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Amphetamine-type psychostimulants (ATS) are used worldwide by millions of patients for several psychiatric disorders. Amphetamine (AMPH) and “ecstasy” (3,4-methylenedioxymethamphetamine or MDMA) are common drugs of abuse. The impact of chronic ATS exposure to neurons and brain aging is still undisclosed. Current neuronal culture paradigms are designed to access acute ATS toxicity. We report for the first time a model of chronic exposure to AMPH and MDMA using long-term rat cortical cultures. In two paradigms, ATS were applied to neurons at day 1 in vitro (DIV) (0, 1, 10 and 100 μM of each drug) up to 28 days (200 μM was applied to cultures up to 14 DIV). Our reincubation protocol assured no decrease in the neuronal media’s drug concentration. Chronic exposure of neurons to concentrations equal to or above 100 μM of ATS up to 28 DIV promoted significant mitochondrial dysfunction and elicited neuronal death, which was not prevented by glutamate receptor antagonists at 14 DIV. ATS failed to promote accelerated senescence as no increase in β-galactosidase activity at 21 DIV was found. In younger cultures (4 or 8 DIV), AMPH promoted mitochondrial dysfunction and neuronal death earlier than MDMA. Overall, AMPH proved more toxic and was the only drug that decreased intraneuronal glutathione levels. Meanwhile, caspase 3 activity increased for either drug at 200 μM in younger cultures at 8 DIV, but not at 14 DIV. At 8 DIV, ATS promoted a significant change in the percentage of neurons and astroglia present in culture, promoting a global decrease in the number of both cells. Importantly, concentrations equal to or below 10 μM of either drug did not promote neuronal death or oxidative stress. Our paradigm of neuronal cultures long-term exposure to low micromolar concentrations of ATS closely reproduces the in vivo scenario, being valuable to study the chronic impact of ATS. [ABSTRACT FROM AUTHOR]

Genetic studies on taste sensitivity, and bitter taste receptors (T2R) in particular, are an essential tool to understand ingestive behavior and its relation to variations of nutritional status occurring in ruminants. In the present study, we conducted a data-mining search to identify T2R candidates in sheep by comparison with the described T2R in cattle and using recently available ovine genome. In sheep, we identified eight orthologs of cattle genes: T2R16, T2R10B, T2R12, T2R3, T2R4, T2R67, T2R13 and T2R5. The in silico predicted genes were then confirmed by PCR and DNA sequencing. The sequencing results showed a 99% to 100% similarity with the in silico predicted sequence. Moreover, we address the chromosomal distribution and compare, in homology and phylogenetic terms, the obtained genes with the known T2R in human, mouse, dog, cattle, horse and pig. The eight novel genes identified map either to ovine chromosome 3 or 4. The phylogenetic data suggest a clustering by receptor type rather than by species for some of the receptors. From the species analyzed, we observed a clear proximity between the two ruminant species, sheep and cattle, in contrast with lower similarities obtained for the comparison of sheep with other mammals. Although further studies are needed to identify the complete T2R repertoire in domestic sheep, our data represent a first step for genetic studies on this field. [ABSTRACT FROM AUTHOR]

Summary: Sonic hedgehog signaling is important for human development, and aberrant regulation of this pathway can result in the development of tumors. The aim of this study was to examine the expression of sonic hedgehog signaling molecules in oral squamous cell carcinoma. By quantitative real-time polymerase chain reaction, the expression of SHH, SMO, PTCH-1, and GLI-1 was analyzed in 30 oral squamous cell carcinoma cases and 8 samples of nonneoplastic oral mucosa and associated to clinical pathologic features. The expression of β-catenin, cyclin D1, Wnt-1, and Egfr was evaluated by immunohistochemistry in 26 available cases of oral squamous cell carcinoma. Normal oral mucosa from healthy individuals was negative for all genes that were evaluated. SHH, PTCH-1, SMO, and GLI-1 were not expressed in nonneoplastic oral mucosa, and low levels of GLI-1 were observed in nonneoplastic oral mucosa that was adjacent to the tumor. All oral squamous cell carcinoma cases expressed high levels of PTCH-1, SMO, and GLI-1 and were devoid of SHH. The expression of SMO was associated with clinical stage (P = .022) and a borderline association in cervical lymph node metastasis (P = .053). PTCH-1 expression showed a strong correlation with SMO (rs = 0.64; P < .001) and GL-1 (rs = 0.70; P < .001); SMO and GLI-1 also correlated with each other (rs, 0.55; P < .001). All proteins evaluated were expressed as cyclin D1 (92% of samples), β-catenin (73%), Egfr (46%), or Wnt-1 (32%). Our data demonstrate that sonic hedgehog signaling is activated in oral squamous cell carcinoma and suggest that this pathway mediates its tumorigenesis. [ABSTRACT FROM AUTHOR]

