Spanish normative studies (NEURONORMA-Plus project): norms for the Wisconsin Card Sorting Test, the Modified Taylor Complex Figure, and the Ruff-Light Trail Learning Test.

OBJECTIVE: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project. METHODS: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (< 50 and ≥ 50 years). RESULTS: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (< 50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥ 50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable. CONCLUSION: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population.

Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task.

INTRODUCTION: Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. METHODS: The sample included 308 cognitively unimpaired individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). RESULTS: Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. CONCLUSIONS: These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population.

Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT-AD): Study Design and Protocol.

BACKGROUND: Speech impairments are an early feature of Alzheimer's disease (AD) and consequently, analysing speech performance is a promising new digital biomarker for AD screening. Future clinical AD trials on disease modifying drugs will require a shift to very early identification of individuals at risk of dementia. Hence, digital markers of language and speech may offer a method for screening of at-risk populations that are at the earliest stages of AD, eventually in combination with advanced machine learning. To this end, we developed a screening battery consisting of speech-based neurocognitive tests. The automated test performs a remote primary screening using a simple telephone. OBJECTIVES: PROSPECT-AD aims to validate speech biomarkers for identification of individuals with early signs of AD and monitor their longitudinal course through access to well-phenotyped cohorts. DESIGN: PROSPECT-AD leverages ongoing cohorts such as EPAD (UK), DESCRIBE and DELCODE (Germany), and BioFINDER Primary Care (Sweden) and Beta-AARC (Spain) by adding a collection of speech data over the telephone to existing longitudinal follow-ups. Participants at risk of dementia are recruited from existing parent cohorts across Europe to form an AD 'probability-spectrum', i.e., individuals with a low risk to high risk of developing AD dementia. The characterization of cognition, biomarker and risk factor (genetic and environmental) status of each research participants over time combined with audio recordings of speech samples will provide a well-phenotyped population for comparing novel speech markers with current gold standard biomarkers and cognitive scores. PARTICIPANTS: N= 1000 participants aged 50 or older will be included in total, with a clinical dementia rating scale (CDR) score of 0 or 0.5. The study protocol is planned to run according to sites between 12 and 18 months. MEASUREMENTS: The speech protocol includes the following neurocognitive tests which will be administered remotely: Word List [Memory Function], Verbal Fluency [Executive Functions] and spontaneous free speech [Psychological and/ or behavioral symptoms]. Speech features on the linguistic and paralinguistic level will be extracted from the recordings and compared to data from CSF and blood biomarkers, neuroimaging, neuropsychological evaluations, genetic profiles, and family history. Primary candidate marker from speech will be a combination of most significant features in comparison to biomarkers as reference measure. Machine learning and computational techniques will be employed to identify the most significant speech biomarkers that could represent an early indicator of AD pathology. Furthermore, based on the analysis of speech performances, models will be trained to predict cognitive decline and disease progression across the AD continuum. CONCLUSION: The outcome of PROSPECT-AD may support AD drug development research as well as primary or tertiary prevention of dementia by providing a validated tool using a remote approach for identifying individuals at risk of dementia and monitoring individuals over time, either in a screening context or in clinical trials.

Características clínicas y resultados de pacientes con fibrosis quística con enfermedad pulmonar avanzada: experiencia en 10 años del Instituto Nacional del Tórax / Clinical features and outcomes of cystic fibrosis patients with advanced lung disease: experience of 10 years at the Instituto Nacional del Tórax

