A review on medicinal plants used for treating ototoxicity and acoustic trauma induced hearing loss

Hearing loss induced by chemotherapy and acoustic trauma is mainly associated with two factors, free radical formation and apoptosis pathway activation. Despite numerous efforts on reducing the effects of these factors, no definite strategy is still determined to interfere with and control these processes. In recent studies, various protective agents, including antioxidants have been used on animal models, to inhibit the formation of free radicals thus improving hearing loss.In this review article we will discuss the role of traditional herbal medicine in treatment of noise/drug induced hearing loss, focusing on medicinal plants’ active substances,as well as their mechanisms of action in reducing or preventing the formation of free radicals thus increasing the rate of survival of cochlea cells. Data have been gathered since year 2000, from scientific publications including the following keywords: deafness, drug toxicity, acute trauma, medicinal herbs and oxidative stress. The study includes all herbs and medicinal plants that have been experimentally used in studies on animal models and clinical trials. The results from these studies indicate the effectiveness of most of these herbs and their active substances through their antioxidative properties. Medicinal plants reported in this review can thus be considered as effective remedies intreating noise/drug induced hearing loss,yet further studies need to be done

A review on medicinal plants used for treating ototoxicity and acoustic trauma induced hearing loss

Hearing loss induced by chemotherapy and acoustic trauma is mainly associated with two factors, free radical formation and apoptosis pathway activation. Despite numerous efforts on reducing the effects of these factors, no definite strategy is still determined to interfere with and control these processes. In recent studies, various protective agents, including antioxidants have been used on animal models, to inhibit the formation of free radicals thus improving hearing loss.In this review article we will discuss the role of traditional herbal medicine in treatment of noise/drug induced hearing loss, focusing on medicinal plants’ active substances,as well as their mechanisms of action in reducing or preventing the formation of free radicals thus increasing the rate of survival of cochlea cells. Data have been gathered since year 2000, from scientific publications including the following keywords: deafness, drug toxicity, acute trauma, medicinal herbs and oxidative stress. The study includes all herbs and medicinal plants that have been experimentally used in studies on animal models and clinical trials. The results from these studies indicate the effectiveness of most of these herbs and their active substances through their antioxidative properties. Medicinal plants reported in this review can thus be considered as effective remedies intreating noise/drug induced hearing loss,yet further studies need to be done.publishersversionpublishe

Intracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer’s Disease

The Almeida lab has been supported by FCTJPCOFUND/0004/2015; Alzheimer’s Association Research Grant (AARG-19-618007); Maratona da Saúde; H2020 Spreading Excellence and Widening Participation, H2020-WIDESPREAD01-2016-2017-TeamingPhase2-GA739572; iNOVA4Health (UID/Multi/04462/2019), a program financially supported by Fundação para a Ciencia e Tecnologia (FCT)/Ministério da Educação e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. CG’s salary is supported by FCT-CEECIND/00410/2017. FM has been the recipient of an FCT doctoral fellowship (PD/BD/128344/2017). CP has been the recipient of an FCT doctoral fellowship (SFRH/BD/128374/2017).Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss. Although AD neuropathological hallmarks are extracellular amyloid plaques and intracellular tau tangles, the best correlate of disease progression is synapse loss. What causes synapse loss has been the focus of several researchers in the AD field. Synapses become dysfunctional before plaques and tangles form. Studies based on early-onset familial AD (eFAD) models have supported that synaptic transmission is depressed by β-amyloid (Aβ) triggered mechanisms. Since eFAD is rare, affecting only 1% of patients, research has shifted to the study of the most common late-onset AD (LOAD). Intracellular trafficking has emerged as one of the pathways of LOAD genes. Few studies have assessed the impact of trafficking LOAD genes on synapse dysfunction. Since endocytic traffic is essential for synaptic function, we reviewed Aβ-dependent and independent mechanisms of the earliest synaptic dysfunction in AD. We have focused on the role of intraneuronal and secreted Aβ oligomers, highlighting the dysfunction of endocytic trafficking as an Aβ-dependent mechanism of synapse dysfunction in AD. Here, we reviewed the LOAD trafficking genes APOE4, ABCA7, BIN1, CD2AP, PICALM, EPH1A, and SORL1, for which there is a synaptic link. We conclude that in eFAD and LOAD, the earliest synaptic dysfunctions are characterized by disruptions of the presynaptic vesicle exo- and endocytosis and of postsynaptic glutamate receptor endocytosis. While in eFAD synapse dysfunction seems to be triggered by Aβ, in LOAD, there might be a direct synaptic disruption by LOAD trafficking genes. To identify promising therapeutic targets and biomarkers of the earliest synaptic dysfunction in AD, it will be necessary to join efforts in further dissecting the mechanisms used by Aβ and by LOAD genes to disrupt synapses.publishersversionpublishe

