Search

ABSTRACT This study evaluated the effects of long-acting injectable progesterone supplementation (P4LA) on embryonic and fetal development and birth weight in Nellore cows seven days after timed artificial insemination (TAI). One hundred and nineteen Nellore female cows became pregnant after the TAI protocol and were divided into two groups: P4LA with cows that received 150mg of P4LA, seven days after insemination, in a single dose, and the control group, with cows who did not receive any hormonal supplementation after TAI. Blood samples were collected on days 17 and 30 after TAI to determine P4 concentration. Embryonic and fetal measurements were performed at 30 and 45 days of gestation, respectively, with the aid of ultrasonography, measuring craniocaudal length and thoracic diameter. No difference was observed in P4 concentration between the groups supplemented with or without injectable P4 on days 17 (P=0.73) and 30 (P=0.62) after TAI. There was no significant difference in embryonic and fetal development or birth weight between the supplemented and non-supplemented groups (P=0.59, P=0.09, and P=0.64, respectively). Supplementation with injectable progesterone seven days after TAI did not interfere with the embryonic and fetal development of Nellore cows, nor did it affect birth weight.

ABSTRACT: The objective of this prospective cohort study was to characterize the metabolic profile, health, milk production, and reproductive outcomes of cows diagnosed with hyperketonemia (HK; β-hydroxybutyrate ≥1.2 mmol/L), hypoglycemia (HG; glucose ≤2.2 mmol/L), or concurrent HK and HG (HKHG). Glucose and β-hydroxybutyrate concentrations in whole blood were assessed using a handheld device (Precision Xtra, Abbott Laboratories) in lactating dairy cows (n = 2,418) between 3 and 9 d postpartum. Cows were categorized into 4 groups: no HK or HG (healthy; Norm = 1,821), HK only (HK = 232), HG only (HG = 161), and concurrent HK and HG (HKHG = 204). Subsequent milk production, along with health and reproductive outcomes, as recorded by farm personnel, were analyzed according to metabolic category. Serum collected on the day of cow-side diagnosis of hyperketonemia and hypoglycemia was evaluated for total calcium (tCa), magnesium (Mg), nonesterified fatty acids (NEFA), triglycerides (TG), and urea using an automated chemistry analyzer (Randox Daytona; Randox Laboratories Ltd.). Statistical analysis was carried out using SAS version 9.4 (SAS Institute Inc.). Hyperketonemia in multiparous cows was associated with greater incidence of metabolic abnormalities (hypomagnesemia, hypocalcemia, and elevated NEFA and urea). Hyperketonemia in primiparous and multiparous cows led to increased adverse health events (culling rate, retained fetal membranes, puerperal metritis, clinical ketosis, left displaced abomasum) relative to Norm cows. Multiparous cows with HKHG had fewer metabolic disturbances (hypomagnesemia, hypocalcemia, elevated NEFA) than HK cows. Cows with HKHG had an increased incidence of clinical ketosis and left displaced abomasum relative to Norm cows. Cows with HG had similar metabolic profiles to Norm cows and had lower incidence of retained fetal membranes and puerperal metritis than cows with HK. Multiparous cows with HG produced more milk than Norm cows from wk 10 to 20, whereas multiparous cows with HK produced less milk than Norm cows. For primiparous cows, HK did not have a negative effect on milk production compared with Norm cows.

