Tratamientos coadyuvantes a la ventilación mecánica invasiva en el manejo del síndrome de distrés respiratorio agudo secundario a covid-19 / Adjuvant treatments to invasive mechanical ventilation in the management of acute respiratory distress syndrome secondary to COVID-19

Introducción: La presente revisión bibliográfica está realizada con el fin de obtener respuestas acerca de aspectos relacionados con las técnicas y tratamientos, así como cuidados asociados al paciente crítico diagnosticado con covid-19. Objetivo: Analizar la evidencia científica disponible sobre la efectividad de la utilización de la ventilación mecánica invasiva junto con otras técnicas coadyuvantes, en la reducción de la tasa de mortalidad en pacientes con síndrome de distrés respiratorio agudo y juicio clínico de covid-19 atendidos en unidades de cuidados intensivos. Metodología: Se realizó una revisión bibliográfica sistematizada en las bases de datos PubMed, CUIDEN, LILACS, Medline, CINAHL y Google Scholar, utilizando términos MeSH (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) y los operadores booleanos correspondientes. Los estudios seleccionados se sometieron a una lectura crítica realizada entre el 6 de diciembre de 2020 y el 27 de marzo de 2021 utilizando la herramienta Critical Appraisal Skills Programme en español y un instrumento de evaluación de estudios epidemiológicos transversales. Resultados: Se seleccionaron un total de 85 artículos. Tras realizar la lectura crítica se incluyeron en la revisión un total de 7 artículos, consistiendo en 6 estudios descriptivos y un estudio de cohortes. Tras el análisis de dichos estudios, se desprende que la técnica que mejor resultados ha obtenido es la oxigenación por membrana extracorpórea, siendo importantes los cuidados proporcionados por el personal de enfermería cualificado y capacitado. Conclusión: La mortalidad por covid-19 aumenta en pacientes tratados con ventilación mecánica invasiva respecto a los pacientes tratados con oxigenación por membrana extracorpórea. Los cuidados de enfermería y la especialización pueden repercutir en una mejora de los resultados en los pacientes.(AU)

Introduction: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with COVID-19. Objective: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with acute respiratory distress syndrome and clinical trial of COVID-19 treated in intensive care units. Methodology: A systematized bibliographic review was carried out in the PubMed, CUIDEN, LILACS, Medline, CINAHL and Google Scholar databases, using MeSH terms (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. Results: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and one a cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is extracorporeal membrane oxygenation, with the care provided by qualified and trained nursing staff being very important. Conclusion: Mortality from COVID-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.(AU)

Associations between self-reported sleep quality and cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease.

Sleep disorders are very common in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Several parameters of polysomnography seem to correlate with cognitive scores and amyloid biomarkers in the different stages of AD. However, there is limited evidence for the relationship between self-reported sleep impairment and disease biomarkers. In this study, we assessed the relationship between self-reported sleep complaints, with the Pittsburgh Sleep Quality Index, and both cognitive function and cerebrospinal fluid biomarkers in 70 patients with MCI and 78 patients with AD. Sleep duration and daytime dysfunction were higher in AD. Daytime dysfunction had a negative correlation with cognitive scores (Mini-Mental-State Examination and Montreal Cognitive Assessment) and with amyloid-beta1-42 protein, and a positive correlation with total tau protein. However, daytime dysfunction was an independent predictor only of t-tau values (F=57.162; 95% CI: [18.118; 96.207], P=0.004). These findings support a relationship between daytime dysfunction, cognitive scores and neurodegeneration, further expanding recent findings that it may signal a risk of dementia.

Adjuvant treatments to invasive mechanical ventilation in the management of acute respiratory distress syndrome secondary to COVID-19.

