Taking care to protect the environment against damage: A meaningless obligation?

Little attention is paid to the obligation of 'care' in Article 55(1) of Additional Protocol I. Beyond a general principle of upholding environmental value in times of armed conflict, what is the scope and content of the obligation? If it is worthless, what makes it so? Since the care provision includes the same high threshold of harm found elsewhere in the environmental provisions, has this stumbling block now been removed by state practice? Rule 44 of the Customary Law Study might appear to suggest that this is so, or does it? Ultimately then, is the care obligation worth caring about? © Copyright International Committee of the Red Cross 2010

Mitochondrial dysfunction - the beginning of the end in Alzheimer's disease? Separate and synergistic modes of tau and amyloid-β toxicity

The pathology of Alzheimer's disease (AD) is characterized by amyloid plaques (aggregates of amyloid-β (Aβ)) and neurofibrillary tangles (aggregates of tau) and is accompanied by mitochondrial dysfunction, but the mechanisms underlying this dysfunction are poorly understood. In this review, we discuss the critical role of mitochondria and the close inter-relationship of this organelle with the two main pathological features in the pathogenic process underlying AD. Moreover, we summarize evidence from AD post-mortem brain as well as cellular and animal AD models showing that Aβ and tau protein trigger mitochondrial dysfunction through a number of pathways, such as impairment of oxidative phosphorylation, elevation of reactive oxygen species production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. A vicious cycle as well as several vicious circles within the cycle, each accelerating the other, can be drawn, emphasizing the synergistic deterioration of mitochondria by tau and Aβ

Regulation of mitochondrial dynamics and bioenergetics : implications of circadian clock and neurosteroids in health and diseases

