Atomic structure and Mott nature of the insulating charge density wave phase of 1T-TaS2.

Using x-ray pair distribution function (PDF) analysis and computer modeling, we explore structure models for the complex charge density wave (CDW) phases of layered 1T-TaS2that both well capture their atomic-level features and are amenable to electronic structure calculations. The models give the most probable position of constituent atoms in terms of 3D repetitive unit cells comprising a minimum number of Ta-S layers. Structure modeling results confirm the emergence of star-of-David (SD) like clusters of Ta atoms in the high-temperature incommensurate (IC) CDW phase and show that, contrary to the suggestions of recent studies, the low-temperature commensurate (C) CDW phase expands upon cooling thus reducing lattice strain. The C-CDW phase is also found to preserve the stacking sequence of Ta-S layers found in the room temperature, nearly commensurate (NC) CDW phase to a large extent. DFT based on the PDF refined model shows that bulk C-CDW 1T-TaS2also preserves the insulating state of individual layers of SD clusters, favoring the Mott physics description of the metal-to-insulator (NC-CDW to C-CDW) phase transition in 1T-TaS2. Our work highlights the importance of using precise crystal structure models in determining the nature of electronic phases in complex materials.

Statistical inference for unreliable grading using the maximum entropy principle.

Quantitatively assessing the level of confidence on a test score can be a challenging problem, especially when the available information is based on multiple criteria. A concrete example beyond the usual grading of tests occurs with recommendation letters, where a recommender assigns a score to a candidate, but the reliability of the recommender must be assessed as well. Here, we present a statistical procedure, based on Bayesian inference and Jaynes' maximum entropy principle, that can be used to estimate the most probable and expected score given the available information in the form of a credible interval. Our results may provide insights on how to properly state and analyze problems related to the uncertain evaluation of performance in learning applied to several contexts, beyond the case study of the recommendation letters presented here.

Inhibition of mitochondrial fission by Drp-1 blockade by short-term leptin and Mdivi-1 treatment improves white adipose tissue abnormalities in obesity and diabetes.

BACKGROUND: Obesity and type 2 diabetes are chronic diseases characterized by insulin resistance, mitochondrial dysfunction and morphological abnormalities. OBJECTIVE: We have investigated if dysregulation of mitochondrial dynamics and biogenesis is involved in an animal model of obesity and diabetes. METHODS: The effect of short-term leptin and mdivi-1 - a selective inhibitor of Drp-1 fission-protein - treatment on mitochondrial dynamics and biogenesis was evaluated in epididymal white adipose tissue (WAT) from male ob/ob mice. RESULTS: An increase in Drp-1 protein levels and a decrease in Mfn2 and OPA-1 protein expression were observed with enhanced and sustained mitochondrial fragmentation in ob/ob mice compared to wt C57BL/6 animals (p < 0.05). The content of mitochondrial DNA and PGC-1α mRNA expression -both parameters of mitochondrial biogenesis- were reduced in ob/ob mice (p < 0.05). Treatment with leptin and mdivi-1 significantly increased mitochondrial biogenesis, improved fusion-to-fission balance and attenuated mitochondrial dysfunction, thus inducing white-to-beige adipocyte transdifferentiation. Measurements of glucose and lipid oxidation in adipocytes revealed that both leptin and mdivi-1 increase substrates oxidation while in vivo determination of blood glucose concentration showed decreased levels by 50% in ob/ob mice, almost to the wt level. CONCLUSIONS: Pharmacological targeting of Drp-1 fission protein may be a potential novel therapeutic tool for obesity and type 2 diabetes.

Improvement in fetal pulmonary hypertension and maturity after reversal of ductal constriction: prospective cohort study.

