Universidade do Estado do Pará

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

The objective of this paper was to present estimates on the prevalence of musculoskeletal pain of five different anatomical areas and ten anatomical sites, and their consequences and risk groups in the general Dutch population. Cross-sectional data from a population-based study of a sex-age stratified sample of Dutch inhabitants of 25 years and older were used. With a postal questionnaire data was assessed on musculoskeletal pain, additional pain characteristics (location, duration, course), its consequences (utilization of health care, sick leave and limitation in daily life) and general socio-demographic characteristics. The top three of self-reported musculoskeletal pain (point prevalence (P(p)) with 95% confidence interval (CI)) was: (1). low back pain, P(p)=26.9% (95% CI 25.5-28.3); (2). shoulder pain, P(p)=20.9% (95% CI 19.6-22.2); and (3). neck pain, P(p)=20.6% (95% CI 19.3-21.9). In most cases the pain was described as continuous or recurrent and mild. In every three out of ten cases the complaints about pain were accompanied by limitations in daily living. Between 33 and 42% of those with complaints consulted their general practitioner about their pain. With the exception of persons who are work disabled, general sociodemographic characteristics cannot be used to identify high risk groups. Musculoskeletal pain is common in all subgroups of the population and has far-reaching consequences for health, work and the use of health care.

OBJECTIVES: The objective of this study was to contribute long-term safety data for infliximab and other therapies in Crohn's disease (CD). METHODS: We prospectively evaluated CD patients enrolled in the large, observational Crohn's Therapy, Resource, Evaluation, and Assessment Tool registry, established to compare infliximab safety with conventional nonbiological medications in CD. RESULTS: A total of 6,273 patients were enrolled and evaluated on or before 23 February 2010; 3,420 received infliximab (17,712 patient-years; 89.9% received ≥ 2 infusions) and 2,853 received other-treatments-only (13,251 patient-years). Mean length of patient follow-up was 5.2 years. More infliximab- than other-treatments-only-treated patients had moderate-to-severe (30.6% vs. 10.7%) or severe-to-fulminant (2.5% vs. 0.6%) disease severity (P < 0.001). In the year before enrollment, more infliximab- than other-treatments-only-treated patients required surgical intervention (17.4% vs. 13.6%), medical hospitalization (14.2% vs. 8.8%), prednisone (47.8% vs. 31.4%), immunomodulators (52.0% vs. 32.1%), and narcotic analgesics (17.3% vs. 9.1%). Patient mortality was similar for infliximab- and other-treatments-only-treated patients (0.58 vs. 0.59/100 patient-years). In multivariate logistic regression analyses, treatment with prednisone (hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.55, 2.95; P < 0.001) or narcotic analgesics (HR = 1.79, 95% CI = 1.29, 2.48; P < 0.001) and age (HR = 1.08, 95% CI = 1.07, 1.09; P < 0.001) were associated with increased mortality risk. Neither infliximab nor immunomodulator treatment was associated with increased mortality risk. Factors independently associated with serious infections included moderate-to-severe disease activity (HR = 2.24, 95% CI = 1.57, 3.19; P < 0.001), narcotic analgesic treatment (HR = 1.98, 95% CI = 1.44, 2.73; P < 0.001), prednisone therapy (HR = 1.57, 95% CI = 1.17, 2.10; P = 0.002), and infliximab treatment (HR = 1.43, 95% CI = 1.11, 1.84; P = 0.006). CONCLUSIONS: Mortality was similar between infliximab- and other-treatments-only-treated CD patients. An increased risk of serious infection with infliximab was observed, although CD severity and use of prednisone or narcotic analgesics carried higher risks.

The authors argue that the study of the complaint of pain falls within the purview of epidemiological study. An analytic survey of 500 randomly selected households on the roster of a group family practice clinic was undertaken. The purpose was to determine the self-reported prevalence rates of any pain complaint and to determine the distribution of pain rates according to selected demographic and socioeconomic variables. Sixteen percent of the individuals sampled from a family practice (H.S.O.) had experienced pain within the 2 weeks preceding the survey. The prevalence rate of those with persistent pain was approximately twice that of those with temporary pain. More women than men reported temporary and persistent pain. The age specific morbidity rate for persistent pain increased with age. The back, lower extremities, and head and face were the most frequently identified sites of pain in both subgroups. Persons with persistent pain used health services, both community physicians and hospital care, more frequently than did those with temporary pain. No significant differences between the two groups were reported for physical, social or emotional function although the persistent pain group characterized their general health status more poorly.

