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Se presenta el caso de un paciente masculino de 14 años, sin antecedentes patológicos conocidos, con historia de 2 semanas de edemas en miembros inferiores a quién se le documentó síndrome nefrótico. El cuadro evolucionó a shock séptico, deterioro hemodinámico y posterior muerte. En la autopsia se documentó la presencia de una crisis drepanocítica generalizada con trombosis de la microvasculatura y nefropatía drepanocítica (glomerulopatía colapsante).

Ophthalmic tacrolimus compounded formulations are usually made from the commercial intravenous presentation, which contains ethanol as a solubilizer due to the low solubility of tacrolimus. The use of cyclodextrins is presented as an alternative to ethanol, an ocular irritant excipient, to avoid its long-term irritant effects. Open-label, sequential, prospective study to compare effectiveness, safety, and adherence of a new formulation of 0.015% tacrolimus with cyclodextrins (TCD) versus 0.03% tacrolimus with ethanol (TE). The ocular evaluation was assessed by ocular signs, corneal staining, subjective questionnaires as Visual Function Questionnaire (VFQ-25) and Visual Analogue Scale (VAS) of symptoms, lacrimal stability, ocular redness, and intraocular pressure. Compliance was assessed by VAS of adherence and empirically (difference between theoretical and actual consumption). Clinical ocular signs and corneal staining score remained stable for most patients 3 months after switching formulations. The TCD formulation did not modify the tear stability and intraocular pressure of the treated patients compared to the TE formulation. TCD eye drops significantly decreased the subjective pain values on VFQ-25 scale and burning sensation on the VAS symptom scale in comparison to TE formulation after 3 months after the change to TCD formulation. The novel tacrolimus in cyclodextrins formulation is a promising alternative for treating inflammatory ocular pathologies refractory to first-line treatments.

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This article presents a participatory research project developed in a school in Cantabria (Spain) that has sought to enhance the participation of the educational community to transform the school. The article focuses on the analysis of the contributions of the students (children from 3 to 12 years of age), key agents and promoters of change. Pedagogical documentation has been used as a tool to narrate the development of this research and to encourage subsequent reflection. The students have experienced what it means to participate, to listen, to be listened to, to feel recognised and to exert influence in their own lives. The results go beyond mere changes in the configuration and use of spaces. The project has made it possible to think of the school as a forum for citizen participation, favouring the experience of a democratic school, the development of otherness, the feeling of belonging and the experience of community.

PurposeTo culturally adapt the Musculoskeletal Health Questionnaire (MSK-HQ) to European Portuguese and evaluate its reliability in individuals with musculoskeletal conditions.Materials and methodsThe study was carried out in two phases. In the first phase, the MSK-HQ was translated and culturally adapted. In the second phase, a longitudinal observational study was carried out with a convenience sample of participants with musculoskeletal conditions. Data collection began at the start of physiotherapy treatments by filling in the MSK-HQ and Numeric Pain Rating Scale (NPRS). After 4-7 days, the participants were asked to fill out the MSK-HQ once again, as well as the Patient Global Improvement Change (PGIC) scale. The data collected was used to study internal consistency, test-retest reliability, and measurement error. Floor and ceiling effects were also analysed.ResultsThe MSK-HQ was successfully translated and adapted into European Portuguese. The second phase of the study had a sample of 191 participants. This study demonstrated high internal consistency (Cronbach's α = 0.885) and excellent test-retest reliability (ICC(2,1) = 0.908). The analysis of measurement error resulted in an SEM of 2.818 and an SDC at 7.811. No floor or ceiling effect was observed.ConclusionsThe MSK-HQ-PT is a reliable instrument for measuring musculoskeletal health. Further studies on its validity and responsiveness are needed.

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance of cellular energy may result crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in cellular energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs metformin (AMPK activator) and baicalin (CPT1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID-19 patients that had been previously treated with metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two indole derivatives, IND6 and IND8 with AMPK activating capacity. Consistently, a reduced time of hospitalization and need of intensive care was observed in COVID-19 patients previously exposed to metformin. Baicalin also mitigated the activation of pro-inflammatory bone marrow-derived macrophages (BMDMs) and reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19. In human epithelial lung and kidney cells, both drugs improved mitochondrial function and prevented TGF-β-induced renal epithelial cell dedifferentiation. Our results support that favoring cellular energy production through enhanced FAO may prove useful in the prevention of COVID-19-induced lung and renal damage.

Longevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient’s clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.

Therapeutic drug monitoring improves the benefit–risk balance of antipsychotic therapy. Ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) is considered the gold-standard method for measuring plasma drug concentrations; however, the Alinity C system has emerged as a promising alternative. This is the first study aimed at comparing UHPLC-MS/MS versus Alinity C in measuring plasma concentrations of aripiprazole and dehydroaripiprazole. A total of 86 plasma samples were analyzed. The active moiety of aripiprazole was measured in 60 samples using both systems and 26 samples were analyzed twice using Alinity C with an intermediate period of 6 months to assess its reproducibility. Spearman’s correlation revealed a good association between the two assays (rs = 0.96) and no significance differences were found by McNemar’s test when classifying samples between infra-, supra- and therapeutic ranges. Passing–Bablock regression showed a good correlation among methods (rs = 0.93) and a slope of 1.12 indicating a slight tendency of Alinity C to measure higher values than UHPLC-MS/MS. In addition, a good intra-method correlation across the two sequential analyses with Alinity C was obtained (rs = 0.99). Nonetheless, clinical decisions could be different in 15% of the cases depending on the chosen method. No differences were found in active moiety determination by Alinity C depending on the concentration of aripiprazole and dehydroaripiprazole of the samples.

