Status epilepticus-Therapeutic management at the pediatric emergency department.

INTRODUCTION: Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus. METHODS: Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus. RESULTS: One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05). CONCLUSIONS: Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes.

PAHs in franciscana dolphins from the Southwestern Atlantic Ocean: Concentration and maternal transfer assessments.

Polycyclic aromatic hydrocarbons (PAHs) are organic compounds ubiquitous in the environment and known for their toxic, mutagenic, and carcinogenic effects. These compounds can bioaccumulate in the biota and be transferred through trophic webs. The franciscana dolphin (Pontoporia blainvillei), as top predators, can be an environmental sentinels. Thus, this study aimed to provide data about PAHs concentration in their hepatic tissue collected on the coast of Espírito Santo (Franciscana Management Area, FMA Ia), Rio de Janeiro (FMA IIa), and São Paulo states (FMA IIb), in Southeastern Brazil. PAHs were detected in 86 % of franciscana dolphins (n = 50). The highest ∑PAHsTotal median concentration was reported in FMA Ia followed by FMA IIb and FMA IIa (1055.6; 523.9, and 72.1 ng.g-1 lipid weight, respectively). Phenanthrene was detected in one fetus and two neonates, showing maternal transfer of PAHs in these dolphins. Evaluating PAHs with potential toxic effects is of utmost importance for the conservation of a threatened species.

Criteria for progressive fibrotic hypersensitivity pneumonitis in a Portuguese patient cohort.

Background: Hypersensitivity pneumonitis (HP) is a syndrome caused by sensitisation to inhaled antigens that leads to an abnormal immune response in the airways and lung parenchyma. Some patients previously diagnosed with certain types of fibrotic interstitial lung diseases (f-ILDs), including fibrotic HP (f-HP), are susceptible to develop a progressive fibrosing phenotype (PF-ILD), despite initial state-of-the-art management. Objectives: To characterise a cohort of patients with a multidisciplinary diagnosis (MTD) of chronic f-HP, who were followed up in an ILD outpatient clinic of a hospital in Portugal, and to assess the prevalence of PF-ILD criteria in these patients. Methods: Data were collected from all patients with a definite or provisional diagnosis of f-HP after a multidisciplinary team discussion. Patients were followed up between December 2014 and July 2019. Data included clinical characteristics, high-resolution chest tomography (HRCT) disease patterns, lung function tests, bronchoalveolar lavage and further immunological work-up, biopsy reports (conventional transbronchial lung biopsy, transbronchial lung cryobiopsy or surgical video-assisted thoracoscopic lung biopsy), all ILD multidisciplinary team records and diagnostic confidence levels. Patients were assessed according to PF-ILD criteria as defined in the INBUILD trial. Results: We identified 83 patients with an MTD of HP, who had been followed up for at least 12 months. Of these, 63 (75.9%) were diagnosed with f-HP. Of the 63 f-HP patients, 33.3% (n=21) fulfilled the predefined criteria for PF-HP: 66.7% had a relative decline of ≥10% forced vital capacity (FVC); 5% a relative decline of 5 - 9% FVC, with worsening symptoms or increased fibrosis on HRCT; and 23.8% had worsening respiratory symptoms with radiological progression. Conclusion: This single-centre cohort study demonstrated that a third of f-HP patients presented with PF-ILD, as determined by progression during initial standard-of-care treatment. A usual interstitial pneumonia (UIP)/UIP-like pattern was present in >70% of patients with f-HP, and two-thirds of these patients had an FVC decline of ≥10%. PF-HP patients were also more exacerbation prone. According to recent trial data, this segment of patients can be considered possible candidates for antifibrotic treatment, with a reasonable prospect of effectiveness. Further efforts should focus on refining knowledge of longitudinal behaviour of large multicentric cohorts of f-HP patients, establishing a consensual and uniform definition of progression for use in clinical practice, as well as developing prognostic prediction tools to better (and early) inform the disease course.

Allergic sensitization to Storage Dust Mites: a prospective study of patients with respiratory allergy

Summary: Objectives. To describe the prevalence of allergic sensitization to Storage Dust Mites (SDM), access whether the place of living and occupational exposure were determinants for SDM sensitization and study association between Lepidoglyphus destructor and other SDM sensitization. Methods. Prospective analysis of patients evaluated for suspected allergic rhinitis and/or asthma that performed Skin Prick Tests (SPT) to SDM between January and December 2018 in our Department. Results. Two hundred consecutive patients were evaluated for rhinitis and/or asthma in our outpatient consultation: 123 (61.5%) presented positivity for at least one SDM, 68.3% were female and the mean age was 33.1 ± 12.12. Lepidoglyphus destructor (69.9%) was the most prevalent, followed by Tyrophagus putrescentiae (50.4%), Blomia tropicalis and Glycyphagus domesticus (48.8%) and Acarus siro (24.4%). Living in a rural place was not associated with a higher prevalence of sensitization to SDM, except for Acarus siro (p = 0.032), and working in a place with storage areas was not associated with sensitization to any of SDM. Sensitization to Lepidoglyphus destructor was associated with sensitization to Blomia tropicalis, Glycyphagus domesticus and Tyrophagus putrescentiae (p less than 0.005), but not with Acarus siro.Conclusions. Our study suggests that our population, independently of their occupational exposure and place of residency, are sensitized to SDM and that evaluation of sensitization to SDM should be considered as standard practice.

Temporal trends of trace elements bioaccumulation by a vulnerable cetacean (Pontoporia blainvillei) before and after one of the largest mining disasters worldwide.

One of the largest environmental disasters worldwide occurred on November 5th, 2015, when the Fundão dam collapsed in Mariana (Minas Gerais State, Southeast Brazil). The tailing mud flooded the Doce River basin and reached the sea in the coast of Espírito Santo State (ES), Southeast Brazil. This coastal region is the habitat of the most isolated population of franciscana dolphins (Pontoporia blainvillei), with the lowest populational census and lowest genetic diversity in Franciscana Management Area Ia (FMA Ia) - 18° 25'S and 21° 17'S. This study aimed to assess the bioaccumulation of trace-elements (As, Cd, Cu, Fe, Hg, Mn, and Zn) in muscle, liver and kidney of franciscana dolphins collected near the Doce River's mouth before (n = 32) and after (n = 19) the tailing mud reached the sea. The Generalized Additive Model (GAM) showed increasing temporal trends of Hg and Zn in muscle and liver after the dam failure, probably related to higher concentrations and bioavailability in the water column and sediments from the Doce River. Declining trends were found for As and Cu muscular and hepatic concentrations and Fe concentrations in kidney due to their lower bioavailability after the disaster, caused by association with tailings mud trapped in the riverbanks and suspended particulate material. Additionally, higher As and Hg concentrations found in the first period of sampling may be due to historical contamination by mining activities. The full extent of the impacts caused by the Fundão dam failure is still unknown. However, due to their rapid increase and remobilization process, toxic effects can be induced in the biota by these elements. Elements' bioaccumulation in this study contributes to the knowledge of franciscana dolphins from FMA Ia. Considering the conservation concern regarding this franciscana population and its scarce knowledge, the impact of this disaster can be alarming for species conservation.

Brasilia tapaculo (Scytalopus novacapitalis) seasonality and site occupancy in altitudinal riparian environments after non-natural burnings and feral pig invasion in Serra da Canastra National Park, Brazil.

