Reconciling communication repertoires: navigating interactions involving persons with severe/profound intellectual disability, a classic grounded theory study.

BACKGROUND: A rights-based agenda, informed by the UNCRPD, that advocates person-centredness, inclusion, empowerment and self-determination is shaping service provision to people with intellectual disability (ID). Listening to their perspectives is fundamental to meeting these goals. However, communication with people with severe/profound ID is challenging and difficult. Therefore, this study aims to generate a theory that explains how people communicate with and understand each other in these interactions. METHODS: Classic grounded theory (CGT) methodology was used as it recognises that knowledge can be captured rather than interpreted. According to CGT, capturing rather than interpreting experiences strengthens findings, particularly in relation to participants with severe/profound ID. Concurrent theoretical sampling, data collection and analysis were undertaken. Twenty-two individuals participated in the study: 3 people with severe/profound ID and 19 people with whom they interact. Data were collected over a 9-month period and involved video recordings, field notes, individual and group interviews. Data were analysed using CGT methods of coding, constant comparison and memoing. RESULTS: The Theory of Reconciling Communication Repertoires was generated. Nurturing a sense of belonging emerged as the main concern and core category that is resolved by reconciling communication repertoires. A communication repertoire refers to the cache of communication skills a person has available to them. To reconcile repertoires is to harmonise or make them compatible with each other in order to communicate. Interactions are navigated through five stages: motivation to interact, connection establishment, reciprocally engaging, navigating understanding and confusion resolution. CONCLUSIONS: The Theory of Reconciling Communication Repertoires explains how interactions involving people with severe/profound ID are navigated. While this is a substantive rather than formal theory, it has the potential to inform practice, policy, management, education and research as it outlines how communication with people with severe/profound ID can take place to design, inform and plan person-centred care.

Temblor y ataxia en COVID-19 / Tremor and ataxia in COVID-19

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A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection

With the ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, there is need for sensitive, specific and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves the detection of viral RNA using RT-qPCR, with many commercial kits now available for this purpose. However, these are expensive and supply of such kits in sufficient numbers cannot always be guaranteed. We therefore developed a multiplex assay using well-established SARS-CoV-2 targets alongside internal controls that monitor sample quality and nucleic acid extraction efficiency. Here, we establish that this test performs as well as widely used commercial assays, but at substantially reduced cost. Furthermore, we demonstrate >1,000-fold variability in material routinely collected by nose-and-throat swabbing. The inclusion of a human control probe in our assay provides additional information that could help reduce false negative rates.

Leishmaniasis visceral: orientación diagnóstica solo con anamnesis, clínica y analítica básica / No disponible

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RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition.

Long INterspersed Element class 1 (LINE-1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition-competent LINE-1s, whose activity is influenced by the combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1 are known LINE-1 repressors and when mutated cause the autoinflammatory disorder Aicardi-Goutières syndrome (AGS). Mutations in RNase H2 are the most common cause of AGS, and its activity was proposed to similarly control LINE-1 retrotransposition. It has therefore been suggested that increased LINE-1 activity may be the cause of aberrant innate immune activation in AGS Here, we establish that, contrary to expectations, RNase H2 is required for efficient LINE-1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE-1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE-1 elements can retrotranspose efficiently without their own RNase H activity. Our findings appear to be at odds with LINE-1-derived nucleic acids driving autoinflammation in AGS.

Estudio prospectivo comparativo entre cistectomía radical laparoscópica y abierta: resultados operatorios y oncológicos / Prospective study comparing laparoscopic and open radical cystectomy: Surgical and oncological results

