Kv7/M channel dysfunction produces hyperexcitability in hippocampal CA1 pyramidal cells of Fmr1 knockout mice.

Fragile X syndrome (FXS), the most frequent monogenic form of intellectual disability, is caused by transcriptional silencing of the FMR1 gene that could render neuronal hyperexcitability. Here we show that pyramidal cells (PCs) in the dorsal CA1 region of the hippocampus elicited a larger action potential (AP) number in response to suprathreshold stimulation in juvenile Fmr1 knockout (KO) than wild-type (WT) mice. Because Kv7/M channels modulate CA1 PC excitability in rats, we investigated if their dysfunction produces neuronal hyperexcitability in Fmr1 KO mice. Immunohistochemical and western blot analyses showed no differences in the expression of Kv7.2 and Kv7.3 channel subunits between genotypes; however, the current mediated by Kv7/M channels was reduced in Fmr1 KO mice. In both genotypes, bath application of XE991 (10 µM), a blocker of Kv7/M channels: produced an increased AP number, produced an increased input resistance, produced a decreased AP voltage threshold and shaped AP medium afterhyperpolarization by increasing mean velocities. Retigabine (10 µM), an opener of Kv7/M channels, produced opposite effects to XE991. Both XE991 and retigabine abolished differences in all these parameters found in control conditions between genotypes. Furthermore, a low concentration of retigabine (2.5 µM) normalized CA1 PC excitability of Fmr1 KO mice. Finally, ex vivo seizure-like events evoked by 4-aminopyiridine (200 µM) in the dorsal CA1 region were more frequent in Fmr1 KO mice, and were abolished by retigabine (5-10 µM). We conclude that CA1 PCs of Fmr1 KO mice exhibit hyperexcitability, caused by Kv7/M channel dysfunction, and increased epileptiform activity, which were abolished by retigabine. KEY POINTS: Dorsal pyramidal cells of the hippocampal CA1 region of Fmr1 knockout mice exhibit hyperexcitability. Kv7/M channel activity, but not expression, is reduced in pyramidal cells of the hippocampal CA1 region of Fmr1 knockout mice. Kv7/M channel dysfunction causes hyperexcitability in pyramidal cells of the hippocampal CA1 region of Fmr1 knockout mice by increasing input resistance, decreasing AP voltage threshold and shaping medium afterhyperpolarization. A Kv7/M channel opener normalizes neuronal excitability in pyramidal cells of the hippocampal CA1 region of Fmr1 knockout mice. Ex vivo seizure-like events evoked in the dorsal CA1 region were more frequent in Fmr1 KO mice, and such an epileptiform activity was abolished by a Kv7/M channel opener depending on drug concentration. Kv7/M channels may represent a therapeutic target for treating symptoms associated with hippocampal alterations in fragile X syndrome.

Evolution of appraisal tool usage preferences in PROSPERO records: a study of non-Cochrane systematic reviews.

OBJECTIVES: This research-on-research substudy uses a data-driven approach to investigate the range of appraisal tools in non-Cochrane systematic reviews and meta-analyses registered in the International Prospective Register of Systematic Reviews (PROSPERO). STUDY DESIGN AND SETTING: A comprehensive web scraping of all completed non-Cochrane registrations in PROSPERO from February 2011 to December 2017 was performed. The focus was classifying the appraisal tools based on study type, assessment aspects, and research topics. RESULTS: After analyzing 17,708 complete records, we found a predominant use of methodological quality assessment tools compared to those for reporting quality or risk of bias (RoB). This indicates a greater emphasis on methodological rigor in the studied protocols. Various tools for assessing methodological quality were observed, reflecting the complexity of such evaluations. Instruments designed for evaluating methodological or reporting quality were mainly intended for non-randomized clinical trials or observational studies, unlike RoB tools more commonly used in randomized clinical trials. No distinct trends in tool usage were observed in specific research conditions or domains, suggesting that tool choice is influenced more by study design than research topic. CONCLUSION: This study provides insights into the preferential use of various assessment tools in conducting non-Cochrane systematic reviews, as evidenced in PROSPERO records. The findings reveal various methodological assessment tools, underscoring their versatility across different study designs and research areas.

Examining the utility of pinhole-type screens for lightfield display.

The use of microlens arrays for lightfield display has the drawback of providing images with strong chromatic aliasing. To overcome this problem, pinhole-type lightfield monitors are proposed. This paper is devoted to evaluating the capability for such lightfield monitors to offer the user a convincing 3D experience with images with enough brightness and continuous aspect. Thus, we have designed a psychophysical test specifically adapted for lightfield monitors, which allowed us to confirm the usability of pinhole-type monitors.