The Brasilia Tapaculo, Scytalopus novacapitalis Sick, 1958, is a rare, geographically restricted, and endangered bird species that inhabits riparian vegetation of Cerrado, mainly Gallery Forests. In Serra da Canastra National Park, southeastern Brazil, wetlands are under threat due to frequent non-natural burnings and invasion by feral pigs, Sus scrofa, Linnaeus, 1758. We aimed to evaluate the possible effects of seasonal variations on S. novacapitalis records in undisturbed habitats and answer questions about how fire and feral pigs may affect site occupancy of the species. Transects alongside riparian environments were used to survey n=21 sites, totalizing 7.5 Km, from 2014 to 2019. Results indicated the season influenced both, spontaneous records and induced encounters by playback method, which were more abundant in breeding period, from early spring to summer. The use of playback significantly increased the amount of records in all seasons. The probability of site occupancy in all studied area was higher in late spring (ψ=0.91) and lower in autumn (ψ=0.73). In burned sites (n=8), the first post-fire month showed the lowest probability of occupancy, but there was a rapid recovery in 2nd month and stabilization similar to control area from the 3rd month ahead. After sites (n=11) were invaded by feral pigs, the estimation of site occupancy indicated a slight drop in first two months, but after the 3rd month of invasion the decreasing pattern enhanced the discrepancy with undisturbed areas. It is important to keep monitoring S. novacapitalis population and their threats, to subsidize management actions, especially to avoid frequently unusual burnings in riparian forests, and to block the access of feral pigs to wetlands.

Brasilia tapaculo (Scytalopus novacapitalis) seasonality and site occupancy in altitudinal riparian environments after non-natural burnings and feral pig invasion in Serra da Canastra National Park, Brazil / Sazonalidade do Tapaculo-de-Brasília (Scytalopus novacapitalis) e ocupação de área em ambientes ripários de altitude após queimadas não naturais e invasão por javaporco no Parque Nacional da Serra da Canastra, Brasil

The Brasilia Tapaculo, Scytalopus novacapitalis Sick, 1958, is a rare, geographically restricted, and endangered bird species that inhabits riparian vegetation of Cerrado, mainly Gallery Forests. In Serra da Canastra National Park, southeastern Brazil, wetlands are under threat due to frequent non-natural burnings and invasion by feral pigs, Sus scrofa, Linnaeus, 1758. We aimed to evaluate the possible effects of seasonal variations on S. novacapitalis records in undisturbed habitats and answer questions about how fire and feral pigs may affect site occupancy of the species. Transects alongside riparian environments were used to survey n=21 sites, totalizing 7.5 Km, from 2014 to 2019. Results indicated the season influenced both, spontaneous records and induced encounters by playback method, which were more abundant in breeding period, from early spring to summer. The use of playback significantly increased the amount of records in all seasons. The probability of site occupancy in all studied area was higher in late spring (ψ=0.91) and lower in autumn (ψ=0.73). In burned sites (n=8), the first post-fire month showed the lowest probability of occupancy, but there was a rapid recovery in 2nd month and stabilization similar to control area from the 3rd month ahead. After sites (n=11) were invaded by feral pigs, the estimation of site occupancy indicated a slight drop in first two months, but after the 3rd month of invasion the decreasing pattern enhanced the discrepancy with undisturbed areas. It is important to keep monitoring S. novacapitalis population and their threats, to subsidize management actions, especially to avoid frequently unusual burnings in riparian forests, and to block the access of feral pigs to wetlands.

O tapaculo-de-Brasília, Scytalopus novacapitalis, Sick 1958, é uma espécie de ave rara, geograficamente restrita e ameaçada de extinção que habita vegetação ripária do Cerrado, principalmente matas de galeria. No Parque Nacional da Serra da Canastra, sudeste do Brasil, áreas úmidas estão ameaçadas devido a frequentes queimadas não naturais e a invasão por javaporco, Sus scrofa Linnaeus, 1758. Avaliamos os possíveis efeitos da sazonalidade na quantidade de registros de S. novacapitalis em habitats sem perturbação e buscamos responder questões sobre como o fogo e a invasão por javaporco pode afetar a ocupação de área pela ave. Transecções paralelas aos ambientes ripários foram usadas para amostrar n=21 áreas, totalizando 7,5 km, de 2014 a 2019. Os resultados indicaram que a estação do ano influenciou na quantidade de registros espontâneos e de registros induzidos por playback, os quais foram mais abundantes durante o período reprodutivo. O uso de playback aumentou significativamente a quantidade de registros em todas as estações. A probabilidade de ocupação considerando toda área de estudo foi maior no fim da primavera (ψ=0,91) e menor no outono (ψ=0,73). Em áreas queimadas (n=8 trechos), o primeiro mês após o fogo apresentou a menor probabilidade de ocupação, mas houve uma rápida recuperação no 2º mês, e estabilização similar na área controle a partir do 3º mês. Após n=11 trechos terem sido invadidos por javaporcos, a estimativa de ocupação de área indicou pequena queda nos dois primeiros meses, mas a partir do 3º mês, o padrão de decréscimo ampliou a discrepância com áreas não perturbadas. É importante continuar monitorando a população de S. novacapitalis e suas ameaças, para subsidiar ações de manejo, principalmente para evitar queimadas não naturais frequentes nas florestas ripárias e bloquear o acesso de javaporcos às áreas úmidas.