Introducción La cistectomía radical laparoscópica con linfadenectomía y derivación urinaria es una cirugía de empleo creciente. Se necesitan estudios que avalen la efectividad oncológica y la seguridad de este abordaje mínimamente invasivo. Pacientes y métodos: Estudio prospectivo comparativo no aleatorizado entre cistectomía radical abierta (CRA) y laparoscópica (CRL) llevado a cabo en un hospital universitario. El objetivo principal fue comparar la supervivencia cáncer-específica, y el objetivo secundario comparar resultados operatorios y complicaciones según la escala Clavien-Dindo. Resultados: Ciento cincuenta y seis pacientes con cáncer vesical invasivo de alto grado fueron tratados mediante CRA (n = 70) o CRL (n = 86). El seguimiento medio fue 33,5 ± 23,8 (rango 12-96) meses. La edad media fue 66,9 + 9,4 años y la proporción hombre/mujer 19:1. Ambos grupos fueron equivalentes en edad, estadio, ganglios positivos, carcinoma in situ, uropatía obstructiva preoperatoria, quimioterapia adyuvante y tipo de derivación urinaria. No hubo diferencias entre grupos en supervivencia cáncer-específica (log-rank; p = 0,71). El estadio histopatológico fue la única variable independiente predictiva de pronóstico. La estancia hospitalaria (p = 0,01) y la tasa de transfusión operatoria (p = 0,002) fueron menores para CRL. La duración de la cirugía fue mayor para CRL (p < 0,001). No hubo diferencias en la tasa de complicaciones totales (p = 0,62) ni complicaciones mayores (p = 0,69). El riesgo de evisceración (p = 0,02), infección de herida quirúrgica (p = 0,005) y neumonía (p = 0,017) fue mayor en CRA. El riesgo de lesión rectal (p = 0,017) y fístula uretrorrectal (p = 0,065) fue mayor en CRL. Conclusión: La CRL es un tratamiento equivalente a la CRA en términos de eficacia oncológica, y ventajoso respecto a tasa de transfusión y estancia hospitalaria, pero no respecto a la ocupación de quirófano o a la seguridad global. Se necesitan estudios que definan mejor el perfil de seguridad específico de cada abordaje

Introduction: Laparoscopic radical cystectomy with lymphadenectomy and urinary diversion is an increasingly widespread operation. Studies are needed to support the oncological effectiveness and safety of this minimally invasive approach. Patients and methods: A nonrandomised, comparative prospective study between open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) was conducted in a university hospital. The main objective was to compare cancer-specific survival. The secondary objective was to compare the surgical results and complications according to the Clavien-Dindo scale. Results: We treated 156 patients with high-grade invasive bladder cancer with either ORC (n = 70) or LRC (n = 86). The mean follow-up was 33.5 ± 23.8 (range 12-96) months. The mean age was 66.9 + 9.4 years, and the male to female ratio was 19:1. Both groups were equivalent in age, stage, positive lymph nodes, in situ carcinoma, preoperative obstructive uropathy, adjuvant chemotherapy and type of urinary diversion. There were no differences between the groups in terms of cancer-specific survival (log-rank; P = .71). The histopathology stage was the only independent variable that predicted the prognosis. The hospital stay (P = .01) and operative transfusion rates (P = .002) were less for LRC. The duration of the surgery was greater for LRC (P < .001). There were no differences in the total complications rate (p = .62) or major complications (P = .69). The risk of evisceration (P = .02), surgical wound infection (P=.005) and pneumonia (P = .017) was greater for ORC. The risk of rectal lesion (P = .017) and urethrorectal fistulae (P = .065) was greater for LRC. Conclusion: LRC is an equivalent treatment to ORC in terms of oncological efficacy and is advantageous in terms of transfusion rates and hospital stays but not in terms of operating room time and overall safety. Studies are needed to better define the specific safety profile for each approach

Microfluidics for rapid cytokeratin immunohistochemical staining in frozen sections.

Frozen sections (FS) of tumor samples represent a cornerstone of pathological intraoperative consultation and have an important role in the microscopic analysis of specimens during surgery. So far, immunohistochemical (IHC) stainings on FS have been demonstrated for a few markers using manual methods. Microfluidic technologies have proven to bring substantial improvement in many fields of diagnostics, though only a few microfluidic devices have been designed to improve the performance of IHC assays. In this work, we show optimization of a complete pan-cytokeratin chromogenic immunostaining protocol on FS using a microfluidic tissue processor into a protocol taking <12 min. Our results showed specificity and low levels of background. The dimensions of the microfluidic prototype device are compatible with the space constraints of an intraoperative pathology laboratory. We therefore anticipate that the adoption of microfluidic technologies in the field of surgical pathology can significantly improve the way FSs influence surgical procedures.

Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium.

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.

Microfluidics-assisted fluorescence in situ hybridization for advantageous human epidermal growth factor receptor 2 assessment in breast cancer.

Fluorescence in situ hybridization (FISH) is one of the recommended techniques for human epidermal growth factor receptor 2 (HER2) status assessment on cancer tissues. Here we develop microfluidics-assisted FISH (MA-FISH), in which hybridization of the FISH probes with their target DNA strands is obtained by applying square-wave oscillatory flows of diluted probe solutions in a thin microfluidic chamber of 5 µl volume. By optimizing the experimental parameters, MA-FISH decreases the consumption of the expensive probe solution by a factor 5 with respect to the standard technique, and reduces the hybridization time to 4 h, which is four times faster than in the standard protocol. To validate the method, we blindly conducted HER2 MA-FISH on 51 formalin-fixed paraffin-embedded tissue slides of 17 breast cancer samples, and compared the results with standard HER2 FISH testing. HER2 status classification was determined according to published guidelines, based on average number of HER2 copies per cell and average HER2/CEP17 ratio. Excellent agreement was observed between the two methods, supporting the validity of MA-FISH and further promoting its short hybridization time and reduced reagent consumption.

Asymptomatic LTP sensitisation is common in plant-food allergic children from the Northeast of Spain

BACKGROUND: The sensitisation profile at molecular level in plant-food allergy is complex. Several allergens may be involved, with different potential for severe reactions. lipid transfer proteins (LTP) are considered the most relevant plant-food allergens in adults in Mediterranean countries, but less is known in children. AIM: To describe the clinical pattern and sensitisation profile of children with plant-food allergy and LTP sensitisation from Northeast Spain. METHODS: Children with history of immediate reaction to plant-food(s), positive skin-prick-test to the culprit plant-food(s) and specific-IgE to plant-food LTPs were analysed. RESULTS: 130 children were included. 69.2% (90/130) had reacted to ≥2 taxonomically unrelated plant-foods. Peach, walnut, hazelnut and peanut were most frequently involved. Reactions severity ranged from anaphylaxis (45.4%, 59/130) to oral symptoms only. Sensitisation to a particular plant-food LTP not always caused clinical symptoms with that plant-food; 69% (40/58) and 63% (17/27) of peach- and walnut-tolerant subjects had positive rPru p 3 and nJug r 3 specific IgE, respectively. 65.4% (85/130) of children were also sensitised to storage proteins, which was associated to anaphylaxis and nut allergy. However, 60% of patients without nuts/seeds allergy were sensitised to storage proteins. Specific-IgE levels to LTPs and/or storage proteins were not useful to predict allergy (vs. tolerance) to peach, walnut, peanut or hazelnut. CONCLUSIONS: Sensitisation to LTP and/or storage proteins without clear clinical significance is relatively common. Prospective longitudinal studies are required to evaluate the relevance of these silent sensitisations over time. Caution is required when interpreting the results of molecular-based diagnostic tools in clinical practice

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Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response.

Aicardi-Goutières syndrome (AGS) provides a monogenic model of nucleic acid-mediated inflammation relevant to the pathogenesis of systemic autoimmunity. Mutations that impair ribonuclease (RNase) H2 enzyme function are the most frequent cause of this autoinflammatory disorder of childhood and are also associated with systemic lupus erythematosus. Reduced processing of eitherRNA:DNAhybrid or genome-embedded ribonucleotide substrates is thought to lead to activation of a yet undefined nucleic acid-sensing pathway. Here, we establishRnaseh2b(A174T/A174T)knock-in mice as a subclinical model of disease, identifying significant interferon-stimulated gene (ISG) transcript upregulation that recapitulates theISGsignature seen inAGSpatients. The inflammatory response is dependent on the nucleic acid sensor cyclicGMP-AMPsynthase (cGAS) and its adaptorSTINGand is associated with reduced cellular ribonucleotide excision repair activity and increasedDNAdamage. This suggests thatcGAS/STINGis a key nucleic acid-sensing pathway relevant toAGS, providing additional insight into disease pathogenesis relevant to the development of therapeutics for this childhood-onset interferonopathy and adult systemic autoimmune disorders.

