Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

Training in cognitive reappraisal normalizes whole-brain indices of emotion regulation in borderline personality disorder.

BACKGROUND: Borderline personality disorder is the prototypical disorder of emotion dysregulation. We have previously shown that borderline personality disorder patients are impaired in their capacity to engage cognitive reappraisal, a frequently-employed adaptive emotion regulation strategy. METHODS: Here we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in borderline patients. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 borderline (14 Female) and 22 healthy control (13 Female) participants received training in psychological distancing and then completed a widely-used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging (fMRI) data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently-defined patterns for negative affect and cognitive reappraisal implementation for each session. RESULTS: Borderline patients showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. They did not, however, show significant change in behavioral self-reports. CONCLUSIONS: To our knowledge, this study represents the first longitudinal fMRI examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of borderline patients.

Systematic Review of the Evaluation of Foster Care Programs.

OBJETIVE: The aim of this study was to conduct an exhaustive synthesis to determine which instruments and variables are most appropriate to evaluate foster care programs (foster, kinship, and professional families). This evaluation includes the children, their foster families, their families of origin, professionals, and foster care technicians. METHOD: The systematic review included randomized, quasi-randomized, longitudinal, and control group studies aimed at evaluating foster care interventions. RESULTS: A total of 86 studies, 138 assessment instruments, 18 constructs, and 73 independent research teams were identified. CONCLUSIONS: (1) although the object of the evaluations was the children, the informants were usually the people in charge of their care; therefore, effort should be made to involve the children in a more participatory way; (2) psychosocial functioning, behavior, and parenting are transversal elements in most evaluations, while quality of life and coping are not sufficiently well incorporated; (3) practical instruments (brief and easy to apply and correct) that are widely used and carry scientific guarantees should be prioritized to ensure the comparability and reliability of the conclusions; and (4) progress should be made in the study of evaluation models for all forms of foster care, including foster, extended, and specialized families.

OBJETIVO: El objetivo es realizar una síntesis exhaustiva que contribuya a determinar qué instrumentos y variables son las más adecuadas para evaluar programas de acogimiento familiar (familias extensas, ajenas y profesionalizadas), incluyendo en esta evaluación a los niños, sus familias acogedoras, sus familias de origen y a los profesionales y técnicos del acogimiento familiar. Método: La revisión sistemática incluyó estudios aleatorizados, cuasialeatorizados, longitudinales y con grupo control dirigidos a evaluar intervenciones de acogimiento familiar. RESULTADOS: Se identificaron 86 estudios, 138 instrumentos de evaluación, 18 constructos y 73 equipos de investigación independientes. CONCLUSIONES: (1) aunque el objeto de las evaluaciones sean los niños, habitualmente los informantes son las personas a cargo de sus cuidados, con lo que se debe hacer un esfuerzo por involucrarlos de forma más participativa; (2) el funcionamiento psicosocial, el comportamiento o la parentalidad son elementos transversales en la mayor parte de evaluaciones, sin embargo la calidad de vida y el afrontamiento no están suficientemente bien incorporados; (3) deben priorizarse instrumentos prácticos (breves y fáciles de aplicar y corregir), de amplio uso y con garantías científicas para asegurar la comparabilidad y fiabilidad de las conclusiones; (4) debe avanzarse en la investigación de modelos de evaluación en todas las modalidades de acogimiento familiar, ya sea en familias ajenas, extensas o especializadas.

Rural-urban differences in the perceived impact of COVID-19 on mental health by European women.

