Oxidative Model of Retinal Neurodegeneration Induced by Sodium Iodate: Morphofunctional Assessment of the Visual Pathway.

Sodium iodate (NaIO3) has been shown to cause severe oxidative stress damage to retinal pigment epithelium cells. This results in the indirect death of photoreceptors, leading to a loss of visual capabilities. The aim of this work is the morphological and functional characterization of the retina and the visual pathway of an animal model of retinal neurodegeneration induced by oxidative stress. Following a single intraperitoneal dose of NaIO3 (65 mg/kg) to C57BL/6J mice with a mutation in the Opn4 gene (Opn4-/-), behavioral and electroretinographic tests were performed up to 42 days after administration, as well as retinal immunohistochemistry at day 57. A near total loss of the pupillary reflex was observed at 3 days, as well as an early deterioration of visual acuity. Behavioral tests showed a late loss of light sensitivity. Full-field electroretinogram recordings displayed a progressive and marked decrease in wave amplitude, disappearing completely at 14 days. A reduction in the amplitude of the visual evoked potentials was observed, but not their total disappearance. Immunohistochemistry showed structural alterations in the outer retinal layers. Our results show that NaIO3 causes severe structural and functional damage to the retina. Therefore, the current model can be presented as a powerful tool for the study of new therapies for the prevention or treatment of retinal pathologies mediated by oxidative stress.

Origin of Retinal Oscillatory Potentials in the Mouse, a Tool to Specifically Locate Retinal Damage.

To determine the origin of oscillatory potentials (OPs), binocular electroretinogram (ERG) recordings were performed under light and dark adaptation on adult healthy C57BL/6J mice. In the experimental group, 1 µL of PBS was injected into the left eye, while the right eye was injected with 1 µL of PBS containing different agents: APB, GABA, Bicuculline, TPMPA, Glutamate, DNQX, Glycine, Strychnine, or HEPES. The OP response depends on the type of photoreceptors involved, showing their maximum response amplitude in the ERG induced by mixed rod/cone stimulation. The oscillatory components of the OPs were affected by the injected agents, with some drugs inducing the complete abolition of oscillations (APB, GABA, Glutamate, or DNQX), whereas other drugs merely reduced the oscillatory amplitudes (Bicuculline, Glycine, Strychnine, or HEPES) or did not even affect the oscillations (TPMPA). Assuming that rod bipolar cells (RBC) express metabotropic Glutamate receptors, GABAA, GABAC, and Glycine receptors and that they release glutamate mainly on Glycinergic AII amacrine cells and GABAergic A17 amacrine cells, which are differently affected by the mentioned drugs, we propose that RBC-AII/A17 reciprocal synapses are responsible for the OP generation in the ERG recordings in the mice. We conclude that the reciprocal synapses between RBC and AII/A17 are the basis of the ERG OP oscillations of the light response, and this fact must be taken into consideration in any ERG test that shows a decrease in the OPs' amplitude.

Phenotype Characterization of a Mice Genetic Model of Absolute Blindness.

Recent technological development requires new approaches to address the problem of blindness. Such approaches need to be able to ensure that no cells with photosensitive capability remain in the retina. The presented model, Opn4-/- × Pde6brd10/rd10 (O×Rd) double mutant murine, is a combination of a mutation in the Pde6b gene (photoreceptor degeneration) together with a deletion of the Opn4 gene (responsible for the expression of melanopsin in the intrinsically photosensitive retinal ganglion cells). This model has been characterized and compared with those of WT mice and murine animal models displaying both mutations separately. A total loss of pupillary reflex was observed. Likewise, behavioral tests demonstrated loss of rejection to illuminated spaces and a complete decrease in visual acuity (optomotor test). Functional recordings showed an absolute disappearance of various wave components of the full-field and pattern electroretinogram (fERG, pERG). Likewise, visual evoked potential (VEP) could not be recorded. Immunohistochemical staining showed marked degeneration of the outer retinal layers and the absence of melanopsin staining. The combination of both mutations has generated an animal model that does not show any photosensitive element in its retina. This model is a potential tool for the study of new ophthalmological approaches such as optosensitive agents.