The cellular metabolism is a highly dynamic process where mitochondria network is a prominent actor in regulation of both energy metabolism and apoptotic pathways. To preserve the integrity of a healthy mitochondrial population within the cell but also the integrity of the cell itself, mitochondrial networks come in varied shapes and ultrastructures to ensure the main energy supply, stored in the form of adenosine triphosphate (ATP), by oxidative reactions from nutritional sources. Therefore, alterations in both mitochondrial dynamics and metabolism are often related to each other as early and prominent events in the pathogenesis of several age-related disorders including Alzheimer’s disease (AD). Advances in the understanding of the mechanisms underlying the coordination between mitochondrial dynamics and the functional state of mitochondria in health are essential for the characterization of disease-related changes of mitochondria in the course of neurodegenerative disorders. The purpose of this thesis was therefore to pinpoint the mechanistic processes that are involved in the regulation of mitochondrial bioenergetics and dynamics. To better understand (I) the tight equilibrium between mitochondrial morphology and function in physiological state and (II) its impact on abnormal mitochondrial, the thesis was divided in two main parts: I. The first aim of the thesis was to investigate the potential influence of (A) the circadian clock and (B) neurosteroids on the maintenance of mitochondrial homeostasis. (A) Since biological clocks are tightly connected to metabolic processes within the cell, we first determined whether mitochondrial dynamics and metabolism are coupled events that are coordinated by the circadian system. (B) Considering compelling evidence that highlighted neuroprotective effects of steroids in the brain, we examined whether different neurosteroids are able to improve mitochondrial bioenergetics to prevent age-related mitochondrial alterations which eventually lead to neurodegeneration. II. In the second part (C), we determined whether amyloid-beta impacts the integrity of the mitochondrial structure–function relationship since both mitochondrial dynamics and bioenergetics are hallmarks of Aβ-induced neuronal toxicity in AD. I. (A) The circadian clock is a hierarchical network of oscillators that coordinate a wide variety of daily biological functions, including metabolic functions, to the optimal time of day anticipating the periodical changes of the external environment for all living organisms. Mitochondria are dynamic organelles at the crossroad of the cellular metabolism that fuse and divide continuously to fulfill their role in the maintenance of the cellular bioenergetic homeostasis. While it is well known that metabolism is a complex biochemical network that is tightly intertwined with the circadian clock through reciprocal regulation from metabolites to transcription factors, the mechanistic connections between the biological clock and the mitochondrial network remain mostly elusive. We therefore addressed the questions whether and how the circadian clock intervenes in the coordination between mitochondrial dynamics and functions and whether the coupled mitochondrial network- metabolism may be able to influence the circadian clock. We demonstrated in vitro and in vivo that mitochondrial fission-fusion dynamics were strongly clock-controlled, as well as all other aspects of mitochondrial metabolic flux, including oxidative phosphorylation, generation of ATP and reactive oxygen species (ROS). The changes in cell cycle-based mitochondrial morphology required the circadian phosphorylation of the key protein, dynamin-related protein 1 (DRP1), the major protein involved in mitochondrial fission. Genetic or pharmacological abrogation of DRP1 activity abolished circadian mitochondrial network dynamics and mitochondrial respiratory activity, as well as eliminated circadian ATP production. The disruption of circadian mitochondrial dynamics furthermore feeds back to impair the core circadian clock. Overall, our findings are consistent with the existence of a crosstalk between the clock and the mitochondrial network that maintains bioenergetic homeostasis in response to circadian metabolic changes. I. (B) We aimed to investigate the potential role of different neurosteroids on mitochondrial bioenergetics and redox homeostasis in neuronal cells. In contrast to steroid hormones produced by endocrine glands, neurosteroids are synthetized within the nervous system itself and are defined as neuroactive molecules acting on the nervous system in an auto/paracrine manner. Neurosteroids exhibit several biological functions that are essential during brain development as well as in the adult brain. Moreover, progressive depletion in neurosteroid content might contribute to an age-related neuronal decline that eventually leads to the development of neurodegenerative disorders including AD. Although compelling evidence has shown that estradiol interacts with mitochondria to counteract oxidative stress occurring in age-related diseases such as AD, the potential role of other neurosteroids on mitochondria is rather poorly investigated and understood. To expand our knowledge on the mechanisms behind the neuroprotective action of neurosteroids, a selection of sex-hormone-related neurosteroids, including progesterone, estradiol, estrone, testosterone, 3-alpha-androstanediol, dehydroepiandrosterone (DHEA) as well as allopregnolone, were tested on mitochondrial function. Using human SH-SY5Y neuroblastoma cells, we determined which of the neurosteroids exhibited the capacity to enhance mitochondrial metabolism by increasing ATP content along with an augmentation of mitochondrial membrane potential and mitochondrial respiration. Interestingly, particular bioenergetic profiles were found for each neurosteroid, which might be due to an involvement of different receptors. When the respective steroid receptors were blocked with specific inhibitors, ATP contents were entirely depleted confirming a receptor-specific mode of action of neurosteroids. Concomitantly with the enhanced mitochondrial metabolism, treatment with neurosteroids induced an augmentation of ROS levels in parallel to an up-regulation of antioxidant defenses suggesting a direct or indirect role of neurosteroids on redox homeostasis in neuronal cells. Collectively, these novel findings demonstrate that neurosteroids are able to differentially improve mitochondrial function as well as to modulate redox homeostasis through distinct receptors. Because of the disparate effects of neurosteroids on mitochondrial metabolism, the underlying mechanisms have to be further elucidated in future studies, particularly the effect of neurosteroids on mitochondrial dynamics, as well as those in models of neurodegenerative diseases, such as AD. II. (C) The aim of the second part of this thesis was to investigate the impact of amyloid-beta on the balance between mitochondrial structure and function since abnormalities in mitochondrial dynamics and bioenergetics are hallmarks of Aβ-induced neuronal toxicity in AD. For that purpose, we examined mitochondrial architecture and bioenergetics in cell-cycle controlled human primary fibroblast cultures treated with amyloid-beta 1-42 peptide compared to non-treated cells. We demonstrated that variations in mitochondrial respiration, ATP and ROS content coincided with the oscillations pattern of the mitochondrial network in physiological conditions in control cells confirming the existence of a direct link between the mitochondrial network and the metabolic state of mitochondria. Indeed, in between the switch from tubular to fragmented mitochondrial network, we observed an increase in ATP level which correlated with a higher oxygen consumption rate (OCR) in the basal respiration as well as in ATP turnover and maximal respiration. In contrast, amyloid-beta 1-42 almost completely dampened the oscillations of mitochondrial dynamics followed by a decline of mitochondrial metabolism including reduced ATP level and OCR. Furthermore, Aβ-induced mitochondrial defects provoked a drastic augmentation in mitochondrial ROS level which might participate, along with an imbalance in the NAD+/NADH ratio, in the generation of oxidative stress confirming the oxidative stress theory of aging and AD. Hence, these new insights support the concept that mitochondrial bioenergetics is coordinated by mitochondrial architecture transitions and that Aβ induced a functional imbalance in the mitochondrial structure-function relationship, which might contribute already at an early disease state to AD pathogenesis. Altogether, in the present thesis, we gained new insights on factors regulating mitochondrial dynamics and metabolism in health and disease states, e.g. AD. We firstly revealed that the circadian clock system, even in nondividing cells and tissues, regulates the phosphorylation of DRP1 resulting in cycles of fission and fusion that are essential for circadian oscillations in ATP production. These findings provide multiple implications into the understanding of metabolic homeostasis in human health as well as in disorders linked to impairments in circadian clock and/ or mitochondrial function. Secondly, we determined that neurosteroids are able to differentially modulate mitochondrial metabolism at the physiological state suggesting that these molecules might be considered as promising candidates in neuroprotective approaches to counterbalance mitochondrial deficiencies. Finally, we contributed to a better understanding of Aβ-induced neurotoxicity that is mediated by mitochondrial malfunctions further emphasizing the mitochondrial cascade hypothesis of AD