PURPOSE: Many studies have documented an adverse impact of the pandemic on women´s mental health. This cross-sectional study aims to explore associations between women's perceived impact of lockdowns and curfews on their mental health and their residential location, along with other contextual and individual factors. METHODS: Using data from the Flash Eurobarometer 2712 "Women in times of COVID-19", conducted between January 25 and February 3, 2022, across the 27 Member States of the European Union (n = 23,671), this study applied bivariate tests and stratified models based on respondent location (rural areas, small or medium-sized towns and urban areas). The exploration sought predictors influencing the perceived mental health impact, encompassing five individual characteristics (age, disability, employment status, educational attainment, and household type), perceptions of violence against women, and country of residence. The dependent variable was assessed subjectively, measured on a scale from 1 (minor negative impact) to 5 (major negative impact). RESULTS: Women living in urban areas generally reported a higher perceived negative impact on mental health compared to women in rural areas or in small/medium-sized towns. Age and disability were significantly linked to perceiving a negative impact on mental health. Similar adjusted odds ratios for age were observed across rural areas (aOR 0.97, 95% CI = 0.97-0.98), small or medium-sized towns (aOR 0.98, 95% CI = 0.97-0.98), and urban areas (aOR 0.97, 95% CI = 0.97-0.98). In terms of disability, the odds were higher in rural areas (aOR 1.44, 95% CI = 1.20-1.73) than in urban ones (aOR 1.36, 95% CI = 1.15-1.62). Among women residing in urban areas, those in childless couples were less likely to perceive a negative impact on mental health (aOR 0.89, 95% CI = 0.80-0.99) compared to women in couples with children. Respondents perceiving increased violence against women due to COVID-19 were more likely to perceive a negative impact on mental health, with higher odds ratios in rural areas (aOR 1.56, 95% CI = 1.40-1.74) compared to urban areas (aOR 1.29, 95% CI = 1.17-1.41). Differences across countries were also found. CONCLUSION: The perceived impact of lockdowns and curfews on mental health exhibited variance between urban and rural areas. These disparities were influenced by individual characteristics such as age, disability, or household type, as well as the effects of COVID-19 on violence against women and contextual variables like country of residence.

Systematic Review of the Evaluation of Foster Care Programs / [Revisión sistemática sobre evaluación de programas de acogimiento familiar]

Objetive: The aim of this study was to conduct an exhaustive synthesis to determine which instruments and variables are most appropriate to evaluate foster care programs (foster, kinship, and professional families). This evaluation includes the children, their foster families, their families of origin, professionals, and foster care technicians. Method: The systematic review included randomized, quasi-randomized, longitudinal, and control group studies aimed at evaluating foster care interventions. Results: A total of 86 studies, 138 assessment instruments, 18 constructs, and 73 independent research teams were identified. Conclusions: (1) although the object of the evaluations was the children, the informants were usually the people in charge of their care; therefore, effort should be made to involve the children in a more participatory way; (2) psychosocial functioning, behavior, and parenting are transversal elements in most evaluations, while quality of life and coping are not sufficiently well incorporated; (3) practical instruments (brief and easy to apply and correct) that are widely used and carry scientific guarantees should be prioritized to ensure the comparability and reliability of the conclusions; and (4) progress should be made in the study of evaluation models for all forms of foster care, including foster, extended, and specialized families.(AU)

Objetivo: El objetivo es realizar una síntesis exhaustiva que contribuya a determinar qué instrumentos y variables son las más adecuadas para evaluar programas de acogimiento familiar (familias extensas, ajenas y profesionalizadas), incluyendo en esta evaluación a los niños, sus familias acogedoras, sus familias de origen y a los profesionales y técnicos del acogimiento familiar. Método: La revisión sistemática incluyó estudios aleatorizados, cuasialeatorizados, longitudinales y con grupo control dirigidos a evaluar intervenciones de acogimiento familiar. Resultados: Se identificaron 86 estudios, 138 instrumentos de evaluación, 18 constructos y 73 equipos de investigación independientes. Conclusiones: (1) aunque el objeto de las evaluaciones sean los niños, habitualmente los informantes son las personas a cargo de sus cuidados, con lo que se debe hacer un esfuerzo por involucrarlos de forma más participativa; (2) el funcionamiento psicosocial, el comportamiento o la parentalidad son elementos transversales en la mayor parte de evaluaciones, sin embargo la calidad de vida y el afrontamiento no están suficientemente bien incorporados; (3) deben priorizarse instrumentos prácticos (breves y fáciles de aplicar y corregir), de amplio uso y con garantías científicas para asegurar la comparabilidad y fiabilidad de las conclusiones; (4) debe avanzarse en la investigación de modelos de evaluación en todas las modalidades de acogimiento familiar, ya sea en familias ajenas, extensas o especializadas.(AU)

Development of the Preschool Life Impact Burn Recovery Evaluation (PS-LIBRE1-5) Profile.

