investigated. The feasibility of acoustic rhinometry in young children was assessed. The prevalence and risk factors of snoring (I) were evaluated by a questionnaire. The random sample included 2100 children aged 1-6 years living in Helsinki. All 3- to 6-year-old children whose parents reported their child to snore always, often, or sometimes were categorized as snorers, and invited to participate to the clinical study (II-IV). Non-snoring children whose parents were willing to participate in the clinical study were invited to serve as controls. Children underwent a clinical ear-nose-throat examination. Emotional, behavioral, and cognitive performances were evaluated by Child Behavioral Checklist (CBCL), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) and NEPSY-A Developmental Neuropsychological Assessment (NEPSY). Nasal volume was measured by acoustic rhinometry, and nasal resistance by rhinomanometry. Lateral and posteroanterior cephalometry were performed. A standard overnight ambulatory polysomnography was performed in the home environment. Twenty-six healthy children were tested in order to assess the feasibility of acoustic rhinometry in young children (V). Snoring was common in children; 6.3% of children snored always or often, whereas 81.3% snored never or occasionally. No differences were apparent between snorers and non-snorers regarding age, or gender. Pediatric snoring was associated with recurrent upper respiratory infections, otitis media, and allergic rhinitis. Exposure to parental tobacco smoke, especially maternal smoking, was more common among snorers. Rhinitis was more common among children who exposured to tobacco smoke. Overnight polysomnography (PSG) was performed on 87 children; 74% showed no signs of significant upper airway obstruction during sleep. Three children had obstructive apnea/hypopnea index (OAHI) greater than 5/h. Age, gender, or a previous adenoidectomy or tonsillectomy did not correlate with OAHI, whereas tonsillar size did correlate with OAHI. Relative body weight and obesity correlated with none of the PSG parameters. In cephalometry, no clear differences or correlations were found in PSG parameters or between snorers and non-snorers. No correlations were observed between acoustic rhinometry, rhinomanometry, and PSG parameters. Psychiatric symptoms were more frequent in the snoring group than in the nonsnoring group. In particular, anxious and depressed symptoms were more prevalent in the snoring group. Snoring children frequently scored lower in language functions. However, PSG parameters correlated poorly with neurocognitive test results in these children. This study and previous studies indicate that snoring without episodes of obstructive apnea or SpO2 desaturations may cause impairment in behavioral and neurocognitive functions. The mechanism of action remains unknown. Exposure to parental tobacco smoke is more common among snorers than non-snorers, emphasizing the importance of a smoke-free environment. Children tolerated acoustic rhinometry measurements well.

Carotid Surgery : A posse ad esse non valet consequentia

According to a large body of evidence, carotid endarterectomy (CEA) can prevent strokes, provided that appropriate inclusion criteria and high-quality perioperative treatment methods are utilised with low complication rates. From the patient s perspective, it is of paramount importance that the operation is as safe and effective as possible. From the community s point of view, it is important that CEA provision prevents as many strokes as possible. In order to define the stroke preventing potential of CEA in different communities, a comparison between eight European countries and Australia was performed including 53 077 carotid interventions. A more detailed evaluation was performed in Finland, the United Kingdom and Egypt. It could be estimated that many potentially preventable strokes occur due to insufficient diagnostics and CEA provision. The number of CEAs should be at least doubled in the Helsinki region. The theoretical power of CEA provision in stroke prevention varied significantly between the countries. Delay from symptom to surgery has been identified as one of the most important factors influencing the effectiveness of CEA. In 2008 only 11% of CEAs in Helsinki university central hospital (HUCH) were performed within the recommended14 days. Registered data of 673 CEAs in HUCH during 2000-2005 was analyzed. There was no systematic error that would have changed the outcome analysis. However it is important that registers are audited regularly and cross matching of different registries is possible. A previously unpublished method of combining medial mandibulotomy, neck incision and carotid artery interposition was carried out as a collaboration of maxillofacial, ear, nose and throat and vascular surgeons. Five patients were operated on with a technique that was feasible and possible to perform with little morbidity, but due to the significant risks involved, this technique should be reserved for carefully selected cases. In stroke prevention, organisational decisions seem far more important than details in interventional procedures when CEA is performed with low complication rates, as was the case in the present study. A TIA clinic approach with close co-operation between the on-call vascular surgeons, neurologists and radiologists should be available at all centres treating these patients. Patients should have a direct and fast admission to the hospital performing CEA.

