The Khartoum Process and human trafficking

The Khartoum Process’s emphasis on stopping northward migration comes at great cost to vulnerable refugees and asylum seekers

Association of Oscillatory Ventilation during Cardiopulmonary Test to Clinical and Functional Variables of Chronic Heart Failure Patients

Objective: The aim of this study is to characterize the presence of exercise oscillatory ventilation (EOV) and to relate it with other cardiopulmonary exercise test (CET) responses and clinical variables. Methods: Forty-six male patients (age: 53.1 +/- 13.6 years oldleft ventricular ejection fraction [LVEF]: 30 +/- 8%) with heart failure were recruited to perform a maximal CET and to correlate the CET responses with clinical variables. The EOV was obtained according to Leite et al. criteria and VE/VCO2 > 34 and peak VO2 34 and peak VO2 34 to patients who just had one of these responses either. Conclusion: The present study showed that there was an incidence of patients with EOV and lower peak VO2 and higher VE/VCO2 slope values, but they showed no difference on other prognostic variables. As well, there was no influence of the presence of EOV on other parameters of CET in this population, suggesting that this variable may be an independent marker of worst prognosis in HF patients.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)Univ Fed Rio de Janeiro, Fac Med, Res Grp Cardioresp Rehabil GECARE, Rio de Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Fac Med, Dept Phys Therapy, Rio de Janeiro, RJ, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Dept Med, Resp Div,Pulm Funct & Clin Exercise Physiol Unit, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Physiotherapy, Resp Div, Sao Paulo, BrazilUniv Fed Sao Carlos UFSCAR, Dept Phys Therapy, Lab Cardiopulm Phys Therapy LACAP, Sao Carlos, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Dept Med, Resp Div,Pulm Funct & Clin Exercise Physiol Unit, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Physiotherapy, Resp Div, Sao Paulo, BrazilWeb of Scienc

Cardiorespiratory adjustments during the accentuation of respiratory sinus arrhythmia: influence from time of maneuver on minute volume, fraction of expired CO 2 , and heart rate variability

La frecuencia cardíaca sufre oscilaciones durante el ciclo respiratorio, fenómeno conocido como arritmia sinusal respiratoria. La maniobra para acentuación de la arritmia sinusal respiratoria (M-ASR) consiste en mantener ventilación educada con frecuencia respiratoria de seis ciclos por minuto con relación al tiempo inspiración/espiración (TI:TE) de 1:1. En este estudio se propone a evaluar la conducta del volumen minuto, de la fracción espirada de CO2 (FeCO2 infiere sobre el PaCO2) y el control autonómico de la frecuencia cardíaca durante la M-ASR con duración mayor de 90s. Se evaluaron 16 varones jóvenes sanos (de 18 a 25 años de edad). Se les orientaron para que realizasen inspiraciones y espiraciones pausadas de 10 segundos de duración por ciclo, TI:TE de 1:1, y consecuente frecuencia respiratoria de seis incursiones por minuto, durante cuatro minutos. Durante la evaluación se recolectaron la frecuencia cardíaca (FC), latido a latido a través de un monitor de frecuencia cardíaca, el volumen minuto (VM) y la FeCO2 mediante un ergoespirómetro. Para el análisis estadístico se empleó ANOVA one-way (con post-hoc de Tukey) o test de Kruskal-Wallis (con post-hoc de Dunn) cuando necesario (pHeart rate (HR) fluctuate during the respiratory cycle. This phenomenon is known as respiratory sinus arrhythmia. The deep breathing test is to keep a paced breathing in six breathing per minute and I:E relationship 1:1. The purpose of this study is to access minute volume, expired fraction of carbon dioxide (EFCO2) and autonomic control of heart rate during deep breathing test longer than 90 seconds. Sixteen young healthy male (18 - 25 years old) were assessed. The subjects were instructed to perform inspirations and expirations with duration of 10 seconds per cycle, I:E = 1:1, and consequently respiratory rate of 6 cycles per minute, for about four minutes with one minute after and before, totaling six minutes. HR was recorded beat-to-beat using a cardio frequencimeter; MV and EFCO2 was measured and recorded using a mobile ergoespirometer. To analyse statistics differences, ANOVA one way (Tuckey post-hoc) and Kruskall Wallis (Dunn post-hoc) were used (pA frequência cardíaca sofre variações durante o ciclo respiratório, fenômeno conhecido como arritmia sinusal respiratória. A manobra para acentuação da arritmia sinusal respiratória (M-ASR) consiste em manter ventilação educada com uma frequência respiratória de seis ciclos por minuto com relação tempo inspiração/expiração (TI:TE) de 1:1. Este estudo tem como objetivo avaliar o comportamento do volume minuto, da fração expirada de CO2 (FeCO2 infere sobre PaCO2) e do controle autonômico da frequência cardíaca durante a M-ASR com duração maior do que 90s. Foram avaliados 16 homens jovens saudáveis (de 18 a 25 anos). Todos foram orientados a realizar inspirações e expirações lentas com duração de 10 segundos por ciclo, TI:TE de 1:1 e consequente frequência respiratória de seis incursões por minuto, durante quatro minutos. Durante a avaliação foi coletada a frequência cardíaca (FC) batimento a batimento por meio de um cardiofrequencímetro, o volume minuto (VM) e a FeCO2 através de um ergoespirômetro. Para análise estatística empregou-se ANOVA one-way (com post-hoc de Tukey) ou teste de Kruskal-Wallis (com post-hoc de Dunn) quando conveniente (