Physical, social, and psychological outcomes have been identified as relevant to the rehabilitation process of children with burn injuries. Existing legacy measures are limited in item content and only cover a few constructs. Condition-specific outcomes are highly relevant to gauge early growth and development. Computerized adaptive tests (CATs) leveraging advanced psychometric technologies minimize respondent burden. This project developed PS-LIBRE1-5 Profile CAT (Preschool Life Impact Burn Recovery Evaluation) to measure relevant postburn outcomes in children aged one to five. Responses to the field-tested PS-LIBRE1-5 Profile (188 items) were measured on a scale of frequency or ability. Scores were coded from 0 to 4 where higher scores reflected better functioning. Factor analysis identified the items retained in the final item bank of each scale. CAT simulations were conducted to estimate the mean score of each scale. The simulated CAT score and full item bank scores were compared based upon the score range, ceiling and floor effects, and marginal reliabilities. The child mean age was 3.0 ± 1.5 years (n = 500). Average burn size and time since burn injury were 4.2% TBSA and 1.1 years, respectively. Psychometric analysis resulted in eight scales: Physical, Communication and Language, Emotional Wellbeing, Mood, Anxiety, Peer Acceptance, Play, and Peer Relations. Ceiling effects were acceptable at <13% for all scales. Marginal reliabilities of the CATs were credible. The PS-LIBRE1-5 Profile CAT contains 111 items, and is a comprehensive measure that captures physical, communication and language, psychological, and social functioning of preschool burn survivors.

Impact of an early 1000-day intervention for obesity prevention on adiposity and BMI at two years of age: A quasi-experimental study.

Background: The 1000-day period encompassing pregnancy and the first two years of postnatal life is critical for preventing childhood obesity. Existing interventions targeting this period have been characterised by great variability in duration, objectives, and evaluation indicators. We aimed to evaluate the impact of an intervention developed during the entire 1000-day period on body mass index and body fat percentage at two years of age. Methods: We designed a prospective, interventional, quasi-experimental study (ie, without randomisation or blinding of both groups) targeting mother-child pairs from the beginning of pregnancy up to two years of age belonging to the basic health area of Puerto Real (Cádiz). We developed and delivered an intervention from pregnancy to two years and assessed its effect. Results: The duration of breastfeeding and vitamin D supplementation increased significantly after the intervention. The intervention group showed lowed skinfolds values, a significantly lower body fat percentage, as well as a lower accumulation of factor at two years than the control group. Conclusions: The intervention has had an impact on body fat percentage at two years, potentially justified through its overall effect and the lower accumulation of early risk factors.

Monitoring and tracking the spread of SARS-CoV-2 in Asturias, Spain.

Mutational analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can quantify the relative importance of variants over time, enable dominant mutations to be identified, and facilitate near real-time detection, comparison and tracking of evolving variants. SARS-CoV-2 in Asturias, an autonomous community of Spain with a large ageing population, and high levels of migration and tourism, was monitored and tracked from the beginning of the pandemic in February 2020 until its decline and stabilization in August 2021, and samples were characterized using whole genomic sequencing and single nucleotide polymorphisms. Data held in the GISAID database were analysed to establish patterns in the appearance and persistence of SARS-CoV-2 strains. Only 138 non-synonymous mutations occurring in more than 1 % of the population with SARS-CoV-2 were found, identifying ten major variants worldwide (seven arose before January 2021), 19 regional and one local. In Asturias only 17 different variants were found. After vaccination, no further regional major variants were found. Only half of the defined variants circulated and no new variants were generated, indicating that infection control measures such as rapid diagnosis, isolation and vaccination were efficient.