What’s the narrative for practice? A review of recommendations on feedback and a guide to writing impactful practical implications

Research on supervisory feedback has burgeoned over the past 20 years. We ask, what does it have to offer to management practitioners, and is this knowledge conveyed in a constructive way? To answer these questions, we conducted a systematic literature review of the practical implications contained in feedback studies. Based on our retained articles (N = 120) and using the W-H questions as our guiding framework, we critically discuss: Why recommendations are offered, What recommendations are endorsed, When and Where the recommendations are presented as most applicable, to Whom those are addressed, and How they are framed by researchers. In so doing, we summarise the indications that scientific research has offered to practitioners; moreover, following the same framework and the insights collected via a follow-up survey of academics (N = 61), we provide recommendations to researchers across the management and psychology disciplines on how to craft their practical implications sections in a way that may help bridge the gap between research and practice.info:eu-repo/semantics/publishedVersio

Effective Implementation of HR Practices: A Multi-Actor Perspective

La implementació de les polítiques de RRHH, com un procés a través del qual es pot explicar la relació entre la gestió de RRHH i l'acompliment de l'empresa, és de fet un tema important i rellevant, que està poc estudiat i requereix més atenció. Sent un tema destacat en la visió dels RRHH com a procés, la seva naturalesa dinàmica amb múltiples actors i etapes requereix una major exploració. Aquesta exploració es porta a terme en primer lloc aclarint el significat d'implementació i d'implementació efectiva, conceptes tots dos sobre els quals no existeix un consens. En segon lloc, es porta a terme una revisió de la literatura centrada en identificar els factors que influeixen en la implementació efectiva de polítiques de RRHH, categoritzant-los en factors de contingut, context i procés. En tercer lloc, la tesi se centra en la naturalesa dinàmica de la implementació i mitjançant un estudi de cas comparatiu, analitza les dimensions de poder dels actors involucrats i en com influeixen en la implementació efectiva de les polítiques. Finalment, s'aprofundeix en l'estudi d'un dels actors amb més poder, el Director General, i s'explora com aquest actor influeix en el procés d'implementació de les polítiques de RRHH directament i indirectament, a través del paper estratègic del departament de RRHH . En resum, aquesta tesi se centra en el paper de diferents actors a l'hora d'influir en la implementació efectiva de les polítiques de RRHH.La implementación de las políticas de RRHH, como un proceso a través del cual se puede explicar la relación entre la gestión de RRHH y el desempeño de la empresa, es de hecho un tema importante y relevante, que está poco estudiado y requiere más atención. Siendo un tema destacado en la visión de los RRHH como proceso, su naturaleza dinámica con múltiples actores y etapas requiere una mayor exploración. Dicha exploración se lleva a cabo en primer lugar aclarando el significado de implementación y de implementación efectiva, conceptos ambos sobre los que no existe un consenso. En segundo lugar, se lleva a cabo una revisión de la literatura centrada en identificar los factores que influyen en la implementación efectiva de políticas de RRHH, categorizándolos en factores de contenido, contexto y proceso. En tercer lugar, la tesis se centra en la naturaleza dinámica de la implementación y a través de un estudio de caso comparativo, analiza las dimensiones de poder de los actores involucrados y en cómo influyen en la implementación efectiva de las políticas. Finalmente, se profundiza en el estudio de uno de los actores con más poder, el Director General, y se explora cómo este actor influye en el proceso de implementación de las políticas de RRHH directa e indirectamente, a través del rol estratégico del departamento de RRHH. En resumen, esta tesis se centra en el rol de distintos actores a la hora de influir en la implementación efectiva de las políticas de RRHH.HR implementation, as a process through which the relationship between HRM and firm performance can be explained, is indeed an important and relevant topic which is understudied and requires more attention. Being brought to the spotlight by the process-based view of HRM, the dynamic nature of this multi-actor and multi-stage process needs further exploration. In doing so, due to the lack of a unified understanding of HR implementation and its effectiveness, this thesis first clarifies the meanings of these two concepts. Second, it provides a literature review on the factors influencing effective HR implementation, categorizing them into content, context, and process antecedents. Third, focusing on the dynamic nature of HR implementation and conducting a multiple comparative case study approach, this thesis looks at the power dimensions of the involved actors and how these dynamics influence HR implementation effectiveness. Finally, taking advantage of a natural shock and using a multiple comparative case study approach, this thesis looks at the roles of one of the powerful actors, the CEO, and explores how this actor influences the HR implementation process directly and indirectly through affecting the strategic role of HR departments. Overall, this thesis emphasizes on the roles of the involved actors and how they impact HR implementation and its effectiveness