Heavy metals in the bottom sediments of the Furo of Laura estuary, Eastern Amazon, Brazil.

The Furo of Laura is an economically important river in the Amazon estuary. Thus, in the present study, we evaluated the metal distribution (Al, Cd, Co, Cu, Cr, Fe, Ni, and Mg) in the bottom sediments of this river. The sediments were sampled at four points every 2months for a year with an Ekman-Birge sampler. After microwave acid digestion, the metal levels were determined by optical emission spectrometry with inductively coupled plasma. The particle size and organic matter content influenced the concentration of the metals. The sediments were not enriched by the analyzed metals; the estuary therefore retained the characteristics of an uncontaminated environment, thus serving as a reference environment for comparison.

Brasilia tapaculo (Scytalopus novacapitalis) seasonality and site occupancy in altitudinal riparian environments after non-natural burnings and feral pig invasion in Serra da Canastra National Park, Brazil

Abstract The Brasilia Tapaculo, Scytalopus novacapitalis Sick, 1958, is a rare, geographically restricted, and endangered bird species that inhabits riparian vegetation of Cerrado, mainly Gallery Forests. In Serra da Canastra National Park, southeastern Brazil, wetlands are under threat due to frequent non-natural burnings and invasion by feral pigs, Sus scrofa, Linnaeus, 1758. We aimed to evaluate the possible effects of seasonal variations on S. novacapitalis records in undisturbed habitats and answer questions about how fire and feral pigs may affect site occupancy of the species. Transects alongside riparian environments were used to survey n=21 sites, totalizing 7.5 Km, from 2014 to 2019. Results indicated the season influenced both, spontaneous records and induced encounters by playback method, which were more abundant in breeding period, from early spring to summer. The use of playback significantly increased the amount of records in all seasons. The probability of site occupancy in all studied area was higher in late spring (=0.91) and lower in autumn (=0.73). In burned sites (n=8), the first post-fire month showed the lowest probability of occupancy, but there was a rapid recovery in 2nd month and stabilization similar to control area from the 3rd month ahead. After sites (n=11) were invaded by feral pigs, the estimation of site occupancy indicated a slight drop in first two months, but after the 3rd month of invasion the decreasing pattern enhanced the discrepancy with undisturbed areas. It is important to keep monitoring S. novacapitalis population and their threats, to subsidize management actions, especially to avoid frequently unusual burnings in riparian forests, and to block the access of feral pigs to wetlands.

Resumo O tapaculo-de-Brasília, Scytalopus novacapitalis, Sick 1958, é uma espécie de ave rara, geograficamente restrita e ameaçada de extinção que habita vegetação ripária do Cerrado, principalmente matas de galeria. No Parque Nacional da Serra da Canastra, sudeste do Brasil, áreas úmidas estão ameaçadas devido a frequentes queimadas não naturais e a invasão por javaporco, Sus scrofa Linnaeus, 1758. Avaliamos os possíveis efeitos da sazonalidade na quantidade de registros de S. novacapitalis em habitats sem perturbação e buscamos responder questões sobre como o fogo e a invasão por javaporco pode afetar a ocupação de área pela ave. Transecções paralelas aos ambientes ripários foram usadas para amostrar n=21 áreas, totalizando 7,5 km, de 2014 a 2019. Os resultados indicaram que a estação do ano influenciou na quantidade de registros espontâneos e de registros induzidos por playback, os quais foram mais abundantes durante o período reprodutivo. O uso de playback aumentou significativamente a quantidade de registros em todas as estações. A probabilidade de ocupação considerando toda área de estudo foi maior no fim da primavera (=0,91) e menor no outono (=0,73). Em áreas queimadas (n=8 trechos), o primeiro mês após o fogo apresentou a menor probabilidade de ocupação, mas houve uma rápida recuperação no 2º mês, e estabilização similar na área controle a partir do 3º mês. Após n=11 trechos terem sido invadidos por javaporcos, a estimativa de ocupação de área indicou pequena queda nos dois primeiros meses, mas a partir do 3º mês, o padrão de decréscimo ampliou a discrepância com áreas não perturbadas. É importante continuar monitorando a população de S. novacapitalis e suas ameaças, para subsidiar ações de manejo, principalmente para evitar queimadas não naturais frequentes nas florestas ripárias e bloquear o acesso de javaporcos às áreas úmidas.

Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors.

BACKGROUND: Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis. RESULTS: Array-CGH of 50 primary WTs without pre-chemotherapy revealed a few recurrent CNAs not previously reported, such as 7q and 20q gains, and 7p loss. Genomic amplifications were exclusively detected in 3 cases of WTs that later relapsed, which also exhibited an increased frequency of gains affecting a 16.2 Mb 1q21.1-q23.2 region, losses at 11p, 11q distal, and 16q, and WT1 deletions. Conversely, aneuploidies of chromosomes 13 and 19 were found only in WTs without further relapse. The 1q21.1-q23.2 gain associated with WT relapse harbours genes such as CHD1L, CRABP2, GJA8, MEX3A and MLLT11 that were found to be over-expressed in WTs. In addition, down-regulation of genes encompassed by focal deletions highlighted new potential tumor suppressors such as CNKSR1, MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2), BBOX and FIBIN (11p13), and PLCG2 (16q). CONCLUSION: This study confirmed the presence of CNAs previously related to WT and characterized new CNAs found only in few cases. The later were found in higher frequency in relapsed cases, suggesting that they could be associated with WT progression.

Effects of the PPARα agonist WY-14,643 on plasma lipids, enzymatic activities and mRNA expression of lipid metabolism genes in a marine flatfish, Scophthalmus maximus.

Fibrates and other lipid regulator drugs are widespread in the aquatic environment including estuaries and coastal zones, but little is known on their chronic effects on non-target organisms as marine fish. In the present study, turbot juveniles were exposed to the PPARα model agonist WY-14,643 for 21 days by repeated injections at the concentrations of 5mg/kg (lo-WY) and 50mg/kg (hi-WY), and samples taken after 7 and 21 days. Enzyme activity and mRNA expression of palmitoyl-CoA oxidase and catalase in the liver were analyzed as first response, which validated the experiment by demonstrating interactions with the peroxisomal fatty acid oxidation and oxidative stress pathways in the hi-WY treatment. In order to get mechanistic insights, alterations of plasma lipids (free cholesterol, FC; HDL associated cholesterol, C-HDL; triglycerides, TG; non-esterified fatty acids, NEFA) and hepatic mRNA expression of 17 genes involved in fatty acid and lipid metabolism were studied. The exposure to hi-WY reduced the quantity of plasma FC, C-HDL, and NEFA. Microsomal triglyceride transfer protein and apolipoprotein E mRNA expression were higher in hi-WY, and indicated an increased formation of VLDL particles and energy mobilization from liver. It is speculated that energy depletion by PPARα agonists may contribute to a higher susceptibility to environmental stressors.

Baastrup's Disease: a poorly recognised cause of back pain.

A 56-year-old male complained about progressive mechanical back pain for more than 10 years, which worsened with prolonged orthostatism and spine extension and improved in fetal position. His lumbar spine radiography revealed enlargement and sclerosis of the spinous processes which was confirmed by computed tomography, suggesting Baastrup's disease. This condition is characterized by enlargement, close approximation and impingement of one spinous process on another ("kissing spines"). There are few studies on Baastrup´s disease epidemiology and their results are inconsistent. Patients often complain of back pain, typically increased with extension and relieved by flexion. Radiographically, spinous process impingement leads to reactive sclerosis, enlargement, flattening, and remodeling of the involved vertebral spines. Physicians frequently miss it on radiographs due to lack of knowledge and overexposure of spinous processes in most X rays. Both conservative and surgical options are available for treatment. Baastrup's disease should be considered in differential diagnosis of back pain, although one must be aware the typical radiographic changes appear to be common with aging and may not be the cause of patient's symptoms.

