What do stakeholders understand by self-determination? Consensus for its evaluation.

BACKGROUND: Advances in international studies on self-determination point out the need for continuous efforts to deepen its understanding and implications. The aim of this study is to obtain a comprehensive pool of items to operationalize the self-determination construct that serves as a starting point towards a valid instrument based on the reports of others. METHOD: We conducted a Delphi study of three rounds involving three panels of experts: ten professionals, five people with intellectual disability and six relatives of people with intellectual disability. Data analysis required both qualitative and quantitative methods. RESULTS: The initial pool of 131 items was refined through the different rounds to a final set composed of 115-some were removed and new ones were added. Content-based evidence is provided. In this study, the present authors generated a potential valid pool of items to develop a new measurement tool based on the latest advances on the self-determination theoretical framework. CONCLUSIONS: The implications for future research focus on strengthening the knowledge of self-determination.

A higher level of ketonaemia does not predict oral rehydration failure in vomiting paediatric patients and routine measurement is unnecessary.

AIM: This study determined if blood levels of beta-hydroxybutyrate were associated with the rate of failure in oral rehydration in paediatric patients with vomiting. METHODS: This was a prospective observational study that was carried out from December 1, 2015 to November 30, 2016 in the Rio Hortega University Hospital, Valladolid, Spain. The study cohort were patients up to 14 years old who attended the emergency department with three or more vomiting episodes in the last four hours and glycaemia higher than 45 mg/dL. Blood was measured for beta-hydroxybutyrate levels prior to the administration of oral rehydration solution for 90 minutes. Two or more vomiting episodes during this period were considered failed oral rehydration. RESULTS: We analysed 248 patients, with a median age of four years and 7.5 months and 233 (94%) of the parents took part. The median number of vomiting episodes in the previous four hours was five and oral rehydration was successful in 183 (78.5%) patients. The multivariate analysis showed that the initial beta-hydroxybutyrate blood level was not associated with the failure of oral rehydration. CONCLUSION: Blood levels of beta-hydroxybutyrate had no predictive value for oral rehydration failure in young patients with vomiting and this routine measurement is unnecessary.

Characterization of the embB gene in Mycobacterium tuberculosis isolates from Barcelona and rapid detection of main mutations related to ethambutol resistance using a low-density DNA array.

OBJECTIVES: Ethambutol resistance has mostly been related to mutations in the embB gene. The objective of the present study was to characterize the embB gene in a collection of ethambutol-resistant and ethambutol-susceptible isolates of Mycobacterium tuberculosis complex (MTBC) from Barcelona, and to develop a DNA microarray for the rapid detection of embB mutations in our area. METHODS: Fifty-three ethambutol-resistant and 702 ethambutol-susceptible isolates of MTBC were sequenced in internal 982-1495 bp fragments of the embB gene. In addition, a low-cost, low-density array was designed to include the embB codons identified as being most frequently mutated in our area (LD-EMB array). RESULTS: The global prevalence of embB mutations found among the ethambutol-resistant isolates was 77.4% (41/53). Substitutions in embB306 were the most common [53.7% (22/41)], followed by substitutions in embB406 [26.8% (11/41)]. The presence of mutations in embB406 was related to higher levels of ethambutol resistance and to multidrug resistance. Among unrelated isolates (from 24-locus MIRU-VNTR genotyping), the percentage of embB-mutated isolates was 72.9% (27/37)--59.3% (16/27) in embB306 and 25.9% (7/27) in embB406. None of the ethambutol-susceptible isolates studied showed a mutation in codon 306 or 406. The LD-EMB array showed 100% sensitivity and specificity in identifying the main embB substitutions in our area. CONCLUSIONS: Mutations at codons 306 and 406 of embB have a relevant role in resistance to ethambutol in our area. The LD-EMB array developed in this study would appear to be a good molecular test for rapid detection of ethambutol resistance.

Identification of fibroblast growth factor 15 as a novel mediator of liver regeneration and its application in the prevention of post-resection liver failure in mice.

OBJECTIVE: Cholestasis is associated with increased liver injury and morbidity after partial hepatectomy (PH), yet bile acids (BAs) are emerging as important mediators of liver regeneration. Fibroblast growth factor 15 (Fgf15, human FGF19) is a BA-induced ileum-derived enterokine that governs BA metabolism. We evaluated the relevance of Fgf15 in the preservation of BA homeostasis after PH and its potential role in the regenerative process. DESIGN: Liver regeneration after PH was studied in Fgf15 (-/-) and Fgf15 (+/+) mice. The effects of the BA sequestrant cholestyramine and adenovirally delivered Fgf15 were examined in this model. The role of Fgf15 in BA-induced liver growth was tested in Fgf15 (-/-) mice upon cholic acid (CA) feeding. The direct mitogenic effect of Fgf15 was evaluated in cultured mouse hepatocytes and cholangiocytes. RESULTS: Fgf15 (-/-) mice showed marked liver injury and mortality after PH accompanied by persistently elevated intrahepatic BA levels. Cholestyramine feeding and adenovirally delivered Fgf15 reduced BA levels and significantly prevented this lethal outcome. Fgf15 also reduced mortality after extensive hepatectomy in Fgf15(+/+) animals. Liver growth elicited by CA feeding was significantly diminished in Fgf15 (-/-) mice. Proliferation of hepatocytes and cholangiocytes was also noticeably reduced in CA-fed Fgf15 (-/-) mice. Fgf15 induced intracellular signalling and proliferation of cultured hepatocytes and cholangiocytes. CONCLUSIONS: Fgf15 is necessary to maintain BA homeostasis and prevent liver injury during liver regeneration. Moreover, Fgf15 is an essential mediator of the liver growth-promoting effects of BA. Preoperative administration of this enterokine to patients undergoing liver resection might be useful to reduce damage and foster regeneration.

The Right to Sexuality, Reproductive Health, and Found a Family for People with Intellectual Disability: A Systematic Review.

Although sexuality, reproductive health, and starting a family are human rights that should be guaranteed for all citizens, they are still taboo issues for people with intellectual disability (ID), and even more so for women with ID. This paper systematically reviews the current qualitative and quantitative evidence on the rights of people with ID in regard to Articles 23 (right to home and family) and 25 (health, specifically sexual and reproductive health) of the Convention on the Rights of Persons with Disabilities (CRPD). A systematic review of the current literature, following PRISMA 2020, was carried out in ERIC, PsychInfo, Scopus, PubMed, ProQuest, and Web of Science. In all, 151 articles were included for review. The studies were categorized into six themes: attitudes, intimate relationships, sexual and reproductive health, sexuality and sex education, pregnancy, and parenthood. There are still many barriers that prevent people with ID from fully exercising their right to sexuality, reproductive health, and parenthood, most notably communicative and attitudinal barriers. These findings underline the need to continue advancing the rights of people with ID, relying on Schalock and Verdurgo's eight-dimensional quality of life model as the ideal conceptual framework for translating such abstract concepts into practice and policy.

Self-Perception of Inclusion in an Inclusive Choir: An Analysis Using the Scale for the Assessment of Inclusion (SAI).

Inclusion promotes equal opportunities, and aims to eliminate discrimination, by ensuring full access, participation, and representation for all individuals in society, with music playing a crucial role in addressing this global challenge, and fostering positive and inclusive change. The aim of this study is to identify perceptions of inclusive culture, policies, values, and practices in one specific inclusive choir in Spain. The sample consisted of 135 members, ranging from 18 to 79 years of age, of which 22.2% have recognised disabilities. All of them filled in the adapted Scale for the Assessment of Inclusion (SAI) form. The results show that, regardless of gender, age, and length of participation in the choir, their members share positive perceptions of the inclusiveness of its values, policies, practices, and culture. However, perceptions vary across the groups surveyed, and are generally more favourable among participants with a disability, those without a university education, or those aged 26 or over. It is found that people who participate in an inclusive choir, in which music is the mediating resource, perceive a high level of inclusion that allows them to feel they belong to a group where diversity, equality, and the promotion of people are respected. The findings are analysed, considering the importance of conducting multidimensional evaluations that include all members of an organisation.

Personal Factors, Living Environments, and Specialized Supports: Their Role in the Self-Determination of People with Intellectual Disability.

The self-determination of people with disabilities, and specifically people with intellectual disabilities (ID), is a growing issue due to its relevance in the field of inclusion and human rights. Although research has shown a significant relationship between self-determination and intelligence, other factors also contribute to its development. The purpose of this study was to understand what other variables may be influencing self-determination. Using the scores from 483 adolescents and adults with ID who completed the AUTODDIS scale, we performed inferential and regression analyses to determine the relationships between levels of self-determination, personal variables (sex, age, severity of ID), and contextual variables (living environment, specialized supports). We found that self-determination is affected by the severity of ID, and when this variable is controlled for, greater self-determination is mainly related to receiving occupational support and support for autonomy and independent living. Results also showed that, together with ID severity, occupational and psychoeducational support, as well as support for autonomy and independent living, were also predictors of the level of self-determination. In conclusion, this study confirms the importance of contextual variables in the development of self-determination in people with ID, placing the focus of intervention on social opportunities.