La enfermedad pulmonar avanzada (EPAV) es la principal causa de morbimortalidad en pacientes con Fibrosis Quística (FQ). Objetivo: describir características clínicas de pacientes con FQ con EPAV y mortalidad en el seguimiento. Método: Estudio descriptivo, retrospectivo de pacientes con FQ y EPAV: VEF1 4 años de vida. Un 75% era portador de infección crónica por Pseudomonas. Un 68% era dependiente de oxígeno y un 18% de ventilación mecánica no invasiva. El 70 % tuvo 2 o más hospitalizaciones el último año de seguimiento. De 27 pacientes derivados a trasplante, 7 se trasplantaron, 3 fallecieron en lista para trasplante, 9 presentaron alguna contraindicación: 4 de ellos por desnutrición y 5 por mala adherencia y escasa red de apoyo. En el seguimiento un 32% (n = 14) falleció, 93% de causa respiratoria. Conclusión: Un 39% de los pacientes tenían EPAV cuyo diagnóstico de FQ en promedio fue a los 11,2 años (SD ± 13 a). Las barreras de ingreso a lista para trasplante fueron: desnutrición, mala adherencia y falta de red de apoyo. Esta es una población con una elevada mortalidad.

Advanced cystic fibrosis lung disease (ACFLD) is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Objective: to describe clinical characteristics of patients with CF with ACFLD and mortality during follow-up. Method: Descriptive, retrospective study of patients with CF and ACFLD: FEVi < 40%, oxygen dependent, and/or referred to a lung transplantprogram. Clinical, microbiological, functional, genetic and mortality characteristics were collected. Results: Of 111 controlled patients, 39% met criteria for ACFLD. 52% were men and the mean age was 29,8 years- old. The average BMI was 19.9 kg/m2, 72% had pancreatic insufficiency and 87% had a genetic study, being the DF508 mutation the most frequent (67%). The average age of diagnosis was 11.2 years (SD ± 13 years), being in 54,5% over the age of 4 years. 75% had chronic Pseudomonas infection. 68% were oxygen dependent and 18% on noninvasive mechanical ventilation. In the last year of follow-up 70% had 2 or more hospitalizations. Of 27 patients who have been referred for transplantation, 7 underwent lung transplantation, 3 died waiting on the transplant list, 9 had contraindications: 4 due to malnutrition and 5 to poor adherence and poor support network. 32% (n = 14) of the ACFLD patients died, 93% due to respiratory causes. Conclusion: 39% of the patients had ACFLD. The average age for CF diagnosis was 11.2 years (SD ± 13 years) Barriers to entering the transplant list are: malnutrition, poor adherence, and lack of a support network. This is a population with a high mortality.

The CORCOBIA study: Cut-off points of Alzheimer's disease CSF biomarkers in a clinical cohort.

INTRODUCTION: The analysis of the core biomarkers of Alzheimer's Disease (AD) in the cerebrospinal fluid (CSF) is recommended in the clinical units where it is available. Because of the absence of universal validated values, the determination of specific cut-off points for each center and its population is recommended. The main objective of the CORCOBIA study was to determine the cut-off points of core AD CSF biomarkers for several centers (Parc de Salut Mar, Barcelona and Hospital General de Granollers), which work with the same reference laboratory (Laboratori de Referència de Catalunya). METHODS: Prospective study including cognitively unimpaired individuals (CU, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer's Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyse amyloid beta peptides (Aß42, Aß40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of sensitivity (SE), specificity (SP), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the CU and AD groups. RESULTS: The resulting cut-offs and their AUC were the following: Aß42 750 pg/mL (AUC 0.809); Aß42/Aß40 0.062 (AUC 0.78); pTau181 69.85 pg/mL (AUC 0.81); tTau 522.0 pg/mL (AUC 0.79); Aß42/tTau 1.76 (AUC 0.86); Aß42/pTau181 10.25 (AUC 0.86). CONCLUSIONS: The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aß42/pTau181 shows the highest AUC and better balance between sensitivity and specificity.

Development, equivalence study, and normative data of version B of the Spanish-language Free and Cued Selective Reminding Test.