INTRODUCTION: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with Covid-19. OBJECTIVE: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with Acute Respiratory Distress Syndrome and clinical trial of Covid-19 treated in intensive care units. METHODOLOGY: A systematized bibliographic review was carried out in the Pubmed, Cuiden, Lilacs, Medline, Cinahl and Google Scholar databases, using MeSH terms (Adult Respiratory Distress Syndrome, Mechanical Ventilation, Prone Position, Nitric Oxide, Extracorporeal Membrane Oxygenation, Nursing Care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. RESULTS: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and 1 cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is ECMO, with the care provided by qualified and trained nursing staff being very important. CONCLUSION: Mortality from Covid-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.

[Adjuvant treatments to invasive mechanical ventilation in the management of acute respiratory distress syndrome secondary to COVID-19]. / Tratamientos coadyuvantes a la ventilación mecánica invasiva en el manejo del síndrome de distrés respiratorio agudo secundario a covid-19.

Introduction: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with COVID-19. Objective: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with acute respiratory distress syndrome and clinical trial of COVID-19 treated in intensive care units. Methodology: A systematized bibliographic review was carried out in the PubMed, CUIDEN, LILACS, Medline, CINAHL and Google Scholar databases, using MeSH terms (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. Results: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and one a cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is extracorporeal membrane oxygenation, with the care provided by qualified and trained nursing staff being very important. Conclusion: Mortality from COVID-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.

The temporal stability of premorbid intelligence: A non-clinical 10-year follow-up study using the Irregular Word Reading Test (TeLPI).

INTRODUCTION: The Cognitive Reserve (CR) describes the brain's ability to actively cope with neurological damage, enabling the maintenance of premorbid cognitive functioning through compensatory processes. The most common way to estimate CR is through formal education, the intelligence quotient (IQ) and participation in cognitive stimulating activities. In the absence of IQ data, the Irregular Word Reading Test (TeLPI) allows you to estimate the premorbid intelligence. OBJECTIVE: The comparison of the TeLPI results between two times of assessment (baseline and re-assessment) with an interval time (IT) of 9 years. To analyze of the stability of their results as a valid dimension for the CR estimation. RESULTS: The TeLPI presented temporal stability of its results between the two evaluation times (IT = 9.07 ± 1.02). The sample, composed by 63 cognitively healthy participants, showed no differences for the estimated Full Scale IQ (t(62) = 0.49, p = .63), for the Estimated Verbal IQ (t(62) = 0.71, p = .48) and for the estimated Performance IQ (t(62) = 0.64, p = .52). Likewise, no differences were found in the number of TeLPI errors at the two assessment times (t(62) = -0.61, p = .54). CONCLUSIONS: Considering that CR is characterized as being relatively stable, the TeLPI should be included in its assessment, as an indicator with proved stability over a long period of time, on the physiological aging spectrum.

Efficacy of the laser at low intensity on primary burning oral syndrome: a systematic review.

BACKGROUND: Primary burning mouth syndrome (BMS) is a chronic clinical condition of idiopathic mainly characterized by pain and a burning sensation in the oral cavity. The application of laser at low intensity therapy is a treatment option. This systematic review evaluated the efficacy of laser therapy in treating symptoms of burning mouth syndrome. MATERIAL AND METHODS: The study was formulated according to the PRISMA and Cochrane guidelines. Seven databases were used as primary sources of research. Only randomized controlled clinical trials were included. The efficacy of the therapy was estimated comparing the values of the visual and numerical scales of pain before and after laser treatment, through qualitative analysis. RESULTS: The search resulted in 348 records and only eight filled the eligibility criteria and were included. All studies evaluated pain and / or a burning sensation considering a time interval of two to ten weeks. The total sample consisted of 314 patients submitted to treatment: 123 from the control group, who participated with laser off or with the tip blocked, and 191 from the intervention group, treated with low-level laser therapy. The female gender stood out and the average age of the participants was 60.89 years. The main symptoms reported were pain and a burning sensation in the oral mucosa and tongue. The parameters adopted by the authors for laser treatment were diverse and the variables were not fully described in the published studies. Visual analog and numerical scales were used to assess symptoms and only three studies showed statistical significance. CONCLUSIONS: It is suggested that laser therapy may be an effective alternative in the treatment of BMS. New randomized clinical trials should consider well-established protocols to better understand the efficacy of laser therapy without confounding the effects.

Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC).

BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.

Adaptación y validez de la escala de motivación en el deporte 2 (EMD-2) para estudiantes universitarios chilenos / Adaptação e validação do escala de motivação no esporte- 2 em estudantes da universidade chileno / Adaptation and validity of motivation scale in sport 2 (SMS- 2 ) for chilean university students

La teoría de la Autodeterminación (TAD) (Deci y Ryan, 1985) asume al ser humano como un organismo integrado en un contexto social, y a la motivación como un constructo organizado en un continuo que va de la motivación intrínseca a la motivación. Las primeras versiones del instrumento denominado Escala de Motivación en el Deporte (Brière,Vallerand, Blais, y Pelletier, 1995;Pelletier, Fortier, Vallerand, Tuson, Brière y Blais, 1995) no cubrían las seis dimensiones del continuum conceptual del modelo. Hubo diversos estudios de validación hasta la construcción de la Escala de Motivación de Deporte-2 (Pelletier, Rocchi, Vallerand, Deci y Ryan, 2013) en inglés, la cual incluye todas las dimensiones del constructo. Hasta la fecha, no contábamos con una adaptación al español de esta última versión del instrumento. La traducción reversa del instrumento se aplicó a una muestra de muestra de 221 deportistas competitivos y recreativos. Los resultados indicaron la adecuación de los datos para hacer un análisis factorial. La confiabilidad general de la prueba fue .78. Hubo diferencias significativas en tres regulaciones entre deportistas competitivos y recreativos. Solamente cuatro de las 6 escalas presentaron ítems con cargas de ítem satisfactorias. Por lo que la prueba requiere estudios posteriores para ser empleada con utilidad en evaluación con deportistas. La escala de regulación integrada de la versión en español del presente estudio se comportó con un excelente ajuste psicométrico, lo cual constituye un importante aporte ya que no se contaba con estos datos en español para una versión de 12 ítems de la escala de motivación en el deporte dentro de la TAD (AU)

The self Determination Theory (SDT) assumes the human being as an integrated organism in social context, and motivation as a construct organized in a continuum that runs from intrinsic motivation to motivation. The firsts versions of the instrument called Sport Motivation Scale (Briere et al., 1995; Pelletieretal., 1995) did not covered the six dimensions of the conceptual continuum of the model. Several validation studies have been developed until the SMS-2version of the test (Pelletier, 2013). Until the present, there was not a Spanish adaptation of this last version of the test. A back translation of the instrument was applied to a sample of 221 recreational and competitive athletes. The results indicated the adequacy of the data for a confirmatory factor analysis. The general reliability was .78. There were significant differences three regulations between competitive and recreational players. Four of the six scales had items with proper factor loadings. The integrated regulation factor in Spanish had an excellent psychometric outcome. We propose to use items based in former studies in Spanish with proper factor loadings, in replacement of ones that had poor factor loadings, to use them in future validation trials of the SMS-2 (AU)

A teoria da Autodeterminação (TAD) (Deci y Ryan, 1985) entende o ser humano como um organismo integrado no seu contexto social, e a motivação como um constructo organizado num continuo que engloba de motivação intrínseca até a não motivação. As primeiras versões do instrumento denominado Escala de Motivação no Esporte- 2(Brièreetal, 1995; Pelletieretal., 1995) não consideravam as seis dimensões do continuo conceitual do modelo. Muitos estudos de validação foram realizados até a construção da Escala de Motivação no Esporte-2 (Pelletieret al., 2013) em inglês, a qual inclui todas as dimensões do constructo. Atualmente, não contávamos com uma adaptação dessa última versão do instrumento ao idioma espanhol. A tradução reversa do instrumento se aplicou a uma amostra de 221 atletas competitivos e recreativos. Os resultados indicam a adequação dos dados para a realização de uma análise fatorial. A confiabilidade geral do teste foi de 0.78. Se encontraram diferenças significativas nas três regulações entre atletas competitivos e recreativo. Somente 4 escalas das 6 aplicadas apresentaram itens com cargas de item satisfatórias. Portanto, o teste requer estudos futuros para poder ser aplicado com utilidade avaliadora em atletas. A escala de regulação integrada da versão em idioma espanhol aplicada no presente estudo demostrou um excelente ajuste psicométrico, o que se constitui num importante aporte considerando que não se haviam dados nesse idioma para uma versão de 12 itens da escala de motivação no esporte dentro da TAD (AU)

