Input-specific control of interneuron numbers in nascent striatal networks.

The assembly of functional neuronal circuits requires appropriate numbers of distinct classes of neurons, but the mechanisms through which their relative proportions are established remain poorly defined. Investigating the mouse striatum, we found that the two most prominent subtypes of striatal interneurons, parvalbumin-expressing (PV+) GABAergic and cholinergic (ChAT+) interneurons, undergo extensive programmed cell death between the first and second postnatal weeks. Remarkably, the survival of PV+ and ChAT+ interneurons is regulated by distinct mechanisms mediated by their specific afferent connectivity. While long-range cortical inputs control PV+ interneuron survival, ChAT+ interneuron survival is regulated by local input from the medium spiny neurons. Our results identify input-specific circuit mechanisms that operate during the period of programmed cell death to establish the final number of interneurons in nascent striatal networks.

Natural history of hepatitis C virus infection in a cohort of asymptomatic post-transfused subjects.

UNLABELLED: BACKGROUND & AIMS. Studies about the natural history of hepatitis C virus (HCV) infection report variable progression to cirrhosis depending on study design. Retrospective cross-sectional liver clinic studies overestimate the rate of fibrosis progression due to inclusion of patients with more severe disease leaving mild and asymptomatic patients underrepresented. We evaluated fibrosis progression in a group of "healthy" asymptomatic subjects, attending to a voluntary campaign for the detection of HCV infection. MATERIAL AND METHODS: A detection campaign was launched on subjects transfused before 1993. Of 1699 volunteers, 61(3.6%) had HCV infection. A liver biopsy was performed in 40 (65%). Assessed risk factors for liver fibrosis were: sex, body mass index, alcohol consumption (> 20 g/d - > 40g/d ), genotype, HLA-DRB1 alleles, present age, age at infection and duration of infection. RESULTS: 25 (62.5%) were women with a median age of 52.5 years. The median duration of infection was 21.5 years with a median age at infection of 27 years. As regards fibrosis, 25 (62.5%) had a Low Stage (F0-F1), 8 patients, 20%, had severe fibrosis, one patient (2.5%) had cirrhosis. Alcohol consumption was the only risk factor associated with fibrosis progression. CONCLUSIONS: The low progression to cirrhosis may be explained by the clinical characteristics of our population: asymptomatic middle-aged "healthy" subjects infected at young age. The progression to severe fibrosis was noticeable; hence a longer follow-up might demonstrate changes in this outcome. Significant alcohol consumption clearly worsens the natural history of HCV infection; this is no so evident for occasional or mild alcohol consumers.

Serotonergic regulation of bipolar cell survival in the developing cerebral cortex.

One key factor underlying the functional balance of cortical networks is the ratio of excitatory and inhibitory neurons. The mechanisms controlling the ultimate number of interneurons are beginning to be elucidated, but to what extent similar principles govern the survival of the large diversity of cortical inhibitory cells remains to be investigated. Here, we investigate the mechanisms regulating developmental cell death in neurogliaform cells, bipolar cells, and basket cells, the three main populations of interneurons originating from the caudal ganglionic eminence and the preoptic region. We found that all three subclasses of interneurons undergo activity-dependent programmed cell death. However, while neurogliaform cells and basket cells require glutamatergic transmission to survive, the final number of bipolar cells is instead modulated by serotonergic signaling. Together, our results demonstrate that input-specific modulation of neuronal activity controls the survival of cortical interneurons during the critical period of programmed cell death.

Cortical wiring by synapse type-specific control of local protein synthesis.

Neurons use local protein synthesis to support their morphological complexity, which requires independent control across multiple subcellular compartments up to the level of individual synapses. We identify a signaling pathway that regulates the local synthesis of proteins required to form excitatory synapses on parvalbumin-expressing (PV+) interneurons in the mouse cerebral cortex. This process involves regulation of the TSC subunit 2 (Tsc2) by the Erb-B2 receptor tyrosine kinase 4 (ErbB4), which enables local control of messenger RNA {mRNA} translation in a cell type-specific and synapse type-specific manner. Ribosome-associated mRNA profiling reveals a molecular program of synaptic proteins downstream of ErbB4 signaling required to form excitatory inputs on PV+ interneurons. Thus, specific connections use local protein synthesis to control synapse formation in the nervous system.

Molecular biomarkers and integrated pathological diagnosis in the reclassification of gliomas.

The present study aimed to evaluate the impact caused by the 2016 World Health Organization (WHO) diagnostic classification of gliomas in 139 patients studied in Argentina. Formalin-fixed paraffin-embedded tissues were used for histological and immunohistochemical analysis [glial fibrillary acidic protein, KI67, synaptophysin and isocitrate dehydrogenase (IDH)1-R132H]. DNA from formalin-fixed paraffin-embedded tissues was used for molecular analysis: 1p/19q co-deletion and mutation status of the IDH gene. These experiments were performed by direct Sanger sequencing and multiplex ligation-dependent probe amplification. According to the new classification, diagnoses included oligodendroglioma IDH-mutant and 1p/19q co-deletion (4.20%), anaplastic oligodendroglioma IDH-mutant and 1p/19q co-deletion (2.52%), diffuse astrocytoma IDH-mutant (6.72%), diffuse astrocytoma IDH-wild type (1.68%), anaplastic astrocytoma IDH-mutant (5.04%), anaplastic astrocytoma IDH-wild type (8.40%), glioblastoma IDH-mutant (5.88%) and glioblastoma IDH-wild type (65.56%). Regarding tumor histology, 60% of oligodendrogliomas, 35% of astrocytoma and 100% of unclassified gliomas were re-classified, while glioblastomas maintained their initial classification. Additionally, the present study evaluated the prognostic value of the histological grade for the 2007 and 2016 WHO classifications of gliomas. The histological subgroup associated with longer overall survival (OS) was grade II glioma (OS-2007WHO, 35.6 months; and OS-2016WHO, 47.7 months). Glioblastoma was the subgroup associated with a poor outcome (OS-2007WHO, 10.4 months; and OS-2016WHO, 11.1 months). The present study evaluated the OS of tumor grade subgroups with respect to their IDH status. For all subgroups, IDH-mutant tumors were associated with an improved prognosis compared with IDH-wild type tumors. The results suggested that the incorporation of molecular biomarkers in the new WHO classification improves tumor characterization and prognostic value of the subgroups.

[Dexketoprofene, selective cox-1 inhibitor nsaids, without gastrointestinal injury in rats]. / Dexketoprofeno. Aine preferencial inhibidor COX-1, sin lesión gastrointestinal, en ratas.

Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition.

Efecto del ultrasonido quirúrgico de alta potencia en el tejido dérmico y adiposo. Estudio experimental para aplicación en marcación abdominal / Effect of high level surgical ultrasound in dermic and fat tissue. Experimental study for use in abdominal marking

Antecedentes y Objetivos. El concepto de marcación abdominal o six packs ha incrementado su demanda entre los pacientes que consultan por remodelación corporal. El uso en liposucción del ultrasonido quirúrgico de tercera generación permite mejorar los resultados y lograr mayor definición de las zonas tratadas. Sin embargo, no está exento de complicaciones como quemaduras cutáneas. Nos planteamos demostrar la potencia y el tiempo de contacto cutáneo perjudicial para la piel. Material y Método. Desarrollamos un estudio experimental sobre 15 piezas de dermolipectomía empleando potencias de ultrasonido del 70% y del 100%, sometiendo las áreas predeterminadas a 15, 30, 45 y 60 segundos de acción sobre la dermis, y estudiándolas después por histopatología. Resultados. A potencia del 100% y más de 15 segundos próximos a la piel se desarrollaron áreas de epidermólisis (quemaduras de 2º grado), mientras que observamos rangos de seguridad, sin cambios histológicos, con el uso al 70% y 60 segundos en contacto directo con la dermis. Conclusiones. Este trabajo pretende, a través de un estudio experimental, dar parámetros de seguridad que ofrezcan tranquilidad al cirujano plástico cuando emplea el ultrasonido quirúrgico para liposucción en zonas próximas a la dermis (AU)

Background and Objectives. The concept of abdominal marking or six packs has increased its demand among patients who consult for body contouring. The use of ultrasound assisted lipoplasty third generation has improved results in body contouring and has achieved greater definition of the treated areas. But this is not exempt of complications, such as skin burns. Our aim is to demonstrate the power and time of detrimental cutaneous contact with the patient's skin. Methods. We developed an experimental study in 15 dermolipectomy specimens using powers of ultrasound at 70 y 100% and modifying action on the dermis exposure time from 15 to 30, 45 and 60 seconds These areas were studied by histopathology. Results. Our data showed that at 100% power and 15 seconds next to the skin, epidermolysis (2 degree burns) was developed, while the safety ranges (no histological changes) were observed using 70% power and 60 seconds in direct contact with the dermis. Conclusions. This paper intends, through an experimental study, giving security settings when using surgical ultrasound for liposuction in the proximity of cutaneous areas (AU)

Association between Helicobacter pylori infection and cirrhosis in patients with chronic hepatitis C virus.

We evaluated, employing a logistic regression model, the association between Helicobacter pylori infection and cirrhosis in a cohort of 106 patients (57 males; mean age, 52.9 years; range, 20-78 years) with chronic hepatitis C virus (HCV) from Rosario, Argentina. HCV was confirmed by ELISA and PCR. H. pylori status was determined by ELISA. Of the 106 patients evaluated, 47 (44.3%) had cirrhosis. A total of 70.2% (33/47) of cirrhotic patients and 47.5% (28/59) of noncirrhotic patients were H. pylori-positive. In univariate analyses, cirrhosis was associated with age (P = 0.016) and H. pylori-positive status (P = 0.019) but not with gender (P = 0.28) or length of infection (P = 0.35). In multivariate analysis, H. pylori infection (P = 0.037; OR = 2.42; 95% CI = 1.06-5.53) and age (P = 0.033; OR = 1.04; 95% CI = 1.00-1.07) of patients remained significant and independently associated with cirrhosis. In conclusion, our results demonstrate an association between H. pylori infection and cirrhosis in patients with hepatitis C virus.

Dexketoprofeno. Aine preferencial inhibidor COX-1, sin lesión gastrointestinal, en ratas. / [Dexketoprofene, selective cox-1 inhibitor nsaids, without gastrointestinal injury in rats]

Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition.

Dexketoprofeno: aine preferencial inhibidor COX-1, sin lesión gastrointestinal, en ratas / Dexketoprofene, selective cox-1 inhibitor nsaids, without gastrointestinal injury in rats

Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition

Dexketoprofeno: aine preferencial inhibidor COX-1, sin lesión gastrointestinal, en ratas / Dexketoprofene, selective cox-1 inhibitor nsaids, without gastrointestinal injury in rats

Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition (AU)