Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Short-term peripheral sensitization by brief exposure to pheromone components in Spodoptera littoralis.

In insects, the olfactory system displays a high degree of plasticity. In Spodoptera littoralis, pre-exposure of males to the sex pheromone has been shown to increase the sensitivity of the olfactory sensory neurons at peripheral level. In this study, we have investigated this sensitization effect by recording the electroantennographic responses of male antennae to the major sex pheromone component (Z,E)-9,11-tetradecadienyl acetate and to the minor components (Z,E)-9,12-tetradecadienyl acetate and (Z)-9-tetradecenyl acetate. Responses to the conjugated diene acetate at 1 and 10 µg and to the unconjugated ester at 10 µg at three different times (11, 22 and 33 min) after pre-exposure (T = 0 min) were significantly higher than those at T = 0, whereas no increase of sensitivity to the pheromone was elicited by any dose of the minor monoene acetate. In addition, pre-exposed antennae to sub-threshold amounts (0.1, 1 and 10 ng) of the major pheromone component also induced an increased response to the chemical at different times (5 and 15 min) after exposure. Our results revealed that pre-exposed isolated antennae display a short-term higher sensitivity at the peripheral level when compared to naive antennae. In addition, we provide evidence of a peripheral sensitization mediated not only by the major pheromone component, but also by the minor unconjugated diene acetate, and the induction of this sensitivity appears to be dependent on the pre-exposure dose and the time span between pre-exposure and subsequent recordings. Possible implications of the sensitization effect displayed by the minor component for a more effective discrimination of the pheromone bouquets of other closely related species are highlighted.

Trends in HIV testing, prevalence among first-time testers, and incidence in most-at-risk populations in Spain: the EPI-VIH Study, 2000 to 2009.

During 2000 to 2009, data on people undergoing HIV testing and on those newly diagnosed with HIV were collected in a network of 20 Spanish clinics specialising in sexually transmitted infections and/or HIV testing and counselling. The number of tests performed, overall and disaggregated by different variables, was obtained. HIV prevalence among first-time testers and HIV incidence among repeat testers were calculated. To evaluate trends, joinpoint regression models were fitted. In total, 236,939 HIV tests were performed for 165,745 individuals. Overall HIV prevalence among persons seeking HIV testing was 2.5% (95% CI: 2.4 to 2.6). Prevalence was highest in male sex workers who had sex with other men (19.0% (95% CI: 16.7 to 21.4)) and was lowest in female sex workers (0.8% (95% CI: 0.7 to 0.9)). Significant trends in prevalence were observed in men who have sex with men (MSM) (increasing) and heterosexual individuals (decreasing). The incidence analysis included 30,679 persons, 64,104 person-years (py) of follow-up and 642 seroconversions. The overall incidence rate (IR) was 1.0/100 py (95% CI: 0.9/100 to 1.1/100). Incidence was significantly higher in men and transgender females than in women (1.8/100 py (95% CI: 1.6 to 1.9), 1.2/100 py (95% CI: 0.5 to 2.8) and 0.1/100 py (95% CI: 0.09 to 0.2) respectively) and increased with age until 35­39 years. IRs in MSM and people who inject drugs were significantly greater than in heterosexual individuals (2.5/100 py (95% CI: 2.3 to 2.7), 1.6/100 py (95% CI: 1.1 to 2.2) and 0.1/100 py (95% CI: 0.09 to 0.2) respectively), and an upward trend was observed in MSM. Our results call for HIV prevention to be reinforced in MSM and transgender women in Spain.

Design and application of GB virus C (GBV-C) peptide microarrays for diagnosis of GBV-C/HIV-1 co-infection.

The main objectives of the design of GB virus C (GBV-C) peptide microarrays are the miniaturisation of antigen-antibody interaction assays, the simultaneous analysis of several peptide sequences and the reduction in the volume of serum required from patients since this always represents a limiting factor in studies to develop new systems for diagnosing human diseases. We herein report the design of a microarray immunoassay based on synthetic peptides derived from the GBV-C E2 protein to evaluate their diagnostic value in detecting anti-E2 antibodies in HIV-1 patients. To this end, peptide microarrays were initially prepared to identify the most relevant epitopes in the GBV-C E2 protein. Thus, 124 peptides composed of 18 amino acids covering the whole E2-protein sequence, with 15 residue overlaps, were spotted in triplicate onto γ-aminopropyl silane-functionalised adsorbent binding slides. The procedure to select the E2 protein epitopes was carried out using serum samples from HIV-1-infected patients. The samples had previously been tested for the presence or absence of GBV-C anti-E2 antibodies by means of the Abbott test. Thus, 11 specific epitopes in the GBV-C E2 protein were identified. Subsequently, peptide antigen microarrays were constructed using the E2 epitopes identified to detect GBV-C anti-E2 antibodies in the serum of HIV-1-infected patients with no known GBV-C co-infection. The 11 peptides selected identified anti-E2 GBV-C antibodies among HIV-1-infected patients, and a reactivity of 47 % was established. The potential antigenic peptides selected could be considered a useful tool for designing a new diagnostic system based on peptide microarrays to determine anti-GBV-C E2 antibodies in the serum of HIV-1-infected patients.