INTRODUCTION: The Free and Cued Selective Reminding Test (FCSRT) is widely used for the assessment of verbal episodic memory, mainly in patients with Alzheimer disease. A Spanish-language version of the FCSRT and normative data were developed within the NEURONORMA project. Availability of alternative, equivalent versions is useful for following patients up in clinical settings. This study aimed to develop an alternative version of the original FCSRT (version B) and to study its equivalence to the original Spanish-language test (version A), and its performance in a sample of healthy individuals, in order to develop reference data. METHODS: We evaluated 232 healthy participants of the NEURONORMA-Plus project, aged between 18 and 90. Thirty-three participants were assessed with both test versions using a counterbalanced design. RESULTS: High intra-class correlation coefficients (between 0.8 and 0.9) were observed in the equivalence study. While no significant differences in performance were observed in total recall scores, free recall scores were significantly lower for version B. CONCLUSIONS: These preliminary results suggest that the newly developed FCSRT version B is equivalent to version A in the main variables tested. Further studies are necessary to ensure interchangeability between versions. We provide normative data for the new version.

Spanish normative studies (NEURONORMA-Plus project): norms for the Wisconsin Card Sorting Test, the Modified Taylor Complex Figure, and the Ruff-Light Trail Learning Test. / Estudios normativos españoles (proyecto NEURONORMA-Plus): Normas para el Wisconsin Card Sorting Test (WCST), la Figura Compleja Modificada de Taylor (FCMT) y el Ruff-Light Trail Learning Test (RULIT).

OBJECTIVE: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project. METHODS: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (<50 and ≥50 years). RESULTS: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (<50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable. CONCLUSION: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population.

Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task. / Estudios normativos españoles (Proyecto NEURONORMA Plus): normas para las pruebas Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Tests (CTT) y Dual Task (DT).

INTRODUCTION: Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. METHODS: The sample included 308 cognitively healthy individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). RESULTS: Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. CONCLUSIONS: These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population.

Clinicopathological factors associated with the presence of hypercapnia at admission in hospitalised cats with decompensated chronic kidney disease.

AIMS: To evaluate associations between clinicopathological variables and hypercapnia measured in cats with decompensated chronic kidney disease (CKD) on admission to a veterinary hospital. METHODS: This is a retrospective, cross-sectional study of cats (n = 39) that presented to a tertiary veterinary hospital in Argentina between June 2015 and December 2017 with blood creatinine concentrations >140 µmol/L, and abdominal ultrasound results consistent with CKD. Data recorded included venous partial pressure of CO2 (PvCO2), blood pH, haematocrit and concentrations of glucose, potassium, sodium, corrected sodium (Na+c), and ionised calcium in blood. A logistic regression model was used to assess associations between the presence of hypercapnia (PvCO2 ≥ 44.7 mmHg) and the other clinicopathologic variables. The duration of hospitalisation was compared in cats with and without hypercapnia using the Wilcoxon Rank Sum test. RESULTS: The final study population comprised 39 cats. Eleven cats (28.2%) had hypercapnia. In the logistic regression model, two independent variables were associated with the presence of hypercapnia at admission in cats with CKD: the concentration of creatinine in blood (OR = 1.06 (95% CI = 1.016-1.108); p = 0.007) and Na+c (OR = 1.33 (95% CI = 1.08-1.63); p = 0.005). There were no statistically significant differences in the length of hospital stay between the two groups. CONCLUSIONS AND CLINICAL RELEVANCE: There appears to be an association between elevated concentrations of creatinine and Na+c in blood, and hypercapnia in cats with CKD, suggesting careful assessment of blood gas and electrolyte parameters during hospitalisation is required. Further prospective studies are needed to evaluate the mechanisms behind this association and the association of hypercapnia with disease outcome including mortality.