Assessment of self-determination in mental health: A new application field of the AUTODDIS scale.

OBJECTIVE: Self-determination enhances well-being and quality of life. It is also considered a fundamental pillar in improving the efficacy of interventions used to treat people with severe mental disorders (SMD). Yet the assessment of self-determination in relation to mental health requires further research. The aim of this study was to analyze the adequacy and psychometric properties of the AUTODDIS scale in a Spanish population with SMD. METHOD: The scale was originally developed and validated to assess self-determination in people with intellectual disability. The scale was administered to a sample of 333 adults with SMD (M = 47.6 years, SD = 11.68), most of whom were receiving treatment in an outpatient setting or at long-stay care facilities in six specialized centers in Spain. RESULTS: The quality of the items and the reliability of the scale and its subscales were analyzed. External validity was also explored, and confirmatory factor analysis was used to analyze the fit of the data to different models. The results indicate that the scale demonstrated sufficient evidence of reliability and validity, supporting the adequacy of its use in the field of mental health. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The use of this scale as a tool to assess self-determination and its domains in the mental health field is warranted. The article also discusses the need for more research and assessment tools to facilitate decision making by clinical and organizational stakeholders in promoting self-determination. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A measurement of self-determination for people with intellectual disability: description of the AUTODDIS scale and evidences of reliability and external validity.

Background: Appropriate supports and instructional practices contribute to the development of self-determination. Also, research shows that the promotion of skills related to self-determination has been linked to the achievement of desired outcomes over the different life stages. Advances in self-determination require the development of assessment instruments because there is a reciprocal relationship between assessment and instruction. The purpose of this paper is to provide a description of the AUTODDIS Scale, along with evidence of its reliability and external validity. Method: A sample of 541 people with intellectual disabilities aged from 11 to 40 was used to validate the scale. Results: The reliability results indicate that the AUTODDIS Scale shows high internal consistency. The total score and subscale scores indicate moderate inter-rater reliability. The scores were also moderately to highly associated with other related measures of self-determination and quality of life (QoL). Conclusion: Our results demonstrate that consistent and valid information can be obtained from the AUTODDIS Scale.

Lack of Abcc3 expression impairs bile-acid induced liver growth and delays hepatic regeneration after partial hepatectomy in mice.

BACKGROUND & AIMS: Bile acids (BA) are increasingly recognized as important modulators of liver regeneration. Increased enterohepatic BA flux has been proposed to generate specific signals that activate hepatocyte proliferation after partial hepatectomy (PH). We have investigated the role of the BA membrane transporter Mrp3 (Abcc3), which is expressed in the liver and gut, in the hepatic growth response elicited by BA and in liver regeneration after PH. METHODS: Liver growth and regeneration, and the expression of growth-related genes, were studied in Mrp3(+/+) and Mrp3(-/-) mice fed a cholic acid (CA) supplemented diet and after 2/3 PH. Activation of the BA receptor FXR was measured in mice after in vivo transduction of the liver with a FXR-Luciferase reporter plasmid. BA levels were measured in portal serum and liver tissue by high performance liquid chromatography-tandem mass spectrometry. RESULTS: Liver growth elicited by CA feeding was significantly reduced in Mrp3(-/-) mice. These animals showed reduced FXR activation in the liver after CA administration and decreased portal serum levels of BA. Liver regeneration after PH was significantly delayed in Mrp3-deficient mice. Proliferation-related gene expression and peak DNA synthesis in Mrp3(-/-) mice occurred later than in wild types, coinciding with a retarded elevation in intra-hepatic BA levels. CONCLUSIONS: Lack of Abcc3 expression markedly impairs liver growth in response to BA and after PH. Our data suggest that Mrp3 plays a non-redundant role in the regulation of BA flux during liver regeneration.

Impaired fitness of Mycobacterium tuberculosis resistant isolates in a cell culture model of murine macrophages.

OBJECTIVES: We analysed the ability of Mycobacterium tuberculosis clinical isolates to penetrate and grow inside murine macrophages as a surrogate of fitness. METHODS: Thirty-five drug-resistant and 10 drug-susceptible M. tuberculosis isolates were studied in a murine macrophage model from the J774.2 cell line in a 6 day protocol, performing semi-quantitative counts in Middlebrook 7H11 medium. The mycobacterial penetration index (MPI) after infection and the mycobacterial growth ratio (MGR) inside the macrophages were determined to evaluate the fitness of isolates. RESULTS: Isolates with the katG S315T mutation and multidrug-resistant (MDR) isolates had a significantly lower MGR compared with drug-susceptible isolates. The MPI of the isolates with the katG S315T mutation showed a significant decrease compared with the MPI of those without this mutation. A trend to significantly lower values was also observed on comparing the MPI of the MDR isolates with that of the drug-susceptible isolates and the isolates resistant to isoniazid. CONCLUSIONS: The isoniazid-resistant and MDR isolates with mutations in the katG gene showed decreased multiplication inside murine macrophages, suggesting a lower fitness of M. tuberculosis with these resistance patterns.