The effect of photobiomodulation on the brain during wakefulness and sleep

Over the last seventy years or so, many previous studies have shown that photobiomodulation, the use of red to near infrared light on body tissues, can improve central and peripheral neuronal function and survival in both health and in disease. These improvements are thought to arise principally from an impact of photobiomodulation on mitochondrial and non-mitochondrial mechanisms in a range of different cell types, including neurones. This impact has downstream effects on many stimulatory and protective genes. An often-neglected feature of nearly all of these improvements is that they have been induced during the state of wakefulness. Recent studies have shown that when applied during the state of sleep, photobiomodulation can also be of benefit, but in a different way, by improving the flow of cerebrospinal fluid and the clearance of toxic waste-products from the brain. In this review, we consider the potential differential effects of photobiomodulation dependent on the state of arousal. We speculate that the effects of photobiomodulation is on different cells and systems depending on whether it is applied during wakefulness or sleep, that it may follow a circadian rhythm. We speculate further that the arousal-dependent photobiomodulation effects are mediated principally through a biophoton – ultra-weak light emission – network of communication and repair across the brain

Biochemical, anatomical, and cognitive influences of exopeptidases truncation in N-terminal Aβ peptide

Les diverses formes provenant du peptide amyloïde (Aβ) procurent une complexité non négligeable à la Maladie Alzheimer (MA) et demandent une meilleure compréhension de leurs rôles. Depuis peu, leur implication dans l’initiation et l’aggravation de la pathologie semble irrévocable, du fait de leur forte présence dans les cerveaux de patients. Des travaux stipulent que la perte de ces fragments, en particulier les Aβs tronqués en N-terminal, améliorent considérablement les fonctions cognitives de plusieurs modèles murins de MA. L’hypothèse de mon projet de recherche a donc été d’analyser l’implication de deux enzymes, pour l’instant peu étudiées dans ce contexte, sur la troncation du peptide Aβ dans la région N-terminale. Durant ma thèse, j’ai étudié le rôle des 2 enzymes candidates à ce clivage : l’Aminopeptidase A (APA) et la Dipeptidyl-peptidase 4 (DPP4). J’ai démontré l’influence des deux exopeptidases dans la troncation du peptide Aβ en N-terminal, dans des modèles in vitro, ex-vivo et in vivo. Les résultats obtenus confortent l’idée que ces enzymes modifient le fragment Aβ en des formes plus toxiques jouant sur les déclins cognitifs, connue dans la pathologie. En effet, après avoir caractérisé les constructions shRNA et les lentivirus dirigés contre APA ou après le traitement chronique avec le RB150 (un inhibiteur pharmacologique d’APA), les résultats mettent en évidence qu’une diminution des formes tronquées d’Aβ en région N-terminale améliore considérablement la maturation des épines dendritiques et les déclins de mémoire spatiale. Biochimiquement, les souris présentent une dégradation d’Aβ par une diminution drastique des plaques amyloïdes au niveau hippocampique ainsi qu’une baisse du niveau d’AβpE3-42 (approche