Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions.

Morphological and genetic characterisation of the root system architecture of selected barley recombinant chromosome substitution lines using an integrated phenotyping approach.

Discoveries on the genetics of resource acquisition efficiency are limited by the ability to measure plant roots in sufficient number and with adequate genotypic variability. This paper presents a root phenotyping study that explores ways to combine live imaging and computer algorithms for model-based extraction of root growth parameters. The study is based on a subset of barley Recombinant Chromosome Substitution Lines (RCSLs) and a combinatorial approach was designed for fast identification of the regions of the genome that contribute the most to variations in root system architecture (RSA). Results showed there was a strong genotypic variation in root growth parameters within the set of genotypes studied. The chromosomal regions associated with primary root growth differed from the regions of the genome associated with changes in lateral root growth. The concepts presented here are discussed in the context of identifying root QTL and its potential to assist breeding for novel crops with improved root systems.

Hybrid model based on Genetic Algorithms and SVM applied to variable selection within fruit juice classification.

Given the background of the use of Neural Networks in problems of apple juice classification, this paper aim at implementing a newly developed method in the field of machine learning: the Support Vector Machines (SVM). Therefore, a hybrid model that combines genetic algorithms and support vector machines is suggested in such a way that, when using SVM as a fitness function of the Genetic Algorithm (GA), the most representative variables for a specific classification problem can be selected.

Genetic control of rhizosheath formation in pearl millet.

The rhizosheath, the layer of soil that adheres strongly to roots, influences water and nutrients acquisition. Pearl millet is a cereal crop that plays a major role for food security in arid regions of sub-Saharan Africa and India. We previously showed that root-adhering soil mass is a heritable trait in pearl millet and that it correlates with changes in rhizosphere microbiota structure and functions. Here, we studied the correlation between root-adhering soil mass and root hair development, root architecture, and symbiosis with arbuscular mycorrhizal fungi and we analysed the genetic control of this trait using genome wide association (GWAS) combined with bulk segregant analysis and gene expression studies. Root-adhering soil mass was weakly correlated only to root hairs traits in pearl millet. Twelve QTLs for rhizosheath formation were identified by GWAS. Bulk segregant analysis on a biparental population validated five of these QTLs. Combining genetics with a comparison of global gene expression in the root tip of contrasted inbred lines revealed candidate genes that might control rhizosheath formation in pearl millet. Our study indicates that rhizosheath formation is under complex genetic control in pearl millet and suggests that it is mainly regulated by root exudation.

Flared Roots Reinforced With Bulk-fill Flowable Composite - Case Report.

This article presents a case report for the treatment of a patient with a flared root. The patient was treated with a bulk-fill flowable composite. This innovative approach seems to be efficient in reinforcing flared roots. The advantages and disadvantages of the technique are presented.

[Drug-induced arterial hypertension]. / Hypertension artériette induite par les médicaments.

In a few clinical cases, controlling arterial hypertension is really very difficult even when using the appropriate treatment(s) at the optimal dosage. In such cases, it is crafty to research any possible drug interferences with the antihypertensive treatment. Two clinical cases will illustrate that arterial hypertension can be either induced or very difficult to control due to opposite physiopathological mechanisms of drugs or to pharmacokinetic interactions. A review of the main interacting drug regimens will complete this paper, attesting that drugs as various as NSAID, corticosteroids, erythropoietin, cyclosporine, antidepressants, beta blockers, carbamazepine, sympathomimetics, antihistamines, tramadol and (...) can induce arterial hypertension.

The effect of C content on the mechanical properties of Ti-Zr coatings.

In this study, Ti-Zr and Ti-Zr-C coatings were deposited at room temperature via pulsed-DC magnetron sputtering. A 70Ti-30Zr at% target and a 99.99% graphite plate were used to deposit samples. In order to modify C content, coatings were deposited at different target powers such as 50, 75 and 100 W. Changes on the structure, microstructure and mechanical properties due to C addition were studied. Results indicate that the as-deposited coatings were partly crystalline and that an increment on C content stabilized α' phase and inhibited the appearance of ω precipitates. Therefore, Ti-Zr-C alloys with C>1.9 at% showed only α' phase whereas the others alloys exhibited α'+ω structures. Hardness values from 12.94 to 34.31 GPa were obtained, whereas the elastic modulus was found between 181.84 and 298 GPa. Finally, a high elastic recovery ratio (0.69-0.87) was observed as a function of composition. The overall properties of these coatings were improved due to C content increment, martensitic α' phase and nanocrystalline grain size (10-16 nm).