Effective Implementation of HR Practices: A Multi-Actor Perspective

La implementació de les polítiques de RRHH, com un procés a través del qual es pot explicar la relació entre la gestió de RRHH i l'acompliment de l'empresa, és de fet un tema important i rellevant, que està poc estudiat i requereix més atenció. Sent un tema destacat en la visió dels RRHH com a procés, la seva naturalesa dinàmica amb múltiples actors i etapes requereix una major exploració. Aquesta exploració es porta a terme en primer lloc aclarint el significat d'implementació i d'implementació efectiva, conceptes tots dos sobre els quals no existeix un consens. En segon lloc, es porta a terme una revisió de la literatura centrada en identificar els factors que influeixen en la implementació efectiva de polítiques de RRHH, categoritzant-los en factors de contingut, context i procés. En tercer lloc, la tesi se centra en la naturalesa dinàmica de la implementació i mitjançant un estudi de cas comparatiu, analitza les dimensions de poder dels actors involucrats i en com influeixen en la implementació efectiva de les polítiques. Finalment, s'aprofundeix en l'estudi d'un dels actors amb més poder, el Director General, i s'explora com aquest actor influeix en el procés d'implementació de les polítiques de RRHH directament i indirectament, a través del paper estratègic del departament de RRHH . En resum, aquesta tesi se centra en el paper de diferents actors a l'hora d'influir en la implementació efectiva de les polítiques de RRHH.La implementación de las políticas de RRHH, como un proceso a través del cual se puede explicar la relación entre la gestión de RRHH y el desempeño de la empresa, es de hecho un tema importante y relevante, que está poco estudiado y requiere más atención. Siendo un tema destacado en la visión de los RRHH como proceso, su naturaleza dinámica con múltiples actores y etapas requiere una mayor exploración. Dicha exploración se lleva a cabo en primer lugar aclarando el significado de implementación y de implementación efectiva, conceptos ambos sobre los que no existe un consenso. En segundo lugar, se lleva a cabo una revisión de la literatura centrada en identificar los factores que influyen en la implementación efectiva de políticas de RRHH, categorizándolos en factores de contenido, contexto y proceso. En tercer lugar, la tesis se centra en la naturaleza dinámica de la implementación y a través de un estudio de caso comparativo, analiza las dimensiones de poder de los actores involucrados y en cómo influyen en la implementación efectiva de las políticas. Finalmente, se profundiza en el estudio de uno de los actores con más poder, el Director General, y se explora cómo este actor influye en el proceso de implementación de las políticas de RRHH directa e indirectamente, a través del rol estratégico del departamento de RRHH. En resumen, esta tesis se centra en el rol de distintos actores a la hora de influir en la implementación efectiva de las políticas de RRHH.HR implementation, as a process through which the relationship between HRM and firm performance can be explained, is indeed an important and relevant topic which is understudied and requires more attention. Being brought to the spotlight by the process-based view of HRM, the dynamic nature of this multi-actor and multi-stage process needs further exploration. In doing so, due to the lack of a unified understanding of HR implementation and its effectiveness, this thesis first clarifies the meanings of these two concepts. Second, it provides a literature review on the factors influencing effective HR implementation, categorizing them into content, context, and process antecedents. Third, focusing on the dynamic nature of HR implementation and conducting a multiple comparative case study approach, this thesis looks at the power dimensions of the involved actors and how these dynamics influence HR implementation effectiveness. Finally, taking advantage of a natural shock and using a multiple comparative case study approach, this thesis looks at the roles of one of the powerful actors, the CEO, and explores how this actor influences the HR implementation process directly and indirectly through affecting the strategic role of HR departments. Overall, this thesis emphasizes on the roles of the involved actors and how they impact HR implementation and its effectiveness

