237 research outputs found
As bad as it gets: Well being deprivation of sexually trafficked women
The International Organization for Migration has collected data on trafficked individuals. The aim of this paper is to use the sub-sample of sexually exploited women in order to explore the relationship between their well being deprivation, their personal characteristics, and their working locations. We use the theoretical framework of the capability approach to conceptualize well being deprivation and we estimate a MIMIC (Multiple Indicators Multiple Causes) model. The utilized indicators measure abuse, freedom of movement, and access to medical care. This model also allows us to estimate the effects of some covariates on this measure of well being
The Italian National Registry for FSHD: an enhanced data integration and an analytics framework towards Smart Health Care and Precision Medicine for a rare disease
Background: The Italian Clinical network for FSHD (ICNF) has established the Italian National Registry for FSHD (INRF), collecting data from patients affected by Facioscapulohumeral dystrophy (FSHD) and their relatives. The INRF has gathered data from molecular analysis, clinical evaluation, anamnestic information, and family history from more than 3500 participants. Methods: A data management framework, called Mediator Environment for Multiple Information Sources (MOMIS) FSHD Web Platform, has been developed to provide charts, maps and search tools customized for specific needs. Patientsâ samples and their clinical information derives from the Italian Clinical network for FSHD (ICNF), a consortium consisting of fourteen neuromuscular clinics distributed across Italy. The tools used to collect, integrate, and visualize clinical, molecular and natural history information about patients affected by FSHD and their relatives are described. Results: The INRF collected the molecular data regarding FSHD diagnosis conducted on 7197 subjects and identified 3362 individuals carrying a D4Z4 Reduced Allele (DRA): 1634 were unrelated index cases. In 1032 cases the molecular testing has been extended to 3747 relatives, 1728 carrying a DRA. Since 2009 molecular analysis has been accompanied by clinical evaluation based standardized evaluation protocols. In the period 2009â2020, 3577 clinical forms have been collected, 2059 follow the Comprehensive Clinical Evaluation form (CCEF). The integration of standardized clinical information and molecular data has made possible to demonstrate the wide phenotypic variability of FSHD. The MOMIS (Mediator Environment for Multiple Information Sources) data integration framework allowed performing genotypeâphenotype correlation studies, and generated information of medical importance either for clinical practice or genetic counseling. Conclusion: The platform implemented for the FSHD Registry data collection based on OpenClinica meets the requirement to integrate patient/disease information, as well as the need to adapt dynamically to security and privacy concerns. Our results indicate that the quality of data collection in a multi-integrated approach is fundamental for clinical and epidemiological research in a rare disease and may have great value in allowing us to redefine diagnostic criteria and disease markers for FSHD. By extending the use of the MOMIS data integration framework to other countries and the longitudinal systematic collection of standardized clinical data will facilitate the understanding of disease natural history and offer valuable inputs towards trial readiness. This approach is of high significance to FSHD medical community and also to rare disease research in general
The activation of α1-adrenoceptors is implicated in the antidepressant-like effect of creatine in the tail suspension test
AbstractThe antidepressant-like activity of creatine in the tail suspension test (TST) was demonstrated previously by our group. In this study we investigated the involvement of the noradrenergic system in the antidepressant-like effect of creatine in the mouse TST. In the first set of experiments, creatine administered by i.c.v. route (1Όg/site) decreased the immobility time in the TST, suggesting the central effect of this compound. The anti-immobility effect of peripheral administration of creatine (1mg/kg, p.o.) was prevented by the pretreatment of mice with α-methyl-p-tyrosine (100mg/kg, i.p., inhibitor of tyrosine hydroxylase), prazosin (1mg/kg, i.p., α1-adrenoceptor antagonist), but not by yohimbine (1mg/kg, i.p., α2-adrenoceptor antagonist). Creatine (0.01mg/kg, subeffective dose) in combination with subeffective doses of amitriptyline (1mg/kg, p.o., tricyclic antidepressant), imipramine (0.1mg/kg, p.o., tricyclic antidepressant), reboxetine (2mg/kg, p.o., selective noradrenaline reuptake inhibitor) or phenylephrine (0.4Όg/site, i.c.v., α1-adrenoceptor agonist) reduced the immobility time in the TST as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of α1-adrenoceptor and that creatine produces synergistic effects in the TST with antidepressants that modulate noradrenaline transporter, suggesting that an improvement in the response to the antidepressant therapy may occur when creatine is combined with these antidepressants. Furthermore, the synergistic effect of creatine (0.01mg/kg, p.o.) and reboxetine (2mg/kg, p.o.) combination was abolished by the α1-adrenoceptor antagonist prazosin, indicating that the antidepressant-like effect of combined therapy is likely mediated by an activation of α1-adrenoceptor
Negotiating care in the context of Finnish and Italian elder care policies
Negotiation is an integral part of all elder care, which by definition involves a relation between at least two people. In this article we analyse negotiations concerning elder care in the context of Finnish and Italian elder care policies. At the macro level negotiations on elder care are shaped by elder care policies and at the micro level by individual skills and resources. Our focus is on the negotiations on eligibility that take place when elders attempt to access care. The data consist of qualitative interviews with Finnish and Italian elders in need of care. The analysis of individual experiences of care negotiations reflects the implementation of elder care policies.