Desarrollo, estudio de equivalencia y datos normativos de la versión española B del Free and Cued Selective Reminding Test / Development, equivalence study, and normative data of version B of the Spanish-language Free and Cued Selective Reminding Test

Introducción: El test Free and Cued Selective Reminding Test (FCSRT) es una prueba de uso extendido para evaluar la memoria episódica verbal, principalmente en el ámbito de la enfermedad de Alzheimer. Existe una versión española de la prueba con datos normativos proveniente del proyecto NEURONORMA.ES. Disponer de versiones alternativas equivalentes de las pruebas resulta útil para el seguimiento de los pacientes en la práctica clínica. El objetivo del presente estudio es ofrecer una versión alternativa a la original, denominada «B», estudiar su equivalencia con la versión original española (A) y el rendimiento en la misma de una muestra de sujetos para proporcionar datos de referencia.MétodosSe evaluaron 232 sujetos sanos de entre 18 y 90 años en el contexto del proyecto NEURONORMA-Plus. A 33 de ellos se les administraron ambas versiones con un diseño contrabalanceado.ResultadosEn el estudio de equivalencia se observaron coeficientes de correlación intraclase elevados (entre 0,8 y 0,9) y diferencias no significativas en las variables de recuerdo total. Sin embargo, sí se hallaron diferencias significativas en los ensayos de evocación libre, en los que el rendimiento en la nueva versión fue menor.ConclusionesLos resultados iniciales sugieren que la versión B del FCSRT aquí presentada resulta equivalente a la versión A en las variables principales de la prueba. Se requieren de futuros estudios para asegurar la total intercambiabilidad entre versiones. Se aportan datos normativos de la versión presentada. (AU)

Introduction: The Free and Cued Selective Reminding Test (FCSRT) is widely used for the assessment of verbal episodic memory, mainly in patients with Alzheimer disease. A Spanish version of the FCSRT and normative data were developed within the NEURONORMA project. Availability of alternative, equivalent versions is useful for following patients up in clinical settings. This study aimed to develop an alternative version of the original FCSRT (version B) and to study its equivalence to the original Spanish test (version A), and its performance in a sample of healthy individuals, in order to develop reference data.MethodsWe evaluated 232 healthy participants of the NEURONORMA-Plus project, aged between 18 and 90. Thirty-three participants were assessed with both versions using a counterbalanced design.ResultsHigh intra-class correlation coefficients (between 0.8 and 0.9) were observed in the equivalence study. While no significant differences in performance were observed in total recall scores, free recall scores were significantly lower for version B.ConclusionsThese preliminary results suggest that the newly developed FCSRT version B is equivalent to version A in the main variables tested. Further studies are necessary to ensure interchangeability between versions. We provide normative data for the new version. (AU)

Comparative Analysis of Different Definitions of Amyloid-ß Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer.

Amyloid-ß (Aß) positivity is defined using different biomarkers and different criteria. Criteria used in symptomatic patients may conceal meaningful early Aß pathology in preclinical Alzheimer. Therefore, the description of sensitive cutoffs to study the pathophysiological changes in early stages of the Alzheimer's continuum is critical. Here, we compare different Aß classification approaches and we show their performance in detecting pathophysiological changes downstream Aß pathology. We studied 368 cognitively unimpaired individuals of the ALFA+ study, many of whom in the preclinical stage of the Alzheimer's continuum. Participants underwent Aß PET and CSF biomarkers assessment. We classified participants as Aß -positive using five approaches: (1) CSF Aß42 < 1098 pg/ml; (2) CSF Aß42/40 < 0.071; (3) Aß PET Centiloid > 12; (4) Aß PET Centiloid > 30 or (5) Aß PET Positive visual read. We assessed the correlations between Aß biomarkers and compared the prevalence of Aß positivity. We determined which approach significantly detected associations between Aß pathology and tau/neurodegeneration CSF biomarkers. We found that CSF-based approaches result in a higher Aß-positive prevalence than PET-based ones. There was a higher number of discordant participants classified as CSF Aß-positive but PET Aß-negative than CSF Aß-negative but PET Aß-positive. The CSF Aß 42/40 approach allowed optimal detection of significant associations with CSF p-tau and t-tau in the Aß-positive group. Altogether, we highlight the need for sensitive Aß -classifications to study the preclinical Alzheimer's continuum. Approaches that define Aß positivity based on optimal discrimination of symptomatic Alzheimer's disease patients may be suboptimal for the detection of early pathophysiological alterations in preclinical Alzheimer.

