Decreased myocardial injury and improved contractility after administration of a peptide derived against the alpha-interacting domain of the L-type calcium channel.

BackgroundMyocardial infarction remains the leading cause of morbidity and mortality associated with coronary artery disease. The L-type calcium channel (IC a-L) is critical to excitation and contraction. Activation of the channel also alters mitochondrial function. Here, we investigated whether application of a alpha-interacting domain/transactivator of transcription (AID-TAT) peptide, which immobilizes the auxiliary β2 subunit of the channel and decreases metabolic demand, could alter mitochondrial function and myocardial injury.Methods and resultsTreatment with AID-TAT peptide decreased ischemia-reperfusion injury in guinea-pig hearts ex vivo (n=11) and in rats in vivo (n=9) assessed with uptake of nitroblue tetrazolium, release of creatine kinase, and lactate dehydrogenase. Contractility (assessed with catheterization of the left ventricle) was improved after application of AID-TAT peptide in hearts ex vivo (n=6) and in vivo (n=8) up to 12 weeks before sacrifice. In search of the mechanism for the effect, we found that intracellular calcium ([Ca(2+)]i, Fura-2), superoxide production (dihydroethidium fluorescence), mitochondrial membrane potential (Ψm, JC-1 fluorescence), reduced nicotinamide adenine dinucleotide production, and flavoprotein oxidation (autofluorescence) are decreased after application of AID-TAT peptide.ConclusionsApplication of AID-TAT peptide significantly decreased infarct size and supported contractility up to 12 weeks postcoronary artery occlusion as a result of a decrease in metabolic demand during reperfusion

Myeloperoxidase-derived oxidants inhibit sarco/endoplasmic reticulum Ca2+-ATPase activity, and perturb Ca2+ homeostasis in human coronary artery endothelial cells

The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) plays a critical role in Ca2+ homeostasis via sequestration of this ion into the sarco/endoplasmic reticulum. The activity of this pump is inhibited by oxidants and impaired in ageing tissues and cardiovascular disease. We have shown previously that the myeloperoxidase- (MPO) derived oxidants HOCl and HOSCN target thiols and mediate cellular dysfunction. As SERCA contains Cys residues critical to ATPase activity, we hypothesized that HOCl and HOSCN might inhibit SERCA activity, via thiol oxidation, and increase cytosolic Ca2+ levels in human coronary artery endothelial cells (HCAEC). Exposure of sarcoplasmic reticulum vesicles to pre-formed or enzymatically-generated HOCl and HOSCN resulted in a concentration-dependent decrease in ATPase activity; this was also inhibited by the SERCA inhibitor thapsigargin. Decomposed HOSCN and incomplete MPO enzyme systems did not decrease activity. Loss of ATPase activity occurred concurrently with oxidation of SERCA Cys residues and protein modification. Exposure of HCAEC, with or without external Ca2+, to HOSCN or HOCl, resulted in a time- and concentration-dependent increase in intracellular Ca2+ under conditions that did not result in immediate loss of cell viability. Thapsigargin, but not inhibitors of plasma membrane or mitochondrial Ca2+ pumps/channels, completely attenuated the increase in intracellular Ca2+ consistent with a critical role for SERCA in maintaining endothelial cell Ca2+ homeostasis. Angiotensin II pre-treatment potentiated the effect of HOSCN at low concentrations. MPO-mediated modulation of intracellular Ca2+ levels may exacerbate endothelial dysfunction, a key early event in atherosclerosis, and be more marked in smokers due to their higher SCN− levels

Sol-gel Barium Titanate Nanohole Array as a Nonlinear Metasurface and a Photonic Crystal

The quest of a nonlinear optical material that can be easily nanostructured over a large surface area is still ongoing. Here, we demonstrate a nanoimprinted nonlinear barium titanate 2D nanohole array that shows optical properties of a 2D photonic crystal and metasurface, depending on the direction of the optical axis. The challenge of nanostructuring the inert metal-oxide is resolved by direct soft nanoimprint lithography with sol-gel derived barium titanate enabling critical dimensions of 120 nm with aspect ratios of 5. The nanohole array exhibits a photonic bandgap in the infrared range when probed along the slab axis while lattice resonant states are observed in out-of-plane transmission configuration. The enhanced light-matter interaction from the resonant structure enables to increase the second-harmonic generation in the near-UV by a factor of 18 illustrating the potential in the flexible fabrication technique for barium titanate photonic devices