ABSTRACT: The objective of this study was to assess the effects of treatment with propylene glycol (PG) and cyanocobalamin (B12) on health, milk production, and reproductive outcomes of cows diagnosed with hyperketonemia (HK), hypoglycemia (HG), or concurrent HKHG. Glucose and β-hydroxybutyric acid (BHBA) concentrations were assessed in whole blood using a handheld device in lactating dairy cows (n = 2,418) between 3 and 9 d postpartum. Cows categorized as HK (n = 232, BHBA ≥1.2 mmol/L), HG (n = 161, glucose ≤2.2 mmol/L), and concurrent HKHG (n = 204, BHBA ≥1.2 mmol/L, and glucose ≤2.2 mmol/L) were randomized to receive treatment or to remain untreated (control). Treatment consisted of a single dose of B12 (10 mg, intramuscularly) and 300 mL of PG orally for 5 d, starting on the day of cow-side testing. Milk production, health, and reproductive outcomes were analyzed according to groups. Statistical analysis was carried out using SAS version 9.4 (SAS/STAT, SAS Institute Inc.). Treatment in HG cows decreased clinical ketosis, increased milk production in the fifth week of lactation for multiparous cows, and tended to increase 305-d mature-equivalent milk yield (305ME) for primiparous cows compared with untreated cows with the same metabolic profile. For cows with HKHG, treatment increased 305ME in multiparous cows and tended to increase 305ME in primiparous cows. No differences were found for treatment among any of the metabolic groups regarding reproductive outcomes, nor were any treatment effects found among HK cows. Glycemic status may help identify metabolically challenged early postpartum dairy cows, which may have differential response to PG and B12 treatment.

Dorsal–ventral (DV) patterning is regulated by the bone morphogenetic pathway (BMP) in Bilateria. In insect DV patterning, the Toll pathway also plays a role, in addition to BMPs. Variations in the relative importance of each pathway for DV patterning have been reported using single species of coleopteran, hymenopteran, hemipteran and orthopteran insects. To investigate if the molecular control of DV patterning is conserved inside an insect order, the emergent model hemiptera species Rhodnius prolixus was studied. We found that R. prolixus BMP pathway controls the entire DV axis, with a broader effect respective to Toll, as shown for the hemiptera Oncopeltus fasciatus. Different from O. fasciatus, the unique R. prolixus short gastrulation (sog) and the twisted gastrulation (tsg) orthologues do not antagonize, but rather favour embryonic BMP signalling. Our results reinforce the hypothesis that hemiptera rely preferentially on BMPs for DV patterning but that, surprisingly, in R. prolixus Sog and Tsg proteins exert only a positive role to establish a dorsal-to-ventral BMP gradient. Since sog has been reported to be lost from orthopteran and hymenopteran genomes, our results indicate that Sog's role to modify BMP activity varies greatly in different insect species.

ABSTRACT: The objectives of this study were to determine the effects of nerve growth factor-β (NGF), purified from bulls' seminal plasma and administered at the time of artificial insemination (AI), on progesterone post-AI, interferon-stimulated genes (ISG), and pregnancy per AI (P/AI) for lactating Holstein dairy cows enrolled in a timed-AI protocol. We hypothesized that administration of NGF at the time of AI would increase plasma progesterone post-AI, upregulate relative abundance of ISG, and improve P/AI in lactating dairy cows. Holstein cows (n = 557) from a single commercial dairy farm were blocked by parity and randomly assigned to receive an intramuscular injection containing 296 µg of bovine purified NGF at the time of AI, diluted in 2 mL of phosphate-buffered saline (NGF: n = 275), or receive only the 2 mL of phosphate-buffered saline (control: n = 282). Plasma progesterone and corpus luteum size were assessed in a subset of cows (NGF: n = 32; control: n = 36) at d 7, 14, and 19 post-AI. Relative mRNA abundance of ISG (ISG15, MX1, MX2, and RTP4) was assessed in peripheral blood leukocytes on d 19 post-AI. Pregnancy diagnosis was performed at 37 and 65 d post-AI. There was an interaction effect between treatment and parity for plasma progesterone; however, plasma progesterone and ISG did not differ between treatments. There were no effects of NGF for P/AI at 37 d post-AI (NGF = 40.0% vs. control = 41.6%), 65 d post-AI (NGF = 36.0% vs. control = 38.1%), and for pregnancy loss (NGF = 8.4% vs. control = 7.7%). The current study revealed that effects to NGF in lactating Holstein cows were minor and contingent with parity for progesterone, and no improvement in ISG relative abundance and P/AI were observed.

Introduction Over this decade, there has been progressive growth and evolution of the concept of autoimmune encephalitis. However, international consensus overly focus on major neurological signs, while discarding some attenuated presentations, sometimes with just psychiatric manifestations. It was only very recently that a new concept arouse from this disorder, named autoimmune psychosis, which can mimic schizophrenia. Unfortunately, there is still a lack of a structured approach of psychotic patients to cover this disorder. This has numerous implications, namely on management and prognosis of these patients. Not only, these patients have an increased risk of neuroleptic malignant syndrome, but it is also important to intervene early in the course of disease. Objectives To conduct a review of the diagnostic and treatment guideliens of autoimmune psychosis Methods The authors conducted a non-systematic review, by resorting to the pubmed database, on the concept of autoimmune psychosis and updated proposals of diagnostic orienting lines. Results Recently, in 2016, Graus et al proposed diagnostic criteria for possible autoimmune encephalitis, in which the authors acknowledge subacute onset of psychiatric symptoms as a possible clinical manifestation. The authors accept normal diagnostic tests, provided that new neurological focal findings exist. Since then, there have been described a list of signs/symptoms, which should raise suspicion for this diagnostic on psychiatric patients, so called red flags. In accordance to diagnostic guidelines for autoimmune psychosis, defined by Pollak et, the presence of this symptoms should lead clinicians to perform diagnostic exams, as MRI, eletroencephalogram and blood serological tests and lumbar puncture. However, others criticize this initial lineup arguing that some patients could be missed, because they do not have any neurological signs, and so they propose new diagnostic criteria. Conclusions Autoimmune psychosis represents an attenuated clinical form of autoimmune encephalitis, although demanding the same medication and prompt initiation of treatment as other autoimmune encephalitis. It is important to acknowledge that there are patients who are seronegative and that some of the diagnostic exams mentioned have sometimes limited availability. As acknowledged by Guasp et al, there are patients with first psychotic episodes that have an autoimmune etiology, but because of the lack of neurological signs, could potentially be missed of treatment. So, it is important to establish formal diagnostic guidelines for this disorder, namely orienting lines for first psychotic episodes, which is the most commson psychiatric manifestation. This also enlightens the need for neurologic and psychiatric cooperation for these patients. Disclosure of Interest None Declared

BackgroundRed blood cell distribution width (RDW) reflects the variability of circulating red blood cells. The relationship between multiple sclerosis (MS) and RDW is not well studied. The main objective of this work was to compare baseline RDW to EDSS at 5 years of diagnosis and verify if RDW predicts worse disability.MethodsWe conduct a retrospective observational study of relapsing-remitting MS (RRMS) patients followed in the Neuroimmunology Clinic that had at least one measuring of RDW at baseline.ResultsWe included 82 patients with RRMS meeting inclusion criteria, 73,2% female with a mean age of 33,56 years old. Median EDSS score at baseline was 1.5.9,8% patients had new T2 lesions in MRI at 5 years and 4,9% showed lesions capturing contrast at 5 years. Regarding DMT, 75,6% were treated with interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate, and 21,9% were under fingolimod, natalizumab, rituximab, and cladribine, and the remaining 2,4% were without treatment at 5 years.A multiple linear regression model confirmed increased disability (EDSS at 5 years) for patients undergoing second-line treatment (β=0,86;p=,003) and higher RDW at baseline (β=0,47;p=,007). Presenting RDW results for quartiles, it was statistically significant for quartile 4 [13,5;16,4[(β=0,74;p=,039), suggesting that a very increased RDW at baseline is strongly associated with higher EDSS at 5 years.ConclusionHigher RDW at baseline was correlated with a worse disability at 5 years in RRMS patients. Furthermore, RDW equal to or higher than 13,5% may be useful in identifying patients that will have a worse disability at 5 years. Resumen: IntroducciónAncho de distribución de glóbulos rojos (RDW) la combinación de los glóbulos rojos circulantes. La relación entre MS y RDW no está bien estudiada. El objetivo principal de este trabajo fue comparar el RDW basal con el EDSS a los 5 años del diagnóstico y verificar si el RDW predice una peor discapacidad.MétodosRealizamos un estudio observacional retrospectivo de EM remitente-recurrente (EMRR) de pacientes en la Clínica de Neuroinmunología que tenían al menos una medición de RDW al inicio del estudio.ResultadosSe incluyeron 82 pacientes con EMRR que cumplieron los criterios de inclusión, el 73,2% mujeres con una edad media de 33,56 años. La puntuación media de la EDSS al inicio del estudio fue de 1,5. El 9,8% de los pacientes presentaron nuevas lesiones T2 en la RM a los 5 años y el 4,9% mostró captación de contraste a los 5 años. En cuanto a DMT, el 75,6% se trató con interferón, acetato de glatiramer, teriflunomida o dimetilfumarato, y el 21,9% con fingolimod, natalizumab, rituximab y cladribina, y el 2,4% restante sin tratamiento a los 5 años.Un modelo de regresión lineal múltiple garantiza un aumento de la discapacidad (EDSS a los 5 años) para los pacientes sin tratamiento de segunda línea (β = 0,86; p = 0,003) y una mayor RDW al inicio del estudio (β = 0 ,47; p = 0,007). Al presentar los resultados de RDW para los cuartiles, fue estadísticamente significativo para el cuartil 4 [13.5; 16.4 [(β = 0.74; p = .039), lo que sugiere que un RDW muy elevado al inicio del estudio está fuertemente asociado con una mayor EDSS a los 5 años.ConclusionesUn mayor RDW al inicio del estudio se correlacionó con una peor discapacidad a los 5 años en los pacientes con EMRR. Además, una RDW igual o superior al 13,5% puede ser útil para identificar a los pacientes que tendrán una discapacidad peor a los 5 años.