[Rett Syndrome: MECP2 gene molecular analysis in Chilean patients]. / Síndrome de Rett: Análisis molecular del gen MECP2 en pacientes chilenas.

INTRODUCTION: Rett syndrome (RTT) is a progressive neurological disorder characterized by regres sion of psychomotor development in previously healthy girls. Most cases are due to pathogenic va riants in the MECP2 gene which encodes for the methyl CpG-binding protein 2. OBJECTIVE: To des cribe the frequency and type of pathogenic variants in the MECP2 gene in Chilean female patients with clinical diagnosis of RTT. PATIENTS AND METHOD: Chilean women with clinical suspicion of RTT were invited to participate in the study. Clinical data were collected through a questionnaire. MECP2 pathogenic variants were analyzed by Sanger sequencing method and Multiplex Ligation-dependent Probe Amplification (MLPA) was used to detect duplications or deletions. RESULTS: The study in cluded 14 patients with suspected RTT, of which eight (57%) patients had pathogenic variants. The other patients remain without molecular diagnosis. CONCLUSIONS: Pathogenic variants in MECP2 are present in Chilean patients with RTT. It is likely that there are other genes or diagnoses involved in patients without MECP2 findings. As of this study, molecular diagnosis is available in Chile.

Síndrome de Rett: Análisis molecular del gen MECP2 en pacientes chilenas / Rett syndrome: MECP2 gene molecular analysis in Chilean patients

INTRODUCCIÓN: El síndrome de Rett (RTT) es un trastorno neurológico progresivo caracterizado por producir una regresión del desarrollo psicomotor en niñas previamente sanas. La mayoría de los casos son causados por variantes patogénicas en el gen MECP2, que codifica para la proteína methyl CpG- binding protein 2. OBJETIVO: Describir la frecuencia y el tipo de variantes patogénicas en MECP2 en mujeres chilenas con diagnóstico clínico de RTT. PACIENTES Y MÉTODO: Se invitó a participar en este estudio a mujeres chilenas con sospecha clínica de RTT. Se reunió información clínica mediante un cuestionario. Se analizaron variantes patogénicas en MECP2 mediante el método de secuenciación de Sanger y se utilizó Multiple Ligation-dependant Probe Amplification (MLPA) para la detección de duplicaciones y deleciones. RESULTADO: El estudio incluyó 14 pacientes con sospecha de RTT, de las cuales 8 (57%) pacientes tuvieron variantes patogénicas. Las restantes permanecen sin diagnóstico molecular. CONCLUSIÓN: Variantes patogénicas en MECP2 están presentes en pacientes chilenas con RTT. Es probable que haya otros genes o diagnósticos involucrados en las pacientes sin hallazgos en MECP2. A partir de este trabajo, el diagnóstico molecular está disponible en Chile.

INTRODUCTION: Rett syndrome (RTT) is a progressive neurological disorder characterized by regres sion of psychomotor development in previously healthy girls. Most cases are due to pathogenic va riants in the MECP2 gene which encodes for the methyl CpG-binding protein 2. OBJECTIVE: To des cribe the frequency and type of pathogenic variants in the MECP2 gene in Chilean female patients with clinical diagnosis of RTT. PATIENTS AND METHOD: Chilean women with clinical suspicion of RTT were invited to participate in the study. Clinical data were collected through a questionnaire. MECP2 pathogenic variants were analyzed by Sanger sequencing method and Multiplex Ligation-dependent Probe Amplification (MLPA) was used to detect duplications or deletions. RESULTS: The study in cluded 14 patients with suspected RTT, of which eight (57%) patients had pathogenic variants. The other patients remain without molecular diagnosis. CONCLUSIONS: Pathogenic variants in MECP2 are present in Chilean patients with RTT. It is likely that there are other genes or diagnoses involved in patients without MECP2 findings. As of this study, molecular diagnosis is available in Chile.

