The experiences of multi-stressed parents who have encountered child protection services

The current neoliberal political narrative has positioned families experiencing multiple stressors and struggling against adversity as responsible for their difficulties, making poor choices and avoiding opportunities to change their lives. Mothers are especially blamed and held responsible for maltreatment of their children, within a framework of child protection. A Grounded Theory approach is used to explore the experiences of mothers who have been through intensive family support programmes as part of the ‘Troubled Families’ initiative. The women describe how they have had little control over their lives, experienced abuse in most of their significant relationships, and end up ‘broken’, losing all sense of self. They shut down and feel intense shame, leading to mental health problems and substance misuse. This is on a background of coping with poverty and inequality, creating immense daily stress. They find strength through their relationships with their children, suggesting removal of them may be detrimental

Big Data and Democracy

One of the biggest questions in the digital age pertains to the relevance of democracy in the era of big data. Unquestioningly, the digital revolution is growing at a rapid pace and many are being caught unaware by its impact in various avenues. The amount of data available has been doubling year on year, and the conditions of usage have been evolving at a pace faster than the policies are being provided to ensure proper usage. Many have started looking for ways of turning big data into big money, an aspect that is coming at the expense of the democratic values countries have upheld for generations. Instead, it is becoming a huge problem as the history of humankind is becoming more documented now and messages are easier to send compared to a century ago. Understanding the impact of big data on democracy can help accentuate the best way of improving democratic institutions and their ability to overcome the pressure coming from evolving technology

Relative efficacy of biological control and cultural management for control of mollusc pests in cool climate vineyards (article)

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordThe dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.3083Restrictions on the use of synthetic molluscicides highlight the importance of developing alternative control methods. Nevertheless, biocontrol agents can be costlier and less effective than synthetic counterparts. One mean of increasing the efficacy of population suppression is to combine inundative biological control with habitat management to reduce population growth of target pests. Vineyards in the cool, wet climate of western England can suffer from outbreak densities of mollusc pests that damage expanding shoots, developing grapes and promote the transmission of fungal pathogens. In this study we combined the biocontrol agent Nemaslug - Phasmarhabditis hermaphrodita (Schneider) -with a simple habitat management approach (regular mowing) to suppress mollusc pests in vineyards in South Western England. Two sites were treated with NemaSlug and or mowing in a factorial design in early spring coinciding with bud burst and the start of mollusc growth and feeding. Mowing was effective management and resulted in the reduction of slug and snail populations and significantly less damaged vines. Nemaslug did not reduce slug numbers overall but did reduce bud damage, snail numbers and lowered the proportion of sucsceptible Deroceras spp in treated plot. However, effect sizes of nematode biocontrol were small, potentially because this product could not be applied to bare soil. Management practice for cool climate vineyards varies considerably from site to site. This study shows the value of simple habitat management for controlling a novel target and emphasizes how consideration of pest biology can lead to effective alternatives.European Regional Development Fund (ERDF)Cornwall CouncilCouncil for the Isles of Scill

Chlorogenic Acid Improves Neuroprotective Effect of PEP-1-Ribosomal Protein S3 Against Ischemic Insult

Chlorogenic acid (CGA) possesses various biological activities such as anti-oxidant, anti-inflammatory, and anti-diabetic activities. In the present study, we examined the effect of CGA on the transduction efficiency of PEP-1-ribosomal protein S3 (PEP-1-rpS3) into cells and brain tissues, and its neuroprotective potential against ischemia/reperfusion. We found that, in the presence of CGA, the transduction efficiency of PEP-1-rpS3 into astrocytes and the CA1 region of the hippocampus was enhanced, compared to its transduction in the absence of CGA. Also, cell viability data demonstrated that the sample treated with CGA + PEP-1-rpS3 exhibited improved cell viability against hydrogen peroxide (H2O2)-induced toxicity more significantly than the sample treated with PEP-1-rpS3 alone. Also, in a gerbil ischemia model, data demonstrated that following the ischemic insult, the group treated with PEP-1-rpS3 + CGA showed markedly enhanced protection of neuron cells in CA1 region of hippocampus, compared to those treated with CGA or PEP-1-rpS3 alone. Taken together, these results suggest that CGA may improve the transduction efficiency of protein transduction domain (PTD) fusion proteins into target cells or tissues, thereby enhancing their therapeutic potential against various diseases

Inhibition of the Nicotinic Acetylcholine Receptors by Cobra Venom α-Neurotoxins: Is There a Perspective in Lung Cancer Treatment?

Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs) and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated

Reactivity of Metal-Free and Metal-Associated Amyloid-?? with Glycosylated Polyphenols and Their Esterified Derivatives

Both amyloid-?? (A??) and transition metal ions are shown to be involved in the pathogenesis of Alzheimer???s disease (AD), though the importance of their interactions remains unclear. Multifunctional molecules, which can target metal-free and metal-bound A?? and modulate their reactivity (e.g., A?? aggregation), have been developed as chemical tools to investigate their function in AD pathology; however, these compounds generally lack specificity or have undesirable chemical and biological properties, reducing their functionality. We have evaluated whether multiple polyphenolic glycosides and their esterified derivatives can serve as specific, multifunctional probes to better understand AD. The ability of these compounds to interact with metal ions and metal-free/-associated A??, and further control both metal-free and metal-induced A?? aggregation was investigated through gel electrophoresis with Western blotting, transmission electron microscopy, UV-Vis spectroscopy, fluorescence spectroscopy, and NMR spectroscopy. We also examined the cytotoxicity of the compounds and their ability to mitigate the toxicity induced by both metal-free and metal-bound A??. Of the polyphenols investigated, the natural product (Verbascoside) and its esterified derivative (VPP) regulate the aggregation and cytotoxicity of metal-free and/or metal-associated A?? to different extents. Our studies indicate Verbascoside represents a promising structure for further multifunctional tool development against both metal-free A?? and metal-A??.open0

PET imaging of the autonomic myocardial function: methods and interpretation.

Cardiac positron emission tomography (PET) is mainly applied in myocardial perfusion and viability detection. Noninvasive imaging of myocardial innervation using PET is a valuable additional methodology in cardiac imaging. Novel methods and different PET ligands have been developed to measure presynaptic and postsynaptic function of the cardiac neuronal system. Obtained PET data can be analysed quantitatively or interpreted qualitatively. Thus far, PET is not a widely used clinical application in autonomic heart imaging; however, due to its technical advantages, the excellent properties of the imaging agents, and the availability of tools for quantification, it deserves a better position in the clinic. From a historical point of view, the focus of PET software packages for image analysis was mainly oncology and neurology driven. Actually, commercially available software for cardiac PET image analysis is still only available for the quantification of myocardial blood flow. Thus far, no commercial software package is available for the interpretation and quantification of PET innervation scans. However, image data quantification and analysis of kinetic data can be performed using adjusted generic tools. This paper gives an overview of different neuronal PET ligands, interpretation and quantification of acquired PET data

A Unique Carrier for Delivery of Therapeutic Compounds beyond the Blood-Brain Barrier

BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB) that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin), across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX) or adriamycin (ADR) and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders, including classes of resident and metastatic brain tumors. It may be prudent, therefore, to consider implementation of this novel delivery platform in various clinical settings for therapeutic intervention in acute and chronic neurological diseases

CNS Delivery Via Adsorptive Transcytosis

Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics