Tau and amyloid-related pathologies in the entorhinal cortex have divergent effects in the hippocampal circuit.

The entorhinal cortex (EC) is affected early in Alzheimer's disease, an illness defined by a co-occurrence of tau and amyloid-related pathologies. How the co-occurrence of these pathologies in the EC affects the hippocampal circuit remains unknown. Here we address this question by performing electrophysiological analyses of the EC circuit in mice that express mutant human amyloid precursor protein (hAPP) or tau (hTau), or both in the EC. We show that the alterations in the hippocampal circuit are divergent, with hAPP increasing but hTau decreasing neuronal/circuit excitability. Most importantly, mice co-expressing hAPP and hTau show that hTau has a dominant effect, dampening the excitatory effects of hAPP. Additionally, compensatory synaptic downscaling, in response to increased excitability in EC was observed in subicular neurons of hAPP mice. Based on simulations, we propose that EC interneuron pruning can account for both EC hyperexcitability and subicular synaptic downscaling found in mice expressing hAPP.

Clinical significance and outcome of Aeromonas spp. infections among 204 adult patients.

The objectives of this investigation were to analyze the clinical patterns, risk groups, prognostic factors, and mortality of infections caused by Aeromonas spp. This was a retrospective study of adult patients with Aeromonas spp. isolates attended at the Hospital del Mar in Barcelona, Spain, between January 2006 and December 2012. Epidemiological data, antimicrobial susceptibility, clinical patterns, underlying illnesses, type of infection, admission to the intensive care unit (ICU), number of episodes, coinfection, antimicrobial therapy, and evolution were analyzed. A total of 221 clinical samples from 204 patients were positive for Aeromonas spp. The mean age of the patients was 67.6 years. The main clinical form of presentation was gastrointestinal (78.4%). Malignancy was the main risk group in 69 (33.8%) patients, and 48 (23.5%) were previously healthy. Twenty-one patients (10.3%) were admitted to the ICU. Infections were acquired in the hospital in 52.5% of the patients, and 28.9% were polymicrobial. The overall mortality (after 1 year of follow-up from the first positive culture) was 26.5%. Univariate analysis identified an association between increased mortality and the following variables: age ≥80 years, hospitalization, admission to the ICU, malignancy, extraintestinal infection, and appropriate antimicrobial therapy. In the multivariate analysis, age ≥80 years [odds ratio (OR), 4.37 [95% confidence interval (CI), 1.68-11.35; p = 0.002]], admission to the ICU (OR, 6.59 [95% CI, 2.17-19.99; p = 0.001]), and malignancy (OR, 3.62 [95% CI, 1.32-9.90; p = 0.012]) were significantly associated with mortality. Aeromonas infections are mainly gastrointestinal. The 1-year follow-up mortality rate was high. Old age (age ≥80 years), admission to the ICU, and malignancy were identified as independent risk factors for mortality.

Comminution and sizing processes of concrete block waste as recycled aggregates.

Due to the environmental impact of construction and demolition waste (CDW), recycling is mandatory. It is also important that recycled concrete aggregates (RCA) are used in concrete to meet market demands. In the literature, the influence of RCAs on concrete has been investigated, but very limited studies have been conducted on how the origin of concrete waste and comminution processes influence RCA characteristics. This paper aims to investigate the influence of three different comminution and sizing processes (simple screening, crushing and grinding) on the composition, shape and porosity characteristics of RCA obtained from concrete block waste. Crushing and grinding implies a reduction of RCA porosity. However, due to the presence of coarse quartz rounded river pebbles in the original concrete block mixtures, the shape characteristics deteriorated. A large amount of powder (<0.15 mm) without detectable anhydrous cement was also generated.

Cría masiva y uso de ninfas de Rhodnius pallescens, Barber, 1932 (Hemiptera, Reduviidae, Triatominae) para ensayos biológicoso / Mass breeding and use of nymph of Rhodnius pallescens, Barber, 1932 (Hemiptera, Reduviidae, Triatominae) for biological test.

Introducción: Rhodnius pallescens es una especie silvestre que hace intrusión a las viviendas en zonas en las cuales se han presentado brotes de Chagas agudo en Colombia; y para el estudio de sus características biológicas y el monitoreo de la susceptibilidad o resistencia de poblaciones de campo a insecticidas, se requiere del uso de una gran cantidad de insectos mantenidos en el laboratorio. Objetivo: Establecer condiciones de cría de ninfas de R. pallescens que permitan su mejor aprovechamiento en ensayos biológicos. Metodología: Se utilizó una cepa de laboratorio de R. pallescens proveniente de San Martin (Cesar, Colombia) y se realizaron bioensayos para: estimar el tiempo de alimentación, establecer condiciones de cría, estimar tiempos de desarrollo ninfal y comparar la fecundidad usando dos fuentes de alimentación y varios tipos de soporte. Resultados: 60 minutos de ofrecimiento de alimento permite la alimentación de 95% de las ninfas. El promedio de oviposición diario/hembra fue de 2,7 huevos y no varío significativamente con el consumo de sangre de gallina o ratón. La duración promedio del ciclo de vida desde huevo hasta el estadio ninfa-V fue de 128,6 días. El uso de cartulina negra y plumas dentro de los frascos de cría mejora la oviposición. Ninfas-V alimentadas desde ninfa-I y pesadas a los 5 o 6 días permite un aprovechamiento del 89% de las ninfas. Conclusiones: Los resultados de este trabajo brindan conocimiento para la cría masiva y el uso de ninfas de Rhodnius pallescens en ensayos biológicos.

Introduction: Rhodnius pallescens is a wild species which makes intrusion into dwellings in areas where there have been acute Chagas disease outbreaks in Colombia. Biologic research on their characteristics, and resistance to insecticides, requires the use of a large insect colony in the laboratory. Objective: To establish optimal breeding conditions of R. pallescens nymphs allowing better use in biological assays. Methodology: A laboratory strain of R. pallescens from San Martin (Cesar, Colombia) was used. Feeding time, breeding conditions, nymphal development times were assessed and fertility using two sources of feeding and different kinds of substrate was compared. Results: Providing food during 60 minutes allowed 95% of nymphs to be fed. The average daily oviposition per female was 2.7 eggs and did not vary significantly with the kind of blood used. The average duration of the life cycle from egg to nymph-V was 128.6 days. Using black cardboard and feathers in breeding jars increased oviposition. Nymphs-V (fed from nymph-I every 15 days) and weigthed at 5 or 6 days allowed the use of 89% of the nymphs. Conclusions: The results of this study allow offering recommendations for mass breeding and use of nymphs of R. pallescens in biological assays.

A year-long study of Cryptosporidium species and subtypes in recreational, drinking and wastewater from the central area of Spain.

A year-long longitudinal study was undertaken to evaluate the presence of Cryptosporidium spp. in drinking water treatment plants (DWTPs), wastewater treatment plants (WWTPs) and freshwater bathing beaches (FBBs) from the central area of Spain. Water samples were collected according to USEPA Method 1623, and concentrated by the IDEXX Filta-Max® system. Cryptosporidium species were detected based on PCR-restriction fragment length polymorphism and sequence analyses of the ssuRNA gene. C. hominis and/or C. parvum isolates were subtyped by DNA sequencing of the Gp60 gene. Among 150 samples, 23 (15.3%) were positive by IFAT and 40 (26.7%) by PCR. Cryptosporidium spp. was more frequent in WWTPs (26.2 and 50.8%) and FBBs (12.5 and 17.5%) by IFAT and PCR respectively. Effluent waters from DWTPs were negative for this parasite suggesting that they are suitable for public use. Tertiary treatment in the WWTPs demonstrated a high removal efficiency of Cryptosporidium in the samples evaluated. Cryptosporidium species identified included C. hominis, C. parvum, C. ubiquitum, C. andersoni and C. muris. Subtyping analysis revealed C. hominis IbA10G2 and IeA11G3T3 alleles, which is the first report of the latter in water samples. Cryptosporidium highest frequency was observed in winter and spring. Our data provide information about the occurrence and diversity of Cryptosporidium in water of human use from the central area of Spain.