AGRADECIMENTOS Em Hamlet, há um trecho que sempre me impressionou.Trata-se de uma fala do próprio príncipe da Dinamarca.Após receber a trupe de atores no palácio, Hamlet pede a Polônio para acomodá-los e o lacaio responde que vai tratá-los conforme eles merecem.Em resposta, Hamlet diz a frase que reproduzo livremente: "Ora, Polônio, se fores tratar os homens conforme eles merecem, a verdade é que ninguém escaparia do chicote.Então, trate-os conforme a tua própria honra e dignidade.Quanto menor merecimento eles tiverem, maior será a tua generosidade".A lembrança dessa fala vem a propósito de homenagear e agradecer ao meu orientador, José Sérgio Fonseca de Carvalho, que a despeito de minhas limitações pessoais, acolheu-me com confiança e dedicação que só vieram a provar o seu grande valor, não só de intelectual comprometido e acadêmico rigoroso, mas também de ser humano generoso e acolhedor.Agradeço também aos meus amigos e amigas que fizeram parte da turma ingressante no programa de pós-graduação em Direitos Humanos no ano de 2007 e aos que integram o Grupo de Estudos de Educação e Pensamento Contemporâneo, por tudo o que o convívio amistoso e desinteressado pode gerar de ânimo quando desanimamos e de esperanças quando nos desesperançamos.Agradeço aos professores do programa de pós para os quais reservo as minhas melhores memórias.Agradeço à minha família pela paciência durante esse período tão difícil, tão solitário e também pela impaciência, que às vezes se revela mais útil.

BACKGROUND: In December 2013, an outbreak of Chikungunya virus (CHIKV) caused by the Asian genotype was notified in the Caribbean. The outbreak has since spread to 38 regions in the Americas. By September 2014, the first autochthonous CHIKV infections were confirmed in Oiapoque, North Brazil, and in Feira de Santana, Northeast Brazil. METHODS: We compiled epidemiological and clinical data on suspected CHIKV cases in Brazil and polymerase-chain-reaction-based diagnostic was conducted on 68 serum samples from patients with symptom onset between April and September 2014. Two imported and four autochthonous cases were selected for virus propagation, RNA isolation, full-length genome sequencing, and phylogenetic analysis. We then followed CDC/PAHO guidelines to estimate the risk of establishment of CHIKV in Brazilian municipalities. RESULTS: We detected 41 CHIKV importations and 27 autochthonous cases in Brazil. Epidemiological and phylogenetic analyses indicated local transmission of the Asian CHIKV genotype in Oiapoque. Unexpectedly, we also discovered that the ECSA genotype is circulating in Feira de Santana. The presumed index case of the ECSA genotype was an individual who had recently returned from Angola and developed symptoms in Feira de Santana. We estimate that, if CHIKV becomes established in Brazil, transmission could occur in 94% of municipalities in the country and provide maps of the risk of importation of each strain of CHIKV in Brazil. CONCLUSIONS: The etiological strains associated with the early-phase CHIKV outbreaks in Brazil belong to the Asian and ECSA genotypes. Continued surveillance and vector mitigation strategies are needed to reduce the future public health impact of CHIKV in the Americas.

The outbreak of COVID 19 made many poor communities in different places of the world face very challenging socio-economic and livelihood consequences. This paper targets to analyse this socio-economic impact to determine how the pandemic is causing various problems to the impoverished. An integrative literature review was carried out to sample the consequences of the global pandemic economic crisis on the poor communities in four different continents. The research points out how it is hard on the poor to adhere to the restrictive measures of social isolation or the lockdown. Immediate strategies that minimize the pandemic impact on the livelihood and the socio-economic activities of the poor are suggested. The research opens future research about more specialised programs for the poor during any future lockdowns.