Anti-Inflammatory Action of Dietary Wild Olive (Acebuche) Oil in the Retina of Hypertensive Mice.

Inflammation plays a crucial role in the course of eye diseases, including many vascular retinopathies. Although olive oil is known to have beneficial effects against inflammatory processes, there is no information available on the anti-inflammatory potential of the wild olive tree (namely, acebuche (ACE) for the primitive Spanish lineages). Here we investigate the anti-inflammatory effects of ACE oil in the retina of a mouse model of arterial hypertension, which was experimentally induced by administration of L-NAME (NG-nitro-L-arginine-methyl-ester). The animals were fed supplements of ACE oil or extra virgin olive oil (EVOO, for comparative purposes). Retinal function was assessed by electroretinography (ERG), and different inflammation-related parameters were measured in the retina and choroid. Besides significant prevention of retinal dysfunction shown in ERG recordings, ACE oil-enriched diet upregulated the expression of the anti-inflammatory markers PPARγ, PPARα and IL-10, while reducing that of major proinflammatory biomarkers, IL-1ß, IL-6, TNF-α and COX-2. This is the first report to highlight the anti-inflammatory properties of an ACE oil-enriched diet against hypertension-related retinal damage. Noteworthy, dietary supplementation with ACE oil yielded better results compared to a reference EVOO.

Visual Disfunction due to the Selective Effect of Glutamate Agonists on Retinal Cells.

One of the causes of nervous system degeneration is an excess of glutamate released upon several diseases. Glutamate analogs, like N-methyl-DL-aspartate (NMDA) and kainic acid (KA), have been shown to induce experimental retinal neurotoxicity. Previous results have shown that NMDA/KA neurotoxicity induces significant changes in the full field electroretinogram response, a thinning on the inner retinal layers, and retinal ganglion cell death. However, not all types of retinal neurons experience the same degree of injury in response to the excitotoxic stimulus. The goal of the present work is to address the effect of intraocular injection of different doses of NMDA/KA on the structure and function of several types of retinal cells and their functionality. To globally analyze the effect of glutamate receptor activation in the retina after the intraocular injection of excitotoxic agents, a combination of histological, electrophysiological, and functional tools has been employed to assess the changes in the retinal structure and function. Retinal excitotoxicity caused by the intraocular injection of a mixture of NMDA/KA causes a harmful effect characterized by a great loss of bipolar, amacrine, and retinal ganglion cells, as well as the degeneration of the inner retina. This process leads to a loss of retinal cell functionality characterized by an impairment of light sensitivity and visual acuity, with a strong effect on the retinal OFF pathway. The structural and functional injury suffered by the retina suggests the importance of the glutamate receptors expressed by different types of retinal cells. The effect of glutamate agonists on the OFF pathway represents one of the main findings of the study, as the evaluation of the retinal lesions caused by excitotoxicity could be specifically explored using tests that evaluate the OFF pathway.

Adrenergic Modulation With Photochromic Ligands.

Adrenoceptors are ubiquitous and mediate important autonomic functions as well as modulating arousal, cognition, and pain on a central level. Understanding these physiological processes and their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio-temporal precision. Here we present a first generation of photochromic ligands (adrenoswitches) obtained via azologization of a class of cyclic amidines related to the known ligand clonidine. Their pharmacology, photochromism, bioavailability, and lack of toxicity allow for broad biological applications, as demonstrated by controlling locomotion in zebrafish and pupillary responses in mice.

Inhibition of MicroRNA 6937 Delays Photoreceptor and Vision Loss in a Mouse Model of Retinitis Pigmentosa.

