Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Optimization and Validation of a Method to Determine Enolones and Vanillin Derivatives in Wines-Occurrence in Spanish Red Wines and Mistelles.

Understanding the chemical nature of wine aroma demands accurate quantitative determinations of different odor-active compounds. Quantitative determinations of enolones (maltol, furaneol, homofuraneol, and sotolon) and vanillin derivatives (vanillin, methyl vanillate, ethyl vanillate, and acetovanillone) at low concentrations are complicated due to their high polarity. For this reason, this paper presents an improved and automated version for the accurate measure of these common trace wine polar compounds (enolones and vanillin derivatives). As a result, a faster and more user-friendly method with a reduction of organic solvents and resins was developed and validated. The optimization of some stages of the solid phase extraction (SPE) process, such as washing with an aqueous solution containing 1% NaHCO3 at pH 8, led to cleaner extracts and solved interference problems. Due to the polarity of these type of compounds, an optimization of the large volume injection was also carried out. Finally, a programmable temperature vaporization (PTV) quartz glass inlet liner without wool was used. The injector temperature was raised to 300 °C in addition to applying a pressure pulse of 180 kPa for 4 min. Matrix effects were solved by the use of adequate internal standards, such as ethyl maltol and 3',4'-(methylenedioxy)acetophenone. Method figures of merit were highly satisfactory: good linearity (r2 > 0.98), precision (relative standard deviation, RSD < 10%), high recovery (RSD > 89%), and low detection limits (<0.7 µg/L). Enolones and vanillin derivatives are associated with wine aging. For this reason, the methodology was successfully applied to the quantification of these compounds in 16 Spanish red wines and 12 mistelles. Odor activity values (OAV) indicate that furaneol should be considered an aroma impact odorant in red wines and mistelles (OAV > 1) while homofuraneol and sotolon could also produce changes in their aroma perceptions (0.1 < OAV < 1).

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.

AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities.

BACKGROUND: Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear. AIMS: We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed. METHOD: This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model. RESULTS: A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = -0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. CONCLUSIONS: Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

Assessment of Concentrated Liquid Coffee Acceptance during Storage: Sensory and Physicochemical Perspective.

Concentrated liquid coffees (CLCs) refer to stored extracts stable at environmental temperature, used as ingredients in the retail market. Their low chemical stability affects the sensory profile. This study was performed in two CLCs, one without additives (BIB) and another with a mix of sodium benzoate and potassium sorbate additives (SD), stored at 25 °C for one year. Quantitative-Descriptive (QDA) and discriminant analyses permitted identifying the critical sensory attributes and their evolution over time. The concentrate without additives presented an acceptance limit of 196 days (evaluated at a 50% acceptance ratio), while the additives increased the shelf life up to 226 days (38.9% improvement). The rejection was related to a decreased aroma, increased acidity, and reduced bitterness. A bootstrapped feature selection version of Partial Least Square analysis further demonstrated that reactions of 5-caffeoylquinic acid (5CQA) and 3,5-dicaffeoylquinic acid (3,5diCQA) could cause changes in the aroma at the first degradation stage. In the following stages, changes in fructose and stearic acid contents, a key indicator of acceptance for both extracts possibly related to non-enzymatic reactions involving fructose and other compounds, might affect the bitterness and acidity. These results provided valuable information to understand flavor degradation in CLCs.

Nonparametric Population Pharmacokinetic Modeling of Isoniazid in Colombian Patients With Tuberculosis.

