Improving the Prediction of Spontaneous and Post-thrombolytic Recanalization in Ischemic Stroke Patients.

BACKGROUND: Endovascular treatment for acute ischemic stroke patients was recently shown to improve recanalization rates and clinical outcome in a well-defined study population. Intravenous thrombolysis (IVT) alone is insufficiently effective to recanalize in certain patients or of little value in others. Accordingly, we aimed at identifying predictors of recanalization in patients treated with or without IVT. METHODS: In the observational Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry, we selected those stroke patients (1) with an arterial occlusion on computed tomography angiography (CTA) imaging, (2) who had an arterial patency assessment at 24 hours (CTA/magnetic resonance angiography/transcranial Doppler), and (3) who were treated with IVT or had no revascularization treatment. Based on 2 separate logistic regression analyses, predictors of spontaneous and post-thrombolytic recanalization were generated. RESULTS: Partial or complete recanalization was achieved in 121 of 210 (58%) thrombolyzed patients. Recanalization was associated with atrial fibrillation (odds ratio , 1.6; 95% confidence interval, 1.2-3.0) and absence of early ischemic changes on CT (1.1, 1.1-1.2) and inversely correlated with the presence of a significant extracranial (EC) stenosis or occlusion (.6, .3-.9). In nonthrombolyzed patients, partial or complete recanalization was significantly less frequent (37%, P < .01). The recanalization was independently associated with a history of hypercholesterolemia (2.6, 1.2-5.6) and the proximal site of the intracranial occlusion (2.5, 1.2-5.4), and inversely correlated with a decreased level of consciousness (.3, .1-.8), and EC (.3, .1-.6) and basilar artery pathology (.1, .0-.6). CONCLUSIONS: Various clinical findings, cardiovascular risk factors, and arterial pathology on acute CTA-based imaging are moderately associated with spontaneous and post-thrombolytic arterial recanalization at 24 hours. If confirmed in other studies, this information may influence patient selection toward the most appropriate revascularization strategy.

Association between ovarian follicle development and pregnancy rates in dairy cows undergoing spontaneous oestrous cycles

Ovarian follicle development continues in a wave-like manner during the bovine oestrous cycle giving rise to variation in the duration of ovulatory follicle development. The objectives of the present study were to determine whether a relationship exists between the duration of ovulatory follicle development and pregnancy rates following artificial insemination (AI) in dairy cows undergoing spontaneous oestrous cycles, and to identify factors influencing follicle turnover and pregnancy rate and the relationship between these two variables. Follicle development was monitored by daily transrectal ultrasonography from 10 days after oestrus until the subsequent oestrus in 158 lactating dairy cows. The cows were artificially inseminated following the second observed oestrus and pregnancy was diagnosed 35 days later. The predominant pattern of follicle development was two follicle waves (74.7%) with three follicle waves in 22.1% of oestrous cycles and four or more follicle waves in 3.2% of oestrous cycles. The interval from ovulatory follicle emergence to oestrus (EOI) was 3 days longer (P < 0.0001) in cows with two follicle waves than in those with three waves. Ovulatory follicles from two-wave oestrous cycles grew more slowly but were approximately 2 mm larger (P < 0.0001) on the day of oestrus. Twin ovulations were observed in 14.2% of oestrous cycles and occurred more frequently (P < 0.001) in three-wave oestrous cycles; consequently EOI was shorter in cows with twin ovulations. Overall, 57.0% of the cows were diagnosed pregnant 35 days after AI. Linear logistic regression analysis revealed an inverse relationship between EOI and the proportion of cows diagnosed pregnant, among all cows (n = 158; P < 0.01) and amongst those with single ovulations (n = 145; P < 0.05). Mean EOI was approximately I day shorter (P < 0.01) in cows that became pregnant than in non-pregnant cows; however, pregnancy rates did not differ significantly among cows with different patterns of follicle development. These findings confirm and extend previous observations in pharmacologically manipulated cattle and show, for the first time, that in dairy cows undergoing spontaneous oestrous cycles, natural variation in the duration of post-emergence ovulatory follicle development has a significant effect on pregnancy rate, presumably reflecting variation in oocyte developmental competence.