BACKGROUND: Long-term mechanical ventilation is the most common situation for which tracheostomy is indicated for patients in intensive care units (ICUs). 'Early' and 'late' tracheostomies are two categories of the timing of tracheostomy. Evidence on the advantages attributed to early versus late tracheostomy is somewhat conflicting but includes shorter hospital stays and lower mortality rates. OBJECTIVES: To evaluate the effectiveness and safety of early (≤ 10 days after tracheal intubation) versus late tracheostomy (> 10 days after tracheal intubation) in critically ill adults predicted to be on prolonged mechanical ventilation with different clinical conditions. SEARCH METHODS: This is an update of a review last published in 2012 (Issue 3, The Cochrane Library) with previous searches run in December 2010. In this version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 8); MEDLINE (via PubMed) (1966 to August 2013); EMBASE (via Ovid) (1974 to August 2013); LILACS (1986 to August 2013); PEDro (Physiotherapy Evidence Database) at www.pedro.fhs.usyd.edu.au (1999 to August 2013) and CINAHL (1982 to August 2013). We reran the search in October 2014 and will deal with any studies of interest when we update the review. SELECTION CRITERIA: We included all randomized and quasi-randomized controlled trials (RCTs or QRCTs) comparing early tracheostomy (two to 10 days after intubation) against late tracheostomy (> 10 days after intubation) for critically ill adult patients expected to be on prolonged mechanical ventilation. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and conducted a quality assessment. Meta-analyses with random-effects models were conducted for mortality, time spent on mechanical ventilation and time spent in the ICU. MAIN RESULTS: We included eight RCTs (N = 1977 participants). At the longest follow-up time available in these studies, evidence of moderate quality from seven RCTs (n = 1903) showed lower mortality rates in the early as compared with the late tracheostomy group (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98; P value 0.03; number needed to treat for an additional beneficial outcome (NNTB) ≅ 11). Divergent results were reported on the time spent on mechanical ventilation and no differences were noted for pneumonia, but the probability of discharge from the ICU was higher at day 28 in the early tracheostomy group (RR 1.29, 95% CI 1.08 to 1.55; P value 0.006; NNTB ≅ 8). AUTHORS' CONCLUSIONS: The whole findings of this systematic review are no more than suggestive of the superiority of early over late tracheostomy because no information of high quality is available for specific subgroups with particular characteristics.

BACKGROUND: Chronic insufficient sleep is a common finding in many pain-related and other medical diseases and is frequently experienced in the general population. Prolonged curtailment of nocturnal sleep has been studied for its adverse effect on cognitive functioning and subjective tiredness, but relatively little is known about its effect on mood and physical symptoms. OBJECTIVE: In order to test whether sleep restriction to 50% of the habitual time over 12 days affects diurnal and day-to-day variation of subjective ratings of mood and physical symptoms, 108 adjectives and statements were self-rated using visual analog scales every 2h during the waking period. DESIGN: Randomized, 16-day controlled in-laboratory study. SETTING: General Clinical Research Center (GCRC). PARTICIPANTS: Forty healthy subjects aged 21-40 years (14 females, 26 males). INTERVENTION: Subjects were randomized to either 4h of sleep per night (11 pm-3 am, N=22) or 8h of sleep per night (11 pm-7 am, N=18) for 12 consecutive days. MAIN OUTCOME MEASURE: Changes in the factor-derived variables optimism-sociability, tiredness-fatigue, anger-aggression, bodily discomfort, and items constituting bodily discomfort were compared between groups. RESULTS: Optimism-sociability progressively declined over consecutive days of sleep restriction by 15%. Bodily discomfort showed a slight, but significant interindividual increase of 3% across days of sleep restriction due to significant increases of generalized body pain, back pain, and stomach pain. Optimism-sociability and tiredness-fatigue showed diurnal variations with a quadratic function period within each day in both conditions. CONCLUSION: The data suggest that chronic insufficient sleep may contribute to the onset and amplification of pain and affect health by compromising optimistic outlook and psychosocial functioning.