Characterization of mutations in streptomycin-resistant Mycobacterium tuberculosis clinical isolates in the area of Barcelona.

OBJECTIVES: To determine the proportion and type of mutations in Mycobacterium tuberculosis isolates resistant to streptomycin, and their relationship with the level of resistance and with the epidemiological molecular pattern of the isolates. METHODS: Sixty-nine streptomycin-resistant isolates from a M. tuberculosis strain collection (1995-2005) from Barcelona were studied. The MIC of streptomycin for each isolate was determined using the proportions method with Middlebrook 7H11 medium. The entire rpsL gene and two specific fragments of the rrs gene (the 530 loop and the 912 region) were sequenced. IS6110-restriction fragment length polymorphism and spoligotyping were performed in each isolate. RESULTS: Twenty-six (26/69, 37.7%) streptomycin-resistant isolates presented a mutation in either the rpsL gene and/or the rrs530 loop, with no mutation in the rrs912 region. Seventeen (24.6%) isolates showed rpsL mutations (codons 43 and 88) associated with high MIC levels. Nine (13.0%) isolates had alterations in the rrs gene (A513T, A513C and C516T). Nineteen isolates (19/64, 29.7%) were classified into seven clusters (containing 2-5 isolates per cluster). Nineteen different spoligotype patterns were found. All the LAM3 spoligotype isolates (10/67, 14.9%) were associated with a C491T change in the rrs gene, being also observed in all LAM3 streptomycin-susceptible isolates. CONCLUSIONS: Mutations in the rpsL and rrs genes were detected in 37.7% of streptomycin-resistant M. tuberculosis isolates. High-level resistance was associated with mutations in the rpsL gene, whereas wild-type isolates showed low MIC levels. The presence of the C491T substitution in the rrs gene in streptomycin-susceptible and -resistant isolates demonstrates that this change is an epidemiological marker associated with LAM3 sublineage.

Student Misbehaviour and Teacher Coercion. A Comparative Study of Contextual Factors in Primary and Secondary Education Teachers.

This study analyses the relation between student misbehaviour and teacher coercion from a teacher perspective by taking further contextual variables into account. Our participants were 480 male/female secondary education and 351 primary education teachers from the Spanish Autonomous Community of Aragón (Spain). This study forms part of the 2017 Coexistence Study in Aragón Education Centres. According to the theoretical framework and the SEM (structural equation modeling), the results revealed a close relationship between student misbehaviour and teacher coercion, although other contextual variables also appeared in the regression equation: in coexistence rules and in teacher competence. We ultimately found a certain degree of difference between the primary and secondary education levels. On the secondary school level, teacher conflicts were associated with student misbehaviour, while coexistence rules and participative and inclusive activities predicted teacher coercion. Conversely, on the primary school level, participative and inclusive activities predict a lower frequency of student misbehaviour, while teacher competence predicts a lower frequency of teacher coercion.

Self-Determination in People with Intellectual Disability: The Mediating Role of Opportunities.

The Convention on the Rights of Persons with Disabilities have proclaimed the basic right of people to make one's own choices, have an effective participation and inclusion. Research in the field of disability have stressed self-determination as a key construct because of its impact on their quality of life and the achievement of desired educational and adulthood related outcomes. Self-determination development must be promoted through specific strategies and especially, by providing tailored opportunities to practice those skills. Providing these opportunities across environments could be especially relevant as a facilitator of self-determination development. This manuscript aims to ascertain if opportunities at home and in the community to engage in self-determined actions are mediating the relationship between people intellectual disability level and their self-determination. Results have confirmed direct effects of intellectual disability level on self-determination scores. Indirect effects also predicted self-determination and almost all its related components (self-initiation, self-direction, self-regulation, self-realization, and empowerment) through opportunities in the community and at home. Autonomy was predicted by the intellectual disability level through an indirect effect of opportunities at home, but not in the community. These results highlight the need for further research to better operationalize and promote contextually rooted opportunities for people with intellectual disability to become more self-determined.