Functional health literacy in Spanish-speaking Latinas seeking breast cancer screening through the National Breast and Cervical Cancer Screening Program

Samantha Garbers1, Karen Schmitt2, Anne Marie Rappa2, Mary Ann Chiasson11Public Health Solutions, New York, NY, USA; 2Columbia University Breast Cancer Screening Program, New York, NY, USABackground: This analysis examines the association between functional health literacy and follow-up after mammography among women receiving breast cancer screening at a National Breast and Cervical Cancer Early Detection Program site in New York City that provides universal bilingual case management.Methods: A total of 707 Latinas who spoke Spanish as their primary language completed a survey of health and demographic characteristics and the Test of Functional Health Literacy in Spanish (TOFHLA-S). Survey results were matched with clinical outcome data.Results: Among the survey participants, 98% were foreign-born and 99% had no health insurance. While the study found significant differences in access to health information and past screening behavior, women without adequate health literacy in Spanish were no less likely to receive clinical resolution of abnormal mammograms within 60 days (81.8% overall; n = 110) or to return for a repeat mammogram within 18 months (57.2% overall; n = 697). In fact, among those referred for a Pap test (n = 310), women without adequate health literacy were more likely to receive a Pap test within 60 days of their mammogram than those with adequate health literacy (82% compared to 71%, OR: 1.83, 95% CI: 1.04–3.22).Discussion: The lack of significantly lower follow-up outcomes among women with inadequate and marginal functional health literacy in this population of primary Spanish-speaking Latinas suggests that, once women have accessed screening services, programmatic approaches may exist to mitigate barriers to follow-up and to ensure optimal cancer screening outcomes for women of all literacy levels.Keywords: health literacy, mammography, Latinas, case management, cancer screenin

Feasibility and efficacy of pairing fecal immunochemical testing with mammography for increasing colorectal cancer screening among uninsured Latinas in northern Manhattan