Chromoblastomycosis is one of the most frequent infections caused by melanized fungi. It is a subcutaneous fungal infection, usually an occupational related disease, mainly affecting individuals in tropical and temperate regions. Although several species are etiologic agents, Fonsecaea pedrosoi and Cladophialophora carrionii are prevalent in the endemic areas. Chromoblastomycosis lesions are polymorphic and must be differentiated from those associated with many clinical conditions. Diagnosis is confirmed by the observation of muriform cells in tissue and the isolation and the identification of the causal agent in culture. Chromoblastomycosis still is a therapeutic challenge for clinicians due to the recalcitrant nature of the disease, especially in the severe clinical forms. There are three treatment modalities, i.e., physical treatment, chemotherapy and combination therapy but their success is related to the causative agent, the clinical form and severity of the chromoblastomycosis lesions. There is no treatment of choice for this neglected mycosis, but rather several treatment options. Most of the patients can be treated with itraconazole, terbinafine or a combination of both. It is also important to evaluate the patient's individual tolerance of the drugs and whether the antifungal will be provided for free or purchased, since antifungal therapy must be maintained in long-term regimens. In general, treatment should be guided according to clinical, mycological and histopathological criteria.

Virus-host interactions determine an infection outcome. The Asian lineage of Zika virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the NS1 gene after 2012 that enhances mosquito infection. Here we report that the same mutation confers NS1 to inhibit interferon-β induction. This mutation enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon-β induction; reversing the mutation in an epidemic ZIKV strain invigorates the virus for interferon-β induction; these mutational effects are lost in IRF3-knockout cells. Additionally, ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also suppress interferon-β production through targeting distinct components of the RIG-I pathway; however, for these proteins, no antagonistic difference is observed among various ZIKV strains. Our results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics.

OBJECTIVE: The blood-brain barrier (BBB) is often perceived as a passive membrane. However, evidence has demonstrated that the BBB plays an active role in normal homeostasis and in certain disease processes. METHODS: Approximately 300 peer-reviewed publications that discussed normal or abnormal BBB function were reviewed. RESULTS: The role of the BBB and how it contributes to disorders of the central nervous system vary, depending on the specific disease process. CONCLUSION: In health and disease and extending to old age, endothelial cells, neurons, and glia constitute a neurovascular unit that regulates the BBB. Advances toward penetrating the BBB must account for both normal and abnormal functions of the neurovascular unit.

BACKGROUND: A number of conditions compromise the passage of food along the digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven technique, although its prolonged use can lead to complications such as lesions to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG), is generally used when there is a need for enteral nutrition for a longer time period. There is a high demand for PEG in patients with swallowing disorders, although there is no consistent evidence about its effectiveness and safety as compared to NGT. OBJECTIVES: To evaluate the effectiveness and safety of PEG compared with NGT for adults with swallowing disturbances. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to January 2014, and contacted the main authors in the subject area. There was no language restriction in the search. SELECTION CRITERIA: We planned to include randomised controlled trials comparing PEG versus NGT for adults with swallowing disturbances or dysphagia and indications for nutritional support, with any underlying diseases. The primary outcome was intervention failure (e.g. feeding interruption, blocking or leakage of the tube, no adherence to treatment). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. For dichotomous and continuous variables, we used risk ratio (RR) and mean difference (MD), respectively with the random-effects statistical model and 95% confidence interval (CI). We assumed statistical heterogeneity when I² > 50%. MAIN RESULTS: We included 11 randomised controlled studies with 735 participants which produced 16 meta-analyses of outcome data. Meta-analysis indicated that the primary outcome of intervention failure, occurred in lower proportion of participants with PEG compared to NGT (RR 0.18, 95% CI 0.05 to 0.59, eight studies, 408 participants, low quality evidence) and this difference was statistically significant. For this outcome, we also subgrouped the studies by endoscopic gastrostomy technique into pull, and push and not reported. We observed a significant difference favouring PEG in the pull subgroup (RR 0.07, 95% CI 0.01 to 0.35, three studies, 90 participants). Thepush subgroup contained only one clinical trial and the result favoured PEG (RR 0.05, 95% CI 0.00 to 0.74, one study, 33 participants) techniques. We found no statistically significant difference in cases where the technique was not reported (RR 0.43, 95% CI 0.13 to 1.44, four studies, 285 participants).There was no statistically significant difference between the groups for meta-analyses of the secondary outcomes of mortality (RR 0.86, 95% CI 0.58 to 1.28, 644 participants, nine studies, very low quality evidence), overall reports of any adverse event at any follow-up time point (ITT analysis, RR 0.83, 95% CI 0.51 to 1.34), 597 participants, 6 studies, moderate quality evidence), specific adverse events including pneumonia (aspiration) (RR 0.70, 95% CI 0.46 to 1.06, 645 participants, seven studies, low quality evidence), or for the meta- analyses of the secondary outcome of nutritional status including weight change from baseline, and mid-arm circumference at endpoint, although there was evidence in favour of PEG for meta-analyses of mid-arm circumference change from baseline (MD 1.16, 95% CI 1.01 to 1.31, 115 participants, two studies), and levels of serum albumin were higher in the PEG group (MD 6.03, 95% CI 2.31 to 9.74, 107 participants).For meta-analyses of the secondary outcomes of time on enteral nutrition, there was no statistically significant difference (MD 14.48, 95% CI -2.74 to 31.71; 119 participants, two studies). For meta-analyses of quality of life measures (EuroQol) outcomes in two studies with 133 participants, for inconvenience (RR 0.03, 95% CI 0.00 to 0.29), discomfort (RR 0.03, 95% CI 0.00 to 0.29), altered body image (RR 0.01, 95% CI 0.00 to 0.18; P = 0.001) and social activities (RR 0.01, 95% CI 0.00 to 0.18) the intervention favoured PEG, that is, fewer participants found the intervention of PEG to be inconvenient, uncomfortable or interfered with social activities. However, there were no significant differences between the groups for pain, ease of learning to use, or the secondary outcome of length of hospital stay (two studies, 381 participants). AUTHORS' CONCLUSIONS: PEG was associated with a lower probability of intervention failure, suggesting the endoscopic procedure may be more effective and safe compared with NGT. There is no significant difference in mortality rates between comparison groups, or in adverse events, including pneumonia related to aspiration. Future studies should include details of participant demographics including underlying disease, age and gender, and the gastrostomy technique.