Association between ovarian follicle development and pregnancy rates in dairy cows undergoing spontaneous oestrous cycles

Ovarian follicle development continues in a wave-like manner during the bovine oestrous cycle giving rise to variation in the duration of ovulatory follicle development. The objectives of the present study were to determine whether a relationship exists between the duration of ovulatory follicle development and pregnancy rates following artificial insemination (AI) in dairy cows undergoing spontaneous oestrous cycles, and to identify factors influencing follicle turnover and pregnancy rate and the relationship between these two variables. Follicle development was monitored by daily transrectal ultrasonography from 10 days after oestrus until the subsequent oestrus in 158 lactating dairy cows. The cows were artificially inseminated following the second observed oestrus and pregnancy was diagnosed 35 days later. The predominant pattern of follicle development was two follicle waves (74.7%) with three follicle waves in 22.1% of oestrous cycles and four or more follicle waves in 3.2% of oestrous cycles. The interval from ovulatory follicle emergence to oestrus (EOI) was 3 days longer (P < 0.0001) in cows with two follicle waves than in those with three waves. Ovulatory follicles from two-wave oestrous cycles grew more slowly but were approximately 2 mm larger (P < 0.0001) on the day of oestrus. Twin ovulations were observed in 14.2% of oestrous cycles and occurred more frequently (P < 0.001) in three-wave oestrous cycles; consequently EOI was shorter in cows with twin ovulations. Overall, 57.0% of the cows were diagnosed pregnant 35 days after AI. Linear logistic regression analysis revealed an inverse relationship between EOI and the proportion of cows diagnosed pregnant, among all cows (n = 158; P < 0.01) and amongst those with single ovulations (n = 145; P < 0.05). Mean EOI was approximately I day shorter (P < 0.01) in cows that became pregnant than in non-pregnant cows; however, pregnancy rates did not differ significantly among cows with different patterns of follicle development. These findings confirm and extend previous observations in pharmacologically manipulated cattle and show, for the first time, that in dairy cows undergoing spontaneous oestrous cycles, natural variation in the duration of post-emergence ovulatory follicle development has a significant effect on pregnancy rate, presumably reflecting variation in oocyte developmental competence.

Morphometric evaluation of gingival overgrowth and regression caused by cyclosporin in rats

Cyclosporin A is a selective immunosuppressant, used in organ transplants to prevent graft rejection. Cyclosporin A can cause various side effects including gingival overgrowth. The aim of this work was to evaluate gingival overgrowth of rats treated daily with 10 mg/kg body weight of Cyclosporin A for 60 days, as well as the regression after the interruption of treatment. All rats treated with Cyclosporin A developed gingival overgrowth, with increased thickness of the epithelium, height and width of the connective tissue. The density of fibroblasts and collagen fibers also increased. Five to 90 days after the interruption of treatment with Cyclosporin A, there was a progressive reduction of the gingival volume and of collagen fibers and fibroblast densities. The reduction was more pronounced in the initial periods and after 90 days did not return to the normal values.

Estimation of spontaneous blinking main sequence in normal subjects and patients with Graves' upper eyelid retraction

Purpose. We quantified the main sequence of spontaneous blinks in normal subjects and Graves' disease patients with upper eyelid retraction using a nonlinear and two linear models, and examined the variability of the main sequence estimated with standard linear regression for 10-minute periods of time. Methods. A total of 20 normal subjects and 12 patients had their spontaneous blinking measured with the magnetic search coil technique when watching a video during one hour. The main sequence was estimated with a power-law function, and with standard and trough the origin linear regressions. Repeated measurements ANOVA was used to test the mean sequence stability of 10-minute bins measured with standard linear regression. Results. In 95% of the sample the correlation coefficients of the main sequence ranged from 0.60 to 0.94. Homoscedasticity of the peak velocity was not verified in 20% of the subjects and 25% of the patients. The power-law function provided the best main sequence fitting for subjects and patients. The mean sequence of 10-minute bins measured with standard linear regression did not differ from the one-hour period value. For the entire period of observation and the slope obtained by standard linear regression, the main sequence of the patients was reduced significantly compared to the normal subjects. Conclusions. Standard linear regression is a valid and stable approximation for estimating the main sequence of spontaneous blinking. However, the basic assumptions of the linear regression model should be examined on an individual basis. The maximum velocity of large blinks is slower in Graves' disease patients than in normal subjects. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Correlation properties of spontaneous motor activity in healthy infants: a new computer-assisted method to evaluate neurological maturation