Resistencia a lambdacihalotrina y fenitrotión en una población de campo de Panstrongylus geniculatus (Hemiptera: Reduviidae: Triatominae) / Lambdacyhalothrin and fenitrothion resistance in a field population of Panstrongylus geniculatus (Hemiptera: Reduviidae: Triatominae)

Introducción: Panstrongylus geniculatus es un triatomino silvestre, vector del Trypanosoma cruzi, intruso en domicilios humanos. Determinar la susceptibilidad a insecticidas de uso común en esta especie es indispensable para detectar prematuramente cepas resistentes. Objetivo: Este estudio se propuso analizar la susceptibilidad a lambdacihalotrina y fenitrotión en dos cepas (laboratorio y campo) de P. geniculatus. Metodología: se estableció la susceptibilidad a lambdacihalotrina y fenitrotión por aplicación tópica, en la cepa de laboratorio-Molagavita 2003 y en la población de campo-Chorreras 2012 en ninfas del primer estadio de P. geniculatus. Se calcularon valores de dosis letal 50 y dosis letal 99 (DL50 y la DL99) para cada insecticida. También se determinaron valores de grado de resistencia (GR) para cada insecticida: DL50 población de campo/DL50 cepa de laboratorio. Resultados: Las DL50 y DL99 en la población de campo y la cepa de laboratorio (en ng/i), fueron: 1,194; 5,764 y 0,024; 0,131 para lambdacihalotrina y 1,476; 7,354 y 0,482; 5,471 para fenitrotión, respectivamente. Los grados de resistencia fueron: GR= 48,9 para lambdacihalotrina y GR= 3,06 para fenitrotión. Conclusiones: La población de campo mostró resistencia a lambdacihalotrina y fenitrotión, probablemente como consecuencia del uso de agroquímicos en la zona. Implementar medidas para la detección temprana de resistencia en triatominos es importante en el diseño de programas de control vectorial.

Introduction: Panstrongylus geniculatus, is a wild triatomine, vector of Trypanosoma cruzy, intruder in human homes. To determine the susceptibility to insecticides commonly used in this specie is essential to detect resistant strains prematurely. Objective: This study aimed to analyze the susceptibility to lambdacyhalothrin and fenitrothion in two strains (laboratory and field) of P. geniculatus. Methodology: susceptibility was established to lambdacyhalothrin and fenitrothion by topical application in the laboratory strain - Molagavita 2003 and field population - Chorreras 2012 in first instar nymphs of P. geniculatus. Values were calculated for lethal dosis 50 and lethal dosis 99 (LD50 and LD99) for each insecticide. Also values were determined to degree of resistance (GR) for each insecticide: field population LD50/LD50 laboratory strain. Results: The LD50 and LD99 in the field population and the laboratory strain (in ng/i) were: 1,194, 5,764 and 0,024, 0,131 for lambdacyhalothrin and 1,476, 7,354 and 0,482, 5,471 to fenitrothion, respectively. The degrees of resistance were: GR=48.9 for lambdacyhalothrin and GR=3.06 for fenitrothion. Conclusions: The field population showed resistance to lambdacyhalothrin and fenitrothion, probably as a result of the use of chemicals in the area. Implement measures for early detection of resistance in triatomines is important in the design of vector control programs.

Bidirectional correlation of NMR and capillary electrophoresis fingerprints: a new approach to investigating Schistosoma mansoni infection in a mouse model.

We demonstrate the statistical integration of nuclear magnetic resonance (NMR) spectroscopy and capillary electrophoresis (CE) data in order to describe a pathological state caused by Schistosoma mansoni infection in a mouse model based on urinary metabolite profiles. Urine samples from mice 53 days post infection with S. mansoni and matched controls were analyzed via NMR spectroscopy and CE. The two sets of metabolic profiles were first processed and analyzed independently and were subsequently integrated using statistical correlation methods in order to facilitate cross assignment of metabolites. Using this approach, metabolites such as 3-ureidopropionate, p-cresol glucuronide, phenylacetylglycine, indoxyl sulfate, isocitrate, and trimethylamine were identified as differentiating between infected and control animals. These correlation analyses facilitated structural elucidation using the identification power of one technique to enhance and validate the other, but also highlighted the enhanced ability to detect functional correlations between metabolites, thereby providing potential for achieving deeper mechanistic insight into the biological process.

Plasma fingerprinting with GC-MS in acute coronary syndrome.

New biomarkers of cardiovascular disease are needed to augment the information obtained from traditional indicators and to illuminate disease mechanisms. One of the approaches used in metabolomics/metabonomics for that purpose is metabolic fingerprinting aiming to profile large numbers of chemically diverse metabolites in an essentially nonselective way. In this study, gas chromatography-mass spectrometry was employed to evaluate the major metabolic changes in low molecular weight plasma metabolites of patients with acute coronary syndrome (n = 9) and with stable atherosclerosis (n = 10) vs healthy subjects without significant differences in age and sex (n = 10). Reproducible differences between cases and controls were obtained with pattern recognition techniques, and metabolites accounting for higher weight in the classification have been identified through their mass spectra. On this basis, it seems inherently plausible that even a simple metabolite profile might be able to offer improved clinical diagnosis and prognosis, but in addition, specific markers are being identified.

Chemical-mineralogical characterization of C&D waste recycled aggregates from São Paulo, Brazil.

This study presents a methodology for the characterization of construction and demolition (C&D) waste recycled aggregates based on a combination of analytical techniques (X-ray fluorescence (XRF), soluble ions, semi-quantitative X-ray diffraction (XRD), thermogravimetric analysis (TGA-DTG) and hydrochloric acid (HCl) selective dissolution). These combined analytical techniques allow for the estimation of the amount of cement paste, its most important hydrated and carbonated phases, as well as the amount of clay and micas. Details of the methodology are presented here and the results of three representative C&D samples taken from the São Paulo region in Brazil are discussed. Chemical compositions of mixed C&D aggregate samples have mostly been influenced by particle size rather than the visual classification of C&D into red or grey and geographical origin. The amount of measured soluble salts in C&D aggregates (0.15-25.4mm) is lower than the usual limits for mortar and concrete production. The content of porous cement paste in the C&D aggregates is around 19.3% (w/w). However, this content is significantly lower than the 43% detected for the C&D powders (<0.15 mm). The clay content of the powders was also high, potentially resulting from soil intermixed with the C&D waste, as well as poorly burnt red ceramic. Since only about 50% of the measured CaO is combined with CO(2), the powders have potential use as raw materials for the cement industry.

New perspective of diabetes response to an antioxidant treatment through metabolic fingerprinting of urine by capillary electrophoresis.

Benefits of capillary electrophoresis to provide a comprehensive snapshot of multiple metabolites in biological samples have been exploited. Afterwards, multivariate statistical methods can be employed in order to mine additional information from the data. Urine fingerprints of control and diabetic rats have shown the clear effects of an antioxidant treatment on diabetic animals, which were not seen in controls, in a rapid, simple and cost-effective way without identifying a single marker. The procedure involves the measurement of samples with a relatively inexpensive tool such as CE-UV, without any previous treatment other than filtration and the application of chemometric tools [PCA (principal components analysis) and PLS-DA (partial least squares discriminant analysis)]. Data pre-treatment of electrophoretic profiles (alignment, normalization and baseline correction) has shown to be key for further chemometric treatment. Once developed, the methodology can easily be applied for a rapid in vivo screening of extracts with potential in vitro activity. Classification was supported by that produced after PCA and PLS-DA of target variables obtained with selectively designed, time and reagent consuming methods.

Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients.

OBJECTIVES: We study the power of IgG synthesis value as a marker of disease activity in multiple sclerosis (MS). MATERIAL AND METHODS: Link index was calculated in 202 MS patients. Time between first, second and third attack and progression index (PI) were compared in patient with normal (NLI) high (HL) or very high Link index (VHLI). RESULTS: Secondary progressive (SP) patients had a higher LI than relapsing-remitting (RR) and primary progressive (PP) courses (1.10 +/- 0.5 for SP vs 0.86 +/- 0.5 for RR and 0.81 +/- 0.5 for PP, P=0.01 and 0.03, respectively). Having a HLI in MS RR and SP patients has no time effect in the development of the second and third attack. PI was higher in patients with VHIL (0.67 +/- 0.7) vs patients with NLI (0.42 +/- 0.4, P=0.008) and with HLI (0.39 +/- 0.3, P=0.001). CONCLUSIONS: This study confirmed that LI is a good marker of subsequent progression of MS.

Gallium diffusion in human root dentin: quantitative measurements by pulsed Nd:YAG laser ablation combined with an inductively coupled plasma mass spectrometer.

OBJECTIVE: The purpose of this work was to determine if gallium nitrate placed in human root canals would diffuse across root dentin and reach concentrations high enough to inhibit osteoclasts (approximately 10(-4) M). BACKGROUND DATA: External root resorption by osteoclasts is a common sequela of dental trauma. If not detected and treated, it can lead to the loss of a tooth. Gallium has recently been reported to inhibit osteoclastic resorption in vitro. METHODS: Roots were cleaned and shaped using standard endodontic procedures and the tips sealed with cyanoacrylate cement. The root canal space was filled with an aqueous solution of 1.0 M gallium nitrate chelated with 1.0 M sodium citrate buffer (pH 7.2). The roots were then sectioned longitudinally into two equal halves. Each half was fixed to a translation stage that moved at a constant rate beneath a frequency-quadrupled Nd-YAG laser (266 nm) laser that was used to sample the concentration of 43Ca, 69Ga, and 71Ga by laser ablation across the thickness of root dentin to the periodontal surface. The plume of ablated dentin was swept into an inductively heated plasma chamber by argon gas and hence into a mass spectrometer. RESULTS: Quantitative analyses of the distribution of gallium showed it was highest adjacent to the root canal space and fell as more peripheral sites were sampled but then rose slightly at the external boundary of the root which is covered with a thin layer of atubular cementum. CONCLUSIONS: Even the lowest concentrations of gallium found in peripheral root dentin exceeded the 10(-4) M concentration required to inhibit osteoclastic activity. This simple endodontic treatment should undergo clinical trials to determine its efficacy in vivo. The laser ablation, inductively coupled mass spectrometry method is a powerful analytic tool for measuring spatial distribution of materials in mineralized tissues.

[Sensitivity and efficiency of intrathecal IgG secretion in multiple sclerosis. Comparison of several indices and formulas using pre-established values of specificity]. / Sensibilidad y eficiencia de la secreción intratecal de IgG en la esclerosis múltiple. Comparación de los distintos índices y fórmulas utilizando valores de especificidad predeterminados.

To furnish greater specificity in the analysis of cerebrospinal fluid from patients suspected of having multiple sclerosis, we studied the sensitivity and efficiency of indices and formulas used to calculate intrathecal IgG synthesis in a group of 49 patients with clinically defined multiple sclerosis, using cutoff values based on preestablished levels of specificity (75 and 90%), and compared the findings to those for a control group of patients with other neurological diseases. The best results were obtained with the indices and formulas based on computer models of brain-blood barrier function set forth most recently, namely Reiber's formula and Ohman's index, which had the highest specificity with the least loss of sensitivity.

[Neuroborreliosis in a patient with progressive supranuclear paralysis. An association or the cause?]. / Neuroborreliosis en un paciente con parálisis supranuclear progresiva: asociación o causa?

INTRODUCTION: Many different neurological conditions may be seen in the later stages of Lyme's Disease, such as blindness, epileptic crises, CVA, extrapyramidal disorders, amyotrophic lateral sclerosis, and dementia may be yet another form of presentation of chronic infection due to Borrelia burgdorferi (Bb). Progressive Supranuclear Paralysis (PSP), a disorder of unknown aetiology, considered to be the commonest cause of Parkinsonism-plus, one of the symptoms of which is dementia, has never been mentioned in this type of differential diagnosis. CLINICAL CASE: We present the case of a 78 year old man with sub-acute mental deterioration, Bb positive serology in both plasma and CSF, and with clinical and epidemiological features compatible with Lyme's Disease. Complementary tests were negative. The syndrome corresponded to Lyme's Disease and improved after treatment with ceftriaxona. CONCLUSIONS: We consider aspects of the aetiology of PSP which are still not clear. In our patient, the aetiology seemed to be Bb infection, according to the criteria of the original description of the disease and in view of the neuropathological findings which have shown Bb in the substancia nigra of the mid-brain and the existence of an animal model in which Bb shows a particular tendency to colonize infratentorial structures.

Tolerance of intravitreous interleukin-1 beta in the treatment of experimental vitreous hemorrhage.

We investigated the tolerance of human recombinant interleukin-1 beta (IL-1 beta) injected intravitreously and its putative role in the clearance of experimental vitreous hemorrhages. Three groups of 10 pigmented rabbits each were injected intravitreously with 0.1 ml autologous whole blood. Mean fundus revisualization times after blood clouding were as follows: group 1 (controls, blood injection only), 5.3 weeks; group 2 (100 units of IL-1 beta injected intravitreously 7 days after blood injection), 3.3 weeks; group 3 (1,000 units of IL-1 beta injected intravitreously 7 days after blood injection), 3.2 weeks. Group 4 (10 rabbits) was injected only with 1,000 units of IL-1 beta. Clinical examinations showed a transient mild inflammatory reaction in group 2 and a transient severe reaction in groups 3 and 4. Vitreous opacities, a whitish retinal reaction and vascular changes were seen in group 4. Electroretinography did not show a b-wave decrease in any group. These results suggest that low concentrations of IL-1 beta may be useful for nonsurgical treatment of human vitreous hemorrhage.

[Validity of intrathecal secretion formulas of IgG in the follow-up of the response to neurosyphilis treatment]. / Validez de las fórmulas de secreción intratecal de IgG en el seguimiento de la respuesta al tratamiento en la neurosífilis.

The different formulas on intrathecal secretion of IgG were evaluated in patients with active neurosyphillis (NS) who did not have HIV infection with the aim of knowing their usefulness and sensitivity in the follow up of response to treatment. Five HIV negative patients with defined criteria of active NS were analyzed. The QAib ratio (albumin LCR/serum x 1,000) and Tourtellotte, Schuller and Reiber formulas of intrathecal secretion and the Link's index were studied prior to and at 15 days and three months following treatment with high intravenous doses of penicillin G over 12 days. A decrease in the QAlb ratio and all the formulas of intrathecal secretion of IgG was observed after treatment. The mean decrease was statistically significant on the third month after treatment for the Tourtellotte formula (116.6 +/- 44 mg/dl in basal control, 60.7 +/- 38 mg/dl at 15 days and 46.5 +/- 59 mg/dl at three months) (p < 0.05). The same evolutive pattern was not observed with the Link's index 1.75 +/- 9 mg/dl in basal control, 1.16 +/- 5 mg/dl at 15 days and 1.79 +/- 1 mg/dl at 3 months) in this series. The formulas of intrathecal secretion of IgG are useful to evaluate the response to treatment of patients with active neurosyphilis. The Tourtellotte formula was shown to be better than the Link index in this evaluation.

[Positive anti-Borrelia antibodies in patients with clinical manifestations compatible with neuroborreliosis]. / Anticuerpos anti-Borrelia positivos en pacientes con manifestaciones clínicas compatibles con neuroborreliosis.

The clinical features of 19 patients with neurological manifestations unexplained by another disease and positive serology for Borrelia burgdorferi were studied. ECM was present in only 11% of the cases and 32% referred tick bite. The characteristic features for suspicion of NB according to our series was the presence of polyneuritis in 84% of the cases specially in the form of multiple mononeuritis and involvement of the facial nerve (79%) leading to even greater suspicion with the association of V pair involvement. Seizures, sleep disorders, and higher mental dysfunction may be found in association with other more characteristic neurological features. The typical triad of NB (aseptic meningitis, facial paralysis and polyradiculoneuritis) was found in 21% of the patients and in the absence of another disease to justify the same neuroborreliosis (NB) seemed evident. In all the cases components of this triad were found. Headache, arthralgia, fever and, less frequently, arthritis are other symptoms often past with the presence of anti-BB antibodies. Patients with the shortest evolution most frequently presented antecedents of facial paralysis, sensory alterations and Romberg's sign than patients of longer evolution. CSF demonstrated the presence of pleocytosis in 24% of the cases and in only one patient a slight increase in the intrathecal activity of IgG was observed which may be of use in differential diagnosis with MS. MR showed alterations in 61% of the patients and, while not specific, the lesions present subcortical predominance.

Atonic pupil: an unusual complication of cataract surgery.

Eight cases of atonic pupil, an unusual complication following cataract surgery, are presented. Six of the eyes involved had intracapsular cataract extraction and anterior chamber intraocular lens implantation; one case underwent extracapsular cataract extraction with a posterior chamber intraocular lens implantation; the other had an extracapsular procedure with no implant. The etiology is unknown, but we believe the most likely one is that the sodium hyaluronate used in all these patients caused a temporary reduction of the iris blood supply by mechanical factors or by a vasoconstriction induced by some toxicity of the material that produced a lesion on the iris sphincter.