Inherited retinal dystrophies (IRDs) are a group of rare retinal conditions, including retinitis pigmentosa (RP), caused by monogenic mutations in 1 out of more than 250 genes. Despite recent advancements in gene therapy, there is still a lack of an effective treatment for this group of retinal conditions. MicroRNAs (miRNAs) are a class of highly conserved small non-coding RNAs that inhibit gene expression. Control of miRNAs-mediated protein expression has been described as a widely used mechanism for post-transcriptional regulation in many physiological and pathological processes in different organs, including the retina. Our main purpose was to test the hypothesis that modulation of a group of miRNAs can protect photoreceptor cells from death in the rd10 mouse model of retinitis pigmentosa. For this, we incorporated modulators of three miRNAs in adeno-associated viruses (AAVs), which were administered through sub-retinal injections. The results obtained indicate that inhibition of the miR-6937-5p slows down the visual deterioration of rd10 mice, reflected by an increased electroretinogram (ERG) wave response under scotopic conditions and significant preservation of the outer nuclear layer thickness. This work contributes to broadening our knowledge on the molecular mechanisms underlying retinitis pigmentosa and supports the development of novel therapeutic approaches for RP based on miRNA modulation.

Painful insight vs. usable insight in schizophrenia. Do they have different influences on suicidal behavior?

BACKGROUND: Suicidal behavior is highly prevalent in schizophrenia. Among the risk factors, insight has been little studied and has yielded contradictory results. In addition, it has been studied neglecting relevant psychological aspects, such as beliefs about illness and coping styles. METHOD: We assessed 133 outpatients diagnosed with schizophrenia according to ICD-10 criteria. Evaluation included sociodemographic, general clinical, psychopathological, psychological and suicidal behavior variables. RESULTS: Neither insight nor insight coupled with negative beliefs and/or coping styles were associated with suicidal behavior. Nevertheless, insight coupled with negative beliefs and/or coping styles was associated with greater hopelessness and depression, internalized stigma, worse control over illness and greater global severity as compared to insight coupled with positive beliefs and coping styles. Suicide attempt and suicidal ideation groups showed greater depression and hopelessness, worse global beliefs and worse control over illness, higher socio-economic level, and greater number of previous psychiatric admissions compared to the non-suicidal group. CONCLUSIONS: Insight coupled with negative beliefs and/or coping style was not associated with suicidal behavior. Nevertheless, it was associated with greater depression and hopelessness, both of which are firmly established risk factors for suicide in schizophrenia. Prospective studies with long-term follow-up and large samples are needed to clarify this issue. Clinicians should assess these psychological features associated with insight, both in patients with insight and in those with poor insight when promoting it.

Deleterious Effect of NMDA Plus Kainate on the Inner Retinal Cells and Ganglion Cell Projection of the Mouse.

Combined administration of N-Methyl-D-Aspartate (NMDA) and kainic acid (KA) on the inner retina was studied as a model of excitotoxicity. The right eye of C57BL6J mice was injected with 1 µL of PBS containing NMDA 30 mM and KA 10 mM. Only PBS was injected in the left eye. One week after intraocular injection, electroretinogram recordings and immunohistochemistry were performed on both eyes. Retinal ganglion cell (RGC) projections were studied by fluorescent-cholerotoxin anterograde labeling. A clear decrease of the retinal "b" wave amplitude, both in scotopic and photopic conditions, was observed in the eyes injected with NMDA/KA. No significant effect on the "a" wave amplitude was observed, indicating the preservation of photoreceptors. Immunocytochemical labeling showed no effects on the outer nuclear layer, but a significant thinning on the inner retinal layers, thus indicating that NMDA and KA induce a deleterious effect on bipolar, amacrine and ganglion cells. Anterograde tracing of the visual pathway after NMDA and KA injection showed the absence of RGC projections to the contralateral superior colliculus and lateral geniculate nucleus. We conclude that glutamate receptor agonists, NMDA and KA, induce a deleterious effect of the inner retina when injected together into the vitreous chamber.

Neuromodulation of the prefrontal cortex facilitates diet-induced weight loss in midlife women: a randomized, proof-of-concept clinical trial.