Qualitative assessment of spontaneous motor activity in early infancy is widely used in clinical practice. It enables the description of maturational changes of motor behavior in both healthy infants and infants who are at risk for later neurological impairment. These assessments are, however, time-consuming and are dependent upon professional experience. Therefore, a simple physiological method that describes the complex behavior of spontaneous movements (SMs) in infants would be helpful. In this methodological study, we aimed to determine whether time series of motor acceleration measurements at 40-44 weeks and 50-55 weeks gestational age in healthy infants exhibit fractal-like properties and if this self-affinity of the acceleration signal is sensitive to maturation. Healthy motor state was ensured by General Movement assessment. We assessed statistical persistence in the acceleration time series by calculating the scaling exponent α via detrended fluctuation analysis of the time series. In hand trajectories of SMs in infants we found a mean α value of 1.198 (95 % CI 1.167-1.230) at 40-44 weeks. Alpha changed significantly (p = 0.001) at 50-55 weeks to a mean of 1.102 (1.055-1.149). Complementary multilevel regression analysis confirmed a decreasing trend of α with increasing age. Statistical persistence of fluctuation in hand trajectories of SMs is sensitive to neurological maturation and can be characterized by a simple parameter α in an automated and observer-independent fashion. Future studies including children at risk for neurological impairment should evaluate whether this method could be used as an early clinical screening tool for later neurological compromise.

ALTERATIONS IN HYPOTHALAMIC CONTENT OF LUTEINIZING HORMONE RELEASING HORMONE AND PITUITARY RESPONSIVENESS ASSOCIATED WITH TESTICULAR REGRESSION INDUCED BY PINEAL RELATED TREATMENTS IN THE GOLDEN HAMSTER

The adult male golden hamster, when exposed to blinding (BL), short photoperiod (SP), or daily melatonin injections (MEL) demonstrates dramatic reproductive collapse. This collapse can be blocked by removal of the pineal gland prior to treatment. Reproductive collapse is characterized by a dramatic decrease in both testicular weight and serum gonadotropin titers. The present study was designed to examine the interactions of the hypothalamus and pituitary gland during testicular regression, and to specifically compare and contrast changes caused by the three commonly employed methods of inducing testicular regression (BL,SP,MEL). Hypothalamic LHRH content was altered by all three treatments. There was an initial increase in content of LHRH that occurred concomitantly with the decreased serum gonadotropin titers, followed by a precipitous decline in LHRH content which reflected the rapid increases in both serum LH and FSH which occur during spontaneous testicular recrudescence. In vitro pituitary responsiveness was altered by all three treatments: there was a decline in basal and maximally stimulatable release of both LH and FSH which paralleled the fall of serum gonadotropins. During recrudescence both basal and maximal release dramatically increased in a manner comparable to serum hormone levels. While all three treatments were equally effective in their ability to induce changes at all levels of the endocrine system, there were important temporal differences in the effects of the various treatments. Melatonin injections induced the most rapid changes in endocrine parameters, followed by exposure to short photoperiod. Blinding required the most time to induce the same changes. This study has demonstrated that pineal-mediated testicular regression is a process which involves dynamic changes in multiply-dependent endocrine relationships, and proper evaluation of these changes must be performed with specific temporal events in mind. ^

Therapeutic potential of p53 restoration in spontaneous tumors

Over 80% of p53 mutations found in human cancers are p53 missense mutations. Recent studies have shown that p53 restoration leads to tumor regression in mice with p53 deletions, but the therapeutic efficacy of p53 restoration in tumors containing p53 missense mutations has not been evaluated. Since p53 mutant such as p53R172H has gain-of-function activities and dominant-negative effect that repress wild type p53, the activity of restored wild-type p53 might be compromised by the mutant p53 in tumors. We hypothesized that p53 restoration in tumors with the p53R172H mutation may be less therapeutically effective as p53 restoration in tumors null for p53. I tested this hypothesis by comparison of the therapeutic outcomes of p53 restoration in mice with spontaneous tumors that either lacked p53 or contained the p53R172H mutation. While p53 restoration causes tumor regression in mice lacking p53, the same p53 restoration halts tumor progression in mice with the p53R172H mutation. This phenotypic difference suggests a dominant-negative activity of the mutant p53. Moreover, I showed that the mutant p53 only inhibits part of the activity of the restored wild-type p53 and that the remaining wild-type activity still causes a delay in tumor progression. We conclude that p53 restoration has therapeutic potential in p53R172H tumors via suppression of tumor progression. This knowledge is of critical importance for p53 targeted cancer therapy because many patients with cancers harbor p53 missense mutations rather p53-null mutations. Since p53R172H mutation represents one of the most frequent and potent p53 missense mutations observed in human cancers, the current findings implicates that p53 restoration may be therapeutically important not only in human cancers characterized by loss of p53 alleles but also in those in which p53 missense mutations play an important pathogenetic role. ^

