Status epilepticus-Therapeutic management at the pediatric emergency department.

INTRODUCTION: Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus. METHODS: Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus. RESULTS: One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05). CONCLUSIONS: Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes.

Contribution of MASK-air® as a mHealth tool for digitally-enabled person-centred care in rhinitis and asthma.

In chronic diseases, mobile health apps may help to (i) improve clinical management and (ii) provide valuable real-world scientific evidence. In allergic rhinitis, a market research study has only identified four mHealth apps which were multilingual, resulted in scientific publications and displayed a comprehensive list of medications. Ot those, MASK-air® was the app with the highest number of scientific publications. MASK-air® has been launched in 2015 and is currently available in 30 countries, having collected data from more than 30,000 users. It comprises a daily monitoring questionnaire, allowing patients to register (i) their daily allergy symptoms by means of visual analogue scales, and (ii) their medication use. The achievements of MASK-air® include the development of two digital biomarkers for daily monitoring of rhinitis and asthma (combined symptom-medication score and electronic daily asthma control score). In addition, MASK-air® data have allowed to assess patients' behaviours, suggesting that patients do not follow guideline recommendations, but rather treat themselves (and often use co-medication) whenever feeling worse. Using MASK-air® data, it has also been possible to quantify the impact of allergic diseases in quality-of-life, school and work productivity. MASK-air® real-world data is being used as a source of evidence for the Allergic Rhinitis and its Impact on Asthma 2024 guidelines, in an innovative process of incorporation of mobile health data into guidelines. This review discusses the clinical and scientific contributions of MASK-air® for person-centred care of rhinitis and asthma, providing an illustrative example on the use of mobile health in chronic diseases.

Probabilistic estimation of the source component of seismic hazard in North-Eastern Brazil.

Stable continental regions pose unique challenges for conducting Probabilistic Seismic Hazard Analysis because the earthquake activity driving mechanisms are poorly understood. For instance, the lower seismicity (hence the paucity of data) and the absence of well-defined active fault systems complicate accurately determining seismic source parameters. Northeastern Brazil is a stable continental region exhibiting moderate-size events recorded with significant seismic intensities and provoking the collapse of poorly constructed buildings in the last century. Thus, assessing the seismic hazard is critical for seismic risk mitigation. The seismic hazard depends on three components: source, path, and site, and here, we present the probabilistic seismic hazard analysis of the source component for NE Brazil. Spatial aggregation of earthquake sources outlined four areal seismic zones. A goodness-of-fit test rejected the Gutenberg-Richter model of magnitude frequency distribution in one of the studied seismic zones. For this reason, we estimated the magnitude probability distribution function in that zone using a nonparametric adaptive kernel estimator. In other zones the Gutenberg-Richter magnitude frequency model was applied. In either way of the magnitude probability distribution modelling we considered the upper bound for magnitude equal to 6.6 mR, based on the upper bound of a 95 % confidence interval for the standard normal distribution of palaeoearthquake sizes. Our findings suggests that potentially damaging events are likely to occur, and we cannot neglect chances for the occurrence of earthquakes exceeding 5.2 mR. The calculated mean return periods indicate significantly shorter intervals between consecutive large events than palaeoseismic records.

Understanding beliefs about inhaled medication in patients with persistent asthma: a cross-sectional analysis of the INSPIRERS studies.