The genomic landscape of familial glioma.

Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.

Subfield and layer-specific depletion in calbindin-D28K, calretinin and parvalbumin immunoreactivity in the dentate gyrus of amyloid precursor protein/presenilin 1 transgenic mice.

The depletion of neuronal calcium binding proteins deprives neurons of the capacity to buffer high levels of intracellular Ca(2+) and this leaves them vulnerable to pathological processes, such as those present in Alzheimer's disease (AD). The aim of the present study was to investigate the expression of the calcium binding proteins, calbindin-D28K, calretinin and parvalbumin in the dentate gyrus (DG) of amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic (Tg) mice and their non-Tg littermates, as well as the relation with the deposition of human amyloid beta (Abeta). We measured the expression of these three proteins at seven different rostro-caudal levels, and in the molecular, granular and polymorphic layers of the DG. We found that, except in the most caudal part of the DG, there is a substantial loss of calbindin-D28K immunoreactivity in all three layers of the DG in APP/PS1 mice compared with the non-Tg mice. Significant loss of calretinin immunoreactivity is present in most of the polymorphic layer of the DG of APP/PS1 mice compared with the non-Tg mice, as well as in the rostral and intermediate part of the inner molecular layer. Compared with the non-Tg mice parvalbumin immunoreactivity is significantly reduced throughout the whole polymorphic layer as well as in the rostral and intermediate part of the granular layer of DG in APP/PS1 mice. The relatively preservation of calbindin immunoreactivity in the caudal part of molecular and granular layers as well as calretinin immunoreactivity in the caudal part of polymorphic layer of the DG is likely related to the lower Abeta expression in those parts of DG. The present data suggest an involvement of calcium-dependent pathways in the pathogenesis of AD and indicate that there exists a subfield and layer-specific decrease in immunoreactivity which is related to the type of calcium-binding protein in APP/PS1 mice. Moreover, it seems that APP expression affects more the calbindin expression then parvalbumin and calretinin expression in the DG of APP/PS1 Tg mice.

Prevalence of M. tuberculosis infection and tuberculosis disease among HIV-infected people in Spain.

OBJECTIVE: To study the prevalence of Mycobacterium tuberculosis infection (MTBI) and past/current tuberculosis (TB) among human immunodeficiency virus (HIV) infected persons in Spain. DESIGN: Longitudinal study conducted between 2000 and 2003 at 10 HIV hospital-based clinics. Data were drawn from clinical records. Associations were measured using odds ratios (ORs) and their 95% confidence intervals (95%CI). RESULTS: Of the 1242 persons who met the eligibility criteria, most were male (75%), aged <40 years (75%) and unemployed (40%). HIV infection occurred through intravenous drug use (53%), heterosexual sex (29%) and sex between men (16%). In the initial evaluation, 315 subjects had evidence of MTBI: 84 (6.8%) had a history of TB, 23 (1.8%) current TB and 208 (16.8%) latent tuberculosis infection (LTBI). MTBI was associated with male sex, age 30-49 years, contact with a TB case, homelessness, poor education, and negatively with CD4 <100 cells/mm(3). Among subjects with MTBI, past/current TB was associated with retirement/disability (OR 6, 95%CI 1.6-22.5), CD4 <200 cells/mm(3) (OR 9.7, 95%CI 3.8-24.6), viral load >55,000 copies (OR 5.3, 95%CI 1.4-20.0), and negatively, with skilled work (OR 0.4, 95%CI 0.1-1.0) or administrative/managerial/professional work (OR 0.05, 95%CI 0.01-0.4). CONCLUSION: Social context has an impact on the effectiveness of HIV and TB control programmes even in industrialised countries with free access to health care.

Regional and laminar organization of projections from the presubiculum and parasubiculum to the entorhinal cortex: an anterograde tracing study in the rat.

The regional and laminar organization of the projections from the presubiculum and the parasubiculum to the entorhinal cortex was analyzed in the rat with the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). The projections from the presubiculum were bilateral and confined to layers III and I of the medial entorhinal area (MEA). Both the ispi- and the contralateral projections showed similar distributions and were almost of equal density. Projections to layer III of the entorhinal cortex arose predominantly from superficial layers of the presubiculum, whereas the fibers that reach layer I of the entorhinal cortex appear to originate preferentially from the deep layers of the presubiculum. These fibers also appeared to innervate weakly layer II of MEA. The parasubiculum distributed projections not only to MEA but also to the lateral entorhinal area (LEA), innervating layer II selectively. The innervation of LEA was quite dense and extensive. Very weak projections from the parasubiculum to the contralateral entorhinal cortex were observed in this study. The position of the terminal plexus in the entorhinal cortex was determined by the point of origin along both the dorsoventral and transverse or proximodistal axes of the presubiculum and parasubiculum. Projections from the presubiculum and parasubiculum entered the entorhinal cortex at the level of the injection, or slightly ventral to it, and the main terminal field was always present ventrally to the injection site. The dorsoventral axis of origin thus corresponded to a similarly oriented axis of termination in the entorhinal cortex. The distribution in relation to the origin along the transverse axis was more complex, and differences between the presubiculum and parasubiculum were present. The proximal presubiculum, i.e., the part closest to the subiculum, projected to the most lateral part of MEA and the central part of the presubiculum sent fibers to the most medial part of MEA. The distal part of the presubiculum, i.e., the part that borders the parasubiculum, projected to the central part of MEA. Projections from the portion of the parasubiculum directly adjacent to the presubiculum, the so-called proximal parasubiculum, reached medial parts of MEA, and those originating in the central part distributed preferentially to lateral parts of MEA and adjacent medial parts of LEA. The distal part of the parasubiculum that borders the entorhinal cortex projected mainly to almost the full mediolateral extent of LEA.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase and NADH-diaphorase chemoarchitectonic subdivisions in the rabbit medial geniculate body.

The distribution of acetylcholinesterase and NADH-diaphorase activities was studied histochemically in the rabbit medial geniculate body, yielding new data useful for the definition of the common structural pattern of this thalamic complex in mammals. Four chemoarchitectonic subdivisions could be detected in transversal, horizontal and sagittal sections that corresponded to the previously described ventral, dorsal and internal nuclei, and to a fourth subdivision, defined as the mediorostral nucleus of the medial geniculate complex in the rabbit. The topography and cellular typology of the mediorostral nucleus suggest its homology with the so-called magnocellular nucleus of other mammals, an identity that was previously assigned to the internal nucleus. The relative position of the rabbit internal and dorsal nuclei and comparative connectional data are combined to suggest their correspondence with the anterodorsal and posterodorsal subnuclei, respectively, of the cat and the monkey. Global functional interpretations of these nuclei as sites of visuoacoustic and somatoacoustic polymodal integration support the notion of a shell region of the medial geniculate, surrounding the principal cochleotopic ventral nucleus and interconnected to the cortical acoustic belt around the primary auditory area. Acetylcholinesterase and NADH-diaphorase chemoarchitectony may be useful for the detection of similar partitions in species where cytoarchitectonic differentiation of the medial geniculate is less clear.

Parallel input to the hippocampal memory system through peri- and postrhinal cortices.

In the rat, the rhinal cortices consist of the perirhinal, postrhinal and entorhinal cortices. The perirhinal and postrhinal cortices, which serve as major input sources to the entorhinal cortex, receive functionally different types of information. In this study we looked at the projections from the perirhinal and postrhinal cortices to the different parts of the entorhinal cortices using an anterograde tracing technique. Our results show that the perirhinal cortex preferentially projects to the lateral entorhinal cortex, whereas the postrhinal cortex mainly sends fibers to the medial entorhinal cortex. Since the lateral and medial entorhinal cortices are differentially connected with the hippocampus, we suggest that functionally different types of information are processed in parallel in the hippocampal memory system.

Reliability of the mini nutritional assessment (MNA) in institutionalized elderly people.