Influence of foam/glass-epoxy interface on the macroscopic compressive failure features

The effect on the macroscopic compressive failure features of introduction of two flexible foam layers, either together at mid-region or separately at two locations that are away from the midregion, into a glass-epoxy (G-E) system is studied in this work. In this experimental approach an attempt to look at the possible influence the foam/G-E interface region has on the way the materials respond to compressive loading is made by involving an analyses of macrofractographic features. While foam-free samples fail by extensive ear formation and separation nearer to the mid-region, the foam bearing ones display pronounced interface separation. The positioning of the foam sheet(s) has a bearing on the failure features.

Worker piping triggers hissing for coordinated colony defence in the dwarf honeybee Apis florea

Defending a large social insect colony containing several thousands of workers requires the simultaneous action of many individuals. Ideally this action involves communication between the workers, enabling coordinated action and a fast response. The Asian dwarf honeybee, Apis florea, is a small honeybee with an open nesting habit and a comparatively small colony size, features that leave them particularly exposed to predators. We describe here a novel defence response of these bees in which the emission of an initial warning signal from one individual (“piping”) is followed 0.3 to 0.7 seconds later by a general response from a large number of bees (“hissing”). Piping is audible to the human ear, with a fundamental frequency of 384 ± 31Hz and lasting for 0.82 ± 0.35 seconds. Hissing is a broad band, noisy signal, clearly audible to the human observer and produced by slight but visible movements of the bees' wings. Hissing begins in individuals close to the piping bee, spreads rapidly to neighbours and results in an impressive coordinated crescendo occasionally involving the entire colony. Piping and hissing are accompanied by a marked decrease, or even cessation, of worker activities such as forager dancing and departures from the colony. We show that whereas hissing of the colony can be elicited without piping, the sequential and correlated piping and hissing response is specific to the presence of potential predators close to the colony. We suggest that the combined audio-visual effect of the hissing might deter small predators, while the cessation of flight activity could decrease the risk of predation by birds and insects which prey selectively on flying bees.

Subdiffusion in hair bundle dynamics: The role of protein conformational fluctuations

The detection of sound signals in vertebrates involves a complex network of different mechano-sensory elements in the inner ear. An especially important element in this network is the hair bundle, an antenna-like array of stereocilia containing gated ion channels that operate under the control of one or more adaptation motors. Deflections of the hair bundle by sound vibrations or thermal fluctuations transiently open the ion channels, allowing the flow of ions through them, and producing an electrical signal in the process, eventually causing the sensation of hearing. Recent high frequency (0.1-10 kHz) measurements by Kozlov et al. Proc. Natl. Acad. Sci. U. S. A. 109, 2896 (2012)] of the power spectrum and the mean square displacement of the thermal fluctuations of the hair bundle suggest that in this regime the dynamics of the hair bundle are subdiffusive. This finding has been explained in terms of the simple Brownian motion of a filament connecting neighboring stereocilia (the tip link), which is modeled as a viscoelastic spring. In the present paper, the diffusive anomalies of the hair bundle are ascribed to tip link fluctuations that evolve by fractional Brownian motion, which originates in fractional Gaussian noise and is characterized by a power law memory. The predictions of this model for the power spectrum of the hair bundle and its mean square displacement are consistent with the experimental data and the known properties of the tip link. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4768902]

Methionine down-regulates TLR4/MyD88/NF-kappa B signalling in osteoclast precursors to reduce bone loss during osteoporosis