Background: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. Methods: Long-term stability at −20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. Results: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. Conclusions: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at −20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Abstract Endothelial adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of vascular tone through stimulating nitric oxide (NO) release in endothelial cells. Since obesity leads to endothelial dysfunction and AMPK dysregulation, AMPK activation might be an important strategy to restore vascular function in cardiometabolic alterations. Here, we report the identification of a novel AMPK modulator, the indolic derivative IND6, which shows affinity for AMPKα1β1γ1, the primary AMPK isoform in human EA.Hy926 endothelial cells. IND6 shows inhibitory action of the enzymatic activity in vitro, but increases the levels of p-Thr174AMPK, p-Ser1177eNOS and p-Ser79ACC in EA.Hy926. This paradoxical finding might be explained by the ability of IND6 to act as a mixed-type inhibitor, but also to promote the enzyme activation by adopting two distinct binding modes at the ADaM site. Moreover, functional assays reveal that IND6 increased the eNOS-dependent production of NO and elicited a concentration-dependent vasodilation of endothelium-intact rat aorta due to AMPK and eNOS activation, demonstrating a functional activation of the AMPK–eNOS–NO endothelial pathway. This kinase inhibition profile, combined with the paradoxical AMPK activation in cells and arteries, suggests that these new chemical entities may constitute a valuable starting point for the development of new AMPK modulators with therapeutic potential for the treatment of vascular complications associated with obesity.

Outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion pumps is postulated as a very promising solution to treat complicated infections, such as endocarditis or osteomyelitis, that require patients to stay in hospital during extended periods of time, thus reducing their quality of life and increasing the risk of complications. However, stability studies of drugs in elastomeric devices are scarce, which limits their use in OPAT. Therefore, we evaluated the stability of ampicillin in sodium chloride 0.9% at two different concentrations, 50 and 15 mg/mL, in an elastomeric infusion pump when stored in the refrigerator and subsequently in real-life conditions at two different temperatures, 25 and 32 °C, with and without the use of a cooling device. The 15 mg/mL ampicillin is stable for up to 72 h under refrigeration, allowing subsequent dosing at 25 °C for 24 h with and without a cooling device, but at 32 °C its concentration drops below 90% after 8 h. In contrast, 50 mg/mL ampicillin only remains stable for the first 24 h under refrigeration, and subsequent administration at room temperature is not possible, even with the use of a cooling system. Our data support that 15 mg/mL AMP is suitable for use in OPAT if the volume and rate of infusion are tailored to the dosage needs of antimicrobial treatments.

Se analiza cómo la situación creada por la covid-19, el confinamiento y la suspensión de la docencia presencial, afectó al alumnado de educación infantil. Se presenta un estudio de caso de un aula de 16 niños y niñas de tres años. A través de asambleas virtuales que combinaron conversaciones con la elaboración de dibujos se recoge su voz, mostrando en el análisis sus preferencias en la vida cotidiana durante el confinamiento y su estado emocional, los aprendizajes que dicen haber adquirido, así como los deseos de futuro ante la vuelta a su rutina diaria. Los resultados, no solo muestran la capacidad de adaptación infantil, sino también cómo llegan a identificar aspectos positivos derivados del confinamiento que inferimos como demandas de la infancia ante la vuelta a su vida diaria.

IntroductionThe COVID-19 pandemic can be seen as a natural experiment to test how bed occupancy affects post-intensive care unit (ICU) patient's functional outcomes. To compare by bed occupancy the frequency of mental, physical, and cognitive impairments in patients admitted to ICU during the COVID-19 pandemic.MethodsProspective cohort of adults mechanically ventilated >48 hours in 19 ICUs from seven Chilean public and private hospitals. Ninety percent of nationwide beds occupied was the cut-off for low versus high bed occupancy. At ICU discharge, 3- and 6-month follow-up, we assessed disability using the World Health Organization Disability Assessment Schedule 2.0. Quality of life, mental, physical, and cognitive outcomes were also evaluated following the core outcome set for acute respiratory failure.ResultsWe enrolled 252 participants, 103 (41%) during low and 149 (59%) during high bed occupancy. Patients treated during high occupancy were younger (P50 [P25-P75]: 55 [44-63] vs 61 [51-71]; pConclusionsThere were no differences in post-ICU outcomes between high and low bed occupancy. Most patients (>90%) had at least one mental, physical or cognitive impairment at ICU discharge, which remained high at 6-month follow-up (57%).Clinical trial registrationNCT04979897 (clinicaltrials.gov).