Objectives: We evaluated the feasibility and efficacy of a program to promote colorectal cancer screening (CRC) among uninsured Latinas receiving mammography through a cancer screening clinic in northern Manhattan. Methods: Between August 2009 and March 2010, unscreened, average CRC risk, uninsured Latinas, aged 50–64 years, undergoing mammography received a screening recommendation, education, and fecal immunochemical test (FIT). Socio-demographic information and level of acculturation was collected. Screening compliance was assessed. Results: Of 651 Latinas evaluated, 210 were eligible and, of these, 94% (n = 197) consented to participate; 441 were excluded because they were up-to-date with CRC screening (n = 130), less than 50 (n = 285) or greater than 64 (n = 26) years of age. After intervention, 177 (90%) completed FIT. Within 2 weeks, 87% completed the FIT, and 69% did so with no reminder calls. Acculturation was significantly lower among screeners (p = 0.014). Compared with non-screeners, screeners were more likely to be foreign-born (p = 0.009), to speak only Spanish (p = 0.043), and to prefer to read (p = 0.037), and think (p = 0.015) in Spanish. Conclusion: This study suggests that pairing CRC education and screening with mammography is both feasible and efficacious

Technical standards for the process of material sterilization in health units: a proposal of nursing

Objetivo: Organizar uma Norma Técnica para a uniformização do processo de esterilização em Unidades Básicas de Saúde (UBS). Método: Estudo exploratório e descritivo para a construção de diretriz sobre o processo de esterilização, desenvolvido em parceria com o Programa de Educação Continuada em Saúde da Universidade do Estado de Santa Catarina -UDESC, o qual seguiu as recomendações éticas da Resolução 466/2012 da Comissão Nacional de Ética em Pesquisa. Resultados: Abordou-se questões relacionadas ao fluxo de materiais unidirecional, padronização das formas de limpeza e empacotamento, rotulagem, tipos de esterilização, testes de validação e registro do processo de esterilização. Conclusões: A norma técnica servirá de base para treinamento de novos colaboradores, minimizando os custos públicos envoltos no reprocessamento de materiais odonto-médico-hospitalares e, assegurando melhor qualidade sanitária aos usuários do Sistema Único de Saúde (SUS).Objetivo: Organizar una guía de Normas Técnicas para la estandarización del proceso de esterilización en Unidades Básicas de Salud (UBS). Método: Se realizó un estudio exploratorio y descriptivo para la construcción de la guía de orientación sobre el proceso de esterilización, desarrollado en colaboración con el Programa de Educación Continua en Salud, Universidad del Estado de Santa Catarina (PECES / UDESC), que siguió las recomendaciones éticas de la Resolución 466 / 2012 de la Comisión Nacional de Ética de la Investigación. Resultados: Se evidencian cuestiones relacionadas con el flujo de material unidireccional, la estandarización de las formas de limpieza y envasado, el etiquetado, los tipos de esterilización, las pruebas de validación y registrar el proceso de esterilización. Conclusiones: La guía de orientación de normas técnicas constituirá la base para la formación de los nuevos empleados, lo que minimiza los costos públicos envueltos en el reprocesamiento, suministros médicos y hospitalarios dentales y garantizar una mejor calidad de la salud de los usuarios del Sistema Único de Salud (SUS).Objective: To organize a Technical Standard for the standardization of the sterilization process in Basic Health Units (BHU). Method: An exploratory and descriptive study for the construction of guidance on the sterilization process, developed in partnership with the Continuing Education Program in Health, University of the State of Santa Catarina - UDESC, which followed the ethical recommendations of Resolution 466 / 2012 of the National Research Ethics Commission. Results: It approaches issues related to the unidirectional material flow, standardization of the forms of cleaning and packaging, labeling, sterilization types, validation tests and record the sterilization process. Conclusions: The technical standard will form the basis for training new employees, minimizing public costs wrapped in reprocessing dental, medical and hospital supplies and ensuring better health quality to users of the Unified Health System (UHS)