Análisis espectroscópico del precipitado formado de la mezcla de Hipoclorito de Sodio y Clorhexidina . Estudio In Vitro . Parte II

l objetivo de este estudio fue analizar el precipitado formado por la interacción de dos disoluciones acuosas: una de hipoclorito de sodio al 5.25% y otra de gluconato de clorhexidina al 2%, por medio de cromatografía de capa fina (TLC) y un análisis detallado de espectroscopia de resonancia magnética nuclear (RMN-¹H a 600 MHz y RMN-¹³C a 100 MHz) en una y dos dimensiones. Para esto, se establecieron 3 grupos de estudio: el Grupo A correspondiente a gluconato puro de clorhexidina que fue liofilizado y secado al vacío, el Grupo B: los precipitados obtenidos al combinar 2 ml de la disolución de gluconato de clorhexidina con 2 ml de la disolución de hipoclorito de sodio y el Grupo C, una muestra comercial de PCA (4-Cloroanilina 98%,). El sólido correspondiente al grupo B, fue lavado, centrifugado y seco en estufa de vacío sin calentamiento por más de 72 horas. Una vez seco, se corrieron placas de capa fina (TLC) en diversas mezclas de elución, y se encontró que el precipitado consistía de una mezcla compleja de sustancias similares a la clorhexidina y que no poseía PCA. Los análisis de espectroscopia de resonancia magnética nuclear mostraron que la señal del carbono base del grupo amino de la PCA, a δ/146.5 ppm (grupo C), no se encontraba en el espectro de ¹³C de las muestras del grupo B lo que implica, la ausencia de PCA en la muestra B. El análisis del grupo B por medio de la misma técnica, mostró una mezcla compleja de señales que corresponden probablemente, a estructuras similares a la clorhexidina y a potenciales derivados aromáticos con una estructura similar a esta, nuevamente, no se encuentran evidencias de PCA.

he aim of this study was to analyze the precipitate formed by the mixture of 5,25% sodium hypochlorite (NaOCl) and 2% chlorhexidine (CHX) through thin layer chromatography and nuclear magnetic resonance spectroscopy (RMN-¹H, 600 MHz and RMN-¹³C to 100 MHz) 1D and 2D spectra. Thus, the following groups were established: Group A corresponds to a pure freeze-dried chlorhexidine gluconate , Group B made-up by a combination of 2ml of chlorhexidine 2% and sodium hypochlorite 5.25% and Group C was a commercial sample of PCA (4-Chloroaniline 98%). The samples of group B were rinsed with distillated water and spinned during 15 minutes at 25°C, the supernatant was eliminated by vacuum and vacuum chamber for 72 hours without heating. Finally, the solid was grinded and dried in vacuum chamber for 24 hours without heating. Thin layer chromatography, shows that sample B were composed by more than one chemical substance and Chlorexidine, the RMN-¹³C showed that the signal of the amino group characteristic of PCA appears down field (δ/146.5 ppm) in C group, meanwhile in group B appears up field (δ/129ppm), which demonstrates the absence of PCA during the process. The analysis of Group B by RMN-¹³C results also, in different signals of low intensity that correspond to similar structures to chlorhexidine and potential aromatics derivatives with similar characteristics structures to chlorhexidine.

Edema pulmonar agudo no cardiogénico secundario a hidroclorotiazida: reporte de un caso y revisión de la literatura / Hydrochlorothiazide induced non-cardiogenic acute pulmonary edema: a case report

Las tiazidas son fármacos frecuentemente usados en la terapia de la hipertensión arterial. Las reacciones adversas de riesgo vital como shock y edema pulmonar agudo son raros. Comunicamos el caso de una mujer de 55 años de edad atendida en Hospital de Puerto Montt, quien tras dos horas de ingerir hidroclorotiazida presentó disnea. Los exámenes de laboratorio generales e imágenes muestran cuadro concordante con edema pulmonar agudo no cardiogénico. Además de la suspensión del fármaco, se realizó soporte hemodinámico y ventilatorio no invasivo, evidenciándose resolución del cuadro a las 48 h. La paciente fue dada de alta 3 días después de su ingreso sin sintomatología.

