A study on correlations between precipitation ETCCDI and airborne pollen/fungal spore parameters in the NE Iberian Peninsula.

Precipitation is one of the meteorological variables usually involved in the aerobiological studies, which presents a complex relationship with atmospheric levels of pollen and fungal spores and the temporal characteristics of their seasons. This complexity is due in a large part to rainfall's twofold impact of having, prior to pollination, a positive influence on subsequent pollen production and of contributing, during pollination, to pollen removal from the air through a wash-out effect. To better explore this impact, we place particular emphasis on extreme rainfall by calculating the correlation between airborne pollen and fungal spore parameters and the precipitation indices that the Expert Team on Climate Change Detection and Indices (ETCCDI) proposed for characterising climate extremes. Parameters for twenty-seven pollen and fungal spore taxa measured in six aerobiological stations in the NE Iberian Peninsula have been considered. We have distinguished between annual and winter ETCCDI in order to compare the correlations between extreme rainfall and airborne pollen concentrations and to avoid the wash-out effect as far as possible. Results show a positive influence from an increase in moderately extreme winter rainfall, specifically on subsequent pollen/fungal spore production: the percentage of all possible significant correlations is higher for winter than for annual rainfall. Furthermore, while annual rainfall in this region has nearly the same number of positive as negative correlations, the positive correlations for winter rainfall are more than twice that of the negative ones. The seasonal consideration on rainfall ETCCDI made with the aim to avoid the confounding overlapping of different rainfall impacts has led to more sharpened observations of its positive and negative effects on airborne pollen and fungal spore concentrations.

Multifractal structure of the monthly rainfall regime in Catalonia (NE Spain): Evaluation of the non-linear structural complexity.

The complex non-linear regime of the monthly rainfall in Catalonia (NE Spain) is analyzed by means of the reconstruction fractal theorem and the multifractal detrended fluctuation analysis algorithm. Areas with a notable degree of complex physical mechanisms are detected by using the concepts of persistence (Hurst exponent), complexity (embedding dimension), predictive uncertainty (Lyapunov exponents), loss of memory of the mechanism (Kolmogorov exponent), and the set of multifractal parameters (Hölder exponents, spectral asymmetry, spectral width, and complexity index). Besides these analyses permitting a detailed description of monthly rainfall pattern characteristics, the obtained results should also be relevant for new research studies concerning monthly amounts forecasting at a monthly scale. On one hand, the number of necessary monthly data for autoregressive processes could change with the complexity of the multifractal structure of the monthly rainfall regime. On the other hand, the discrepancies between real monthly amounts and those generated by some autoregressive algorithms could be related to some parameters of the reconstruction fractal theorem, such as the Lyapunov and Kolmogorov exponents.

[One homeless person out of ten suffers from cognitive disorders: What do we know about these impairments? A systematic review of homeless people's cognition]. / Une personne SDF sur 10 souffre de troubles cognitifs : que sait-on de ces troubles ? Une revue de littérature sur la cognition des personnes SDF.

OBJECTIVES: Homelessness is associated with several issues (psychiatric and neurological disorders, neurodevelopmental difficulties, malnutrition…) which are also risk factors for cognitive disorders. However, little is known about the relationship between the cognition of homeless people and these eventual explicative etiologies. The aim of this work is to complete the results of Depp et al. about cognition in homelessness by proposing a systematic review of the neuropsychological disorders of homeless people associated with an analysis of the etiologies likely to explain these disorders. METHODS: We followed the PRISMA recommendations to build up this work. We analyzed the abstracts of 385 papers found on databases PSYCINFO and PubMed. Twenty-two studies have been selected for respecting our criteria (at least one valid neuropsychological test ; general group of homeless people and not a sub-group of this population ; study published in English). The prevalence quality has been evaluated through the criteria of Loney et al. Cognitive scores and etiological factors have been compared between studies. RESULTS: The 22 studies represent only nine countries. More than half of them are considered as having a poor prevalence quality. In total, 4,256 participants have been evaluated. Their mean age was around 40 years, and 85 % of the participants were men. The results show a prevalence of cognitive disorders (MMSE) in 8.77 % of the sample. The mean IQ was 87.47 and the premorbid IQ 94.59. We also notice possible disorders affecting the episodic memory and the executive functions. Mean scores for short-term memory, speech and visuo-spatial functions are relatively low. None of the studies evaluated the praxia, the gnosia or the social cognition. The heterogeneity of studies and the lack of data did not allow us to give general conclusions about the etiology of these disorders. However, we see that around 40 % of the time subjects had histories of brain injuries and 89 % of childhood trauma. Intellectual disability is found in 49 % of the sample of a single study. Also, 70 % of the homeless population have been diagnosed with substance-related disorders and 65 % with psychiatric disorders. It appears that the only factors correlated with cognitive disorders would be the history of brain injuries and childhood traumas. CONCLUSIONS: We confirm that homeless people often suffer from cognitive difficulties, and some of these difficulties (memory, executive functioning) are severe. Yet the etiology of these disorders remain relatively unknown: even if we observe a high prevalence of psychiatric, substance-related, neurodevelopmental and neurological issues by the homeless population, only a few of them (brain injury history and childhood trauma) seem to be correlated with cognition in homelessness. The potential explicative factors have been too rarely explored to bring a powerful explanation of cognitive disorders in homeless people. Further research needs to be done in order to give a more precise neuropsychological profile of the homeless population and to better understand what the disorders are rooted in. Last but not least, all this research and knowledge should be applied more to the care of homeless people by providing neuropsychological assessment and rehabilitation and by training the team to detect cognitive disorders and to support the person with a cognitive disability.

Is the antidepressant effect of ketamine separate from its psychotomimetic effect? A review of rodent models.

Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.

A neuropsychological approach in a paediatric acquired brain injury unit under the public health system.

INTRODUCTION: Paediatric acquired brain injury (ABI) causes cognitive and behavioural difficulties and alters the course of child development. The ABI unit at Hospital Infantil Universitario Niño Jesús is the first within the public Spanish health system to provide comprehensive coverage to these patients and their families. OBJECTIVE: This study aims to show the working methodology followed with patients and their families, and to describe the clinical characteristics of the patients treated and the outcomes of treatment. PATIENTS: Fifty-three patients aged between 3 months and 16 and a half years received treatment. The conditions treated were brain tumours, stroke, traumatic brain injury, damage secondary to epilepsy surgery, and hypoxia. METHODS: All patients were evaluated at admission and at discharge. Treatments were adapted to each patient's difficulties and their severity, as well as to the patient's age. Families received individual and group therapy. RESULTS: Older age was associated with better cognitive recovery and shorter duration of treatment. Different conditions show differential impact on intelligence quotient and developmental quotient scores at the beginning of treatment, with hypoxia and encephalitis being associated with greatest severity. Intelligence quotient and developmental quotient scores and visual memory and attention scores at discharge improved significantly after the faceted neuropsychological treatment with respect to scores registered at admission. CONCLUSIONS: The care of patients with ABI should include neuropsychological rehabilitation programmes and provide emotional support to the family so that they may actively participate in the recovery of the child or adolescent.

Promoting psychological well-being in preschool children: study protocol for a randomized controlled trial of a mindfulness- and yoga-based socio-emotional learning intervention.

BACKGROUND: Mental health issues in youths have cascading negative effects on school outcomes, professional life, and physical health. Psychological well-being (P-WB) is an important protective factor against mental illness. Preliminary research suggests that mindfulness- and yoga-based socio-emotional learning (SEL) interventions can each have a positive impact on preschoolers P-WB. The objective of this trial is to rigorously evaluate the effect of a 24-week combined mindfulness- and yoga- based SEL intervention in preschool children from a French socio-economically disadvantaged area. METHODS: The P-WB promotion intervention is compared to a wait-list control condition in a cluster randomized controlled trial (RCT). Sixty-four pre-Kindergarten classrooms are randomized to the intervention or control group. Primary outcomes measure self-management capacity and core P-WB components: connection, insight, engagement, and positive relationship. Secondary outcomes include measures of mental health, executive functioning, and school performance. Primary and secondary outcomes are assessed through teacher questionnaires, standardized observations of children in school context, and experimental tasks and by collecting results of the national evaluation at first grade. All children-level outcomes are evaluated at pre-intervention, at the end of the intervention, and 1 year later (follow-up analysis), to the exception of school performance which is evaluated at follow-up only. Intention-to-treat analyses, accounting for clustering within classes, will adopt a random effects linear regression model to examine outcomes for the intervention versus control children. DISCUSSION: This is the first trial to rigorously evaluate a combined mindfulness- and yoga-based P-WB promotion intervention, and the first RCT evaluating a SEL curriculum in French schools. Results may have key implications for P-WB promotion in preschool children. TRIAL REGISTRATION: https://www.drks.de/ DRKS00028623. Retrospectively registered on 30 May 2022.

[Relapse in schizophrenia: an exploratory study of the joint conceptions of patients, parents and caregivers]. / Regards croisés sur les signes précoces de rechute des sujets schizophrènes.

INTRODUCTION: The question of the course of schizophrenia relapses, is of considerable interest in different clinical and social areas such as prognosis, quality of life, therapeutic relationship, psychoeducation, rehabilitation and so on. The more the schizophrenic relapses, the higher the level of handicap. Although there is a widespread agreement that it is essential to detect early signs of relapses in order to prevent them, there still remain theoretical and methodological difficulties in identifying these signs because they are personal, heterogeneous and not always specific to psychosis. That is why the notion of "relapse signature" seems relevant by taking into account differentiated and personal assessment of early signs of relapse. This implies the consideration of the different visions of relapse given by patients, parents and caregivers. OBJECTIVE: We propose a qualitative study of the joint appraisal of patients, patients' parents and medical staff. The aim of this study is to regroup the expertises in order to further our understanding of the early signs of relapse. We assume that patients and parents are able to describe signs that are not considered as pathological symptoms, but refer to a personal manner of initiating the relapse process. This should then help in designing early intervention and provide reinforced therapeutic alliance and more positive responses to psychoeducation programs. METHOD: We have interviewed 30 subjects divided in three groups: 10 schizophrenic patients, 10 caregivers (including physicians, psychologists and nurses) and 10 parents of schizophrenics. The patients met the following criteria: patients with a diagnosis of schizophrenia (DSM IV criteria), under neuroleptic treatment, and stabilized. The mean duration of illness was 15 years. The patients as well as caregivers were recruited in two external hospital structures. All the subjects gave their written consent for this study and its methods. We did not recruit parents who were not living with their schizophrenic child or who did not see or have frequent contact with him or her for this study. We conducted a semistructured interview and analysed the transcripts of the narratives provided by our three groups on the definition of relapse and early signs of relapse. Recorded interviews were processed using the Alceste Method, a computer program of textual analysis that identifies the word patterns most frequently used by the subjects. Alceste creates classes of words using a hierarchical descending classification. The description of each class is presented in the form of a word list (with the value of the word's Chi(2) association in this class). We assessed the awareness of problems using the 8-Q. RESULTS: The three groups described relapses as a distressed, even traumatic experience. This experience is shared by the patients' siblings who sometimes mention violent situations and difficulties at home. The analysis showed that each group uses a compartmentalized universe of speech. This raises the question of the communication and the sharing of information between the different groups. Parents who didn't live the relapse of their children and the caregivers gave prepsychotic or psychotic symptoms of relapse. Conversely, parents who had lived relapse(s) of their children gave nonspecific and very personalized signs of relapse (e.g., "When she relapses, our daughter eats much more cheese than usually"). The patients with a low level of awareness of his/her problem were able to describe early signs of relapse. They described mood and sleep disturbances. This is an unexpected result and calls for a debate on the need or not to have good insight in order to follow a psychoeducation program. CONCLUSION: This study insists on the complementarity of different conceptions of all persons involved in schizophrenic relapse in order to identify as accurately as possible the "relapse signature" of patients. According to us, and in order to promote suitable subjective data to increase insight, compliance and therapeutic alliance, psychoeducation programs should rely on these personal criteria rather than propose systematic programs. Then the relapse signature could be the first step to the appropriation of the course of illness and control of psychotic symptoms by schizophrenic patients.