pharmacologique) et Aβ1-42 (lentivirus) dans la fraction insoluble. En parallèle, DPP4 présente un rôle apriori plus complexe. En effet, les résultats par spectrométrie de masse et immunoprécipitation dénotent que DPP4 clive Aβ40 en Aβ3-40. L’approche lentivirale atteste d’une baisse significative du niveau de plaques amyloïdes et d’Aβ40 et Aβ42 dans la fraction insoluble en Elisa et d’une amélioration de l’apprentissage. Cependant, le traitement à la sitagliptine montre peu d’effets bénéfiques en tests comportementaux ou après analyses biochimiques. Par ailleurs, l’activité enzymatique d’APA et de DPP4 mesurée dans des cerveaux de patients montre une augmentation au stade précoce de la pathologie. L’ensemble de ces résultats renforce indéniablement l’implication de ces enzymes dans l’initiation et/ou le développement de la pathologie. APA et DPP4 se révèlent d’être des candidats intéressants pour des approches thérapeutiques visant à bloquer la formation des formes d’Aβs tronquées en région N-terminale.The diversity of amyloid peptides (Aβs) forms significantly contributes to the complexity of the pathology requiring a better understanding of their roles. Recently, their involvement in the initiation and worsening of Alzheimer’s Disease (AD) seemed irrevocable, due to their strong presence in patients’ brains. Studies have shown that the loss of these fragments, in particular the Aβ forms truncated at N-terminal end, considerably improve cognitive functions in several mouse models of the disease. The hypothesis of my project was to analyze the implication of two enzymes, so far little studied in this context, on the truncation of the Aβ peptide at the N-terminal region. Over these years, I have studied the role of 2 candidate enzymes: Aminopeptidase A (APA) and Dipeptidyl-peptidase 4 (DPP4).During my thesis, I proved the influence of two exopeptidases in the truncation of the Aβ peptide in the N-terminal region with in vitro, ex-vivo and in vivo models. The results support the idea that these enzymes modify the Aβ fragment into more toxic forms by participating on cognitive declines, known in the pathology. In fact, after the characterization of shRNA constructs and lentiviruses against APA or after chronic treatment with RB150, the results show that a decrease in truncated forms of Aβ significantly improves maturation of dendritic spines and spatial memory declines. Biochemically, mice show a degradation of Aβ by a drastic decrease in amyloid plaques at the hippocampal level as well as a decrease in the level of AβpE3-42 (pharmacological approach) and Aβ1-42 (lentivirus) in the insoluble fraction by Elisa. In parallel, DPP4 presents a more complex role. Indeed, the results obtained by mass spectrometry and immunoprecipitation show that DPP4 cleaves Aβ40 into Aβ3-40. The lentiviral approach shows a significant decrease in the level of amyloid plaques and an improvement in learning (Water Maze). Moreover, the enzymatic activity of DPP4 and APA in patient’s brains shows an increase at the early stage of the pathology. APA and DPP4 are proving to be interesting candidates for therapeutic approaches aiming at blocking the formation of truncated Aβ forms at the N-terminal region

Influences biochimiques, anatomiques et cognitives de la troncation exopeptidasique N-terminale du peptide Aβ