Spontaneous Abortions and Shift Work in a Cohort of Nurses in Norway

Background: An association between spontaneous abortions and shift work has been suggested, but present research results are conflicting. The aim of the study is to evaluate the relationship between spontaneous abortions among nurses, shift schedules, and nights worked. Methods: This is a longitudinal study where we identified 914 females from a cohort of nurses in Norway who had worked the same type of shift schedule 2008-2010; either permanent day shift, three-shift rotation or permanent night shift. Information on age, work and life-style factors, as well as spontaneous abortions during lifetime and the past three years (2008-2010) was obtained by annual questionnaires. Results: A higher prevalence of experienced spontaneous abortions before study start (2008) was found among nurses working permanent night shift compared to other nurses. In a linear regression analysis, a risk of 1.3 was found for experienced spontaneous abortions before study start among permanent night shift nurses, with day shift as reference, when adjusting for age, smoking, caffeine and job strain, but the finding was not statistical significant (95 per cent confidence interval 0.8-2.1). Permanent night shift workers had a risk of 1.5 experiencing spontaneous abortions in 2008-2010 compared to day shift nurses, although not statistical significant (95 per cent confidence interval 0.7-3.5). The number of night shifts the past three years was not associated with experiencing spontaneous abortions 2008-2010, but associated with a reduced risk of experiencing spontaneous abortions during lifetime. The results must be interpreted in the light of a possible selection bias; both selections into the occupation of nursing and into the different shift types of the more healthy persons may have occurred in this population. Conclusion: No significant increased risk of spontaneous abortion among permanent night shift nurses compared to day-time nurses was found in this study, and no association was found between spontaneous abortions and the number of worked night shifts.

Censored Linear Regression Models For Irregularly Observed Longitudinal Data Using The Multivariate-t Distribution.

In acquired immunodeficiency syndrome (AIDS) studies it is quite common to observe viral load measurements collected irregularly over time. Moreover, these measurements can be subjected to some upper and/or lower detection limits depending on the quantification assays. A complication arises when these continuous repeated measures have a heavy-tailed behavior. For such data structures, we propose a robust structure for a censored linear model based on the multivariate Student's t-distribution. To compensate for the autocorrelation existing among irregularly observed measures, a damped exponential correlation structure is employed. An efficient expectation maximization type algorithm is developed for computing the maximum likelihood estimates, obtaining as a by-product the standard errors of the fixed effects and the log-likelihood function. The proposed algorithm uses closed-form expressions at the E-step that rely on formulas for the mean and variance of a truncated multivariate Student's t-distribution. The methodology is illustrated through an application to an Human Immunodeficiency Virus-AIDS (HIV-AIDS) study and several simulation studies.

Patient With Numerous Papules And Spontaneous Pneumothorax.

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Comparing Near-infrared Conventional Diffuse Reflectance Spectroscopy And Hyperspectral Imaging For Determination Of The Bulk Properties Of Solid Samples By Multivariate Regression: Determination Of Mooney Viscosity And Plasticity Indices Of Natural Rubber.

Conventional reflectance spectroscopy (NIRS) and hyperspectral imaging (HI) in the near-infrared region (1000-2500 nm) are evaluated and compared, using, as the case study, the determination of relevant properties related to the quality of natural rubber. Mooney viscosity (MV) and plasticity indices (PI) (PI0 - original plasticity, PI30 - plasticity after accelerated aging, and PRI - the plasticity retention index after accelerated aging) of rubber were determined using multivariate regression models. Two hundred and eighty six samples of rubber were measured using conventional and hyperspectral near-infrared imaging reflectance instruments in the range of 1000-2500 nm. The sample set was split into regression (n = 191) and external validation (n = 95) sub-sets. Three instruments were employed for data acquisition: a line scanning hyperspectral camera and two conventional FT-NIR spectrometers. Sample heterogeneity was evaluated using hyperspectral images obtained with a resolution of 150 × 150 μm and principal component analysis. The probed sample area (5 cm(2); 24,000 pixels) to achieve representativeness was found to be equivalent to the average of 6 spectra for a 1 cm diameter probing circular window of one FT-NIR instrument. The other spectrophotometer can probe the whole sample in only one measurement. The results show that the rubber properties can be determined with very similar accuracy and precision by Partial Least Square (PLS) regression models regardless of whether HI-NIR or conventional FT-NIR produce the spectral datasets. The best Root Mean Square Errors of Prediction (RMSEPs) of external validation for MV, PI0, PI30, and PRI were 4.3, 1.8, 3.4, and 5.3%, respectively. Though the quantitative results provided by the three instruments can be considered equivalent, the hyperspectral imaging instrument presents a number of advantages, being about 6 times faster than conventional bulk spectrometers, producing robust spectral data by ensuring sample representativeness, and minimizing the effect of the presence of contaminants.

