Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

BACKGROUND: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio

Photochemistry of 1-allyl-4-aryltetrazolones in solution; structural effects on photoproduct selectivity

The photochemistry of tetrazolones derived from the carbocyclic allylic alcohols cyclohex-2-enol and 3-methylcyclohex-2-enol and from the natural terpene alcohol nerol was investigated in solution with the aim of assessing the effect of solvent and of structural constraints imposed by bulky allylic moieties on photoproduct selectivity and stability. Photolysis of tetrazolones derived from nerol and cyclohex-2-enol afforded the corresponding pyrimidinones as major products through a pathway that appears to be similar to that proposed for other 1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones derived from acyclic and unhindered allylic alcohols previously investigated but photolysis of the tetrazolone derived from the bulkier 3–methylcyclohex-2-enol 4c leads to formation of a benzimidazolone, indicating that, in this case, cyclization of the biradical formed upon extrusion of N2 involves the phenyl substituent and not the allylic moiety. Theoretical calculations (DFT(B3LYP)/3-21G*) were conducted to support the interpretation of the experimental results and mechanistic proposals. Laser flash photolysis experiments were conducted with the aim of clarifying the nature of the intermediate involved in the primary photocleavage process

A Weyl's law for black holes

We discuss a Weyl's law for the quasi-normal modes of black holes that recovers the structural features of the standard Weyl's law for the eigenvalues of the Laplacian in compact regions. Specifically, the asymptotics of the counting function $N(\omega)$ of quasi-normal modes of $(d+1)$-dimensional black holes follows a power-law $N(\omega)\sim \mathrm{Vol}_d^{\mathrm{eff}}\omega^d$, with $\mathrm{Vol}_d^{\mathrm{eff}}$ an effective volume determined by the light-trapping and decay properties of the black hole geometry. Closed forms are presented for the Schwarzschild black hole and a quasi-normal mode Weyl's law is proposed for generic black holes. As an application, such Weyl's law could provide a probe into the effective dimensionality of spacetime and the relevant resonant scales of actual astrophysical black holes, upon the counting of sufficiently many overtones in the observed ringdown signal of binary black hole mergers.Comment: 12 pages, 4 figures, preliminary versio

Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

Background: Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. Methods: For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. Results: In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. Conclusion: In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.This work was supported by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and projects POCI-01-0145-FEDER-029017 and POCI-01-0145-FEDER-016390. Diana Pádua acknowledges FCT for financial support through a PhD fellowship (SFRH/BD/146186/2019). The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

A hierarchical detection method in external communication for self-driving vehicles based on TDMA

Security is considered a major challenge for self-driving and semi self-driving vehicles. These vehicles depend heavily on communications to predict and sense their external environment used in their motion. They use a type of ad hoc network termed Vehicular ad hoc networks (VANETs). Unfortunately, VANETs are potentially exposed to many attacks on network and application level. This paper, proposes a new intrusion detection system to protect the communication system of self-driving cars; utilising a combination of hierarchical models based on clusters and log parameters. This security system is designed to detect Sybil and Wormhole attacks in highway usage scenarios. It is based on clusters, utilising Time Division Multiple Access (TDMA) to overcome some of the obstacles of VANETs such as high density, high mobility and bandwidth limitations in exchanging messages. This makes the security system more efficient, accurate and capable of real time detection and quick in identification of malicious behaviour in VANETs. In this scheme, each vehicle log calculates and stores different parameter values after receiving the cooperative awareness messages from nearby vehicles. The vehicles exchange their log data and determine the difference between the parameters, which is utilised to detect Sybil attacks and Wormhole attacks. In order to realize efficient and effective intrusion detection system, we use the well-known network simulator (ns-2) to verify the performance of the security system. Simulation results indicate that the security system can achieve high detection rates and effectively detect anomalies with low rate of false alarms

Analysis of Nursing Dissertations and Theses on Mental Health, Brazil, 1979-2007

This bibliographic study analyzes scientific texts published in the CEPEn database in the mental health field (1979-2007). A total of 280 abstracts were investigated, of which 208 were Master’s theses. The individuals investigated in these studies were professionals (57), patients (50), and professors and/or students (18). Among the themes addressed between 2000 and 2007 were the following: Nursing Care in Mental Health (40), Perception in Mental Health (37); and Transversality in Mental Health Care (27). This study provided an overview of the scientific research produced in the mental health field in Brazilian nursing graduate programs. We expect this study to elicit reflections concerning mental health care practice and enable new approaches for nursing promoting health and the prevention of diseases in order to enable patients to recover their citizenship, autonomy and quality of life.Se trata de un estudio bibliográfico, con el objetivo de analizar los textos científicos divulgados en la base de datos CEPEn en el área de salud mental (1979-2007). El total de resúmenes estudiados fueron 280, de los cuales 208 eran disertaciones de maestría. Los sujetos que se destacaron fueron los profesionales (57) y pacientes (50). Entre las temáticas abordadas se evidenciaron (2000-2007): el Cuidado de Enfermería en Salud Mental (40) y la Percepción en Salud Mental (37). Este trabajo posibilitó obtener una visión panorámica sobre la producción científica en salud mental en los cursos de Posgraduación en Enfermería en Brasil. Esperamos que el estudio incentive la reflexión sobre las prácticas de cuidado en salud mental y posibilite nuevos abordajes en enfermería con el objetivo de promover la salud y prevenir daños, de forma a favorecer la ciudadanía, la autonomía y la calidad de vida de los sujetos envueltos.Trata-se de estudo bibliográfico, com o objetivo de analisar os textos científicos, divulgados na base de dados CEPEn, na área de saúde mental (1979-2007). O total de resumos estudados foi 280, dos quais 208 constituíam-se de dissertações de mestrado. Os sujeitos que se destacaram foram os profissionais (57) e pacientes (50). Dentre as temáticas abordadas evidenciaram-se (2000-2007): o cuidado de enfermagem em saúde mental (40) e a percepção em saúde mental (37). Este trabalho possibilitou visualização panorâmica acerca da produção científica em saúde mental nos cursos de pós-graduação em enfermagem, no Brasil. Espera-se, aqui, que o estudo suscite reflexões acerca das práticas de cuidado em saúde mental e possibilite novas abordagens em enfermagem, com vistas à promoção da saúde e prevenção de agravos que favoreçam a cidadania, autonomia e qualidade de vida dos sujeitos envolvidos

Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches

PMCID: PMC3668194SEP was directly funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. SN acknowledges support from the Oxford NIHR Biomedical Research Centre and from the Oxford British Heart Foundation Centre of Research Excellence. SP and PL are funded by a BHF Senior Clinical Research fellowship. RC is supported by a BHF Research Chair and acknowledges the support of the Oxford BHF Centre for Research Excellence and the MRC and Wellcome Trust. PMM gratefully acknowledges training fellowships supporting his laboratory from the Wellcome Trust, GlaxoSmithKline and the Medical Research Council

Financiamento das corporações : perspectivas do desenvolvimento brasileiro

É permitida a reprodução deste texto e dos dados nele contidos, desde que citada a fonte. Reproduções para fins comerciais são proibidas.Inclui bibliografias