Telomere length dynamics over 10-years and related outcomes in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been proposed as a disease of accelerated aging. Several cross-sectional studies have related a shorter telomere length (TL), a marker of biological aging, with COPD outcomes. Whether accelerated telomere shortening over time relates to worse outcomes in COPD patients, is not known. METHODS: Relative telomere length (T/S) was determined by qPCR in DNA samples from peripheral blood in 263 patients at baseline and up to 10 years post enrolment. Yearly clinical and lung function data of 134 patients with at least two-time measures of T/S over this time were included in the analysis. RESULTS: At baseline, T/S inversely correlated with age (r = - 0.236; p < 0.001), but there was no relationship between T/S and clinical and lung function variables (p > 0.05). Over 10 years of observation, there was a median shortening of TL of 183 bp/year for COPD patients. After adjusting for age, gender, active smoking and mean T/S, patients that shortened their telomeres the most over time, had worse gas exchange, more lung hyperinflation and extrapulmonary affection during the follow-up, (PaO2 p < 0.0001; KCO p = 0.042; IC/TLC p < 0.0001; 6MWD p = 0.004 and BODE index p = 0.009). Patients in the lowest tertile of T/S through the follow-up period had an increased risk of death [HR = 5.48, (1.23-24.42) p = 0.026]. CONCLUSIONS: This prospective study shows an association between accelerated telomere shortening and progressive worsening of pulmonary gas exchange, lung hyperinflation and extrapulmonary affection in COPD patients. Moreover, persistently shorter telomeres over this observation time increase the risk for all-cause mortality.

Neural Processing of Second-Order Motion in the Suprasylvian Cortex of the Cat.

Neuronal responses to second-order motion, that is, to spatiotemporal variations of texture or contrast, have been reported in several cortical areas of mammals, including the middle-temporal (MT) area in primates. In this study, we investigated whether second-order responses are present in the cat posteromedial lateral suprasylvian (PMLS) cortex, a possible homolog of the primate area MT. The stimuli used were luminance-based sine-wave gratings (first-order) and contrast-modulated carrier stimuli (second-order), which consisted of a high-spatial-frequency static grating (carrier) whose contrast was modulated by a low-spatial-frequency drifting grating (envelope). Results indicate that most PMLS neurons responded to second-order motion and for the vast majority of cells, first- and second-order preferred directions were conserved. However, responses to second-order stimuli were significantly reduced when compared to those evoked by first-order gratings. Circular variance was increased for second-order stimuli, indicating that PMLS direction selectivity was weaker for this type of stimulus. Finally, carrier orientation selectivity was either absent or very broad and had no influence on the envelope's orientation selectivity. In conclusion, our data show that PMLS neurons exhibit similar first- and second-order response profiles and that, akin primate area MT cells, they perform a form-cue invariant analysis of motion signals.

Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

BACKGROUND: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. MATERIALS AND METHODS: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). RESULTS: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. CONCLUSIONS: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. CLINICAL TRIAL NUMBER: NCT01086826, www.clinicaltrials.gov.

Contingent screening for preterm pre-eclampsia.

OBJECTIVE: Effective screening for pre-eclampsia resulting in delivery < 37 weeks' gestation (preterm PE) is provided by assessment of a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) at 11-13 or 19-24 weeks' gestation. This study explores the possibility of carrying out routine screening for preterm PE by maternal factors and MAP in all pregnancies and reserving measurements of UtA-PI and PlGF for a subgroup of the population, selected on the basis of the risk derived from screening by maternal factors and MAP alone. METHODS: Study data were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 11-13 and/or 19-24 weeks' gestation. Bayes' theorem was used to derive the a-priori risk for preterm PE from maternal factors and MAP. The posterior risk was obtained by the addition of UtA-PI and PlGF. We estimated the detection rate (DR) of preterm PE, at an overall false-positive rate (FPR) of 10%, from a policy in which first-stage screening by a combination of maternal factors and MAP defines screen-positive, screen-negative and intermediate-risk groups, with the latter undergoing second-stage screening by UtA-PI and PlGF. RESULTS: At 11-13 weeks' gestation, the model-based DR of preterm PE, at a 10% FPR, when screening the whole population by maternal factors, MAP, UtA-PI and PlGF was 74%. A similar DR was achieved by two-stage screening, with screening by maternal factors and MAP in the first stage and reserving measurement of UtA-PI and PlGF for the second stage and for only 50% of the population. If second-stage screening was offered to 30% of the population, there would be only a small reduction in DR from 74% to 71%. At 19-24 weeks, the model-based DR of preterm PE, at a 10% FPR, when screening the whole population by maternal factors, MAP, UtA-PI and PlGF was 84%. A similar DR was achieved by two-stage screening with measurements of UtA-PI and PlGF in only 70% of the population; if second-stage screening was offered to 40% of the population, the DR would be reduced from 84% to 81%. CONCLUSIONS: High DR of preterm PE can be achieved by two-stage screening in the first and second trimesters with maternal factors and MAP in the whole population and measurements of UtA-PI and PlGF in only some of the pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Enriched environment exposure during development positively impacts the structure and function of the visual cortex in mice.