Spontaneous puberty in girls with early diagnosis of Turner syndrome

OBJECTIVE: To verify if the frequency of spontaneous pubertal development among girls with Turner syndrome (TS) diagnosed in infancy and childhood is greater than that of patients diagnosed later. SUBJECTS AND METHODS: Thirty three girls aged < 10 years at the time of diagnosis were evaluated regarding pubertal development. The frequency of spontaneous puberty was compared with that of girls aged > 13 years diagnosed at the same service. RESULTS: Sixteen of 32 informative patients had signs of spontaneous puberty, a frequency greater than that of patients diagnosed later. In six patients, there was no progression of puberty; menarche occurred in six, and one became pregnant, but the fetus was a stillborn. Spontaneous puberty was absent in all cases with 45,X karyotype. CONCLUSIONS: The greater prevalence of spontaneous puberty in girls whose diagnosis was not based on pubertal delay suggests that, among those diagnosed later, there is a bias towards patients with hypogonadism. Arq Bras Endocrinol Metab. 2012;56(9):653-7

Array-CGH testing in spontaneous abortions with normal karyotypes

In about 50% of first trimester spontaneous abortion the cause remains undetermined after standard cytogenetic investigation. We evaluated the usefulness of array-CGH in diagnosing chromosome abnormalities in products of conception from first trimester spontaneous abortions. Cell culture was carried out in short- and long-term cultures of 54 specimens and cytogenetic analysis was successful in 49 of them. Cytogenetic abnormalities (numerical and structural) were detected in 22 (44.89%) specimens. Subsequent, array-CGH based on large insert clones spaced at ~1 Mb intervals over the whole genome was used in 17 cases with normal G-banding karyotype. This revealed chromosome aneuplodies in three additional cases, giving a final total of 51% cases in which an abnormal karyotype was detected. In keeping with other recently published works, this study shows that array-CGH detects abnormalities in a further ~10% of spontaneous abortion specimens considered to be normal using standard cytogenetic methods. As such, array-CGH technique may present a suitable complementary test to cytogenetic analysis in cases with a normal karyotype.

Reproductive behavior, development and eye regression in the cave armored catfish, Ancistrus cryptophthalmus Reis, 1987 (Siluriformes: Loricariidae), breed in laboratory

The troglobitic armored catfish, Ancistrus cryptophthalmus (Loricariidae, Ancistrinae) is known from four caves in the São Domingos karst area, upper rio Tocantins basin, Central Brazil. These populations differ in general body shape and degree of reduction of eyes and of pigmentation. The small Passa Três population (around 1,000 individuals) presents the most reduced eyes, which are not externally visible in adults. A small group of Passa Três catfish, one male and three females, reproduced spontaneously thrice in laboratory, at the end of summertime in 2000, 2003 and 2004. Herein we describe the reproductive behavior during the 2003 event, as well as the early development of the 2003 and 2004 offsprings, with focus on body growth and ontogenetic regression of eyes. The parental care by the male, which includes defense of the rock shelter where the egg clutch is laid, cleaning and oxygenation of eggs, is typical of many loricariids. On the other hand, the slow development, including delayed eye degeneration, low body growth rates and high estimated longevity (15 years or more) are characteristic of precocial, or K-selected, life cycles. In the absence of comparable data for close epigean relatives (Ancistrus spp.), it is not possible to establish whether these features are an autapomorphic specialization of the troglobitic A. cryptophthalmus or a plesiomorphic trait already present in the epigean ancestor, possibly favoring the adoption of the life in the food-poor cave environment. We briefly discuss the current hypotheses on eye regression in troglobitic vertebrates.