OBJECTIVE: To assess the arrangement of myocardial bridges. DESIGN: A necropsy study of 90 consecutive hearts (56 male, 34 female). RESULTS: Myocardial bridges, either single or multiple, were seen in 50 (55.6%) of the 90 hearts. The left anterior descending artery was the most commonly affected artery. Thirty five of the 50 hearts which contained in total 41 muscle bridges were dissected further with a magnifying glass. Two different types of muscle bridges could be identified. Thirty one of these 41 myocardial bridges were superficial, crossing the artery transversely towards the apex of the heart at an acute angle or perpendicularly. The remaining 10 myocardial bridges crossed the left anterior descending coronary artery and surrounded it by a muscle bundle that arose from the right ventricular apical trabeculae and crossed the artery transversely, obliquely, or helically before terminating in the interventricular septum. CONCLUSIONS: The superficial type of myocardial bridge does not seem to constrict the artery during systole but the deep muscle bridges, by virtue of their relation with the left anterior descending coronary artery, could twist the vessel and thus compromise its diastolic flow. This may result in ischaemia.

Estudo de coorte sobre a mortalidade neonatal na pesquisa Nascer no Brasil, com entrevista e avaliação de prontuários de 23.940 puérperas entre fevereiro de 2011 e outubro de 2012. Utilizou-se modelagem hierarquizada para análise dos potenciais fatores de risco para o óbito neonatal. A taxa de mortalidade foi 11,1 por mil; maior nas regiões Norte e Nordeste e nas classes sociais mais baixas. O baixo peso ao nascer, o risco gestacional e condições do recém-nascido foram os principais fatores associados ao óbito neonatal. A inadequação do pré-natal e da atenção ao parto indicaram qualidade não satisfatória da assistência. A peregrinação de gestantes para o parto e o nascimento de crianças com peso &lt; 1.500g em hospital sem UTI neonatal demonstraram lacunas na organização da rede de saúde. Óbitos de recém-nascidos a termo por asfixia intraparto e por prematuridade tardia expressam a evitabilidade dos óbitos. A qualificação da atenção, em especial da assistência hospitalar ao parto se configura como foco prioritário para maiores avanços nas políticas públicas de redução das taxas e das desigualdades na mortalidade infantil no Brasil.