Summary: Background. Identifying factors influencing adherence, such as patients' beliefs about medication, is essential for effective asthma management. This study aims to assess and gain insight into the beliefs of patients with asthma regarding inhaled medication. Methods. This is a secondary analysis of the INSPIRERS studies. Patients aged ≥ 13 y.o., with persistent asthma and a prescription for inhaled controller were recruited from 60 primary and secondary care centres in Portugal from 2017 to 2020. Demographic and clinical characteristics were collected in a face-to-face visit. The Specific-Beliefs about Medicine Questionnaire was administered 1-week later by telephone interview. Mann-Whitney U and Kruskal-Wallis tests were used to explore relations between patients' beliefs and characteristics. Results. A total of 552 participants (mean 32.8 ± 17.3 y.o.; 64.5% female) were analysed. The Necessity score (Median 19 [p25-p75 16,22]) was significantly higher than the Concerns score (15 [16,22], p less than 0.001), resulting in a positive Necessity-Concern differential (Median 4 [0,7]). Acceptance (high necessity, low concerns) characterized 61% of participants, while 19% were ambivalent (high necessity, high concerns). Adolescents exhibited lower Necessity (Median 16 vs 20; p less than 0.001) and Concerns scores (Median 11 vs 15; p = 0.002) than adults. In primary care setting, patients had significantly lower Necessity (Median 18 vs 19; p = 0.027) and Concerns (Median 14 vs 15; p = 0.05) compared to the secondary care. Conclusions. A predominantly positive perception of inhaled asthma medication necessity was found, although ambivalence or indifference exists in about 1/5 of patients. Our findings highlight the importance of personalized approaches to address beliefs and optimise patient education.

Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

From MASK-air and SILAM to CATALYSE (Climate Action To Advance HeaLthY Societies in Europe).

Plant species vary under different climatic conditions and the distribution of pollen in the air. Trends in pollen distribution can be used to assess the impact of climate change on public health. In 2015, the Mobile Airways Sentinel networK for rhinitis and asthma (MASK-air®) was launched as a project of the European Innovation Partnership on Active and Healthy Ageing (EIP-on-AHA, DG Santé and DG CONNECT). This project aimed to develop a warning system to inform patients about the onset of the pollen season, namely, the System for Integrated modeLling of Atmospheric coMposition (SILAM). A global-to-meso-scale dispersion model was developed by the Finnish Meteorological Institute (FMI). It provides quantitative information on atmospheric pollution of anthropogenic and natural origins, particularly on allergenic pollens. Impact of Air Pollution on Asthma and Rhinitis (POLLAR, EIT Health) has combined MASK-air clinical data with SILAM forecasts. A new Horizon Europe grant (Climate Action to Advance HeaLthY Societies in Europe [CATALYSE]; grant agreement number 101057131), which came into force in September 2022, aims to improve our understanding of climate change and help us find ways to counteractit. One objective of this project is to develop early warning systems and predictive models to improve the effectiveness of strategies for adapting to climate change. One of the warning systems is focused on allergic rhinitis (CATALYSE Task 3.2), with a collaboration between the FMI (Finland), Porto University (Portugal), MASK-air SAS (France), ISGlobal (Spain), Hertie School (Germany), and the University of Zurich (Switzerland). It is to be implemented with the support of the European Academy of Allergy and Clinical Immunology. This paper reports the planning of CATALYSE Task 3.2.

Review: Non-surgical artificial insemination and embryo recovery as safe tools for genetic preservation in small ruminants.

Artificial insemination (AI) and in vivo embryo production (or multiple ovulation and embryo transfer, MOET) programs are both instrumental in accelerating the propagation of genetically and economically superior goats and sheep. The aim of this review was to present the current gestalt of non-surgical AI and embryo recovery (NSER) procedures in small ruminants. Small body size, precluding rectal palpation, and highly limited penetrability of the uterine cervix in ewes are the major reasons for the scarce use of non-surgical assisted reproduction techniques in this species. As a result, AI and embryo recovery techniques in sheep mainly involve laparoscopy or laparotomy (LAP). In does, however, the Embrapa method of AI allows for successful intrauterine deposition of semen, resulting in pregnancy rates from 50 to 80% under field conditions (>3 000 goats inseminated) when frozen-thawed semen is used. After the administration of prostaglandin F2α (PGF2α), non-surgical (transcervical) embryo recovery is also feasible in goats, with the cervical penetration rate approaching 100%. There is a paucity of information on the efficacy of non-surgical AI using frozen semen in sheep, but the results are satisfactory with fresh, cooled, or chilled ram semen. An application of the NSER technique in ewes has greatly improved over the last decade, and cervical penetration rates of ∼90% can be achieved when a hormonal cervical dilation protocol using PGF2α, oxytocin, and/or estradiol ester (e.g., estradiol benzoate) is applied. In some genotypes of sheep, sufficient cervical dilation can be induced without estradiol ester included in the protocol. Several studies indicated that recovery of transferable quality ovine embryos using NSER is comparable to that employing a ventral midline laparotomy, and NSER is evidently a method of choice when animal welfare is concerned. Considering both the number of retrievable embryos and animal well-being, the NSER is a viable alternative for surgical procedures. With further developments, it has the makings of a primary, if not exclusive, embryo recovery technique in small ruminants worldwide.