El presente trabajo se inscribe en el marco de la investigación y práctica de danza contemporánea llevada a cabo con el equipo Archivo e imaginarios vivos. El cuerpo habitado que danza (convocatoria CePIAbierto 2018-2021). En esta investigación atendemos a la práctica practicada (Fernández, 2018) como objeto de estudio y abordamos una propuesta metodológica basada en la descripción de los tonos y enunciados del decir y la configuración de corporalidades y registros sensibles. Durante el desarrollo del presente trabajo, trataremos de mostrar el modo en cómo se fueron entramando en la práctica las nociones de archivo, imaginarios vivos y cuerpo habitado que danza, transformando esa trama en una textura densa que necesitó ir enlazando otros hilos para permitirnos ver en ese nuevo tejido la manera en qué, decir-imaginario-escritura-práctica practicada lograron mostrarse. Sabiendo que nuestro objeto de investigación es la práctica danzada, situada en los entrenamientos compartidos donde proponemos consignas que atienden a la palabra, la voz y el ritmo para configurar una corporalidad, creamos entonces —cuerpo a cuerpo— un acontecimiento tramado a partir del movimiento. Las prácticas físicas y sensibles que guiamos tienen una relación con el decir y consideramos que hay un repertorio de la voz, como palabra y sonido, junto al del movimiento. Las descripciones que diseñamos para movernos y mover a otres se apoyan tanto en un sensorium, asiento de la sensación donde un organismo vivo experimenta o interpreta los entornos en los que existe, como en un imaginario. Las consignas que guiaron los ejercicios propuestos para la práctica en el marco de la investigación no fueron diagramadas de manera exclusiva ni excluyente. Consideramos que es parte de nuestro metier el conocimiento en la utilización de métodos empleados en otros espacios de entrenamiento de manera que, no nos resultó relevante destacar la singularidad de los ejercicios realizados sino la expresión de la vivencia a la que condujo quien “orientó” y experimentó la práctica grupal.

Organic-matter decomposition is a key ecosystem process in freshwater ecosystems as it influences food web dynamics, represents a considerable flux in the global carbon cycle and can provide a useful measure of the ‘health’ of freshwater habitats. While organic-matter decomposition has been well studied among lotic ecosystems, research from small standing waterbodies such as ponds is largely missing, and decomposition studies are usually conducted on a single freshwater habitat type. However, there is a need to consider ecosystem processes across multiple freshwater habitats and connected ecosystems to better characterise ecosystem functioning at the landscape-scale, given the interdependence of landscape elements. This study provides a comparative analysis of organic-matter decomposition using a standardised field assay (cotton-strip assay) in the water column, riparian zone and land zone of urban pond and stream habitats. The average daily tensile-strength loss of the cotton strips (a process that corresponds to the catabolism of cellulose by microbes) was significantly higher in the aquatic habitats than riparian and land zones when all sites were considered, and when stream and pond sites were considered separately. Furthermore, the average decomposition rate was significantly higher within the water column in river habitats compared to pond habitats, although no difference was observed among riparian and land zones. Woody debris had a negative unimodal association with average per day tensile strength loss within streams, and a positive unimodal association within pond sites. Both nitrate and shading had positive unimodal associations with average per day tensile strength loss within stream sites. Among pond habitat, urban land coverage within 250m of each site was identified to have a negative association with average per day tensile strength loss. Here we demonstrated that urban freshwater habitats have heterogeneous organic matter decomposition rates, and that the responses can be complex. Understanding key ecosystem processes at a multihabitat scale will ensure the effective inclusion of ecosystem process in freshwater assessment and conservation protocols and improve the health and resilience of urban freshwater ecosystems.

Introduction Meningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two ‘Core Outcome Sets’ (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysis Two systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and dissemination Institutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration number COMET study ID 1508

Background: Inhaled ethanol in the early stages of SARS-CoV-2 infection may reduce the viral load, decreasing progression and improving prognosis. The ALCOVID-19 trial was designed to study the efficacy and safety of inhaled ethanol in older adults at initial phases of infection. Methods: Randomized, triple-blind, placebo-controlled phase II clinical trial. Experimental group (n = 38) inhaled 65° ethanol through an oxygen flow, while in the control group (n = 37), water for injection was used. General endpoint was to evaluate disease progression according to the modified World Health Organization (WHO) Clinical Progression Scale. Specific effectiveness endpoints were body temperature, oxygen saturation, viral load assessed by cycle threshold (Ct) on real-time polymerase chain reaction (RT-PCR), analytical biomarkers and use of antibiotics or corticosteroids. Specific safety outcomes were the absence of ethanol in plasma, electrographic, analytical, or respiratory alterations. Results: In the intention-to-treat population, no differences were found regarding disease progression. Mean Ct values increased over time in both groups, being numerically higher in the ethanol group, reaching a value above 33 only in the ethanol group on day 14, a value above which patients are considered non-infective. No differences were found in the other specific effectiveness endpoints. Inhaled ethanol was proven to be safe as no plasma ethanol was detected, and there were no electrocardiographic, analytical, or respiratory alterations. Conclusions: The efficacy of inhaled ethanol in terms of the progression of SARS-CoV-2 infection was not demonstrated in the present trial. However, it is positioned as a safe treatment for elderly patients with early-stage COVID-19.