Cytomegalovirus antigenemia in acquired immunodeficiency syndrome patients with untreated cytomegalovirus retinitis.

PURPOSE: To determine the frequency of cytomegalovirus (CMV) viremia in patients with acquired immunodeficiency syndrome (AIDS) and untreated CMV retinitis using conventional cell culture isolation and the sensitive CMV antigenemia assay. METHODS: We examined 24 AIDS patients with ophthalmologic diagnosis of untreated CMV retinitis and 24 AIDS patients without present or past retinitis (control patients) from three medical centers between September 1992 and March 1994. Cytomegalovirus antigenemia was detected by an indirect peroxidase staining in 300,000 cytocentrifuged neutrophils, using a mixture of murine monoclonal antibodies directed against the pp65 lower matrix protein of CMV. RESULTS: Positive antigenemia was demonstrated in eight (33.3%) of the 24 retinitis patients and in none of the 24 control patients (P < .001). Only two of the eight antigenemia-positive patients had a concurrent positive CMV isolation from blood leukocytes by conventional cell culture assay. CONCLUSIONS: These results emphasize the risk of extraocular disease in AIDS patients with CMV retinitis because the virus is often present in peripheral blood leukocytes. The CMV antigenemia assay may be a simple and rapid means of identifying those patients with unilateral retinitis at highest risk of developing CMV retinitis of the fellow eye or of visceral CMV disease if intravitreal injections or implants are used as sole treatment for CMV retinitis.

Herpes simplex virus type 2 infection in pregnancy: asymptomatic viral excretion at delivery and seroepidemiologic survey of two socioeconomically distinct populations in São Paulo, Brazil.

The objective of the present study was to estimate the prevalence of herpes simplex virus type 2 (HSV 2) antibodies in child bearing women of 2 Brazilian populations with different socioeconomic status and to determine the risk of neonatal HSV exposure by means of maternal cultures at the onset of labor. The study was conducted at 2 hospitals: A, serving very low income patients and B, serving middle socioeconomic class. 173 participants from group A and 127 from B answered a questionnaire which showed that the patients had similar ages (27.7 and 26.8 years, respectively) but differed with regard to socioeconomic status, age at first intercourse (18.6 vs 20.6 years), number of sex partners (1.5 vs 1.2) and previous sexually transmitted diseases (15% vs. 1.5%). History of genital herpes was given by 11% of group A participants and by a similar number, 7%, of patients from group B. In addition, 200 serum samples from population A and 455 from B were tested by ELISA for anti HSV antibodies and 92% and 86%, respectively, were found to be positive. Sixty seropositive samples from group A and 90 from B were further analyzed by Western blot, which showed the presence of type 2 specific antibodies in 46% and 36%, respectively, suggesting an overall HSV 2 prevalence of 42% in group A and 31% in B. Cervical specimens were obtained for culture from 299 asymptomatic patients of population A and 313 of B. HSV was isolated from one specimen in each group, indicating a 0.3% incidence of asymptomatic viral excretion in both populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytomegalovirus infection in children with Down syndrome in a day-care center in Brazil.