Pseudohypoparathyroidism type I-b with neurological involvement is associated with a homozygous PTH1R mutation.

Pseudohypoparathyroidism type 1b (PHP1b) is characterized by hypocalcemia, hyperphosphatemia, increased levels of circulating parathyroid hormone (PTH), and no skeletal or developmental abnormalities. The goal of this study was to perform a full characterization of a familial case of PHP1b with neurological involvement and to identify the genetic cause of disease. The initial laboratory profile of the proband showed severe hypocalcemia, hyperphosphatemia and normal levels of PTH, which was considered to be compatible with primary hypoparathyroidism. With disease progression the patient developed cognitive disturbance, PTH levels were found to be slightly elevated and a picture of PTH resistance syndrome seemed more probable. The diagnosis of PHP1b was established after the study of family members and blunted urinary cAMP results were obtained in a PTH stimulation test. Integration of whole genome genotyping and exome sequencing data supported this diagnosis by revealing a novel homozygous missense mutation in PTH1R (p.Arg186His) completely segregating with the disease. Here, we demonstrate segregation of a novel mutation in PTH1R with a phenotype of PHP1b presenting with neurological symptoms, but no bone defects. This case represents the extreme end of the spectrum of cognitive impairment in PTH dysfunction and defines a possible novel form of PHP1b resulting from the impaired interaction between PTH and PTH1R.

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result.

Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases.

Sporadic Creutzfeldt-Jakob disease diagnostic accuracy is improved by a new CSF ELISA 14-3-3γ assay.

Protein 14-3-3 is a reliable marker of rapid neuronal damage, specifically increased in cerebrospinal fluid (CSF) of sporadic Creutzfeldt-Jakob disease (sCJD) patients. Its detection is usually performed by Western Blot (WB), prone to methodological issues. Our aim was to evaluate the diagnostic performance of a recently developed quantitative enzyme-linked immunosorbent (ELISA) assay for 14-3-3γ, in comparison with WB and other neurodegeneration markers. CSF samples from 145 patients with suspicion of prion disease, later classified as definite sCJD (n=72) or Non-prion diseases (Non-CJD; n=73) comprised our population. 14-3-3 protein was determined by WB and ELISA. Total Tau (t-Tau) and phosphorylated Tau (p-Tau) were also evaluated. Apolipoprotein E gene (ApoE) and prionic protein gene (PRNP) genotyping was assessed. ELISA 14-3-3γ levels were significantly increased in sCJD compared to Non-CJD patients (p<0.001), showing very good accuracy (AUC=0.982; sensitivity=97%; specificity=94%), and matching WB results in 81% of all cases. It strongly correlated with t-Tau and p-Tau (p<0.0001), showing slightly higher specificity (14-3-3 WB - 63%; Tau - 90%; p-Tau/t-Tau ratio - 88%). From WB inconclusive results (n=44), ELISA 14-3-3γ correctly classified 41 patients. Additionally, logistic regression analysis selected ELISA 14-3-3γ as the best single predictive marker for sCJD (overall accuracy=93%). ApoE and PRNP genotypes did not influence ELISA 14-3-3γ levels. Despite specificity for 14-3-3γ isoform, ELISA results not only match WB evaluation but also help discrimination of inconclusive results. Our results therefore reinforce this assay as a single screening test, allowing higher sample throughput and unequivocal results.

