Speech rate in Parkinson's disease: A controlled study. / Estudio controlado del ritmo del habla en la enfermedad de Parkinson.

INTRODUCTION: Speech disturbances will affect most patients with Parkinson's disease (PD) over the course of the disease. The origin and severity of these symptoms are of clinical and diagnostic interest. PURPOSE: To evaluate the clinical pattern of speech impairment in PD patients and identify significant differences in speech rate and articulation compared to control subjects. Speech rate and articulation in a reading task were measured using an automatic analytical method. PATIENTS: A total of 39 PD patients in the 'on' state and 45 age-and sex-matched asymptomatic controls participated in the study. None of the patients experienced dyskinesias or motor fluctuations during the test. RESULTS: The patients with PD displayed a significant reduction in speech and articulation rates; there were no significant correlations between the studied speech parameters and patient characteristics such as L-dopa dose, duration of the disorder, age, and UPDRS III scores and Hoehn & Yahr scales. CONCLUSION: Patients with PD show a characteristic pattern of declining speech rate. These results suggest that in PD, disfluencies are the result of the movement disorder affecting the physiology of speech production systems.

Deficit of vitamin D in pregnancy and growth and overweight in the offspring.

BACKGROUND: Maternal vitamin D status during fetal development may influence offspring growth and risk of obesity; however, evidence in humans is limited. OBJECTIVE: To investigate whether maternal circulating 25-hydroxyvitamin D3 (25(OH)D3) concentration in pregnancy is associated with offspring prenatal and postnatal growth and overweight. METHODS: Plasma 25(OH)D3 concentration was measured in pregnant women (median weeks of gestation 14.0, range 13.0-15.0) from the INMA (INfancia y Medio Ambiente) cohort (Spain, 2003-2008) (n = 2358). Offspring femur length (FL), biparietal diameter (BPD), abdominal circumference (AC) and estimated fetal weight (EFW) were evaluated at 12, 20 and 34 weeks of gestation by ultrasound examinations. Fetal overweight was defined either as AC or as EFW ⩾ 90th percentile. Child's anthropometry was recorded at ages 1 and 4 years. Rapid growth was defined as a weight gain z-score of >0.67 from birth to ages 6 months and 1 year. Age- and sex-specific z-scores for body mass index (BMI) were calculated at ages 1 and 4 years (World Health Organization referent); infant's overweight was defined as a BMI z-score ⩾ 85th percentile. RESULTS: We found no association of maternal 25(OH)D3 concentration with FL and a weak inverse association with BPD at 34 weeks. Maternal deficit of 25(OH)D3 (<20 ng ml(-1)) was associated with increased risk of fetal overweight defined as AC ⩾ 90th percentile (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.01-2.21; P = 0.041) or either as EFW ⩾ 90th percentile (OR = 1.47, 95% CI: 1.00-2.16; P = 0.046). No significant associations were found with rapid growth. Deficit of 25(OH)D3 in pregnancy was associated with an increased risk of overweight in offspring at age 1 year (OR = 1.42, 95% CI: 1.02-1.97; P = 0.039); however, the association was attenuated at age 4 years (OR = 1.19, 95% CI: 0.83-1.72; P = 0.341). CONCLUSIONS: Vitamin D deficiency in pregnancy may increase the risk of prenatal and early postnatal overweight in offspring. Clinical trials are warranted to determine the role of vitamin D in the early origins of obesity.

Associations of maternal circulating 25-hydroxyvitamin D3 concentration with pregnancy and birth outcomes.