This study evaluates the transmission of CMV infection in 120 children aged 1 to 15 years with Down syndrome who attended a day-care center for handicapped children in São Paulo, Brazil. A blood sample was obtained from each children at the beginning of the study for detection of IgG and IgM cytomegalovirus (CMV) antibodies by an immunofluorescence assay. Samples of saliva and urine were obtained every 3 months from the children with CMV antibodies to detect shedding of the virus by culture in human foreskin fibroblasts, by detection of pp65 CMV-antigen and by a nested PCR assay. The prevalence of anti CMV-IgG antibodies was 76.6% (92/120), and IgM anti-CMV antibodies were detected in 13% (12/92) of the seropositive children. During the first viral evaluation, CMV was detected in the urine and/or saliva in 39/90 (43.3%) of the seropositive children. In the second and third evaluations, CMV was detected in 41/89 (46%) and in 35/89 (39.3%) children, respectively. Detection of CMV was shown both in urine and saliva in 28/39 (71.8%), 19/41(46.3%) and 20/35 (57.1%) of the children excreting the virus, respectively. Additionally, in 3(3/4)9 (67.4%) of the excreters CMV could be demonstrated in urine or saliva in at least two out of the three virological evaluations carried out sequentially in a six month period. Of the 28 initially seronegative children, 26 were re-examined for anti-CMV IgG antibodies about 18 months after the negative sample; seroconversion was found in 10/26 (38.5%). Taking all 536 samples of urine or saliva examined by virus culture and pp65 antigen detection during the study into account, 159 (29.6%) were positive by virus culture and 59 (11%) gave a positive result with the pp65 assay. These data demonstrate the high prevalence of CMV shedding and the high risk of CMV infection in children with Down syndrome attending a day-care center for mentally handicapped patients. The virus culture was more sensitive than the pp65 CMV antigen assay for CMV detection in both urine and saliva samples.

[Isolation, sequencing and ultrastructure of HTLV-I and HTLV-II retroviruses. Presence of the HTLV-II subtype b among Spanish intravenous drug addicts]. / Aislamiento, secuenciación y ultraestructura de los retrovirus HTLV-I y HTLV-II. Presencia del HTLV-II subtipo b entre adictos a drogas por vía parenteral españoles.

BACKGROUND: Six cases of HTLV-I/II infection were selected for isolation and characterization of these retrovirus. METHODS: Detection of anti-HTLV antibodies was carried out by enzyme immunoassay (EIA), immunofluorescence (IFI), and Western blot (WB). Analysis of proviral DNA was performed by PCR. Viral culture and partial sequencing of the pol and pX genes were carried out. Electron microscopy morphologically characterized the viral particles. RESULTS: Serologic study demonstrated four cases of HTLV-II, one of HTLV-I, and one non-typeable HTLV infections. This last case was confirmed as positive for HTLV-II by PCR. Five new HTLV-II and one HTLV-I infected cell lines have been established by co-culture. Electron microscopy allowed morphologic characterization of the viral particles found in the infected cells. The sequence of the five strains of HTLV-II was identical demonstrating a divergence of 0.49% in the pX region and of 4.5% in the pol region compared with the HTLV-II Mo prototype. Comparison of these sequences with those corresponding to different strains of HTLV-II isolates from American Indians (subtypes b) suggest that these Spanish strains are more closely related with the subtype b than with the subtype a (HTLV-II Mo). Genetic variability study did not reveal any change in the sequence of these stains suggesting that the variability of these retroviruses in very infrequent in the regions studied. The analysis of the pol region of the HTLV-I strain demonstrated a divergence of 3.4% with respect to the sequence of the ATK-1 prototype (Japan) and of 1.7% of the strain HS-35 (Caribbean) showing a greater relation with the Caribbean strains than with those from Japan. CONCLUSIONS: The presence of HTLV-II subtype has been confirmed among intravenous drug addicts in Spain. Isolation and characterization of the HTLV-I strain demonstrated that this also circulating around Spain despite its South American origin.

Regulation of energy metabolism and mitochondrial function in skeletal muscle during lipid overfeeding in healthy men.

CONTEXT/OBJECTIVE: The aim of this study was to evaluate the regulation of the fuel partitioning and energy metabolism in skeletal muscle during lipid overfeeding in healthy men. Design/Participants/Intervention: Thirty-nine healthy volunteers were overfed for 56 days with a high-fat diet (3180 kJ/d). Energy metabolism (indirect calorimetry) was characterized in the fasting state and during a test meal before and at the end of the diet. Skeletal muscle biopsies were taken at day 0 and day 56. MAIN OUTCOME MEASURES: Change in gene expression, mitochondrial respiration, nicotinamide adenine dinucleotide (NAD(+)) content, and acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in skeletal muscle was measured. RESULTS: Overfeeding increased body weight (+2.6 kg) and fat mass concomitantly with a shift in the use of substrates as energy fuel toward preferential oxidation of carbohydrates instead of lipids. Changes in lipid metabolic gene expression supported this observation, with a reduction in pyruvate dehydrogenase kinase 4 expression that could be the consequences of decreased NAD(+) concentration and reduced deacetylase activity of the sirtuins, as supported by hyperacetylation of PGC-1α after overfeeding. Interestingly, this reduction of the sirtuin PGC-1α pathway was associated with increased mitochondrial gene expression and higher respiration rate under these conditions. CONCLUSION: Adaptation to lipid overfeeding and regulation of fuel partitioning in human muscle appear to rely on a dissociation between the regulatory functions of the sirtuin-PGC-1α pathway on fatty acid oxidation and on mitochondrial regulation. This may facilitate lipid storage during a period of positive energy balance while maintaining mitochondrial functions and oxidative capacities.

NAD+ as a signaling molecule modulating metabolism.

The ability of NAD(+) to act as a metabolic cofactor and as a rate-limiting cosubstrate for many enzymes, particularly the sirtuins, has led to the identification of a pivotal role of NAD(+) levels in the control of whole-body metabolic homeostasis. Bioavailability and compartmentalization of NAD(+) have become highly relevant issues that we need to understand in order to elucidate how NAD(+) acts both as a readout of the metabolic milieu and as an effector triggering appropriate cellular adaptations.

Quiste epidermoide gigante en reloj de arena del piso de la cavidad oral / Giant hourglass shaped epidermoid cyst in the floor of mouth

El quiste epidermoide es un quiste de tejido blando de origen ectodérmico que se encuentra con poca frecuencia en la cavidad oral. Clínicamente se caracteriza por ser una lesión asintomática, de larga evolución, recubierta con mucosa normal, y usualmente se diagnostica cuando el aumento de volumen genera molestias en el paciente. El tratamiento varía de acuerdo a su tamaño y localización anatómica. Presentamos el caso de una paciente de 29 años de edad con un quiste epidermoide de gran tamaño, en reloj de arena, del piso de boca. Se describen las características específicas histológicas y clínicas, y se discute la conducta terapéutica seguida.

The epidermoid cyst is a soft tissue cyst of ectodermal origin found infrequently in the oral cavity. Clinically, it is characterized by an asymptomatic lesion, of long evolution, covered with normal mucosa, and is usually diagnosed when the volume increases and generates patient discomfort. Treatment varies according to its size and anatomical location. We report the case of a 29 year old patient with a large, hourglass shaped, epidermoid cyst in the floor of the mouth. Specific histological and clinical characteristics are described and the therapeutic behavior followed is discussed.

[Percutaneous Endoscopic Gastrostomy (PEG): ten years of experience]. / Gastrostomía Endoscópica Percutánea (PEG): diez años de experiencia.

INTRODUCTION: The PEG is shown as a technique rather aggressive and with few complications. These characteristics have become the route of choice for enteral nutrition in patients who require nutritional support for prolonged periods. OBJECTIVES: To know the evolution and quality of life of patients and caregivers with nutrition through PEG. METHODS: Retrospective study of patients with PEG in a district hospital from July 1998 to July 2009. We reviewed hospital records and telephone contact with patients. RESULTS: There were 299 patients with PEG during the study period. There was a gradual increase in its use for nutritional therapy. Males were 152 (50.8%). There were 152 (50,8%) males. The age was 73.62 ± 13,05 years, males being the youngest (t = 5.07, P < 0.001). The most frequent indication was "neurological disease" 222 (85.7%). The duration of nutrition therapy was 390 days (range 1-2,913) showing independent from the rest of the variables. The completion of treatment was on death 134 (93.1%) or recovering the mouth 10 (6.9%). The QL was significantly improved in both patients (Z = -6.59, p < 0.001) and caregivers (Z = -6.83, P < 0.001) after PEG. CONCLUSIONS: There is a progressive increase in the use of PEG. with the mean time of treatment greater than one year, and being complete in most patients with the death. The quality of life experienced an improvement after PEG in both patients and caregivers in this series.

Contrasting effects of immunosuppression on Theiler's virus infection in mice.