Association of Lower Age and Cardiorespiratory Events during Intra-Arterial Chemotherapy for Retinoblastoma: A Prospective Observational Study.

BACKGROUND AND PURPOSE: Retinoblastoma is the most common primary intraocular tumor in childhood. Intra-arterial chemotherapy is becoming the standard of care for both first-line and rescue therapy, thus improving survival rates and decreasing the adverse effects of retinoblastoma treatment. Cardiorespiratory adverse events during general anesthesia for intra-arterial chemotherapy, including decreased lung compliance and bradycardia, have been described, but data regarding associated factors are still lacking. We aimed to assess the characteristics of patients and procedures associated with cardiorespiratory events during intra-arterial chemotherapy. MATERIALS AND METHODS: We performed a prospective monocenter observational study in children diagnosed with retinoblastoma undergoing intra-arterial chemotherapy under general anesthesia. The occurrence of cardiorespiratory events was registered. We also assessed clinical and procedural characteristics potentially associated with these events. RESULTS: A cardiorespiratory event was observed in 22 (12.5%) procedures, predominantly a decrease in tidal volume observed in 16 (9%) procedures. The median age was lower in the procedures with a cardiorespiratory event (20.43 [SD, 11.76] months versus 30.11 [SD, 24.17] months) (P < .05). Other variables such as bilateral disease or a previous intra-arterial chemotherapy treatment were not associated with the occurrence of a cardiorespiratory event. CONCLUSIONS: In children undergoing intra-arterial chemotherapy for retinoblastoma treatment, cardiorespiratory events were observed in 12.5% of procedures. Lower age was associated with this complication. Although predominantly mild, these events should have prompt diagnosis and treatment to prevent further deterioration and worse outcomes.

Miopatía miotubular ligada al cromosoma X: informe clínico y revisión del fenotipo leve / X-linked myotubular myopathy: a clinical report and a review of the mild phenotype

Introducción: La miopatía miotubular ligada al X es una miopatía centronuclear rara que afecta aproximadamente a 1 de cada 50.000 recién nacidos varones causada por variantes patógenas en el gen de la miotubularina 1 (MTM1). La gravedad clínica varía; sin embargo, la necesidad de soporte ventilatorio ocurre casi invariablemente. Caso clínico: Presentamos el caso de un niño de 4 años que presentaba hipotonía muscular leve a los 12 meses, trastorno del lenguaje expresivo, retraso global del desarrollo y trastorno del procesamiento sensorial. La secuenciación clínica del exoma identificó la variante hemicigótica c.722G>A p.(Arg241His) en el exón 9 del gen de la miotubularina 1 (NM_000252.2). La madre es portadora heterocigota de la misma variante. Se estableció el diagnóstico de una forma leve de miopatía miotubular ligada al cromosoma X de herencia materna. El niño presentó una mejoría significativa con terapias del habla, ocupacional y física, sin intercurrencias respiratorias ni dependencia de ventilador. Conclusión: La presentación de una forma leve de esta miopatía miotubular, al notificarse más raramente, añadió desafío al diagnóstico. La combinación de hipotonía leve, dificultades de alimentación y trastorno del lenguaje expresivo debe hacer sospechar una enfermedad neuromuscular. Se carece de puntuaciones motoras o de desarrollo verificadas específicas de esta miopatía para determinar el pronóstico y la necesidad de otras terapias. Aunque actualmente la gravedad de la miopatía miotubular se clasifica según la dependencia del ventilador, esto puede ser insuficiente e inaplicable a los casos más leves. Es evidente la necesidad de un sistema de clasificación para los casos leves y moderados que evalúe la debilidad muscular y la fatiga, las limitaciones de la vida diaria, el retraso del desarrollo motor, las puntuaciones fenotípicas tempranas o las infecciones respiratorias recurrentes.(AU)