BACKGROUND: Isoniazid (INH) is a first-line antituberculosis (TB) agent with a pharmacokinetic profile characterized by high interindividual variation; however, population pharmacokinetic studies in patients with TB are scarce. The aim was to develop a population model for INH in Colombian patients with TB suitable for predicting drug exposure and assessing the probability of target attainment of pharmacodynamic goals. METHODS: Ten hospitalized adult patients with TB undergoing INH treatment were recruited. After an 8-hour fasting, subjects took 300 mg of INH, and 10 samples were taken from 0 to 12 hours. INH was quantified by high-performance liquid chromatography-UV, and data were analyzed with the Pmetrics R package software. A Monte Carlo simulation with the model parameters was run to determine the probability of target attainment for optimal efficacy. RESULTS: The best model included 2 compartments, first-order absorption (Ka), delayed absorption (Tlag), and linear clearance (CL). Median Tlag was 0.25 hours, 5.54 hour for Ka, (Equation is included in full-text article.)for CL, (Equation is included in full-text article.)for the volume of the central compartment (Vc), 1.04 L/h for intercompartmental clearance (Q), and 788 L for the volume of the peripheral compartment (Vp). CL and Vc were allometrically scaled on basis of the normalized body weight. CONCLUSIONS: The Monte Carlo simulation indicated that 300 mg of INH per day is appropriate for Mycobacterium tuberculosis strains with minimal inhibitory concentration (MIC) up to 0.03 mg/L (target: area under the concentration-time curve/MIC >597); however, to cover strains with MIC up to 0.125 mg/L (80% of clinical isolates), a dose of 900 mg per day would be required.

3D print model for surgical planning in a case of recurrent osteoblastic osteosarcoma of the left maxilla. A case report.

Osteosarcoma (OS) of the head and neck is a rare and aggressive disease characterized by the formation of osteoid by malignant osteoblasts. The mandible or maxilla are the most common sites of presentation. Radiologically, these tumors show considerable, destructive growth with periosteal reaction, which can suggest the diagnosis of OS. 3D printing, as an emerging technology, can play a role in orthopedic oncology by providing patient-specific 3D printed models to improve surgical planning and facilitate patient understanding. We present the case of a male in his early 30s with a final histological diagnosis of recurrent osteosarcoma of the left maxilla, where a 3D printed model was helpful for the diagnostic workup, surgical planning, and the procedure.

Exploring Chemical Markers Related to the Acceptance and Sensory Profiles of Concentrated Liquid Coffees: An Untargeted Metabolomics Approach.

In this study, we aimed to apply an untargeted LC/QTOF-MS analysis for the identification of compounds that positively and negatively affect the acceptance of coffee beverages from liquid coffee concentrates (CLCs) before and after storage. The metabolomic results were integrated with physicochemical and sensory parameters, such as color, pH, titratable acidity, and oxygen contents, by a bootstrapped version of partial least squares discriminant analysis (PLS-DA) to select and classify the most relevant variables regarding the rejection or acceptance of CLC beverages. The OPLS-DA models for metabolite selection discriminated between the percent sensory acceptance (the Accepted group) and rejection (the Rejected group). Eighty-two molecular features were considered statistically significant. Our data suggest that coffee sample rejection is associated with chlorogenic acid hydrolysis to produce ferulic and quinic acids, consequently generating methoxybenzaldehydes that impact the perceived acidity and aroma. Furthermore, acceptance was correlated with higher global scores and sweetness, as with lactones such as feruloyl-quinolactone, caffeoyl quinolactone, and 4-caffeoyl-1,5-quinolactone, and significant oxygen levels in the headspace.

Correlation between cognitive performance and structural neuroanatomy in patients with type I bipolar affective disorder treated with and without lithium.

INTRODUCTION: Lithium treatment of bipolar disorder (BD) has been associated with less cognitive impairment and fewer changes in structural brain anatomy compared to other treatments. However, the studies are heterogeneous and few assess whether these effects are related. The objective of this study was to evaluate and relate cognitive performance and structural neuroanatomy in patients treated with and without lithium. METHODS: Cross-sectional study that included 48 subjects with BD-I, of which 22 were treated with lithium and 26 without lithium. Performance was assessed on Wechsler III (WAIS III), TMT A and B (Trial Making Test) neuropsychological tests, California verbal learning test (CVLT), Rey complex figure test and Wisconsin card sorting test. Brain structures obtained by magnetic resonance imaging (MRI) were evaluated. The standardised mean difference (SMD) between both groups was calculated, adjusted for confounding variables using a propensity score, and the Spearman correlation coefficient (ρ) was used to assess the relationship between cognitive performance and neuroanatomical regions. RESULTS: Compared to the group without lithium, the group with lithium had fewer perseverative errors in the Wisconsin test (SMD = -0.69) and greater left and right cortical areas (SMD = 0.85; SMD = 0.92); greater surface area in the left anterior cingulate (SMD = 1.32), right medial orbitofrontal cortex (SMD = 1.17), right superior frontal gyrus (SMD = 0.82), and right and left precentral gyrus (SMD = 1.33; SMD = 0.98); greater volume of the right amygdala (SMD = 0.57), right hippocampus (SMD = 0.66), right putamen (SMD = 0.87) and right thalamus (SMD = .67). In the lithium group, a correlation was found with these errors and the thickness of the left precentral gyrus (ρ = -0.78), the volume of the right thalamus (ρ = -0.44), and the right amygdala (ρ = 0.6). CONCLUSIONS: The lithium group had better cognitive flexibility and greater dimension in some frontal and subcortical cortical regions. Furthermore, there was a moderate to high correlation between performance in this executive function and the thickness of the right precentral gyrus, and the volumes of the thalamus and the right amygdala. These findings could suggest a neuroprotective effect of lithium.

Correlation Between Cognitive Performance and Structural Neuroanatomy in Patients with Type I Bipolar Affective Disorder Treated with and Without Lithium. / Correlación entre el desempeño cognitivo y la neuroanatomía estructural en pacientes con trastorno afectivo bipolar tipo I tratados con y sin litio.

INTRODUCTION: Lithium treatment of bipolar disorder (BD) has been associated with less cognitive impairment and fewer changes in structural brain anatomy compared to other treatments. However, the studies are heterogeneous and few assess whether these effects are related. The objective of this study was to evaluate and relate cognitive performance and structural neuroanatomy in patients treated with and without lithium. METHODS: Cross-sectional study that included 48 subjects with BD-I, of which 22 were treated with lithium and 26 without lithium. Performance was assessed on Wechsler III (WAIS III), TMT A and B (Trial Making Test) neuropsychological tests, California verbal learning test (CVLT), Rey complex figure test and Wisconsin card sorting test. Brain structures obtained by magnetic resonance imaging (MRI) were evaluated. The standardised mean difference (SMD) between both groups was calculated, adjusted for confounding variables using a propensity score, and the Spearman correlation coefficient (ρ) was used to assess the relationship between cognitive performance and neuroanatomical regions. RESULTS: Compared to the group without lithium, the group with lithium had fewer perseverative errors in the Wisconsin test (SMD = -0.69) and greater left and right cortical areas (SMD = 0.85; SMD = 0.92); greater surface area in the left anterior cingulate (SMD = 1.32), right medial orbitofrontal cortex (SMD = 1.17), right superior frontal gyrus (SMD = 0.82), and right and left precentral gyrus (SMD = 1.33; SMD = 0.98); greater volume of the right amygdala (SMD = 0.57), right hippocampus (SMD = 0.66), right putamen (SMD = 0.87) and right thalamus (SMD=.67). In the lithium group, a correlation was found with these errors and the thickness of the left precentral gyrus (ρ = -0.78), the volume of the right thalamus (ρ =-0.44), and the right amygdala (ρ = 0.6). CONCLUSIONS: The lithium group had better cognitive flexibility and greater dimension in some frontal and subcortical cortical regions. Furthermore, there was a moderate to high correlation between performance in this executive function and the thickness of the right precentral gyrus, and the volumes of the thalamus and the right amygdala. These findings could suggest a neuroprotective effect of lithium.

Rostral Middle Frontal Volumetric Differences in Bipolar Offspring versus Community Controls Offspring.

Neuroanatomical findings in the anterior limbic network in bipolar disorder (BD) adults have not been replicated in other populations such as bipolar offspring (BO). The aim of this study was to compare some brain areas volumes between BO with and without a lifetime affective disorder (AD) to a group of community control offspring (CCO). Methods: A descriptive observational cross-sectional study was carried out, with multiple comparison groups. Seven subjects (11-17 years old) from the BO with AD group were compared to seven subjects from the BO without AD group and seven subjects from the CCO group (match by age, gender and Tanner stage). Magnetic resonance imaging was performed with a Philips 3 Teslas device and volumetric segmentation was performed with the Freesurfer image analysis suite. Results: A larger size was found in the right middle frontal rostral region in the BO with AD group compared to the other two groups (p = 0.041). A higher volume was also found in BO with AD group in the left pars opercularis (Cohen d = 0.63) and in the right cingulate isthmus (d = 0.53) when compared with BO without AD group, and in the right hippocampus (d = 0.53) when compared to CCO group. A smaller volume was found in the BO without AD group versus CCO group in the left anterior caudate (d = 0.6). The BO groups (with and without AD) compared to CCO have a higher volume in the right frontal pole (d = 0.52). These volumetric differences can be attributed to the condition of BO with AD.

Los hallazgos neuroanatómicos en la red límbica anterior en el trastorno bipolar (TB) en adultos no se han replicado en otras poblaciones, como en los hijos de pacientes con trastorno bipolar (HPTB). El objetivo de este estudio fue comparar los volúmenes de áreas del cerebro entre HPTB, con y sin algún trastorno afectivo (TA) a lo largo de la vida, con un grupo de hijos de padres control de la comunidad (HPC). Métodos: Se realizó un estudio observacional, descriptivo y transversal, con múltiples grupos de comparación. Siete sujetos (11-17 años) del grupo HPTB con TA se compararon con siete sujetos del grupo HPTB sin TA y siete sujetos del grupo HPC (pareados por edad, sexo y estadio Tanner). La resonancia magnética nuclear se realizó con un resonador Philips 3 Teslas y la segmentación volumétrica se realizó con el conjunto de análisis de imagen Freesurfer. Resultados: Se encontró un tamaño mayor en la región frontal rostral medial derecha en el grupo HPTB con TA en comparación con los otros dos grupos (p = 0.041). También se encontró un mayor volumen en el grupo HPTB con TA en el opérculo frontal izquierdo (Cohen d = 0, 63) y en el istmo del giro del cíngulo derecho (d = 0, 53) cuando se comparó con el grupo sin TA, y en el hipocampo derecho (d = 0, 53) en comparación con el grupo HPC. Se encontró un volumen más pequeño en el grupo HPTB sin TA versus grupo HPC en el caudado anterior izquierdo (d = 0, 6). Los grupos HPTB (con y sin TA) en comparación con HPC tienen un volumen mayor en el polo frontal derecho (d = 0.52). Estas diferencias volumétricas pueden atribuirse a la condición de HPTB con TA.

Imaging Social and Environmental Factors as Modulators of Brain Dysfunction: Time to Focus on Developing Non-Western Societies.

Social and environmental factors are known risk factors and modulators of mental health disorders. We here conducted a nonsystematic review of the neuroimaging literature studying the effects of poverty, urbanicity, and community violence, highlighting the opportunities of studying non-Western developing societies such as those in Latin America. Social and environmental factors in these communities are widespread and have a large magnitude, as well as an unequal distribution, providing a good opportunity for their characterization. Studying the effect of poverty in these settings could help to explore the brain effect of economic improvements, disentangle the effect of absolute and relative poverty, and characterize the modulating impact of poverty on the underlying biology of mental health disorders. Exploring urbanicity effects in highly unequal cities could help identify the specific factors that modulate this effect as well as examine a possible dose-response effect by studying megacities. Studying brain changes in those living among violence, which is particularly high in places such as Latin America, could help to characterize the interplay between brain predisposition and exposure to violence. Furthermore, exploring the brain in an adverse environment should shed light on the mechanisms underlying resilience. We finally provide examples of two methodological approaches that could contribute to this field, namely a big cohort study in the developing world and a consortium-based meta-analytic approach, and argue about the potential translational value of this research on the development of effective social policies and successful personalized medicine in disadvantaged societies.

Estimulación cerebral profunda del globo pálido interno en el síndrome de distonía mioclónica: serie de 3 casos y revisión de la literatura / Deep brain stimulation of the internal globus pallidus in myoclonus-dystonia syndrome: a case series and review of the literature

RESUMEN INTRODUCCIÓN: La distonía mioclónica es un trastorno del movimiento con poca prevalencia, pero muy discapacitante, en el cual es frecuente la refractariedad al tratamiento médico. Cómo opción terapéutica se ha planteado la estimulación cerebral profunda, buscando con ello mejorar la función motora, la discapacidad y la calidad de vida de estos pacientes. MATERIALES Y MÉTODOS: Se presentan 3 pacientes con diagnóstico clínico de distonía mioclónica sin confirmación genética, que fueron llevados a estimulación cerebral profunda bilateral del globo pálido interno. RESULTADOS: Se evidenció una mejoría significativa en la evaluación de la escala unificada de mioclonías (80-90 %) y en la escala de distonía de Burke-Fahn-Marsden (tanto en movilidad como en discapacidad). La mejoría clínica se evidenció en los tres pacientes, en periodos de seguimiento que estuvieron entre los 6 meses y los 5 años luego de la estimulación cerebral profunda. DISCUSIÓN Y CONCLUSIONES: Los hallazgos en esta serie de 3 pacientes colombianos son consistentes con lo reportado en la literatura. Sin embargo, aportan información sobre el desenlace de pacientes sin genotipificación sometidos a estimulación cerebral profunda, dado que la eficacia de la intervención en pacientes con distonía sin confirmación genética aún no ha sido determinada, y depende de otros factores como la edad, el tiempo de evolución y el tipo de distonía.

ABSTRACT INTRODUCTION: Myoclonic dystonia is a movement disorder with low prevalence, but very disabling, where refractoriness to medical treatment is frequent. Deep brain stimulation has been proposed as a therapeutic option, seeking to improve motor function, disability and quality of life in these patients. MATERIALS AND METHODS: We present 3 patients with a clinical diagnosis of Myoclonic-Dystonia without genetic confirmation, who underwent bilateral deep brain stimulation of the Globus Pallidus Internus. RESULTS: A significant improvement was evidenced in the evaluation of the unified myoclonus scale (80-90 %) and in the Burke-Fahn-Marsden dystonia scale (both in mobility and in disability). The clinical improvement was evidenced in the 3 patients, in follow-up periods that were between 6 months and 5 years after deep brain stimulation. DISCUSSION AND CONCLUSIONS: Findings in this Colombian case series are consistent with that reported in the literature. However, the current description provides information on the outcome of patients without genotyping undergoing deep brain stimulation, considering that the efficacy of the intervention in these types of patients without genetic confirmation has not been determined and depends on other factors.

Correlación entre el desempeño cognitivo y la neuroanatomía estructural en pacientes con trastorno afectivo bipolar tipo I tratados con y sin litio / Correlation Between Cognitive Performance and Structural Neuroanatomy in Patients with Type I Bipolar Affective Disorder Treated with and Without Lithium

RESUMEN Introducción: El tratamiento del trastorno afectivo bipolar (TAB) con litio se ha relacionado con menos deterioro cognitivo y menores cambios en la anatomía estructural cerebral comparado con otros tratamientos. Sin embargo, los estudios son heterogéneos y son pocos los que evalúan si estos efectos están relacionados. El objetivo de este estudio es evaluar y relacionar el desempeno cognitivo y la neuroanatomía estructural en pacientes tratados con y sin litio. Métodos: Estudio de corte trasversal que incluyó a 48 sujetos con TAB I: 22 tratados con litio y 26 sin litio. Se evaluó el desempeno en las pruebas neuropsicológicas Wechsler III (WAIS III), TMTAyB (Trial Making Test), prueba de aprendizaje verbal de California (TAVEC), prueba de Figura compleja de Rey y prueba de clasificación de tarjetas de Wisconsin. Se evaluaron estructuras cerebrales obtenidas por resonancia magnétiva (RM) cerebral. Se calculó la diferencia de medias estandarizada (DME) entre ambos grupos, con ajuste por variables de confusión mediante puntuación de propensión, y se empleó el coeficiente de correlación de Spearman (p) para evaluar la relación existente entre el desempeno cognitivo y las regiones neuroanatómicas. Resultados: Respecto al grupo sin litio, el grupo con litio tuvo menos errores perseverativos en el Wisconsin (DME = -0,69) y mayores áreas corticales derecha e izquierda (DME = 0,85 y DME = 0,92); mayor superficie en el cíngulo anterior izquierdo (DME = 1,32), la corteza orbi-tofrontal medial derecha (DME = 1,17), el giro frontal superior derecho (DME = 0,82), los giros precentrales derecho e izquierdo (DME = 1,33 y DME = 0,98); mayor volumen de la amígdala derecha (DME = 0,57), el hipocampo derecho (DME = 0,66), el putamen derecho (DME = 0,87) y el tálamo derecho (DME = 0,67). En el grupo con litio, se encontró una correlación con dichos errores y el espesor del giro precentral izquierdo (p = -0,78), el volumen del tálamo derecho (p = -0,44) y la amígdala derecha (p = 0,6). Conclusiones: El grupo con litio tuvo mejor flexibilidad cognitiva y mayor dimensión en algunas regiones corticales frontales y subcorticales. Además, hubo correlación moderada a alta entre el desempeno en esta función ejecutiva y el espesor del giro precentral derecho, y los volúmenes del tálamo y la amígdala derecha. Estos hallazgos podrían indicar un efecto neuroprotector del litio

ABSTRACT Introduction: Lithium treatment of bipolar disorder (BD) has been associated with less impairment and fewer changes in structural brain anatomy compared to other treatments. However, the studies are heterogeneous and few assess whether these effects are related. The objective of this study was to evaluate and relate cognitive performance and structural neuroanatomy in patients treated with and without lithium. Methods: Cross-sectional study that included 48 subjects with BD-I, of which 22 were treated with lithium and 26 without lithium. Performance was assessed on Wechsler III (WAIS III), TMT A and B (Trial Making Test) neuropsychological tests, California verbal learning test (CVLT), Rey complex figure test and Wisconsin card sorting test. Brain structures obtained by magnetic resonance imaging (MRI) were evaluated. The standardised mean difference (SMD) between both groups was calculated, adjusted for confounding variables using a propen-sity score, and the Spearman correlation coefficient (p) was used to assess the relationship between cognitive performance and neuroanatomical regions. Results: Compared to the group without lithium, the group with lithium had fewer perse-verative errors in the Wisconsin test (SMD = -0.69) and greater left and right cortical areas (SMD = 0.85; SMD = 0.92); greater surface area in the left anterior cingulate (SMD = 1.32), right medial orbitofrontal cortex (SMD = 1.17), right superior frontal gyrus (SMD = 0.82), and right and left precentral gyrus (SMD = 1.33; SMD = 0.98); greater volume of the right amyg-dala (SMD = 0.57), right hippocampus (SMD = 0.66), right putamen (SMD = 0.87) and right thalamus (SMD=.67). In the lithium group, a correlation was found with these errors and the thickness of the left precentral gyrus (p = -0.78), the volume of the right thalamus (p =-0.44), and the right amygdala (p = 0.6). Conclusions: Thelithium group had better cognitive flexibility and greater dimension in some frontal and subcortical cortical regions. Furthermore, there was a moderate to high correlation between performance in this executive function and the thickness of the right precentral gyrus, and the volumes of the thalamus and the right amygdala. These findings could suggest a neuroprotective effect of lithium.

An improved HPLC-DAD method for clavulanic acid quantification in fermentation broths of Streptomyces clavuligerus.

Clavulanic acid (CA) is an important secondary metabolite commercially produced by cultivation of Streptomyces clavuligerus (Sc). It is a potent inhibitor of bacterial ß-lactamases. In this work, a specific and improved high performance liquid chromatography (HPLC) method, using a C-18 reversed phase column, diode array detector and gradient elution for CA quantification in fermentation broths of Sc, was developed and successfully validated. Samples were imidazole-derivatized for the purpose of creating a stable chromophore (clavulanate-imidazole). The calibration curve was linear over a typical range of CA concentration between 0.2 and 400mg/L. The detection and quantification limits were 0.01 and 0.02mg/L, respectively. The precision of the method was evaluated for CA spiked into production media and a recovery of 103.8%, on average, was obtained. The clavulanate-imidazole complex was not stable when the samples were not cooled during the analysis. The recovery rate was 39.3% on average. This assay was successfully tested for CA quantification in samples from Sc fermentation, using both, a chemically defined and a complex medium.

Pronóstico en pacientes con ataque cerebrovascular isquémico de circulación posterior / Functional outcome in posterior circulation acute ischemic stroke patients

RESUMEN INTRODUCCIÓN: El ochenta por ciento de los ataques cerebrovasculares son isquémicos, y uno de cada cinco afecta la circulación posterior. Su diagnóstico es difícil y los datos disponibles sobre el pronóstico y la mortalidad son discordantes. OBJETIVO: Evaluar el desenlace funcional a 180 días de los pacientes con ataque cerebrovascular (ACV) isquémico de circulación posterior (CP). MATERIALES Y MÉTODOS: Seguimiento prospectivo a pacientes con ACV de CP que ingresaron al Instituto Neurológico de Colombia entre septiembre del 2017 y septiembre del 2018. El desenlace clínico fue determinado mediante la escala Rankin modificada (mRS) al mes, a los seis meses y al año. RESULTADOS: Fueron incluidos 68 pacientes. La edad promedio fue 61 ±17 años y 60,3 % fueron hombres. El 85% tenía un mRS previo al ACV ≤ 1 y el 63 % un NIHSS basal ≤ 4. Nueve pacientes (13,2 %) recibieron terapia de reperfusión aguda (rtPA, TEV o ambas) y siete (10,3 %) adicionales arteriografía diferida. Dieciséis pacientes (23,5 %) presentaron una mejoría del NIHSS basal ≥ 4 puntos. Cuarenta y seis pacientes (74,2 %) presentaron un desenlace excelente mRS 0-1 a los seis meses y 87,1 % fueron categorizados mRS favorable (mRS 0-2). En el análisis ajustado, el NIHSS ≥ 4 fue un predictor de desenlace desfavorable a seis meses (RR 6,4; IC95 % 2,9-14,2). Seis pacientes (9,0 %) fallecieron, cuatro relacionados con el episodio actual o su recurencia. CONCLUSIONES: La mayoría de los pacientes con ACV de CP tienen desdenlaces favorables y una baja mor%talidad. La escala de NIHSS basal es un factor pronóstico independiente.

SUMMARY BACKGROUND: Ischemic strokes account for 80 % of all strokes, and one of every five compromises the posterior circulation. The diagnosis is difficult, and the data available about the outcome and mortality are discordant in the literature. OBJECTIVE: To investigate the clinicai outcome of patients at 180 days after posterior circulation ischemic stroke METHODS: Patients with diagnosis of posterior circulation stroke admitted to Instituto Neurológico de Colombia between September 2017 to 2018 were prospective included. The functional outcome by modified Rankin scale score (mRS) was determined at 1-month, 6-month, and 12-month after disease onset. RESULTS: 68 patients were included. The median age was 61 years ± 17 and 60.3 % were male. 85 % had a baseline mRS ≤ 1, and 63 % had a baseline National Institute Stroke Scale (NIHSS) ≤ 4. Nine patients were taken to acute recanalization therapies (rtPA, endovascular therapy or both) and seven more delayed arteriography. Sixteen patients (23.5 %) demonstrated an improvement of four or more points over the baseline NIHSS. Forty-six patients (74.2 %) had an excellent outcome 0-1 at six months and 87,1 % were categorized favorable mRS (mRS 0-2). In the adjusted analysis an NIHSS > 4 was a predictor of an unfavorable outcome at 6-month (RR 6.4; IC95 % 2.9-14.2). Six patients died (9 %); four of them in relation to the current event or an ischemic stroke recurrence. CONCLUSION: Most of the patients with posterior ischemic stroke have favorable outcomes and a low mortality. The baseline NIHSS is an independent prognostic risk factor.

Coping with matrix effects in headspace solid phase microextraction gas chromatography using multivariate calibration strategies.