Abstract: Lesions of the orbital prefrontal cortex (OPFC) and the nucleus accumbens core (AcbC) can disrupt performance in inter-temporal choice tasks, possibly by increasing the organism''s sensitivity to delay and/or magnitude of reinforcement. This experiment examined whether exposure to an inter-temporal choice would induce neuronal activation in these areas, as indicated by enhanced expression of the Fos protein. Twelve rats were trained to press levers A and B under an adjusting-delay schedule in which a response on A delivered 50μl of a sucrose reinforcer after 2 or 18s, whereas a response on B delivered the same reinforcer after a delay that was adjusted in accordance with the rat''s choices. Another 12 rats were trained under a similar schedule in which a response on A delivered an immediate reinforcer of size 20 or 180μl, whereas a response on B delivered an immediate reinforcer whose size was adjusted in accordance with the rat''s choices. A third group received training under a schedule that did not entail variation of reinforcer size or delay, or choice between reinforcers, and a control group underwent food restriction without behavioural training. Exposure to the adjusting-delay schedule was associated with enhanced Fos expression in both the OPFC and AcbC, whereas exposure to the adjusting-magnitude schedule was associated with enhanced Fos expression in the OPFC but not the AcbC, compared to the control group. The results are consistent with previous findings that implicated the AcbC and OPFC in delay discounting, and the OPFC in sensitivity to reinforcer size. [Copyright &y& Elsevier]

Abstract: Objective: This study aims to compare venous clinical severity scores in patients with healed venous ulcers due to varicose veins of the lower limbs (the clinical, etiologic, anatomic, and pathophysiologic data (CEAP) classification: C5 EpAsPr) treated by saphenous stripping and phlebectomy or by ultrasound-guided foam sclerotherapy. Method: Sixty patients were included: 29 underwent saphenous stripping and phlebectomy for varices in saphenous tributaries and 27 were treated by ultrasound-guided foam sclerotherapy; four cases were lost to follow-up. The main outcome measure was venous clinical severity scores (pain, oedema, inflammation, hyperpigmentation and lipodermatosclerosis). An ultrasound examination was carried out prior to treatment and 30, 60 and 180 days after the procedure to assess the relative efficacy of the methods in obliterating the saphenous trunk. Results: The mean venous clinical severity scores measured before and after 180 days were as follows: Surgery group – pain: before 1.97 standard deviation (SD) 0.19, 180 days 0.72 SD 0.53; oedema: before 1.66 SD 0.48, 180 days 0.55 SD 0.63; inflammation: before 1.55 SD 0.63, 180 days 0.72 SD 0.45. Foam sclerotherapy group – pain: before 1.81 SD 0.40, 180 days 0.56 SD 0.51; oedema: before 1.70 SD 0.47, 180 days 0.48 SD 0.64; inflammation: before 1.67 SD 0.68, after 0.89 SD 0.32. All scores showed statistically significant reductions in both patient groups. The saphenous vein had been obliterated, 180 days after treatment, in 78% of the surgery group, compared with 90% in the foam sclerotherapy group. Conclusions: Ultrasound-guided foam sclerotherapy is a safe and effective option for patients with chronic venous disorders. [Copyright &y& Elsevier]

Abstract: Previous experiments using progressive-delay schedules showed that destruction of the nucleus accumbens core (AcbC) altered rats’ choice between food reinforcers differing in size and delay. Application of a quantitative model of inter-temporal choice suggested that lesions of the AcbC increase the delay-dependent degradation of reinforcer value (delay discounting) without altering instantaneous reinforcer value. This experiment examined the effect of lesions of the AcbC on inter-temporal choice using an adjusting-delay schedule. Rats received excitotoxin-induced lesions of the AcbC or sham lesions. They were trained to press levers A and B for food-pellet reinforcers in an adjusting-delay schedule in which the delay to the larger reinforcer, d B , varied in accordance with the rats’ choices between the two levers. In two experimental conditions, the reinforcers associated with levers A and B were 1 vs. 4 and 2 vs. 4 pellets. The AcbC-lesioned group showed shorter indifference delays to reinforcer B (d B(50)) than the sham-lesioned group under both conditions. In confirmation of a prediction derived from the model of inter-temporal choice, the ratio of the indifference delays from the two conditions did not differ between the groups. Analysis of the cyclical changes in d B by Fourier transform showed that the period of oscillation and power within the dominant frequency band did not differ between the groups, suggesting that the lesion did not disrupt the rats’ ability to detect short-term changes in delay of reinforcement. The results are consistent with previous findings that indicate a role for the AcbC in delay discounting. [Copyright &y& Elsevier]

