Clast shape-fabric analysis: A comprehensive and efficient methodology to measure particle-orientation data in solid and loose volcaniclastic deposits.

Fabric analysis is essential for understanding the evolution of volcaniclastic deposits. Here we present a comprehensive and efficient methodology, called "Clast shape-fabric analysis," which is part of the Quantitative Textural Analysis (QTA). This methodology combines high-resolution image analysis techniques with geospatial data processing tools. The fabric of a deposit refers to the three-dimensional orientation of the particles with respect to space, where the degree of iso-orientation of the major axes of the particles is taken into account. The process begins with the collection of oriented samples in the field. Then, in the laboratory, the samples are processed to obtain high-resolution images. The final stage involves the analysis of these images using the FabricS program, which combines image processing techniques and circular statistics. An application of the method was made at the Joya Honda Maar in Mexico, where shape-fabric analysis was used to identify the emission centers of pyroclastic materials. In summary, the "Clast shape-fabric analysis" is a reliable, low-cost and high-potential methodology that can be applied in several geoscientific disciplines and other areas of scientific research.•New Methodology for shape-fabric analysis is presented.•The methodology involves field work, laboratory work and image analysis.•Identification of particle orientations in volcaniclastic deposits.

Transferable mechanisms of quinolone resistance are more frequent among enterotoxigenic Escherichia coli isolates displaying low-level quinolone resistance.

This study analysed the mechanisms of quinolone resistance among enterotoxigenic Escherichia coli (ETEC) in a periurban area of Lima, Peru. The susceptibility to nalidixic acid and ciprofloxacin, the role of Phe-Arg-b-Naphtylamyde inhibitable-(PAbN) efflux pumps, the presence of mutations in gyrA and parC as well as the presence of aac(6')Ib-cr, qepA, qnrA, qnrB, qnrC, qnrD, qnrVC and oqxAB were determined in 31 ETEC from previous case/control studies of children's diarrhoea. Discordances between disk diffusion, with all isolates showing intermediate or fully resistance to nalidixic acid, and minimal inhibitory concentration (MIC), with 7 isolates being below considered resistance breakpoint, were observed. Twenty-one isolates possessed gyrA mutations (19 S83L, 2 S83A). AAC(6') Ib-cr, QnrS, QnrB and QepA were found in 7, 6, 2 and 1 isolates respectively, with 3 isolates presenting 2 transferable mechanisms of quinolone resistance (TMQR) concomitantly. TMQR were more frequent among isolates with MIC to nalidixic acid ranging from 2 to 16 mg/L (p=0.03), while gyrA mutations were more frequent among isolates with nalidixic acid MIC >= 128 mg/L (p=0.0002). In summary, the mechanisms of quinolone resistance present in ETEC isolates in Peru have been described. Differences in the prevalence of underlying mechanisms associated with final MIC levels were observed. The results suggest two different evolutive strategies to survive in the presence of quinolones related to specific bacterial genetic background.

Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España / Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study

Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neu-rodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en Espa˜na en2019.Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de lospacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda Espa˜na.Resultados: Se obtuvo información de 1933 pacientes procedentes de 11 Comunidades Autóno-mas, de 47 neurólogos o genetistas. Edad media: 53,64 a˜nos ± 20,51 desviación estándar (DE);938 varones (48,5%), 995 mujeres (51,5%). En 920 pacientes (47,6%) no se conoce el defectogenético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados dePEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más fre-cuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEHrecesiva más frecuente es la SPG7.Conclusiones: La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se haconseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuira estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentespara hacer los screenings por comunidades, y favorecer los ensayos clínicos.(AU)

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes.We aimed to determine the prevalence of these disorders in Spain in 2019.Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descrip-tive study of patients with ataxia and hereditary spastic paraplegia in Spain between March2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities,provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51)years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect wasunidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%)had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegiawere estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequenttype of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia wasFriedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in oursample was SPG4, and the most frequent recessive type was SPG7.Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic para-plegia was 7.73 cases per 100 000 population. This rate is similar to those reported for othercountries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, ourstudy provides useful data for estimating the necessary healthcare resources for these patients,raising awareness of these diseases, determining the most frequent causal mutations for localscreening programmes, and promoting the development of clinical trials.(AU)

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials.

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

A neglected symptom? Parietal gait lateropulsion as primary manifestation of acute is-chemic stroke. / ¿Un síntoma negado? Lateropulsión parietal de la marcha como manifestación inicial de ictus isquémico agudo.

INTRODUCTION: Gait disorders are commonly overlooked as a presenting manifestation of stroke and underrepresented in case series. We describe four cases of sudden-onset gait lateropulsion as primary manifestation of parietal lobe stroke. CASE REPORT: Four patients presented after sudden-onset gait lateropulsion. On neurological examination, all patients had at least one cortical sensory deficit and wide-based gait with lateropulsion towards the side of the cortical deficit. Neuroimaging revealed a subacute parietal lobe stroke contralateral to the side of gait lateropulsion. In two patients we found bilateral lateropulsion with predominance towards the side of cortical deficit and increase of unsteadiness with eye closure (an apparent Romberg sign), with neuroimaging revealing bilateral parietal strokes (subacute contralateral and chronic ipsilateral to gait lateropulsion). CONCLUSION: We report gait lateropulsion as a novel primary manifestation of acute stroke of the parietal lobe (parietal gait lateropulsion). Given its role as the destination of proprioceptive pathways, parietal strokes can result in gait lateropulsion, with bilateral lesions even mimicking sensory ataxia with bilateral lateropulsion and unsteadiness upon eye closure.

TITLE: ¿Un síntoma negado? Lateropulsión parietal de la marcha como manifestación inicial de ictus isquémico agudo.Introducción. Los trastornos de la marcha no suelen considerarse dentro de las manifestaciones de presentación del ictus y están subrepresentados en las series de casos. Presentamos cuatro casos de lateropulsión de la marcha de inicio súbito como manifestación primaria de ictus del lóbulo parietal. Caso clínico. Cuatro pacientes se presentaron tras el inicio súbito de lateropulsión de la marcha. En el examen neurológico, todos tenían al menos un déficit sensitivo cortical, marcha de base amplia con lateropulsión ipsilateral al déficit cortical. En la neuroimagen se corroboró un ictus subagudo parietal contralateral al lado de lateropulsión de la marcha. Dos pacientes tenían lateropulsión bilateral con predominio ipsilateral al déficit cortical e incremento de inestabilidad con los ojos cerrados (simulando signo de Romberg), en quienes la neuroimagen demostró un ictus parietal bilateral (subagudo contralateral, crónico ipsilateral al lado de lateropulsión de la marcha). Conclusión. Describimos la lateropulsión de la marcha como una nueva manifestación inicial de ictus agudo del lóbulo parietal (lateropulsión parietal de la marcha), contralateral al lado de desviación de la marcha. Dado el papel del parietal como destino de las vías de propiocepción, los ictus pueden originar alteraciones de la marcha, con lesiones bilaterales que semejan ataxia sensitiva con inestabilidad al eliminar la aferencia visual.

A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

¿Un síntoma negado? Lateropulsión parietal de la marcha como manifestación inicial de ictus isquémico agudo / A neglected symptom? Parietal gait lateropulsion as primary manifestation of acute is-chemic stroke

Introducción: Los trastornos de la marcha no suelen considerarse dentro de las manifestaciones de presentación del ictus y están subrepresentados en las series de casos. Presentamos cuatro casos de lateropulsión de la marcha de inicio súbito como manifestación primaria de ictus del lóbulo parietal.Caso clínico: Cuatro pacientes se presentaron tras el inicio súbito de lateropulsión de la marcha. En el examen neurológico, todos tenían al menos un déficit sensitivo cortical, marcha de base amplia con lateropulsión ipsilateral al déficit cortical. En la neuroimagen se corroboró un ictus subagudo parietal contralateral al lado de lateropulsión de la marcha. Dos pacientes tenían lateropulsión bilateral con predominio ipsilateral al déficit cortical e incremento de inestabilidad con los ojos cerrados (simulando signo de Romberg), en quienes la neuroimagen demostró un ictus parietal bilateral (subagudo contralateral, crónico ipsilateral al lado de lateropulsión de la marcha). Conclusión: Describimos la lateropulsión de la marcha como una nueva manifestación inicial de ictus agudo del lóbulo parietal (lateropulsión parietal de la marcha), contralateral al lado de desviación de la marcha. Dado el papel del parietal como destino de las vías de propiocepción, los ictus pueden originar alteraciones de la marcha, con lesiones bilaterales que semejan ataxia sensitiva con inestabilidad al eliminar la aferencia visual.(AU)

Introduction: Gait disorders are commonly overlooked as a presenting manifestation of stroke and underrepresented in case series. We describe four cases of sudden-onset gait lateropulsion as primary manifestation of parietal lobe stroke. Case report: Four patients presented after sudden-onset gait lateropulsion. On neurological examination, all patients had at least one cortical sensory deficit and wide-based gait with lateropulsion towards the side of the cortical deficit. Neuroimaging revealed a subacute parietal lobe stroke contralateral to the side of gait lateropulsion. In two patients we found bilateral lateropulsion with predominance towards the side of cortical deficit and increase of unsteadiness with eye closure (an apparent Romberg sign), with neuroimaging revealing bilateral parietal strokes (subacute contralateral and chronic ipsilateral to gait lateropulsion).Conclusion: We report gait lateropulsion as a novel primary manifestation of acute stroke of the parietal lobe (parietal gait lateropulsion). Given its role as the destination of proprioceptive pathways, parietal strokes can result in gait lateropulsion, with bilateral lesions even mimicking sensory ataxia with bilateral lateropulsion and unsteadiness upon eye closure.(AU)

Fecal concentration of intravenous vancomycin preparation after oral administration in an experimental model: preclinical assay.

INTRODUCTION: Clostridioides difficile (C. difficile) infection is the main cause of nosocomial diarrhea. First-line treatment is oral vancomycin, but that presentation is not commercially available in Latin America. Our aim was to determine the fecal concentration of the oral administration of the conventional dose of an intravenous vancomycin preparation (VCM), in an experimental model. METHODS: A preclinical trial was conducted on 18 male mice (Balb/c strain), in three batches. The following doses of VCM were administered: 125 mg in batch A; 500 mg in batch B; and VCM-placebo in batch C. After receiving the doses, the mice were placed in metabolic cages, by batch. Feces were collected and the fecal concentration of VCM was analyzed through high pressure liquid chromatography 2, 4 and 6 h after drug administration. RESULTS: The 125 mg dose of VCM reached the minimum inhibitory concentration (MIC) for C. difficile, without reaching the minimum bactericidal concentration (MBC90), at 2, 4, and 6 h (521, 688, and 280 mg/L, respectively). Likewise, the 500 mg dose of VCM reached the MIC at 2 h, increased gradually, and reached MBC90 between 4 and 6 h, in feces (1,062 and 1,779 mg/L, respectively), ANOVA, p = 0.0005. CONCLUSION: The fecal concentration of vancomycin was dependent on the intragastric dose administered. Only the 500 mg dose of VCM reached therapeutic concentration for C. difficile (MIC and MBC90), in the mice. We suggest starting a dose of 500 mg QID for achieving therapeutic concentration against C. difficile, as soon as 4 h after the first dose.

Impact of Arrhythmia in Hospital Mortality in Acute Ischemic Stroke Patients: A Retrospective Cohort Study in Northern Mexico.

BACKGROUND: Atrial fibrillation has been associated with higher morbidity and mortality rates in acute ischemic stroke patients (AIS). However, there is scarce information regarding the clinical outcomes and strokes' characteristics among AIS patients with other type of arrhythmias. OBJECTIVE: Our study aims to analyze the hospital mortality rate, stroke characteristics, and clinical and demographical data of patients with any post-stroke arrhythmia. METHODS: Retrospective cohort study of AIS patients with 24h-Holter monitoring during hospital admission recruited between 2015-2020, outcomes were measured using the modified Rankin scale. RESULTS: 597 patients (61.13±13.61 years; 352 men) were included. Arrhythmias were diagnosed in 33 (5.5%), with atrial fibrillation as the most common finding (82%). Age was related to a higher rate of arrhythmia (P = 0.014). A larger prevalence of cardioembolic strokes (69.7% vs 16.6%, P < 0.05) and AIS in the middle cerebral artery's vascular territory (78.8% vs 58.7%, P < 0.05) were found amongst patients with an arrhythmia. No significant association was found between NIHSS at admission with neither incidence of arrhythmia nor mortality. Within the arrhythmia group, three in-hospital deaths were reported: one AF, one ventricular arrhythmia and one second-degree atrioventricular block. In a logistic regression analysis, patients with any kind of arrhythmia had a higher mortality rate (9.1% vs 1.2%, P = 0.011; OR 6.766, 95% CI 1.552 - 29.500). CONCLUSION: Arrhythmia detection after an AIS was associated with increased in-hospital mortality. Risk factors related to arrhythmia detection were a higher mean age, cardioembolic strokes and AIS affecting the middle cerebral artery.