Optimal conditions of development have been of interest for decades, since genetics alone cannot fully explain how an individual matures. In the present study, we used optical brain imaging to investigate whether a relatively simple enrichment can positively influence the development of the visual cortex of mice. The enrichment paradigm was composed of larger cages housing multiple mice that contained several toys, hiding places, nesting material and a spinning wheel that were moved or replaced at regular intervals. We compared C57BL/6N adult mice (> P60) that had been raised either in an enriched environment (EE; n = 16) or a standard (ST; n = 12) environment from 1 week before birth to adulthood, encompassing all cortical developmental stages. Here, we report significant beneficial changes on the structure and function of the visual cortex following environmental enrichment throughout the lifespan. More specifically, retinotopic mapping through intrinsic signal optical imaging revealed that the size of the primary visual cortex was greater in mice reared in an EE compared to controls. In addition, the visual field coverage of EE mice was wider. Finally, the organization of the cortical representation of the visual field (as determined by cortical magnification) versus its eccentricity also differed between the two groups. We did not observe any significant differences between females and males within each group. Taken together, these data demonstrate specific benefits of an EE throughout development on the visual cortex, which suggests adaptation to their environmental realities.

Abnormal cortical processing of pattern motion in amblyopia: evidence from fMRI.

Converging evidence from human psychophysics and animal neurophysiology indicates that amblyopia is associated with abnormal function of area MT, a motion sensitive region of the extrastriate visual cortex. In this context, the recent finding that amblyopic eyes mediate normal perception of dynamic plaid stimuli was surprising, as neural processing and perception of plaids has been closely linked to MT function. One intriguing potential explanation for this discrepancy is that the amblyopic eye recruits alternative visual brain areas to support plaid perception. This is the hypothesis that we tested. We used functional magnetic resonance imaging (fMRI) to measure the response of the amblyopic visual cortex and thalamus to incoherent and coherent motion of plaid stimuli that were perceived normally by the amblyopic eye. We found a different pattern of responses within the visual cortex when plaids were viewed by amblyopic as opposed to non-amblyopic eyes. The non-amblyopic eyes of amblyopes and control eyes differentially activated the hMT+ complex when viewing incoherent vs. coherent plaid motion, consistent with the notion that this region is centrally involved in plaid perception. However, for amblyopic eye viewing, hMT+ activation did not vary reliably with motion type. In a sub-set of our participants with amblyopia we were able to localize MT and MST within the larger hMT+ complex and found a lack of plaid motion selectivity in both sub-regions. The response of the pulvinar and ventral V3 to plaid stimuli also differed under amblyopic vs. non-amblyopic eye viewing conditions, however the response of these areas did vary according to motion type. These results indicate that while the perception of the plaid stimuli was constant for both amblyopic and non-amblyopic viewing, the network of neural areas that supported this perception was different.

Pattern-motion selective responses in MT, MST and the pulvinar of humans.