OBJECTIVE: To investigate the association of maternal circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration with pregnancy and birth outcomes. DESIGN: Prospective cohort study. SETTING: Four geographical areas of Spain, 2003-2008. POPULATION: Of 2382 mother-child pairs participating in the INfancia y Medio Ambiente (INMA) Project. METHODS: Maternal circulating 25(OH)D3 concentration was measured in pregnancy (mean [SD] 13.5 [2.2] weeks of gestation). We tested associations of maternal 25(OH)D3 concentration with pregnancy and birth outcomes. MAIN OUTCOME MEASURES: Gestational diabetes mellitus (GDM), preterm delivery, caesarean section, fetal growth restriction (FGR) and small-for-gestational age (SGA), anthropometric birth outcomes including weight, length and head circumference (HC). RESULTS: Overall, 31.8% and 19.7% of women had vitamin D insufficiency [25(OH)D3 20-29.99 ng/ml] and deficiency [25(OH)D3 < 20 ng/ml], respectively. After adjustment, there was no association between maternal 25(OH)D3 concentration and risk of GDM or preterm delivery. Women with sufficient vitamin D [25(OH)D3 ≥ 30 ng/ml] had a decreased risk of caesarean section by obstructed labour compared with women with vitamin D deficiency [relative risk (RR) = 0.60, 95% CI 0.37, 0.97). Offspring of mothers with higher circulating 25(OH)D3 concentration tended to have smaller HC [coefficient (SE) per doubling concentration of 25(OH)D3, -0.10 (0.05), P = 0.038]. No significant associations were found for other birth outcomes. CONCLUSION: This study did not find any evidence of an association between vitamin D status in pregnancy and GDM, preterm delivery, FGR, SGA and anthropometric birth outcomes. Results suggest that sufficient circulating vitamin D concentration [25(OH)D3 ≥ 30 ng/ml] in pregnancy may reduce the risk of caesarean section by obstructed labour.

Indoor and outdoor concentrations and determinants of NO2 in a cohort of 1-year-old children in Valencia, Spain.

UNLABELLED: Nitrogen dioxide (NO2) is produced from the exhausts of vehicles and gas appliances and is known to pose certain health risks. In this study, we characterize the exposure to this substance during the first year of life, which is an important period of development. To this end, we used passive samplers to measure indoor and outdoor NO2 levels for 2 weeks in the homes of 352 children. To compensate for the fact that NO2 levels were measured only once in each home, a correction factor was calculated to assign each child an outdoor NO2 exposure value for the first year of life. The outdoor NO2 concentrations were 26.1 microg/m(3) while those measured indoors averaged 18.0 microg/m(3). A multivariate linear regression analysis showed that the main determinants of outdoor NO2 levels were the degree of urbanization and the frequency of vehicle traffic at the location of the residence while for indoor NO2 levels the principal determinants were the type of cooking range and water heater present in the home, the season of the year, and both the country of origin and educational level of the mother. PRACTICAL IMPLICATIONS: Exposure to NO2 has been related to respiratory and other health problems among children. Precise identification of the main sources of both indoor and outdoor NO2 should shed light on appropriate intervention periods and methods. Our results indicate that while population density and traffic-related variables are the main determinants of outdoor NO2 levels, the use of gas appliances have the greatest impact on indoor levels. Strategies should thus be developed to reduce such exposure, especially with regard to reducing emissions from vehicle traffic.

Seasonality of suicide: a multi-country multi-community observational study.

AIMS: We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations. METHODS: Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986-2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression. RESULTS: We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33-1.62) to 1.05 (95% CI: 1.01-1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05). CONCLUSIONS: Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.

Air pollution and cardiovascular admissions association in Spain: results within the EMECAS project.