Technical standards for the process of material sterilization in health units: a proposal of nursing

Objetivo: Organizar uma Norma Técnica para a uniformização do processo de esterilização em Unidades Básicas de Saúde (UBS). Método: Estudo exploratório e descritivo para a construção de diretriz sobre o processo de esterilização, desenvolvido em parceria com o Programa de Educação Continuada em Saúde da Universidade do Estado de Santa Catarina -UDESC, o qual seguiu as recomendações éticas da Resolução 466/2012 da Comissão Nacional de Ética em Pesquisa. Resultados: Abordou-se questões relacionadas ao fluxo de materiais unidirecional, padronização das formas de limpeza e empacotamento, rotulagem, tipos de esterilização, testes de validação e registro do processo de esterilização. Conclusões: A norma técnica servirá de base para treinamento de novos colaboradores, minimizando os custos públicos envoltos no reprocessamento de materiais odonto-médico-hospitalares e, assegurando melhor qualidade sanitária aos usuários do Sistema Único de Saúde (SUS).Objetivo: Organizar una guía de Normas Técnicas para la estandarización del proceso de esterilización en Unidades Básicas de Salud (UBS). Método: Se realizó un estudio exploratorio y descriptivo para la construcción de la guía de orientación sobre el proceso de esterilización, desarrollado en colaboración con el Programa de Educación Continua en Salud, Universidad del Estado de Santa Catarina (PECES / UDESC), que siguió las recomendaciones éticas de la Resolución 466 / 2012 de la Comisión Nacional de Ética de la Investigación. Resultados: Se evidencian cuestiones relacionadas con el flujo de material unidireccional, la estandarización de las formas de limpieza y envasado, el etiquetado, los tipos de esterilización, las pruebas de validación y registrar el proceso de esterilización. Conclusiones: La guía de orientación de normas técnicas constituirá la base para la formación de los nuevos empleados, lo que minimiza los costos públicos envueltos en el reprocesamiento, suministros médicos y hospitalarios dentales y garantizar una mejor calidad de la salud de los usuarios del Sistema Único de Salud (SUS).Objective: To organize a Technical Standard for the standardization of the sterilization process in Basic Health Units (BHU). Method: An exploratory and descriptive study for the construction of guidance on the sterilization process, developed in partnership with the Continuing Education Program in Health, University of the State of Santa Catarina - UDESC, which followed the ethical recommendations of Resolution 466 / 2012 of the National Research Ethics Commission. Results: It approaches issues related to the unidirectional material flow, standardization of the forms of cleaning and packaging, labeling, sterilization types, validation tests and record the sterilization process. Conclusions: The technical standard will form the basis for training new employees, minimizing public costs wrapped in reprocessing dental, medical and hospital supplies and ensuring better health quality to users of the Unified Health System (UHS)

Cationic surfactants as a non-covalent linker for oxidised cellulose nanofibrils and starch-based hydrogels

International audienceRheological properties of hydrogels composed of TEMPO-oxidised cellulose nanofibrils (OCNF)-starch in the presence of cationic surfactants were investigated. The cationic surfactants dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB) were used to trigger gelation of OCNF at around 5mM surfactant. As OCNF and DTAB/CTAB are oppositely charged, an electrostatic attraction is suggested to explain the gelation mechanism. OCNF (1 wt%) and soluble starch (0.5 and 1 wt%) were blended to prepare hydrogels, where the addition of starch to the OCNF resulted in a higher storage modulus. Starch polymers were suggested to form networks with cellulose nanofibrils. The stiffness and viscosity of OCNF-Starch hydrogels were enhanced further by the addition of cationic surfactants (5mM of DTAB/CTAB). ζ -potential and amylose-iodine complex analyses were also conducted to confirm surface charge and interaction of OCNF-starch-surfactant in order to provide an in-depth understanding of the surfactant-induced gel networks