The diversity of amyloid peptides (Aβs) forms significantly contributes to the complexity of the pathology requiring a better understanding of their roles. Recently, their involvement in the initiation and worsening of Alzheimer’s Disease (AD) seemed irrevocable, due to their strong presence in patients’ brains. Studies have shown that the loss of these fragments, in particular the Aβ forms truncated at N-terminal end, considerably improve cognitive functions in several mouse models of the disease. The hypothesis of my project was to analyze the implication of two enzymes, so far little studied in this context, on the truncation of the Aβ peptide at the N-terminal region. Over these years, I have studied the role of 2 candidate enzymes: Aminopeptidase A (APA) and Dipeptidyl-peptidase 4 (DPP4).During my thesis, I proved the influence of two exopeptidases in the truncation of the Aβ peptide in the N-terminal region with in vitro, ex-vivo and in vivo models. The results support the idea that these enzymes modify the Aβ fragment into more toxic forms by participating on cognitive declines, known in the pathology. In fact, after the characterization of shRNA constructs and lentiviruses against APA or after chronic treatment with RB150, the results show that a decrease in truncated forms of Aβ significantly improves maturation of dendritic spines and spatial memory declines. Biochemically, mice show a degradation of Aβ by a drastic decrease in amyloid plaques at the hippocampal level as well as a decrease in the level of AβpE3-42 (pharmacological approach) and Aβ1-42 (lentivirus) in the insoluble fraction by Elisa. In parallel, DPP4 presents a more complex role. Indeed, the results obtained by mass spectrometry and immunoprecipitation show that DPP4 cleaves Aβ40 into Aβ3-40. The lentiviral approach shows a significant decrease in the level of amyloid plaques and an improvement in learning (Water Maze). Moreover, the enzymatic activity of DPP4 and APA in patient’s brains shows an increase at the early stage of the pathology. APA and DPP4 are proving to be interesting candidates for therapeutic approaches aiming at blocking the formation of truncated Aβ forms at the N-terminal region.Les diverses formes provenant du peptide amyloïde (Aβ) procurent une complexité non négligeable à la Maladie Alzheimer (MA) et demandent une meilleure compréhension de leurs rôles. Depuis peu, leur implication dans l’initiation et l’aggravation de la pathologie semble irrévocable, du fait de leur forte présence dans les cerveaux de patients. Des travaux stipulent que la perte de ces fragments, en particulier les Aβs tronqués en N-terminal, améliorent considérablement les fonctions cognitives de plusieurs modèles murins de MA. L’hypothèse de mon projet de recherche a donc été d’analyser l’implication de deux enzymes, pour l’instant peu étudiées dans ce contexte, sur la troncation du peptide Aβ dans la région N-terminale. Durant ma thèse, j’ai étudié le rôle des 2 enzymes candidates à ce clivage : l’Aminopeptidase A (APA) et la Dipeptidyl-peptidase 4 (DPP4). J’ai démontré l’influence des deux exopeptidases dans la troncation du peptide Aβ en N-terminal, dans des modèles in vitro, ex-vivo et in vivo. Les résultats obtenus confortent l’idée que ces enzymes modifient le fragment Aβ en des formes plus toxiques jouant sur les déclins cognitifs, connue dans la pathologie. En effet, après avoir caractérisé les constructions shRNA et les lentivirus dirigés contre APA ou après le traitement chronique avec le RB150 (un inhibiteur pharmacologique d’APA), les résultats mettent en évidence qu’une diminution des formes tronquées d’Aβ en région N-terminale améliore considérablement la maturation des épines dendritiques et les déclins de mémoire spatiale. Biochimiquement, les souris présentent une dégradation d’Aβ par une diminution drastique des plaques amyloïdes au niveau hippocampique ainsi qu’une baisse du niveau d’AβpE3-42 (approche pharmacologique) et Aβ1-42 (lentivirus) dans la fraction insoluble. En parallèle, DPP4 présente un rôle apriori plus complexe. En effet, les résultats par spectrométrie de masse et immunoprécipitation dénotent que DPP4 clive Aβ40 en Aβ3-40. L’approche lentivirale atteste d’une baisse significative du niveau de plaques amyloïdes et d’Aβ40 et Aβ42 dans la fraction insoluble en Elisa et d’une amélioration de l’apprentissage. Cependant, le traitement à la sitagliptine montre peu d’effets bénéfiques en tests comportementaux ou après analyses biochimiques. Par ailleurs, l’activité enzymatique d’APA et de DPP4 mesurée dans des cerveaux de patients montre une augmentation au stade précoce de la pathologie. L’ensemble de ces résultats renforce indéniablement l’implication de ces enzymes dans l’initiation et/ou le développement de la pathologie. APA et DPP4 se révèlent d’être des candidats intéressants pour des approches thérapeutiques visant à bloquer la formation des formes d’Aβs tronquées en région N-terminale

Analysis of CX3CR1 haplodeficiency in male and female APPswe/PSEN1dE9 mice along Alzheimer disease progression

International audienceMicroglia, the resident immune cells of the brain, have recently emerged as key players in Alzheimer Disease (AD) pathogenesis, but their roles in AD remain largely elusive and require further investigation. Microglia functions are readily altered when isolated from their brain environment, and microglia reporter mice thus represent valuable tools to study the contribution of these cells to neurodegenerative diseases such as AD. The CX3CR1+/eGFP mice is one of the most popular microglia reporter mice, and has been used in numerous studies to investigate in vivo microglial functions, including in the context of AD research. However, until now, the impact of CX3CR1 haplodeficiency on the typical features of Alzheimer Disease has not been studied in depth. To fill this gap, we generated APPswe/PSEN1dE9:CX3CR1+/eGFP mice and analyzed these mice for Alzheimer's like pathology and neuroinflammation hallmarks. More specifically, using robust multifactorial statistical and multivariate analyses, we investigated the impact of CX3CR1 deficiency in both males and females, at three typical stages of the pathology progression: at early stage when Amyloid-β (Aβ) deposition just starts, at intermediate stage during Aβ accumulation phase and at more advanced stages when Aβ plaque number stabilizes. We found that CX3CR1 haplodeficiency had little impact on the progression of the pathology in the APPswe/PSEN1dE9 model and demonstrated that the APPswe/PSEN1dE9:CX3CR1+/eGFP line is a relevant and useful model to study the role of microglia in Alzheimer Disease. In addition, although Aβ plaques density is higher in females compared to age-matched males, we show that their glial reaction, inflammation status and memory deficits are not different

Neurotoxicity of a Biopesticide Analog on Zebrafish Larvae at Nanomolar Concentrations

Despite the ever-increasing role of pesticides in modern agriculture, their deleterious effects are still underexplored. Here we examine the effect of A6, a pesticide derived from the naturally-occurring α-terthienyl, and structurally related to the endocrine disrupting pesticides anilinopyrimidines, on living zebrafish larvae. We show that both A6 and an anilinopyrimidine, cyprodinyl, decrease larval survival and affect central neurons at micromolar concentrations. Focusing on a superficial and easily observable sensory system, the lateral line system, we found that defects in axonal and sensory cell regeneration can be observed at much lower doses, in the nanomolar range. We also show that A6 accumulates preferentially in lateral line neurons and hair cells. We examined whether A6 affects the expression of putative target genes, and found that genes involved in apoptosis/cell proliferation are down-regulated, as well as genes reflecting estrogen receptor activation, consistent with previous reports that anilinopyrimidines act as endocrine disruptors. On the other hand, canonical targets of endocrine signaling are not affected, suggesting that the neurotoxic effect of A6 may be due to the binding of this compound to a recently identified, neuron-specific estrogen receptor

A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine

International audienceMidbrain dopamine (DA) neurons are key players in motivation and reward processing. Increased DA release is thought to be central in the initiation of drug addiction. Whereas dopamine neurons are generally considered to be activated by drugs such as nicotine, we report here that nicotine not only induces excitation of ventral tegmental area (VTA) DA cells but also induces inhibition of a subset of VTA DA neurons that are anatomically segregated in the medial part of the VTA. These opposite responses do not correlate with the inhibition and excitation induced by noxious stimuli. We show that this inhibition requires D2 receptor (D2-R) activation, suggesting that a dopaminergic release is involved in the mechanism. Our findings suggest a principle of concurrent excitation and inhibition of VTA DA cells in response to nicotine. It promotes unexplored roles for DA release in addiction contrasting with the classical views of reinforcement and motivation, and give rise to a new interpretation of the mode of operation of the reward system