Cognitive decline in adult-onset temporal lobe epilepsy: Insights from aetiology.

PURPOSE: To identify patients with adult-onset temporal lobe epilepsy (TLE) at risk of developing cognitive decline. Detecting which patients, aetiologies, or factors are most closely related with memory decline would allow us to identify patients that would eventually benefit from more specific treatment. METHODS: Single centre, retrospective analysis of a prospectively followed-up cohort study, including all patients with the diagnosis of adult-onset TLE during 2013, with a minimum follow-up of five years. Memory and cognitive decline were analysed at 5 years and at last follow-up. RESULTS: Of 89 initially selected patients, 71 were included. After 5 years, 11/71 (15.5%) patients suffered cognitive decline, of which 1/71 (4%) developed dementia. At last follow-up (range 65-596 m) a total of 34/71 (47.8%) patients were diagnosed with cognitive decline, specifically either memory decline or dementia. Cognitive decline at 5 years was related to: 1. Age at onset: 62.65 years (SD 9.04) in the group with cognitive decline vs 50.33 y. (SD 13.02 in the group without cognitive decline; p=0.004); 2. Onset as status epilepticus (3/6 in patients with memory decline vs 8/65 in patients without cognitive decline; p=0.04); 3. Immune aetiology: 42% compared with unknown (10%) and structural (10%) aetiologies; p=0.036; 4. Hippocampal sclerosis on MRI: 5/11 patients with cognitive decline vs 9/51 patients without cognitive decline; p=0.035. Cognitive decline was not related to seizure frequency, sex, or age (p=0.78; p=0.40; p=0.95, respectively). CONCLUSIONS: Older age at epilepsy onset, onset as status epilepticus, immune aetiology, and hippocampal sclerosis are risk factors for developing cognitive decline in patients with adult-onset temporal lobe epilepsy.

Field efficacy of Metarhizium anisopliae oil formulations against Rhipicephalus microplus ticks using a cattle spray race.

Rhipicephalus microplus tick is the main ectoparasite of cattle in Brazil. The exhaustive use of chemical acaricides to control this tick has favored the selection of resistant tick populations. Entomopathogenic fungi, as Metarhizium anisopliae, has been described as a potential biocontroller of ticks. Therefore, the aim of this study was to evaluate the in vivo efficacy of two oil based formulations of M. anisopliae for the control of the cattle tick R. microplus under field conditions using a cattle spray race as a method of treatment. Initially, in vitro assays were carried out with an aqueous suspension of M. anisopliae, using mineral oil and/or silicon oil. A potential synergism between oils and fungus conidia for tick control was demonstrated. Additionally, the usefulness of silicon oil in order to reduce mineral oil concentration, while improving formulation efficacy was illustrated. Based on the in vitro results, two formulations were selected for use in the field trial: MaO1 (107 conidia/mL plus 5% mineral oil) and MaO2 (107 conidia/mL plus 2.5% mineral oil and 0.01% silicon oil). The adjuvants concentrations (mineral and silicon oils) were chosen since preliminary data indicate that higher concentrations caused significant mortality in adult ticks. For this, 30 naturally infested heifers were divided into three groups based on previous tick counts. The control group did not receive treatment. The selected formulations were applied on animals using a cattle spray race. Subsequently, tick load was evaluated weekly by counting. The MaO1 treatment significantly reduced the tick count only on day +21, reaching approximately 55% efficacy. On the other hand, MaO2 showed significantly lower tick counts on days +7, +14, and +21 after treatment, with weekly efficacy achieving 66%. The results showed a substantial reduction of tick infestation, up to day +28, using a novel formulation of M. anisopliae based in the mixture of two oils. Moreover, we have shown, for the first time, the feasibility of employing formulations of M. anisopliae for large-scale treatment methods, such as a cattle spray race, which in turn, may increase the use and adhesion to biological control tools among farmers.

Morphometric variants of the paranasal sinuses in a Mexican population: expected changes according to age and gender.