ABSTRACT Bovine Trichomoniasis (BT) is an infectious disease caused by Tritrichomonas foetus that can be transmitted either sexually or by fomites. In males, the disease is asymptomatic and permanent. T. foetus has been detected in semen samples where it is able to remain viable even when frozen. The objective of this study was to investigate the presence of T. foetus in 27 samples of commercial frozen bovine semen by culture and Polymerase Chain Reaction (PCR). Samples were thawed in water at 37°C. Part of the samples was inoculated in a test tube containing Diamond’s medium and incubated at 35°C. Growth was evaluated every 24 hours via direct examination under a microscope. The other part was placed in an Eppendorf tube and frozen for later molecular analysis. After 10 days of culture, all samples were negative for T. foetus. The Quick-DNA Miniprep Kit (Zymo Research) without proteinase K was used for DNA extraction. The primers used in PCR were TRF3 and TRF4. PCR results were negative for all samples. In conclusion, bovine semen samples were negative for T. foetus in both diagnostic methods, according to the adopted methodology.

Abstract Background Hypersensitivity reactions to drugs are unpredictable and can be very complex and severe, even life threatening. Assess its impact on patient’s health related quality of life (HRQoL) is crucial. The Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) is the only validated disease-specific HRQoL questionnaire. We aimed to translate and cross-cultural validate the DrHy-Q to the Portuguese population. It was also our purpose to determine the impact of drug hypersensitivity on patients’ HRQoL. Methods The translation and cross-cultural adaptation of the DrHy-Q to Portuguese was performed according to standards. Reliability of the DrHy-Q Portuguese version was assessed in terms of internal consistency and test–retest reliability. Structural validity, divergent validity (with a generic health related QoLQ-PGWBI) and discriminant validity were also evaluated. Forty patients accepted to participate in the validation phase. The Portuguese version of the DrHy-Q was applied to 260 consecutively adult patients, studied in our Department for suspected drug hypersensitivity. Results The Portuguese DrHy-Q showed adequate internal consistency (Cronbach’s ɑ = 0.938), good test–retest reliability [ICC = 0.713 (95% CI 0.488–0.850] and one-dimensional structure. No significant correlation was found between the DrHy-Q and the PGWBI total scores (r = − 0.010, p = 0.957). Two hundred of patients completed the study: 78.5% female; mean age = 44 ± 15 years. Mean DrHy-Q score was 36.8 ± 12.6. Two clinical factors significantly predict DrHy-Q total score: clinical manifestations and number of suspected drugs. Patients with anaphylaxis (β = 11.005; 95% CI 5.523; 16.487), urticaria/angioedema (β = 7.770; 95% CI 2.600; 12.940) and other manifestations (β = 7.948; 95% CI 1.933; 13.962) are more likely to have higher DrHy-Q total score than patients with maculopapular exanthema. Patients with ≥ 2 suspected drugs are also more likely to have worse QoL (β = 7.927; 95% CI 3.687; 12.166). Conclusion The Portuguese version of DrHy-Q revealed adequate validity and reliability, indicating that it is appropriate to assess the impact of drug hypersensitivity on patients’ HRQoL, providing data for a better comprehension and management of our patients. Moreover, our results highlight that the severity of the drug hypersensitivity reaction and the number of suspected drugs have impact on patient’s DrHy-QoL.