BACKGROUND: High body mass index (BMI) is associated with neurocognitive impairments that contribute to overeating and interfere with weight loss efforts. Overweight and obesity at midlife can accelerate neurodegenerative changes and increase the risk of late-life dementia. Noninvasive neuromodulation represents a novel, affordable and scalable approach to improve neurocognitive function in this context. The purpose of this proof-of-concept study was to examine whether transcranial direct current stimulation (tDCS) aimed at enhancing prefrontal cortex activity could enhance weight loss, in combination with a hypocaloric diet, and study underlying mechanisms. METHODS: Overall, 38 women with BMI 25-35 kg/m2 underwent a 4 week randomized, double-blinded, sham-controlled, and parallel-design intervention, during which they received eight sessions of tDCS (n = 18 sham, n = 20 active) in combination with a diet (caloric goal of 20 kcal/kg/day). We evaluated longitudinal changes in body weight, appetite and food craving. In addition, we examined the contribution of cognitive-executive processes via food-modified computerized tasks. RESULTS: We found that the active group had more reduction in body weight than the sham group throughout the study (p = 0.020) and significant weekly weight loss. At 4 weeks, the active group lost 2.32% of initial body weight (sham: 1.29%). Components of subjective appetite and food craving showed a trend toward more reduction in the active group. These changes were paralleled by significant improvements in task performance in the active group, particularly in a dual task that required inhibitory control and working memory (p = 0.007-0.031). Improvement in inhibitory control performance predicted reduction in lack of control overeating, explaining 43.5% of its variance at the end of the study (p = 0.003). No significant adverse effects were observed. CONCLUSIONS: Our results provide proof-of-concept validation of prefrontal-targeted tDCS, combined with a diet, in midlife women with excess body weight, paving the way for larger studies evaluating clinical efficacy and long-term effects of this intervention.

La controversia científico-técnica sobre las benzodiacepinas en profesionales de la salud pública de Uruguay / A controvérsia científico-técnica sobre as benzodiazepinas entre profissionais de saúde pública do Uruguai / The scientific-technical controversy over benzodiazepines among public health professionals in Uruguay

Resumen La controversia científico-técnica internacional sobre las benzodiacepinas, intensa durante los años ochenta y noventa, cuestionó su lugar en la práctica clínica, por su potencialidad adictiva, y por el abuso que médicos y pacientes parecerían realizar. Este artículo presenta resultados de una investigación que tuvo como objetivo analizar el papel de dicha controversia en las prácticas médica, psiquiátrica y psicológica en los servicios de salud pública uruguayos. Se utilizó metodología cualitativa y se combinó relevamiento de artículos académicos nacionales (1960-2012), entrevistas en profundidad a 45 profesionales y dos grupos de discusión. Se efectuó análisis de contenido desde cuatro ejes: ansiedad en la clínica, prescripción, relación tratamientos farmacológicos con no farmacológicos y valoración de benzodiacepinas. Se obtuvo un panorama diacrónico de la controversia académica y se identificó una valoración condicional de estos medicamentos realizada por los profesionales que supone: reconocimiento de atributos positivos y negativos de las benzodiacepinas, uso mesurado, médicos y pacientes vigilantes de sus propios comportamientos. Se concluye que la controversia se plantea en términos individuales, lo que obstaculiza una discusión global de las dimensiones políticas y colectivas implicadas.

Resumo A controvérsia científico-técnica internacional sobre as benzodiazepinas, intensa durante os anos 1980 e 1990, questionou seu lugar na prática clínica devido a sua potencialidade aditiva e pelo abuso que médicos e pacientes pareciam realizar. Este artigo apresenta resultados de uma pesquisa que teve como objetivo analisar o papel dessa controvérsia nas práticas médica, psiquiátrica e psicológica nos serviços de saúde pública do Uruguai. Utilizou-se metodologia qualitativa e combinou-se um levantamento de artigos acadêmicos nacionais (1960-2012), entrevistas em profundidade com 45 profissionais e dois grupos de discussão. Realizou-se análise de conteúdo a partir de quatro eixos: ansiedade na clínica, prescripção, relação entre tratamentos farmacológicos e não farmacológicos e avaliação das benzodiacepinas. Obteve-se um panorama diacrônico da controvérsia acadêmica e identificou-se uma avaliação condicional desses medicamentos realizada pelos profissionais, que supõe: reconhecimento de atributos positivos e negativos das benzodiazepinas, uso controlado, médicos e pacientes vigilantes de seus próprios comportamentos. Conclui-se que a controvérsia é levantada em termos individuais, o que obstaculiza uma discussão global das dimensões políticas e coletivas implicadas.

Abstract The international technoscientific controversy on benzodiazepines, especially intense during the 1980s and 1990s, questioned the place of benzodiazepines in clinical practice because of its addictive potentiality and the abuse of physicians and patients. This article presents some results from a research that aimed to analyze the role of benzodiazepine controversy in medical, psychiatric and psychological practices in Uruguayan public health services. This research methodology was qualitative, combining a review of national academic articles (1960-2012), in-depth interviews with 45 professionals and two discussion groups. Content analysis was carried out using four axes: anxiety in clinic practice, prescription, relationship between pharmacologic and non-pharmacologic treatment, and benzodiazepines valoration. We obtained a diachronic pictures of the academic controversy and we identified a conditional assessment of these medicines made by the professionals. This assessment implies: the recognition of positive and negative attributes of benzodiazepines, a controlled use of benzodazepines, and professionals and patients that must watch their own behaviors. We conclude that the controversy is presented mainly in individual terms, and this prevents a global discussion on the political and collective dimensions involved.

Variables asociadas a la no adherencia en pacientes con trastorno bipolar en estabilidad clínica / Variables associated with nonadherence in clinically stable patients with bipolar disorder

Introducción. La no adherencia es un problema altamente prevalente en el trastorno bipolar y puede conllevar importantes consecuencias. Sorprendentemente apenas existen estudios sobre factores de riesgo en pacientes en estado de estabilidad clínica. Metodología. La adherencia se evaluó en 76 pacientes con trastorno bipolar en estabilidad clínica, mediante métodos objetivos y subjetivos, abarcando el momento transversal y un periodo retrospectivo de 3 años. Se evaluó su posible asociación con variables sociodemográficas, clínicas, relacionadas con el tratamiento, psicopatológicas, psicológicas y de aspectos subjetivos, y de resultado. Resultados. Un 36,8% de los pacientes fueron no adherentes. Estos mostraron mayor preocupación sobre la medicación, peor funcionalidad, mayor número de episodios, episodios depresivos, y mayores prevalencias de comorbilidad con otros trastornos psiquiátricos, consumo de tóxicos actual y/o pasado y de antecedentes de episodios con síntomas psicóticos. Tras el análisis multivariante, la preocupación por la medicación, el consumo actual y/o pasado de tóxicos y la comorbilidad con otros trastornos psiquiátricos se asociaron de manera independiente con la no adherencia. Conclusiones. La no adherencia en el trastorno bipolar es un fenómeno frecuente, incluso en pacientes en estabilidad. El clínico debería explorar las creencias y actitudes del paciente hacia la medicación, y ayudarle a reevaluarlas desde un punto de vista más realista. Por su parte, deben realizarse intervenciones para evitar el consumo de tóxicos. La identificación de factores de riesgo asociados a la no adherencia en estabilidad añade información al perfil de riesgo disponible para el trastorno bipolar

Introduction. Nonadherence is an important and highly prevalent issue in bipolar disorder, which may have serious consequences. Surprisingly, few studies have been carried out in patients with clinical stability to explore risk factors for nonadherence. Method. Adherence was assessed in 76 bipolar disorder patients with clinical stability using objective and subjective methods, both with a cross-sectional approach and a 3-year retrospective period. Possible associations between nonadherence and sociodemographic, clinical, treatment-related, psychopathological, psychological-subjective and result variables were also assessed. Results. 36.8% of patients were nonadherent. These patients showed greater concerns about medicines, worse functionality, a greater number of episodes and depressive episodes, higher prevalence of psychiatric comorbidities, present and/or past substance use or abuse and a history of depressive episodes with psychotic symptoms. A multivariate analysis revealed that concern about medicines, present and/or past substance use or abuse and psychiatric comorbidities were independently associated with nonadherence. Conclusions. Nonadherence is a frequent phenomenon in bipolar disorder, even in patients with clinical stability. Clinicians should assess patients’ beliefs and attitudes towards medicines and help them reevaluate those issues with a more realistic perspective. Clinicians should also take actions to prevent substance use or abuse. Identification of nonadherence risk profile in bipolar disorder patients in clinical stability, adds complementary information to the identified risk profile in acute phases of the disease

Variables associated with nonadherence in clinically stable patients with bipolar disorder.