OBJECTIVES: To measure the reliability of the Mini Nutritional Assessment (MNA) in institutionalized elderly people. DESIGN: 12 day interobserver reliability study. PARTICIPANTS AND SETTING: All subjects admitted to two long term geriatric units in Mataró (Barcelona, Spain) over 4 months during 1996 (n=67). MEASUREMENTS: in each center, different trained nurses independently administered the MNA on two separate occasions. RESULTS: Mean (standard deviation) scores for the two assessments of the MNA were 20.8 (5.4) and 21.3 (4.6) respectively. Internal consistency, estimated by the Cronbach's Alpha, were 0.83 and 0.74 for the first and second assessment respectively. Test-retest reliability, according to the intraclass correlation coefficient (ICC), was 0.89 for the total MNA score and higher than 0.89 for its continuous items. According to the Kappa index, test-retest reliability for the stratified total MNA was substantial (0.78); for the 18 ordinal or nominal items of the MNA it was 'almost perfect' or 'substantial' in 12 items, 5 were 'moderate' to 'fair' and in I item it was 'slight'. Subjective health evaluation, the number of glasses of liquids per day, and brachial circumference (this former with an ICC=0.91) were the items with the lowest Kappa indices. CONCLUSION: The MNA test has good levels of reliability, according to its internal consistency and its test-retest reproducibility. Some improvements can still be introduced by refining the categorization and content of some items with low reliability.

Blood levels of polychlorinated dibenzodioxins, polychlorinated dibenzofurans and polychlorinated biphenyls in the general population of a Spanish Mediterranean city.

Polychlorinated dibenzodioxins (PCDDs), Polychlorinated dibenzofurans (PCDFs) and Polychlorinated biphenyls (PCBs) are among the most toxic environmental pollutants. We determined blood levels of these compounds in a population sample of the city of Mataró, Spain. Blood samples were drawn from a randomly selected sample of 198 subjects, of both genders, aged 18 to 69 years. These samples were pooled into 10 groups for laboratory analysis. For males, total level of PCDDs was 505.7 ppt, of PCDFs was 26.7 ppt, and the international toxic equivalent (I-TEQ) was 12.5. For females the levels were 739 ppt, 28.8 ppt and 14.71-TEQ, respectively. The most important contributors to the total I-TEQ were HexaCDD, PentaCDD and PentaCDF. The blood concentration of total PCBs was 2.02 mg/l in males, and 1.58 mg/l in females. Levels of PCDDs, PCDFs and PCBs increased by age in both sexes. The levels of PCDDs and PCDFs in residents of this Mediterranean city are among the lowest observed in industrialized countries.

Biomonitoring study of people living near or working at a municipal solid-waste incinerator before and after two years of operation.

The authors conducted a biomonitoring study in the town of Mataró, Spain, of 104 subjects who lived near (i.e., within 0.5-1.5 km) an incinerator, 97 subjects who lived far (i.e., within 3.5 km-4.0 km) from an incinerator, and 17 workers at a new municipal solid-waste incinerator. The study commenced before the incinerator started functioning in 1995, and 2 y later (1977) the authors undertook the final part of the study. Dioxins, furans, and polychlorinated biphenyls were studied in pooled blood samples (n = 22), and individual blood and urine samples were analyzed for the detection of lead, chromium, cadmium, and mercury. In 1995, dioxin blood levels were low-both among those living close to the incinerator (mean = 13.5 ng international-dioxin toxic equivalents/kg fat) and among those living far away (mean = 13.4 ng international-dioxin toxic equivalents/kg fat). In 1997, dioxin and polychlorinated biphenyl levels had increased in both groups of residents by approximately 25% and 12%, respectively. (The increase in dioxin levels was about 10% when the authors took into account the mean of two repeated quality-control analyses.) Blood lead levels decreased, but no difference was observed for chromium, cadmium, and mercury. Minimal changes were seen among workers. Given the low dioxin stack emissions from this plant (mean = 2.5-0.98 ng international-dioxin toxic equivalents/m3) and that the blood dioxin levels did not depend on distance of residence from the incinerator, it would appear unlikely that the small increase in dioxin blood levels resulted from the incinerator's emissions.

[Determinants associated wtih the presence of risk behaviors in HIV infected patients]. / Determinantes asociados al mantenimiento de comportamientos de riesgo para la transmisión del VIH en pacientes ya infectados.

BACKGROUND: Determinants associated with risk behaviours are evaluated in a known HIV-infected population not belonging to the great metropolitan nuclei. PATIENTS AND METHODS: 110 unselected HIV+ patients were interviewed, including 77 variables. Their association with sharing needles, and unprotected sex is analysed. RESULTS: Sharing needles was associated to: low academic achievement (p = 0.045), no children (p = 0.045), any physical limitation (p = 0.004), previous admission to detoxification unit (p = 0.014), and depression. With unprotected sex were associated: low academic achievement (p = 0.005), lesser time of HIV infection (p = 0.009), no family support (p = 0.005), and scanty information about HIV transmission (p = 0.018). CONCLUSIONS: A cohort of HIV-infected subjects who persist with risk practices is remaining. Some easily recognizable variables may be useful for their early recognition.

Proteomic and transcriptomic analysis of rice tranglutaminase and chloroplast-related proteins.

The recently cloned rice transglutaminase gene (tgo) is the second plant transglutaminase identified to date (Campos et al. Plant Sci. 205-206 (2013) 97-110). Similarly to its counterpart in maize (tgz), this rice TGase was localized in the chloroplast, although in this case not exclusively. To further characterise plastidial tgo functionality, proteomic and transcriptomic studies were carried out to identify possible TGO-related proteins. Some LHCII antenna proteins were identified as TGO related using an in vitro proteomic approach, as well as ATPase and some PSII core proteins by mass spectrometry. To study the relationship between TGO and other plastidial proteins, a transcriptomic in vivo Dynamic Array (Fluidigm™) was used to analyse the mRNA expression of 30 plastidial genes with respect to that of tgo, in rice plants subjected to different periods of continuous illumination. The results indicated a gene-dependent tendency in the expression pattern that was related to tgo expression and to the illumination cycle. For certain genes, including tgo, significant differences between treatments, principally at the initiation and/or at the end of the illumination period, connected with the day/night cycling of gene expression, were observed. The tgo expression was especially related to plastidial proteins involved in photoprotection and the thylakoid electrochemical gradient.

Short-term impact of particulate matter (PM2.5) on daily mortality among the over-75 age group in Madrid (Spain).

BACKGROUND: The 2006 World Health Organization Air Quality Guidelines recommend using particulate matter having a diameter of under 2.5 micra (PM(2.5)) rather than PM(10) as an indicator of air particle concentration, a pattern followed by new European directives. Nevertheless, few studies have analysed this new indicator's impact at a European level on daily mortality among a high-risk group, such as persons aged over 75 years. OBJECTIVE: This study sought to analyse and quantify the effect of PM(2.5) on daily cause-specific mortality among the over-75 age group in the city of Madrid. METHODS: Using Poisson regression with Generalized Additive Models (GAM), a longitudinal, ecological time-series study examined the following causes of death: all causes except accidents (International Classification of Diseases-9th revision (ICD 9): 1-799); circulatory causes (ICD 9: 390-459); and respiratory causes (ICD 9: 460-519). These were adjusted for other chemical, biotic and acoustic pollutants. Further control variables considered were: trend; seasonality; influenza epidemics; and autocorrelation between mortality series. RESULTS: A significant statistical association was detected between daily mean PM(2.5) particle concentrations and all-cause mortality in the city of Madrid. This association was not in evidence for PM(10) concentrations. The Relative Risks found for an increase of 25 microg/m(3) in PM(2.5) concentrations were as follows: all-cause mortality, 1.057 (1.025-1.088); circulatory-cause mortality, 1.088 (1.041-1.135); and respiratory-cause mortality, 1.122 (1.056-1.189). The Attributable Risks were 5.41%, 8.12% and 10.90% respectively. This effect was observed in the short term (lags 1-2). CONCLUSION: Our results indicate a strong impact of PM(2.5) concentrations on daily mortality among the over-75 age group in Madrid, and underscore the need for measures aimed at lowering the concentration levels of this primary air pollutant in large cities, particularly by reducing motor vehicle traffic, the main source of such pollutant emission in urban atmospheres.

Classification of surgical procedures for epidemiologic assessment of sporadic Creutzfeldt-Jakob disease transmission by surgery.