The results indicate that the most negotiated eligibility criteria when seeking access to elder care are need, money and social relations. These criteria are negotiated when seeking eligibility to different sources of care: informal care, grey market, market-based, non-profit and public services. In Italy, negotiation is particularly crucial when accessing grey market care. Cash as the main Italian elder care policy tool tends to enhance the role of and need for negotiation. In Finland, a greater part of elder care is provided by the public sector and therefore the process of negotiation is more standardized than in Italy
Large genotypeâphenotype study in carriers of D4Z4 borderline alleles provides guidance for facioscapulohumeral muscular dystrophy diagnosis
Facioscapulohumeral muscular dystrophy (FSHD) is a myopathy with prevalence of 1 in 20,000. Almost all patients affected by FSHD carry deletions of an integral number of tandem 3.3 kilobase repeats, termed D4Z4, located on chromosome 4q35. Assessment of size of D4Z4 alleles is commonly used for FSHD diagnosis. However, the extended molecular testing has expanded the spectrum of clinical phenotypes. In particular, D4Z4 alleles with 9â10 repeat have been found in healthy individuals, in subjects with FSHD or affected by other myopathies. These findings weakened the strict relationship between observed phenotypes and their underlying genotypes, complicating the interpretation of molecular findings for diagnosis and genetic counseling. In light of the wide clinical variability detected in carriers of D4Z4 alleles with 9â10 repeats, we applied a standardized methodology, the Comprehensive Clinical Evaluation Form (CCEF), to describe and characterize the phenotype of 244 individuals carrying D4Z4 alleles with 9â10 repeats (134 index cases and 110 relatives). The study shows that 54.5% of index cases display a classical FSHD phenotype with typical facial and scapular muscle weakness, whereas 20.1% present incomplete phenotype with facial weakness or scapular girdle weakness, 6.7% display minor signs such as winged scapula or hyperCKemia, without functional motor impairment, and 18.7% of index cases show more complex phenotypes with atypical clinical features. Family studies revealed that 70.9% of relatives carrying 9â10 D4Z4 reduced alleles has no motor impairment, whereas a few relatives (10.0%) display a classical FSHD phenotype. Importantly all relatives of index cases with no FSHD phenotype were healthy carriers. These data establish the low penetrance of D4Z4 alleles with 9â10 repeats. We recommend the use of CCEF for the standardized clinical assessment integrated by family studies and further molecular investigation for appropriate diagnosis and genetic counseling. Especially in presence of atypical phenotypes and/or sporadic cases with all healthy relatives is not possible to perform conclusive diagnosis of FSHD, but all these cases need further studies for a proper diagnosis, to search novel causative genetic defects or investigate environmental factors or co-morbidities that may trigger the pathogenic process. These evidences are also fundamental for the stratification of patients eligible for clinical trials. Our work reinforces the value of large genotypeâphenotype studies to define criteria for clinical practice and genetic counseling in rare diseases
The diacylglycerol kinase α/Atypical PKC/ÎČ1 integrin pathway in SDF-1α mammary carcinoma invasiveness
Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5ÎČ1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of ÎČ1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and ÎČ1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - ÎČ1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells
â'Subaltern Victimsâ or âUseful Resourcesâ? Migrant Women in the Lega Nord Ideology and Politics"
Since the mid-2000s we have witnessed the emergence of a new phenomenon in several European countries: the mobilisation of issues of womenâs rights and gender equality by populist radical right parties (PRR)1 in anti-immigration campaigns. Recent contributions have illustrated some aspects and contradictions of these phenomena, for instance in relation to the PRR partiesâ embrace not only of womenâs but also gay rights (Bracke 2011). Others have described the double standard applied to migrant men and women in the context of raising hostility towards the Muslim population, not only by PRR parties, but within the mainstream more generally; whereas Muslim men have been mostly described as representing a social and cultural danger to European societies as well as being inherently misogynist, Muslim women have been portrayed prevalently as victims to be rescued (Abu-Lughod 2013). Little however has been written on the gendered ideology and strategies of these parties, particularly when it comes to addressing the issue of migrant women. This chapter aims to address these gaps in the scholarly literature by focusing on the gendered dimensions of anti-immigration ideology, policy and politics in the case of the LN. In particular, we draw on the empirical findings of two research projects to analyse the instrumental mobilisation of womenâs rights by the LN to stigmatise migrant, particularly Muslim, communities
How Grandparents Matter: Support for the Cooperative Breeding Hypothesis in a Contemporary Dutch Population
Low birth rates in developed societies reflect womenâs difficulties in combining work and motherhood. While demographic research has focused on the role of formal childcare in easing this dilemma, evolutionary theory points to the importance of kin. The cooperative breeding hypothesis states that the wider kin group has facilitated womenâs reproduction during our evolutionary history. This mechanism has been demonstrated in pre-industrial societies, but there is no direct evidence of beneficial effects of kinâs support on parentsâ reproduction in modern societies. Using three-generation longitudinal data anchored in a sample of grandparents aged 55 and over in 1992 in the Netherlands, we show that childcare support from grandparents increases the probability that parents have additional children in the next 8 to 10Â years. Grandparental childcare provided to a nephew or niece of childless children did not significantly increase the probability that those children started a family. These results suggest that childcare support by grandparents can enhance their childrenâs reproductive success in modern societies and is an important factor in peopleâs fertility decisions, along with the availability of formal childcare
Monitoring Alzheimer Amyloid Peptide Aggregation by EPR
Plaques containing the aggregated ÎČ-Amyloid (AÎČ) peptide in the brain are the main indicators of Alzheimerâs disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of AÎČ. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue AÎČ peptide variant containing an N-terminal cysteine (cys-AÎČ) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Î-pyrroline-3-methyl] methanethiosulfonate spin label (SL-AÎČ). Fibril formation in solutions of pure SL-AÎČ and of SL-AÎČ mixed with AÎČ was shown by Congo-red binding and electron microscopy. Continuous-wave 9Â GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric AÎČ, one to a multimer (8â15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation
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