Red Blood Cell Transfusion after Postpartum Hemorrhage: Clinical Variables Associated with Lack of Postpartum Hemorrhage Etiology Identification.

Postpartum hemorrhage (PPH) remains a significant obstetric emergency worldwide and a leading cause of maternal death. However, it is commonly underreported, which can represent a major concern for maternal morbidity and mortality. This retrospective case series study analyzed patients with red blood cell transfusion (RBCt) in the postpartum period over a four-year interval at a specific center. A total of 18,674 patients delivered between January 2018 and December 2021. Patients with postpartum RBCt were classified into two groups: those with identified PPH (i-PPH) and those without (non-i-PPH). Clinical variables, delivery details, blood loss data, and treatment information were collected. Statistical analysis involved a comparison of variables between the i-PPH and non-i-PPH groups. Univariate and multivariate analyses were performed, aiming to identify significant associations between the clinical variables and a lack of PPH identification. The incidence of RBCt was 1.26% (236 cases). Patients receiving RBCt had higher rates of cesarean delivery, twin pregnancy, labor induction, and previous cesarean section. Among patients with postpartum RBCt, 34.3% lacked an identified PPH. The rarity of postpartum RBCt contrasts with the increasing rates of PPH, highlighting the importance of diagnosing PPH and postpartum anemia. A strategy of systematic quantification of blood loss during delivery could help detect PPH and anemia before adverse consequences occur.

Study protocol of a randomized trial of STRIPES: a schoolyear, peer-delivered high school intervention for students with ADHD.

BACKGROUND: Youth with ADHD are at risk of academic impairments, dropping out of high school, and dysfunction in young adulthood. Interventions delivered early in high school could prevent these harmful outcomes, yet few high school students with ADHD receive treatment due to limited access to intervention providers. This study will test a peer-delivered intervention (STRIPES) for general education 9th grade students with impairing ADHD symptoms. METHODS: A type 1 hybrid effectiveness-implementation design will be used to evaluate the effectiveness of STRIPES and explore the intervention's implementability. Analyses will test the impact of STRIPES vs. enhanced school services control on target mechanisms and determine whether differences in basic cognitive profiles moderate intervention response. The acceptability and feasibility of STRIPES and treatment moderators will also be examined. DISCUSSION: This study will generate knowledge about the effectiveness and implementability of STRIPES, which will inform dissemination efforts in the future. A peer-delivered high school intervention for organization, time management, and planning skills can provide accessible and feasible treatment targeting declines in academic motivation, grades, and attendance during the ninth-grade year. TRIAL REGISTRATION: This study is registered on OSF Registries (10.17605/OSF.IO/Q8V6S).

Modafinil's effects on cognition and sleep quality in affectively-stable patients with bipolar disorder: a pilot study.

Introduction: Despite advances in the treatment of bipolar disorder (BD), most patients do not achieve complete inter-episode recovery and functional disability is common. During periods of relative remission, many patients continue to experience neurocognitive dysfunction, reduced daytime activity levels, and sleep disturbances. This 8-week, randomized, placebo-controlled pilot study evaluated the feasibility, safety and preliminary efficacy of the wake-promoting drug, modafinil (Provigil®), on neurocognitive functioning, daytime sleepiness, and sleep quality in affectively-stable BD patients. Methods: Twelve individuals with affectively-stable BD were recruited and randomized to a flexible dose of modafinil (100 to 200 mg/day) or placebo, adjunctive to a therapeutic dose of a mood stabilizer. Weekly in-person visits tracked sleep quality and daytime sleepiness as well as side effects and mood symptoms. Neurocognitive functioning was assessed at baseline, week 4, and week 8. Results: No serious adverse events were reported. Newly emergent side effects in the modafinil group included heart palpitations, itching, fatigue, and decreased energy. Two patients discontinued modafinil owing to side effects and one of these patients withdrew from the study. One patient discontinued placebo and was withdrawn from the study. Preliminary evaluations of clinical efficacy showed a marginally significant interaction between treatment group and time in two cognitive domains (speed of processing and verbal learning), indicating greater improvement in the modafinil group versus placebo. Additionally, there was a marginally significant effect of treatment group on daytime sleepiness, suggesting lower daytime sleepiness in the modafinil group versus placebo. Counterintuitively, we found a significant treatment group by time interaction effect on sleep quality, suggesting greater improvement in sleep quality in the placebo group versus the modafinil group. Discussion: Results suggest that modafinil is a relatively safe medication for affectively-stable BD patients when given with adjunctive mood stabilizers. Results are suggestive of cognitive benefit and improved daytime sleepiness, but worse sleep quality in those patients prescribed modafinil. A fully powered clinical trial is warranted with specific attention to the characteristics of patients who are most likely to benefit from treatment with modafinil and other methodological lessons learned from this pilot. Clinical trial registration: ClinicalTrials.gov, identifier NCT01965925.

Transfusion-transmission of hepatitis E virus through red blood cell transfusion but not through platelet concentrates: A case report from Spain.

BACKGROUND: Few cases of transfusion-transmitted hepatitis E virus (HEV) have been published in Spain. Here, we describe a well-characterized lookback investigation of a transfusion-transmitted HEV case at the Community Centre for Blood and Tissues of Asturias (Spain). CASE REPORT: A female patient with chronic myeloid leukemia underwent an allogeneic bone marrow transplant in March 2019 and showed alterations in liver function shortly afterwards. This patient received blood components from 30 different donors in the 3 months before the transplant. Frozen plasma samples from these donations were investigated for the presence of HEV-RNA. One frequent donor was identified as asymptomatic HEV RNA-positive at the time of his whole blood donation. The investigation revealed that this donor's plasma unit, originally intended for the fractionation industry, had a viral RNA concentration of 1.9 × 104 copies/mL. HEV RNA was detected initially in the index patient who received the red cell concentrate from this donor 25 days after the transfusion. HEV RNA isolated from both donor and recipient were identified as subtype 3f. The recipient of platelet concentrate (PC), treated with a riboflavin-based pathogen reduction technology (PRT) was not infected, being negative for the presence of HEV IgM, IgG, and HEV RNA before and after the transfusion. CONCLUSION: This case study shows that HEV was transmitted through red cell transfusion to a recipient, while the patient who received riboflavin/UV light treated PC did not develop signs of infection. A causal relationship between PRT treatment of the PC and the non-transmission of HEV remains to be established.

Needs of patients with multi-morbidity and heart failure for the development of a mHealth to improve their self-management: A qualitative analysis.

Objective: To provide practical information regarding needs, preferences of content and format of an app to assist the self-management in patients with multi-morbidity and heart failure (HF). Methods: The three-phase study was conducted in Spain. Six integrative reviews, a qualitative methodology based on Van Manen's hermeneutic phenomenology through semi-structured interviews and user stories were used. Data collection continued until data saturation was reached. All data were transcribed verbatim and analysed using a framework approach. Thematic analysis technique following the methods of Braun and Clarke was used for emerging themes. Results: Integrative reviews conducted included practical recommendations to include in the content and format of the App and helped create the interview guide. Interviews revealed 15 subthemes that captured the meaning of narratives offering contextual insights into the development of the App. The main effective mechanisms of multicomponent interventions for patients with HF must contain (a) components that increase the patient's understanding of HF, (b) self-care, (c) self-efficacy and participation of the family/informal caregiver, (4) psychosocial well-being and (5) professional support and use of technology. User stories revealed that patients prioritized improvements in direct contact with health services in case of emergency (90%), nutritional information (70%), type of exercises in order to improve their physical condition (75%) and information about food and drug interaction (60%). The importance of motivation messages (60%) was highlighted by transversal way. Conclusions: The three-phase process integrating theoretical basis, evidence from integrative reviews and research findings from target users has been considered a guide for future app development.

Specific correction of pyruvate kinase deficiency-causing point mutations by CRISPR/Cas9 and single-stranded oligodeoxynucleotides.

Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder caused by mutations in the PKLR gene. PKD-erythroid cells suffer from an energy imbalance caused by a reduction of erythroid pyruvate kinase (RPK) enzyme activity. PKD is associated with reticulocytosis, splenomegaly and iron overload, and may be life-threatening in severely affected patients. More than 300 disease-causing mutations have been identified as causing PKD. Most mutations are missense mutations, commonly present as compound heterozygous. Therefore, specific correction of these point mutations might be a promising therapy for the treatment of PKD patients. We have explored the potential of precise gene editing for the correction of different PKD-causing mutations, using a combination of single-stranded oligodeoxynucleotides (ssODN) with the CRISPR/Cas9 system. We have designed guide RNAs (gRNAs) and single-strand donor templates to target four different PKD-causing mutations in immortalized patient-derived lymphoblastic cell lines, and we have detected the precise correction in three of these mutations. The frequency of the precise gene editing is variable, while the presence of additional insertions/deletions (InDels) has also been detected. Significantly, we have identified high mutation-specificity for two of the PKD-causing mutations. Our results demonstrate the feasibility of a highly personalized gene-editing therapy to treat point mutations in cells derived from PKD patients.

The Preschool Eating, Lifestyle, and Sleeping Attitudes Scale (PRELSA Scale): Construction and Pilot Testing of a Tool to Measure Factors Associated with Childhood Obesity.

(1) Background: Childhood obesity poses a global health challenge. In the period from two to six years, the fundamental risk factors are associated with modifiable habits, related to parental attitudes. In this study, we will analyze the construction and pilot test of the PRELSA Scale, designed to be a comprehensive tool that covers the whole problem of childhood obesity, from which we can later develop a brief instrument. (2) Methods: First, we described the scale construction process. After that, we conducted a pilot test on parents to check the instrument's comprehensibility, acceptability, and feasibility. We detected items to be modified or eliminated through two criteria: the frequencies of the categories of each item and responses in the Not Understood/Confused category. Finally, we sought expert opinion through a questionnaire to ensure the content validity of the scale. (3) Results: The pilot test on parents detected 20 possible items for modification and other changes in the instrument. The experts' questionnaire showed good values on the scale's content, highlighting some feasibility problems. The final version of the scale went from 69 items to 60. (4) Conclusions: Developing scales that detect parental attitudes associated with the onset of childhood obesity may be the basis for future interventions to address this health challenge.

Absolute quantification of myocardial uptake of 99mTc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR).

PURPOSE: To determine the diagnostic contribution of the absolute quantification of the myocardial deposit of 99mTc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR). MATERIALS AND METHODS: SPECT/CT was performed in 41 patients with positive scintigraphic results for ATTR cardiac amyloidosis. The patients were divided into two groups (Perugini grades 2 and 3) and the SUVmax at the level of the bone and both ventricles and the percentage of dose calculated in these areas were calculated. The Student's t-test was used to compare results and the area under the curve (AUC) was calculated to assess differential efficacy and establish discriminatory cut-off points between both groups of patients. RESULTS: Statistically significant differences were observed in all the study variables, with the exception of bone SUVmax. The differences with the greatest statistical power were observed in the variables SUVmaxRV and the percentage of dose in both ventricles (p < 0.001). The cut-off point obtained for the variable SUVmaxLV was 8.620 (sensitivity 87.9% and specificity 100%; AUC 0.966), while that of the variable SUVmaxRV was 6.195 (sensitivity 81.8% and specificity 100%; AUC 0.955). CONCLUSIONS: The absolute quantification of myocardial uptake of 99mTc-DPD in the SPECT/CT images of patients with suspected cardiac amyloidosis due to transthyretin deposits represents a new diagnostic tool that allows adequate classification of patients according to the Perugini visual grading scale.

Older adult Cubans moving to the Canary Islands (Spain): Migrants' strategies in later life.

The research on migration to Spain of Cuban citizens in later life proposes to overcome the lack of academic knowledge from these analytical perspectives: migrations of older adult people beyond the issue of lifestyle mobility; the transnational diasporic nexus favoring migrations; and the Cuban community residing abroad, outside the United States of America. The combination of these elements in this case study shows the agency of older adult Cuban citizens who move to the Canary Islands, trying to achieve a greater level of material well-being and taking advantage of the diasporic ties between the Canary Islands and Cuba; but this is a process that brings out, simultaneously, feelings of dislocation and nostalgia in the stage of old age. The development of a mixed methodology and the focus on the life course of migrants offer an opportunity to reflect on the cultural and social construction of ageing in migration studies. Consequently, this research allows a deepening of knowledge on human mobility from the perspective of ageing in a counter-diasporic migration, showing the relationship between emigration and life cycle and demonstrating the strength and spirit of achievement of those individuals who decide to emigrate despite their advanced age.

Ultrasonic Vitrectomy Performance Assessment Using Micro-Extensional Rheology.

Purpose: The purpose of this study was to assess the performance of ultrasonic (US) vitrectomy devices by quantifying and comparing its impact on extracted vitreous properties to conventional pneumatic blade (PB) cutters using micro-extensional rheology. US vitrectomy is a new technology that offers an alternative to PB cutters used in vitreo-retinal surgeries. Methods: Thirty-six porcine vitreous samples were extracted using US and PB cutters. Each sample was kept at 4°C and tested within 24 hours postmortem and 4 hours post-vitrectomy. A recently developed micro-extensional rheology technique is used to infer the relative protein fragment size of extracted vitreous by quantifying the extensional relaxation time. Results: US-extracted vitreous exhibited extensional relaxation times orders of magnitude lower than PB-extracted vitreous (0.37 ms and 27.25 ms, respectively). Relaxation time is directly correlated to the fragment size of the collagen fibers in the vitreous. The formation of beads-on-a-string droplets within the PB samples indicates the presence of larger collagen fragments. These droplets were not seen on US samples. Conclusions: This new micro-extensional rheology technique can identify significant differences in physical properties of extracted vitreous. Long relaxation times and beads-on-a-string droplets within the PB vitreous samples indicate larger protein fragments compared to the US samples. Translational Relevance: Higher fragmentation of vitreous and lower extensional relaxation times may improve retina safety due to a reduction in vitreo-retinal traction resulting from the continuous shear action and aspiration applied by ultrasonic vitrectomy technology.

Development of a web tool to calculate the cumulative dose of glucocorticoids.

INTRODUCTION: Glucocorticoids are associated with serious side effects related to dosing and time of use. Unfortunately, there is no standard method for determining glucocorticoid exposure, especially in patients undergoing long-term treatment. OBJECTIVE: The aim of this work was to create a free and easy-to-use web application to calculate, in a systematic way, the total cumulative dose of corticosteroids. METHODS: The total cumulative dose is calculated as the sum of all periods of treatment with different doses of corticosteroids, and is expressed as the equivalent dose of prednisone in mg. Glucocorticoid doses during periods in which the available information is missing or incomplete are estimated by systematic assumptions. RESULTS: A simulation exercise using standard patterns of steroid use in polymyalgia rheumatica, and giant cell arteritis showed that even when the period of no information reached 50% of the time, the accuracy of the calculator had a mean absolute percentage error (MAPE)<7%. CONCLUSION: This tool simplifies and standardizes the glucocorticoids cumulative dose calculation, thereby minimizing bias in the assessment of glucocorticoid cumulative dose.