Effects of DC Magnetic Fields on Magnetoliposomes.

The potential use of magnetic nanoparticles (MNPs) in biomedicine as magnetic resonance, drug delivery, imagenology, hyperthermia, biosensors, and biological separation has been studied in different laboratories. One of the challenges on MNP elaboration for biological applications is the size, biocompatibility, heat efficiency, stabilization in physiological conditions, and surface coating. Magnetoliposome (ML), a lipid bilayer of phospholipids encapsulating MNPs, is a system used to reduce toxicity. Encapsulated MNPs can be used as a potential drug and a gene delivery system, and in the presence of magnetic fields, MLs can be accumulated in a target tissue by a strong gradient magnetic field. Here, we present a study of the effects of DC magnetic fields on encapsulated MNPs inside liposomes. Despite their widespread applications in biotechnology and environmental, biomedical, and materials science, the effects of magnetic fields on MLs are unclear. We use a modified coprecipitation method to synthesize superparamagnetic nanoparticles (SNPs) in aqueous solutions. The SNPs are encapsulated inside phospholipid liposomes to study the interaction between phospholipids and SNPs. Material characterization of SNPs reveals round-shaped nanoparticles with an average size of 12 nm, mainly magnetite. MLs were prepared by the rehydration method. After formation, we found two types of MLs: one type is tense with SNPs encapsulated and the other is a floppy vesicle that does not show the presence of SNPs. To study the response of MLs to an applied DC magnetic field, we used a homemade chamber. Digitalized images show encapsulated SNPs assembled in chain formation when a DC magnetic field is applied. When the magnetic field is switched off, it completely disperses SNPs. Floppy MLs deform along the direction of the external applied magnetic field. Solving the relevant magnetostatic equations, we present a theoretical model to explain the ML deformations by analyzing the forces exerted by the magnetic field over the surface of the spheroidal liposome. Tangential magnetic forces acting on the ML surface result in a press force deforming MLs. The type of deformations will depend on the magnetic properties of the mediums inside and outside the MLs. The model predicts a coexistence region of oblate-prolate deformation in the zone where χ = 1. We can understand the chain formation in terms of a dipole-dipole interaction of SNP.

Efficiency of integrated electrooxidation and anaerobic digestion of waste activated sludge.

BACKGROUND: Most of the organic content of waste activated sludge (WAS) comprises microbial cells hard to degrade, which must be pre-treated for energy recovery by anaerobic digestion (AD). Electrooxidation pre-treatment (EOP) with boron-doped diamond (BDD) electrode have been considered a promising novel technology that increase hydrolysis rate, by the disintegrating cell walls from WAS. Although electrochemical oxidation could efficiently solubilize organic substances of macromolecules, limited reports are available on EOP of WAS for improving AD. In this endeavour, the mathematical optimization study and the energy analysis of the effects of initial total solids concentrations [TS] of WAS and current density (CD) during EOP on the methane production and removal of chemical oxygen demand (COD) and volatile solids (VS) were investigated. Because limited reports are available on EOP of WAS for improving biogas production, it is not well understood; however, it has started to attract interest of scientists and engineers. RESULTS: In the present work, the energy recovery as biogas and WAS conversion were comprehensively affected by CD and [TS], in an integrated EOP and AD system. When working with WAS at 3% of [TS] pre-treated at current density of 24.1 mA/cm2, the highest COD and VS removal were achieved, making it possible to obtain the maximum methane (CH4) production of 305 N-L/kg VS and a positive energy balance of 1.67 kWh/kg VS. Therefore, the current densities used in BDD electrode are adequate to produce the strong oxidant (hydroxyl radical, ·OH) on the electrode surface, allow the oxidation of organic compounds that favours the solubilization of particulate matter and VS from WAS. CONCLUSIONS: The improvement of VS removal and COD solubilization were due to the effects of pre-treatments, which help to break down the microbial cells for faster subsequent degradation; this allows a decomposition reaction that leads to biodegrade more compounds during AD. The balance was positive, suggesting that even without any optimization the energy used as electricity could be recovered from the increased methane production. It is worth noting that this kind of analysis have not been sufficiently studied so far. It is therefore important to understand how operational parameters can influence the pre-treatment and AD performances. The current study highlights that the mathematical optimization and energy analysis can make the whole process more convenient and feasible.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study.