Análise histomorfométrica do útero na espécie canina do nascimento aos seis meses de idade / Histomorphometric analysis of the uterus in dogs from birth to six months of age

Objetivou-se caracterizar para a espécie canina o desenvolvimento histológico uterino do nascimento aos seis meses de idade. Foram analisados úteros (n=32) de animais com idades entre um e 180 dias pós-nascimento (DPN), distribuídos em oito grupos: G1-1 DPN (1 Yorkshire Terrier, 1 Poodle, 2 Sem Raça Definida (SRD)/peso médio (Pm)=190g), G2-15 DPN (2 Yorkshire Terrier e 2 SRD/Pm=354g), G3-30 DPN (1 Rottweiler, 1 Poodle, 2 SRD/Pm=985g), G4-45 DPN (1 Poodle, 3 SRD/Pm=1,1kg), G5-60 DPN (1 Yorkshire Terrier, 1 Poodle e 2 SRD/Pm=1,4kg), G6-90 DPN (4 SRD/Pm=2,8kg), G7-120 DPN (1 Poodle e 3 SRD/Pm=6,6kg) e G8-180 DPN (1 Rottweiler, 1 Poodle e 2 SRD/Pm=11kg). A análise histológica constituiu de mensurações das espessuras (µm) da parede uterina, miométrio, endométrio, assim como diâmetro (µm) e número de glândulas endometriais. A análise estatística demonstrou estabilidade e homogeneidade nas estruturas avaliadas com coeficientes de variação baixos (<10%). Observou-se: útero com um DPN: epitélio com células cúbicas simples, miométrio rudimentar, presença de perimétrio e ausência de glândulas endometriais; aos 15 DPN: desenvolvimento de estrutura primordial de formação das glândulas endometriais; dos 30 aos 45 DPN: endométrio e glândulas endometriais simples; aos 60 DPN: glândulas endometriais em lâmina própria com ramificações e discreto pregueamento endometrial; de 90 a 180 DPN: todas as estruturas uterinas apresentaram histoarquitetura de um animal maduro. Todas as variáveis analisadas apresentaram correlação positiva com a idade pós-nascimento (R2≥72,2%). Conclui-se que o útero da cadela desenvolve-se continuamente do nascimento à 180 dias de vida e que apresenta-se desprovido de glândulas endometriais ao nascimento. As primeiras glândulas endometriais são observadas aos 15 dias de vida e apresenta conformação histológica de um animal adulto após 60 dias do nascimento.

This study aimed to characterize canine species' uterine histological development from birth to six months of age. Uteri (n = 32) of animals aged between one and 180 days postnatal (PND), distributed into eight groups were analyzed: G1-1 PND (1 Yorkshire Terrier, Poodle 1, 2 Mixed Breed (MB)/Medium weight (Mw) = 190g), G2-15 PND (2 Yorkshire Terrier and 2 MB/Mw = 354g), G3-30 PND (1 Rottweiler, 1 Poodle, 2 MB/Mw = 985g), G4-45 PND (1 Poodle, 3 MB/Mw = 1.1kg), G5-60 PND (1 Yorkshire Terrier, Poodle 1 and 2 MB/Mw = 1.4kg), G6-90 PND (4 MB/Mw = 2.8kg), G7-120 PND (1 Poodle and 3 MB/Mw = 6.6kg) and G8-180 PND (1 Rottweiler, Poodle 1 and 2 MB/Mw = 11kg). Histological examination consisted of thickness measurement (µm) of the uterine wall, myometrium, endometrium, as well as diameter (µm) and number of endometrial glands. Statistical analysis showed stability and uniformity in the evaluated structures with low coefficients of variation (<10%). We observed: uterus with one PND: simple cubic epithelium cells, rudimentary myometrium, perimetrium presence and absence of endometrial glands; at 15 PND: development of primordial structure formation of endometrial glands; from 30 to 45 PND: simple endometrium and endometrial glands; PND 60: endometrial glands in the lamina propria with branches and discreet endometrial pleating; 90-180 PND: uterine all structures presented histoarchitecture of a mature animal. All variables were positively correlated with postnatal age (R2 ≥ 72.2%). It is concluded that the uterus of the bitch continuously evolves from birth to 180 days old and is presented devoid of endometrial glands at birth. The first endometrial glands are observed at 15 days of life and present histological conformation to an adult 60 days after birth.