BACKGROUND: There are developmental variations in the paranasal sinuses. Our objective was to determine their dimensions and volume stratified by age and sex and define the expected growth pattern. MATERIALS AND METHODS: A retrospective, observational study was performed including computed tomography (CT) of patients between 1 and 20 years of age. The volumes of the frontal, sphenoid, and maxillary sinuses were obtained. RESULTS: A total of 210 CT were included with a mean age of 10 ± 6.1 years, 106 (50.5%) were female. Groups were categorised in ranges of 5 years. Spearman correlation coefficients between the right and left sides were 0.843, 0.711, 0.916 for the frontal, sphenoid and maxillary sinuses. Post-hoc for the categorical age groups demonstrated statistically significant differences with values of p < 0.01, except between age groups 11-15 against ≥ 16 years of age (p = 0.8). Gender-related differences were evident with a higher air volume in girls in the 5-10-year-old group, while boys predominated in the rest of the groups. CONCLUSIONS: Computed tomography is ideal for pre-surgical sinus assessment. The maximum volume of paranasal sinuses is reached at the age of 15. There is a clear volumetric difference between age and gender groups. There is a direct relationship between a volume and its contralateral counterpart.

Clinical and molecular characterization of hereditary spastic paraplegia in a spanish Southern region.

INTRODUCTION: Spastic paraplegia (SPG) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations. Despite of the new molecular technologies, many patients remain yet undiagnosed. OBJECTIVE: The purpose of this study was to describe the clinical presentation and molecular characteristics of a cohort of 27 patients from 18 different families with SPG in the south of Spain. METHODS: We used a targeted next-generation sequencing (NGS) approach to study a proband from each family. RESULTS: Variants in SPG11 gene were the most common cause of SPG in our area. We made a genetic diagnosis in 52% of cases, identified 3 novel variants and reclassified one uncertain variant in SPG11 gene as pathogenic variant. We identified a patient with two truncanting mutations in SPG11 gene and late onset disease and report another missense mutation outside of motor domain of KIF1A gene in a family with pure SPG. CONCLUSION: Our study contributes to enhance the scientific knowledge of SPG. It is important to note the large group of cases (48%) that were not genetically diagnosed in our cohort. Therefore NGS approach is an efficient diagnostic tool, but it still large the number of non-diagnosed subjects, suggesting further genetic heterogeneity.

[Thyrotropin reference ranges during pregnancy in the province of Huelva, Spain]. / Intervalos de referencia de la tirotropina durante la gestación en la provincia de Huelva.

OBJECTIVE: The correct diagnosis of hypothyroidism during pregnancy requires knowledge of the local trimester-specific thyrotropin (TSH) reference ranges. When these are not available, the guidelines recommend upper limits of 2.5, 3.0, and 3.0µU/ml for the 1st, 2nd, and 3rd trimesters, respectively. The aim is to establish the reference range for our local population. MATERIAL AND METHODS: A population-based observational study was performed on healthy pregnant women from 11 healthcare centres in the province of Huelva. Women were recruited consecutively during 2016 through the pregnancy process. Women were excluded who had a history of thyroid or medical disease, a poor obstetric history, multiple pregnancy, thyroid autoimmunity, and extreme TSH values (<0.4µU/ml or>10µU/ml), as well as women treated with levothyroxine for thyroid dysfunction. RESULTS: The study included a total of 186 pregnant women, with a mean age of 30.7 years (95% CI: 29.8-31.6) and a body mass index (BMI) of 23.6 (95% CI: 23.2-24.0). Most of them had the first laboratory tests performed before week 11 of pregnancy. Valid subjects for analysis were 145, 105, and 67 pregnant women in the 1st, 2nd, and 3rd trimesters, respectively, after excluding those due to abortion (18.9%), autoimmunity (6.5%), hypo/hyperthyroidism (2.2%), and levothyroxine treatment during the 2nd/3rd trimester (18.6%). The 97.5% TSH percentile for the 1st, 2nd, and 3rd trimester was 4.68, 4.83, and 4.57µU/ml, respectively. Thyroid dysfunction was identified in 80 women (55.2%), 33 of whom received treatment with Levothyroxine (22.7%). With the new criteria, thyroid dysfunction prevalence would be reduced to 6.2%, and the need for treatment to 4.1%. CONCLUSION: The reference range for TSH in our population differs from that proposed by the guidelines. Unnecessary treatment was being given to 18.6% of pregnant women.

[Type 1 Diabetes Mellitus: brief review of the main associated psychological factors]. / Diabetes mellitus tipo 1: breve revisión de los principales factores psicológicos asociados.

Type 1 Diabetes Mellitus (T1DM) is a widespread chronic disease among children and adolescents. Diagnosis and evolution usually involves a significant burden on the patient, and their families must change various aspects of their lifestyle to fulfill the demands of treatment. This study aims to identify the main psychological, family, and adjustment to illness features of children and adolescents diagnosed with DM1 and, in particular to highlight the associated psychopathological factors. The methodology involved a systematic literature search in the main scientific databases. Due to the biopsychosocial impact of DM1 usually assumed in the life of the child and family, and how it may compromise the quality of life and emotional well-being of both, different studies have agreed on the importance of identifying the set of psychological factors involved in healthy adjustment to illness in the child and adolescent with DM1.

Dimethyl sulfide biofiltration using immobilized Hyphomicrobium VS and Thiobacillus thioparus TK-m in sugarcane bagasse.

Sugarcane bagasse was used as a carrier material of microorganisms in two different biofilters used to remove dimethyl sulfide (DMS) from a gas stream. The first biofilter was inoculated with Hyphomicrobium VS and the second with Thiobacillus thioparus Tk-m. During the operation of the biofilters the empty bed residence time (EBRT) was varied from 90 to 180 seconds and the inlet concentration of DMS from 12 to 50 ppmv. The inlet load was varied in the range of 0.62 to 5.2 (g DMS/m3 h). The maximum elimination capacity (EC) of the biofilter inoculated with Hyphomicrobium VS was 5 g DMS/m3 h; however, for the biofilter inoculated with T. thioparus Tk-m the maximum EC was 3.9 g DMS/m3 h. For T. thioparus TK-m the maximum removal efficiency (RE) obtained was 85.1 +/- 5.2% at 12 ppmv DMS inlet concentration, inlet load of 0.62 g DMS/m3 h and 180 s EBRT. The highest removal efficiency for Hyphomicrobium VS was 97.6 + 4.8% at 12 ppmv DMS inlet concentration, load of 0.62 g DMS/m3 h and 180 s EBRT.

Premenstrual asthma and leukotriene variations in the menstrual cycle.

BACKGROUND: Several authors have reported an increase in leukotriene C4 in the premenstrual phase in women with severe premenstrual asthma, indicating that antileukotrienes could be used in treatment. OBJECTIVE: To analyse the role of leukotrienes in premenstrual asthma. METHODS: A questionnaire on respiratory symptoms and peak flow during one complete menstrual cycle was given to women of fertile age to define them as asthmatics who suffered from premenstrual asthma or not. Premenstrual asthma (PMA) was defined as a clinical or functional deterioration (≥20%) in the premenstrual phase compared with the preovulatory phase. Blood samples to measure leukotriene C4 were taken during the preovulatory and premenstrual phases. RESULTS: Blood samples were taken in 62 asthmatic women, 34 of whom (54.3%) presented PMA criteria, all with a premenstrual deterioration of between 20 and 40%. There was no difference in leukotriene C4 levels between the preovulatory and premenstrual phases in the women who suffered from PMA (1.50ng/mL vs. 1.31ng/mL; p=0.32) and those who did not (1.40ng/mL vs. 1.29ng/mL; p=0.62). Neither were there any differences in leukotriene levels between women with or without PMA. The results were similar for each category of asthma severity. CONCLUSIONS: Our data show that leukotriene C4 does not appear to be involved in the pathogenesis of premenstrual asthma, or support the use of anti-leukotrienes in the specific treatment of premenstrual asthma, at least in women with a moderate premenstrual deterioration. No differences appeared in any of the categories of asthma severity.

[Determination of brain natriuretic peptide in patients undergoing different haemodiafiltration techniques]. / Determinación del péptido natriurético cerebral en pacientes sometidos a diferentes técnicas de hemodiafiltración.

UNLABELLED: IB-type natriuretic peptide is a cardíac neurohormone secreted by the cardíac ventricules in response to ventricular dilatation so plasma BNP level correlate with left ventricular mass and dysfunction. Dialysis patients have much greater levels of BNP due to the volume overload and because of reduced renal clearance. The aim of this study was to mesure and compare the BNP levels in three groups of patients who received different hemodiafiltration techniques: Daily online hemodiafiltration (HDFOLd), on-line hemodiafiltration (HDFOL) and low convective volume hemodiafiltration (HDF). Fifteen patients were included, five in each group. Pre and postdialysis BNP leves were measured during 8 weeks. The measure was done at the beginning of the week (long period), and at the end (short period), in order to study if there were significative differences between techniques and periods. We found significative differences between predialysis BNP levels in the short period (BNPpreC) and the long period (BNPpre-L). We also found significative differences with the posdialysis BNP in both periods; BNPpre- L vs. BNPpos-L (1069+/-1031 vs. 612 +/- 540). After comparing the three techniques the study showed significative differences between BNPpreC in HDF and HDFOL compared with HDFOld. And also after dialysis between BNPpos-C in HDFOLd compared with the other techniques. CONCLUSION: Although previous papers have shown that BNP levels have limited potential for assessment of hydration in hemodialysis patients, in this study our data demonstrate that after dialysis BNP levels decline in a significative way in the long and short period and we have found that patients on daily hemodialysis show lower BNP levels, and maybe this could be explained because daily on-line haemodiafiltration patients had lower weight rise between dialysis sessions and also better haemodynamic tolerance.

[Oxidative stress analysis in patients on hemodiafiltration on-line]. / Análisis del estrés oxidativo en pacientes en hemodiafiltración en línea.

Patients with chronic renal disease have a very high mortality due to cardiovascular disease. However, the traditional risk factors are not the only one explanation. Nowadays, there are new risk factors becoming, and one of these is the oxidative stress. Besides today we know that when these patients receive haemodialysis are being exposed to an additional oxidative stress. The aim of this study was to measure and to compare the degree of oxidative stress in two groups of patients on different dialysis techniques: a) On-Line Haemodiafiltration three times / week (OL-HDF). b) Daily Om-Line haemodiafiltration ( six times / week ) ( dOL-HDF) We studied 9 patients with chronic renal disease stage 5 on hemodialysis. They all were men, with a medium age of 72,5 +/- 6 years. Five patients were on dOL-HDFand four on tOL-HDF. Glutathione (GSH) concentration of patients on dOL-HDF before dialysis was 742+/- 153 nmol/ml and post-dialysis de 878+/- 223. Blood GSSG concentration before and after dialysis was 34+/- 14 nmol/ml y 137+/- 74 nmol/ml (p< 0,03). GSSG/GSH ratio pre-dialysis was 58+/-10 and post-dialysis 169+/-65 ( p < 0,03). In OL-HDF group GSSG concentration and the ratio GSSG/GSH also increased in a significative way from 99+/-45 nmol/ml to 179+/-66 nmol/ml, and from 161+/- 99 to 337+/-143 ( p<0,05). We also found differences in pCR concentrations between both groups; 3+/-1,4 g/l in dOL-HDF and 8,75+/-5,8 g/l in HDF OL. (p< 0,05). We did not find differences between xatine-oxidase activity before and after hemodialysis and between groups. In conclusion, patient with terminal chronic renal disease on OL-HDF receive an additional load of oxidative stress, as the increase in GSSG/GSH ratio in both groups shows. However patients on dHDF-OL shows low ratios GSSG/GSH post-hemodialysis and low pCR concentrations, and maybe this could be explained because daily on line haemodiafiltration improves purification of inflammatory mediators. Clue words: Hemodialysis, oxidative stress, glutathione, gssg/gsh ratio, xantine oxidasa.

Beneficios independientes de la reducción de la presión arterial en pacientes tratados con nifedipina en microgránulos / Independent benefits of the reduction of the arterial pressure in patients treaties with nifedipine in micro-granules

El estado dippers es un factor de riesgo independiente en los pacientes hipertensos (Risers-R-) Non-dippers-ND-> Dippers-D>Dippers extremos-DE). Se evaluó el efecto de la nueva nifedipina en microgránulos (NMG) una vez al día en la disminución de la presión arterial nocturna medida a través del MAPA con Mobil-o-Graph-CE0434-(I.E.MGmbh-Cockerillstr. 69 D-Stolberg. Germany). Se incluyeron pacientes hipertensos (PAS mayor igual 140 y/o PAD mayor igual 90 mmHg, medidas con esfigmomanómetro de Hg) que recibieron de 30 a 60 mgrs/día de NMG, en un estudio prospectivo abierto comparativo y cruzado en time-doses 8 am ó 8 pm; que luego de 6 semanas de tratamiento mantuvieran PAS < 140 mmHg. Se reclutaron 73 pacientes. 40 pacientes (54.8 por ciento), mantuvieron su estado: NDn = 22 (disminución de la PAS nocturna entre 0 y 10 por ciento), D n= 16 (disminución de PAS nocturna entre 10 y 20 por ciento) y Rn = 2 (incremento de la PAS nocturna). Los otros 33 pacientes (45.2 por ciento) modificaron su estado: cinco: 3D y 2ND cambiaron a DE (disminución de la PAS nocturna > 20 por ciento), once: 2DE y 9ND se transformaron en D, catorce: 6R, 1DE y 7D hacia ND y 3D cambiaron a R. No hubo diferencias significativas en el cambio de estado dippers en ambos grupos (30 ó 60 mgrs), 17 pacientes mejoraron su estado (9ND y 2DE) se transformaron en D y 6R pasaron a ND; 16 pacientes dipper se mantuvieron. Estos resultados sugieren que la NMG ofrece en el 45 por ciento de los pacientes estudiados un beneficio independiente de la reducción de la presión arterial, manteniendo o mejorando el estado dippers ofreciendo una mejor predicción en la disminución de eventos cardiovasculares y del pronóstico de los accidentes cerebrovasculares

Atypical thyroiditis in Huelva, Spain.

OBJECTIVE: To report an epidemic of atypical thyroiditis that occurred in southwestern Europe during 1995. METHODS: We present the clinical, laboratory, morphologic, and histologic features of 672 cases of thyroiditis and describe the results of treatment. RESULTS: During 1995, atypical thyroiditis was diagnosed in 672 of 725 patients with thyroid disorders encountered at our medical center in Huelva, Spain. Of these patients, 98% were women with normal ovarian function. The clinical findings were acute or subacute manifestation of diffuse nodular enlargement of the thyroid and spontaneous, severe pain on deglutition and palpation of the gland. Initial hematology and serum biochemistry studies, free triiodothyronine, free thyroxine, thyrotropin, and thyroid-stimulating immunoglobulins were in the normal range, but after the second week, the thyrotropin level began to increase. Thyroid antibodies (thyroglobulin and thyroid peroxidase) increased up to 300 times the high-normal level. Ultrasonography exhibited diffuse nodular enlargement of the thyroid gland, with irregular hypoechoic, normal, and hyperechoic zones. Fine-needle aspiration biopsy showed abundant lymphocytic infiltration. The best treatment results were obtained with the combination of levothyroxine and deflazacort. Because the epidemic appeared after a severe drought of 5-year duration (1991 to 1995) and affected women with normal ovarian function, our etiopathogenetic hypothesis was that an estrogen-like chemical substance polluted the area swamps. The high concentration of the pollutant was attributable to diminished water levels (8% of their capacity at the end of the drought period), and this situation may have affected the population through tap water used for human consumption. CONCLUSION: We describe an atypical autoimmune thyroiditis that affected primarily women of reproductive age, after a severe drought. The main features were a very painful, diffuse nodular enlargement of the thyroid gland, substantially increased thyroid antibodies, good response to levothyroxine and deflazacort combination treatment, and a benign evolution to chronic thyroiditis. Pollutants from various sources should be considered when atypical thyroiditis occurs in any community.