INTRODUCTION: Nonadherence is an important and highly prevalent issue in bipolar disorder, which may have serious consequences. Surprisingly, few studies have been carried out in patients with clinical stability to explore risk factors for nonadherence. METHOD: Adherence was assessed in 76 bipolar disorder patients with clinical stability using objective and subjective methods, both with a cross-sectional approach and a 3-year retrospective period. Possible associations between nonadherence and sociodemographic, clinical, treatment-related, psychopathological, psychological-subjective and result variables were also assessed. RESULTS: 36.8% of patients were nonadherent. These patients showed greater concerns about medicines, worse functionality, a greater number of episodes and depressive episodes, higher prevalence of psychiatric comorbidities, present and/or past substance use or abuse and a history of depressive episodes with psychotic symptoms. A multivariate analysis revealed that concern about medicines, present and/or past substance use or abuse and psychiatric comorbidities were independently associated with nonadherence. CONCLUSIONS: Nonadherence is a frequent phenomenon in bipolar disorder, even in patients with clinical stability. Clinicians should assess patients’ beliefs and attitudes towards medicines and help them reevaluate those issues with a more realistic perspective. Clinicians should also take actions to prevent substance use or abuse. Identification of nonadherence risk profile in bipolar disorder patients in clinical stability, adds complementary information to the identified risk profile in acute phases of the disease.

Estereotipia social en los profesionales de la salud pública de Uruguay acerca del uso de benzodiazepinas / Social stereotyping in public health professionals of Uruguay on benzodiazepine use

Se presentan los resultados de una investigación cualitativa que tuvo como objetivo analizar el papel de la controversia sobre la utilidad clínica de las benzodiazepinas en las prácticas de la Medicina General, la Psiquiatría y la Psicología en los servicios de salud pública del Uruguay. La metodología empleada combinó la realización de entrevistas en profundidad y los grupos de discusión y una revisión documental. Se observa un desplazamiento de la valoración (positiva o negativa) de la sustancia, a la valoración de su utilización por parte de los médicos y los usuarios, moralizando sus conductas. Se identificaron en los profesionales distintos procesos de estereotipación y moralización de las conductas de los pacientes, que complejizan la práctica clínica y el acto de prescripción, obstaculizando la posibilidad de visualizar alternativas al uso de las benzodiazepinas.(AU)

This article presents the results of a qualitative study that aimed at analyzing the role of controversy on the clinical utility of benzodiazepines in clinical practices of General Medicine, Psychiatry and Psychology of public health services in Uruguay. Themethodology associated the conduction of in depth interviews with discussion groups and a documental review. It is seen a shift from the substance assessment (positive or negative) to the assessment of the benzodiazepine use by physicians and users, thus moralizing their behavior. Stereotyping and moralizing processes of the patients' behavior were identifid among diffrent health professionals, which make the clinical practice and the act of prescribing more complex, hindering the chance of visualizing alternatives to the use of benzodiazepines.(AU)

Estereotipia social en los profesionales de la salud pública de Uruguay acerca del uso de benzodiazepinas / Social stereotyping in public health professionals of Uruguay on benzodiazepine use

Se presentan los resultados de una investigación cualitativa que tuvo como objetivo analizar el papel de la controversia sobre la utilidad clínica de las benzodiazepinas en las prácticas de la Medicina General, la Psiquiatría y la Psicología en los servicios de salud pública del Uruguay. La metodología empleada combinó la realización de entrevistas en profundidad y los grupos de discusión y una revisión documental. Se observa un desplazamiento de la valoración (positiva o negativa) de la sustancia, a la valoración de su utilización por parte de los médicos y los usuarios, moralizando sus conductas. Se identificaron en los profesionales distintos procesos de estereotipación y moralización de las conductas de los pacientes, que complejizan la práctica clínica y el acto de prescripción, obstaculizando la posibilidad de visualizar alternativas al uso de las benzodiazepinas.