Midriasis benigna episódica. Experiencia en una consulta monográfica de neuro-oftalmología de un hospital terciario / Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic of a tertiary hospital

Introducción: Las anisocorias son un motivo de consulta relativamente frecuente en unidades de neuro-oftalmología (UNO). Suponen un reto diagnóstico por la variedad de procesos que pueden ocasionarla. En ausencia de síntomas acompañantes, suelen estar ocasionadas por procesos benignos. La midriasis benigna episódica (MBE) es una causa aislada de asimetría pupilar intermitente, de fisiopatología no esclarecida y predominio en mujeres jóvenes migrañosas. Sujetos, material y métodos: Describimos las características epidemiológicas y clínicas de los pacientes con MBE valorados en una UNO de un hospital terciario. Resultados: Un total de 7 pacientes fueron diagnosticadas de MBE. Todas eran mujeres, con edad media de 33 ± 10 años. Los motivos de consulta fueron asimetría pupilar (n = 5) y visión borrosa (n = 2) de presentación fundamentalmente unilateral (n = 6). La duración fue variable, desde minutos hasta 48 h. Cuatro pacientes (57%) presentaban como antecedente migraña sin aura. En estas, los episodios eran recidivantes (75%), de minutos de duración (75%) y asociaban visión borrosa (50%). Los estudios de neuroimagen (resonancia magnética cerebral) fueron normales. Discusión: La midriasis benigna episódica se presenta predominantemente en mujeres jóvenes. Se asocia al antecedente de migraña y hace plantear si se trata de un síntoma acompañante de la migraña, un aura migrañosa o de migraña oftalmopléjica. De predominio unilateral, puede sin embargo existir alternancia del ojo afectado o ser bilateral de forma simultánea, lo que nos hace cuestionarnos la idoneidad del término. En ausencia de síntomas acompañantes y en episodios de corta duración, no consideramos necesaria la realización de pruebas de imagen

Introduction: Anisocorias are a relatively frequent reason for consultation in neuro-ophthalmology units. They remain a diagnostic challenge for specialists as they may be due to several etiological factors. In the absence of other accompanying symptoms, anisocorias are usually due to benign processes. Benign episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in which the pathophysiology is still not fully understood, and is predominant in young women with migraine. Subjects, material and methods: We describe the epidemiological and clinical characteristics of patients with BEM, assessed in a neuro-ophthalmology unit in a tertiary hospital. Results: A total of 7 patients were diagnosed with BEM, all of them females, with a mean age of 33 ± 10 yrs. The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2), and 6 of the 7 patients had unilateral involvement. The duration of impairment varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history of migraine without aura. The episodes in these 4 patients were recurrent (75%), often lasted for a few minutes (75%), and had associated blurred vision (50%). The neuroimaging studies were normal. Discussion: BEM appears predominantly in young women. It is frequently related to a previous history of migraine, and the specialist must consider if it is a concomitant symptom of common migraine, migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral predominance, there may be alternation of the affected eye or even bilateral impairment during the same episode, which makes us question the adequacy of the term to describe the process. Imaging tests are not recommended in the absence of other accompanying symptoms, or in short-term episodes

Immunohistochemical expression of cyclooxygenase-2 (COX-2) in feline endometrial adenocarcinoma and in normal and hyperplastic endometria.