SPME is extremely sensitive to experimental parameters affecting liquid-gas and gas-solid distribution coefficients. Our aims were to measure the weights of these factors and to design a multivariate strategy based on the addition of a pool of internal standards, to minimize matrix effects. Synthetic but real-like wines containing selected analytes and variable amounts of ethanol, non-volatile constituents and major volatile compounds were prepared following a factorial design. The ANOVA study revealed that even using a strong matrix dilution, matrix effects are important and additive with non-significant interaction effects and that it is the presence of major volatile constituents the most dominant factor. A single internal standard provided a robust calibration for 15 out of 47 analytes. Then, two different multivariate calibration strategies based on Partial Least Square Regression were run in order to build calibration functions based on 13 different internal standards able to cope with matrix effects. The first one is based in the calculation of Multivariate Internal Standards (MIS), linear combinations of the normalized signals of the 13 internal standards, which provide the expected area of a given unit of analyte present in each sample. The second strategy is a direct calibration relating concentration to the 13 relative areas measured in each sample for each analyte. Overall, 47 different compounds can be reliably quantified in a single fully automated method with overall uncertainties better than 15%.

Simultaneous determination of free and bonded forms of odor-active carbonyls in wine using a headspace solid phase microextraction strategy.

This paper presents a new strategy for the direct evaluation of odor-active carbonyls in the wine headspace and for the simultaneous estimation of their amounts in odorless bonded forms. In the final developed strategy, 25 mL of wine are spiked with internal and surrogate standards and let to equilibrate for at least 12 h in an oxygen-free chamber. Ten milliliter of the sample are then transferred to a standard headspace vial. Carbonyls in the headspace are preconcentrated on a PDMS/DVD fiber keeping the sample unstirred at 45°C for just 10 min and are further analyzed on a GC-MS equipped with a quadrupole in SIM mode. Normalized peak analyte areas interpolated in calibration plots built with synthetic wines give estimations of the concentrations of free forms, while the ratios of the areas of surrogates observed in wines to those observed in synthetic wine make it possible to get estimations of the proportion of each analyte present in bonded non-volatile form. The validity of this approach has been demonstrated both via standard recovery experiments and via the analysis of samples previously incubated with glyoxal in order to break aldehyde-bisulfite complexes. In general, method detection limits (below 1 µg L(-1)), precision (RSD (%)<10%) and accuracy are satisfactory for 12 studied carbonyls. Results demonstrate that wine contain relevant amounts of aldehydes (more than 95% in some cases) in the form of reversible odorless complexes, supporting a previous observation about the potential implication of these complexes on the development of oxidized aroma.

Automated and quantitative headspace in-tube extraction for the accurate determination of highly volatile compounds from wines and beers.

An automatic headspace in-tube extraction (ITEX) method for the accurate determination of acetaldehyde, ethyl acetate, diacetyl and other volatile compounds from wine and beer has been developed and validated. Method accuracy is based on the nearly quantitative transference of volatile compounds from the sample to the ITEX trap. For achieving that goal most methodological aspects and parameters have been carefully examined. The vial and sample sizes and the trapping materials were found to be critical due to the pernicious saturation effects of ethanol. Small 2 mL vials containing very small amounts of sample (20 µL of 1:10 diluted sample) and a trap filled with 22 mg of Bond Elut ENV resins could guarantee a complete trapping of sample vapors. The complete extraction requires 100 × 0.5 mL pumping strokes at 60 °C and takes 24 min. Analytes are further desorbed at 240 °C into the GC injector under a 1:5 split ratio. The proportion of analytes finally transferred to the trap ranged from 85 to 99%. The validation of the method showed satisfactory figures of merit. Determination coefficients were better than 0.995 in all cases and good repeatability was also obtained (better than 7% in all cases). Reproducibility was better than 8.3% except for acetaldehyde (13.1%). Detection limits were below the odor detection thresholds of these target compounds in wine and beer and well below the normal ranges of occurrence. Recoveries were not significantly different to 100%, except in the case of acetaldehyde. In such a case it could be determined that the method is not able to break some of the adducts that this compound forms with sulfites. However, such problem was avoided after incubating the sample with glyoxal. The method can constitute a general and reliable alternative for the analysis of very volatile compounds in other difficult matrixes.