Thiazides are drugs often used in management of high arterial blood pressure. Shock and acute pulmonary edema are rarely described as adverse reactions related to this drug. We report the case of a 55 years-old woman admitted at Hospital de Puerto Montt, Chile. Two hours after having her first dose of hydrochlorothiazide she presented dyspnea. Laboratory tests and images support the diagnosis of non-cardiogenic pulmonary edema. Resolution of her clinical picture was observed 48 hours after hydrochlorothiazide administration was discontinued and hemodynamic and non invasive ventilation support were supplied. The patient was discharged without symptoms, 3 days after entering to hospital.

Nonlinear cerebral atrophy patterns across the Alzheimer's disease continuum: impact of APOE4 genotype.

The progression of Alzheimer's disease (AD) is characterized by complex trajectories of cerebral atrophy that are affected by interactions with age and apolipoprotein E allele ε4 (APOE4) status. In this article, we report the nonlinear volumetric changes in gray matter across the full biological spectrum of the disease, represented by the AD-cerebrospinal fluid (CSF) index. This index reflects the subject's level of pathology and position along the AD continuum. We also evaluated the associated impact of the APOE4 genotype. The atrophy pattern associated with the AD-CSF index was highly symmetrical and corresponded with the typical AD signature. Medial temporal structures showed different atrophy dynamics along the progression of the disease. The bilateral parahippocampal cortices and a parietotemporal region extending from the middle temporal to the supramarginal gyrus presented an initial increase in volume which later reverted. Similarly, a portion of the precuneus presented a rather linear inverse association with the AD-CSF index whereas some other clusters did not show significant atrophy until index values corresponded to positive CSF tau values. APOE4 carriers showed steeper hippocampal volume reductions with AD progression. Overall, the reported atrophy patterns are in close agreement with those mentioned in previous findings. However, the detected nonlinearities suggest that there may be different pathological processes taking place at specific moments during AD progression and reveal the impact of the APOE4 allele.

Biological characteristics of geographically isolated populations of Meccus mazzottii (Hemiptera: Reduviidae) in southern Mexico.

Chagas disease, caused by Trypanosoma cruzi Chagas, is one of the most epidemiologically important vector-borne zoonoses in Mexico. Among the 32 reported triatomine species from Mexico, Meccus mazzottii (Usinger) (Hemiptera: Reduviidae) is one of the most important vectors of T. cruzi in the southern part of the country. Variability among populations of triatomines has been recorded for several species (Meccus longipennis (Usinger) and Meccus pallidipennis (Stal)) that are closely related to M. mazzottii, showing an apparent influence of local environmental conditions on the biology of each population, which could modify the impact of vector control measurements. Therefore, this study sought to compare the biological features of populations of M. mazzottii from two geographically far apart areas that have similar environmental characteristics and to compare populations from close geographical areas that have different environmental characteristics. The mean longevity, percentages of mortality of nymphs, the total mean number of bloodmeals to molt (considered instar by instar), the mean number of eggs laid by females, and the percentage of hatched eggs were similar between the two localities that are geographically far apart but have similar environmental characteristics. On the other hand, important differences were noticed when a comparison was carried out on the two localities with similar environmental conditions with respect to that locality with different conditions, independent of geographic distance. Most of the studied parameters led us to conclude that the three studied populations are very highly influenced by local environmental conditions. The results of this study indicate the importance of studying the biological characteristics of local populations of triatomines to carry out specific control measurements, instead of using standard ones that could fail if they are not adapted to the target population.