The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Prognosis of status epilepticus in elderly patients.

PURPOSE: To evaluate the clinical features and prognosis of status epilepticus (SE) in patients above 70 years old. METHODS: Retrospective analysis of all patients ≥70 years old with SE registered prospectively during 4 years. Follow-up after discharge was performed. RESULTS: Ninety patients were evaluated. Acute symptomatic etiology was the most prevalent. The mean number of antiepileptic drugs (AEDs) used was 2.7 ± 1.2, and 21% of the patients required sedation. A poor outcome was considered when death (31.1%) or developing of new neurological impairment at discharge (32.2%) occurred. After multivariate analysis, four variables predicted a poor outcome: acute symptomatic etiology (OR: 6.320; 95% CI: 1.976-20.217; P = .002), focal motor SE type (OR: 9.089; 95% CI: 2.482-33.283; P = .001), level of consciousness (OR: 4.596; 95% CI: 1.903-11.098; P = .001), and SE duration >12 hours (OR: 3.763; 95% CI: 1.130-12.530; P = .031). Independent predictive factors of mortality were SE duration >12 hours (OR: 4.306; 95% CI: 1.044-17.757; P = .043), modified Status Epilepticus Severity Score (mSTESS) (OR: 2.216; 95% CI: 1.313-3.740; P = .003), and development of complications (OR: 3.334; 95% CI: 1.004-11.070, P = .049). Considering long-term mortality, age (HR 1.036; 95% CI 1.001-1.071; P = .044), a potentially fatal underlying cause (HR 2.609; 95% CI 1.497- 4.548; P = .001), and mSTESS score >4 (HR 1.485; 95% CI 1.158-1.903; P = .002) remained as predictive factors. There was no association between sedation and the number of AEDs used with outcome at discharge or long-term mortality (P > .05). CONCLUSIONS: SE above 70 years old has a high morbimortality. Prognosis is not related to treatment aggressiveness.

Physical Restraint Use With Elderly Patients: Perceptions of Nurses and Nursing Assistants in Spanish Acute Care Hospitals.

BACKGROUND: Physical restraint is often used during the hospitalization of elderly people. However, this procedure is associated with adverse outcomes; therefore, it is necessary to be aware of the circumstances that promote restraint use, such as the perceptions of professionals who use it. OBJECTIVES: The purpose of the research was to determine the situations in which nursing staff considered the use of physical restraint as most important and to evaluate the possible associations with the sociodemographic and professional variables. METHODS: A descriptive cross-sectional multicenter study was carried out in 52 units of eight Spanish acute hospitals. A survey of registered nurses and nursing assistants was used to collect data related to sociodemographic characteristics, experience, training in restraint use, and the Perception of Restraint Use Questionnaire (PRUQ)-which assesses the perceived importance of reasons frequently given for the use of physical restraint. RESULTS: The sample comprised 508 registered nurses and 347 nursing assistants. Almost all (98%) had used physical restraint, and 82% thought their training in the use of physical restraint was insufficient. Nursing assistants scored higher than registered nurses (p < .005, d = .68) on PRUQ total score and individual item scores, suggesting they thought the factors were more important in restraint use. Both registered nurses and nursing assistants considered restraint as most important in the prevention of falls and in the removal of medical devices such as intravenous lines and urinary catheters. Associations between PRUQ total score and other variables (unit type, sociodemographic factors, hospital) were nonsignificant. DISCUSSION: The professionals considered restraint as very important in preventing safety problems. In order to improve the quality of care, it is essential to identify the factors that can have an effect on the application of physical restraint. Educational programs are of fundamental importance, but to be more effective in reducing the use of physical restraint, they should address commonly held views on rationale for restraint use and be accompanied by institutional policies promoting a restraint-free environment.

Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours.

