Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

The interaction between pain and movement

Study DesignClinical commentary.Introduction/PurposePain and movement are universally relevant phenomena that influence human experiences in readily observable ways. Improved understanding of pain-movement relationships can guide medical and rehabilitative approaches to recovery and decrease risk of dysfunctional long-term consequences of otherwise normal neuromuscular responses. Therefore, the overall intent of this article is to elucidate the relationships between pain and movement as they relate to clinical decision making.ConclusionsMotor output is highly adaptable, can be influenced by multiple mechanisms at various levels along the nervous system, and may vary between individuals despite similar diagnoses. Therefore, interventions need to be individualized and consider both the types of motor response observed (ie, whether the response is protective or maladaptive), and the patient's acute physical activity tolerance when prescribing exercise/movement.     

Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice

Objective Interferon-induced transmembrane protein 3(IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/-mice.     

Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Combining proteomics and lipid analysis to unravel Confidor stress response in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is a useful model for studying the influence of different stress factors on eukaryotic cells. In this work we used the pesticide imidacloprid, in the Confidor formulation, as the stress factor and analyzed its influence on the metabolic activity, proteome and lipid content and composition of Saccharomyces cerevisiae yeast. During the cultivation of yeast, the lowest recommended application dose of Confidor (0.025%, v/v) was added to the growth media and its influence on the mitochondria, cytosol with microsomes, and the whole yeast cells was monitored. The results show that under the stress provoked by the toxic effects of Confidor, yeast cells density significantly decreased and the percentage of metabolically disturbed cells significantly increased comparing with untreated control. Also, there was a downregulation of majority of glycolytic, gluconeogenesis, and TCA cycle enzymes (Fba1, Adh1, Hxk2, Tal1, Tdh1,Tdh3, Eno1) thus providing enough acetyl‐CoA for the lipid restructuring and accumulation mechanism since we have found the changes in the cell and mitochondrial lipid content and FA composition. This data suggest that lipids could be the molecules that orchestrate the answer of the cells in the stress response to the Confidor treatment.     

互联网形势下医院离退休干部管理工作探索

当前我国科技技术进一步提升,国民生活水平也在不断地进步,对于医院离退休干部管理服务的要求也越来越高。对于医院的工作来说,处理好医院的退离休老干部是一项十分重要的工作,所以医院工作管理人员需要提高对于离退休老干部管理工作的重视。而在传统意义下医院离退休干部的管理服务,存在着较多的问题,而当前在互联网的形势下却能够实现更加具有科学化、合理化的服务。通过创新服务理念,对于管理方式进行改革,可以有效地改善当前对于医院离退休干部的管理服务水平,青年团员可以自行组成相应的志愿者,加强对于退休老人的关心,了解老干部在生活以及学习中出现的问题,并且采取有效的措施进行解决。本文通过以阐述我国当前离退休干部管理工作的现状作为切入点,进行分析探究,进一步提出互联网模式下提高我国医院离退休干部管理的对应措施。     

Measuring hope amongst Tanzanian women who participate in microfinance: An evaluation of the Snyder hope scale

ABSTRACT

Measuring hope reliably and accurately remains an important research objective, not least in less prosperous settings where ‘holding on to hope’ may be critically important in the struggle against adverse life conditions. The State Hope Scale was designed for use in the US. Despite reported application in diverse cultures and using translations the scale has not been extensively validated outside US populations. This study contributes to a larger project exploring the measurement of hope and provides a critique of Snyder’s scale as used in a Tanzanian female population of 1021 urban microfinance participants. We evaluate the scale’s validity through assessment of the empirical distribution of scores, item response profiles, internal consistency and discriminatory ability. Participants mostly scored very high and many reached very near the maximum attainable score. Hardly any endorsed the negative half of the response scale. Several problems are discussed including poor discrimination and strong evidence of acquiescence response bias. We also found little association of the scale scores with hypothesised correlates of hope. Future improvements on the measurement of hope are recommended, especially in studies outside the narrow Western context in which the scale was devised.     

The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.