• Forest patches with natural edge are also influenced by the edge effect. • Soil variables are influenced by distance from the edge in forest patches. • Shape and size are important drivers of tree community of natural forest patches. • Edge and interior habitats show strong differentiation in species composition. Our knowledge of biodiversity responses to fragmentation comes from human-driven fragmentation processes. However, evaluating forest patches with natural edge can produce useful models to understand how the micro-environmental gradient between forest edge and interior shapes the plant communities, regardless habitat loss. Here, we tested how forest edges and interiors differ in soil characteristics, communities' structure and diversity metrics, and the extent to which these differences are related to forest size and shape of patches. We present data of ten tropical montane cloud forest patches surrounded by native non-forest vegetation (highland grasslands) of southeast Brazil. In each forest, we established five plots right on the edge and five randomly distributed over the forest interior. Our dataset covers a total of 5495 trees, and the main findings showed that patches with natural edges are also influenced by the edge effect, affecting the structure, species composition and soil variables. We found that with the increase in distance from the forest edge, the soils became more acid, with greater accumulation of organic matter, phosphorus, silt and sand, in contrast, the content of total exchangeable bases and clay decreased. When accounting for the effect of patch size and shape in the relationships between forest habitat and the structural community metrics, tree density and upper 95-percentile stem diameter tended to be higher in larger patches. In contrast, aboveground biomass and median stem diameter were positively related to patch shape in forest interiors. In addition, species composition showed marked differences between habitats, but rarefied species richness and Fisher's diversity index were higher, in the interior, only in large patches. These results indicate that besides differences between forest habitats, with increasing patch size and circularity, the differences become more pronounced. We would like to highlight that in conservation and management decisions, peculiarities of each habitat must be taken into account, with techniques that assess the surrounding matrix (man-made or natural) and that consider the edge and the interior as distinct habitats. [ABSTRACT FROM AUTHOR]

Simultaneous pancreas/kidney transplants require a long graft survival and the recipient to present with more benefits than risks. We evaluated the risk factors of receptor's death and pancreatic graft loss on 2 occasions (3 and 12 months' postoperatively) in 292 transplants in whom 22 variables were evaluated. Variables were selected, 9 receivers, 8 donors, and 5 variables related to the surgical procedure. All independent variables were compared with the dependent variables of pancreatic graft losses and patient deaths. Those considered significant according to univariate analysis were analyzed by using multiple logistic regression techniques in an attempt to develop a mathematical model capable of predicting both pancreatic graft and patient losses. Lastly, based on the resulting models with all significant variables, scores were created to determine the risk of patient death and pancreatic graft loss. In the adjusted multivariate analysis, the significant variables were donor age, receiver's body mass index, initial pancreas implant, iliac venous drainage, and use of induction therapy related to pancreatic loss within 3 months after transplantation. Independent risk factors regarding the loss of patients within 12 months were body mass index and receptor induction therapy. The variables related to pancreatic graft loss within 3 months were donor age, receiver body mass index, initial use of pancreatic graft, iliac venous drainage, and induction therapy; these variables can be used for creating a risk score. The donor body mass index and the induction therapy were independently related to patient loss within 12 months after the transplant. [ABSTRACT FROM AUTHOR]

Abstract: Along with developments in transplantation there have been major breakthroughs in the techniques of assisted reproduction. The areas of common interest include requesting semen collection from organ donors with a diagnosis of brain death. After the recent report of two cases in the Search Service of Organs and Tissues, we analyzed legislation in our country, which still lacks specific guidance in such situations. Organ transplantation progressively established itself as an effective therapeutic option in our country since the 1960s. It represents viable alternative to improve both the quality and length of life as well as to decrease long-term costs of patients with severe end-stage organ failure. These programs have specific rules and laws that are necessary to guide all stages of transplantation: donor identification, authorization and execution as well as recipients selection of implantation techniques. Assisted reproduction also needs legislation specific for human infertility, a public health problem that affects medical, psychological, and legitimate desires of people. The World Health Organization estimates that infertility reaches 20% of the population demanding the development and use of techniques for its treatment. Brazilian legislation includes regulations for transplantation of organs and tissues in law no. 9434 of February 04, 1997; it provides for the removal of organs, tissues, and human body parts for transplantation and other treatments. This law is regulated by Decree no. 2268 of June 30, 1997, establishing the National Transplant System, which standardizes these processes. The postmortem organ and tissue provision must be preceded by a diagnosis of via the Brain Death Protocol (Federal Council of Medicine-Brazil). The sole paragraph of Article 1 makes clear that its provisions do not apply to blood, sperm, or ovules as confirmed by the sole paragraph of Article 1 in the Decree 2.268/97 regulation. Since there is no specific legislation, assisted reproduction in our country is also regulated by The Federal Council of Medicine resolution, which was recently updated (Resolution no. 1957 December 15, 2010 in item VIII), which provides ethical standards for the use of assisted reproduction techniques provides that “It is unlawful ethical assisted reproduction postmortem since there is specific prior authorization of (a) late (a) to the use of cryopreserved biological material, in accordance with current legislation.” Standardization is specific to material collected before the diagnosis of brain death, including being subject to expressed and informed consent of both spouses (item 3, item 1, attached single Resolution 1.957/2010 Federal Council of Medicine). We cannot yet find support in these legal provisions even after brain death for postmortem collection of sperm or ovules. Despite the evolution of the assisted reproduction techniques and the recognition of people''s rights and wishes to procreate, this matter still creates complicated ethical and legal issues that seem to be far from being solved in our country. [Copyright &y& Elsevier]