BACKGROUND: Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study. We analysed the relationship between clinicopathological and molecular factors with survival. Analysis of hMLH1, hMSH2 and EGFR expression was carried out by immunohistochemistry. Methylation status of the hMLH1 promoter was determined by pyrosequencing analysis in selected cases. EGFR exons 19, 20, 21 were analysed by PCR labeled-fragments and MSI status was determined using standard Multiplex MSI assays. RESULTS: Classical pathological factors such as lymphovascular invasion, high percentage of embryonal carcinoma, rete testis invasion or tumour size ≥4 cm showed a significant relationship with a higher risk of relapse. Additionally, it was found that an epididymis invasion proved to be a significant independent poor prognostic factor of recurrence (p = 0.001). hMLH1 or hMSH2 expression showed no significant association with risk of relapse and no MSI was found. EGFR expression was observed in 30.4% of samples and its expression was associated with higher risk of relapse (HR 3.5; 95% CI 1.3-9.8; p = 0.016). None of the cases presented EGFR kinase domain mutations. CONCLUSIONS: Epididymis invasion and EGFR expression, but not hMLH-1/hMSH-2 or MSI, could be potentially useful as new prognostic factors of recurrence for CS I TGCT.

Systematic reviews and meta-analyses on psoriasis: role of funding sources, conflict of interest and bibliometric indices as predictors of methodological quality.

BACKGROUND: The quality of systematic reviews and meta-analyses on psoriasis, a chronic inflammatory skin disease that severely impairs quality of life and is associated with high costs, remains unknown. OBJECTIVES: To assess the methodological quality of systematic reviews published on psoriasis. METHODS: After a comprehensive search in MEDLINE, Embase and the Cochrane Database (PROSPERO: CDR42016041611), the quality of studies was assessed by two raters using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. Article metadata and journal-related bibliometric indices were also obtained. Systematic reviews were classified as low (0-4), moderate (5-8) or high (9-11) quality. A prediction model for methodological quality was fitted using principal component and multivariate ordinal logistic regression analyses. RESULTS: We classified 220 studies as high (17·2%), moderate (55·0%) or low (27·8%) quality. Lower compliance rates were found for AMSTAR question (Q)5 (list of studies provided, 11·4%), Q10 (publication bias assessed, 27·7%), Q4 (status of publication included, 39·5%) and Q1 (a priori design provided, 40·9%). Factors such as meta-analysis inclusion [odds ratio (OR) 6·22; 95% confidence interval (CI) 2·78-14·86], funding by academic institutions (OR 2·90, 95% CI 1·11-7·89), Article Influence score (OR 2·14, 95% CI 1·05-6·67), 5-year impact factor (OR 1·34, 95% CI 1·02-1·40) and article page count (OR 1·08, 95% CI 1·02-1·15) significantly predicted higher quality. A high number of authors with a conflict of interest (OR 0·90, 95% CI 0·82-0·99) was significantly associated with lower quality. CONCLUSIONS: The methodological quality of systematic reviews published about psoriasis remains suboptimal. The type of funding sources and author conflicts may compromise study quality, increasing the risk of bias.

Usefulness of dual-energy computed tomography with and without dedicated software in identifying uric acid kidney stones.

OBJECTIVE: To prospectively evaluate the usefulness of dual-energy computed tomography (DECT) with and without dedicated software in identifying uric acid kidney stones in vivo. MATERIAL AND METHODS: We studied 65 kidney stones in 63 patients. All stones were analyzed in vivo by DECT and ex vivo by spectrophotometry. We evaluated the diagnostic performance in identifying uric acid stones with DECT by analyzing the radiologic densities with dedicated software and without using it (through manual measurements) as well as by analyzing the attenuation ratios of the stones in both energies with and without the dedicated software. RESULTS: The six uric acid stones included were correctly identified by evaluating the attenuation ratios with a cutoff of 1.21, both with the dedicated software and without it, yielding perfect diagnostic performance without false positives or false negatives. The study of the attenuations of the stones obtained the following values on the receiver operating characteristic curves in the classification of the uric acid stones: 0.92 for the measurements done with the software and 0.89 for the manual measurements; a cutoff of 538 HU yielded 84% (42/50) diagnostic accuracy for the software and 83.1% (54/65) for the manual measurements. CONCLUSIONS: DECT enabled the uric acid stones to be identified correctly through the calculation of the ratio of the attenuations in the two energies. The results obtained with the dedicated software were similar to those obtained manually.

Solid phase extraction-capillary electrophoresis determination of sulphonamide residues in milk samples by use of C18-carbon nanotubes as hybrid sorbent materials.