Orientación hacia el paciente en la enseñanza de farmacia en España / Patient centeredness in Pharmacy education in Spain

La educación de un profesional consiste en la aportación de conocimientos, actitudes y habilidades que hacen posible el ejercicio. El paradigma de la enseñanza universitaria se ha desplazado desde el ‘sabe’, o incluso el ‘sabe cómo’, hacia el ‘muestra cómo’ y, más importante aún, el ‘hace’. Este era uno de los fundamentos en los que se basaba la modernización del Espacio Europeo de Educación Superior (EEES), creado por la Declaración de Boloña. Como consecuencia de esta normativa, los currículos de los estudios de farmacia han sufrido modificaciones en los pasados años. Varios organismos internacionales apoyan el movimiento del papel del farmacéutico hacia el de un profesional involucrado en los cuidados directos al paciente. Este enfoque en el paciente de la práctica farmacéutica, debería estar basado en similar enfoque en la educación del farmacéutico, lo que no siempre se está consiguiendo en España y en la mayoría de los países del EEES

Education of professionals comprises providing knowledge, attitudes and skills that enable them to practice. The paradigm of university education has shifted from ‘knows’, or even ‘knows how’, to ‘shows how’ and, even more important, to ‘does’. This was one of the fundamentals to build the modern European Higher Education Area (EHEA) created with the Bologna Declaration. As a consequence of this regulation, pharmacy curricula have been modified in the past years. Several international institutions support the movement of pharmacists’ role towards a professional involved on direct patient care. This patient focusing of pharmacy practice should be supported by a similar patient focus pharmacy education, which not always has been achieved in Spain and the majority of EHEA members

Immunohistochemical assessment of PTEN in vulvar cancer: best practices for tissue staining, evaluation, and clinical association.

BACKGROUND: Pten encodes a well-characterized protein that is important in several cancers due to its tumor suppressor function. Yet, the detection and evaluation of PTEN by immunohistochemistry (IHC) for clinical practice have not been standardized. Thus, in this study, we performed a literature review of protocols for PTEN assessment by IHC and the possible differences in evaluation, based on our experience with vulvar carcinomas. Also, we report some of our most recent findings regarding the clinical impact of PTEN in this type of tumor. METHODS: In total, 150 FFPE vulvar carcinoma samples in a tissue microarray were examined by IHC with regard to PTEN, PI3K, AKT, and mTOR. All evaluations were performed by slide digitalization and quantification using APERIO ImageScope software. All measurements were converted into HScore values for the statistical analysis. RESULTS: Sharp and specific PTEN expression was observed in the nuclei and cytoplasmic compartments. Its HScore values ranged from 3.5 to 226, with a median of 92.5. mTOR expression was robust in all cases (mean HScore=248.1). AKT and PI3K had median HScore values of 200.5 and 156.5, respectively. In addition, PTEN expression was associated with higher rates of patient survival. CONCLUSION: The preanalytical step is the first issue in the immunohistochemical evaluation of PTEN. With regard to the analytical procedure, the antigen retrieval step yielded better stains for protocols with high-pH buffers, and antibody clone 6H2.1 effected the most reliable results. PTEN is a good prognostic marker for vulvar cancer, correlating with higher rates of patient survival. Our data underscore the importance of technical standardization to ensure more reliable and reproducible evaluation of PTEN in clinical practice.

Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.

Tophaceous Gout: a tragic course for a preventable disease.

A 66-year-old man, with a history of chronic tophaceous gout since the age of 30, presented with multiple tophi and significant deformity of all fingers that caused substantial function loss. Due to osteomyelitis refractory to antimicrobial therapy, he underwent disarticulation of several fingers. Finally, both his hands were amputated.

Sexuality in spondyloarthritis--the impact of the disease.

INTRODUCTION: The impact of rheumatic diseases on patients' sexual life has been gathering the attention of the scientific community over the last decade. The existing studies are scarce, especially related to spondyloarthritis, and particularly to psoriatic arthritis. Several factors associated with the disease may condition sexual function: pain, stiffness, decreased range of motion, joint swelling and extraarticular features such as fatigue, enthesopathy and cutaneous lesions in psoriatic arthritis. OBJECTIVES: To assess sexual satisfaction and limitations in sexual activity in a cohort of patients with spondyloarthritis. METHODS: An anonymous questionnaire was performed, consisting in two parts. One part consisted in a questionnaire filled by the doctor with data on the disease; the other part was filled by the patient, with demographic data, multiple choice questions and questions to be answered through a visual analogic scale, including items approached in some validated indexes of sexual function and satisfaction assessment. Statistical treatment was performed using SPPS system, version 17.0. RESULTS: 76 patients with the diagnosis of spondyloarthritis were enrolled; 31 had psoriatic arthritis, 30 had ankylosing spondylitis, 9 had undifferentiated spondyloarthritis and 6 had inflammatory bowel disease spondyloarthritis. In a visual analogic scale, the perception of conditioning in the conjugal relationship was 33.68±31.56 mm; limitation on sexual activity was 32.72±31.06 mm; limitation imposed by pain, joint swelling, fatigue, stiffness, decreased range of motion, decreased libido and cutaneous lesions ranged from 29.17±28.51 mm (swelling) to 46.94±32.31 mm (fatigue); there was no significant difference between sexes, diagnose and type of involvement. A strong correlation was identified between some analysed factors and ASQoL and HAQ values, but only moderate between them and disease function and activity indexes. Most of patients did not talk about their sexual limitations with their partners or with health professionals. CONCLUSION: This work highlights the impact of spondyloarthritis on patients' sexual function. The type of disease and joint involvement didn't imply statistically significant differences on the analyzed parameters in this cohort. This work also emphasizes the unawareness of health professionals towards this subject, whose approach is equally difficult to the patients, and might deserve greater attention.

A commercial box for dog semen transport: What happens inside when the environmental temperature is increasing?

Environmental temperatures may influence the temperature inside commercial transport boxes during semen shipment and thereby storage conditions of diluted dog semen. To evaluate the temperature changes inside boxes and their influence on sperm quality, split semen samples (n=8) were placed in Neopor boxes(®) exposed for 48h to room temperature (RT) (Box 1), 40°C for 6h and then kept at RT (Box 2) or 40°C (Box 3). A fourth subsample was kept at 4-5°C in a refrigerator (control). Inside Box 1 temperature initially decreased to <3°C before it stabilized at 7-8°C, while in Box 2 no decrease occurred and temperature was at 7-8°C for 48 h. Temperature inside Box 3 was at 14-15°C for 24h and, thereafter, increased to 36.1°C. Analysis of sperm motility (CASA) and viability (PI and FITC-PNA) after 24 and 48 h revealed marked sensitivity of dog spermatozoa to temperature fluctuations (Box 1). A constant storage temperature of 7-8°C (Box 2) provided the most desirable semen quality in terms of motility, viability, as well as osmotic resistance when samples were stored for 48 h. Furthermore, results indicate that during 24h preservation a storage temperature of 14-16°C may provide optimum conditions for maintenance of sperm viability and function. An increase of the inside temperature to >30°C (Box 3) resulted in an almost complete loss in sperm integrity. In conclusion, results suggest a revision of current recommendations for storage temperature of diluted dog semen. Boxes for semen transport should be prepared depending on the expected environmental temperatures.