Clinical impact of high-definition endoscopic ultrasonography (EUS) in a district hospital.

OBJECTIVES: Evaluation of the impact of EUS in clinical practice. METHODS: All exploration performed during the first 18 months of implementation of the technique were analyzed. Agreement was assessed by radiographic techniques or surgical specimens in those cases allowed. RESULTS: 277 exploration were performed. There have been only 2 complications and they were related to sedation in both cases. The demand increased gradually, reaching 70 scans per 100,000 inhabitants. Main indications were bile (34.3%) and pancreatic processes. No pathology was found in 10% of cases; 29 cases had choledocholithiasis (93% confirmed and treated endoscopically). Chronic pancreatitis was diagnosed in 19 cases (only 15.78% of the cases were diagnosed by computed tomography). 32 patients with idiopathic acute pancreatitis were evaluated: 20 of them had evidence of microlithiasis (80% cholecystectomized and asymptomatic after a mean follow-up of 21.5 months), two cases of choledocholithiasis, 1 with chronic pancreatitis and 9 cases remained free of filial etiology. We performed 56 punctures: 39 samples of pancreas in 33 patients (81.1% of the samples were diagnostic; adenocarcinoma and serous cystadenoma were the most common diagnoses), 13 enlarged nodes and 4 abdominal masses. CONCLUSIONS: EUS is a growing demand technique that has low risks and leads to better decision-making in a significant number of patients with different diseases. Therefore, its inclusion in routine clinical practice must be considered.

[Detection, isolation and characterization of Shiga toxin-producing Escherichia coli (STEC) in fresh ground beef from butcher shops in Concepción, Tucumán Province]. / Detección, aislamiento y caracterización de Escherichia coli productor de toxina Shiga a partir de carne molida fresca proveniente de carnicerías de Concepción, provincia de Tucumán.

Shiga toxin-producing Escherichia coli is an emerging foodborne pathogen. There are many STEC serotypes associated with human diseases, being the O157:H7 serotype the most prevalent. Ground beef is the main transmission vehicle. In Concepción city, Tucumán Province, between September and December 2004, two hemolytic uremic syndrome (HUS) cases were diagnosed. The main objective of this work was to detect, isolate and characterize STEC O157 and non-O157 strains in fresh ground beef. Between September and December 2004, 53 fresh ground beef samples were collected from butcher shops in Concepción city. The USDA-FSIS (2002) methodology was used for detection, isolation and characterization of STEC O157:H7. Two PCR techniques for E. coli non-O157 detection and a previous intra-laboratory validated methodology for the isolation and characterization of these strains were used. The stx2 gen was identified in seven samples and the rfbO157 gene also in four of them. However, only one E. coli O157:H7 strain, biotype C, carrying the eae, stx2 and ehxA genes, was isolated. The present study shows the importance of implementing techniques for the detection of this emerging pathogen in meat samples.

A neuropsychological approach in a paediatric acquired brain injury unit under the public health system. / Abordaje neuropsicológico en una unidad pediátrica de daño cerebral adquirido del sistema público de salud.

INTRODUCTION: Paediatric acquired brain injury (ABI) causes cognitive and behavioural difficulties and alters the course of child development. The ABI unit at Hospital Infantil Universitario Niño Jesús is the first within the public Spanish health system to provide comprehensive coverage to these patients and their families. OBJECTIVE: This study aims to show the working methodology followed with patients and their families, and to describe the clinical characteristics of the patients treated and the outcomes of treatment. PATIENTS: Fifty-three patients aged between three months and 16 and a half years received treatment. The conditions treated were brain tumours, stroke, traumatic brain injury, damage secondary to epilepsy surgery, and hypoxia. METHODS: All patients were evaluated at admission and at discharge. Treatments were adapted to each patient's difficulties and their severity, as well as to the patient's age. Families received individual and group therapy. RESULTS: Older age was associated with better cognitive recovery and shorter duration of treatment. Different conditions show differential impact on intelligence quotient and developmental quotient scores at the beginning of treatment, with hypoxia and encephalitis being associated with greatest severity. Intelligence quotient and developmental quotient scores and visual memory and attention scores at discharge improved significantly after the faceted neuropsychological treatment with respect to scores registered at admission. CONCLUSIONS: The care of patients with ABI should include neuropsychological rehabilitation programmes and provide emotional support to the family so that they may actively participate in the recovery of the child or adolescent.

[Clinical and neuropsychological characteristics in congenital central hypoventilation syndrome]. / Aspectos clinicos y neuropsicologicos del sindrome de hipoventilacion central congenita.

INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) syndrome is a rare disease caused by mutations in the PHOX2B gene. Patients show a reduced response to hypercapnia and hypoxia accompanied by diffuse disturbances of the autonomic nervous system and occasionaly also disturbances in neuroimaging. A specific neuropsychological profile has not been described in children and adolescents with CCHS. CASE REPORTS: We describe three cases (aged between 4 and 19 years) with different profiles of affectation in cognitive and functionality. These profiles are compared with the features described in the literature about neuropsychology in CCHS. CONCLUSIONS: The profile of functional impairment in the CCHS is variable: in case 1, a severe global developmental delay with autistic features and marked functional involvement is described. In case 2, bilateral atrophy of the hippocampus is associated with involvement in social cognition and in executive functions with moderate functional repercussion. Case 3 shows difficulties in some cognitive executive functions (planning and non-verbal fluency), but without functional repercussion. Neuropsychological assessment can help in the clinical management of these patients by determining and guiding the need for rehabilitation treatments.

TITLE: Aspectos clinicos y neuropsicologicos del sindrome de hipoventilacion central congenita.Introduccion. El sindrome de hipoventilacion central congenita (SHCC) es una enfermedad rara producida por mutaciones en el gen PHOX2B. Los pacientes muestran una reducida respuesta a la hipercapnia e hipoxia acompañada de alteraciones difusas del sistema nervioso autonomo y ocasionalmente alteraciones en neuroimagen. No se ha descrito un perfil neuropsicologico especifico en los niños y adolescentes con SHCC. Casos clinicos. Se presentan tres casos (de edades comprendidas entre 4 y 19 años) con diferente perfil de afectacion cognitiva y funcional. Se comparan los perfiles de los tres casos con los hallazgos descritos en la bibliografia sobre neuropsicologia en el SHCC. Conclusiones. El perfil de afectacion funcional en el SHCC es variable: en el caso 1 se describe un grave retraso global en el desarrollo con rasgos autistas y acusadas implicaciones funcionales. En el caso 2, la atrofia bilateral del hipocampo se asocia a deficit en cognicion social y alteraciones en funciones ejecutivas con moderada repercusion funcional. El caso 3 muestra dificultades en algunas funciones ejecutivas cognitivas (planificacion y fluidez no verbal), pero sin repercusion funcional. La evaluacion neuropsicologica puede ayudar en el manejo clinico de estos pacientes determinando y orientando la necesidad de tratamientos rehabilitadores.

Abordaje neuropsicológico en una unidad pediátrica de daño cerebral adquirido del sistema público de salud / A neuropsychological approach in a paediatric acquired brain injury unit under the public health system

Introducción: El daño cerebral adquirido (DCA) pediátrico provoca dificultades cognitivo/conductuales y altera el curso del desarrollo. La unidad de DCA del Hospital Infantil Universitario Niño Jesús es la primera dentro del sistema público de salud en dar cobertura integral a pacientes y familias.ObjetivoSe pretende mostrar la metodología de trabajo con los niños y sus familias, describir las características clínicas de los pacientes atendidos y los resultados en cuanto a los tratamientos aplicados.Sujetos53 niños entre los tres meses y los 16 años y medio recibieron tratamiento. Las patologías atendidas son tumores cerebrales, accidentes cerebrovasculares, traumatismos craneoencefálicos, daño tras cirugía de la epilepsia e hipoxia.MétodoA todos los pacientes se le realizó una evaluación al ingreso y otra al alta. Los tratamientos se modulan en función de las dificultades y su gravedad, así como de la edad del niño. Las familias son atendidas tanto individualmente como en formato grupal.ResultadosUna mayor edad del niño se asocia con mejor recuperación del nivel cognitivo y menor duración del tratamiento. Las patologías tienen un impacto diferencial en el CI/CD evaluado al inicio de tratamiento, la hipoxia y las encefalitis son las que asocian mayor gravedad. Las puntuaciones al alta del CI/CD, así como las de memoria verbal y atención, mejoraron significativamente respecto a las del ingreso tras el tratamiento neuropsicológico multicomponente.ConclusionesLa atención al DCA debe incluir programas de rehabilitación neuropsicológica y proporcionar soporte emocional a la familia para que pueda participar activamente en la recuperación del niño o adolescente. (AU)

Introduction: Paediatric acquired brain injury (ABI) causes cognitive and behavioural difficulties and alters the course of child development. The ABI unit at Hospital Infantil Universitario Niño Jesús is the first within the public Spanish health system to provide comprehensive coverage to these patients and their families.ObjectiveThis study aims to show the working methodology followed with patients and their families, and to describe the clinical characteristics of the patients treated and the outcomes of treatment.PatientsFifty-three patients aged between three months and 16 and a half years received treatment. The conditions treated were brain tumours, stroke, traumatic brain injury, damage secondary to epilepsy surgery, and hypoxia.MethodsAll patients were evaluated at admission and at discharge. Treatments were adapted to each patient's difficulties and their severity, as well as to the patient's age. Families received individual and group therapy.ResultsOlder age was associated with better cognitive recovery and shorter duration of treatment. Different conditions show differential impact on intelligence quotient and developmental quotient scores at the beginning of treatment, with hypoxia and encephalitis being associated with greatest severity. Intelligence quotient and developmental quotient scores and visual memory and attention scores at discharge improved significantly after the faceted neuropsychological treatment with respect to scores registered at admission.ConclusionsThe care of patients with ABI should include neuropsychological rehabilitation programmes and provide emotional support to the family so that they may actively participate in the recovery of the child or adolescent. (AU)

Functional surgery in pediatric drug-resistant posterior cortex epilepsy: Electro-clinical findings, cognitive and seizure outcome.

PURPOSE: Epilepsies originated from the occipital, parietal and/or the posterior edge of the temporal lobe are grouped together into posterior cortex epilepsy (PCE). Our objective was firstly to describe electro-clinical and imaging findings in the presurgical evaluation of children with PCE, and secondly to identify potential factors associated with surgical and cognitive outcomes. METHOD: From the total of patients referred to the Epilepsy Monitoring Unit of 'Hospital Universitario Niño Jesús' from 2003 to 2016, 55 had drug-resistant PCE. Different variables obtained from the multimodal presurgical work-up were analyzed among patients achieving seizure freedom after surgery (ILAE class 1) and patients with persistent seizures. Categorical variables were compared with Fishers exact test and numeric variables with t-Student for independent samples, and multiple logistic regression were used to analyze predictive values. RESULTS: Median duration of epilepsy until surgery was 5 years [3-10 years]. Fifty patients showed lesions in the MRI, and 62.5% had concordant MRI-PET corregistration. 37 (67%) patients were operated (lesionectomy in 21 subjects, tailored resection based on intracranial studies in 16), and 23 (62,2%) reached ILAE class 1, with a mean follow-up period of 3.51 [1-12] years. A lower number of basal seizures and antiepileptic drugs, a well-defined lesion on the MRI, an epileptogenic zone (EZ) restricted to the posterior quadrant and the normalization of postsurgical EEGs were associated with seizure freedom (p<0.05). Additionally, 65% of patients had a long-term improvement of cognitive performances. CONCLUSIONS: Epilepsy surgery should be considered in children with drug-resistant PCE, especially in those with a restricted EZ.

Inhibition of serotonin receptor type 1 in acute myeloid leukemia impairs leukemia stem cell functionality: a promising novel therapeutic target.

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous neoplasia with poor outcome, organized as a hierarchy initiated and maintained by a sub-population with differentiation and self-renewal capacities called leukemia stem cells (LSCs). Although currently used chemotherapy is capable of initially reducing the tumor burden producing a complete remission, most patients will ultimately relapse and will succumb to their disease. As such, new therapeutic strategies are needed. AML cells differentially expressed serotonin receptor type 1 (HTR1) compared with healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome. Inhibition of HTR1s activated the apoptosis program, induced differentiation and reduced the clonogenic capacity, while minimal effect was observed on healthy blood cells. In vivo regeneration capacity of primary AML samples was disrupted upon inhibition of HTR1. The self-renewal capacity remaining in AML cells upon in vivo treatment was severely reduced as demonstrated by serial transplantation. Thus, treatment with HTR1 antagonists showed antileukemia effect, especially anti-LSC activity while sparing healthy blood cells. Our results highlight the importance of HTR1 in leukemogenesis and LSC survival and identify this receptor family as a new target for therapy in AML with prognostic value.

Spectroscopic characterization of flavocytochrome c-552 from the photosynthetic purple sulfur bacterium Chromatium vinosum.

The identities of the axial ligands to the two hemes of the flavocytochrome c-552 isolated from the photosynthetic purple sulfur bacterium Chromatium vinosum have been investigated by visible/near-infrared absorption and magnetic circular dichroism (MCD) spectroscopies, with parallel electron paramagnetic resonance (EPR) studies. One of the hemes has histidine and methionine as axial ligands and has a local environment that is relatively insensitive to the composition of the bulk medium. The second heme, the local environment of which is sensitive to changes in the composition of the bulk medium, exists as a mixture of two forms, only one of which has histidine/methionine axial ligation. On the basis of its EPR characteristics, the other form most likely has histidine/lysine axial ligation. In aqueous solution near neutral pH, more than half of the second heme is present as the histidine/lysine form, while in 50:50 water/ethylene glycol the histidine/methionine form is the dominant one.

Comparison of cyclosporine concentrations 2 hours post-dose determined using 3 different methods and trough level in pediatric renal transplantation.

Immunosuppression has been one of the great challenges in pediatric recipients of kidney allografts. Cyclosporine (CsA) has evolved during the past 25 years of transplantation. It requires frequent blood level monitoring because of its narrow therapeutic window and interpatient and intrapatient variability. Neoral (Novartis) is no exception. Ideally, monitoring of blood levels should also include determination of the area under the time-concentration curve (AUC) to better target the therapeutic window, thus avoiding underdosing or overdosing, especially in pediatric patients. A single blood concentration measurement 2 hours after Neoral administration (C2) has been shown to be a more for accurate predictor of drug exposure than trough levels (C0). Therefore, its use may lead to reduction in the incidence and severity of cellular rejection and of CsA toxicity. Some studies have shown that the metabolites/CsA ratio is substantially lower using C2 than C0, however, the between-assay differences for C2 monitoring have not been considered. The purpose of this study was to evaluate CsA C0 and C2 levels, determined using monoclonal fluorescence polarization immunoassay (FPIA)/TDx and enzyme multiplied immunoassay (EMIT). CsA levels were determined using a radioimmunoassay (RIA) in 30 pediatric transplant recipients with stable renal function within 42.7 mean months follow-up. Mean age was 13.4 years; 15 children were girls; 23 patients were recipients of cadaveric kidneys. The mean CsA microemulsion dose was 5.7 mg/kg/d. The 3 methods showed a high correlation between C0 and C2 (r > or = 0.97). A linear regression slope was significantly higher for C0 than C2 (P < .001). The CsA concentrations both at C0 and C2 were significantly higher with FPIA than with RIA (P < .009) but no differences were found for EMITT (P = .2). The mean C0 level for FPIA was 22% and 26% higher than RIA and EMIT, respectively. The mean C2, for FPIA was 7% and 12% higher than RIA and EMIT, respectively. In conclusion, CsA levels determined using RIA or EMIT are better than using FPIA/Tx; also, C2 CsA levels are more accurate than C0 in pediatric transplantation patients.

Late detection of a shigellosis outbreak in a school in Madrid.

Even though shigellosis in Spain is rare, an indigenous outbreak is occasionally detected. We describe an outbreak in a school in Madrid caused by person-to-person transmission of Shigella sonnei. After the detection of Shigella sonnei in a stool sample from a 3 year old girl, an investigation at her school was initiated. Questionnaires were distributed to the parents of 520 pupils attending the school. A case was defined as a school case if it was the first case in a child's household, and as a household case if other members of the household had fallen ill first. We identified 88 cases (60 pupils and 28 of their family members). The attack rate (AR) was 12% in the school and 32% in the families. There was a significant association between higher AR and lower age. The outbreak lasted for two months. The length and the shape of the epidemic curve of the 60 cases in pupils suggests person-to-person transmission. Shigella sonnei isolated from 5 different cases were typed by pulsed field gel electrophoresis (PFGE) and was found to be an identical strain. The prolonged duration of the outbreak was probably due to delayed detection, and stopped as soon as control measures were introduced.

[Diffuse pulmonary calcification in a patient with renal insufficiency]. / Calcinosis pulmonar difusa en paciente con insuficiencia renal.

We report the case of a 37-year-old man with chronic renal insufficiency, on hemodialysis, with no respiratory symptoms but whose chest radiograph showed parenchymal consolidation in the middle and upper lung fields. High resolution computed tomography showed a high-attenuating diffuse alveolar pattern that indicated calcium deposits. Bronchoscopy revealed metastatic calcification on the interalveolar septa and bronchiolar and arteriolar. The present report, based on radiologic and bronchoscopic findings, describes the pathogenesis and anatomical distribution of the patient's diffuse pulmonary calcification.

Adenomatous hyperplasia of the rete testis. A review and report of new cases.

Adenomatous hyperplasia of the rete testis (AHRT) is an uncommon benign lesion that preferentially involves the septal rete testis and mediastinal rete testis. It is usually an incidental finding in surgical specimens from cryptorchidism and testicular tumour. It can be found in autopsy specimens from patients dying with different chronic diseases and newborns with kidney diseases. Since its first description many articles have been published communicating new cases and putting forward some hypotheses on its aetiology and pathogenic mechanisms. Some authors suggest a role for hormonal changes, tumour invasion and action of chemical agents. We think that AHRT should be categorised into two main aetiological categories: congenital and acquired. The cases associated with different kidney and spermatic duct diseases, most cases associated with cryptorchidic testis and some cases associated with testicular germ cell tumour should be included in the congenital group. The remaining cases associated with chemical agents, some hormonal changes (i.e. androgen blockade) and most of the germ cell tumour cases can be considered as acquired AHRT. Differential diagnosis must be established mainly with metastatic adenocarcinoma of prostate to testis and primary adenocarcinoma of the rete testis. Pseudohyperplasia of the rete testis must also be considered in atrophic testes. Here we review the papers published on this subject and report our recent cases.