The exceptional sorption capabilities of carbon nanotubes were used to preconcentrate trace sulphonamides from milk samples. To this end, single walled carbon nanotubes (SWNTs) and multi-walled carbon nanotubes (MWNTs) dispersed in the ionic liquid 1-hexyl-3-methylimidazolium hexafluorophosphate were retained on a C18 stationary phase to obtain a hybrid material in a simple manner. In this approach ionic liquids are an excellent alternative to improve the dispersion of CNTs, without chemical modification or the use of solid substances or organic solvents. MWNTs provided better results than SWNTs. Carbon nanotubes retained in the C18 sorbent matrix were found to confer aromatic character, increasing its preconcentration capacity as a result. The conventional C18 stationary phase played a two-fold role: as a support to retain carbon nanotubes in the cartridge and as a medium to prevent their aggregation. The modified MWNT/C18 and SWNT/C18 materials were used to preconcentrate residual sulphonamides (SAs) in milk samples for their determination at concentrations as low as 0.03-0.069 mg L(-1) by capillary electrophoresis. Analyte recoveries from spiked samples ranged from 103.2 to 98.8% and precision, as RSD, from 8.2 to 5.4%.

Conservation of endangered Spanish cattle breeds using markers of candidate genes for meat quality.

The aim was to analyze the allelic and genotypic frequencies for two genes associated with tenderness of meat (CAPN1 and CAST) and one with fat deposits (DGAT1) in three endangered Spanish cattle breeds: Berrenda en Colorado (BC), Berrenda en Negro (BN), and Cardena Andaluza (CA) to utility of their involvement in the selection of them and to help the adoption of conservation measurement. Seventy-five males and 298 females of those breeds were genotyped. Genotypic and allelic frequencies for each polymorphic locus were estimated. There were significant differences in the genotypic frequencies among breeds in CAPN1 and DGTA1 genes and in the case of the genic frequencies in CAPN1, CAST, and DGAT1 genes. The three breeds analyzed (BC, BN, and CA) presented high allelic frequencies for the favorable allele of the three markers (from 0.41 to 0.75). The association between the favorable allele and meat quality must be confirmed. In cases of association with differences in quality meat, the absence of differences in the genotypic and genic frequency distributions between the sexes is advantageous in mating planning because it implies that there is no handicap to be overcome for the conservation program and it would allow the use of sires to promote the increase in improvements within a short period of time.

Development of an automated colorimeter controlled by Raspberry Pi4.

A low-cost new instrument to carry out automated colorimetric analysis has been developed. The device consists of a carousel sampler, built by a 3D-printer, and a Raspberry Pi4-controlled signal measurement module based on the RGBC (red, green, blue and clear) responses of a TCS34725 color light-to-digital converter with IR filter. The device has been tested with calibration standards of different food dyes (Tartrazine, Red Allure AC and Brilliant Blue FCF) and three food samples containing one of each food dye. The new device provides R2 > 0.995 and a LOD of 1.1, 1.4 and 0.1 µmol L-1 for each food dye, respectively. The results are statistically comparable to those obtained with a conventional benchtop spectrophotometer. The proposed device achieves a reduction in sample and waste volume and in analysis time, minimizes the use of energy, and allows in situ measurements, being an automated method it is safer for operators in comparison to the reference method, yielding similar analytical results and following the principles of green analytical chemistry.

Identifying gaps in the cascade of care for latent TB infection in a low-incidence setting.

BACKGROUND: The End TB Strategy calls for the global scale-up of treatment for latent TB infection (LTBI). We aimed to evaluate a nurse-led care programme for LTBI by identifying gaps in the care cascade in a low-incidence TB setting.METHODS: We included people at risk of TB over a 15-year period. We define three main outcomes in the LTBI care cascade: 1) attendance at the first appointment, 2) completion of the evaluation process, and 3) completion of treatment.RESULTS: We identified 6,126 individuals (2,369 TB contacts, 1,749 biological therapy candidates, and 2,008 transplant candidates). Overall, 5,938 (96.9%) attended, 5,872/5,938 (98.9%) completed the evaluation and 1,624/1,847 (87.9%) completed treatment. Pre-biological (aOR 2.32, 95% CI 1.54-3.49) and pre-transplant (aOR 1.82, 95% CI 1.20-2.76) candidates were more likely to attend the first appointment, while age was associated with completing the evaluation process (aOR 1.02, 95% CI 1.003-1.04). Female sex (aOR 1.47, 95% CI 1.08-1.99) was associated with completing the treatment.CONCLUSION: Successful assessment and treatment of LTBI is achievable when delivered as a part of a comprehensive, nurse-led, patient-centred programme in specialist TB clinics.

Corneal Edema after Cataract Surgery.