Investigating the association of endocytic trafficking regulator CD2AP gene variant K633R and the risk of developing Alzheimer's disease

In the central nervous system, excitatory synaptic transmission mainly takes place at dendritic spines, structures rich in actin. Actin stabilizes and regulates dendritic spine structures. The stabilization of spines is essential for the maintenance of long-term memory and proper neural circuit formation. Therefore, actin plays a central role in synapse assembly and function. In late-onset Alzheimer’s disease (LOAD) the earliest memory alterations are due to synaptic dysfunction, yet the causal mechanisms are not known. Amyloid-β (Aβ) accumulation plays a central role in AD pathology. Aβ is produced by sequential cleavage of amyloid precursor protein (APP) by BACE1 and γ-secretase at the earlyendosomal membrane during intracellular trafficking of APP through the endocytic pathways. Altered trafficking of APP can disrupt Aβ production. For the past decade, several rare coding variants were identified in LOAD genetic risk factors that have created a broader picture of the cellular mechanisms involved in AD risk. One of which is CD2-associated protein (CD2AP), an adaptor molecule with a binding site for actin that regulates membrane trafficking and has been reported to be involved in the intracellular trafficking of APP. The role of the CD2AP mutation associated with a higher risk of AD however is not yet understood. Here, we present evidence that the LOAD risk gene CD2AP and its AD-associated genetic variant K633R play an important role in the postsynaptic development of neurons by regulating spinal actin. We found that CD2AP is enriched in dendritic spines and colocalizes with post-synaptic density protein. Its knockdown impairs spine development and synapse formation by actin-related mechanisms. Importantly, the C-terminal domain is required for CD2AP localization to spines. These findings identify CD2AP as a novel regulator of synaptic function and neuronal networks. We investigated the effect of CD2AP overexpression and KD/KO on intracellular Aβ and APP distribution and APP degradation in neuronal cells. We observed that CD2AP, both wild-type and mutant increased intracellular Aβ42 levels. CD2AP increases APP sorting to the lumen of the Rab5-positive endosomes. While in cells expressing the mutant form of the protein, APP does not sort into the lumen and remains at the endosomal membrane. Moreover, the CD2AP mutant reduced the degradation of APP which happens at a faster rate compared to the mutant-expressing cells. We showed that increased intracellular APP levels in cells expressing the mutant protein may be the reason for the increased accumulation of Aβ42 at synaptic sites, observed in primary neurons. These results may explain the impaired cellular function of the CD2AP mutation the AD risk factor, in APP processing and degradation, leading to Aβ42 accumulation and creation of the senile plaques, an important hallmark in AD. In summary, we discovered that the CD2AP(K633R) LOAD rare coding mutation contributes to AD pathology through two distinct yet related mechanisms.CD2AP LOAD mutation can contribute to AD pathology by impairing APP degradation and increasing the accumulation of Aβ42 in the cells and at the synapses. We also found that CD2AP LOAD mutation can impact neurons independent of Aβ, and through actin by regulating synaptic architecture. Thus, CD2AP mutation exerts its dual function in neurons and on synapses by first, regulating spinal actin, and second, by altering vesicular trafficking and APP degradation, yet both mechanisms are related since elevated Aβ levels produced due to impaired APP degradation, accumulate at synaptic sites, the spines, which are found in higher density in mutant cells, a synergy that can potentially cause an overexcitability of neurons, an early pathological event in AD

How can CEOs influence HRM implementation? Unfolding top management’s role in HRM

This paper investigates how CEOs can influence the implementation of HRM policies in their organizations. It does so by comparing the HRM implementation roles of the same CEO in two different companies as well as those of different CEOs in the same firm. Based on the findings, the study inductively develops a model that describes different types of CEO direct and indirect influence, unfolding the generic label of CEO “support” into a wide catalogue of actions, and identifying further behaviours other than support. The results also challenge some established ideas, such as the view of CEOs’ HRM role solely as strategic decision makers, or that CEO influence necessarily involves overt action. Finally, our findings open several avenues for future research on a relevant and, so far, underdeveloped topic.info:eu-repo/semantics/acceptedVersio