OBJECTIVE: To evaluate the short term effect of air pollution on cardiovascular admissions in 14 Spanish cities METHODS: The period under study was from 1995 to 1999. Daily emergency admissions for all cardiovascular diseases (CVD) and heart diseases (HD) were obtained from hospital records, and the corresponding daily levels of particulates, SO2, NO2, CO, and ozone were recorded. The magnitude of association was estimated using Poisson generalised additive models controlling for confounding and overdispersion. For each cause, lagged effects, up to three days, of each pollutant were examined and combined estimates were obtained. For ozone the analyses were restricted to the warm period. One and two pollutant models were performed. RESULTS: Associations were more consistent in lag 0 (concurrent day) and 1 (lag 0-1), except in the case of ozone where there was a more delayed relation (lag 2-3). For combined estimates an increase of 10 microg/m3 in the PM10 levels in lag 0-1 was associated with an increase of 0.9% (95% CI: 0.4 to 1.5%) in the number of hospital admissions for CVD, and 1.6% (0.8 to 2.3%) for HD. For ozone the corresponding estimates for lag 2-3 were 0.7% (0.3 to 1.0) for CVD, and 0.7% (0.1 to 1.2) for HD. An increase of 1 mg/m3 in CO levels was associated with an increase of 2.1% (0.7 to 3.5%) in CVD admissions, and 4.2% (1.3 to 7.1%) in HD admissions. SO2 and NO2 estimates were more sensitive in two pollutant models CONCLUSIONS: A short term association between increases in daily levels of air pollutants and the number of daily admissions for cardiovascular diseases, with specificity for heart diseases, has been described in Spanish cities.

Mediterranean dietary pattern in pregnant women and offspring risk of overweight and abdominal obesity in early childhood: the INMA birth cohort study.

BACKGROUND: Animal models have suggested that maternal diet quality may reduce offspring obesity risk regardless of maternal body weight; however, evidence from human studies is scarce. OBJECTIVE: The aim of this study was to evaluate associations between adherence to the Mediterranean diet (MD) during pregnancy and childhood overweight and abdominal obesity risk at 4 years of age. METHODS: We analysed 1827 mother-child pairs from the Spanish 'Infancia y Medio Ambiente' cohort study, recruited between 2003 and 2008. Diet was assessed during pregnancy using a food frequency questionnaire and MD adherence by the relative Mediterranean diet score (rMED). Overweight (including obesity) was defined as an age-specific and sex-specific body mass index ≥85th percentile (World Health Organization referent), and abdominal obesity as a waist circumference (WC) >90th percentile. Multivariate adjusted linear and logistic regression models were used to evaluate associations between pregnancy rMED and offspring overweight and abdominal obesity. RESULT: There was no association between rMED and body mass index z-score, whereas there was a significant association between higher adherence to MD and lower WC (ß of high vs. low rMED: -0.62 cm; 95% confidence interval: -1.10, -0.14 cm, P for trend = 0.009). CONCLUSION: Pregnancy adherence to the MD was not associated with childhood overweight risk, but it was associated with lower WC, a marker of abdominal obesity.

Postnatal development of microtubules and neurofilaments in the rat optic nerve: a quantitative study.

In this paper the postnatal changes in the cytoskeleton of the rat optic nerve fibers are described and quantified. These changes are also compared with other parameters such as myelination and axonal caliber with the aim of describing a general pattern of optic nerve maturation from a morphological point of view. The results showed that during the first postnatal week microtubules outnumbered neurofilaments but between days 8 and 20 the neurofilaments rapidly increased and on day 20 were about twice as numerous as microtubules. This proportion remained almost unaltered from the end of the third week to the 44th postnatal day. The comparison with other parameters suggested that the cytoskeleton, and in particular the proportion between its components, may be a more reliable index for measuring optic nerve maturation than other variables commonly used.

Reversible peripheral neuropathy induced by a single administration of high-dose paclitaxel.

Peripheral neuropathy (PN) is the main side effect with cycles of paclitaxel at standard doses (175 mg/m2 for 21 days). Administration of a single high-dose paclitaxel (HDP) is a novel approach for the treatment of cancer. We have prospectively measured neurotoxicity induced by HDP during a phase I trial. Nineteen patients were treated with escalating doses of paclitaxel by 24-hour infusion. In our study, PN induced by HDP was moderate, reversible, and not dose limiting. Severe PN was seen in patients who had received previous neurotoxic chemotherapy, and caution on the administration of HDP in this setting is warranted.

