Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview

Immunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism\u2019s survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials. Immunotoxins can be theoretically used to eliminate any unwanted cell responsible for a pathological condition. The best results have been obtained in cancer therapy, especially in hematological malignancies. Among plant toxins, the most frequently employed to generate immunotoxins are ribosome-inactivating proteins, the most common being ricin. This review summarizes the various approaches and results obtained in the last four decades by researchers in the field of plant toxin-based immunotoxins for cancer therapy

Ovariohysterectomy in the Bitch

Ovariohysterectomy is a surgical procedure widely employed in practice by vets. It is indicated in cases of pyometra, uterine tumours, or other pathologies. This procedure should only be undertaken if the bitch is in a fit state to withstand general anaesthesia. However, the procedure is contradicated if the bitch presents a generalised condition with hypothermia, dehydration, and mydriasis. Ovariohysterectomy is generally performed via the linea alba. Per-vaginal hysterectomy can also be performed in the event of uterine prolapse, if the latter cannot be reduced or if has been traumatised to such an extent that it cannot be replaced safely. Specific and nonspecific complictions can occur as hemorrhage, adherences, urinary incontinence, return to oestrus including repeat surgery. After an ovariectomy, bitches tend to put on weight, it is therefore important to inform the owner and to reduce the daily ration by 10%

Dear Maliha,

Dear Maliha is a short documentary film exploring the complexities of spiritual abuse through Maliha Fairooz. Spiritual abuse is a form of abuse that uses spiritual or religious beliefs to control or manipulate others. In some cases, spiritual abuse can be used to describe a religious leader who abuses their platform. But in Maliha’s story, we explore the concept of parental spiritual abuse. However, we learn more about this through Maliha Fairooz and the creative use of her journal. For Maliha journaling is a form of therapy she uses to process her feelings and days. She also uses it as a way to heal from an abusive relationship with her mother and tries to reconnect with her faith. Among the decorated pages of her journals, she has a collection of about 10, Maliha also writes about her adventures after moving out of her family’s house. After several years of her mother’s abuse, she now experiences anxiety during prayer. Whenever Maliha would pray her mother would stand over her and police her movements as well as her recitation. Through the eyes of her mother, Maliha never prayed perfectly enough so she would tell her to read louder or quieter to move faster or slower. This made what is normally a calming and meditative act, a very anxious one for Maliha. Additionally, Maliha has a page dedicated to exploring her senses- this is because whenever Maliha was feeling a certain sense her mother would contradict it and tell her ‘No you are not feeling this sense you’re feeling just fine.” In this documentary, we also see Maliha enjoying the simple pleasures of adulthood such as grocery shopping and setting up her new apartment. This is a luxury she never believed she would have because there was so much control over her life as a child and an adult. We also hear her contemplative voice and we will also see the way she creates her journal entries. My goal is to inform people about this specific form of spiritual abuse as well as spread awareness on mental and physical healing after surviving abuse. https://vimeo.com/661098060/73acbbc8e

Multiuser Detection with Decision-Feedback Detectors and PIC in MC-CDMA System

In this paper we propose an iterative parallel decision feedback (P-DF) receivers associated with parallel interference cancellation (PIC) for multicarrier code division multiple access (MC-CDMA) systems in a Rayleigh fading channel (cost 207). First the most widely detection techniques, minimum mean-squared error MMSE, Maximum Likelihood ML and PIC were investigated in order to compare their performances in terms of Bit Error Rate (BER) with parallel feedback detection P-DFD. A MMSE DF detector that employs parallel decision-feedback (MMSE-P-DFD) is considered and shows almost the same BER performance with MMSE and ML, which present a better result than the other techniques. In a second time, an iterative proposed method based on the multi-stage techniques P-DFD (parallel DFD with two stages) and PIC was exploited to improve the performance of the system

Comparison of Adaptive Neuroprotective Mechanisms of Sulforaphane and its Interconversion Product Erucin in in Vitro and in Vivo Models of Parkinson's Disease