BACKGROUND: We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF/PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. RESULTS: Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. CONCLUSIONS: BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy.

Effects of Chlorpyrifos Over Reproductive Traits of Three Sympatric Freshwater Crustaceans.

The exposure to environmentally relevant chlorpyrifos concentrations (0.03, 0.06 and 0.12 µg chlorpyrifos L-1) causes increases in precopulatory guardian behavior time, amplexus reformulation after exposure and in the number of ovigerous females in the amphipod Hyalella curvispina. Effects in incubation period, effective hatching and median lethal concentration on the decapods Macrobrachium borellii and Aegla uruguayana, both in adults and embryos, were achieved at higher concentrations than those found in the environment. Environmentally relevant chlorpyrifos concentrations appear not to affect decapods but several effects in reproductive traits of amphipods were observed.

[Diffusion tensor imaging of the corticospinal pathway and its association with the prognosis of acute cerebral infarction: experience with a cohort in Mexico]. / Imagen del tensor de difusión de la vía corticoespinal y su asociación con el pronóstico del infarto cerebral agudo: experiencia de una cohorte en México.

INTRODUCTION: Magnetic resonance diffusion tensor imaging through the fraction of anisotropy allows evaluation of the integrity of the motor pathways after cerebral infarction. AIMS: To correlate the fraction of anisotropy with the clinical scales and the prognosis of cerebral infarction. SUBJECTS AND METHODS: Prospective study of patients with cerebral infarction to compare the fraction of anisotropy in different regions of interest with functional evaluations and with controls free of infarction. A subgroup of subjects with rehabilitation underwent an initial MRI scan and another at three months, with clinical follow-up for six months. RESULTS: Thirty-eight consecutive patients with middle cerebral artery infarction were included. The fraction of anisotropy values were lower in the ipsilateral corticospinal pathway than the fraction of anisotropy of the corticospinal pathway of the controls. The values of the fraction of anisotropy in the ipsilateral corticospinal pathway were associated with the value of the functional scale on admission. Changes in the fraction of anisotropy values between the initial MRI and the scan performed at three months correlated with the score on the functional scale and the modified Rankin scale at three and six months. CONCLUSIONS: The value of the fraction of anisotropy in the ipsilateral internal capsule is associated with the presence of a lesion and with its presenting symptoms. Changes in the fraction of anisotropy at three months suggest long-term clinical recovery.

TITLE: Imagen del tensor de difusión de la vía corticoespinal y su asociación con el pronóstico del infarto cerebral agudo: experiencia de una cohorte en México.Introducción. La imagen del tensor de difusión por resonancia magnética a través de la fracción de anisotropía permite evaluar la integridad de las vías motoras después de un infarto cerebral. Objetivo. Correlacionar la fracción de anisotropía con las escalas clínicas y el pronóstico del infarto cerebral. Sujetos y métodos. Estudio prospectivo de pacientes con infarto cerebral para comparar la fracción de anisotropía en diferentes regiones de interés con evaluaciones funcionales y con controles sin infarto. En un subgrupo con rehabilitación, se realizó una resonancia magnética inicial y a los tres meses, con un seguimiento clínico durante seis meses. Resultados. Se incluyó a 38 pacientes consecutivos con infarto cerebral de la arteria cerebral media. Los valores de la fracción de anisotropía fueron menores en la vía corticoespinal ipsilateral que en la vía corticoespinal de los controles. Los valores de la fracción de anisotropía en la vía corticoespinal ipsilateral se asociaron con el valor de la escala funcional en el momento de su admisión. Los cambios en los valores de la fracción de anisotropía entre la resonancia magnética inicial y a los tres meses se correlacionaron con la puntuación en la escala funcional y en la escala de Rankin modificada a los tres y a los seis meses. Conclusiones. El valor de la fracción de anisotropía en la cápsula interna ipsilateral se asocia a la presencia de lesión y a su presentación clínica. Los cambios en la fracción de anisotropía a los tres meses sugieren la recuperación clínica a largo plazo.