A versatile and simple method for staining nervous tissue using Giemsa dye.

A method for staining nervous tissue with Giemsa dye is described. The procedure is easy to perform and works well on paraffin, celloidin and frozen sections. The results combine the properties of the Nissl stains with the polychromatism of the Romanowsky dyes. The method also provides good results for counterstaining autoradiographies, or when applied after horseradish or peroxidase-antiperoxidase techniques. In the latter case, Giemsa dye darkens the immunoreactive product in the same manner as osmium tetroxide but avoids the well-known risks of handling this toxic agent.

Nematosomes in external horizontal cells of white perch (Roccus americana) retina: changes during dark and light adaptation.

Cytoplasmic inclusions resembling nucleoli and termed nematosomes have been described in several areas of the nervous system but not in the retina. Here we report the presence of these structures in the external horizontal cells of white perch (Roccus americana). Nematosomes were larger and more numerous in dark-adapted retinas than in light-adapted ones. An inverse relation of horizontal cell spinules was found in these cells, suggesting that electron-dense material observed in spinules may originate from nematosomes.

Morphological effects of chronic haloperidol administration on the postnatal development of the striatum.

The aim of this paper is to describe the morphological changes induced in the striatum after the administration of haloperidol during the first postnatal month, a period in which a lack of tolerance to treatment with neuroleptics has been reported. At the end of the treatment several morphological parameters were evaluated including neuron size and density and the synaptic profile areas of cross-sectioned dendrites and axon terminals. The results evidenced a loss of the smallest dendritic profiles without the rest of the parameters examined being affected. This response differs from the one observed in the adult rat striatum that does develop tolerance to haloperidol. It seems to more closely correspond to the changes found in the prefrontal cortex, a region that does not develop tolerance after chronic treatment with neuroleptics.

Axon types classified by morphometric and multivariate analysis in the rat optic nerve.

Calibers of the rat optic nerve axons distribute unimodally and it is difficult to distinguish groups among them. However, these fibers arose from 3 types of ganglion cells and showed 3 conduction velocities. Performing a cluster analysis over several ultrastructural parameters we found 3 main groups of fibers. These groups are present in a very similar proportion to the ganglion cells groups described in the rat retina.

Brain lesions and water-maze learning deficits after systemic administration of kainic acid to adult rats.

The relationship between hippocampal damage and spatial learning deficiencies was studied in rats injected with kainic acid (10 mg/kg i.p.). A single injection was given either before or after the acquisition phase of the Morris water-maze task. In this acquisition phase, the animals were required to find a hidden underwater platform starting from four different points. The task was repeated twice a day for 10 days. In the retention phase after 10 days rest, the rats repeated the same task. The damage caused by the treatment occurred in several prosencephalic areas, including the piriform and enthorhinal cortices, the thalamus and the hippocampus. In the latter, greatest damage was seen in CA1 followed by CA3 while CA2 and the gyrus dentatus appeared almost unaffected. The behavioural results indicated that kainic acid impaired but did not preclude the acquisition of the water-maze task. During the retention phase, no significant differences in latencies were found between animals that were treated before and after acquisition, thus, indicating that pretraining does not play an important role in the recovery of these spatial abilities following hippocampal lesions.

Postnatal development of striatal connections in the rat: a transport study with wheat germ agglutinin-horseradish peroxidase.

This paper deals with the postnatal development of afferent and efferent connections of the rat striatum as revealed by the transport of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP). Tracer was injected weekly from birth to the end of the first postnatal month in the head of the caudate nucleus. To control for transport from cortical areas contaminated by the micropipette, injections in newborn rats were made by either vertical or lateral penetrations. In addition some newborn and 14-day-old animals were injected only in the cortex. The results showed that at birth there was retrograde transport to the thalamus, substantia nigra and raphe nuclei. Labelling in the cortex was seen at birth but was probably due to cortical contamination. Transport from the striatum was clearly established on day 7, when a few labelled neurons were observed on both the ipsi and contralateral sides. These neurons increased in number and were distributed through layers III to VI by day 14. At this time labelled cell bodies were observed in the claustrum and lateral amygdaloid nucleus as well as in the globus pallidus and entopeduncular nucleus. On day 21 the contralateral labelling of the lateral amygdaloid nucleus was apparent. The anterograde transport from the striatum to globus pallidus, entopeduncular nucleus and substantia nigra was already visible at birth although its intensity increased during the first postnatal month.

