A tetracationic porphyrin with dual anti-prion activity

Prions are deadly infectious agents made of PrPSc, a misfolded variant of the cellular prion protein (PrPC) which self-propagates by inducing misfolding of native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrPC, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrPC fold, hindering conversion to PrPSc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrPC endocytosis and lysosomal degradation, thus reducing the substrate for PrPSc generation. Zn(II)-BnPyP inhibits propagation of different prion strains in vitro, in neuronal cells and organotypic brain cultures. These results identify a PrPC-targeting compound with an unprecedented dual mechanism of action which might be exploited to achieve anti-prion effects without engendering drug resistance

Revisión de diferentes enfoques de evaluación y tratamiento de los problemas de comportamiento

El presente documento se centra en disminuir conductas que, quizás, es algo más complejo ya que los profesionales deben adquirir mayor responsabilidad debido a las técnicas que se pueden utilizar. Dirigido a maestros, ayudantes, personal institucional, diseñadores de programas, miembros de los comités de manejo conductual o comités de procedimientos restrictivos. Se centra en personas con retraso mental severo y profundo ya que hay menos textos disponibles para tratarles que con niveles más altos de discapacidad. Los procedimientos se presentan de acuerdo con el Modelo de Tratamiento Menos Restrictivo que se ha desarrollado para proteger las libertades civiles de las personas con retraso en el desarrollo

How service‐users with intellectual disabilities understand challenging behaviour and approaches to managing it

Background This study explored understandings that service‐users with intellectual disabilities and challenging behaviour held around their behaviour, what shaped these understandings, and the relationship between how behaviours are managed and well‐being. Methods Eight participants (three female, five male) partook in individual semi‐structured qualitative interviews. Interviews were transcribed and analysed using interpretative phenomenological analysis. Results Three master themes emerged from this analysis: (a) challenging behaviour can be explained via an internal or external frame of reference, with each framework having different implications for how participants attempted to manage behaviour. (b) Positive relationships provide a long‐term buffer to challenging behaviour, with positive relationships with family, staff and peers operating through different mechanisms to achieve this. (c) A greater ability to exert power and control in day‐to‐day life was perceived to reduce challenging behaviour in the long term. Conclusions Implications for practice are discussed

The effect of culture on Corporate Governance Practices in Nigeria

This study focuses on the effect of culture on the application of corporate governance practices in Nigeria. Corporate governance has been receiving serious attention in emerging markets over the past two decades. But relatively little attention has been given to the study on corporate governance in a country study. The current situations in Nigerian public and private sectors such as the corporate scandal resulting from Lever Brothers Nigeria plc, Siemens, Shell, Halliburton, and Cadbury Nigeria plc, have shown that the issue of fraud, corruption, and corporate scandals cannot be overlooked. Most top management, as this study argues, bring in beliefs acquired from their early childhood into their senior management roles and responsibilities. This study adopts a grounded theory and reports on the effect of culture on the implementation of corporate governance in Nigeria. Based on the interview with 32 staffs, this study identifies the effect of culture that shapes corporate governance and they include abuse of power by top management, weak legal framework, poor recruitment and ineffective control. Although having efficient corporate governance is worth pursuing, this depends on the power of top management, the strength of internal control procedures and the legal framework put in place by management