DESAFIOS E PERCALÇOS DA INSERÇÃO DA MULHER NOS JOGOS OLÍMPICOS (1894-1965)

Resumo: Este artigo analisa a trajetória da mulher nos Jogos Olímpicos (JO), destacando fatos históricos mundiais e avançando para o contexto contemporâneo, trazendo feitos e particularidades da participação da mulher brasileira. Tem cunho bibliográfico de caráter histórico, utilizando-se da análise documental com a técnica da depuração da informação, tendo por fontes o Boletim Olímpico do COI, Relatórios Oficiais dos JO e a legislação esportiva brasileira. Evidenciamos o desinteresse inicial do COI na participação feminina, canalizado principalmente por Pierre de Coubertin. Como resultado dessas diretrizes institucionais, as modalidades femininas tiveram uma tardia inserção no programa olímpico, e ainda mais lenta a participação das atletas brasileiras na competição. Até hoje as atletas brasileiras são menos presentes nos Jogos que os homens e a análise documental no Brasil evidencia que os desafios dessas atletas não foi menor que os do contexto mundial.Palavras-chave: Mulher; Jogos Olímpicos; Atletas brasileiras; Comitê Olímpico Internacional.Challenges and mishaps in the insertion of women in the Olympic Games (1894-1965)Abstract: This study analyzes the history of women in the Olympic Games, highlighting global historical facts and advancing to the contemporary context, reflecting on the achievements and particularities of the Brazilian women's participation. This is a bibliographic study of historical character, using documentary analysis with the debugging technique, having as sources the Olympic Bulletin of the IOC, the Official Reports of the Olympic Games and the Brazilian sports law. The initial disinterest of the IOC on the women's participation was evident. As a result of these institutional guidelines, women's sports were later included in the Olympic program and this was also reflected in the increased participation of Brazilian female athletes in the competition. Even today, Brazilian female athletes are still less present at the Games than men, and the Brazilian documentary analysis shows that the challenges faced by the "New World" female athletes were not minor when compared to what was experienced by women in a global context.Keywords: Sports; Woman; Olympic Games; Brazilian Female Athletes; International Olympic Committee. Desafíos de la inserción de las mujeres en los Juegos Olímpicos (1984-1965) Resumen: Esta investigación analiza la trayectoria de la mujer en los Juegos Olímpicos, destacando factos históricos internacionales y avanzando para el contexto contemporáneo, con especificidad a la mujer brasileña. Tiene carácter bibliográfico e histórico, con análise documental con la técnica de la depuración de informaciones, a partir del Boletín Olímpico del COI, Informes Oficiales de los Juegos Olímpicos y la legislación deportiva brasileña. Destacamos el desinterese del COI en la participación femenina, sobre todo por parte de Coubertin. Como resultado de estas directrices, el deporte femenino tuve entrada tardía en los Juegos, y aún más lenta fue el desarrollo de las brasileñas. Hasta hoy, atletas brasileñas tienen participación más pequeña que los hombres, indicando que en nuestro contexto el desafío fue tan grande como alrededor el mundo.Palabras-clave: Mujer; Juegos Olímpicos; deportistas brasileñas; Comité Olímpico Internacional

Associative memory impairments are associated with functional alterations within the memory network in schizophrenia patients and their unaffected first-degree relatives: an fMRI study

Memory impairments are a major characteristic of schizophrenia (SZ). In the current study, we used an associative memory task to test the hypothesis that SZ patients and first-degree relatives have altered functional patterns in comparison to healthy controls. We analyzed the fMRI activation pattern during the presentation of a face-name task in 27 SZ patients, 23 first-degree relatives, and 27 healthy controls. In addition, we performed correlation analyses between individual psychopathology, accuracy and reaction time of the task and the beta scores of the functional brain activations. We observed a lower response accuracy and increased reaction time during the retrieval of face-name pairs in SZ patients compared with controls. Deficient performance was accompanied by abnormal functional activation patterns predominantly in DMN regions during encoding and retrieval. No significant correlation between individual psychopathology and neuronal activation during encoding or retrieval of face-name pairs was observed. Findings of first-degree relatives indicated slightly different functional pattern within brain networks in contrast to controls without significant differences in the behavioral task. Both the accuracy of memory performance as well as the functional activation pattern during retrieval revealed alterations in SZ patients, and, to a lesser degree, in relatives. The results are of potential relevance for integration within a comprehensive model of memory function in SZ. The development of a neurophysiological model of cognition in psychosis may help to clarify and improve therapeutic options to improve memory and functioning in the illness

Validation of the FAM19A4/mir124-2 DNA methylation test for both lavage- and brush-based self-samples to detect cervical (pre)cancer in HPV-positive women

Objectives DNA methylation analysis of cancer-related genes is a promising tool for HPV-positive women to identify those with cervical (pre)cancer (CIN3+) in need of treatment. However, clinical performance of methylation markers can be influenced by the sample type utilized. We describe a multiplex quantitative methylation-specific PCR that targets FAM19A4 and mir124-2 loci, to detect CIN3+ using both HPV-positive lavage- and brush self-samples. Methods We determined methylation thresholds for clinical classification using HPV-positive training sets comprising lavage self-samples of 182 women (including 40 with CIN3+) and brush self-samples of 224 women (including 61 with CIN3+). Subsequently, independent HPV-positive validation sets of 389 lavage self-samples (including 78 with CIN3+), and 254 brush self-samples (including 72 with CIN3+) were tested using the preset thresholds. Furthermore, the clinical performance of combined methylation analysis and HPV16/18 genotyping was determined. Results Training set analysis revealed similar FAM19A4 and mir124-2 thresholds for both self-sample types to yield highest CIN3+ sensitivity at 70% specificity. Validation set analysis resulted in a CIN3+ sensitivity of 70.5% (95%CI: 60.4-80.6) at a specificity of 67.8% (95%CI: 62.7-73.0) for lavage self-samples, and a CIN3+ sensitivity of 69.4% (95%CI: 58.8-80.1) at a 76.4% (95%CI: 70.2-82.6) specificity for brush self-samples. In combination with HPV16/18 genotyping, CIN3+ sensitivity and specificity were 88.5% (95%CI: 81.4-95.6) and 46.0% (95%CI: 40.4-51.5) for lavage self-samples, and 84.7% (95%CI: 76.4-93.0) and 54.9% (95%CI: 47.7-62.2) for brush self-samples. Conclusions FAM19A4/mir124-2 methylation analysis performs equally well in HPV-positive la

Associative Memory Impairments Are Associated With Functional Alterations Within the Memory Network in Schizophrenia Patients and Their Unaffected First-Degree Relatives: An fMRI Study

Memory impairments are a major characteristic of schizophrenia (SZ). In the current study, we used an associative memory task to test the hypothesis that SZ patients and first-degree relatives have altered functional patterns in comparison to healthy controls. We analyzed the fMRI activation pattern during the presentation of a face-name task in 27 SZ patients, 23 first-degree relatives, and 27 healthy controls. In addition, we performed correlation analyses between individual psychopathology, accuracy and reaction time of the task and the beta scores of the functional brain activations. We observed a lower response accuracy and increased reaction time during the retrieval of face-name pairs in SZ patients compared with controls. Deficient performance was accompanied by abnormal functional activation patterns predominantly in DMN regions during encoding and retrieval. No significant correlation between individual psychopathology and neuronal activation during encoding or retrieval of face-name pairs was observed. Findings of first-degree relatives indicated slightly different functional pattern within brain networks in contrast to controls without significant differences in the behavioral task. Both the accuracy of memory performance as well as the functional activation pattern during retrieval revealed alterations in SZ patients, and, to a lesser degree, in relatives. The results are of potential relevance for integration within a comprehensive model of memory function in SZ. The development of a neurophysiological model of cognition in psychosis may help to clarify and improve therapeutic options to improve memory and functioning in the illness

The benefits, costs and feasibility of a low incidence COVID-19 strategy.

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure 'test-trace-isolate-support' becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust

Digital tillsynsteknik i djurhållning utomhus

I enlighet med Jordbruksverkets förfrågan behandlar denna rapport tre områden för digital teknik vid övervakning och kontroll av djur som vistas utomhus på stora ytor: (1) kamerateknologi, t.ex. användning av drönare, (2) positioneringsteknologi som GPS och (3) teknologi för att styra djurens rörelser, som drivning med drönare och användning av s.k. virtuella stängsel. De tre teknikområdena överlappar delvis varandra. Digital tillsyn av utegående djur är beroende av att sensorer mäter det man tror att de mäter med tillräcklig noggrannhet och att data kan överföras och bearbetas till information som lagras och analyseras på ett säkert och korrekt sätt. Sådana teknologier benämns med samlingsnamnet ’Precision Livestock Farming’ (PLF). Användningen av informationen är avgörande för teknikens användbarhet i tillsyns- och djurskyddsarbete. Tillämpningarna är till viss del reglerade av gällande lagstiftning, exempelvis genom krav på tillsyn, begränsad användning av elektricitet för att styra djurs beteende, användning av obemannade luftfarkoster, d.v.s. drönare, samt åtgärder för att förhindra att utrustning skadar djuren eller påverkar deras hälsa och beteende. Inom PLF används en rad olika sensorer som direkt eller indirekt kan mäta djurens miljö och djurens beteende och fysiologiska tillstånd. Den teknologiska utvecklingen har främst varit inriktad på mjölkkor, fjäderfän och grisar och endast i liten utsträckning berört häst, får och get. För djur på bete är överföringen av data från en enhet på eller vid djuret till en mottagare särskilt problematisk p.g.a. stora avstånd, men det sker en snabb teknisk utveckling mot effektivare överföring. PLF-teknologin innebär i de flesta fall att djuren övervakas kontinuerligt och att avvikelser i t.ex. deras hälsotillstånd och välfärd i princip kan upptäckas i realtid, vilket ska ställas mot nuvarande lagkrav på tillsyn minst en eller två gånger dagligen. Sensorer kan ge information om ett stort antal fysiologiska tillstånd och beteenden. En av de vanligaste teknikerna är sensorer för aktivitet. Indirekt kan de också ge information om idissling, liggtid, stegantal och ättid och utlösa larm om exempelvis brunst, hälsoproblem, hälta och kalvning. Sensorer kan även placeras i förmagen hos idisslare (s.k. våmbolus) där de mäter våm-pH och kan larma om störningar i magfunktionen, eller utformas som termometrar som kan larma om hälsostörningar, kalvning och vattenintag eller mikrofoner som kan mäta idissling och larma om brunst, kalvning och onormalt idisslingsmönster. Med kamerateknik kan man mäta aktivitet, kroppsform och hudtemperatur, vilket kan ge information om ketosstatus, hull, hälta och juverhälsa. Kameror monterade på drönare kan användas för att lokalisera och räkna djur, bestämma deras position, habitatval och till viss del deras beteende, särskilt när djuren rör sig över stora arealer. Det finns flera elektroniska positioneringsteknologier varav passiv ’Radio Frequency Identification RFID’ är den vanligaste. Räckvidden är kort med denna teknik men den kan vara användbar om man t.ex. vill mäta hur ofta djuren besöker en vattenpost. Andra teknologier kan med hjälp av antenner följa djurens positioner i realtid. GPS-enheter monterade i halsband kan regelbundet registrera djurens geografiska position. Användningen av GPS har blivit relativt vanlig i renskötseln vilket tycks ha lett till en förbättrad arbetssituation för renskötarna. Positionering med GPS ger inte alltid exakta uppgifter men tekniken har visat sig användbar för studier av habitatval, sociala interaktioner och gruppdynamik. Med positionerna från GPS har man också kunnat styra djur till områden med bättre betestillgång. Med en tillräckligt frekvent bestämning av position med hjälp av GPS (ca en gång per minut) är det möjligt att bestämma betestiden för nötkreatur på ett tillförlitligt sätt. En användning av drönare i djurskötsel och djurtillsyn kan vara att med hjälp av kamera lokalisera djuren över stora ytor. Denna användning begränsas dock av nuvarande bestämmelser om att föraren måste ha ögontakt med drönaren. I renskötseln har drönare börjat användas för att förflytta djur men denna tillämpning är ännu inte juridiskt reglerad. Virtuella stängsel är strukturer som bestäms med kartkoordinater eller elektronisk sändare på marken. Stängslen fungerar som inhägnader, hinder eller gränser. Djuren mottar signaler (vanligen ljud) och stimuli (vanligen elstötar från ett halsband) som gör det möjligt för dem att lära sig var stängslet finns. I vetenskapliga studier har man med varierande framgång lyckats lära djuren att associera ljudsignaler och elstötar med en gräns som inte får passeras. Förmågan att lära sig skiljer mellan olika djurslag, liksom mellan individer. Det finns fortfarande många obesvarade frågeställningar om hur djur kan anpassa sig till virtuella stängselsystemet, liksom hur de påverkas, både under inlärningsfas och bruksfas