Introduction: X-linked myotubular myopathy is a rare centronuclear myopathy that affects approximately 1 in 50,000 male newborns caused by pathogenic variants in the myotubularin 1 gene (MTM1). The clinical severity varies, however the need for ventilatory support occurs almost invariably. Case report: We report the case of a 4-year-old boy presenting mild muscle hypotonia at 12 months-old, expressive language disorder, global developmental delay, and a sensory processing disorder. Clinical exome sequencing identified the hemizygous variant c.722G>A p.(Arg241His) in exon 9 of the myotubularin 1 gene (NM_000252.2). The mother is a heterozygous carrier of the same variant. A diagnosis of a mild form of maternal inherited X-linked myotubular myopathy was established. The child presented significant improvement with speech, occupational, and physical therapies, with no respiratory intercurrences or ventilator dependency. Conclusion: The presentation of a mild form of this myotubular myopathy, being less commonly reported, added challenge to the diagnosis. The combination of mild hypotonia, feeding difficulties and expressive language disorder should raise suspicion of a neuromuscular disease. There is a lack of verified motor or developmental scores specific to this myopathy to further determine prognosis and need of other therapies. While currently the severity myotubular myopathy is classified according to ventilator dependency, this may be insufficient and unapplicable to milder cases. There is an evident need for a grading system for mild and moderate cases assessing muscle weakness and fatigue, daily life limitations, motor developmental delay, early phenotypical scores, or recurrent respiratory infections.(AU)

X-linked myotubular myopathy: a clinical report and a review of the mild phenotype. / Miopatía miotubular ligada al cromosoma X: informe clínico y revisión del fenotipo leve.

INTRODUCTION: X-linked myotubular myopathy is a rare centronuclear myopathy that affects approximately 1 in 50,000 male newborns caused by pathogenic variants in the myotubularin 1 gene (MTM1). The clinical severity varies, however the need for ventilatory support occurs almost invariably. CASE REPORT: We report the case of a 4-year-old boy presenting mild muscle hypotonia at 12 months-old, expressive language disorder, global developmental delay, and a sensory processing disorder. Clinical exome sequencing identified the hemizygous variant c.722G>A p.(Arg241His) in exon 9 of the myotubularin 1 gene (NM_000252.2). The mother is a heterozygous carrier of the same variant. A diagnosis of a mild form of maternal inherited X-linked myotubular myopathy was established. The child presented significant improvement with speech, occupational, and physical therapies, with no respiratory intercurrences or ventilator dependency. CONCLUSION: The presentation of a mild form of this myotubular myopathy, being less commonly reported, added challenge to the diagnosis. The combination of mild hypotonia, feeding difficulties and expressive language disorder should raise suspicion of a neuromuscular disease. There is a lack of verified motor or developmental scores specific to this myopathy to further determine prognosis and need of other therapies. While currently the severity myotubular myopathy is classified according to ventilator dependency, this may be insufficient and unapplicable to milder cases. There is an evident need for a grading system for mild and moderate cases assessing muscle weakness and fatigue, daily life limitations, motor developmental delay, early phenotypical scores, or recurrent respiratory infections.