Several studies suggest that an increase of glutathione (GSH) through activation of the transcriptional nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the dopaminergic neurons may be a promising neuroprotective strategy in Parkinson's disease (PD). Among Nrf2 activators, isothiocyanate sulforaphane (SFN), derived from precursor glucosinolate present in Brassica vegetables, has gained attention as a potential neuroprotective compound. Bioavailability studies also suggest the contribution of SFN metabolites, including erucin (ERN), to the neuroprotective effects of SFN. Therefore, we compared the in vitro neuroprotective effects of SFN and ERN at the same dose level (5 \u3bcM) and oxidative treatment with 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells. The pretreatment of SH-SY5Y cells with SFN recorded a higher (p < 0.05) active nuclear Nrf2 protein (12.0 \ub1 0.4 vs 8.0 \ub1 0.2 fold increase), mRNA Nrf2 (2.0 \ub1 0.3 vs 1.4 \ub1 0.1 fold increase), total GSH (384.0 \ub1 9.0 vs 256.0 \ub1 8.0 \u3bcM) levels, and resistance to neuronal apoptosis elicited by 6-OHDA compared to ERN. By contrast, the simultaneous treatment of SH-SY5Y cells with either SFN or ERN and 6-OHDA recorded similar neuroprotective effects with both the isothiocyanates (Nrf2 protein 2.2 \ub1 0.2 vs 2.1 \ub1 0.1 and mRNA Nrf2 2.1 \ub1 0.3 vs 1.9 \ub1 0.2 fold increase; total GSH 384.0 \ub1 4.8 vs 352.0 \ub1 6.4 \u3bcM). Finally, in vitro finding was confirmed in a 6-OHDA-PD mouse model. The metabolic oxidation of ERN to SFN could account for their similar neuroprotective effects in vivo, raising the possibility of using vegetables containing a precursor of ERN for systemic antioxidant benefits in a similar manner to SFN

From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer\u2019s disease

The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer\u2019s disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains antiacetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Ab42 self aggregation, Ab42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Ab42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and antiinflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the diseas

Atmospheric Consequences of Cosmic Ray Variability in the Extragalactic Shock Model II: Revised ionization levels and their consequences

It has been suggested that galactic shock asymmetry induced by our galaxy's infall toward the Virgo Cluster may be a source of periodicity in cosmic ray exposure as the solar system oscillates perpendicular to the galactic plane. Here we investigate a mechanism by which cosmic rays might affect terrestrial biodiversity, ionization and dissociation in the atmosphere, resulting in depletion of ozone and a resulting increase in the dangerous solar UVB flux on the ground, with an improved ionization background computation averaged over a massive ensemble (about 7 x 10^5) shower simulations. We study minimal and full exposure to the postulated extragalactic background. The atmospheric effects are greater than with our earlier, simplified ionization model. At the lower end of the range effects are too small to be of serious consequence. At the upper end of the range, ~6 % global average loss of ozone column density exceeds that currently experienced due to effects such as accumulated chlorofluorocarbons. The intensity is less than a nearby supernova or galactic gamma-ray burst, but the duration would be about 10^6 times longer. Present UVB enhancement from current ozone depletion ~3% is a documented stress on the biosphere, but a depletion of the magnitude found at the upper end of our range would double the global average UVB flux. For estimates at the upper end of the range of the cosmic ray variability over geologic time, the mechanism of atmospheric ozone depletion may provide a major biological stress, which could easily bring about major loss of biodiversity. Future high energy astrophysical observations will resolve the question of whether such depletion is likely.Comment: 22 pages, 5 figures, to be published in Journal of Geophysical Research--Planets. This is an update and replacement for our 2008 paper, with a much more extensive simulation of air shower ionization. Ionization effects and ozone depletion are somewhat large

Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)

Prostate Intrafraction Translation Margins for Real-Time Monitoring and Correction Strategies

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose