Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study

Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation.

The location of paravertebral catheters placed using the landmark technique

The aim of this prospective clinical study was to evaluate the location of paravertebral catheters that were placed using the classical landmark puncture technique and to correlate the distribution of contrast dye injected through the catheters with the extent of somatic block. Paravertebral catheter placement was attempted in 31 patients after video-assisted thoracic surgery. In one patient, an ultrasound-guided approach was chosen after failed catheter placement using the landmark method. A fluoroscopic examination in two planes using contrast dye was followed by injection of local anaesthetic and subsequent clinical testing of the extent of the anaesthetised area. In nine patients (29%), spread of contrast dye was not seen within the paravertebral space as intended. Misplaced catheters were in the epidural space (three patients), in the erector spinae musculature (five patients), and in the pleural space (one patient). There was also a discrepancy between the radiological findings and the observed distribution of loss of sensation. We have demonstrated an unacceptably high misplacement rate of paravertebral catheters using the landmark method. Additional research is required to compare the efficacy and safety of continuous paravertebral block using ultrasound-guided techniques or surgical inserted catheters.

Gender distribution of suicide attempts among immigrant groups in European countries--an international perspective

Studies report high rates of suicide attempts for female immigrants. This study assesses variations in the distribution of suicide attempts across gender in immigrant and non-immigrant groups in Europe.

The Sociolinguistics of Hungarian Outside Hungary

This study describes the sociolinguistic situation of the indigenous Hungarian national minorities in Slovakia (c. 600,000), Ukraine (c. 180,000), Romania (c. 2,000,000), Yugoslavia (c. 300,000), Slovenia (c. 8,000) and Austria (c. 6,000). Following the guidelines of Hans Goebl et al, the historical sociolinguistic portrait of each minority is presented from 1920 through to the mid-1990s. Each country's report includes sections on geography and demography, history, politics, economy, culture and religion, language policy and planning, and language use (domains of minority and/or majority language use, proficiency, attitudes, etc.). The team's findings were presented in the form of 374 pages of manuscripts, articles and tables, written in Hungarian and English. The core of the team's research results lies in the results of an empirical survey designed to study the social characteristics of Hungarian-minority bilingualism in the six project countries, and the linguistic similarities and differences between the six contact varieties of Hungarian and Hungarian in Hungary. The respondents were divided by age, education, and settlement group - city vs. village and local majority vs. local minority. The first thing to be observed is that Hungarian is tending to be spoken less to children than to parents and grandparents, a familiar pattern of language shift. In contact varieties of Hungarian, analytic constructions may be used where monolingual Hungarians would use a more synthetic form. Mr Kontra gives as an example the compound tagdij, which in Standard Hungarian means "membership fee" but which is replaced in contact Hungarian by the two-word phrase tagsagi dij. Another similar example concerns the synthetic verb hegedult "played the violin" and the analytic expression hegedun jatszott. The contrast is especially striking between the Hungarians in the northern Slavic countries, who use the synthetic form frequently, and those in the southern Slavic countries, who mainly use the analytic form. Mr. Kontra notes that from a structural point of view, there is no immediate explanation for this, since Slovak or Ukrainian are as likely to cause interference as is Serbian. He postulates instead that the difference may be attributable to some sociohistoric cause, and points out that the Turkish occupation of what is today Voivodina caused a discontinuity of the Hungarian presence in the region, with the result that Hungarians were resettled in the area only two and a half centuries ago. However, the Hungarians in today's Slovakia and Ukraine have lived together with Slavic peoples continuously for over a millennium. It may be, he suggests, that 250 years of interethnic coexistence is less than is needed for such a contact-induced change to run its course. Next Mr. Kontra moved on to what he terms "mental maps and morphology". In Hungarian, the names of cities and villages take the surface case (eg. Budapest-en "in Budapest") whereas some names denoting Hungarian settlements and all names of foreign cities take the interior case (eg. Tihany-ban "in Tihany" and Boston-ban "in Boston). The role of the semantic feature "foreign" in suffix-choice can be illustrated by such minimal pairs as Velence-n "in Velence, a village in Hungary" versus Velence-ben "in Velence [=Venice], a city in Italy", and Pecs-en "in Pecs, a city in Hungary" vs. Becs-ben "in Becs, ie. Vienna". This Hungarian vs. foreign distinction is often interpreted as "belonging to historical (pre-1920) Hungary" vs. "outside historical Hungary". The distinction is also expressed in the dichotomy "home" vs. "abroad'. The 1920 border changes have had an impact on both majority and minority Hungarians' mental maps, the maps which govern the choice of surface vs. interior cases with placenames. As there is a growing divergence between the mental maps of majority and minority Hungarians, so there will be a growing divergence in their use of the placename suffixes. Two placenames were chosen to scratch the surface of this complex problem: Craiova (a city in Oltenia, Romania) and Kosovo (Hungarian Koszovo) an autonomous region in southeast Yugoslavia. The assumption to be tested was that both placenames would be used with the inessive (interior) suffixes categorically by Hungarians in Hungary, but that the superessive suffix (showing "home") would be used near-categorically by Hungarians in Romania and Yugoslavia (Voivodina). Minority Hungarians in countries other than Romania and Yugoslavia would show no difference from majority Hungarians in Hungary. In fact, the data show that, contrary to expectation, there is considerable variation within Hungary. And although Koszovo is used, as expected, with the "home" suffix by 61% of the informants in Yugoslavia, the same suffix is used by an even higher percentage of the subjects in Slovenia. Mr. Kontra's team suggests that one factor playing a role in this might be the continuance of the former Yugoslav mentality in the Hungarians of Slovenia, at least from the geographical point of view. The contact varieties of Hungarian show important grammatical differences from Hungarian in Hungary. One of these concerns the variable use of Null subjects (the inclusion or exclusion of the subject of the verb). When informants were asked to insert either megkertem or megkertem ot - "I asked her" - into a test sentence, 54.9% of the respondents in the Ukraine inserted the second phrase as opposed to only 27.4% in Hungary. Although Mr. Kontra and his team concentrated more on the differences between Contact Hungarian and Standard Hungarian, they also discovered a number of similarities. One such similarity is demonstrable in the distribution of what Mr. Kontra calls an ongoing syntactic merger in Hungarian in Hungary. This change means effectively that two possibilities merge to form a third. For instance, the two sentences Valoszinuleg kulfoldre fognak koltozni and Valoszinu, hogy kulfoldre fognak koltozni merge to form the new construction Valszinuleg, hogy kulfoldre fognak koltozni ("Probably they will move abroad."). When asked to choose "the most natural" of the sentences, one in four chose the new construction, and a chi-square test shows homogeneity in the sample. In other words, this syntactic change is spreading across the entire Hungarian-speaking region in the Carpathian Basin Mr. Kontra believes that politicians, educators, and other interested parties now have reliable and up-to-date information about each Hungarian minority. An awareness of Hungarian as a pluricentric language is being developed which elevates the status of contact varieties of Hungarian used by the minorities, an essential process, he believes, if minority languages are to be maintained.

Quantitative mRNA analysis of adrenergic receptor subtypes in the intestines of healthy dairy cows and dairy cows with cecal dilatation-dislocation

OBJECTIVE: To investigate the distribution of mRNA coding for 9 adrenoceptor subtypes in the intestines of healthy dairy cows and cows with cecal dilatationdislocation (CDD). SAMPLE POPULATION: Full-thickness specimens of the intestinal wall were obtained from the ileum, cecum, proximal loop of the ascending colon (PLAC), and external loop of the spiral colon (ELSC) of 15 cows with CDD (group 1) and 15 healthy (control) cows (group 2, specimens collected during laparotomy; group 3, specimens collected after slaughter). PROCEDURES: Concentrations of mRNA for 9 adrenoceptor subtypes (alpha(1A), alpha(1B), alpha(1D), alpha(2AD), alpha(2B), alpha(2C), beta(1), beta(2), and beta(3)) were measured by quantitative real-time reverse transcriptase-PCR assay. Results were expressed relative to mRNA expression of a housekeeping gene. RESULTS: Expression of mRNA for alpha(1B)-, alpha(2AD)-, alpha(2B)-, beta(1)-, and beta(2)-adrenoceptors was significantly lower in cows with CDD than in control cows. In the ileum, these receptors all had lower mRNA expression in cows with CDD than in control cows. The same effect was detected in the ELSC for mRNA for alpha(2AD)-, alpha(2B)-, beta(1)-, and beta(2)-adrenoceptors, and in the cecum and PLAC for alpha(2B)- and beta(2)-adrenoceptors. Groups did not differ significantly for alpha(1A)-adrenoceptors. The mRNA expression for alpha(1D)-, alpha(2C)-, and beta(3)-adrenoceptors was extremely low in all groups. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in expression of mRNA coding for adrenoceptors, most pronounced in the ileum and spiral colon, between cows with CDD and control cows support the hypothesis of an implication of adrenergic mechanisms in the pathogenesis of CDD in dairy cows.

Distribution of RTX toxin genes in strains of [Actinobacillus] rossii and [Pasteurella] mairii

Strains of [Actinobacillus] rossii, [Pasteurella] mairii and [Pasteurella] aerogenes can be isolated from abortion in swine. The RTX toxin Pax has previously been found only in those [P.] aerogenes strains isolated from abortion. Nothing is known about RTX toxins in field isolates of the other two species. To gain insight into the distribution of selected RTX toxin genes and their association with abortion, PCR screening for the pax, apxII and apxIII operons on 21 [A.] rossii and seven [P.] mairii isolates was done. Since species can be phenotypically misidentified, the study was backed up by a phylogenetic analysis of all strains based on 16S rRNA, rpoB and infB genes. The pax gene was detected in all [P.] mairii but not in [A.] rossii strains. No apx genes were found in [P.] mairii but different gene combinations for apx were detected in [A.] rossii strains. Most of these strains were positive for apxIII, either alone or in combination with apxII. Whereas pax was found to be associated to strains from abortion no such indication could be found with apx in [A.] rossii strains. Phylogenetically [A.] rossii strains formed a heterogeneous cluster separated from Actinobacillus sensu stricto. [P.] mairii strains clustered with [P.] aerogenes but forming a separate branch. The fact that [P.] aerogenes, [P.] mairii and [A.] rossii can phylogenetically clearly be identified and might contain distinct RTX toxin genes allows their proper diagnosis and will further help to investigate their role as pathogens.

Immunohistochemical localization and quantitative assessment of GnRH-, FSH-, and LH-receptor mRNA Expression in canine skin: a powerful tool to study the pathogenesis of side effects after spaying

It has been proposed that gonadotropins and/or gonadotropin releasing hormone (GnRH) could be involved in the pathophysiology of the side effects after spaying in bitches, such as urinary incontinence and an increased production of a woolly undercoat. In order to provide tools to investigate the role of these hormones in dogs we developed immunohistochemical techniques and real-time RT-PCR to study whether GnRH-, LH-, and FSH-receptors exist in canine skin and urinary bladder. Tissue samples from the skin of the flank region and the ventral midline of the urinary bladder from euthanised dogs were examined. We were able to quantify mRNA expression of GnRH-, FSH-, and LH-receptors in canine skin and bladder biopsies with a high primer efficacy. Immunohistochemical studies showed that GnRH-, FSH-, and LH-receptors are expressed in vessel walls, the epidermis, the hair follicle and in sebaceous and sweat glands in canine skin and in transitional epithelium, and smooth muscle tissue in the urinary bladder. Our data provide the fundamentals to examine the distribution of FSH-, LH-, and GnRH-receptors in canine skin and urinary bladder and to assess gene activity at the transcriptional level by real-time RT-PCR.

Prevalence, incidence and distribution of erosion

There is some evidence that the presence of erosion is growing steadily. Because of different scoring systems, samples and examiners, it is difficult to compare and judge the outcome of the studies. Preschool children aged between 2 and 5 years showed erosion on deciduous teeth in 6-50% of the subjects. Young schoolchildren (aged 5-9) already had erosive lesions on permanent teeth in 14% of the cases. In the adolescent group (aged between 9 and 17) 11-100% of the young people examined showed signs of erosion. Incidence data (= increase of subjects with erosion) evaluated in three of these studies were 12% over 2 years, 18% over 5 years and 27% over 1.5 years. In adults (aged between 18 and 88), prevalence data ranged between 4 and 82%. Incidence data are scarce; only one study was found and this showed an incidence of 5% for the younger and 18% for the older examined group (= increase of tooth surfaces with erosion). Prevalence data indicated that males had somewhat more erosive tooth wear than females. The distribution of erosion showed a predominance of occlusal surfaces (especially mandibular first molars), followed by facial surfaces (anterior maxillary teeth). Oral erosion was frequently found on maxillary incisors and canines. Overall, prevalence data are not homogeneous. Nevertheless, there is already a trend for more pronounced rate of erosion in younger age groups. Therefore, it is important to detect at-risk patients early to initiate adequate preventive measures.

POOR PERFORMANCE OF BOOTSTRAP CONFIDENCE INTERVALS FOR THE LOCATION OF A QUANTITATIVE TRAIT LOUCS

The aim of many genetic studies is to locate the genomic regions (called quantitative trait loci, QTLs) that contribute to variation in a quantitative trait (such as body weight). Confidence intervals for the locations of QTLs are particularly important for the design of further experiments to identify the gene or genes responsible for the effect. Likelihood support intervals are the most widely used method to obtain confidence intervals for QTL location, but the non-parametric bootstrap has also been recommended. Through extensive computer simulation, we show that bootstrap confidence intervals are poorly behaved and so should not be used in this context. The profile likelihood (or LOD curve) for QTL location has a tendency to peak at genetic markers, and so the distribution of the maximum likelihood estimate (MLE) of QTL location has the unusual feature of point masses at genetic markers; this contributes to the poor behavior of the bootstrap. Likelihood support intervals and approximate Bayes credible intervals, on the other hand, are shown to behave appropriately.

Sensitivity Analysis for the Assessment of Causal Vaccine Effects on Viral Load in HIV Vaccine Trials

Vaccines with limited ability to prevent HIV infection may positively impact the HIV/AIDS pandemic by preventing secondary transmission and disease in vaccine recipients who become infected. To evaluate the impact of vaccination on secondary transmission and disease, efficacy trials assess vaccine effects on HIV viral load and other surrogate endpoints measured after infection. A standard test that compares the distribution of viral load between the infected subgroups of vaccine and placebo recipients does not assess a causal effect of vaccine, because the comparison groups are selected after randomization. To address this problem, we formulate clinically relevant causal estimands using the principal stratification framework developed by Frangakis and Rubin (2002), and propose a class of logistic selection bias models whose members identify the estimands. Given a selection model in the class, procedures are developed for testing and estimation of the causal effect of vaccination on viral load in the principal stratum of subjects who would be infected regardless of randomization assignment. We show how the procedures can be used for a sensitivity analysis that quantifies how the causal effect of vaccination varies with the presumed magnitude of selection bias.

NONLINEAR TUBE-FITTING FOR THE ANALYSIS OF ANATOMICAL AND FUNCTIONAL STRUCTURES

We are concerned with the estimation of the exterior surface of tube-shaped anatomical structures. This interest is motivated by two distinct scientific goals, one dealing with the distribution of HIV microbicide in the colon and the other with measuring degradation in white-matter tracts in the brain. Our problem is posed as the estimation of the support of a distribution in three dimensions from a sample from that distribution, possibly measured with error. We propose a novel tube-fitting algorithm to construct such estimators. Further, we conduct a simulation study to aid in the choice of a key parameter of the algorithm, and we test our algorithm with validation study tailored to the motivating data sets. Finally, we apply the tube-fitting algorithm to a colon image produced by single photon emission computed tomography (SPECT)and to a white-matter tract image produced using diffusion tensor `imaging (DTI).

Endoscopic scoring of the tracheal septum in horses and its clinical relevance for the evaluation of lower airway health in horses

REASONS FOR PERFORMING STUDY: Although endoscopic scoring of the tracheal septum thickness is used as a diagnostic tool for evaluation of lower airway disease, its clinical relevance and reliability have never been critically assessed in the horse. OBJECTIVES: To investigate if septum thickness scores (STS) are reliable and serve as a clinically useful indicator of lower airway disease status and/or inflammation. METHODS: The variance of STS attributable to the horse, observer and changes over time was determined. The distribution of STS in a population of clinically normal horses and correlations of STS with age, gender, as well as mucus accumulation and cell differentials of tracheobronchial secretions and bronchoalveolar lavage fluid were investigated. Effects of altered pulmonary ventilation, induced by different drugs, on STS were assessed. Finally, STS of horses affected with recurrent airway obstruction (RAO) were compared to those of clinically normal horses. RESULTS: Recorded STS showed excellent intra- and satisfactory interobserver agreement Established clinical, endoscopic and cytological measures of lower airway inflammation, i.e. mucus accumulation scores and airway neutrophilia, did not correlate with STS. In horses age > or = 10 years, septum scores were significantly higher (P = 0.022) than in younger horses. Septum thickness scores did not differ significantly between clinically normal and RAO-affected horses both in exacerbation and in remission. Horses with markedly increased breathing effort (i.e. with metacholine- or lobeline hydrochloride-challenge), often differed markedly (up to 1.9 scores), but the average of end-inspiratory and end-expiratory STS did not differ from baseline STS. CONCLUSIONS AND CLINICAL RELEVANCE: Endoscopic STS are a reproducible measure, but STS did not correlate with clinical, endoscopic and cytological findings indicative of RAO or inflammatory airway disease.

Distribution of lactate dehydrogenase in healthy and degenerative canine stifle joint cartilage

In dogs, degenerative joint diseases (DJD) have been shown to be associated with increased lactate dehydrogenase (LDH) activity in the synovial fluid. The goal of this study was to examine healthy and degenerative stifle joints in order to clarify the origin of LDH in synovial fluid. In order to assess the distribution of LDH, cartilage samples from healthy and degenerative knee joints were investigated by means of light and transmission electron microscopy in conjunction with immunolabeling and enzyme cytochemistry. Morphological analysis confirmed DJD. All techniques used corroborated the presence of LDH in chondrocytes and in the interterritorial matrix of healthy and degenerative stifle joints. Although enzymatic activity of LDH was clearly demonstrated in the territorial matrix by means of the tetrazolium-formazan reaction, immunolabeling for LDH was missing in this region. With respect to the distribution of LDH in the interterritorial matrix, a striking decrease from superficial to deeper layers was present in healthy dogs but was missing in affected joints. These results support the contention that LDH in synovial fluid of degenerative joints originates from cartilage. Therefore, we suggest that (1) LDH is transferred from chondrocytes to ECM in both healthy dogs and dogs with degenerative joint disease and that (2) in degenerative joints, LDH is released from chondrocytes and the ECM into synovial fluid through abrasion of cartilage as well as through enhanced diffusion as a result of increased water content and degradation of collagen.

The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles

The role of macrophages in the clearance of particles with diameters less than 100 nm (ultrafine or nanoparticles) is not well established, although these particles deposit highly efficiently in peripheral lungs, where particle phagocytosis by macrophages is the primary clearance mechanism. To investigate the uptake of nanoparticles by lung phagocytes, we analyzed the distribution of titanium dioxide particles of 20 nm count median diameter in macrophages obtained by bronchoalveolar lavage at 1 hour and 24 hours after a 1-hour aerosol inhalation. Differential cell counts revealing greater than 96% macrophages and less than 1% neutrophils and lymphocytes excluded inflammatory cell responses. Employing energy-filtering transmission electron microscopy (EFTEM) for elemental microanalysis, we examined 1,594 macrophage profiles in the 1-hour group (n = 6) and 1,609 in the 24-hour group (n = 6). We found 4 particles in 3 macrophage profiles at 1 hour and 47 particles in 27 macrophage profiles at 24 hours. Model-based data analysis revealed an uptake of 0.06 to 0.12% ultrafine titanium-dioxide particles by lung-surface macrophages within 24 hours. Mean (SD) particle diameters were 31 (8) nm at 1 hour and 34 (10) nm at 24 hours. Particles were localized adjacent (within 13-83 nm) to the membrane in vesicles with mean (SD) diameters of 592 (375) nm at 1 hour and 414 (309) nm at 24 hours, containing other material like surfactant. Additional screening of macrophage profiles by conventional TEM revealed no evidence for agglomerated nanoparticles. These results give evidence for a sporadic and rather unspecific uptake of TiO(2)-nanoparticles by lung-surface macrophages within 24 hours after their deposition, and hence for an insufficient role of the key clearance mechanism in peripheral lungs.

Distribution of amyloid precursor protein and amyloid-beta immunoreactivity in DBA/2J glaucomatous mouse retinas

PURPOSE: Evidence suggests that altered metabolism of amyloid precursor protein (APP) may play a role in the pathophysiology of retinal ganglion cell (RGC) death in the etiology of glaucoma. The authors sought to determine the distribution of APP and amyloid-beta (Abeta) in DBA/2J glaucomatous mouse retinas. METHODS: The retinas of 3- and 15-month-old DBA/2J mice and C57/BL-6 mice (control group) were fixed with 4% paraformaldehyde and processed for immunohistochemistry. Antibodies used included a polyclonal antibody to the C terminus of Abeta 40 and a polyclonal antibody to the APP ectodomain. Immunohistochemically stained tissue was graded using light microscopy. Distribution and semiquantitative expression of APP and Abeta in young and old glaucomatous and normal retinas were determined and compared. RESULTS: Strong APP and Abeta immunoreactivity was found in the RGC layer, optic nerve, and pia/dura of old DBA/2J retinas, with considerably higher intensity found in the old compared with the young DBA/2J mice. In contrast to glaucomatous mice, the control group did not show any notable age-related difference. CONCLUSIONS: Disruption of the homeostatic properties of secreted APP with consecutive Abeta cytotoxicity might be a contributing factor of ganglion cell loss in glaucomatous mouse retinas.