En la sociedad hipermedia donde predomina el uso indiscriminado de múltiples pantallas desde edades cada vez más tempranas, es necesaria no solo la convivencia digital, sino además el respeto a los derechos de la infancia. Aspectos a los que debe unirse la responsabilidad por parte de los medios y también de las familias que educan a los menores. En este contexto surge esta investigación donde se revisa la literatura existente y se identifican dos planteamientos diferentes en torno a los dispositivos móviles e infancia; el referido a usos y posibilidades educativas y de enriquecimiento personal para los pequeños y, el que apunta usos abusivos y problemas derivados de su utilización. Este estudio de corte teórico muestra una revisión y reflexión basada en las ideas de un importante conjunto de autores que, en la era digital cuando la sociedad en general y de forma concreta la infancia utilizan la tecnología, apuestan por el empoderamiento del niño para convertirle en un receptor crítico. Por tanto, teniendo en cuenta que la infancia convive con los medios y que existen diferentes niveles de actividad de los niños frente a estos, se plantea una propuesta de niveles centrada en la actividad, la creación y la crítica social. Una propuesta que es posible alcanzar teniendo en cuenta la educación en, con y para los medios. Así mismo, en el marco de la CDN se propone que familias y escuelas potencien un uso adecuado de medios y pantallas por parte de la infancia.

Abstract Background Parkinsonian variant of multiple system atrophy is a neurodegenerative disorder frequently misdiagnosed as Parkinson’s disease. No early imaging biomarkers currently differentiate these disorders. Methods Simple visual imaging analysis of the substantia nigra and locus coeruleus in neuromelanin-sensitive magnetic resonance imaging and nigrosome 1 in susceptibility-weighted sequences was performed in thirty patients with parkinsonian variant of multiple system atrophy fulfilling possible/probable second consensus diagnostic criteria. The neuromelanin visual pattern was compared to patients with Parkinson’s disease with the same disease duration (n = 10) and healthy controls (n = 10). Substantia nigra semi-automated neuromelanin area/signal intensity was compared to the visual data. Results Groups were similar in age, sex, disease duration, and levodopa equivalent dose. Hoehn & Yahr stage was higher in parkinsonian multiple system atrophy patients, 69% of whom had normal neuromelanin size/signal, significantly different from Parkinson’s disease patients, and similar to controls. Nigrosome 1 signal was lost in 74% of parkinsonian multiple system atrophy patients. Semi-automated neuromelanin substantia nigra signal, but not area, measurements were able to differentiate groups. Conclusions In patients with parkinsonism, simple visual magnetic resonance imaging analysis showing normal neuromelanin substantia nigra and locus coeruleus, combined with nigrosome 1 loss, allowed the distinction of the parkinsonian variant of multiple system atrophy from Parkinson’s disease and healthy controls. This easy and widely available method was superior to semi-automated measurements in identifying specific imaging changes in substantia nigra and locus coeruleus.

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Background Deaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups. Methods and findings We used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording. Conclusions In this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL. In a registry-based study, Evangelos Kontopantelis and colleagues examine the excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation and region in England & Wales during 2020. Author summary Why was this study done? The Coronavirus Disease 2019 (COVID-19) pandemic generated large numbers of excess deaths (additional deaths over those predicted from trends in previous years). These excess deaths were also unevenly distributed across different geographic areas and socioeconomic groups, exacerbating prepandemic inequalities. Up to a quarter of the excess deaths during the pandemic were attributable to coronary heart disease, dementia, and other noninfectious causes, and not directly to COVID-19 infection. Most measures of excess deaths do not fully account for differences in the ages at which people die in different social groups. If the pandemic killed disproportionally more young people in more deprived areas, then inequalities resulting from the pandemic will have been underestimated. Measuring years of life lost (YLL) rather than excess deaths would address this problem. What did the researchers do and find? In England and Wales, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL during the first 42 weeks of the pandemic, of which 15% were not directly attributed to COVID-19 or another respiratory cause. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were as follows: 11 times as many for 15- to 44-year-olds, 3 times as many for 45- to 64-year-olds, 40% higher in 75- to 84-year-olds, and not significantly higher for those aged 85 or over. This pattern of disproportionately higher mortality in younger age groups exacerbated prepandemic inequalities between the most and least deprived areas, and varied widely across regions, with the North West particularly affected. What do these findings mean? Inequalities between socioeconomic and geographic groups resulting from the COVID-19 pandemic are more pronounced than previously reported. Future plans to manage pandemics, including decisions about vaccination rollout, should include an understanding of regional and socioeconomic variation in YLL and how this has exacerbated long-standing health inequalities. Immediate and longer-term recovery planning for communities and their health and social services should reflect historical disparities as well as the impact of the pandemic on YLL. Limitations of this study include the observational nature of the data and the need for accurate and timely recording of the deaths and their causes.