[Emotional components of language in multi-infarct dementia]. / Estudio de los componentes emocionales del lenguaje en la demencia multiinfarto.

BACKGROUND: Prosody is the faculty of language by which different meanings may be referred through variations in the tone, rhythm and accent with independence of the words and grammatical structures. Alteration of this sphere may modify the emotional components and proposals of the language. The aim of this study was to evaluate the existence of aprosody in a series of patients with multiinfartion dementia, quantify the disorder and ascertain the factors to which it is related. METHODS: Fourteen patients with criteria of multiinfarction dementia were included in the study. Aprosody was evaluated according to the Monrad-Krohn criteria. Neuropsychological examination included the MiniMental State Examination, the Blessed scale and the Hachinshi ischemic scale. RESULTS: Changes were seen in the prosody of 13 patients. Upon univariant statistical analysis a significant correlation was observed between the grade of alteration in prosody and the deterioration observed in the MiniMental and Blessed scale. This finding was confirmed following correction of the influence of depressive symptoms, age and time of evolution by multivariant analysis. CONCLUSIONS: The disturbances in prosody are a sensitive indicator of right hemisphere lesion in vascular dementia and are fundamentally related with the degree of neuropsychological deterioration.

[Intractable aqueous diarrhea associated with carbamazepine intake]. / Diarrhée aqueuse intraitable associée à la prise de carbamazépine.

Diarrhea is usually a minor side-effect of carbamazepine. We report two severe diarrhea cases, leading to drug withdrawal.

[Comparison of two methods in the analysis of the short-term effect of air pollution on health]. / Comparación de dos métodos en el análisis del efecto a corto plazo de la contaminación atmosférica en la salud.

OBJECTIVE: We compare two methods to analyse the relationship between air pollution and health. One of them (ME) is based on a generalized linear model, while the other one (MN) incorporates a generalized additive model (GAM). Besides the statistical model used, both methods schow additional discrepancies for the type and number of variables used in the control of confounding. METHOD: An analysis was carried out for each lag of black smoke (0 to 5) and several health indicators from the city of Valencia (Spain) following both methods. Results were compared examining the sequence and the lag of the higher coefficient. The ratio between confidence intervals width and the percent difference in the estimates were also obtained. RESULTS: The discrepancies in results according to the methodology were small. The sequence shaped and the lag of higher coefficient generally remained invariant. Coefficients were similar (percent difference of MN over ME was not greater than 10%). Confidence intervals were more precise for MN, although the reduction was not very strong (the width ratio was around 90%). CONCLUSIONS: The short variation of the results guarantees the applicability of both MN and ME methods, although the systematic reduction of the standard error of MN supports its use as a more efficient procedure to control for confounding.

[Estimate of daily cases of influenza from the cases notified to the Reportable Disease System: usefulness in time series studies]. / Estimación de los casos diarios de gripe a partir de los casos declarados al Sistema de Enfermedades de Declaración Obligatoria: utilidad en estudios de series temporales.

In time series analyses assessing the relationship between risk factors and respiratory diseases or mortality, influenza incidence is a potential cofounder and, therefore, must be controlled. Available influenza data come from weekly compulsory notifiable disease (EDO system). Furthermore, its graphical distribution, suggests that information may be underestimated in holiday periods. We have applied a procedure for estimate daily influenza series from the weekly cases, using less, a non-parametric local fit. Findings show that smoothing could avoid stepping and sudden peaks in the original series.