BACKGROUND: In this preparatory phase of a case-control study, we propose and evaluate a new tool for classifying surgical procedures (SPs) in categories useful for epidemiologic research on surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: All SPs reported to the Swedish National Hospital Discharge Registry in the period 1974-2002, and undergone by 212 Swedish patients with registered diagnosis of CJD at death, hospital discharge or notification, in the period 1987-2002, 1060 age-, sex- and residence-matched controls and 1340 randomly chosen population controls, were reclassified into one of six categories of hypothetical transmission risk level. For that purpose the following two attributes were used: non-disposable instruments involved; and highest assigned ad-hoc risk level for four tissues or anatomical structures contacting such instruments. RESULTS: A total of 1170 different SP codes were reclassified as follows: 3.1% in the high-risk, 59.1% in the lower-risk, 24.4% in the lowest-risk, and 2.1% in the no-risk groups, with 11.3% procedures negatively defined by rubric as "other than..." being assigned to two spurious diluted-high and diluted-lower risk categories. The high-risk group mainly comprised neurosurgical (53%) and ophthalmic (39%) procedures. Sensitivity of neurosurgery and of ophthalmic surgery excluding neurosurgery, for the high- and diluted-high risk vs. other categories was 46% and 84%, while specificity was 98% and 95%, respectively. Sensitivity analysis based on these indices revealed that non-significant odds ratio effects of 1.4 and 1.3 for neurosurgery and ophthalmic surgery corresponded to statistically significant values of 5.1 after reclassification. CONCLUSIONS: This classification might contribute to quantify effects masked by use of body-system SP-categories in case-control studies on sCJD transmission by surgery.

Determinants of health system delay among confirmed tuberculosis cases in Spain.

BACKGROUND: Health system delay (HSD) is an important issue in tuberculosis (TB) control. This report investigates HSD and associated factors in a cohort of Spanish culture-confirmed TB patients. METHODS: Data were collected from clinical records. Using logistic regression with two different cut-off points to define HSD (median and 75th percentile), adjusted odds ratios were used to estimate the association between HSD and different variables. RESULTS: A total of 5184 culture-confirmed TB cases were included. Median and 75th percentile HSD were 6 and 25 days respectively. HSD significantly greater than the median was associated with: age >44 years, past or present intravenous drug use, diagnosis at a primary-care centre, prior preventive therapy, positive histology, request for drug-sensitivity testing, presence of silicosis or neoplasia in addition to TB, presence of non-TB related symptoms, and gastrointestinal site. HSD greater than the 75th percentile was related to the same variables, with the exception of diagnosis at a primary-care centre, positive histology, silicosis, non-TB-related symptoms and gastrointestinal site, for which the association disappeared; in contrast, an association with female gender emerged. CONCLUSION: Despite free health care being universally available in Spain, there are some groups of TB patients whose treatment is unduly delayed.

Projections from the presubiculum and the parasubiculum to morphologically characterized entorhinal-hippocampal projection neurons in the rat.

The relations between the inputs from the presubiculum and the parasubiculum and the cells in the entorhinal cortex that give rise to the perforant pathway have been studied in the rat at the light microscopical level. Projections from the presubiculum and the parasubiculum were labeled anterogradely, and, in the same animal, cells in the entorhinal cortex that project to the hippocampal formation were labeled by retrograde tracing and subsequent intracellular filling with Lucifer Yellow. The distribution and the number of appositions between the afferent fibers and hippocampal-projection neurons in the various layers of the entorhinal cortex were analyzed. The results show that layers I-IV of the entorhinal cortex contain neurons that give rise to projections to the hippocampal formation. The morphology of these projection neurons is highly variable and afferents from the presubiculum and the parasubiculum do not show a preference for any specific morphological cell type. Both inputs preferentially innervate the dendrites of their target cells. However, presubicular and parasubicular projections differ with respect to the layer of entorhinal cortex they project to. The number of appositions of presubicular afferents with cells that have their cell bodies in layer III of the entorhinal cortex is 2-3 times higher than with cells in layer II. In contrast, afferents from the parasubiculum form at least 2-3 times as many synapses on the dendrites of cells located in layer II than on neurons that have their cell bodies in layer III. Cells in layers I and IV of the entorhinal cortex receive weak inputs from the presubiculum and parasubiculum. Not only is the presubiculum different from the parasubiculum with respect to the distribution of projections to the entorhinal cortex, they also differ in their afferent and efferent connections. In turn, cells in layer II of the entorhinal cortex differ in their electrophysiological characteristics from those in layer III. Moreover, layer II neurons give rise to the projections to the dentate gyrus and field CA3/CA2 of the hippocampus proper, and cells in layer III project to field CA1 and the subiculum. Therefore, we propose that the interactions of the entorhinal-hippocampal network with the presubiculum are different from those with the parasubiculum.