Cyclooxygenase-2 (COX-2) is overexpressed in several human and animal neoplasms, including the human endometrial carcinoma. It has been suggested as a prognostic marker and a potential therapeutic target. This study aimed to (i) clarify histological aspects of feline endometrial adenocarcinomas (FEA) of the papillary serous type and (ii) characterize COX-2 immunohistochemical expression in normal, hyperplastic and neoplastic endometrium in this species. Archived paraffin-embedded tissue samples of 33 FEA, eight cystic endometrial hyperplasias (CEHs) and 21 samples of normal, healthy endometrium in the follicular (FS; n = 10) and luteal (LS; n = 11) stages were evaluated. Histological evaluation of haematoxylin and eosin-stained sections of the FEA revealed a papillary proliferation of neoplastic cells of serous type, accompanied by clear and multinucleated cells. Other architectural arrangements mainly included solid and tubular growth. Randomly distributed areas of necrosis within the tumours were commonly observed. Invasion of the myometrium, of the serosa and of the vascular and/or lymphatic vessels was not constant features. The mean number of mitoses was higher in FEA compared to non-neoplastic endometrium. COX-2 scores were lower in FEA (p = 0.003) and CEH (p = 0.05) when compared to normal epithelium (NE). The loss of the membrane apical reinforcement in epithelial cells was observed in FEA samples, which was accompanied by the dislocation of COX-2 labelling into the cytoplasm and the perinuclear area; in contrast, in epithelial cells in the healthy and hyperplastic endometria, the immunoreaction showed the characteristic pattern of apical membrane reinforcement, suggestive of the membrane polarization. COX-2 epithelial scores were higher in the FS than in the LS. No differences were found in stromal COX-2 expression between normal, CEH and FEA groups, but it was higher in the LS than in the FS. In summary, loss of COX-2 compartmentalization in neoplastic epithelial cells might be one of the molecular events underlying endometrial carcinogenesis.

Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic of a tertiary hospital.

INTRODUCTION: Anisocorias are a relatively frequent reason for consultation in neuro-ophthalmology units. They remain a diagnostic challenge for specialists as they may be due to several etiological factors. In the absence of other accompanying symptoms, anisocorias are usually due to benign processes. Benign episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in which the pathophysiology is still not fully understood, and is predominant in young women with migraine. SUBJECTS, MATERIAL AND METHODS: We describe the epidemiological and clinical characteristics of patients with BEM, assessed in a neuro-ophthalmology unit in a tertiary hospital. RESULTS: A total of 7 patients were diagnosed with BEM, all of them females, with a mean age of 33 ± 10 yrs. The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2), and 6 of the 7 patients had unilateral involvement. The duration of impairment varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history of migraine without aura. The episodes in these 4 patients were recurrent (75%), often lasted for a few minutes (75%), and had associated blurred vision (50%). The neuroimaging studies were normal. DISCUSSION: BEM appears predominantly in young women. It is frequently related to a previous history of migraine, and the specialist must consider if it is a concomitant symptom of common migraine, migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral predominance, there may be alternation of the affected eye or even bilateral impairment during the same episode, which makes us question the adequacy of the term to describe the process. Imaging tests are not recommended in the absence of other accompanying symptoms, or in short-term episodes.

A time series analysis of Prochilodus nigricans landings caught by small-scale fisheries in the lower stretch of the Amazon River.

We developed a time series analysis using data on curimatã (Prochilodus nigricans), which landed in Santarém, a small city located on the right banks of the Amazon River. A 10-year record of monthly average catches per day of P. nigricans was analyzed using forecasting procedures in the open-source software GRETL 1.7.8. We established two models from the identifications made with the correlograms of hyperparametrization and seasonal differences. The autoregressive terms of the model reach three years, indicating that individuals of the species are being caught around the age of three. This may indicate that the curimatãs in the landings at Santarém from 1992 to 2002 were more than two years old, potentially a sign of a lack of fishing pressure on the lower age groups.

Prodromal metabolic phenotype in MCI cybrids: implications for Alzheimer's disease.

Mild cognitive impairment (MCI) is considered a nosological entity or a translational state between normal aging and sporadic Alzheimer's disease (AD). From brain tissue to peripheral blood samples, it is evident that the early markers of metabolic dysfunction observed in AD have also been found in MCI subjects. These observations obtained from MCI and AD subjects leave open the possibility that mitochondrial dysfunction-induced oxidative damage happening a priori of symptom onset, may trigger other pathological hallmarks, namely Aß oligomerization. In this study, we used a citoplasmic hybrid (cybrid) model created by the repopulation of human teratocarcinoma (NT2) cells depleted of endogenous mitochondrial DNA (mtDNA) with platelets from age-matched controls, MCI and AD subjects. We found mitochondrial deficits in MCI and AD cybrids as compared with controls, such as a decrease in cytochrome c oxidase (COX) activity, a decrease in mitochondrial membrane potential and in mitochondrial cytochrome c content. Consequently, we analyzed parameters of oxidative damage and found that AD and MCI cybrids exhibit an increase in lipid peroxides, higher production of superoxide radicals, and higher content in protein carbonyls. Since our data clearly show alterations in mitochondrial-mediated oxidative damage in MCI cybrids we propose that mitochondrial dysfunction is an early event in idiopathic AD. Moreover, we found that mitochondrial Aß oligomeric content increases in AD, which may exacerbate initial mitochondrial damage. Altogether, our data strongly supports a key role for mitochondria/ mtDNA in aged-driven AD pathology.

Epigenetic regulation of BACE1 in Alzheimer's disease patients and in transgenic mice.

In Alzheimer's disease (AD) the complex interplay between environment and genetics has hampered the identification of effective therapeutics. However, epigenetic mechanisms could underlie this complexity. Here, we explored the potential role of epigenetic alterations in AD by investigating gene expression levels and chromatin remodeling in selected AD-related genes. Analysis was performed in the brain of the triple transgenic animal model of AD (3xTg-AD) and in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with AD or Mild Cognitive Impairment (MCI). BACE1 mRNA levels were increased in aged 3xTg-AD mice as well as in AD PBMCs along with an increase in promoter accessibility and histone H3 acetylation, while the BACE1 promoter region was less accessible in PBMCs from MCI individuals. Ncstn was downregulated in aged 3xTg-AD brains with a condensation of chromatin and Sirt1 mRNA levels were decreased in these animals despite alterations in histone H3 acetylation. Neither gene was altered in AD PBMCs. The ADORA2A gene was not altered in patients or in the 3xTg-AD mice. Overall, our results suggest that chromatin remodeling plays a role in mRNA alterations in AD, prompting for broader and more detailed studies of chromatin and other epigenetic alterations and their potential use as biomarkers in AD.

Localization of tumor necrosis factor in the canine testis, epididymis and spermatozoa.

Tumor necrosis factor (TNF), formerly known as Tumor necrosis factor alpha is now regarded as a natural component of the mammalian seminal plasma (SP). Although not completely clarified, its functions in the SP have been associated with paradoxal roles, such as sperm survival in the female genital tract, while at high levels negatively affect sperm survival and fertility potential. Recently, it has been discovered that canine inseminated spermatozoa display a strong immunoreaction for TNF when lining the female endometrium. As a continuation of this finding, the present work aimed at documenting TNF localization in the canine testes and epididymis and in freshly ejaculated spermatozoa (SPZ) through immunohisto- or cytochemistry. Immunoreaction for TNF was found in all samples used. In the dog testis, TNF immunoexpression was limited to the seminiferous tubules, where late round spermatids (SPD) showed weak intensity of immunostaining, while elongating and elongated SPD evidenced moderate and the residual bodies a strong intensity. In the epididymis, a gradual progressive increase of TNF immunolabelling was found throughout the epididymal regions, ranging from a weak intensity at the caput epididymis to a moderate intensity at the cauda. TNF immunolabelling was found in mature SPZ during the epididymal transit and also in freshly ejaculated SPZ, which showed a strong midpiece immunolabelling. Data presented here provide important information on expression of TNF in spermatozoa, which is acquired by the SPZ during their formation at the testis. It further provides the basis for subsequent studies on the physiological importance of cytokines in sperm function.