Introduction: Pulmonary hypertension (PH) (mean pulmonary arterial pressure [mPAP] > 25 mm Hg) is frequently observed during the postoperative period after liver transplantation (LT).Objective: The objective was to compare respiratory function, intensive care unit (ICU) length of stay (LOS), and 30-day survival rates among patients evolving with PH with those who do versus do not develop it during the postoperative period after LT.Methods: Fifty-seven patients undergoing LT from January 1999 to December 2000 were divided into 2 groups: Group 1 (G1; n = 26), without PH; and Group 2 (G2; n = 31), with moderate PH. Preoperative parameters were Child-Pugh''s classification, pulmonary function tests, mPAP, and P(A-a)O2. During the intraoperative period, warm and cold ischemic times and the amount of blood transfusion were evaluated, whereas mPAP, PaO2/FiO2 ratio, weaning time, ICU LOS, and 30-day survival rates were evaluated postoperatively.Results: mPAP in early postoperative period was 21 ± 13 mm Hg and 32 ± 4 mm Hg in G1 and G2, respectively (P < .0001). PaO2/FiO2 was 310 ± 82 mm Hg in G1 and 272 ± 84 mm Hg in G2 (P = .48). In G1 and G2, 77% and 74% of patients, respectively, were successfully weaned in the first 24 hours postoperative (P = .10). ICU LOS was 111 hours (range, 45–1098 hours) in G1 and 102 hours (range, 59–284 hours) in G2 (P = .36). The 30-day survival rate was 20 of 26 (77%) in G1 and 26 of 31 (84%) in G2 (P = .44).Conclusion: Our data suggest that moderate PH during the early postoperative phases of LT cannot be considered an additional risk factor for pulmonary dysfunction, and for an increased ICU LOS or 30-day mortality rate. [Copyright &y& Elsevier]

Introduction/Background Epiglottic retroflexion seems to be an important mechanism of airway protection during swallowing. Although epiglottic dysfunction has been correlated with aspiration, the kinematics alterations underlying this condition remain unclear. Two distinct movements of epiglottic inversion were described in videofluoroscopic swallowing studies (VFSS). The first epiglottic movement brings the epiglottis to a horizontal position and the second consists of its full inversion. Material and method Retrospective cohort study of 28 patients with post-stroke dysphagia admitted to our institution in 2017. Based on VFSS images, and in regard with the epiglottic mobility, two groups were assigned for comparison: one group with complete epiglottic inversion and other with partial inversion. Other parameters of VFSS were also compared. Results Of the 28 patients in the study, 68% were male (19) and 32% female (9); 28.6% of the patients had hemorrhagic stroke, 67.9% ischemic, and 3.5% ischemic stroke with hemorrhagic transformation. We found significant statistical correlation between epiglottic mechanics alterations and risk of laryngeal penetration (Fisher's exact-test; P = 0.036). Regarding other evaluated parameters, only the absence of the cough reflex was shown to statistically correlate with the risk of laryngeal penetration (Pearson's Chi 2 ; P = 0.007). Conclusion The results suggest that epiglottis movement is an important mechanism to avoid penetration-aspiration. The absence of cough reflex in patients with laryngeal penetration (silent aspiration) emphasizes the importance of the VFSS. We are also of the opinion that this result may be related to the pre selection of patients with suspected silent aspiration. Further studies are needed to better understand the influence of these epiglottic movement alterations in the swallowing process. [ABSTRACT FROM AUTHOR]