TITLE: Miopatía miotubular ligada al cromosoma X: informe clínico y revisión del fenotipo leve.Introducción. La miopatía miotubular ligada al X es una miopatía centronuclear rara que afecta aproximadamente a 1 de cada 50.000 recién nacidos varones causada por variantes patógenas en el gen de la miotubularina 1 (MTM1). La gravedad clínica varía; sin embargo, la necesidad de soporte ventilatorio ocurre casi invariablemente. Caso clínico. Presentamos el caso de un niño de 4 años que presentaba hipotonía muscular leve a los 12 meses, trastorno del lenguaje expresivo, retraso global del desarrollo y trastorno del procesamiento sensorial. La secuenciación clínica del exoma identificó la variante hemicigótica c.722G>A p.(Arg241His) en el exón 9 del gen de la miotubularina 1 (NM_000252.2). La madre es portadora heterocigota de la misma variante. Se estableció el diagnóstico de una forma leve de miopatía miotubular ligada al cromosoma X de herencia materna. El niño presentó una mejoría significativa con terapias del habla, ocupacional y física, sin intercurrencias respiratorias ni dependencia de ventilador. Conclusión. La presentación de una forma leve de esta miopatía miotubular, al notificarse más raramente, añadió desafío al diagnóstico. La combinación de hipotonía leve, dificultades de alimentación y trastorno del lenguaje expresivo debe hacer sospechar una enfermedad neuromuscular. Se carece de puntuaciones motoras o de desarrollo verificadas específicas de esta miopatía para determinar el pronóstico y la necesidad de otras terapias. Aunque actualmente la gravedad de la miopatía miotubular se clasifica según la dependencia del ventilador, esto puede ser insuficiente e inaplicable a los casos más leves. Es evidente la necesidad de un sistema de clasificación para los casos leves y moderados que evalúe la debilidad muscular y la fatiga, las limitaciones de la vida diaria, el retraso del desarrollo motor, las puntuaciones fenotípicas tempranas o las infecciones respiratorias recurrentes.

Self-reported adverse reactions to subcutaneous airborne allergen immunotherapy: a real-life, single center study.

Summary: Background. To estimate the prevalence of self-reported adverse reactions (AdR) to subcutaneous airborne allergen immunotherapy (SCIT) and to describe factors associated with its occurrence. Methods. Real-life, observational, descriptive study of all patients treated with SCIT at a Portuguese allergy unit between 03/2017 and 06/2019, and who answered ≥ 1 time to a pre-SCIT evaluation questionnaire assessing the occurrence of local and/or systemic AdR in the previous administration. Results. 939 questionnaires from 231 patients (42% female, 35% with asthma) were included. Most (60%) SCIT preparations had multiple allergens with concentration adjusted to prevent dilution (MA-NoDil), 26% were single allergen with standard concentration (SA-SC), 10% single allergen with higher than standard concentration (SA-HC), and 4% mixtures without concentration adjustment (MA-Dil). SCIT-related AdR were self-reported in 313 (33%) administrations, 97% at the injection site and 11% grade 1 systemic symptoms. In a multivariable model, being a female and having asthma were associated with higher risk of AdR. MA-NoDil SCIT presented a lower risk of AdR compared to SA-SC SCIT. Conclusions. SCIT-related AdR were self-reported in 1/3 of the administrations, most at the injection site. The risk of AdR was higher in females and in patients with asthma. The lower risk of adverse reactions observed in SCIT preparations with multiple allergens with no dilutional effect should be further explored in future, targeted studies.

ConectAR: Collaborative network of patients with asthma and carers actively involved in health research: a protocol for patient and public involvement.

Summary: Background. Patients and Public Involvement in every stage of the patient-centered health research cycle is the key to the development of innovative solutions with an impact on patients' care. Methods. This protocol describes the development of ConectAR, a network to promote the involvement of patients with asthma and their carers in the health research cycle. Results. This protocol comprehends 4 tasks: 1) define the mission, vision, governance and activities of the network through focus groups; 2) establish the communication strategy and tools; 3) test the feasibility of the network in a Delphi study on the research priorities for asthma in Portugal; 4) coordination and dissemination activities. Conclusions. This network will improve research by ensuring that patients and carers have an active role in the co-creation of impactful solutions for asthma.

Effects of different doses of estradiol benzoate used in a cervical relaxation protocol on the success of non-surgical embryo recovery and luteal function in superovulated ewes.

This study investigated the effectiveness of different doses of estradiol benzoate (EB) to promote cervical relaxation and their effects on luteal function and outcomes of non-surgical embryo recovery (NSER) in sheep. Multiparous (MULT) and nulliparous (NULL) crossbred Lacaune X Santa Inês ewes were superovulated and naturally bred. Seven days after progesterone withdrawal, females were randomly assigned to one of three distinct cervical relaxation protocols, consisting of i.m. treatment with 37.5 µg d-cloprostenol and different doses of EB: 0.0 mg (0.0EB group; n = 3 NULL and 14 MULT); 0.5 mg (0.5EB group; n = 4 NULL and 12 MULT) or 1.0 mg (1.0EB group, n = 6 NULL and 11 MULT) 16 h before NSER. All ewes received 50 IU of oxytocin 20 min before NSER (D17). Blood samples were collected and ultrasound exams (B-mode and color Doppler) were performed at two timepoints: immediately before d-cloprostenol and EB treatments and prior to NSER. Estrous behavior, corpora lutea count and NSER success outcomes were not affected by EB treatments nor parity (P > 0.05). Embryo recovery rate was greater for ewes in the 0.5EB group and in the NULL ewes (P < 0.05). Ovarian biometrics differed between the two evaluation timepoints in all groups (P < 0.05). Plasma estradiol increased over time, reaching a significant greater level in 1.0EB ewes compared to controls on D17 (P < 0.05), whereas progesterone concentrations decreased over time in all groups (P > 0.05). In conclusion, treatments did not affect NSER success but they did affect luteal function by altering P4 and E2 concentrations. Therefore, the NSER technique can be successfully performed in ewes with or without prior treatment with EB.

Single dose of 300 IU hCG in the early luteal phase in superovulated ewes: Effects on corpora lutea, progesterone profile, and embryo recovery.

This study aimed to evaluate the effects of hCG treatment during the early luteal phase on ovarian function, progesterone profile, and embryo yield in superovulated ewes. Superovulated sheep were randomly assigned to receive 300 IU hCG i.m. (GhCG, n = 24) or not (GControl, n = 25) at 96 h after the removal of the progesterone (P4) device (D13). Non-surgical embryo recovery (NSER) was performed eight days after P4 withdrawal. Ultrasound evaluations were performed on D13, D14, D16, and D17. Blood samples were collected on D14, D16, and D17. Superovulation scores were recorded based on the number of corpora lutea (CL) as follows: 1 (≤ 2), 2 (3-5), 3 (6-8), and 4 (≥ 9). NSER efficiency, superovulation response, and luteal tissue area were similar in both groups (P > 0.05). Structural luteolysis tended to be higher in GControl (P = 0.07; 47.0 %) while functional luteolysis was similar in both groups (P > 0.05; 0.0 % and 5.9 %). The recovery rate was greater (P < 0.05) in GhCG (89.8 %) compared with GControl (71.0 %), with similar overall ova/embryo numbers observed for both groups (P > 0.05). GhCG showed a higher concentration of animals with a superovulatory response score of 4 (54.5 %; P < 0.05) compared with the lowest scores. Plasma progesterone on D16 was higher (P < 0.05) in GhCG ewes (11.1 ± 1.5 vs 6.9 ± 1.5 ng/mL). In conclusion, the hCG treatment improved circulating P4 and embryo recovery rate, tended to maintain luteal functionality, and thus constitutes an additional tool for improving embryo yield in superovulated ewes.

Influence of particle size on the SARS-CoV-2 spike protein detection using IgG-capped gold nanoparticles and dynamic light scattering.

Due to the unprecedented and ongoing nature of the coronavirus outbreak, the development of rapid immunoassays to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its highly contagious variants is an important and challenging task. Here, we report the development of polyclonal antibody-functionalized spherical gold nanoparticle biosensors as well as the influence of the nanoparticle sizes on the immunoassay response to detect the SARS-CoV-2 spike protein by dynamic light scattering. By monitoring the increment in the hydrodynamic diameter (ΔDH) by dynamic light scattering measurements in the antigen-antibody interaction, SARS-CoV-2 S-protein can be detected in only 5 min. The larger the nanoparticles, the larger ΔDH in the presence of spike protein. From adsorption isotherm, the calculated binding constant (K D ) was 83 nM and the estimated limit of detection was 13 ng/mL (30 pM). The biosensor was stable up to 90 days at 4 °C. Therefore, the biosensor developed in this work could be potentially applied as a fast and sensible immunoassay to detect SARS-CoV-2 infection in patient samples.

Síndrome PURA en una niña con retraso grave del desarrollo: un diagnóstico desafiante / PURA syndrome in a child with severe developmental delay: a challenging diagnosis

Introducción: El síndrome PURA es una condición autosómica dominante poco común causada por variantes patogénicas de novo en el gen PURA y que se caracteriza por un fenotipo multisistémico que incluye retraso del neurodesarrollo global, hipotonía temprana, ausencia de habla, dificultades para alimentarse, hipersomnolencia, epilepsia y trastornos del movimiento. Caso clínico: Presentamos una niña de 9 años con hipotonía y dificultades para alimentarse con retraso del crecimiento desde el período neonatal. A la edad de 3 años era evidente el retraso motor e intelectual, tenía una marcha de base amplia, no hablaba y una respuesta de sobresalto acústico exagerada. Desarrolló estereotipias de mano-boca y epilepsia a los 6 años. La monitorización electroencefalográfica continua de 24 horas reveló una actividad lenta global y una actividad epileptiforme frecuente en las áreas temporal izquierda y centrotemporal. La resonancia magnética del cerebro reveló un retraso en la mielinización. A los 6 años, la secuenciación clínica del exoma identificó una variante patógena heterocigótica en el gen PURA, c.153delA p. (Leu54CysfsTer24). Conclusión: El síndrome PURA tiene características clínicas similares a otros trastornos neurológicos, pero la asociación con algunas características clínicas, no tan comunes en otras entidades neurológicas, como no poder hablar, pero poder seguir órdenes simples, y una respuesta de sobresalto acústico exagerado, deben ser factores de sospecha de síndrome PURA y servir para realizar un análisis genético para confirmar el diagnóstico y proporcionar una intervención multidisciplinar precoz.(AU)

Introduction: PURA syndrome is a rare autosomal dominant condition caused by de novo pathogenic variants in PURA gene and characterized by a multisystemic phenotype that includes global neurodevelopmental delay, early hypotonia, absence of speech, feeding difficulties, hypersomnolence, epilepsy and movement disorders. Case report: We report a 9-year-old girl with hypotonia and feeding difficulties with failure to thrive since the neonatal period. At the age of 3 years motor and intellectual delay were evident, she had a wide-based gait, no speech and an exaggerated acoustic startle response. She developed hand-mouthing stereotypies and epilepsy at 6 years old. The 24 hours continuous electroencephalogram monitoring revealed global slow activity and frequent epileptiform activity in left temporal and centrotemporal areas. The brain MRI revealed delayed myelination. At 6 years old the clinical exome sequencing identified a heterozygous pathogenic variant in the PURA gene, c.153delA p.(Leu54CysfsTer24). Conclusion: PURA syndrome has clinical features similar to other neurological disorders but the association with some clinical features, not as common in other neurological entities, like never being able to speak but being able to follow simple orders and exaggerated acoustic startle response, should raise the suspicion of PURA syndrome and genetic analysis must be performed to confirm the diagnosis and provide early multidisciplinary intervention.(AU)

PURA syndrome in a child with severe developmental delay: a challenging diagnosis. / Síndrome PURA en una niña con retraso grave del desarrollo: un diagnóstico desafiante.

INTRODUCTION: PURA syndrome is a rare autosomal dominant condition caused by de novo pathogenic variants in PURA gene and characterized by a multisystemic phenotype that includes global neurodevelopmental delay, early hypotonia, absence of speech, feeding difficulties, hypersomnolence, epilepsy and movement disorders. CASE REPORT: We report a 9-year-old girl with hypotonia and feeding difficulties with failure to thrive since the neonatal period. At the age of 3 years motor and intellectual delay were evident, she had a wide-based gait, no speech and an exaggerated acoustic startle response. She developed hand-mouthing stereotypies and epilepsy at 6 years old. The 24 hours continuous electroencephalogram monitoring revealed global slow activity and frequent epileptiform activity in left temporal and centrotemporal areas. The brain MRI revealed delayed myelination. At 6 years old the clinical exome sequencing identified a heterozygous pathogenic variant in the PURA gene, c.153delA p.(Leu54CysfsTer24). CONCLUSION: PURA syndrome has clinical features similar to other neurological disorders but the association with some clinical features, not as common in other neurological entities, like never being able to speak but being able to follow simple orders and exaggerated acoustic startle response, should raise the suspicion of PURA syndrome and genetic analysis must be performed to confirm the diagnosis and provide early multidisciplinary intervention.

TITLE: Síndrome PURA en una niña con retraso grave del desarrollo: un diagnóstico desafiante.Introducción. El síndrome PURA es una condición autosómica dominante poco común causada por variantes patogénicas de novo en el gen PURA y que se caracteriza por un fenotipo multisistémico que incluye retraso del neurodesarrollo global, hipotonía temprana, ausencia de habla, dificultades para alimentarse, hipersomnolencia, epilepsia y trastornos del movimiento. Caso clínico. Presentamos una niña de 9 años con hipotonía y dificultades para alimentarse con retraso del crecimiento desde el período neonatal. A la edad de 3 años era evidente el retraso motor e intelectual, tenía una marcha de base amplia, no hablaba y una respuesta de sobresalto acústico exagerada. Desarrolló estereotipias de mano-boca y epilepsia a los 6 años. La monitorización electroencefalográfica continua de 24 horas reveló una actividad lenta global y una actividad epileptiforme frecuente en las áreas temporal izquierda y centrotemporal. La resonancia magnética del cerebro reveló un retraso en la mielinización. A los 6 años, la secuenciación clínica del exoma identificó una variante patógena heterocigótica en el gen PURA, c.153delA p. (Leu54CysfsTer24). Conclusión. El síndrome PURA tiene características clínicas similares a otros trastornos neurológicos, pero la asociación con algunas características clínicas, no tan comunes en otras entidades neurológicas, como no poder hablar, pero poder seguir órdenes simples, y una respuesta de sobresalto acústico exagerado, deben ser factores de sospecha de síndrome PURA y servir para realizar un análisis genético para confirmar el diagnóstico y proporcionar una intervención multidisciplinar precoz.

The use of remote care during the Coronavirus disease 2019 pandemic: a perspective of Portuguese and Spanish physicians.

Summary: This study aimed to characterise how the follow-up of outpatients was done during the first months of COVID-19 pandemic by a multidisciplinary group of physicians involved in an asthma mHealth project. A cross-sectional study based on a web survey was conducted. The survey was sent to 123 physicians working at secondary care centres of Portugal and Spain, that participate in the INSPIRERS project. A total of 65 physicians completed the survey (53% response rate). They had a mean of 18 (11) years of clinical practice and 14% were residents. More than half were allergists (58%), 22% pulmonologists and 20% paediatricians. Most were working in Portugal (89%) and in public hospitals (88%). All were conducting consultations: 71% presential (median [p25 , p75] duration 30 [20, 30] min), 91% telephonic (15 [10, 20] min) and 20% video consultations (20 [10, 28] min). The median duration of presential consultations was significantly higher than pre-COVID-19 (20 [20, 30] min; p = 0.021). From the physicians conducting video consultations, 92% were allergists and only 54% considered that their institution provided adequate conditions. The physicians of the INSPIRERS group used telephonic consultations as the main alternative to presential ones and 1/5 used video consultations. These results suggest the need to rethink clinical follow-up services for outpatients in the near future increasing the use of telemedicine, especially video consultations.