Plaid stimuli are often used to investigate the mechanisms involved in the integration and segregation of motion information. Considering the perceptual importance of such mechanisms, only a very limited number of visual brain areas have been found to be specifically involved in motion integration. These are the human (h)MT+ complex, area V3 and the pulvinar. The hMT+ complex can be functionally subdivided into two separate areas, middle temporal area (MT) and medial superior temporal area (MST); however, it is currently unclear whether these distinct sub-regions have different responses to plaid stimuli. To address this issue we used functional magnetic resonance imaging to quantify the relative response of MT and MST to component and pattern motion. Participants viewed plaid stimuli that were constrained to result in the perception of either component motion (segregation of motion information) or pattern motion (integration of motion information). MT/MST segregation was achieved using a moving dot stimulus that allowed stimulation of each visual hemifield either in unison or separately. We found pattern motion selective responses in both MT and MST. Consistent with previous reports, activity indicative of pattern motion selectivity was also found in the pulvinar as well as in other extrastriate areas. These results demonstrate that MT, MST and the pulvinar are involved in the complex motion integration mechanisms that are triggered by plaid stimuli. This reinforces the concept that integrative computations take place in a distributed neuronal circuit both in cortical and sub-cortical networks.

Associations of serum sclerostin levels with body composition, pulmonary function, and exacerbations in COPD patients.

BACKGROUND: In COPD, the bronchial epithelium shows a pathologically activated Wnt pathway. Sclerostin (SOST) is a secreted glycoprotein that is associated with bone metabolism and blocks the Wnt pathway. We hypothesized that low sclerostin levels might be associated with lung function and COPD exacerbations in patients. METHODS: We studied 139 outpatients with stable COPD and normal kidney function. We assessed the serum levels of SOST and bone metabolism parameters, body composition, clinical characteristics and lung function at baseline. We followed the patients prospectively for 12 months after enrolment. Moderate exacerbations and hospital admissions were recorded during follow-up. RESULTS: The serum SOST levels were 23.98±7.6 pmol/l (men: 25.5±7.7 pmol/l, women: 20.3±5.9 pmol/l (p < 0.001)). SOST showed correlations with age (r = 0.36), FFMI (r = 0.38), FEV1 (r = 0.27), DLCO (r = 0.39), 6MWD (r = 0.19) and CAT (r = -0.24). In multivariate linear regression analysis, only age (beta=0.264) and FFMI (beta=1.241) remained significant. SOST showed a significant negative correlation with serum phosphorus (r = -0.29). Cox proportional risk analysis indicated that patients in the lower tertile of SOST levels were at higher risk of moderate COPD exacerbation (HR 2.015, CI95% 1.136-3.577, p = 0.017) and hospital admission due to COPD (HR 5.142, CI95% 1.380-19.158, p = 0.015) than the rest of the patients. CONCLUSIONS: SOST levels are associated with body composition and lung function in patients with COPD. Furthermore, lower SOST levels predict a higher risk of exacerbations and hospitalization.

The 6-min walk distance in healthy subjects: reference standards from seven countries.

The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR(max)) during the 6-min walk test/the predicted maximum HR (HR(max) % pred), Borg dyspnoea score and oxygen saturation. The mean ± sd 6MWD was 571 ± 90 m (range 380-782 m). Males walked 30 m more than females (p < 0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR(max) % pred (adjusted r² = 0.38; p < 0.001), but there was variability across centres (adjusted r² = 0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p < 0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.

Octenol as attractant to Nyssomyia neivai (Diptera:Psychodidae:Phlebotominae) in the field.

The kairomone octenol is known as attractive to hematophagous Diptera such as mosquitoes, tsetse flies, and midges. There is little evidence that traps baited with octenol are also effective in attracting phlebotomine sand flies. The present report evaluated octenol in modified Centers for Disease Control and Prevention (CDC) traps in two experiments: 1) modified CDC trap without light and 2) modified CDC trap with light. The traps were baited with octenol at concentrations of 0.5, 27, and 43 mg/h in Rincão locality, São Paulo, Brazil. Traps without octenol were used as controls. The sand fly Nyssomyia neivai (Pinto) (= Lutzomyia neivai) (Diptera: Psychodidae: Phlebotominae) was the prevalent species (99.9%) in both experiments. The results of the experiments showed that traps baited with octenol at 27 and 43 mg/h caught significantly more N. neivai than control and octenol at 0.5 mg/h with and without light. This is the first report that shows that octenol itself is attractive to N. neivai and associated with light traps significantly increases the catches.

Bimodal modulation and continuous stimulation in optical imaging to map direction selectivity.

In the visual system, neurons with similar functional properties such as orientation and direction selectivity are clustered together to form modules. Optical imaging recordings in combination with episodic paradigms have been previously used to estimate direction selectivity, a fundamental property of visual neurons. The major drawback of the episodic approach is that the extraction of the signal from various forms of physiological noise is difficult, leading to a poor estimation of direction. Recent work, based on periodic stimulation and Fourier decomposition improved the extraction of periodic stimulus responses from noise and thus, reduced the recording time considerably. Given the success of this new paradigm in mapping orientation, the present study evaluated its reliability to measure direction selectivity in the visual cortex of anesthetized cats. Here, a model that exploits the harmonics of the Fourier decomposition is proposed where the first harmonic is related to direction responses, and the second to orientation. As expected, the first harmonic was absent when a static stimulus was presented. Contrarily, the first harmonic was present when moving stimuli were presented and the amplitude was greater with random dots kinematograms than with drifting gratings. The phase of the first harmonic showed a good agreement with direction preference measured by episodic paradigm. The ratio of the first/the second harmonic amplitude, related to a direction index, was weaker in fracture. It was also weaker in areas of the ventral pathway (areas 17 and 21a) where direction selectivity is known to be reduced. These results indicate that a periodic paradigm can be easily used to measure specific parameters in optical signals, particularly in situations when short acquisition periods are needed.

Successful management of a Clostridioides difficile ribotype 027 outbreak with a lean intervention bundle.

BACKGROUND: In a 2015 point-prevalence study, Clostridioides difficile 027, a hypervirulent ribotype, was absent from healthcare institutions in Switzerland. In late 2016, we detected an outbreak of C. difficile infection (CDI) with ribotype 027 occurring across several hospitals in the same hospital network. METHODS: The first cases of CDI due to ribotype 027 triggered an outbreak investigation, including whole genome sequencing (WGS) to identify outbreak strains. FINDINGS: Twenty-eight patients with CDI caused by ribotype 027 between December 2016 and December 2017 were identified, out of which 20 were caused by a single clone. Commonalities among these patients were hospitalization in the same room or on the same ward, receiving care from the same healthcare workers, and shared toilet areas. In addition to the epidemiological links suggesting possible transmission pathways between cases, WGS confirmed the clonality of this C. difficile 027 outbreak. The outbreak was contained by isolation precautions, raising awareness among healthcare workers, harmonizing diagnostic algorithms, and switching to a sporicidal agent for environmental disinfection. Of note, neither default gowning and gloving nor hand washing with water and soap were implemented. CONCLUSION: This C. difficile 027 outbreak was recognized belatedly due to lack of screening for this ribotype in some hospitals, and was contained by a swift response with simple infection prevention measures and adapting the laboratory approach. In order to have a better understanding of C. difficile epidemiology, diagnostic approaches should be standardized, CDI declared notifiable, and longitudinal data on prevalent ribotypes collected in countries where this is not established.

[Design and validation of the second edition of the Women's Sexual Function Questionnaire, FSM-2]. / Diseño y validación de la segunda edición del Cuestionario de Función Sexual de la Mujer, FSM-2.

OBJECTIVE: To design and validate the second edition of the Female Sexual Function questionnaire (FSF-2). MATERIAL AND METHODS: A cross-sectional and multicentre study was conducted on 187 women (18-70 years) who completed a test (preliminary questionnaire FSF-2), and then answered a structured anamnesis on female sexual function. Four weeks later they completed a retest, which was equal to the test but with an additional question about possible influence of recent events in their sex life. RESULTS: The mean age of the women was 43.51 years. Internal consistency of the questionnaire: Cronbach's α of the 0.919 test, of structured anamnesis 0.921, of the 0.920 retest. Test-retest reliability: mean test scores 30.53 ± 8.605, retest 30.05 ± 8.770, without significant differences. Correlation between total test and retest scores (intraclass correlation coefficient) 0.960, significant (P<.01); between total test scores and structured anamnesis 0.977, significant (P<.01). Concordance between test questions and structured anamnesis (kappa index), minimum 0.706, maximum 0.915; between test and retest questions, minimum 0.630, maximum 0.802. Content validity by expert consensus. Criteria validity: specificity of the questionnaire exceeding 90% for all items/domains, sensitivity greater than 80%, except for items 5, 6, 9 (70-80%). Validity of the construct through factor analysis, grouping of items into 2 components (they explain 66.586% of variance). CONCLUSIONS: The FSF-2 questionnaire is reliable and valid. It evaluates the sexual response of women, describing important aspects of their sexual activity as a couple: anticipatory anxiety, initiative, confidence to communicate, preferences and events that may influence. It can detect sexual dysfunction in the couple.

[Design and validation of a Male Sexual Function Questionnaire]. / Diseño y validación del Cuestionario de Función Sexual del Hombre, FSH.

OBJECTIVE: The objective of this work was to design and validate a questionnaire on Male Sexual Function (MSF) in the Spanish language, following the criteria contemplated in the Diagnostic and Statistical Manual of Mental Disorders, DSM-5, for the diagnosis of sexual dysfunctions. MATERIAL AND METHODS: A cross-sectional and multicentre study was conducted on 163 men (18-70 years) who self-completed a test (MSF questionnaire). They then answered questions on the Structured History of Male Sexual Function (AMSF). Four weeks later they completed a re-test, which was the same, but including a supplementary question about the possible influence of recent events. RESULTS: Internal consistency: Cronbach's α test 0.840, AMSF 0.835, retest 0.855. Test-retest reliability: mean test scores 33.13±6.566, retest 33.11±6.791; Student t 0.122, not significant (P=.903); correlation total test-retest scores (intraclass correlation coefficient) 0.979, significant correlation (P<.01); total correlations test-AMSF scores (intraclass correlation coefficient) 0.966, significant correlation (P<.01). Concordance: between questions of the AMSF test (Kappa index) minimum 0.749, maximum 0.934; between test-retest questions: 0.724, 0.844. Content validity using expert consensus. Criteria validity: specificity>90% for all items / domains, sensitivity>80% except item 4 (76%). Content validity: using factor analysis, grouping of items into 4 components (explain 75% variance); high correlation between "sexual desire" and "confidence in erection". CONCLUSIONS: The MSF questionnaire is reliable, stable and valid, with high specificity and sensitivity. It evaluates the sexual response of the male, describing aspects of interest: anticipatory anxiety, initiative, confidence to communicate preferences, events that may influence. Can detect sexual dysfunction in the couple.

Sex differences in mortality in patients with COPD.

Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George's Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan-Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second.

Survival, population size, and gonotrophic cycle duration of Nyssomyia neivai (Diptera: Psychodidae) at an endemic area of American cutaneous leishmaniasis in southeastern Brazil.

The survival, absolute population size, gonotrophic cycle duration, and temporal and spatial abundance of Nyssomyia neivai (Pinto) were studied in a rural area endemic for American cutaneous leishmaniasis (ACL) in Conchal, São Paulo State, southeastern Brazil, using mark-release-recapture techniques and by monitoring population fluctuation. The monthly abundance exhibited a unimodal pattern, with forest and domicile habitats having the highest relative abundances. A total of 1,873 males and 3,557 females were marked and released during the six experiments, of which 4.1-13.0% of males and 4.1-11.8% of females were recaptured. Daily survivorship estimated from the decline in recaptures per day was 0.681 for males and 0.667 for females. Gonotrophic cycle duration was estimated to be 4.0 d. Absolute population size was calculated using the Lincoln Index and ranged from 861 to 4,612 males and from 2,187 to 19,739 females. The low proportion of females that reach the age when they are potentially infective suggests that N. neivai has a low biological capacity to serve as a vector and that factors such as high biting rates and opportunistic feeding behavior would be needed to enable Leishmania (Viannia) braziliensis Vianna transmission. This agreed with the epidemiological pattern of ACL in southeastern Brazil that is characterized by low incidence, with isolated cases acquired principally within domiciliary habitats.

Distribution and Morphology of Cortical Terminals in the Cat Thalamus from the Anterior Ectosylvian Sulcus.

Two main types of cortical terminals have been identified in the cat thalamus. Large (type II) have been proposed to drive the response properties of thalamic cells while smaller (type I) are believed to modulate those properties. Among the cat's visual cortical areas, the anterior ectosylvian visual area (AEV) is considered as one of the highest areas in the hierarchical organization of the visual system. Whereas the connections from the AEV to the thalamus have been recognized, their nature (type I or II) is presently not known. In this study, we assessed and compared the relative contribution of type I and type II inputs to thalamic nuclei originating from the AEV. The anterograde tracer BDA was injected in the AEV of five animals. Results show that (1) both type I and II terminals from AEV are present in the Lateral Posterior- Pulvinar complex, the lateral median suprageniculate complex and the medial and dorsal geniculate nuclei (2) type I terminals significantly outnumber the type II terminals in almost all nuclei studied. Our results indicate that neurons in the AEV are more likely to modulate response properties in the thalamus rather than to determine basic organization of receptive fields of thalamic cells.

Validation and comparison of reference equations for the 6-min walk distance test.

Exercise impairment as measured by the 6-min walk distance (6MWD) test afflicts many patients with chronic obstructive pulmonary disease (COPD) and is known to predict mortality. Reference equations for the 6MWD in adults have been published but not yet validated. The present authors prospectively followed 1,379 COPD patients for 55+/-30 months and tested the predictive value of the baseline 6MWD in metres, the 6MWD work (kg.m(-1)) and as a percentage of predicted values the 6MWD in meters according to two reference equations. All-cause mortality was the validating outcome. The best threshold values were identified for each of the tests using receiver operating characteristic (ROC) curves. The threshold values obtained were: 350 m for the 6MWD, 25,000 kg.m(-1) for the 6MWD work, and 67 and 54% predicted for the two reference equations. All modalities of the testing were similar at predicting COPD mortality and correlated well with the 6MWD test. In conclusion, all modalities of testing predict mortality in chronic obstructive pulmonary disease equally well. In the 6-min walk distance test, a value <350 m is associated with increased mortality and should be regarded as abnormal.

Complex motion sensitivity of neurons, in the visual part of the anterior ectosylvian cortex in cats.

In cats, it is generally believed that the visual part of the anterior ectosylvian cortex (AEV) is involved in motion integration. It receives a substantial proportion of its afferents from cortical (e.g. lateral suprasylvian cortex) and subcortical (e.g. lateral posterior-pulvinar complex) areas known to participate in complex motion analysis. It has been established that a subset of AEV neurons can code the veridical motion of a moving plaid pattern (pattern-motion selectivity). In our study, we have further investigated the possibility that AEV neurons may play a role in higher-order motion processing by studying their responses to complex stimuli which necessitate higher order spatial and temporal integration. Experiments were performed in anesthetized adult cats. Classical receptive fields were stimulated with (1) complex random-dot kinematograms (RDKs), where the individual elements of the pattern do not provide coherent motion cues; (2) optic flow fields which require global spatial integration. We report that a large proportion of AEV neurons were selective to the direction and speed of RDKs. Close to two-thirds of the cells were selective to the direction of optic flow fields with about equal proportions being selective to contraction and expansion. The complex RDK and optic flow responsive units could not be systematically characterized based on their responses to plaid patterns; they were either pattern- or component-motion selective. These findings support the proposal that AEV is involved in higher-order motion processing. Our data suggest that the AEV may be more involved in the analysis of motion of visual patterns in relation to the animal's behavior rather than the analysis of the constituents of the patterns.

Cellular origin of intrinsic optical signals in the rabbit retina.

Optical imaging of retinal intrinsic signals is a relatively new method that provides spatiotemporal patterns of retinal activity through activity-dependent changes in light reflectance of the retina. The exact physiological mechanisms at the origin of retinal intrinsic signals are poorly understood and there are significant inter-species differences in their characteristics and cellular origins. In this study, we re-examined this issue through pharmacological dissection of retinal intrinsic signals in the rabbit with simultaneous ERG recordings. Retinal intrinsic signals faithfully reflected retinal activity as their amplitude was strongly associated with stimulation intensity (r2=0.85). Further, a strong linear relation was found using linear regression (r2=0.98) between retinal intrinsic signal amplitude and the ERG b wave, which suggests common cellular origins. Intravitreal injections of pharmacological agents were performed to isolate the activity of the retina's major cell types. Retinal intrinsic signals were abolished when the photoreceptors' activity was isolated with aspartate, indicative that they are not at the origin of this signal. A small but significant decrease in intrinsic response (20%) was observed when ganglion and amacrine cells' activity was inhibited by TTX injections. The remaining intrinsic responses were abolished in a dose-dependent manner through the inhibition of ON-bipolar cells by APB. Our results indicate that, in rabbits, retinal intrinsic signals reflect stimulation intensity and originate from the inner retina with a major contribution of bipolar cells and a minor one from ganglion or amacrine cells.