OBJECTIVES: To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial flow acceleration time to ejection time (AT/ET ratio), increases after reversal of fetal ductus arteriosus constriction by reducing maternal intake of the causal agent (prostaglandin inhibitors, such as polyphenol-rich foods or non-steroidal anti-inflammatory drugs), and that these effects are independent of gestational age, which are inferences not yet demonstrated in the clinical setting. METHODS: This was a prospective cohort study comparing Doppler echocardiographic ductal flow dynamics, MPAP and pulmonary arterial flow AT/ET ratio in third-trimester fetuses (≥ 28 weeks' gestation) with ductus arteriosus constriction, at the time of diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors either by suspending the use of pharmacological agents with potential for prostaglandin inhibition or by restricting the consumption of polyphenol-rich foods. MPAP was estimated using the Dabestani equation (MPAP = 90 - (0.62 × AT)), and pulmonary vascular maturity was assessed using the AT/ET ratio, according to reported validation studies. Student's t-test was used for comparison of variables at diagnosis with those after reversal of ductal constriction. Change in MPAP and pulmonary AT/ET ratio between the two assessments was compared with the expected change in the same gestational period in normal fetuses based on reference curves of MPAP and pulmonary AT/ET ratio constructed in normal fetuses from healthy pregnant women at 19-37 weeks' gestation, encompassing the same gestational age range as the study group (28-37 weeks). RESULTS: Seventy pregnancies with fetal ductus arteriosus constriction were included in the study. After 2 weeks of reduced maternal intake of prostaglandin inhibitors, normalization of mean systolic (change from 1.86 ± 0.34 m/s at diagnosis to 1.38 ± 0.41 m/s; P < 0.001) and diastolic (change from 0.41 ± 0.11 m/s to 0.21 ± 0.065 m/s; P < 0.001) ductal velocities and of mean pulsatility index (change from 1.99 ± 0.20 to 2.55 ± 0.42; P < 0.001) was demonstrated. MPAP decreased between the assessments (change from 66.7 ± 6.90 mmHg at diagnosis to 54.5 ± 6.70 mmHg after 2 weeks; P < 0.001) and mean pulmonary AT/ET ratio increased (change from 0.20 ± 0.06 to 0.33 ± 0.07; P < 0.001). Change in MPAP between diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors was -12.2 ± 0.30 mmHg, which was 5.3-times higher than that in 305 normal fetuses over 2 weeks during the same gestational period (-2.3 ± 0.19 mmHg) (P < 0.001), and change in pulmonary AT/ET ratio between the two assessments was 0.13 ± 0.08, which was 8.7-times higher than that in normal fetuses in the same gestational period (0.015 ± 0.08) (P < 0.001). CONCLUSIONS: Resolution of fetal ductal constriction is followed by a fall in MPAP and by an increase in pulmonary vascular maturity, to a significantly greater degree than is observed in normal fetuses in the same gestational-age period. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Understanding Allogrooming Through a Dynamic Social Network Approach: An Example in a Group of Dairy Cows.

For gregarious species such as domestic cattle, the social environment is a very important determinant of their welfare and fitness. Understanding the complexity of cows' relationships can assist the development of management practices that are more integrated with the cows' social behavioral processes. The two aims of this study were: (1) to determine the dynamics of affiliative relationships, as indicated by allogrooming, by means of stochastic actor-oriented modeling, in dairy cows during early lactation; (2) to explore the underlying processes and the individual attributes, such as age, social rank and reproductive state, that could shape network pattern changes in grooming contacts between individual. We observed the allogrooming behavior of a dynamic group of 38 dairy cows for 4 h per day for 30 days. Using stochastic actor-oriented models, we modeled the dynamics of weekly contacts and studied how structural processes (e.g., reciprocity, transitivity, or popularity) and individual attributes (i.e., age, social rank, and reproductive state) influence network changes. We found that cows tended to groom individuals that had previously groomed them, implying a possible cooperation. Cows that groomed more actively did not appear to have a preference for specific individuals in the herd, and in return, tended to be groomed by fewer cows over time. Older individuals groomed more cows than younger ones, indicating that allogrooming could be related to seniority. Cows groomed mainly individuals of similar age, suggesting that familiarity and growing up together enhanced social grooming. Over time, cows with higher social rank were groomed by fewer cows and individuals recently reintroduced to the group groomed more herdmates. The study of social network dynamics can be used to better understand the complexity and non-linearity of cow relationships. Our findings, along with further research, can complement and strengthen the design of improved management practices that are more in line with the natural social behavior of cows.

Multilayer hazes over Saturn's hexagon from Cassini ISS limb images.

In June 2015, Cassini high-resolution images of Saturn's limb southwards of the planet's hexagonal wave revealed a system of at least six stacked haze layers above the upper cloud deck. Here, we characterize those haze layers and discuss their nature. Vertical thickness of layers ranged from 7 to 18 km, and they extended in altitude ∼130 km, from pressure level 0.5 bar to 0.01 bar. Above them, a thin but extended aerosol layer reached altitude ∼340 km (0.4 mbar). Radiative transfer modeling of spectral reflectivity shows that haze properties are consistent with particles of diameter 0.07-1.4 µm and number density 100-500 cm-3. The nature of the hazes is compatible with their formation by condensation of hydrocarbon ices, including acetylene and benzene at higher altitudes. Their vertical distribution could be due to upward propagating gravity waves generated by dynamical forcing by the hexagon and its associated eastward jet.