Introduction Obsessive Compulsive Disorder (OCD) is a psychiatric disorder associated with suffering and disability. The serotoninergic system is implicated in the neurobiological processes of OCD and serotonin reuptake inhibitors (SRIs) are the first-line treatment. However, clinical improvement after starting SRIs can take long and patients may not fully recover. Meanwhile, recent data suggests that activation of 5-HT receptors may exert a therapeutic action in obsessional symptoms. Some psychedelics are strong 5-HT2 receptor agonists and there is a growing research interest as they can be a promising therapeutic approach to OCD. Objectives We aim to provide an overview on the current evidence on the therapeutic potential of serotoninergic psychoactive substances in the treatment of OCD. Methods Non-systematic review. Literature search in the PubMed database using the terms psychedelics and obsessive-compulsive disorder. Results Although research is currently limited to a few small studies, the ones conducted so far showed clinically meaningful acute reduction of OCD symptoms after treatment with serotoninergic psychoactive drugs, as well as possible longer-lasting benefits, particularly with psilocybin and lysergic acid diethylamide (LSD). Furthermore, substance-assisted psychotherapy with psychedelics has been showing promising results, being suitable for OCD treatment. It is important to add that, to date, studies have indicated relatively good tolerability to these drugs. Conclusions These promising early findings highlight the role of psychedelics in OCD treatment and the need for further research into efficacy, therapeutic mechanisms and safety, in order to determine whether these drugs may be worthy options for OCD treatment in the future. Disclosure No significant relationships.

Introduction There have been reports of myopathic dysfunction with creatinine kinase (CK) elevation associated with neuroleptics, particularly, in clozapine-treated patients. The patients in these reports did not have any other clinical symptoms or signs indicative of neuropleptic malignant syndrome. Myopathic dysfunction was supported by the presence of CK elevations and either proximal limb weakness or fatigue, characteristic electrophysiologic abnormalities, or both. It has also been reported that CK elevation is neither dose nor treatment-duration dependent. The underlying mechanism is still unknown although it has been postulated that it is associated with cytochrome P450 interactions and/or calmodulin antagonism. Objectives To report a case of elevation of CK during treatment with clozapine. Methods The authors report a case of elevation of CK during treatment with clozapine. A non-systematic review was conducted by searching the PubMed database, using the terms “clozapine”, “myotoxicity”. Results A 36-year-old man was admitted after abandoning treatment with clozapine. During the titration of the medication, he developed complaints of muscle fatigue in conjunction with an elevation of CK. CK levels normalized after intravenous hydration and with dose reduction. Furthermore, CK levels would increase with clozapine re-titration. Conclusions Clozapine has numerous side effects. Myopathic dysfunction with CK elevation is a possible side effect which could have serious consequences such as renal impairment. In such cases, appropriate treatment should be implemented. Therefore, clinicians should be aware of this potential side effect. Disclosure No significant relationships.