SEOM clinical guideline for the diagnosis and treatment of gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA) (2019).

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, it represents the sixth cause of cancer death. In Western countries, the incidence is decreasing slightly, with an increase in gastroesophageal junction adenocarcinoma (GEJA), a different entity that we separate specifically in the guideline. Molecular biology advances have been done recently, but do not yet lead to the choice in treatment approach except in advanced disease with overexpression of HER2. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors and preliminary immune therapy resulting in advanced disease are the main treatment innovations in the GC/GEJA treatment. We describe the different evidences and recommendations following the statements of the American College of Physicians.

Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group.

BACKGROUND: The bevacizumab-Avastin® adjuVANT (AVANT) study did not meet its primary end point of improving disease-free survival (DFS) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III colon cancer (CC). We report here the long-term survival results (S-AVANT). PATIENTS AND METHODS: Patients with curatively resected stage III CC were randomly assigned to FOLFOX4, FOLFOX4-bevacizumab, or XELOX-bevacizumab. RESULTS: A total of 2867 patients were randomized: FOLFOX4: n = 955, FOLFOX4-bevacizumab: n = 960, XELOX-bevacizumab: n = 952. With a median of 6.73 years follow-up (interquartile range 5.51-10.54), 672 patients died, of whom 198 (20.7%), 250 (26.0%), and 224 (23.5%) were in the FOLFOX4, FOLFOX4-bevacizumab, and XELOX-bevacizumab arms, respectively. The 10-year overall survival (OS) rates were 74.6%, 67.2%, and 69.9%, (P = 0.003) and 5-year disease-free survival (DFS) rates were 73.2%, 68.5%, and 71.0% (P = 0.174), respectively. OS and DFS hazard ratios were 1.29 [95% confidence interval (CI) 1.07-1.55; P = 0.008] and 1.16 (95% CI 0.99-1.37; P = 0.063) for FOLFOX4-bevacizumab versus FOLFOX4 and 1.15 (95% CI 0.95-1.39; P = 0.147) and 1.1 (95% CI 0.93-1.29; P = 0.269) for XELOX-bevacizumab versus FOLFOX4, respectively. CC-related deaths (n = 542) occurred in 157 (79.3%) patients receiving FOLFOX4, 205 (82.0%) receiving FOLFOX4-bevacizumab, and 180 (80.4%) receiving XELOX-bevacizumab (P = 0.764), while non-CC-related deaths occurred in 41 (20.7%), 45 (18.0%), and 44 (19.6%) patients, respectively. Cardiovascular-related and sudden deaths during treatment or follow-up were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in the FOLFOX4, FOLFOX4-bevacizuamb, and XELOX-bevacizumab arms, respectively (P = 0.789). Treatment arm, sex, age, histological differentiation, performance status, T/ N stages, and localization of primary tumor were independent prognostic factors of OS in stage III. CONCLUSIONS: S-AVANT confirms the initial AVANT report. No benefit of the bevacizumab addition to FOLFOX4 adjuvant therapy in patients with stage III CC was observed in terms of DFS with a negative effect in OS, without increase in non-CC related deaths. CLINICAL TRIAL IDENTIFICATION: NCT00112918.

Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE).

BACKGROUND: Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma (PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels. PATIENTS AND METHODS: CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC. In part 1, 10 patients were evaluated for pharmacokinetics and safety. In part 2, patients with high free serum IGF-1 levels were randomized 1 : 1 to receive either istiratumab [2.8 g intravenously (i.v.) every 2 weeks] or placebo combined with gemcitabine/nab-paclitaxel at approved dose schedule. The co-primary endpoints were progression-free survival (PFS) in patients with high IGF-1 levels and PFS in patients with both high serum IGF-1 levels and heregulin (HRG)+ tumors. Key secondary endpoints were overall survival (OS), objective response rate (ORR) by RECIST v.1.1, and adverse events (AEs) rate. RESULTS: A total of 317 patients were screened, with 88 patients randomized in part 2 (experimental arm n = 43; control n = 45). In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42). Median OS and ORR for the overall population were similar between two arms. No significant difference in serious or grade ≥3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) versus control arm (24.4%). CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. High serum IGF-1 levels did not appear to be an adverse prognostic factor when compared with non-biomarker-selected historic controls. CLINICAL TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02399137; EUDRA CT: 2014-004572-34.