[Hyperalphalipoproteinemias and medical advise in primary care. Changes of the lipid pattern]. / Las hiperalfalipoproteinemias y el consejo médico en atención primaria. Modificaciones del patrón lipídico.

OBJECTIVE: To analyse the modifications in the lipid pattern experienced in the observance of patients with Hyperalpha-lipoproteinaemia (HAL). DESIGN: A prospective follow-up study. SETTING: La Orden Primary Care Centre, Huelva. PATIENTS: 120 diagnosed with HAL (cHDL higher than the 90 percentile of their same age and sex group from a reference population with cLDL and Triglycerides less than 150 and 200 mg/dl, respectively) and observed for 2.5 +/- 1.5 years. MEASUREMENTS AND RESULTS: Blood pressure, weight, size, cholesterol, cHDL, cLDL, Triglycerides, Glucaemia and Uric acid were determined. The modifications in the diagnosis of HAL, and changes in averages and percentages of several variables, were calculated. Out of 95 people (79.1%) (Age: 42.6 +/- 16), HAL was confirmed in 42.1% (CI, 24.8-59.4) and Hypercholesterolaemia 11a in 20%. There was no lipid disorder in 37.9%. CONCLUSIONS: HAL at a high rate was not confirmed. After HAL is diagnosed, we must be cautious in our advice on cardiovascular protection, as it could be secondary or be modified over time.

470 million years of conservation of microsatellite loci among fish species.

Primers for 18 microsatellite loci originally isolated from whiting (Merlangius merlangus, n = 6), stickleback (Gasterosteus aculeatus, n = 5) and cod (Gadus morhua, n = 7) were tested across a panel of diverse fish species, representing the three principal superclasses and most principal superorders of fish, to examine conservation of microsatellite regions across distantly related taxa. Three methods were used. First, amplified fragments were analysed by Southern blotting using the relevant microsatellite motif probes. A total of 17 of the tested primer pairs gave a product in the expected size range in at least four of 11 tested species. Second, for two study loci the amplified polymerase chain reaction products were cloned and sequenced in five fish species to reveal a high level of conservation of the flanking and microsatellite sequences. Finally, the 17 loci successfully amplified in non-source species were tested for polymorphism in groups of unrelated individuals from nine species, in several cases revealing extensive polymorphism. Levels of polymorphism were generally high in species from which the loci were derived or among closely related species. The conservation of flanking sequences for particular microsatellite motifs over the span of fish evolution represented in the test species (470 million years) far exceeds that hitherto reported and lends support to the suggestion (derived from studies of whales and marine turtles) that the rate of base substitution in nuclear and mitochondrial sequences is lower in aquatic than terrestrial organisms. A further explanation could be that these sequences, although generally considered neutral, may play an important role in eukaryotic genomes, and may be under strong selective constraints. The study suggests that heterologous primers will be a ready source of polymorphic markers among fish species, but also indicates that caution should be used in cross-species comparisons of variability.

Analysis of N-acyl aminonaphthalene sulphonic acid derivatives with potential anti-human immunodeficiency virus activity by thin-layer chromatography and flame ionization detection.

A method for checking the purity of N-acyl aminonaphthalene disulphonic acid derivatives was required for a systematic study of the anti-human immunodeficiency virus activity of these agents. We describe the use of thin-layer chromatography and flame ionization detection for the separation of these compounds, which are difficult to analyse by conventional methods. All the samples were prepared in methanol solutions (1 microliter) containing 5 micrograms of aminonaphthalene derivative. These samples were applied to each type SIII Chromarod by a single injection and developed with pure methanol or a methanol-chloroform-ammonium hydroxide (35:55:10, v/v/v) solvent system.

A new surfactant series, the N-alkylamino-1-deoxylactitols: application for extraction of 'op' opiate receptors from frog brain.

A new series of surfactants, the N-alkylamino-1-deoxylactitols, was prepared and employed to extract 'op' opiate receptors from frog brain. These surfactants are both cheap and convenient to prepare. Receptors were reproducibly extracted in a good yield using N-nonylamino-1-deoxylactitol. This derivative, which was not denaturing during the extraction process, could thus be used instead of the more costly digitonin, whose rather variable purity affects yield.