The shift from mass tourism to more personalized travel denotes great importance in the construction of tourist itineraries. Given the negative impacts of transport and tourism on the environment, sustainability criteria play an important role. The Tourist Trip Design Problem is related to the design of itineraries for tourists. Planning is complex in tourist regions of developing countries where the information associated with tourist activities is difficult to access, vague, and incomplete. With this information, tourists must plan their trip, and the conditions and limitations they establish for it are flexible and imprecise. Fuzzy optimization can address problems with this type of information and constraints. Therefore, in this paper, an analysis of the tourism supply chain is carried out, taking as a case study the Department of Sucre on Colombia's Caribbean coast. A Multiconstraint Multimodal Team Orienteering Problem with Time Windows and fuzzy constraints is developed to model the tourism trip design problem that maximizes profit and minimizes CO2 emissions. The model is tested using datasets from the literature and the real world. The results demonstrate consistency with the fuzzy approach and generate a set of low-emission solutions.

ABSTRACT Introduction: It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes. Aim: To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients. Methods: Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m2. Results: Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease (p = 0.28), nor with glycated hemoglobin (p = 0.19) or c-reactive protein (p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease (p = 0.038); neither cystatin C (p = 0.096) nor minimal residual renal function (p = 0.756) reached a significant association with cardiovascular disease. Conclusions: In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.

Se reporta la influencia del ángulo de incidencia de un sistema de concentración solar que se aplicará a la generación directa de vapor. Dicho sistema consta de un colector cilindro parabólico y un receptor a través del cual fluye el agua como fluido de trabajo. El colector se encuentra inclinado según la coordenada de latitud, curvado parabólicamente y con seguimiento en un eje. El colector se analiza matemáticamente utilizando los datos de un año solar típico y se compara con un colector sin inclinación. Hay una mejora significativa en la eficiencia óptica coseno durante todo el año en el colector cilindro parabólico polar, especialmente en la temporada de invierno. Este colector también se analiza empleando herramientas informáticas basadas en la metodología Tonatiuh Ray-Tracing, y se calculan las dimensiones óptimas del receptor. El colector cilindro parabólico polar es un colector prometedor para sistemas de energía solar concentrada en latitudes subtropicales, ya que proporciona un mejor aprovechamiento del recurso solar para los procesos involucrados en la obtención de calor o generación de electricidad, especialmente en aplicaciones de mediana y baja escala.

Las celdas de combustible permiten la conversión electroquímica de la energía contenida en ciertos compuestos como ser hidrógeno o alcoholes ricos en hidrógeno, en energía eléctrica en forma eficiente y no contaminante. El núcleo de la celda de combustible está constituido por cinco capas, las cuales se encuentran estrechamente interrelacionadas; éstas son la membrana conductora de protones, las capas difusoras de gases y las capas catalíticas tanto anódicas como catódicas. En este trabajo se desarrollan y se evalúan las partes constitutivas del ensamble, poniéndolas a prueba en una celda de combustible unitaria para evaluar su eficiencia en el laboratorio.

Abstract The persistence of the global severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic has brought to the forefront the need for safe and effective vaccination strategies. In particular, the emergence of several variants with greater infectivity and resistance to current vaccines has motivated the development of a vaccine that elicits a broadly neutralizing immune response against all variants. In this study, we used a nanoparticle‐based vaccine platform for the multivalent display of the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike (S) protein, the primary target of neutralizing antibodies. Multiple copies of RBD were conjugated to the SpyCatcher‐mi3 protein nanoparticle to produce a highly immunogenic nanoparticle‐based vaccine. RBD‐SpyCatcher‐mi3 vaccines elicited broadly cross‐reactive antibodies that recognized the spike proteins of not just an early isolate of SARS‐CoV‐2, but also three SARS‐CoV‐2 variants of concern as well as SARS‐CoV‐1. Moreover, immunization elicited high neutralizing antibody titers against an early isolate of SARS‐CoV‐2 as well as four variants of concern, including the delta variant. These results reveal the potential of RBD‐SpyCatcher‐mi3 as a broadly protective vaccination strategy.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at −20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at −20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support.Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use.Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app ≥30 days was used as the cut-off for higher app use.Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25–P75) 16–36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3–45] days, translated on a median use rate of 15 [3–38]%. Median inhaler adherence assessed through the app was 34 [4–73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6–83]% and 43 [3–73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen.Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.

This article carries out a systematic review of the scientific literature on child participation in the formal education system in Spain between 2010 and 2022. Recognising the importance of child participation in the context of the European Union, the theoretical principles of this study are in line with the perspective that child participation involves recognising the fundamental right of children to be heard and taken into consideration from an early age and providing them with the opportunity to convert that listening into positive changes to aspects that affect their lives. Child participation has significant benefits, both from an individual point of view (the child's own development and the recognition that all rights are for all children), and a social and collective point of view (the strengthening of democracy itself making the school a school for participation). The systematic review of the scientific literature was conducted according to the PRISMA statement 2020. The analysis of the selected articles was based on the Lundy model of child participation (2007) which considers four dimensions: space, voice, audience and influence. The results show that despite the Spanish scientific community's growing interest in child participation in the field of early childhood education, school culture is still very adult-centric. Aspects related to the dimensions of voice, audience and influence could be improved for which more research is required. There is a clear need to broaden the techniques and instruments required for making child participation effective, and experiences that go beyond consultative participation should be developed. This would enable forms of child participation focused on improving their lives based on their own needs being heard and taken into consideration.