In the present study, cyclophosphamide and rabbit anti-mouse thymocyte serum were used to immunosuppress SJL/J mice infected with Theiler's mouse encephalomyelitis virus (TMEV) in order to delineate the potential mechanism(s) of virus-induced cellular injury in this infection. Whereas both immunosuppressive agents produced a significant increase in mortality, this treatment had differing effects on the pathological involvement of gray and white-matter structures in the central nervous system. The central nervous system of immunosuppressed TMEV-infected mice had increased microglial cell proliferation and neuronal necrosis, longer maintenance of high virus levels and spread of virus antigen to involve the neocortex and hippocampal complex. These observations indicate that TMEV causes a cytolotic infection of neurons and possibly other cells in gray matter. In contrast, immunosuppression produced a dramatic reduction in mononuclear inflammatory cells in the leptomeninges and spinal cord white matter of infected mice and prevented demyelination. Further, virus antigen was not detected in the leptomeninges and white matter of immunosuppressed and infected mice. These findings suggest that demyelination of TMEV infection is immune mediated.

Endovascular repair of abdominal aortic aneurysm using a pararenal fenestrated stent-graft.

PURPOSE: To report an unusual case of endovascular abdominal aortic aneurysm (AAA) exclusion in which a fenestrated stent-graft was used to seal a proximal Type I endoleak. METHODS AND RESULTS: An 84-year-old man with a 6.0-cm AAA underwent an aortomonoiliac aneurysm exclusion procedure that was complicated by a proximal endoleak. Because the patient had no right kidney, an additional stent-graft was designed to cover the right renal artery stump while preserving left renal perfusion through a fenestration in the graft material. This approach was successful in obliterating the endoleak around the proximal attachment site, but flow through the lumbar arteries remained. CONCLUSIONS: The use of a fenestrated stent-graft is feasible, but the type of fenestration in this case has limited applicability owing to the rarity of patients with suitable anatomy.

Aortic stent-grafts in patients with renal transplants.

PURPOSE: To report the endovascular treatment of abdominal aortic aneurysms (AAA) in 2 patients with pelvic renal transplants. METHODS AND RESULTS: Two men with multiple comorbidities and pelvic transplant kidneys underwent endovascular AAA repair using an aortomonoiliac system with femorofemoral bypass grafting. The arterial end-to-side anastomosis in both patients was to the external iliac artery. Tapered aortomonoiliac grafts were fashioned from Gianturco Z-stents covered with Dacron graft material and implanted with the distal attachment site in the iliac system ipsilateral to the transplant kidney arterial anastomosis. The body of the stent-graft was reinforcement with a Wallstent in each case before the contralateral common iliac artery was occluded and the cross-femoral bypass constructed. Both patients recovered uneventfully from the procedure and are free of endoleak or other complications related to their aneurysm repair at 7 and 34 months. CONCLUSIONS: The presence of a pelvic renal transplant in a patient undergoing endovascular AAA repair increases the complexity of procedural planning and endograft implantation, but a good outcome can be achieved.

Endovascular repair of abdominal aortic aneurysm: getting out of trouble.

The standard techniques of endovascular aneurysm repair sometimes fail to produce atraumatic stent-graft delivery of hemostatic implantation, and additional maneuvers are required to avoid conversion to open repair. Between June 1996 and May 1997 elective endovascular aneurysm repair was performed in 33 high risk patients, using a Z-stent-based prosthesis. Challenging anatomic features included: short neck (< 15 mm) in four cases, angulated neck (> 60 degrees) in seven, iliac aneurysm in six, and iliac tortuosity (> 80 degrees) in 24. There were no deaths, no renal failure, no pulmonary failure, no graft thrombosis, no migration, and no conversions to open surgery. Deviations from standard technique were required to treat iliac artery dissection, iliac artery stenosis, and leaks resulting from proximal stent malalignment, proximal stent malposition, and distal stent malposition. The necessary adjunctive maneuvers included: additional stent placement, additional stent-graft placement, and balloon dilatation. Mean operating time was 191 +/- 72 min, mean contrast volume was 148 +/- 76 ml, and mean blood loss was 314 +/- 427 ml. Mean time from operation to discharge from the hospital was 3.5 +/- 1.67 days. These short-term results demonstrate that endovascular aneurysm repair is safe and effective in high risk patients, only if adjunctive maneuvers are available to supplement standard technique.