Background and PurposeStudies have demonstrated that a moderate intake of amino acids is associated with development of bone health. Methionine, a sulphur-containing essential amino acid, has been largely implicated for improving cartilage formation, however its physiological significance on bone integrity and functionality have not been elucidated. We investigated whether methionine can prevent osteoporotic bone loss. Experimental ApproachThe anti-resorptive effect of methionine, (250mgkg(-1) body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized (OVX) rats by monitoring changes in bone turnover, formation of osteoclasts from blood-derived mononuclear cells and changes in the synthesis of pro-osteoclastogenic cytokines. Key resultsMethionine improved bone density and significantly decreased the degree of osteoclast development from blood mononuclear cells in OVX rats, as indicated by decreased production of osteoclast markers tartarate resistant acid phosphatase b (TRAP5b) and MIP-1. siRNA-mediated knockdown of myeloid differentiation primary response 88 MyD88], a signalling molecule in the toll-like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP-1 in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR-4/MyD88/NF-B pathway. Conclusions and ImplicationsTLR-4/MyD88/NF-B signalling pathway is integral for osteoclast development and this is down-regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis.

Functions for rice RFL in vegetative axillary meristem specification and outgrowth

Roles for the transcription factor RFL in rice axillary meristem development were studied. Its regulatory effects on LAX1, CUC1, and OsPIN3 reveal its functions in axillary meristem specification and outgrowth.Axillary meristems (AMs) are secondary shoot meristems whose outgrowth determines plant architecture. In rice, AMs form tillers, and tillering mutants reveal an interplay between transcription factors and the phytohormones auxin and strigolactone as some factors that underpin this developmental process. Previous studies showed that knockdown of the transcription factor gene RFL reduced tillering and caused a very large decrease in panicle branching. Here, the relationship between RFL, AM initiation, and outgrowth was examined. We show that RFL promotes AM specification through its effects on LAX1 and CUC genes, as their expression was modulated on RFL knockdown, on induction of RFL:GR fusion protein, and by a repressive RFL-EAR fusion protein. Further, we report reduced expression of auxin transporter genes OsPIN1 and OsPIN3 in the culm of RFL knockdown transgenic plants. Additionally, subtle change in the spatial pattern of IR4 DR5:GFP auxin reporter was observed, which hints at compromised auxin transport on RFL knockdown. The relationship between RFL, strigolactone signalling, and bud outgrowth was studied by transcript analyses and by the tillering phenotype of transgenic plants knocked down for both RFL and D3. These data suggest indirect RFL-strigolactone links that may affect tillering. Further, we show expression modulation of the auxin transporter gene OsPIN3 upon RFL:GR protein induction and by the repressive RFL-EAR protein. These modified forms of RFL had only indirect effects on OsPIN1. Together, we have found that RFL regulates the LAX1 and CUC genes during AM specification, and positively influences the outgrowth of AMs though its effects on auxin transport.

Conceptual design of three-dimensional scaffolds of powder-based materials for bone tissue engineering applications

Purpose - The purpose of this paper is to investigate the possibility to construct tissue-engineered bone repair scaffolds with pore size distributions using rapid prototyping techniques. Design/methodology/approach - The fabrication of porous scaffolds with complex porous architectures represents a major challenge in tissue engineering and the design aspects to mimic complex pore shape as well as spatial distribution of pore sizes of natural hard tissue remain unexplored. In this context, this work aims to evaluate the three-dimensional printing process to study its potential for scaffold fabrication as well as some innovative design of homogeneously porous or gradient porous scaffolds is described and such design has wider implication in the field of bone tissue engineering. Findings - The present work discusses biomedically relevant various design strategies with spatial/radial gradient in pore sizes as well as with different pore sizes and with different pore geometries. Originality/value - One of the important implications of the proposed novel design scheme would be the development of porous bioactive/biodegradable composites with gradient pore size, porosity, composition and with spatially distributed biochemical stimuli so that stem cells loaded into scaffolds would develop into complex tissues such as those at the bone-cartilage interface.

Time-Instant Sampling Based Encoding of Time-Varying Acoustic Spectrum

The inner ear has been shown to characterize an acoustic stimuli by transducing fluid motion in the inner ear to mechanical bending of stereocilia on the inner hair cells (IHCs). The excitation motion/energy transferred to an IHC is dependent on the frequency spectrum of the acoustic stimuli, and the spatial location of the IHC along the length of the basilar membrane (BM). Subsequently, the afferent auditory nerve fiber (ANF) bundle samples the encoded waveform in the IHCs by synapsing with them. In this work we focus on sampling of information by afferent ANFs from the IHCs, and show computationally that sampling at specific time instants is sufficient for decoding of time-varying acoustic spectrum embedded in the acoustic stimuli. The approach is based on sampling the signal at its zero-crossings and higher-order derivative zero-crossings. We show results of the approach on time-varying acoustic spectrum estimation from cricket call signal recording. The framework gives a time-domain and non-spatial processing perspective to auditory signal processing. The approach works on the full band signal, and is devoid of modeling any bandpass filtering mimicking the BM action. Instead, we motivate the approach from the perspective of event-triggered sampling by afferent ANFs on the stimuli encoded in the IHCs. Though the approach gives acoustic spectrum estimation but it is shallow on its complete understanding for plausible bio-mechanical replication with current mammalian auditory mechanics insights.

Electrostatic Interactions Between Glycosaminoglycan Molecules

The electrostatic interactions between nearest-neighbouring chondroitin sulfate glycosaminoglycan (CS-GAG) molecular chains are obtained on the bottle brush conformation of proteoglycan aggrecan based on an asymptotic solution of the Poisson-Boltzmann equation the CS-GAGs satisfy under the physiological conditions of articular cartilage. The present results show that the interactions are associated intimately with the minimum separation distance and mutual angle between the molecular chains themselves. Further analysis indicates that the electrostatic interactions are not only expressed to be purely exponential in separation distance and decrease with the increasing mutual angle but also dependent sensitively on the saline concentration in the electrolyte solution within the tissue, which is in agreement with the existed relevant conclusions.

生物力学进展和趋向(续)

<正> 三、运动关节力学 运动关节(diarthrodial joint)的功能在于使动物能灵巧地运动肢体。译成力学术语就是:传递载荷,吸收冲击、振动,承受相当高的应力,且运动时摩擦系数很小。L.L.Malcom曾精细地测量过牛肱关节的摩擦系数,在正应力1—20kg/cm~2的范围内,动摩擦系数为0.0025—0.0040,而最好的工程材料的摩擦系数为0.01—0.05,整整差一个量级。

From molecules to organs : Microscopy and multi-scale nature of development

Morphogenesis is a phenomenon of intricate balance and dynamic interplay between processes occurring at a wide range of scales (spatial, temporal and energetic). During development, a variety of physical mechanisms are employed by tissues to simultaneously pattern, move, and differentiate based on information exchange between constituent cells, perhaps more than at any other time during an organism's life. To fully understand such events, a combined theoretical and experimental framework is required to assist in deciphering the correlations at both structural and functional levels at scales that include the intracellular and tissue levels as well as organs and organ systems. Microscopy, especially diffraction-limited light microscopy, has emerged as a central tool to capture the spatio-temporal context of life processes. Imaging has the unique advantage of watching biological events as they unfold over time at single-cell resolution in the intact animal. In this work I present a range of problems in morphogenesis, each unique in its requirements for novel quantitative imaging both in terms of the technique and analysis. Understanding the molecular basis for a developmental process involves investigating how genes and their products- mRNA and proteins-function in the context of a cell. Structural information holds the key to insights into mechanisms and imaging fixed specimens paves the first step towards deciphering gene function. The work presented in this thesis starts with the demonstration that the fluorescent signal from the challenging environment of whole-mount imaging, obtained by in situ hybridization chain reaction (HCR), scales linearly with the number of copies of target mRNA to provide quantitative sub-cellular mapping of mRNA expression within intact vertebrate embryos. The work then progresses to address aspects of imaging live embryonic development in a number of species. While processes such as avian cartilage growth require high spatial resolution and lower time resolution, dynamic events during zebrafish somitogenesis require higher time resolution to capture the protein localization as the somites mature. The requirements on imaging are even more stringent in case of the embryonic zebrafish heart that beats with a frequency of ~ 2-2.5 Hz, thereby requiring very fast imaging techniques based on two-photon light sheet microscope to capture its dynamics. In each of the hitherto-mentioned cases, ranging from the level of molecules to organs, an imaging framework is developed, both in terms of technique and analysis to allow quantitative assessment of the process in vivo. Overall the work presented in this thesis combines new quantitative tools with novel microscopy for the precise understanding of processes in embryonic development.

Efeitos do controle da jaqueira, Artocarpus heterophyllus L., sobre a comunidade de pequenos mamíferos e a rede de dispersão de sementes na Ilha Grande, RJ

Atualmente observa-se uma expressiva perda de biodiversidade global resultante de atividades antrópicas, sendo a introdução de espécies exóticas uma das mais impactantes. A jaqueira Artocarpus heterophyllus é uma espécie exótica introduzida no Brasil durante o período colonial, sendo considerada invasora em diversas localidades. Na Mata Atlântica invade áreas de mata aberta e de borda, habitualmente associadas a ambientes antrópicos. Na Ilha Grande é encontrada em grande abundância em decorrência do histórico de ocupação humana. Para compreender como a mastofauna responde a presença da jaqueira, o Laboratório de Ecologia de Mamíferos da Universidade do Estado do Rio de Janeiro (UERJ) vem desenvolvendo um estudo ao longo de seis anos nos arredores da Vila Dois Rios, localizada na face oceânica da Ilha Grande. A partir dos resultados prévios iniciou-se uma segunda etapa do estudo no mesmo local que buscou avaliar diferentes métodos de controle das jaqueiras. O presente estudo é uma continuação direta desses dois trabalhos anteriores e teve como objetivo acompanhar as respostas da comunidade de pequenos mamíferos no período imediatamente posterior ao controle. Durante 18 meses foram amostradas bimestralmente 18 grades, 10 aonde foi efetuado o controle das jaqueiras e 8 aonde não foi constatada a presença desta árvore. Em cada grade foram colocadas 11 armadilhas de captura viva sendo banana a isca utilizada. Os mamíferos capturados foram medidos e suas fezes coletadas. A quantidade de jacas em cada área também foi anotada bimensalmente. As fezes foram analisadas em laboratório e as sementes encontradas identificadas. Os resultados obtidos indicam que a influência de A. heterophyllus sobre a estrutura da comunidade de pequenos mamíferos foi menor após o tratamento de controle. A única espécie que parece ainda responder a abundância de jaqueiras é o roedor Trinomys dimidiatus, que apresentou densidades mais elevadas nas áreas em tratamento, porém mais próximas a resultados obtidos para espécies congêneres em áreas pouco antropizadas. Utilizando uma abordagem de redes complexas observamos que, embora T. dimidiatus seja a espécie mais abundante em termos de número de indivíduos, o gambá Didelphis aurita parece ser a espécie de mamífero mais importante para dispersão de sementes nativas, aparecendo como espécie com maior número de conexões com espécies de sementes nas redes contruídas para as áreas sem jaqueiras e com jaqueiras antes e após o tratamento. Finalmente, a partir dos dados obtidos criamos um modelo matemático para a população de T. dimidiatus dos arredores da Vila Dois Rios, baseado em um crescimento logístico. Os resultados do modelo proposto se mostraram correlacionados com os dados de abundância reais, de modo que ele parece ser um simulador adequado da população local.

四川地区出土古玻璃的质子激发X荧光分析

abstract {Proton induced X-ray emission (PIXE) technique is an effective method for the chemical composition analysis of ancient glass samples without destruction. Chemical composition of the ancient glass samples dated from the Warring States Period (770-476 B.C.) to the Six Dynasties Period (220-589 A.D.), which were unearthed in Sichuan area, was quantitatively determined by the PIXE technique. The results show that the glass Bi (disc) and the glass eye beads of the Warring States Period all belong to the PbO-BaO-SiO₂ system. According to the composition and shape, we infer that these glass Bi and eye beads were made in China. Whereas, the chemical compositions of the glass ear pendants and beads of the Six Dynasties Period are varied, including K₂O-CaO-SiO₂, K₂O-SiO₂ and other glass systems. Based on the obtained results and those from literatures, some questions related to the technical propagation of the ancient Chinese glass are discussed.}