Precision medicine in the age of big data: The present and future role of large-scale unbiased sequencing in drug discovery and development.

High throughput molecular and functional profiling of patients is a key driver of precision medicine. DNA and RNA characterization has been enabled at unprecedented cost and scale through rapid, disruptive progress in sequencing technology, but challenges persist in data management and interpretation. We analyze the state-of-the-art of large-scale unbiased sequencing in drug discovery and development, including technology, application, ethical, regulatory, policy and commercial considerations, and discuss issues of LUS implementation in clinical and regulatory practice.

Síndrome vascular acral paraneoplásico / Paraneoplastic Acral Vascular Syndrome

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FR-Utilización de psicofármacos en dermatología / Psychotropic Drugs in Dermatology

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Evidence of a molecular clock in the ovine ovary and the influence of photoperiod.

The influence of the central circadian clock on reproductive timing is well established. Much less is known about the role of peripheral oscillators such as those in the ovary. We investigated the influence of photoperiod and timing of the LH surge on expression of circadian clock genes and genes involved in steroidogenesis in ovine ovarian stroma. Seventy-two Suffolk cross ewes were divided into two groups, and their estrous cycles were synchronized. Progestagen sponge removal was staggered by 12 hours between the groups such that expected LH peak would occur midway through either the light or dark phase of the photoperiodic cycle. Four animals from each group were killed, and their ovaries were harvested beginning 36 hours after sponge removal, at 6-hour intervals for 48 hours. Blood was sampled every 3 hours for the period 24 to 48 hours after sponge removal to detect the LH surge. The interval to peak LH did not differ between the groups (36.2 ± 1.2 and 35.6 ± 1.1 hours, respectively). There was an interaction between group and the time of sponge removal on the expression of the core clock genes ARNTL, PER1, CRY1, CLOCK, and DBP (P < 0.01, P < 0.05, P < 0.01, P < 0.01, and P < 0.01, respectively). As no significant interaction between group and time of day was detected, the datasets were combined. Statistically significant rhythmic oscillation was observed for ARNTL, CLOCK, CRY1 (P < 0.01, respectively), PTGS2, DBP, PTGER2, and CYP17A1 (P < 0.05, respectively), confirming the existence of a time-sensitive functionality within the ovary, which may influence steroidogenesis and is independent of the ovulatory cycle.

Opiniones y expectativas de los padres respecto a las infecciones respiratorias agudas de lactantes y pre-escolares. Influencia en la disposición a consultar / Opinions and expectations of the parents regarding acute respiratory infections of infants and pre-school children. Influence on the facility to consult

Objetivos: Describir las opiniones y expectativas de los padres relacionadas con la disposición a consultar por infecciones respiratorias agudas de lactantes y pre-escolares. Métodos: Estudio transversal con muestra oportunista de padres de niños menores de cinco años. Se diseñó un cuestionario que exploraba las opiniones acerca de la frecuencia, sintomatología, gravedad y tratamiento de las infecciones respiratorias agudas, así como las expectativas respecto a la atención médica por esas enfermedades, y la disposición de los padres a consultar con el médico en distintas situaciones. Se realizó un análisis multivariante exploratorio para identificar las variables más relacionadas con la disposición a consultar. Resultados: Se recogieron 317 encuestas. El 54,6% de los niños del estudio eran varones, la edad mediana (amplitud intercuartil) era de 2,0 (0,6-3,3 años) y un 5,7% había estado alguna vez hospitalizado por enfermedades respiratorias. El modelo multivariante encontró siete variables asociadas a la disposición a consultar, agrupables en tres dominios: 1) percepción de vulnerabilidad del niño (menor edad y antecedentes de hospitalización); 2) percepción de una amenaza (creencia en la gravedad de las infecciones respiratorias y expectativa de que el médico le indique si es grave); y 3) percepción de eficacia del tratamiento farmacológico (creer en la eficacia de medicinas para tos y mocos, creer en la eficacia de antibióticos, y esperar una prescripción en la consulta). Conclusiones: La disposición a consultar por las infecciones respiratorias agudas de lactantes y pre-escolares se asocia a un conjunto definido de opiniones y expectativas de los padres