Essential oils have shown promise as antiviral agents against several pathogenic viruses. In this work we hypothesized that essential oil components may interact with key protein targets of the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A molecular docking analysis was carried out using 171 essential oil components with SARS-CoV-2 main protease (SARS-CoV-2 Mpro), SARS-CoV-2 endoribonucleoase (SARS-CoV-2 Nsp15/NendoU), SARS-CoV-2 ADP-ribose-1″-phosphatase (SARS-CoV-2 ADRP), SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp), the binding domain of the SARS-CoV-2 spike protein (SARS-CoV-2 rS), and human angiotensin−converting enzyme (hACE2). The compound with the best normalized docking score to SARS-CoV-2 Mpro was the sesquiterpene hydrocarbon (E)-β-farnesene. The best docking ligands for SARS−CoV Nsp15/NendoU were (E,E)-α-farnesene, (E)-β-farnesene, and (E,E)−farnesol. (E,E)−Farnesol showed the most exothermic docking to SARS-CoV-2 ADRP. Unfortunately, the docking energies of (E,E)−α-farnesene, (E)-β-farnesene, and (E,E)−farnesol with SARS-CoV-2 targets were relatively weak compared to docking energies with other proteins and are, therefore, unlikely to interact with the virus targets. However, essential oil components may act synergistically, essential oils may potentiate other antiviral agents, or they may provide some relief of COVID-19 symptoms.

The traditional reconstructive ladder has withstood the test of time, serving as a thought paradigm to guide surgeons in choosing their method of wound closure for an assortment of defects. Advances in anatomical understanding and technological innovations have improved our ability to achieve definitive closure in a wide variety of patients. In this article, the older construct is updated to reflect the use of negative-pressure wound therapy and dermal matrices. Perforator flap concepts are also discussed in terms of their inclusion as a rung on the ladder.

Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing. Overall, the NTT and LDT behaviors demonstrate a generally good cross-test correlation in vivo, whereas meta-analyses of published literature show that both tests have similar sensitivity to zebrafish anxiety-like states. Finally, NTT evokes higher levels of cortisol, likely representing a more stressful procedure than LDT. Collectively, our study reappraises NTT and LDT for studying anxiety-like states in zebrafish, and emphasizes their developing utility for neurobehavioral research. These findings can help optimize drug screening procedures by choosing more appropriate models for testing anxiolytic or anxiogenic drugs.

This work demonstrates that the integration of variable-speed wind systems with doubly fed induction generators (DFIG) and a four-quadrant AC-to-AC converter connected to the rotor windings increases the transient stability margin of the electrical grids, when compared with the case where the fixed speed wind systems with cage generators are used. It is due to the influence of the two dedicated rotor current regulators of the DFIG on the dynamic behavior of the other generators in the system. Besides, adequate models to represent the behavior of the DFIG in transient stability studies are presented. From the simulation results, some important conclusions can be extracted to guide the integration of the wind farms on weak or strong grids.

Prion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized by amyloid deposition, astrogliosis, microglial activation, tissue vacuolation and neuronal loss. In the ME7 model of prion disease in the C57BL/6 J mouse, we have shown previously that these animals display behavioural changes that indicate the onset of neuronal dysfunction. The current study examines the neuropathological correlates of these early behavioural changes. After injection of ME7-infected homogenate into the dorsal hippocampus, we found statistically significant impairment of burrowing, nesting and glucose consumption, and increased open field activity at 13 weeks. At this time, microglia activation and PrPSc deposition was visible selectively throughout the limbic system, including the hippocampus, entorhinal cortex, medial and lateral septum, mamillary bodies, dorsal thalamus and, to a lesser degree, in regions of the brainstem. No increase in apoptosis or neuronal cell loss was detectable at this time, while in animals at 19 weeks postinjection there was 40% neuronal loss from CA1. There was a statistically significant reduction in synaptophysin staining in the stratum radiatum of the CA1 at 13 weeks indicating loss of presynaptic terminals. Damage to the dorsal hippocampus is known to disrupt burrowing and nesting behaviour. We have demonstrated a neuropathological correlate of an early behavioural deficit in prion disease and suggest that this should allow insights into the first steps of the neuropathogenesis of prion diseases.