Validation of ActiGraph and Fitbit in the assessment of energy expenditure in Huntington's disease.

BACKGROUND: Consumer and research activity monitors have become popular because of their ability to quantify energy expenditure (EE) in free-living conditions. However, the accuracy of activity trackers in determining EE in people with Huntington's Disease (HD) is unknown. RESEARCH QUESTION: Can the ActiGraph wGT3X-B or the Fitbit Charge 4 accurately measure energy expenditure during physical activity, in people with HD compared to Indirect Calorimetry (IC) (Medisoft Ergo Card)? METHODS: We conducted a cross-sectional, observational study with fourteen participants with mild-moderate HD (mean age 55.7 ± 11.4 years). All participants wore an ActiGraph and Fitbit during an incremental test, running on a treadmill at 3.2 km/h and 5.2 km/h for three minutes at each speed. We analysed and compared the accuracy of EE estimates obtained by Fitbit and ActiGraph against the EE estimates obtained by a metabolic cart, using with Intra-class correlation (ICC), Bland-Altman analysis and correlation tests. RESULTS: A significant correlation and a moderate reliability was found between ActiGraph and IC for the incremental test (r = 0.667)(ICC=0.633). There was a significant correlation between Fitbit and IC during the incremental test (r = 0.701), but the reliability was poor at all tested speeds in the treadmill walk. Fitbit significantly overestimated EE, and ActiGraph underestimated EE compared to IC, but ActiGraph estimates were more accurate than Fitbit in all tests. SIGNIFICANCE: Compared to IC, Fitbit Charge 4 and ActiGraph wGT3X-BT have reduced accuracy in estimating EE at slower walking speeds. These findings highlight the need for population-specific algorithms and validation of activity trackers.

Cómo estimar la composición corporal en la enfermedad de Huntington. Estudio transversal y observacional con bioimpedancia de múltiples frecuencias / How to estimate body composition in Huntington’s disease. A cross-sectional, observational study using multiple frequencies bioimpedance

Introducción La enfermedad de Huntington (EH) es un trastorno raro neurodegenerativo. La información fiable del estado nutricional, especialmente de la composición corporal, es crítica en clínica y en investigación. La facilidad de aplicación y portabilidad del análisis de la bioimpedancia de múltiples frecuencias (mfBIA) la convierten en una herramienta atractiva para medirla, pero se desconoce su precisión en la EH. Objetivo Evaluar la precisión del mfBIA frente a la absorciometría dual de rayos X (DEXA) en la EH. Pacientes y métodos Estudio transversal, observacional y unicéntrico. La EH se midió con la subescala motora de la escala unificada de valoración de la EH y con la capacidad funcional total. La composición corporal se valoró según la masa libre de grasa (MLG), la masa grasa (MG), el índice de masa libre de grasa (IMLG) y el índice de masa grasa (IMG). Se utilizó el coeficiente de correlación intraclase con intervalos de confianza al 95% y estimaciones de sesgo mediante gráficos de Bland-Altman. Resultados Se incluyó a 16 pacientes, siete hombres y nueve mujeres, con edad media de 58,5 (32-68) años, capacidad funcional total de 10 (3-13) y escala unificada de valoración de la EH de 31 (7-85). La fiabilidad era alta entre el mfBIA y la DEXA para el IMLG en hombres, 0,88 (intervalo de confianza al 95%: 0,17-0,98), y mujeres, 0,9 (intervalo de confianza al 95%: 0,61-0,98); y para el IMG en hombres, 0,97 (intervalo de confianza al 95%: 0,83-0,99), y mujeres, 0,91 (intervalo de confianza al 95%: 0,68-0,98). El mfBIA sobreestimó ligeramente la MLG, la MG, el IMG y el IMLG en los hombres, pero subestimó el IMLG en las mujeres. Conclusiones El mfBIA es un método fácil de usar, seguro, no invasivo y preciso para medir la composición corporal y el estado nutricional en pacientes con EH leve-moderada. (AU)

INTRODUCTION Huntington´s disease (HD) is a rare neurodegenerative disorder. Reliable information about nutritional status, especially body composition from individuals with HD is critical for clinical care and research. The ease of application and portability of multiple frequencies bioelectrical impedance analysis (mfBIA) make it an attractive tool for measuring body composition, but its accuracy in HD is unknown. AIM To evaluate the accuracy of mfBIA vs. Dual X-ray absorptiometry (DEXA) in HD. PATIENTS AND METHODS Cross-sectional, observational, and single-center study. HD severity was measured using motor subscale of the unified Huntington´s disease rating scale (m-UHDRS) and the total functional capacity (TFC). Body composition was measured in terms of fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), and fat mass index (FMI). Using Bland-Altman plots, we analyzed reliability between DEXA and mfBIA using the Intraclass Correlation Coefficient with 95% confidence intervals (CI) and bias estimates for all. RESULTS We included 16 patients with HD, 7 men, and 9 women, median age of 58.5 (32;68) years, TFC: 10 (3;13), and m-UHDRS: 31 (7;85). The reliability between mfBIA and DEXA were high for FFMI in men: 0.88 (95% CI 0.17-0.98), and women: 0.90 (95% CI 0.61- 0.98); for FMI, men: 0.97 (95% CI 0.83-0.99), and women: 0.91 (95% CI 0.68-0.98). Compared to DEXA, mfBIA slightly overestimated FFM, FM, FMI and FFMI in men and underestimated FFMI in women. CONCLUSIONS mfBIA is an easy-to-use, safe, non-invasive, accurate method for measuring body composition and nutritional status in patients with mild-moderate HD. (AU)

The unequal functional redundancy of Arabidopsis INCURVATA11 and CUPULIFORMIS2 is not dependent on genetic background.

The paralogous genes INCURVATA11 (ICU11) and CUPULIFORMIS2 (CP2) encode components of the epigenetic machinery in Arabidopsis and belong to the 2-oxoglutarate and Fe (II)-dependent dioxygenase superfamily. We previously inferred unequal functional redundancy between ICU11 and CP2 from a study of the synergistic phenotypes of the double mutant and sesquimutant combinations of icu11 and cp2 mutations, although they represented mixed genetic backgrounds. To avoid potential confounding effects arising from different genetic backgrounds, we generated the icu11-5 and icu11-6 mutants via CRISPR/Cas genome editing in the Col-0 background and crossed them to cp2 mutants in Col-0. The resulting mutants exhibited a postembryonic-lethal phenotype reminiscent of strong embryonic flower (emf) mutants. Double mutants involving icu11-5 and mutations affecting epigenetic machinery components displayed synergistic phenotypes, whereas cp2-3 did not besides icu11-5. Our results confirmed the unequal functional redundancy between ICU11 and CP2 and demonstrated that it is not allele or genetic background specific. An increase in sucrose content in the culture medium partially rescued the post-germinative lethality of icu11 cp2 double mutants and sesquimutants, facilitating the study of their morphological phenotypes throughout their life cycle, which include floral organ homeotic transformations. We thus established that the ICU11-CP2 module is required for proper flower organ identity.

Humans inherit artificial intelligence biases.

Artificial intelligence recommendations are sometimes erroneous and biased. In our research, we hypothesized that people who perform a (simulated) medical diagnostic task assisted by a biased AI system will reproduce the model's bias in their own decisions, even when they move to a context without AI support. In three experiments, participants completed a medical-themed classification task with or without the help of a biased AI system. The biased recommendations by the AI influenced participants' decisions. Moreover, when those participants, assisted by the AI, moved on to perform the task without assistance, they made the same errors as the AI had made during the previous phase. Thus, participants' responses mimicked AI bias even when the AI was no longer making suggestions. These results provide evidence of human inheritance of AI bias.

How can I assess my patients with Parkinson's disease during a busy clinic day?

BACKGROUND: The evaluation of motor impairment in Parkinson's disease (PD) is mainly assessed with the motor subdomain of the Unified Parkinson's Disease Rating scale (UPDRS part III) and, lately, with the MDS-UPDRS part III. To optimize efforts and special needs during specific circumstances in clinical practice, we sought to identify the most sensitive items to assess motor impairment in PD. METHODS: We included the COPPADIS-PD cohort and collected the UPDRS part III at baseline (V0), 12 months (V1), and 24 months (V2). Factor analysis and effect size using Cohen's d formula were performed in the Off and On states at V0, V1, and V2. RESULTS: We included 667 patients with PD, mean age of 62.59 ± 8.91 years, 410 (60.2%) males, with a median HY stage of 2.00 (1.00; 4.00) at baseline. Over time, the most discriminating items were postural stability and body bradykinesia ("arise from chair" and "gait") in the Off state, right and left upper extremity bradykinesia ("finger tap", "hand movements" and "prono/supination") in the On state. Body bradykinesia and right-left finger tapping were the items with the largest effect size (0.93, 0.84, 0.83, respectively) to assess motor improvement after receiving antiparkinsonian medications over time. CONCLUSION: Under specific circumstances, selecting a few items of the UPDRS part III, including postural stability, body bradykinesia, and upper extremity bradykinesia, could be used to create a quick clinical judgment of motor status and improvement in PD.

Clinical and Epidemiological Profiles of Primary Healthcare Professionals with COVID-19 Infection and Long COVID: An Observational Study.

Health professionals have been one of the groups most affected by the SARS-CoV-2 virus. Currently, there is little scientific evidence on the similarities and differences between COVID-19 infection and the development of long COVID in primary care (PC) workers. Therefore, it is necessary to analyse their clinical and epidemiological profiles in depth. This study was observational and descriptive, including PC professionals who were divided into three comparison groups based on the diagnostic test for acute SARS-CoV-2 infection. The responses were analysed using descriptive and bivariate analysis to examinate the relationship between independent variables and the presence or not of long COVID. Binary logistic regression analysis was also conducted, with each symptom as the dependent variable and each group as the independent variable. The results describe the sociodemographic characteristics of these population groups, revealing that women in the health sector are the most affected by long COVID and that being in this group is associated with its development. Furthermore, individuals with long COVID exhibited the highest number of symptoms and pathologies. Certain symptoms were found to be associated with long COVID development in this population, including an altered sense of smell, pneumonia, fever, and sore throat, among others. Similarly, altered senses of smell and taste, chest tightness, and joint pain, among others, were found to be associated with acute COVID-19 infection. Additionally, patients with pre-existing overweight or obesity were more likely to experience acute COVID-19 and develop long COVID. The data obtained can be crucial for improving the detection, diagnosis, and treatment of long COVID patients, ultimately leading to an enhancement in their quality of life.

Pharmacogenetics in the Treatment of Huntington's Disease: Review and Future Perspectives.

Huntington's disease (HD) is an autosomal dominant progressive brain disorder, caused by a pathological expansion of a CAG repeat that encodes the huntingtin gene. This genetic neurodegenerative rare disease is characterized by cognitive, motor, and neuropsychiatric manifestations. The aim of the treatment is symptomatic and addresses the hyperkinetic disorders (chorea, dystonia, myoclonus, tics, etc.) and the behavioural and cognitive disturbances (depression, anxiety, psychosis, etc.) associated with the disease. HD is still a complex condition in need of innovative and efficient treatment. The long-term goal of pharmacogenetic studies is to use genotype data to predict the effective treatment response to a specific drug and, in turn, prevent potential undesirable effects of its administration. Chorea, depression, and psychotic symptoms have a substantial impact on HD patients' quality of life and could be better controlled with the help of pharmacogenetic knowledge. We aimed to carry out a review of the available publications and evidence related to the pharmacogenetics of HD, with the objective of compiling all information that may be useful in optimizing drug administration. The impact of pharmacogenetic information on the response to antidepressants and antipsychotics is well documented in psychiatric patients, but this approach has not been investigated in HD patients. Future research should address several issues to ensure that pharmacogenetic clinical use is appropriately supported, feasible, and applicable.

Related Factors with Depression and Anxiety in Mastectomized Women Breast Cancer Survivors.

Breast cancer (BC) is the most common cancer diagnosis with the highest mortality rate worldwide. The aim of this study was to identify factors related to depression and anxiety in mastectomized women BC survivors. A cross-sectional study was conducted with a sample of 198 women diagnosed with BC aged 30-80 years in Mexico. Depression and anxiety were assessed using the 14-item Hospital Anxiety and Depression Scale (HADS). The results showed that 94.44% and 69.18% of the women scored more than eight points on HADS in the anxiety and depression subscales, respectively; 70.20% and 10.60% were identified as pathological. The following variables were analyzed: age, time elapsed since the start of treatment, received treatment at the time of the evaluation, type of surgery, family history, marital status and employment status. Time elapsed since surgery, having a partner, and employment showed significant results as factors associated to levels of depression and anxiety in these patients. In conclusion, it has been shown that BCSs under 50 years of age receiving some kind of treatment, without family history, without a partner, with a job, with more than secondary education and with more than 5 years since diagnosis could have higher rates of clinical depression. On the other hand, BCSs older than 50 years receiving some kind of treatment, without family history, without a partner, with a job, with more than secondary education and with more than 5 years since diagnosis, could have higher rates of clinical anxiety. In conclusion, the variables studied provide valuable information for the implementation of psychotherapy plans in healthcare systems to reduce the risk of depression and/or anxiety in women with BC who have undergone mastectomy.

Long COVID Symptomatology and Associated Factors in Primary Care Patients: The EPICOVID-AP21 Study.

Persistent COVID-19 condition includes a wide variety of symptoms and health problems of indeterminate duration. The present study examined the sociodemographic and clinical characteristics of the population with Long COVID seen in Primary Care using a questionnaire based on the existing scientific literature. It was an observational and descriptive study of the characteristics of the Spanish population with Long COVID over 14 years of age. The responses were analysed by means of a descriptive analysis of the variables recorded, in addition to a bivariate analysis to determine the existence of a relationship between persistent COVID-19 and variables such as gender, age, vaccination status or concomitant pathology. The results obtained clearly describe the sociodemographic characteristics of the population, highlighting the predominance of female gender and the prevalence of tiredness and fatigue. Furthermore, relevant information was obtained on the differences in symptomatology according to gender, age, previous pathologies and alterations derived from infection and/or vaccination. These data are important for better detection, diagnosis and treatment of Long COVID and the improvement of the quality of life of this population.

Environmental enrichment alleviates cognitive and psychomotor alterations and increases adult hippocampal neurogenesis in cocaine withdrawn mice.

Cocaine is a widely used psychostimulant drug whose repeated exposure induces persistent cognitive/emotional dysregulation, which could be a predictor of relapse in users. However, there is scarce evidence on effective treatments to alleviate these symptoms. Environmental enrichment (EE) has been shown to be associated with improved synaptic function and cellular plasticity changes related to adult hippocampal neurogenesis (AHN), resulting in cognitive enhancement. Therefore, EE could mitigate the negative impact of chronic administration of cocaine in mice and reduce the emotional and cognitive symptoms present during cocaine abstinence. In this study, mice were chronically administered with cocaine for 14 days, and control mice received saline. After the last cocaine or saline dose, mice were submitted to control or EE housing conditions, and they stayed undisturbed for 28 days. Subsequently, mice were evaluated with a battery of behavioural tests for exploratory activity, emotional behaviour, and cognitive performance. EE attenuated hyperlocomotion, induced anxiolytic-like behaviour and alleviated cognitive impairment in spatial memory in the cocaine-abstinent mice. The EE protocol notably upregulated AHN in both control and cocaine-treated mice, though cocaine slightly reduced the number of immature neurons. Altogether, these results demonstrate that EE could enhance hippocampal neuroplasticity ameliorating the behavioural and cognitive consequences of repeated administration of cocaine. Therefore, environmental stimulation may be a useful strategy in the treatment cocaine addiction.

Temozolomide treatment inhibits spontaneous motivation for exploring a complex object in mice: A potential role of adult hippocampal neurogenesis in "curiosity".

Intrinsic exploratory biases are an innate motivation for exploring certain types of stimuli or environments over others, and they may be associated with cognitive, emotional, and even personality-like traits. However, their neurobiological basis has been scarcely investigated. Considering the involvement of the hippocampus in novelty recognition and in spatial and pattern separation tasks, this work researched the role of adult hippocampal neurogenesis (AHN) in intrinsic exploratory bias for a perceptually complex object in mice. Spontaneous object preference tasks revealed that both male and female C57BL/6J mice showed a consistent unconditioned preference for exploring "complex"-irregular-objects over simpler ones. Furthermore, increasing objects' complexity resulted in an augmented time of object exploration. In a different experiment, male mice received either vehicle or the DNA alkylating agent temozolomide (TMZ) for 4 weeks, a pharmacological treatment that reduced AHN as evidenced by immunohistochemistry. After assessment in a behavioral test battery, the TMZ-treated mice did not show any alterations in general exploratory and anxiety-like responses. However, when tested in the spontaneous object preference task, the TMZ-treated mice did not display enhanced exploration of the complex object, as evidenced both by a reduced exploration time-specifically for the complex object-and a lack of preference for the complex object over the simple one. This study supports a novel role of AHN in intrinsic exploratory bias for perceptual complexity. Moreover, the spontaneous complex object preference task as a rodent model of "curiosity" is discussed.

Quality of Life in Breast Cancer Survivors in Relation to Age, Type of Surgery and Length of Time since First Treatment.

(1) Background: Quality of life assessment is a critical aspect of breast cancer patient outcomes, as diagnosis, prognosis and treatment can have a major impact on quality of life. The aim of this study was to describe the characteristics of the sample and to verify the relationship between quality of life (QOL) in women diagnosed with breast cancer (BC) and their age, type or surgery and time since treatment; (2) Methods: a cross-sectional, descriptive study was conducted with 183 women diagnosed with BC, aged 30−80 years in Mexico. Women's QOL was assessed using two questionnaires, The European Organization for Research and Treatment of Cancer-Quality of Life Core Questionnaire (EORTC QLQ-C30) and The Breast Cancer Module (EORTC QLQ-BR23). (3) Results: the results show significant differences in several items when the variable age is taken into account, indicating that younger women have poorer social and sexual function, as well as poorer sexual enjoyment and lower expectations of the future. The type of surgery also indicates a significantly better QOL in those women who receive conservative treatment versus a mastectomy; the time elapsed since surgery does not show any significant results, except for sexual functioning and breast-related symptoms where >5 years implies better scores on the items. (4) Conclusions: in conclusion, it is important to take into account the characteristics of women with BC, particularly at the time of treatment, in order to mitigate the impact of the disease on their QOL with the help of a multidisciplinary team.

Accelerometer Cut-Points for Physical Activity Assessment in Adults with Mild to Moderate Huntington's Disease: A Cross-Sectional Multicentre Study.

Accelerometers can estimate the intensity, frequency, and duration of physical activity in healthy adults. Although thresholds to distinguish varying levels of activity intensity using the Actigraph wGT3X-B have been established for the general population, their accuracy for Huntington's disease (HD) is unknown. We aimed to define and cross-validate accelerometer cut-points for different walking speeds in adults with mild to moderate HD. A cross-sectional, multicentre, case-control, observational study was conducted with a convenience sample of 13 symptomatic ambulatory HD participants. The accelerometer was placed around the right hip, and a heart monitor was fitted around the chest to monitor heart rate variability. Participants walked on a treadmill at three speeds with light, moderate and vigorous intensities. Correlation and receiver operation curve analyses were performed between the accelerometer magnitude vector with relative oxygen and heart rate. Optimal cut-points for walking speeds of 3.2 km/h were ≤2852; 5.2 km/h: >2852 to ≤4117, and in increments until their maximum velocity: >4117. Our results support the application of the disease-specific cut-points for quantifying physical activity in patients with mild to moderate HD and promoting healthy lifestyle interventions.

Context Properties Modulate Flavor Neophobia Habituation.

BACKGROUND: One issue that has received relatively little attention in the analyses of the neophobic responses to a novel flavor is the influence of the context in which the flavor is first encountered, along with the effect of this context on the habituation of neophobia when the flavor is repeatedly consumed. Considering the predictions of the Contextual Safety Hypothesis, which proposes that the previous appetitive or aversive history of the context will modulate the intensity of neophobia and its habituation, we designed an experiment to evaluate the role played by the context in neophobia and its habituation to a new flavor. METHOD: Male Wistar rats had access to a new flavor solution (0.1% sacharin) in presence of a context previously submitted to a treatment intended to turn it into appetitive, aversive or merely familiar. An additional group of rats received the new flavor in their home cages. RESULTS: After four days of saccharin exposure, those animals in the Appetitive and Home conditions showed significant faster neophobia habituation as compared to those in the Aversive and Familiar groups. CONCLUSIONS: These results revealed the potential applied value of using contextual manipulations to promote healthy eating behavior both in animals and humans.

Context Properties Modulate Flavor Neophobia Habituation / Las Propiedades del Contexto Modulan la Habituación de la Neofobia Gustativa

Background: One issue that has received relatively little attention in the analyses of the neophobic responses to a novel flavor is the influence of the context in which the flavor is first encountered, along with the effect of this context on the habituation of neophobia when the flavor is repeatedly consumed. Considering the predictions of the Contextual Safety Hypothesis, which proposes that the previous appetitive or aversive history of the context will modulate the intensity of neophobia and its habituation, we designed an experiment to evaluate the role played by the context in neophobia and its habituation to a new flavor. Method: Male Wistar rats had access to a new flavor solution (0.1% sacharin) in presence of a context previously submitted to a treatment intended to turn it into appetitive, aversive or merely familiar. An additional group of rats received the new flavor in their home cages. Results: After four days of saccharin exposure, those animals in the Appetitive and Home conditions showed significant faster neophobia habituation as compared to those in the Aversive and Familiar groups. Conclusions: These results revealed the potential applied value of using contextual manipulations to promote healthy eating behavior both in animals and humans. (AU)

Antecedentes: la influencia del contexto en presencia del que aparece un sabor nuevo sobre la neofobia gustativa y su habituación es un aspecto que ha recibido relativamente poca atención en la investigación. En este artículo describimos un experimento diseñado para evaluar el papel que juega el contexto sobre la neofobia y su habituación partiendo de las predicciones de la Hipótesis de Seguridad Contextual, que propone que la historia previa apetitiva o aversiva del contexto modulará la intensidad de la neofobia y su habituación. Método: se expuso una muestra de ratas Wistar macho a una disolución de un sabor nuevo (sacarina al 0,1%) en presencia de un contexto previamente sometido a un tratamiento diseñado para convertirlo en apetitivo, aversivo o meramente familiar. Un grupo adicional de ratas recibió el nuevo sabor en sus jaulas hogar. Resultados: después de cuatro días de exposición a la sacarina, los animales en las condiciones Apetitivo y Hogar mostraron una habituación a la neofobia significativamente más rápida que los de los grupos Aversivo y Familiar. Conclusiones: estos resultados revelan el potencial valor aplicado del uso de manipulaciones contextuales para promover conductas alimentarias saludables tanto en animales como en humanos. (AU)

[Bartonella endocarditis associated with glomerulonephritis and neuroretinitis]. / Endocarditis por Bartonella asociada a glomerulonefritis y neurorretinitis.

Blood-culture negative endocarditis is a diagnostic challenge. Both Bartonella and Coxiella can cause it with similar clinical presentations mimicking a systemic vasculitis. The identification of the etiologic agent is essential because they differ in treatment type and duration. We present a case of blood-culture negative endocarditis caused by Bartonella henselae, associated with glomerulonephritis and neuroretinitis, with negative blood culture, positive anti-neutrophil cytoplasmic and antiproteinase 3 antibodies. The serology was positive for Bartonella with crossreactivity to Coxiella burnetti. The etiological diagnosis was achieved by polymerase chain reaction amplification and sequencing of a ribC gene fragment. The patient received antibiotic and immunosuppressive treatment followed by replacement of the aortic valve with favorable medium-term evolution.

La endocarditis bacteriana con hemocultivo negativo constituye un dilema diagnóstico. Tanto Bartonella como Coxiella pueden causarla, con presentaciones clínicas similares que pueden simular una vasculitis sistémica no infecciosa. Sin embargo, difieren en el tipo y la duración del tratamiento, por lo que es fundamental identificar el agente etiológico. Presentamos un caso de endocarditis por Bartonella henselae asociada a glomerulonefritis y neurorretinitis, con hemocultivo negativo, anticuerpos anticitoplasma de neutrófilos y antiproteinasa 3 positivos, y serología positiva para Bartonella con reacción cruzada para Coxiella burnetti. El diagnóstico etiológico fue confirmado a posteriori mediante amplificación y secuenciación parcial del gen ribC a partir de tejido de la válvula cardíaca. El paciente recibió tratamiento antibiótico e inmunosupresor seguido de recambio valvular aórtico y presentó evolución favorable.

Endocarditis por bartonella asociada a glomerulonefritis y neurorretinitis / Bartonella endocarditis associated with glomerulonephritis and neuroretinitis

La endocarditis bacteriana con hemocultivo negativo constituye un dilema diagnóstico. Tanto Bartonella como Coxiella pueden causarla, con presentaciones clínicas similares que pueden simular una vasculitis sistémica no infecciosa. Sin embargo, difieren en el tipo y la duración del tratamiento, por lo que es fundamental identificar el agente etiológico. Presentamos un caso de endocarditis por Bartonella henselae asociada a glomerulonefritis y neurorretinitis, con hemocultivo negativo, anticuerpos anticitoplasma de neutrófilos y antiproteinasa 3 positivos, y serología positiva para Bartonella con reacción cruzada para Coxiella burnetti. El diagnóstico etiológico fue confirmado a posteriori mediante amplificación y secuenciación parcial del gen ribC a partir de tejido de la válvula cardíaca. El paciente recibió tratamiento antibiótico e inmunosupresor seguido de recambio valvular aórtico y presentó evolución favorable.

Blood-culture negative endocarditis is a diagnostic challenge. Both Bartonella and Coxiella can cause it with similar clinical presentations mimicking a systemic vasculitis. The identification of the etiologic agent is essential because they differ in treatment type and duration. We present a case of blood-culture negative endocarditis caused by Bartonella henselae, associated with glomerulonephritis and neuroretinitis, with negative blood culture, positive anti-neutrophil cytoplasmic and antiproteinase 3 antibodies. The serology was positive for Bartonella with cross-reactivity to Coxiella burnetti. The etiological diagnosis was achieved by polymerase chain reaction amplification and sequencing of a ribC gene fragment. The patient received antibiotic and immunosuppressive treatment followed by replacement of the aortic valve with favorable medium-term evolution.

Conditioned increase of locomotor activity induced by haloperidol.

Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol can act as an unconditioned stimulus, we carried out two experiments in which the administration of haloperidol was repeatedly paired with the presence of distinctive contextual cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a dose-dependent increase in locomotor activity following conditioning with dopamine antagonist (Experiments 1) that was susceptible of extinction when the conditioned stimulus was presented repeatedly by itself after conditioning (Experiment 2). These data are interpreted from an associative perspective, considering them as a result of a classical conditioning process.

INCURVATA11 and CUPULIFORMIS2 Are Redundant Genes That Encode Epigenetic Machinery Components in Arabidopsis.

All critical developmental and physiological events in a plant's life cycle depend on the proper activation and repression of specific gene sets, and this often involves epigenetic mechanisms. Some Arabidopsis thaliana mutants with disorders of the epigenetic machinery exhibit pleiotropic defects, including incurved leaves and early flowering, due to the ectopic and heterochronic derepression of developmental regulators. Here, we studied one such mutant class, the incurvata11 (icu11) loss-of-function mutants. We have identified ICU11 as the founding member of a small gene family that we have named CUPULIFORMIS (CP). This family is part of the 2-oxoglutarate/Fe(II)-dependent dioxygenase superfamily. ICU11 and its closest paralog, CP2, have unequally redundant functions: although cp2 mutants are phenotypically wild type, icu11 cp2 double mutants skip vegetative development and flower upon germination. This phenotype is reminiscent of loss-of-function mutants of the Polycomb-group genes EMBRYONIC FLOWER1 (EMF1) and EMF2 Double mutants harboring icu11 alleles and loss-of-function alleles of genes encoding components of the epigenetic machinery exhibit synergistic, severe phenotypes, and some are similar to those of emf mutants. Hundreds of genes are misexpressed in icu11 plants, including SEPALLATA3 (SEP3), and derepression of SEP3 causes the leaf phenotype of icu11 ICU11 and CP2 are nucleoplasmic proteins that act as epigenetic repressors through an unknown mechanism involving histone modification, but not DNA methylation.