Eye lens radiation exposure in paediatric interventional treatment of retinoblastoma.

Retinoblastoma represents 3% of cancers in children under fifteen years of age. The standard paediatric treatment for saving the affected eye is supraselective intra-arterial chemotherapy performed in interventional rooms. In order to address the radiation toxicity due to the angiography, the aim of this study was to determine the typical dose value corresponding to the procedure, estimate the paediatric patients' eye lens dose and study the relationship between dose indicators and dose to the lens. An automatic dose management software was installed in two interventional rooms to obtain the distribution of the dose indicators kerma-area product and reference-point air kerma, getting a typical value 16 Gy·cm2 and 130 mGy, respectively (n = 35). The eye lens dose estimates were obtained with photoluminescent dosimeters placed on the patient's eyelids. In the left eye, the entrance surface air kerma was 44.23 ± 2.66 mGy, and 12.72 ± 0.89 mGy in the right eye (n = 10). There was a positive correlation between dose to the lens per procedure and dose indicators, with R2 > 0.65 for both eyes. Based on this information, the threshold for the onset of radiation-induce cataracts (500 mGy) will be exceeded if the treatment is performed for more than 8 sessions.

El impacto de los espacios formativos acerca de las competencias sociales y laborales en la carrera de medicina veterinaria

El presente trabajo da cuenta de una propuesta de espacios formativos destinados a la adquisición de habilidades sociales en los estudiantes próximos a finalizar la carrera de Medicina Veterinaria de la Facultad de Ciencias Veterinarias de la Universidad Nacional del Litoral, Argentina. Dichos espacios, brindados desde el Servicio de Orientación Educativa, se organizaron en cuatro talleres inspirados en la teoría de las habilidades sociales y laborales. Los cuatro ejes principales fueron autoconocimiento, inserción laboral, habilidades sociales y competencias laborales. Los cuatros ejes principales fueron: autoconocimiento, inserción laboral, habilidades sociales y competencias laborales. El valor pedagógico de la propuesta se evaluó a través de la aplicación de encuestas de opinión y valoraciones de frases significativas. La metodología de abordaje se caracterizó por ser cualitativa, consistente en una estrategia de intervención dentro del ámbito educativo. Algunos resultados preliminares dan cuenta de la necesidad de articular talleres de habilidades sociales a la estructura curricular de la formación universitaria. Los protagonistas de este proceso enfatizan la significatividad que aportan estos espacios como oportunidades válidas para su formación, a la vez que se transforman en instancias de aprendizaje compartido.

The present work accounts for a proposal of training spaces aimed at the acquisition of social skills in students close to finishing the career of Veterinary Medicine of the Faculty of Veterinary Sciences of Universidad Nacional del Litoral, Argentina. These spaces, provided by the Educational Guidance Service, were organized in four workshops inspired by the theory of social and work skills. The four main axes were self-knowledge, labor insertion, social skills and labor competencies. The four main axes were: self-knowledge, labor insertion, social skills and labor competencies. The pedagogical value of the proposal was evaluated through the application of opinion surveys and judgments of significant sentences. The approach methodology was characterized as being qualitative, consisting of an intervention strategy within the educational environment. Some preliminary results show the need to articulate social skills workshops to the curricular structure of university education. The protagonists of this process emphasize the significance that these spaces provide as valid opportunities for their formation, while they are transformed into instances of shared learning.

[Transient reading disorders associated with interictal epileptiform paroxysmal discharges in invasive videocorticography]. / Trastornos transitorios de la lectura asociados a descargas paroxisticas epileptiformes interictales en videocorticografia invasiva.

INTRODUCTION: Epilepsy in pediatric age are frequently associated with cognitive disorders. Different studies correlated the presence of transient cognitive disorders with the presence of interictal epileptiform discharges (IEDs). CASE REPORT: A 23-year-old woman with pharmacoresistant focal epilepsy was evaluated with invasive videoEEG in the context of epilepsy surgery. There were selected 300 periods of 10 seconds duration from the invasive videoEEG, which were classified into two groups. Group 1 showed IEDs restricted to the cortex of the middle frontal gyrus, inferior temporal gyrus, left lateral and medial occipitotemporal gyrus (dominant hemisphere). In group 2, IEDs was observed in the upper and middle frontal gyrus, precentral, the inferior and middle temporal left gyrus. The patient read the same text during the selected peirods. The number of words read in each period was counted. The working memory was evaluated by the inverse digit test. In group 1, the average number of words read was 10.2 (95% CI: 10.04-10.35); in group 2 it was 2.3 (95% CI: 2.12-2.27; t(146) = 94.55; p < 0.0001). In group 1, the average of inverse digits was 4.05 (95% CI: 3.81-4.30); in group 2 it was 2.67 (95% CI: 2.48-2.86; t(33) = 10.34; p < 0.0001). CONCLUSIONS: Our finding allows us to infer that the interference of IEDs in the cortex of the upper and middle frontal gyrus, precentral, middle and lower temporal gyrus of the dominant hemisphere, causes a dysfunction of neural networks involved in reading.

TITLE: Trastornos transitorios de la lectura asociados a descargas paroxisticas epileptiformes interictales en videocorticografia invasiva.Introduccion. La epilepsia en la edad pediatrica se asocia frecuentemente a trastornos cognitivos. Distintos estudios correlacionaron la presencia de trastornos cognitivos transitorios con la presencia de descargas epilepticas interictales (DEI). Caso clinico. Mujer de 23 años, con epilepsia focal farmacorresistente evaluada con videoelectroencefalograma (video-EEG) invasivo en el contexto de cirugia de la epilepsia. Del video-EEG invasivo se seleccionaron 300 epocas de 10 s de duracion, que se clasificaron en dos grupos. El grupo 1 evidencio DEI restringidas a la corteza del giro frontal medio, el giro temporal inferior y los giros occipitotemporales lateral y medial izquierdos (hemisferio dominante). En el grupo 2 se observaron DEI en el giro frontal superior y medio, el giro precentral y los giros temporales medio e inferior izquierdos. La paciente leyo el mismo texto durante las epocas seleccionadas. Se contabilizo el numero de palabras leidas en cada epoca. Se evaluo la memoria de trabajo mediante la prueba de digitos inversos. En el grupo 1, la media de palabras leidas fue de 10,2 (IC 95%: 10,04-10,35); en el grupo 2, de 2,3 (IC 95%: 2,12-2,27; t(146) = 94,55; p < 0,0001). En el grupo 1, la media de digitos inversos fue de 4,05 (IC 95%: 3,81-4,30); en el grupo 2, de 2,67 (IC 95%: 2,48-2,86; t(33) = 10,34; p < 0,0001). Conclusion. El hallazgo permite inferir que la interferencia de las DEI en la corteza del giro frontal superior y medio, el giro precentral, y los giros temporales medio e inferior del hemisferio dominante provoca una disfuncion de las redes neuronales implicadas en los mecanismos de la lectura.

Healthcare accreditation as trigger of organisational change: The view of professionals.

BACKGROUND: Healthcare accreditation seeks to promote the organisational change in healthcare organisations from an approach that values the level of progress achieved through a validated reference framework. The aim of this paper is to analyse the role played by accreditation through the experience perceived by health professionals during the process of self-assessment and external evaluation, taking into account three dimensions of analysis: focus on the patient, internal organisation and leadership, and impact on the clinical aspects of healthcare. MATERIAL AND METHODS: Design: Semi-structured interviews with key informants from clinical management units (CMU) within the Andalusian Health System (Spain). PARTICIPANTS: The key informants in each CMU were the clinical leader, the head of nursing and two health professionals (doctors and nurses). A qualitative research protocol was employed to conduct the semi-structured interviews (n=52 interviews) with physicians and nurses, in order to analyse their experience with the accreditation process. RESULTS: The analysis identified four main outcomes related to the accreditation process perceived by professionals: (1) A benchmarking conceptualisation of the process; (2) Improvements in patient-centred care, quality of clinical records, and organisational culture of the units; (3) Improvement of patient safety culture; (4) As negative outcomes, a slight perception of bureaucratisation and standardisation of the clinical practice. CONCLUSIONS: The described initiative of accreditation process in Andalusia (Spain) is widely perceived as positive by health professionals since it fosters the organisational change, although it also has a slightly negative bureaucratisation effect on clinical practice.

Deep sequencing and miRNA profiles in alcohol-induced neuroinflammation and the TLR4 response in mice cerebral cortex.

Alcohol abuse can induce brain injury and neurodegeneration, and recent evidence shows the participation of immune receptors toll-like in the neuroinflammation and brain damage. We evaluated the role of miRNAs as potential modulators of the neuroinflammation associated with alcohol abuse and the influence of the TLR4 response. Using mice cerebral cortex and next-generation sequencing (NGS), we identified miRNAs that were differentially expressed in the chronic alcohol-treated versus untreated WT or TLR4-KO mice. We observed a differentially expression of miR-183 Cluster (C) (miR-96/-182/-183), miR-200a and miR-200b, which were down-regulated, while mirR-125b was up-regulated in alcohol-treated WT versus (vs.) untreated mice. These miRNAs modulate targets genes related to the voltage-gated sodium channel, neuron hyperexcitability (Nav1.3, Trpv1, Smad3 and PP1-γ), as well as genes associated with innate immune TLR4 signaling response (Il1r1, Mapk14, Sirt1, Lrp6 and Bdnf). Functional enrichment of the miR-183C and miR-200a/b family target genes, revealed neuroinflammatory pathways networks involved in TLR4 signaling and alcohol abuse. The changes in the neuroinflammatory targets genes associated with alcohol abuse were mostly abolished in the TLR4-KO mice. Our results show the relationship between alcohol intake and miRNAs expression and open up new therapeutically targets to prevent deleterious effects of alcohol on the brain.

Tratamiento endovascular de aneurismas micóticos de aorta: reporte de tres casos / Endovascular treatment of mycotic aortic aneurysms: A report of three cases

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Increase of prostaglandin E2 in the reversal of fetal ductal constriction after polyphenol restriction.

OBJECTIVE: Anti-inflammatory substances that inhibit the synthesis of prostaglandins, such as non-steroidal anti-inflammatory drugs (NSAIDs) and polyphenol-rich foods, can cause constriction of the fetal ductus arteriosus. This study aimed to test the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods, in the third trimester of pregnancy, is accompanied by increased plasma levels of prostaglandin E2 (PGE2). METHODS: This was a controlled clinical trial of women with singleton pregnancy ≥ 28 weeks undergoing fetal echocardiography. The intervention group included pregnancies with diagnosis of fetal ductal constriction and not exposed to NSAIDs. The control group consisted of third-trimester normal pregnancies. Both groups answered a food frequency questionnaire to assess the amount of total polyphenols in their diet, underwent Doppler echocardiographic examination and had blood samples collected for analysis of plasma levels of PGE2. Intervention group participants received dietary guidance to restrict the intake of polyphenol-rich foods. The assessments were repeated after 2 weeks in both groups. RESULTS: Forty normal pregnancies were assessed in the control group and 35 with fetal ductal constriction in the intervention group. Mean maternal age (26.6 years) and mean body mass index (30.12 kg/m2 ) were similar between the two groups. Intragroup analysis showed that dietary guidance reduced the median consumption of polyphenols (from 1234.82 to 21.03 mg/day, P < 0.001), increasing significantly the plasma concentration of PGE2 (from 1091.80 to 1136.98 pg/mL, P < 0.05) in the intervention group after 2 weeks. In addition, Doppler echocardiography showed reversal of fetal ductal constriction in the intervention group. No significant changes were observed in the control group. CONCLUSIONS: Dietary intervention for maternal restriction of polyphenol-rich foods in the third trimester of pregnancy is accompanied by increase in plasma levels of PGE2 and reversal of fetal ductal constriction. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Isquemia retiniana y proliferación fibrovascular tardía asociada a coloboma de nervio óptico / Retinal ischaemia and delayed fibrovascular proliferation associated with an optic nerve coloboma

CASO CLÍNICO: Paciente con coloboma de nervio óptico izquierdo, que desarrolla tardíamente (a los 15 años de edad) proliferación fibrovascular vitreorretiniana y desprendimiento de retina traccional (DRT). Se realiza fotocoagulación retiniana sectorial con regresión del tejido proliferativo y la exudación asociada. DISCUSIÓN: Las anomalías congénitas del nervio óptico pueden asociar avascularidad e isquemia retiniana significativa y proliferación fibrovascular de aparición tardía. El tratamiento láser es efectivo para obtener la regresión del tejido neovascular y prevenir la progresión del DRT

CASE REPORT: A patient with a left optic nerve coloboma with late development (at 15 years of age) of vitreoretinal fibrovascular proliferation and tractional retinal detachment (TRD). Sectorial retinal photocoagulation was performed with regression of the proliferative tissue and exudation. DISCUSSION: Congenital optic nerve anomalies may be associated with significant retinal avascularity, ischaemia and late fibrovascular proliferation. Laser is effective for regression of the neovascular tissue and preventing TRD progression

Retinal ischaemia and delayed fibrovascular proliferation associated with an optic nerve coloboma.

CASE REPORT: A patient with a left optic nerve coloboma with late development (at 15 years of age) of vitreoretinal fibrovascular proliferation and tractional retinal detachment (TRD). Sectorial retinal photocoagulation was performed with regression of the proliferative tissue and exudation. DISCUSSION: Congenital optic nerve anomalies may be associated with significant retinal avascularity, ischaemia and late fibrovascular proliferation. Laser is effective for regression of the neovascular tissue and preventing TRD progression.

First report of Trypanosoma evansi in a canine in Argentina.

An Argentinian Dogo which suffered from anorexia, lymphadenopathy, cachexia and paresis of the hind limbs was diagnosed with trypanosomiasis in Argentina in 2013. In this study, we describe the clinical profile and its evolution as well as the molecular method employed to identify and quantify Trypanosoma evansi.

Abnormal mitochondrial fusion-fission balance contributes to the progression of experimental sepsis.

Sepsis-associated multiple organ failure is a major cause of mortality characterized by a massive increase of reactive oxygen and nitrogen species (ROS/RNS) and mitochondrial dysfunction. Despite intensive research, determining events in the progression or reversal of the disease are incompletely understood. Herein, we studied two prototype sepsis models: endotoxemia and cecal ligation and puncture (CLP)-which showed very different lethality rates (2.5% and 67%, respectively)-, evaluated iNOS, ROS and respiratory chain activity, and investigated mitochondrial biogenesis and dynamics, as possible processes involved in sepsis outcome. Endotoxemia and CLP showed different iNOS, ROS/RNS, and complex activities time-courses. Moreover, these alterations reverted after 24-h endotoxemia but not after CLP. Mitochondrial biogenesis was not elicited during the first 24 h in either model but instead, 50% mtDNA depletion was observed. Mitochondrial fusion and fission were evaluated using real-time PCR of mitofusin-2 (Mfn2), dynamin-related protein-1 (Drp1), and using electron microscopy. During endotoxemia, we observed a decrease of Mfn2-mRNA levels at 4-6 h, and an increase of mitochondrial fragmentation at 6 h. These parameters reverted at 24 h. In contrast, CLP showed not only decreased Mfn2-mRNA levels at 12-18 h but also increased Drp1-mRNA levels at 4 h, and enhanced and sustained mitochondrial fragmentation. The in vivo pretreatment with mdivi-1 (Drp1 inhibitor) significantly attenuated mitochondrial dysfunction and apoptosis in CLP. Therefore, abnormal fusion-to-fission balance, probably evoked by ROS/RNS secondary to iNOS induction, contributes to the progression of sepsis. Pharmacological targeting of Drp1 may be a potential novel therapeutic tool for sepsis.

Shared genetic factors influence risk for bipolar disorder and alcohol use disorders.

Bipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes. Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD. We examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives. All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders. The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence the risk for comorbid bipolar and AUD independent of anxiety. Our findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology.

Expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors.

We studied the expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors. The study was performed on tissue specimens obtained during surgery from patients with uterine leiomyoma and leiomyosarcoma (mean age 34 and 51 years, respectively). ACA was present in leiomyoma, leiomyosarcoma, and control myometrium. Intracellular expression of ACA varied in different types of tumors and was minimum in normal myometrium and maximum in leiomyosarcoma. Membrane localization of the protein is typical of common and cellular leiomyoma, while in the growth zones of mitotically active leiomyoma and leiomyosarcoma the reaction product was primarily located in tumor cell cytoplasm. TRA was detected in some leiomyosarcoma cells. Thus, ACA dysregulation was revealed in the growth zones of leiomyomas and in leiomyosarcomas, which manifested in enhanced expression of this protein and its detachment from the plasma membrane, which leads ACA translocation into the cytoplasm and nucleus of tumor cells and potentiates their proliferative activity.