Diagnostic validity of the Alzheimer's disease functional assessment and change scale in mild cognitive impairment and mild to moderate Alzheimer's disease.

BACKGROUND: The Alzheimer's Disease Functional Assessment and Change Scale (ADFACS) is a functional assessment instrument widely used in clinical research. AIMS: To test the diagnostic and concurrent validity of the Spanish version of this scale and to describe the functional deficit pattern for mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. METHODS: The ADFACS, the Interview for Deterioration in Daily Living Activities in Dementia (IDDD), and the Mini Mental State Examination (MMSE) were administered to 146 control subjects (CS) and 165 patients (67 MCI and 98 AD). Nonparametric tests were used to compare the diagnostic groups. Cronbach's α and correlations with the MMSE and the IDDD were calculated. Sensitivity, specificity and predictive values were studied. RESULTS: The ADFACS had a high internal consistency (α = 0.95). Three cutoff points of 1, 4, and 17 were provided to separate CS and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients, respectively. The ADFACS strongly correlated with functional (IDDD, 0.927) and cognitive (MMSE, 0.747) measures. A similar pattern of dysfunction, but in different grades, was found for the MCI and AD groups. CONCLUSION: The ADFACS is a reliable, valid, and sensitive instrument to assess functional abilities; it is useful in dementia assessment for elderly populations.

Estudios normativos españoles en población adulta joven (proyecto NEURONORMA jóvenes): normas para las pruebas Rey-Osterrieth Complex Figure (copia y memoria) y Free and Cued Selective Reminding Test / Spanish normative studies in young adults ( NEURONORMA young adults project): norms for the Rey-Osterrieth Complex Figure (copy and memory) and Free and Cued Selective Reminding Test

Introducción: El test Rey-Osterrieth Complex Figure (ROCF) y el Free and Cued Selective Reminding Test (FCSRT) son pruebas ampliamente utilizadas en la práctica clínica. El ROCF es de gran utilidad para la exploración de la percepción visual, la praxis constructiva y la memoria visuoespacial. El FCSRT evalúa aprendizaje y memoria verbal. Objetivo: En el presente estudio, que forma parte del proyecto de obtención de datos normativos españoles en adultos jóvenes (proyecto NEURONORMA jóvenes), se aportan datos normativos ajustados por edad y escolaridad para ambos test mediante la aplicación de regresiones lineales. Material y métodos: Se incluyó a 179 participantes sanos de entre 18 y 49 años de edad. Se aportan tablas para convertir las puntuaciones brutas en escalares, así como tablas de ajuste por los factores sociodemográficos. Resultados: Los resultados obtenidos muestran influencia de la escolaridad en diversas variables de memoria y en la copia de la figura. La edad únicamente afecta el rendimiento en memoria visuoespacial y el efecto del género es despreciable. Conclusiones: Las referencias obtenidas son de gran utilidad clínica para la evaluación neuropsicológica de población adulta joven española (AU)

Introduction: The Rey-Osterrieth Complex Figure (ROCF) and the Free and Cued Selective Reminding Test (FCSRT) are widely used in clinical practice. The ROCF assesses visual perception, constructional praxis, and visuo-spatial memory. The FCSRT assesses verbal learning and memory. Objective: In this study, as part of the Spanish normative studies project in young adults (NEURONORMA young adults), we present age- and education-adjusted normative data for both tests obtained by using linear regression techniques. Material and methods: The sample consisted of 179 healthy participants ranging in age from 18 to 49 years. We provide tables for converting raw scores to scaled scores in addition to tables with scores adjusted by socio-demographic factors. Results: The results showed that education affects scores for some of the memory tests and the figure-copying task. Age was only found to have an effect on the performance of visuo-spatial memory tests, and the effect of sex was negligible. Conclusions: The normative data obtained will be extremely useful in the clinical neuropsychological evaluation of young Spanish adults (AU)