This systematic review investigates the prevalence and underlying causes of corneal edema following cataract surgery employing manual phacoemulsification. A comprehensive search encompassing databases such as PubMed, Embase, ProQuest, Cochrane Library, and Scopus was conducted, focusing on variables encompassing cataract surgery and corneal edema. Two independent reviewers systematically extracted pertinent data from 103 articles, consisting of 62 theoretical studies and 41 clinical trials. These studies delved into various aspects related to corneal edema after cataract surgery, including endothelial cell loss, pachymetry measurements, visual performance, surgical techniques, supplies, medications, and assessments of endothelial and epithelial barriers. This review, encompassing an extensive analysis of 3060 records, revealed significant correlations between corneal edema and endothelial cell loss during phacoemulsification surgery. Factors such as patient age, cataract grade, and mechanical stress were identified as contributors to endothelial cell loss. Furthermore, pachymetry and optical coherence tomography emerged as valuable diagnostic tools for assessing corneal edema. In conclusion, this systematic review underscores the link between corneal edema and endothelial cell loss in manual phacoemulsification cataract surgery. It highlights the relevance of factors like patient demographics and diagnostic modalities. However, further research is essential to unravel the complexities of refractive changes and the underlying mechanisms.

Evaluation of the susceptibility of Tritrichomonas foetus to extracts of Lantana camara (Verbenaceae) by flow cytometry.

Bovine Trichomonosis (BT), a sexually transmitted disease endemic in countries with extensive cattle farming and natural service, is one of the most common causes of reproductive failure. 5-nitroimidazoles and their derivatives are used for its treatment, mainly metronidazole. The emergence of drug resistance mechanisms and treatment failures raise the need to investigate the effectiveness of new active compounds that contribute to parasite control. In this regard, extracts of Lantana camara (Verbenacea) have shown high biocidal potential against isolates of Trypanosoma cruzi and Leishmania braziliensis in vitro assays, although their effect on Tritrichomonas foetus has not been demonstrated yet. The available information on in vitro susceptibility of trichomonicidal drugs comes from the use of a diversity of methodologies and criteria, especially the observation of parasite motility under the optical microscope to assess their viability. Recently, in our laboratory, the use of flow cytometry has been described for the first time as a rapid and efficient method to evaluate the viability of T. foetus against metronidazole. The present study aimed to evaluate the cytostatic effect of L. camara extracts against T. foetus isolates by flow cytometry. Under aerobic conditions, IC50 values of 22.60 µg/mL were obtained on average. Under anaerobic conditions, the IC50 oscilated around 29.04 µg/mL. The results obtained allowed describing the susceptibility exhibited by these protozoa, being a valuable information for the development of potential BT treatments.

[EPICAP: educational intervention using instructional clips in patients with epilepsy. A randomised clinical trial]. / EPICAP: intervención educativa mediante cápsulas audiovisuales en pacientes con epilepsia. Ensayo clínico aleatorizado.

AIMS: In patients with epilepsy health education has a positive influence on self-management of the disease, improves prognosis and enhances patient well-being. The aim of this study was to evaluate an educational intervention using instructional clips in patients with epilepsy in a video-electroencephalographic monitoring unit. SUBJECTS AND METHODS: We conducted a randomised clinical trial with two groups (intervention and control). Adult patients with epilepsy admitted to the video-electroencephalographic monitoring unit were recruited. Nine videos about the diagnosis and treatment of epilepsy, together with recommendations on lifestyle, were produced and administered to the intervention group while admitted. Patients' knowledge of their disease was assessed by means of a questionnaire designed specifically for this study. A pre-assessment was conducted at the beginning of the study, at hospital discharge and at three months, and the knowledge of epilepsy in the two groups was compared at each time considered in the study. RESULTS: Sixty-six patients were included, with a mean age of 39 ± 14.7 years (range: 17-76) and a median of 8 years since disease onset (range: 1-60 years). Fifty-three per cent of the patients were women. Focal epilepsy was the most frequent type (95.5%). The mean score on the pre-intervention test was 57.2 ± 15.3. Patients who received the educational intervention showed better post-test scores at discharge from hospital (81.8 ± 11.2 versus 62.8 ± 13.7; p = 0.001) and at three months (76 ± 9.6 versus 63.2 ± 12.8; p = 0.001). CONCLUSIONS: The EPICAP educational intervention using instructional clips significantly improves patients' knowledge of epilepsy-related diagnostic, therapeutic and lifestyle issues.

TITLE: EPICAP: intervención educativa mediante cápsulas audiovisuales en pacientes con epilepsia. Ensayo clínico aleatorizado.Objetivos. La educación sanitaria en pacientes con epilepsia influye positivamente en el autocontrol de la enfermedad, mejora su pronóstico y favorece el bienestar del paciente. El objetivo de este estudio fue evaluar una intervención educativa mediante cápsulas audiovisuales en pacientes con epilepsia en una unidad de monitorización videoelectroencefalográfica. Sujetos y métodos. Es un ensayo clínico aleatorizado con dos grupos (intervención y control). Se reclutó a pacientes adultos con epilepsia que ingresaron en la unidad de monitorización videoelectroencefalográfica. Se crearon nueve vídeos sobre el diagnóstico y el tratamiento de la epilepsia, y recomendaciones de estilo de vida, que se administraron al grupo de intervención durante el ingreso. Se evaluó el conocimiento del paciente sobre su enfermedad con un cuestionario diseñado específicamente para este estudio. Se realizó una evaluación previa en el inicio del estudio, en el alta hospitalaria y a los tres meses, y se comparó el conocimiento sobre la epilepsia en ambos grupos en cada momento del estudio. Resultados. Se incluyó a 66 pacientes, con edad media de 39 ± 14,7 años (rango: 17-76) y una mediana de 8 años de evolución de la enfermedad (rango: 1-60 años). Un 53% eran mujeres. El tipo de epilepsia más frecuente fue el focal (95,5%). La puntuación media en el test preintervención fue de 57,2 ± 15,3. Los pacientes que recibieron la intervención educativa mostraron mejores puntuaciones en el postest en el alta hospitalaria (81,8 ± 11,2 frente a 62,8 ± 13,7; p = 0,001) y a los tres meses (76 ± 9,6 frente a 63,2 ± 12,8; p = 0,001). Conclusiones. La intervención educativa EPICAP mediante píldoras audiovisuales mejora de forma significativa el conocimiento de los pacientes sobre aspectos diagnósticos, terapéuticos y estilo de vida relacionados con la epilepsia.

The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome.

BACKGROUND: Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. METHODS: We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. RESULTS: We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by ß adrenergic receptors. A reduction in extracellular Ca2+ concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, ß adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice. LIMITATIONS: We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells. CONCLUSIONS: Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS.

Coiled carbon nanotubes combined with ionic liquid: a new soft material for SPE.

For the first time a soft material formed from coiled carbon nanotubes and 1-hexyl-3-methylimidazolium hexafluorophosphate has been used as sorbent material. The soft material has high stability as well as a high capacity to adsorb analytes. In this work we propose using a natural cotton fiber impregnated with the soft material to miniaturize the system. The system was tested for the analysis of polycyclic aromatic hydrocarbons in spiked river water samples. The absolute recovery ranged between 97.5 and 105.5%, demonstrating the usefulness of the soft material. The limit of detection ranged from 2.5 to 6.1 µg/L and the precision expressed as the relative standard deviation for the analysis of five consecutive analyses ranged between 2.5 and 5.8%.

Simulating images seen by patients with inhomogeneous sensitivity losses.

PURPOSE: We aim to simulate how colored images are perceived by subjects with local achromatic and chromatic contrast sensitivity losses in the visual field (VF). METHODS: The spatiochromatic corresponding pair algorithm, introduced in a previous article (J Opt Soc Am (A) 2004;21:176-186), has been implemented with a linear model of the visual system. Spatial information is processed separately by the chromatic and achromatic mechanisms by means of a multiscale model, with sensors selective to frequency, orientation, and spatial position, whose mechanism-dependent relative weights change with the spatial location of the image. These weights have been obtained from perimetric data from a patient with Leber's Hereditary Optic Neuropathy and an age-matched sample of normal subjects, using achromatic, red-green, and blue-yellow gratings of different spatial frequencies. Distortion contours for each mechanism have been derived from the images simulating the perception of these subjects at different locations in the VF. RESULTS: The images simulating the perception of normal subjects at different locations of the VF show a fast decrease in image quality with eccentricity. The same analysis carried out with the Leber's Hereditary Optic Neuropathy patient reveals worse overall image quality throughout the VF, plus a color vision defect resembling red-green dichromacy at fovea and trichromatic anomaly in the rest of the VF. CONCLUSIONS: In the present article, we show that implementing the algorithm with a spatial vision model that considers the changes in contrast sensitivity with spatial location of the stimulus may reveal the local effects that are suffered, in general, by pathological subjects, and that are ignored by simpler spatial vision models.