Abstract The data produced by the scientific community impacts on academia, clinicians, and the general public; therefore, the scientific community and other regulatory bodies have been focussing on ethical codes of conduct. Despite the measures taken by several research councils, unethical research, publishing and/or reviewing behaviours still take place. This exploratory study considers some of the current unethical practices and the reasons behind them and explores the ways to discourage these within research and other professional disciplinary bodies. These interviews/discussions with PhD students, technicians, and academics/principal investigators (PIs) (N=110) were conducted mostly in European higher education institutions including UK, Italy, Ireland, Portugal, Czech Republic and Netherlands. Through collegiate discussions, sharing experiences and by examining previously published/reported information, authors have identified several less reported behaviours. Some of these practices are mainly influenced either by the undue institutional expectations of research esteem or by changes in the journal review process. These malpractices can be divided in two categories relating to (a) methodological malpractices including data management, and (b) those that contravene publishing ethics. The former is mostly related to “committed bias”, by which the author selectively uses the data to suit their own hypothesis, methodological malpractice relates to selection of out-dated protocols that are not suited to the intended work. Although these are usually unintentional, incidences of intentional manipulations have been reported to authors of this study. For example, carrying out investigations without positive (or negative) controls; but including these from a previous study. Other methodological malpractices include unfair repetitions to gain statistical significance, or retrospective ethical approvals. In contrast, the publication related malpractices such as authorship malpractices, ethical clearance irregularities have also been reported. The findings also suggest a globalised approach with clear punitive measures for offenders is needed to tackle this problem.

The 2008 Wenchuan earthquake resulted in a large number of fatalities and caused significant economic losses. Thousands of landslides, many of which are very large, were triggered by the earthquake. A majority of catastrophic landslides were distributed along the central Longmenshan fault system, at the eastern margin of the Tibetan Plateau. Some of the landslides resulted in sudden damming of rivers causing flooding, which in turn induced secondary sliding disasters. Among the most significant landslides, the Daguangbao landslide was the largest in volume with the maximum thickness. For this, a numerical model of the Daguangbao landslide, using the material point method (MPM), was developed to simulate the interaction of the seismic loads imposed on the slope. The numerical results then are compared with the post-earthquake profile. As a consequence of the landslide, a nearly vertical head scarp with a maximum height of about 700 m was generated. This is considered as a high risk situation that requires constant monitoring and evaluation. Finally, we propose a methodology based on Bayesian networks (BNs) to manage the risk associated with the stability of the rockwall at the Daguangbao landslide site. Keywords: Wenchuan earthquake, Longmenshan fault, Daguangbao landslide, Material point method (MPM), Rockwall

Production costs in extensive and semi-intensive fish culture in earthen ponds are often too high to offer sustainable economic activity due to the low productivity of these systems. The right combination of commercial finfish species with inorganic (primary producers) and organic extractive (bivalves) species in Integrated MultiTrophic Aquaculture (IMTA) create a balanced system with higher profitability and risk reduction. To achieve this, it is crucial to understand the role of each functional groups within the system what we did by comparing three different IMTA production three different IMTA production treatments with distinct combinations of trophic levels: • fish, filter feeders, phytoplankton and macroalgae, • fish, filter feeders and phytoplankton • fish, phytoplankton and macroalgaeEach treatment was carried out in two similar ponds under semi-intensive conditions and flow through system, in a total of 6 earthen ponds of 500 m2 surface and depth of 1.5 m.Results showed that the presence of oysters in the ponds enhanced water quality by decreasing turbidity and by controlling phytoplankton which led to regulation of dissolved oxygen levels. The enhanced water quality in these systems lead to improved fish performance and higher biomass production contributing to greater profitability. The combination of fish, oyster, phytoplankton and macroalgae was particularly good providing much more fish supply compared with the other two treatments. • Oysters enhanced water quality in the ponds by decreasing turbidity and controlling phytoplankton which regulated the dissolved oxygen levels. • The enhanced water quality in systems with oysters improve fish performance resulting in higher biomass production and greater profitability. • The combination of fish, oyster, phytoplankton and macroalgae was particularly good providing much more fish supply compared with the other two treatments. Method name: Pond IMTA, Keywords: Aquaculture, IMTA, Meagre, White seabream, Grey mullet, Japanese oyster, Phytoplankton, Ulva