Aim: Describe the parents' beliefs and expectations related to the willingness to consult for acute respiratory infections in infants and preschool children. Methods: Cross-sectional study of an opportunistic sample of parents of children of less than five years. A questionnaire was designed to explore beliefs about frequency, symptoms, severity and treatment of acute respiratory infections, expectations on health care from doctors, and willingness to consult in certain circumstances. In an exploratory multivariate analysis, the main variables related to willingness to consult were identified. Results:. There were 317 questionnaires collected; 54.6 percent of children were male, their median age (interquartile range) was 2.0 years (0.6-3.3 years), and 5.7% had been hospitalized because respiratory diseases. The multivariate model found seven variables related to the willingness to consult, that could be clustered in three domains: 1) perception of vulnerability in children (lower age and previous hospitalization); 2) perception of threat (beliefs about severity of respiratory diseases and expectations that the doctor says whether the disease is severe); and 3) perception of efficacy of drugs (beliefs about efficacy of symptomatic drugs and of antibiotics, and expectations of being prescribed a drug). Conclusions:. The willingness to consult for acute respiratory infections in infants and preschool children is related to a definite set parents' beliefs and expectations

Prevalence and clinical profile of difficult-to-control severe asthma in children: Results from pneumology and allergy hospital units in Spain

BACKGROUND: Severe asthma is often poorly controlled and its prevalence in Spanish children is unknown. The aim was to determine the prevalence of difficult-to-control severe asthma in children, the agreement of asthma control between physicians and Spanish Guidelines for Asthma Management (GEMA), and the health-related quality of life (HRQoL) for children and parents. METHODS: Observational, cross-sectional, two-phase, multicentre study. In the first phase, all children who attended pneumology and allergy units during a three-month period were classified according to physicians' criteria as patients with: asthma, severe asthma, or difficult-to-control severe asthma. Patients aged 6-14 years with severe asthma (difficult-to-control or controlled) were included in the second phase. RESULTS: 12,376 asthmatic children were screened in the first phase. According to physicians' criteria, 8.8% (95% CI 8.3-9.3%) had severe asthma. Of these, 24.2% (95% CI, 21.7-26.8%) had difficult-to-control severe asthma. 207 patients with severe asthma (mean age 10.8 ± 2.3 years; 61.4% male; mean of 5.5 ± 3.4 years since asthma diagnosis) were included in the second phase. Compared to the patients with controlled asthma, children with difficult-to-control asthma had a higher number of exacerbations, emergency room or unscheduled primary care visits in the previous year (p < 0.0001, all) and poor HRQoL (p < 0.0001, both children and caregivers). 33.3% of patients with controlled asthma according to physicians' criteria were poorly controlled according to GEMA. CONCLUSIONS: Around one in four asthmatic children with severe disease had difficult-to-control asthma, although one third was underestimated by physicians. Children with difficult-to-control severe asthma had a poor HRQoL that also affected their parents

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Epidemiología de la historia de alergia a proteínas de la leche de vaca en niños mayores de un año de edad y su tolerancia / Epidemiology of cow's milk allergy and its tolerance in children more than one year old