End-Stage Renal Disease (ESRD) is one of the major causes of morbidity and mortality worldwide. Although the incidence of ESRD is relatively stable, the prevalence of maintenance dialysis is increasing, and it is expected to reach a staggering 5439 million patients worldwide by 2030. Despite the great technological evolution that has taken place in recent years, most patients are still treated with in-centre haemodialysis and their prognosis remains far from desirable.Since 1980, there has been an increasing interest in the development of a portable device for renal replacement therapy (RRT), which ultimately led to the creation of the Wearable Artificial Kidney (WAK) and the Wearable Ultrafiltration (WUF) system. Portable RRT devices may be acceptable alternatives that deal with several unmet clinical needs of ESRD patients. So far, 3 important human studies with WAK and WUF have been carried out and, although these devices require considerable technological improvement, their safety and efficacy in solute clearance and fluid removal is undeniable.In this article, we review the evolution of the WAK and the WUF and the main clinical trials performed, highlighting some of their technical features. Some of the main possible clinical advantages that could be achieved with these devices, as well as some economic aspects, are also pointed out.In the future, all renal replacement therapy techniques should evolve to perfectly match the clinical and personal needs of each patient, allowing for an improved health-related quality of life. Resumen: La enfermedad renal crónica terminal (ERCT) es una de las principales causas de morbimortalidad mundial. Aunque la incidencia de esta enfermedad es relativamente estable, la prevalencia en diálisis está aumentando, y se espera que llegue a la cifra de 5.439 millones de pacientes en todo el mundo en el año 2030. A pesar de la gran evolución tecnológica ocurrida en los últimos años, la mayoría de los pacientes continúan siendo tratados con hemodiálisis, y su pronóstico queda lejos de lo deseable.Desde 1980, existe un interés creciente en el desarrollo de dispositivos portátiles para la terapia de sustitución de la función renal (TSFR), y que llevaron a la creación del Wearable Artificial Kidney (WAK) y del Wearable Ultrafiltration (WUF) system. Estos pueden ser alternativas aceptables que permiten alcanzar las necesidades de los pacientes con ERCT, que hasta ahora no se han alcanzado. A pesar de que estos dispositivos necesitan mejoras tecnológicas, su seguridad y eficacia en el aclaramiento de solutos y la eliminación de fluidos es innegable.Revisamos la evolución del WAK y del WUF, y los principales ensayos clínicos desarrollados, destacando algunas de sus particularidades tecnológicas. Adicionalmente, señalamos algunas de las posibles ventajas clínicas que podrían ser alcanzadas con estos dispositivos, así como algunos aspectos económicos.En el futuro, todas las TSFR deben evolucionar para satisfacer todas las necesidades clínicas y personales de cada paciente, permitiendo una mejor calidad de vida relacionada con la salud. Keywords: Vascular access, Wearable Artificial Kidney, Wearable Ultrafiltration device, Renal replacement therapy, End-Stage Renal Disease, Health-related quality of life, Palabras clave: Acceso vascular, Riñón Artificial Portátil, Dispositivo de ultrafiltración portátil, Terapia de sustitución renal, Enfermedad renal crónica terminal, Calidad de vida relacionada con la salud

Introduction: The treatment of urinary tract infections has become more challenging due to the increasing frequency of multidrug-resistant Escherichia coli in human populations. Objective: To characterize multidrug-resistant E. coli isolates causing community-acquired urinary tract infections in Cumaná, Venezuela, and associate possible risk factors for infection by extended-spectrum beta-lactamases (ESBL)-producing isolates. Materials and methods: We included all the patients with urinary tract infections attending the urology outpatient consultation and emergency unit in the Hospital de Cumaná, Estado Sucre, Venezuela, from January through June, 2014. blaTEM, blaSHV and blaCTX-M genes detection was carried out by PCR. Results: We found a high prevalence of multidrug-resistant E. coli (25.2%) with 20.4% of the isolates producing ESBL. The ESBL-producing isolates showed a high frequency (66.7%) of simultaneous resistance to trimethoprim-sulphamethoxazole, fluoroquinolones and aminoglycosides compared to non-producing isolates (2.4%). Of the resistant isolates, 65.4% carried the blaTEM gene, 34.6% the blaCTX-M and 23.1% the blaSHV. The blaCTX-M genes detected belonged to the CTX-M-1 and CTX-M-2 groups. Plasmid transfer was demonstrated by in vitro conjugation in 17 of the 26 ESBL-producing isolates. All three genes detected were transferred to the transconjugants. Age over 60 years, complicated urinary tract infections and previous use of a catheter predisposed patients to infection by ESBL-producing E. coli. Conclusions: The high frequency of multidrug-resistant ESBL-producing isolates should alert the regional health authorities to take measures to reduce the risk of outbreaks caused by these types of bacteria in the community.

Granulomatous pneumonitis is a rare complication of bacillus Calmette-Guerin immunotherapy following intravesical administration of bacillus Calmette-Guerin. The authors present an unusual case of a 67-year-old man who developed mild and non-specific symptoms, following intravesical bacillus Calmette-Guerin instillations. Examinations revealed features of miliary tuberculosis and granuloma suggestive of mycobacterial infection. Anti-tuberculosis treatment resulted in a remarkable improvement in his symptoms and gradually upgrading of radiological appearance. The symptoms were less severe than some others described but this case provides evidence that, even in some cases, specific treatment may be necessary. We highlight the importance of recognizing miliary Mycobacterium bovis as a probable complication of bacillus Calmette-Guerin immunotherapy. The clinical disease course can be mild, despite extensive bilateral miliary nodules on primary presentation.

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.

Background: Functional mobility (FM) is the person's ability to move to accomplish daily living tasks and activities. FM limitations are common in Parkinson's disease, increase with disease progression, and can be highly disabling. Although several studies in Parkinson's disease (PD) field use this concept, only recently, a formal definition has been proposed.Objective: We aimed to explore patient's and health professional's perspectives of FM in PD.Methods: A focus group methodology has been used. Four focus groups, with a total of 10 patients and 10 health professionals, were performed. Six patients were early stage and four advanced stage. The health professional's group was composed of five neurologists and five physiotherapists. The suitability of the new concept, the impact of FM limitations in PD patient's daily routine, and the potential benefit of walking aids have been discussed.Results: All participants were able to provide a spontaneous definition of FM, matching with the proposed concept. All agreed that PD affects patient's FM, increasing the limitations with disease progression, and with the existence of a serious prejudice with walking aids that hinders its use. Early-stage patient's perspective seems to be more in line with neurologist's perspective, while the views of advanced-stage patients were closer to physiotherapist's views.Conclusion: FM concept was considered as intuitive and useful. FM limitations have an important physical and social impact in the advanced stage of the disease. Although patients and health professionals acknowledge walking aid's benefit improving patient's FM, the prejudice associated with this type of tools limits its recommendation and use.

A psitacose, também conhecida como ornitose, é geralmente uma doença com manifestações sistémicas proeminentes e alguns sintomas respiratórios, causada por Chlamydia psittaci. Os pássaros psitacinos são o principal reservatório e meio de transmissão da doença para os humanos. Descreve-se o caso clínico de uma doente de 50 anos, trabalhadora num armazém agro-avícola, que foi observada três vezes em contexto de urgência por quadro de dispneia, tosse seca, toracalgia, cansaço generalizado e febre. Relata-se o seu percurso e evolução até ao diagnóstico de pneumonia a Chlamydia psittaci. Este relato de caso reforça a importância de realizar sempre uma adequada anamnese, revelando-se preponderante para o sucesso diagnóstico e terapêutica dirigida.

Introduction: The satisfactory symptomatic control of the axial symptoms of Parkinson's disease (PD) remains challenging. As these symptoms are an important cause of disability, new therapeutic strategies should be developed and evaluated. To do this, it is necessary to select the outcomes to be measured and reported in a clinical trial. In this study, we sought to identify the most responsive outcome measures for assessing the efficacy of a multidisciplinary intervention on the axial symptoms of PD.Methods: An exploratory prospective clinical study was conducted. PD patients engaged in a pre-defined multidisciplinary intervention program for parkinsonian patients were assessed at admission and discharge by a multidisciplinary team. The responsiveness to intervention was evaluated and the smallest sample size needed to enable statistically significant results for an expected 30% change from baseline for each outcome was calculated.Results: Twenty-two patients were included in the study. The effect size detected varied between 0.04 and 0.83. The Movement Disorder Society—Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score and each subsection, the N-FOG questionnaire, the 10-m walk test, and Frenchay Dysarthria Assessment-2 Edition (FDA-2) showed a medium to large effect size. Sample size calculations for 90% power and assuming 30% change from baseline ranged from eight to 180 participants. The outcome measures that require a small number of participants to enable statistically significant results were the FDA-2 rating scale (n = 4 participants), the MDS-UPDRS total score (n = 9), the 10-m walk test (n = 9), and the MDS-UPDRS motor examination (n = 10).Conclusions: The MDS-UPDRS part III and total score and the 10-m walk test were the outcomes with the best responsiveness to a multidisciplinary intervention and required a small number of participants to enable statistically significant results. Further studies are needed to clarify the suitability of the Timed Up and Go test.

Cuando existe una ingente cantidad de dispositivos tec-nológicos y pantallas, que son cada vez más utilizados, resulta fundamental contar con recursos que integren la realidad social en el contexto académico. Más allá de los informes nacionales e internacionales que certifican la proliferación de tecnología y dispositivos digitales, surge la necesidad de contar con manuales que determinen una hoja de ruta propia para contribuir a la introducción de estos nuevos recursos en la ecología pedagógica. Una demanda que justifica el contacto que la generación móvildigital mantiene con la tecnología. Además de ello, se hace preceptiva una modificación de las políticas educativas y de los currículos, hecho que no siempre se produce. Por todo ello, en esta investigación se revisa el currículo de español en educación infantil y primaria, y se describen de forma somera, parte de los múltiples recursos existentes, fundamentalmente en España, para enseñar con tecnología. Esta realidad se relaciona con las 5 áreas del Marco común de competencia digital docente y con las 12 claves educativas que se establecen para la sociedad digital. En este sentido, no se busca ofrecer soluciones pedagógicas a la cambiante realidad, sino que se trata de visibilizar la situación legislativa y el grado de presencia de las TIC en la misma. Centra el interés la justificación de la necesidad de cambio pedagógico para enseñar a los movildigitales mediante metodologías y recursos que les resulten familiares y que les permitan alcanzar el aprendizaje significativo y funcional propio de la educación por competencias que focaliza la atención de la pedagogía actual.

Concurrent chemoradiotherapy with high-dose cisplatin (100 mg/m2 every 3 weeks) is the preferred regimen with curative intent for patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). This treatment is associated with acute and late toxicities, including myelosuppression, severe nausea/vomiting, irreversible renal failure, hearing loss, and neurotoxicity. Because of cisplatin's safety profile, treatment adherence to high-dose cisplatin can be suboptimal. Patients commonly receive less than the total cumulative target dose of 300 mg/m2 or the minimum recommended dose of 200 mg/m2, which can have a negative impact on locoregional control and survival. Alternatively, cetuximab plus radiotherapy may be most suitable for patients at high risk of non-adherence to high-dose cisplatin. We discuss the baseline characteristics dictating the unsuitability/borderline unsuitability of cisplatin and the available alternative evidence-based treatment regimens for patients with LA SCCHN. We non-systematically reviewed published phase II and III trials and retrospective analyses of high-dose cisplatin-based chemoradiation in LA SCCHN conducted between 1987 and 2018, focusing on recent key phase III studies. We defined the baseline characteristics and associated prescreening tests to determine unsuitability and borderline unsuitability for high-dose cisplatin in combination with radiotherapy in patients with LA SCCHN. Patients with any pre-existing comorbidities that may be exacerbated by high-dose cisplatin treatment can be redirected to a non-cisplatin-based option to minimize the risk of treatment non-adherence. High-dose cisplatin plus radiotherapy remains the preferred treatment for fit patients with unresected LA SCCHN; patients who are unsuitable or borderline unsuitable for high-dose cisplatin could be identified using available tests for potential comorbidities and should be offered alternative treatments, such as cetuximab plus radiotherapy.

The work aims to know the perspective maintained by families and teachers in relation to different elements of the transition process between Childhood Education and Primary Education: its importance or transcendence, the changes that occur and the challenges faced by the children, as well as the mechanisms and actions implemented by the centers to encourage it. 460 families and professors participated in the study completing a questionnaire. The results show the existence of a significant gap in thinking about the importance and transcendence given to the transitions that are experienced in early childhood between families and teachers despite also finding other aspects converging. Considering these findings, the generation of educational transition programs adapted to the needs and demands of each school which encourage the participation of all the people involved in this important process.

Summary Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery–Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot–Marie–Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Köbberling-like); mild hypertrophic cardiomyopathy, with Wolff–Parkinson– White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA. This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA-associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant.

La democracia en la escuela implica una consideración de la infancia como competente y capaz, concretada en el presente (en su presente), en posibilitar el desarrollo de sus derechos y en crear espacios de vida (en nuestro caso la escuela) en los que pueda participar. El constructo sobre el que se desarrolla este texto son los ejes pedagógicos: las identidades, la participación, la experiencia y el significado. Así, la identidad se fundamenta en la forma en cómo la infancia elabora su propia identidad en consonancia con el otro cuando comparten acciones. La pedagogía de la participación aborda cómo la escuela es capaz de posibilitar una infancia protagónica de su propia realidad, cómo hacemos una verdadera pedagogía de la escucha o qué tipo de oportunidades para la participación brindamos a los niños. La pedagogía de la experiencia, nos habla de los lenguajes, de las posibilidades ofertadas a la comunicación y las técnicas utilizadas para ello. Por último, la pedagogía del significado, nos sitúa ante la manera en cómo se elabora el pensamiento de forma colectiva, favorecedor de en un discurso compartido. Todo este constructo teórico, inspira un proyecto de innovación docente desarrollado en colaboración universidad-escuela que teniendo como foco temático “los espacios escolares” plantea potenciar la participación, entendiendo el espacio escolar como generador de procesos participativos que lleve a reconocer y valorar las diferentes identidades que están presentes en la escuela y que posibilite una verdadera transformación del territorio escolar en base a las prácticas que en él se realicen.

Se presenta el caso de un paciente masculino de 38 años, en condición de indigencia, toxicómano, sin antecedentes patológicos conocidos; a quien, en estudio por pérdida de peso, hematemesis y diarrea sanguinolenta, se le documentó síndrome de inmunodeficiencia adquirida con infección por tuberculosis (TB) pulmonar; se le inició terapia antifímica. Después de 15 días de iniciada la terapia antituberculosa se dio inicio a terapia antiretroviral (TARV). El cuadro evolucionó con deterioro hemodinámico y el paciente falleció. La autopsia demostró hallazgos compatibles con tuberculosis diseminada.