Introduction Mood destabilization and induced manic episodes are well-known phenomenon under antidepressant medications. However, even with a cautious introduction of antidepressants, it’s important to be aware of possible pharmacological interactions. Terbinafine is a known inhibitor of CYP2D6, a major hepatic metabolizer of a full list of antidepressant medications, and so capable of raising their serum levels and potentiating their side effects. Objectives With this case report we aim to emphasize the importance of cautious usage of Terbinafine when combined with antidepressant medications. Methods We present a clinical case of an induced first manic episode after the introduction of Terbinafine in a patient under antidepressant medication and a qualitative review on the topic, using PubMed database. Results A 66-year-old woman, with an history of Major Depressive Disorder, previously medicated with Venlafaxine 75mg/day and Mirtazapine 30mg/day, was brought to the emergency department because of psychomotor agitation. She also had an history of seasonal fluctuating mood, although never fulfilling the criteria for Bipolar Disorder. At admission, her clinical status was compatible with a manic episode. This episode followed two months after the initiation of Terbinafine for onychomycosis. Conclusions There are few studies that have shown antidepressant toxicity mediated by an interaction with Terbinafine. As far as we know this is the first case of induced mania after the introduction of Terbinafine. Therefore, it is important to remind that Terbinafine is a potential interacting agent when combined with psychotropic medications.

Introduction Valproic Acid (VPA) is one of the most commonly used mood stabilizer drugs. Although uncommon, serious adverse effects have been reported. One particularly relevant side effect is the induced encephalopathy, usually secondary to Hyperammonemia. However, some descriptions have shown an altered mental state with normal serum levels of ammonia. Objectives We aim to present a case of VPA induced-encephalopathy without hyperammonemia and emphasize its suspicion when patients taking VPA present altered mental states. Methods We present a clinical case of VPA induced-encephalopathy without Hyperammonemia and a qualitative review of this topic using the Pubmed database. Results A 66-year-old woman, with an history of Major Depressive Disorder, previously medicated with Venlafaxine 75mg/day and Mirtazapine 30mg/day, was admitted in our acute psychiatric inpatient unit due to a first manic episode. During the stay, her antidepressants were interrupted, and she was started on VPA, then optimized to 750mg/day. After that, she presented an altered mental state with confusion and prostration. Analytical results were normal including normal ammonia levels and no imagiological abnormalities. Despite these results, we decided to stop VPA empirically. The patient clinical status resolved the day after. Conclusions Studies have shown that only a few patients have developed encephalopathy with normal serum levels of ammonia. Although the pathogenesis behind this remains unknown, a few mechanisms have been proposed. Therefore, it is important to remind that even without abnormal analytical status, VPA is a possible cause of encephalopathy. We also emphasize the need for further studies on the mechanisms behind this phenomenon. Disclosure No significant relationships.

This paper reports on the qualitative and quantitative screening of groundwater sources for integration into the public water supply system of the Algarve, Portugal. The results are employed in a decision support system currently under development for an integrated water resources management scheme in the region. Such a scheme is crucial for several reasons, including the extreme seasonal and annual variations in rainfall, the effect of climate change on more frequent and long-lasting droughts, the continuously increasing water demand and the high risk of a single-source water supply policy. The latter was revealed during the severe drought of 2004 and 2005, when surface reservoirs were depleted and the regional water demand could not be met, despite the drilling of emergency wells. For screening and selection, quantitative criteria are based on aquifer properties and well yields, whereas qualitative criteria are defined by water quality indices. These reflect the well's degree of violation of drinking water standards for different sets of variables, including toxicity parameters, nitrate and chloride, iron and manganese and microbiological parameters. Results indicate the current availability of at least 1100 l s−1 of high quality groundwater (55% of the regional demand), requiring only disinfection (900 l s−1) or basic treatment, prior to human consumption. These groundwater withdrawals are sustainable when compared to mean annual recharge, considering that at least 40% is preserved for ecological demands. A more accurate and comprehensive analysis of sustainability is performed with the help of steady-state and transient groundwater flow simulations, which account for aquifer geometry, boundary conditions, recharge and discharge rates, pumping activity and seasonality. They permit an advanced analysis of present and future scenarios and show that increasing water demands and decreasing rainfall will make the water supply system extremely vulnerable, with a high risk of groundwater salinization and ecosystem degradation.