Introducción: la alergia a las proteínas de la leche de vaca (PLV) es una afección frecuente en el primer año de vida, cuya incidencia parece estar aumentando en los países desarrollados. Objetivos: estudiar, en el ámbito de la Atención Primaria, la prevalencia acumulada de alergia IgE-mediada a las PLV en niños mayores de un año de edad y la adquisición de tolerancia, y factores que pueden estar asociados a ella. Material y métodos: estudio retrospectivo de las historias clínicas de los pacientes menores de 14 años de un centro de salud en Palencia (2805 niños). Resultados: el 2,35% (66) presentó alergia a las PLV. El 57,6% consiguió tolerar las PLV, la edad media a la que se logró fue de 34,6 meses. No se encontró ningún factor asociado al hecho de alcanzar la tolerancia. Los niños que no presentaban manifestaciones respiratorias de atopia tendían a tolerar antes, pero no de forma estadísticamente significativa. Conclusiones: se encontró en el ámbito sanitario de la Atención Primaria, una prevalencia elevada de alergia a las PLV IgE-mediada. La probabilidad de alcanzar la tolerancia a las PLV disminuye con la edad y es máxima entre los dos y los tres años. Se necesita realizar un diagnóstico preciso, tanto para el bienestar de los pacientes y sus familias como para evitar gastos sanitarios innecesarios(AU)

Introduction: allergy to cow's milk (CM) proteins is a frequent condition in the first year of life and its incidence seems to be increasing in the developed countries. Objectives: to study the accumulated prevalence of IgE-mediated cow's milk allergy (CMA) in children more than one year old at primary care, and tolerance development and factors that can be associated to it. Material and methods: retrospective study of (2,805) clinical histories of patients under 14 years in a primary health centre. Results: we found cow's milk allergy in 2.35% (66); 57.6% were able to tolerate CM at an average age of 34.6 months. We did not find any factors associated to the development of tolerance. Children who did not suffer respiratory symptoms tended to reach tolerance earlier but there was not statistical significance. Conclusions: we found a high prevalence of IgE-mediated CMA in primary care. The probability to develop tolerance to CM falls with age being the maximum in the second and third years of life. Carrying out an appropriated diagnosis is needed for patient and family comfort and for avoiding unnecessary health care expenditure(AU)

Situación actual y factores que condicionan la lactancia materna en Castilla y León / Current situation and factors conditioning the start of breastfeeding in Castilla y León

Objetivos: conocer la prevalencia de inicio de lactancia materna exclusiva en la comunidad de Castilla y León y los factores que influyen en su inicio y duración. Métodos: estudio descriptivo observacional realizado en la comunidad de Castilla y León (España) de enero a diciembre 2007, en niños entre seis y 12 meses de vida que acudían por cualquier motivo a las consultas de algún miembro del Programa de Pediatría de la Red Centinela Sanitaria de Castilla y León. Resultados: el porcentaje de mujeres que eligieron lactancia materna exclusiva después del parto fue del 81,2%, el 10,7% optó por la lactancia mixta y el 8,1% por la lactancia artificial. El abandono de la lactancia natural fue progresivo mes a mes llegando al sexto mes solo el 36,5% de los niños que la habían iniciado. Conclusiones: los índices de lactancia materna exclusiva, y sobre todo su mantenimiento hasta los seis meses de vida, continúan alejados de los estándares propuestos a nivel mundial. Es imprescindible una mayor implicación en el fomento de la lactancia natural no solo del personal sanitario sino de la sociedad en general (AU)

Objectives: to describe the prevalence of exclusive breastfeeding in the community of Castilla y León, and to determine the factors that condition its duration. Methods: descriptive, observational study carried out in Castilla y León (Spain) in children aged 6 to 12 months attending the consultation of any member of the Health Sentinel Network of Castilla y Leon in 2007. Results: the percentage of women choosing exclusive postpartum breastfeeding was 81.2%, 10.7% mixed feeding and 8.1% artificial feeding. The drop-out of breastfeeding was progressive month by month and only 36.5% of children who initiated it reached six months. Conclusions: the rates of exclusive breastfeeding and the maintenance up to the six months of life are still away from the proposed global standards. It is essential to improve the involvement of health personnel and general society in encouraging breastfeeding (AU)

X-linked agammaglobulinaemia. Mutation A1246G (R372G)

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