CD200 is a useful marker in the diagnosis of chronic lymphocytic leukemia.

BACKGROUND: The diagnosis of CLL is supported by a typical morphology and immunophenotype and usually does not present difficulties. Nevertheless, some patients with CLL can show an atypical phenotype, this raising the possibility of a lymphoproliferative disorder other than CLL. It has been recently shown that the expression of CD200 could be a rather consistent marker for CLL. METHODS: The expression of CD200 was investigated in 120 consecutive patients with B-cell chronic lymphoproliferative disorders (B-CLPD) (65 cases diagnosed as typical CLL, 16 atypical CLL, and 39 non-CLL before entering the study) by using multiparametric flow cytometry with four color combinations. CD200 was analyzed as percentage of positive cells (≥30%) and MFIR expression. ROC curves were used to determine the cut-off for the CD200 MFIR. Matutes score (MS) was used as comparator. RESULTS: All 81 (100%) patients classified as CLL and 25 of 39 (64.1%) classified as non-CLL expressed high CD200 expression (≥30%). CD200 expression showed a high sensitivity (100%) and a low specificity (35.9%), and the accuracy was similar to that of Matutes score markers (range: 79.2%-86.7%); except SmIg that was 59.1%. The addition of CD200 to the Matutes score correctly identified 74 of 81 (91.4%) CLL cases including 9 of 16 atypical CLL cases. As per non CLL cases, 37 of 39 (94.9%) were correctly diagnosed by the modified system. Altogether, CD200 improved the diagnostic accuracy of Matutes score from 86.7% to 92.5% (P < .01). CONCLUSION: These results show that CD200 is a valuable, albeit not specific, CLL diagnostic marker. © 2018 International Clinical Cytometry Society.

Chronic Lymphocytic Leukemia: Clinical Stages Maintain Their Prognostic Significance Over the Course of the Disease and Are Surrogates for Response to Therapy.

BACKGROUND: To determine whether in patients with chronic lymphocytic leukemia (CLL), the clinical stage maintains prognostic significance over time and can be considered as a surrogate for the response to therapy. PATIENTS AND METHODS: The data from 229 CLL patients were retrospectively evaluated. The main aims of the study were to describe the changes in clinical stage during the course of CLL as a result of the response to treatment and to determine the time to next therapy (TTNT) and overall survival (OS) according to those changes, in particular, among the heterogeneous International Workshop on CLL (IWCLL) partial response (PR) category. RESULTS: Among the patients in the IWCLL PR category, differences were found in TTNT and OS according to the clinical stage at the response evaluation. With a median follow-up period of 91 months (range, 2-390 months), patients with a PR- Binet A at the response evaluation had significantly longer TTNT and OS compared with those with PR-Binet B/C (median TTNT, 26 vs. 11 months; P = .00; median OS, 63 vs. 43 months; P = .047). CONCLUSION: The results of the present study have shown that for patients with CLL, the Binet clinical stages are good outcome predictors throughout the disease course and also suggest that changes in Binet clinical stage could be useful as response surrogates and to divide the IWCLL PR category into different prognostic subgroups.

Use of Thymidine Kinase Recombinant Adenovirus and Ganciclovir Mediated Mouse Liver Preconditioning for Hepatocyte Xenotransplantation.

Hepatocyte transplantation is the best approach to maintain and propagate differentiated hepatocytes from different species. Host liver has to be adapted for transplanted hepatocytes productive engraftment and proliferation being required a chronic liver injury to eliminate host hepatocytes and provide a proliferative advantage to the transplanted hepatocytes. Most valuable mouse models for xenograft hepatocyte transplantation are based on genetically modified animals to cause a chronic liver damage and to limit host hepatocyte regeneration potential. We present a methodology that generates a chronic liver damage and can be applied to any host mouse strain and animal species based on the inoculation of a recombinant adenovirus to express herpes simplex thymidine kinase in host hepatocytes sensitizing them to ganciclovir treatment. This causes a prolonged liver damage that allows hepatocyte transplantation and generation of regenerative nodules in recipient mouse liver integrated by transplanted cells and host sinusoidal. Obtained chimeric animals maintain functional chimeric nodules for several weeks, ready to be used in any study.

FcγRIIb expression in early stage chronic lymphocytic leukemia.

In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d. Moreover, patients with low FcγRIIb expression (69/155, 44.5%) required therapy earlier than those with high FcγRIIb expression (86/155, 55.5%) (median 151.4 months vs. not reached; p=.071). These results encourage further investigation on the role of FcγRIIb in CLL biology and prognostic significance in larger series of patients.