Alkaline phosphatase (ALP) is important in calcification and its expression seems to be associated with the inflammatory process. We investigated the in vitro acute effects of compounds used for the prevention or treatment of cardiovascular diseases on total ALP activity from male Wistar rat heart homogenate. ALP activity was determined by quantifying, at 410 nm, the p-nitrophenol released from p-nitrophenylphosphate (substrate in Tris buffer, pH 10.4). Using specific inhibitors of ALP activity and the reverse transcription-polymerase chain reaction, we showed that the rat heart had high ALP activity (31.73 ± 3.43 nmol p-nitrophenol·mg protein-1·min-1): mainly tissue-nonspecific ALP but also tissue-specific intestinal ALP type II. Both ALP isoenzymes presented myocardial localization (striated pattern) by immunofluorescence. ALP was inhibited a) strongly by 0.5 mM levamisole, 2 mM theophylline and 2 mM aspirin (91, 77 and 84%, respectively) and b) less strongly by 2 mM L-phenylalanine, 100 mL polyphenol-rich beverages and 0.5 mM progesterone (24, 21 to 29 and 11%, respectively). β-estradiol and caffeine (0.5 and 2 mM) had no effect; 0.5 mM simvastatin and 2 mM atenolol activated ALP (32 and 36%, respectively). Propranolol (2 mM) tended to activate ALP activity and corticosterone activated (18%) and inhibited (13%) (0.5 and 2 mM, respectively). We report, for the first time, that the rat heart expresses intestinal ALP type II and has high total ALP activity. ALP activity was inhibited by compounds used in the prevention of cardiovascular pathology. ALP manipulation in vivo may constitute an additional target for intervention in cardiovascular diseases.

Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents (selective serotonin reuptake inhibitors) used in the treatment of panic disorder. The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind, randomized, flexible-dose trial conducted with outpatients. After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P

O presente trabalho tem como objetivo mostrar a possibilidade de aproximar um problema NP-Difícil da computação intervalar, através do uso de heurísticas com ênfase em algoritmos baseados no Método de Monte Carlo. A fim de apresentar heurísticas para o problema genérico de estimar numericamente, dada uma precisão ", o valor esperado de uma função racional f(x1, ..., xn) com (x1, ..., xn) 2 Qn k=1 ×Ik escolhidos de acordo com uma função de densidade de probabilidade P(x1, ..., xn) conjunta, com Ik sendo intervalos, mostramos para o particular caso de um grafo regular de grau 2, cujos vértices podem assumir somente dois valores −1 e +1, o que restringe os intervalos a serem todos discretos Ik = [−1, 1] \ Z, k = 1, ..., n. Verificamos que o problema do valor esperado entre os pares de vértices adjacentes, tivera seu custo reduzido de O(2n) operações, através do cálculo exato, para O(Nsample) que seria a complexidade encontrada quando aproximamos o resultado obtido pela Heurística, onde Nsample é o número de amostras de configurações escolhidas através do processo de amostragem por importância no contexto do algoritmo de Metrópolis.

Neste trabalho, descrevem-se as estruturas para as obras de reforço de potência do empreendimento hidroeléctrico de Miranda, que consistiram na construção de um novo circuito hidráulico e numa central semi-enterrada. Foram realizados ensaios geotécnicos para a caracterização mecânica, hidromecânica e do estado de tensão do maciço rochoso. Foram estabelecidos Planos de Observação para controlo da segurança das estruturas durante a construção e a entrada em serviço das novas estruturas. Apresentam-se alguns resultados significativos relativos à observação, que são comparados com resultados numéricos.

Neste trabalho, procura-se sintetizar a experiência do LNEC na caracterização da deformabilidade de fundações de maciços rochosos, sendo dado especial ênfase às técnicas in situ habitualmente utilizadas. Refere-se, ainda, a experiência japonesa na utilização de ensaios de carga com placa. Efectua-se, em seguida, uma análise de ensaios de deformabilidade efectuados para uma barragem de emocamento, no Japão.

O LNEC tem vindo a desenvolver o método das almofadas pequenas (SFJ) para quantificação do estado de tensão in situ em maciços rochosos, baseado no método de libertação de tensões por abertura de rasgos, que permite ainda avaliar a deformabilidade dos maciços. Para interpretação do método SFJ, foi desenvolvido um novo modelo admitindo comportamentos isótropos e anisótropos, com base no uso de um modelo de cálculo tridimensional por elementos finitos.