This article presents the results of a qualitative study that aimed at analyzing the role of controversy on the clinical utility of benzodiazepines in clinical practices of General Medicine, Psychiatry and Psychology of public health services in Uruguay. Themethodology associated the conduction of in depth interviews with discussion groups and a documental review. It is seen a shift from the substance assessment (positive or negative) to the assessment of the benzodiazepine use by physicians and users, thus moralizing their behavior. Stereotyping and moralizing processes of the patients' behavior were identifid among diffrent health professionals, which make the clinical practice and the act of prescribing more complex, hindering the chance of visualizing alternatives to the use of benzodiazepines.

Determination of the ortho to para ratio of H2Cl+ and H2O+ from submillimeter observations.

The opening of the submillimeter sky with the Herschel Space Observatory has led to the detection of new interstellar molecular ions, H2O(+), H2Cl(+), and HCl(+), which are important intermediates in the synthesis of water vapor and hydrogen chloride. In this paper, we report new observations of H2O(+) and H2Cl(+) performed with both Herschel and ground-based telescopes, to determine the abundances of their ortho and para forms separately and derive the ortho-to-para ratio. At the achieved signal-to-noise ratio, the observations are consistent with an ortho-to-para ratios of 3 for both H2O(+) and H2Cl(+), in all velocity components detected along the lines-of-sight to the massive star-forming regions W31C and W49N. We discuss the mechanisms that contribute to establishing the observed ortho-to-para ratio and point to the need for a better understanding of chemical reactions, which are important for establishing the H2O(+) and H2Cl(+) ortho-to-para ratios.

Involvement of the N-terminal B-box domain of Arabidopsis BBX32 protein in interaction with soybean BBX62 protein.

Previous studies have demonstrated that Arabidopsis thaliana BBX32 (AtBBX32) represses light signaling in A. thaliana and that expression of AtBBX32 in soybean increases grain yield in multiple locations and multiyear field trials. The BBX32 protein is a member of the B-box zinc finger family from A. thaliana and contains a single conserved Zn(2+)-binding B-box domain at the N terminus. Although the B-box domain is predicted to be involved in protein-protein interactions, the mechanism of interaction is poorly understood. Here, we provide in vitro and in vivo evidence demonstrating the physical and functional interactions of AtBBX32 with another B-box protein, soybean BBX62 (GmBBX62). Deletion analysis and characterization of the purified B-box domain indicate that the N-terminal B-box region of AtBBX32 interacts with GmBBX62. Computational modeling and site-directed mutagenesis of the AtBBX32 B-box region identified specific residues as critical for mediating the interaction between AtBBX32 and GmBBX62. This study defines the plant B-box as a protein interaction domain and offers novel insight into its role in mediating specific protein-protein interactions between different plant B-box proteins.

Hopelessness and suicidal risk in bipolar disorder. A study in clinically nonsyndromal patients.

OBJECTIVE: Attempted suicide and death due to suicide are not uncommon among patients with bipolar disorder. Although some risk factors for suicidality in bipolar patients have been identified, little is known about hopelessness and other possible trait or diathesis-related factors. Consequently, the objective of this study was to investigate variables associated with suicidal risk in clinically nonsyndromal bipolar patients. METHODS: A sample of 102 outpatients with a diagnosis of bipolar disorder according to International Classification of Diseases, 10th Revision criteria during nonsyndromal stage were evaluated. On the basis of suicidal history, patients were divided into suicide attempt, suicidal ideation, and nonsuicidal groups. Sociodemographic, clinical, and psychopathological variables were assessed. RESULTS: As compared with the nonsuicidal group, female sex, combined psychopharmacologic treatment, and hopelessness were independently associated with suicide attempt. Hopelessness and insight into having a mental disorder were independently associated with history of suicidal ideation. CONCLUSIONS: Patients with bipolar disorder and suicidal history are characterized by the presence of hopelessness, which probably confers greater vulnerability for suicidal behavior in the presence of stress factors. This identification of the risk profile for suicidal behavior in nonsyndromal bipolar patients adds complementary information to risk factors established for suicidality during acute phases of the disease, allows for differentiated preventive and treatment approaches of patients at risk, and suggests psychotherapy as an advisable intervention in this group of patients.