ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.

Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection. Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed. Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency. Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity.

Stereoselective α-Deuteration of Serine, Cysteine, Selenocysteine, and 2,3-Diaminopropanoic Acid Derivatives.

Efficient methodologies for synthesizing enantiopure α-deuterated derivatives of serine, cysteine, selenocysteine, and 2,3-diaminopropanoic acid have been developed. H/D exchange was achieved by deprotonation of a chiral bicyclic serine equivalent followed by selective deuteration. Additionally, diastereoselective additions of thiols, selenols, and amines to a chiral bicyclic dehydroalanine in deuterated alcohols allowed site-selective deuteration at the Cα atom of cysteine, selenocysteine, and 2,3-diaminopropanoic acid derivatives. A deuterated analogue of carbocysteine, a drug for the treatment of bronchiectasis, was synthesized.

[Translated article] Spanish Asthma Management Guidelines (GEMA) v.5.1. Highlights and Controversies.

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FENO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis.

Spanish Asthma Management Guidelines (GEMA) VERSION 5.1. Highlights and Controversies. / Guía española para el manejo del asma (GEMA) versión 5.1. Aspectos destacados y controversias.

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FENO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis.

Respuesta ecológica multitaxón a la pérdida de hábitat y fragmentación del paisaje en la Amazonía occidental reveladas por evaluaciones de biodiversidad RAPELD / Multi-taxa ecological responses to habitat loss and fragmentation in western Amazonia as revealed by RAPELD biodiversity surveys

La pérdida y fragmentación del hábitat causada por la deforestación es un importante impulsor antropogénico de cambios sobre la biodiversidad en la selva amazónica. Sin embargo, la magnitud y dirección de los efectos sobre la composición y distribución de las especies aún es incomprendida. Evaluamos las respuestas de cuatro grupos taxonómicos - aves, anfibios, abejas de orquídeas y escarabajos peloteros - a la pérdida y fragmentación del hábitat, tanto a nivel de especies como de ensamblaje, en la Amazonía norte ecuatoriana. Tomamos muestras de quince parcelas de 250 m de largo en remanentes de bosque de tierra firme. Calculamos un índice de fragmentación del paisaje (fragindex), que considera la cobertura forestal continua, densidad del borde y el aislamiento en el paisaje, y nueve métricas de configuración del paisaje para analizar las respuestas de especies y ensamblajes. Más del 80% de las especies de aves, anfibios o abejas de orquídeas y el 60% de los escarabajos peloteros se vieron afectados negativamente por la pérdida y fragmentación del hábitat. La composición por especies se vio significativamente afectada por las diferencias en la cobertura forestal y la conectividad, mientras que la forma y el área de los parches de bosque determinaron la magnitud y la dirección del efecto en las respuestas de las especies. Por lo tanto, los cambios en la configuración del paisaje de la Amazonía ecuatoriana deben minimizarse para disminuir los efectos de la pérdida y fragmentación del hábitat sobre la presencia de especies y la composición de los ensambles. (AU)

Impact of Pseudomonas aeruginosa Infection on Patients with Chronic Inflammatory Airway Diseases.

Pseudomonas aeruginosa (P. aeruginosa) is a ubiquitous and opportunistic microorganism and is considered one of the most significant pathogens that produce chronic colonization and infection of the lower respiratory tract, especially in people with chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis. From a microbiological viewpoint, the presence and persistence of P. aeruginosa over time are characterized by adaptation within the host that precludes any rapid, devastating injury to the host. Moreover, this microorganism usually develops antibiotic resistance, which is accelerated in chronic infections especially in those situations where the frequent use of antimicrobials facilitates the selection of "hypermutator P. aeruginosa strain". This phenomenon has been observed in people with bronchiectasis, CF, and the "exacerbator" COPD phenotype. From a clinical point of view, a chronic bronchial infection of P. aeruginosa has been related to more severity and poor prognosis in people with CF, bronchiectasis, and probably in COPD, but little is known on the effect of this microorganism infection in people with asthma. The relationship between the impact and treatment of P. aeruginosa infection in people with airway diseases emerges as an important future challenge and it is the most important objective of this review.

Bronchiectasis: A Complex, Heterogeneous Disease. / Las bronquiectasias: una enfermedad compleja y heterogénea.

Most areas of respiratory medicine continue to use an Oslerian approach, based on signs and symptoms, in which the disease is the center of all activity. However, this paradigm is changing. Now that lung diseases have been recognized as heterogeneous and complex, we are moving towards more personalized, precise, patient-oriented medicine. The aim of this review was to define the current state of the knowledge on bronchiectasis, or, more accurately, the bronchiectasis syndrome, as a multidimensional, systemic, heterogeneous, complex disease. We explore the advances that have already been made, and above all the many steps that are still to be taken. We also propose some tools which might facilitate the application of these concepts in clinical practice, and help us continue our journey towards a more holistic view of this disease.

Spanish Guidelines on the Evaluation and Diagnosis of Bronchiectasis in Adults. / Normativa sobre la valoración y el diagnóstico de las bronquiectasias en el adulto.

In 2008, the Spanish Society of Pulmonology (SEPAR) published the first guidelines in the world on the diagnosis and treatment of bronchiectasis. Almost 10 years later, considerable scientific advances have been made in both the treatment and the evaluation and diagnosis of this disease, and the original guidelines have been updated to include the latest scientific knowledge on bronchiectasis. These new recommendations have been drafted following a strict methodological process designed to ensure the quality of content, and are linked to a large amount of online information that includes a wealth of references. These guidelines cover aspects ranging from a consensual definition of bronchiectasis to an evaluation of the natural course and prognosis of the disease. The topics of greatest interest and some new areas are addressed, including epidemiology and economic costs of bronchiectasis, pathophysiological aspects, the causes (placing particular emphasis on the relationship with other airway diseases such as chronic obstructive pulmonary disease and asthma), clinical and functional aspects, measurement of quality of life, radiological diagnosis and assessment, diagnostic algorithms, microbiological aspects (including the definition of key concepts, such as bacterial eradication or chronic bronchial infection), and the evaluation of severity and disease prognosis using recently published multidimensional tools.

Spanish Guidelines on Treatment of Bronchiectasis in Adults. / Normativa sobre el tratamiento de las bronquiectasias en el adulto.

In 2008, the Spanish Society of Pulmonology (SEPAR) published the first guidelines in the world on the diagnosis and treatment of bronchiectasis. Almost 10 years later, considerable scientific advances have been made in both the treatment and the evaluation and diagnosis of this disease, and the original guidelines have been updated to include the latest therapies available for bronchiectasis. These new recommendations have been drafted following a strict methodological process designed to ensure quality of content, and are linked to a large amount of online information that includes a wealth of references. The guidelines are focused on the treatment of bronchiectasis from both a multidisciplinary perspective, including specialty areas and the different healthcare levels involved, and a multidimensional perspective, including a comprehensive overview of the specific aspects of the disease. A series of recommendations have been drawn up, based on an in-depth review of the evidence for treatment of the underlying etiology, the bronchial infection in its different forms of presentation using existing therapies, bronchial inflammation, and airflow obstruction. Nutritional aspects, management of secretions, muscle training, management of complications and comorbidities, infection prophylaxis, patient education, home care, surgery, exacerbations, and patient follow-up are addressed.

Two New Species of Sucking Lice (Phthiraptera: Anoplura: Polyplacidae) From Endangered, Hibernating Lemurs (Primates: Cheirogaleidae).

Lemurpediculus robbinsi sp. nov. is described from Crossley's dwarf lemur, Cheirogaleus crossleyi A. Grandidier, and Lemurpediculus claytoni sp. nov. is described from Sibree's dwarf lemur, Cheirogaleus sibreei Forsyth Major, from Madagascar. Both sexes of each new louse species are illustrated and distinguished from the two previously known species of Lemurpediculus: L. verruculosus (Ward) and L. petterorum Paulian. With the addition of two new species to the genus, an amended description of Lemurpediculus is provided. The two hosts of the new louse species are morphologically similar, endangered, obligately hibernating lemurs. These two species of lemurs are sometimes sympatric in rainforests in eastern Madagascar. Despite the morphological similarity of the two host species, their lice are morphologically distinct and are easiest to identify based on the shape of the subgenital plate of the female and the shape of the genitalia in the male. Both new species of lice should be considered to be endangered because their hosts are endangered. It is not known if either of the new species of lice are vectors of pathogens or parasites to their hosts.

Species discovery and validation in a cryptic radiation of endangered primates: coalescent-based species delimitation in Madagascar's mouse lemurs.

Implementation of the coalescent model in a Bayesian framework is an emerging strength in genetically based species delimitation studies. By providing an objective measure of species diagnosis, these methods represent a quantitative enhancement to the analysis of multilocus data, and complement more traditional methods based on phenotypic and ecological characteristics. Recognized as two species 20 years ago, mouse lemurs (genus Microcebus) now comprise more than 20 species, largely diagnosed from mtDNA sequence data. With each new species description, enthusiasm has been tempered with scientific scepticism. Here, we present a statistically justified and unbiased Bayesian approach towards mouse lemur species delimitation. We perform validation tests using multilocus sequence data and two methodologies: (i) reverse-jump Markov chain Monte Carlo sampling to assess the likelihood of different models defined a priori by a guide tree, and (ii) a Bayes factor delimitation test that compares different species-tree models without a guide tree. We assess the sensitivity of these methods using randomized individual assignments, which has been used in bpp studies, but not with Bayes factor delimitation tests. Our results validate previously diagnosed taxa, as well as new species hypotheses, resulting in support for three new mouse lemur species. As the challenge of multiple researchers using differing criteria to describe diversity is not unique to Microcebus, the methods used here have significant potential for clarifying diversity in other taxonomic groups. We echo previous studies in advocating that multiple lines of evidence, including use of the coalescent model, should be trusted to delimit new species.

[Three cases of primary pulmonary plasmacytoma]. / Plasmocitoma pulmonar primario: aportación de 3 casos.

Extramedullary plasmacytoma is a plasma cell malignancy that most commonly occurs in the upper respiratory tract. Plasmocytoma located in the lung is an unusual finding, and in such cases the disease may be confined to the lung and regional lymph nodes or may be disseminated. When only located in the lower respiratory tract (primary pulmonary plasmacytoma), diagnosis is difficult and is usually based on the excised tissue. We present 3 cases, 2 of which were particularly unusual in that diagnosis was confirmed by bronchial biopsy. Other important findings included the detection of paraprotein in the blood and urine of 2 of the patients, and follow-ups over 10 and 15 years without recurrence of the disease in 2 of the cases.

Assessing reproductive profiles in female brown mouse lemurs (Microcebus rufus) from Ranomafana National Park, southeast Madagascar, using fecal hormone analysis.

Studies on reproductive endocrinology in wild primate populations have greatly increased in the last decades owing to the development of noninvasive techniques that can be applied under field conditions. However, small-bodied nocturnal species are not well represented on the long list of primates surveyed in the wild, and reproductive inferences regarding these animals in their natural habitats have not benefited from direct observations of hormonal changes. We collected fecal samples from female brown mouse lemurs (Microcebus rufus) in a southeastern rainforest of Madagascar in order to determine whether or not fecally excreted steroid levels show a consistent pattern of change during the reproductive season and are a useful complement to reproductive observations in wild-trapped individuals. Initial data show variation in reproductive hormone levels before and after estrus and estimated day of parturition. Elevated levels of excreted estradiol (E(2)) were observed around the time of estrus, whereas high levels of fecal progesterone (P) were seen during later stages of pregnancy and around parturition. A more complete picture of reproductive profiles in female mouse lemurs, and how they may change over the life span, can be obtained if hormone analyses are used to supplement field observations.

Estudio comparativo de crecimiento y desarrollo del recien nacido pretérmino y de bajo peso, manejado por dos métodos: Ambulatorio y Tradicional / Comparative study of growth and development of the newborns preterm and of low weigh, by two methods: Ambulatory and Traditional

Del estudio realizado se obtuvieron las siguientes conclusiones: 1. Durante el año en estudio, junio 1987 a junio 1988 nacieron 861 niños de los cuales 107, fueron a pretérmino y de bajo peso; entre los cuales se tomó en cuenta a 60 niños para el presente estudio. Estos niños representan el 56 por ciento de los 107 y el 77 por ciento de los 78 nacidos vivos. Tomando 30 niños para el método tradicional y 30 niños para el método ambulatorio, entre los cuales se tuvo una mortalidad del 5 por ciento (3 niños) de los 60 en estudio. 2. La inestabilidad civil que de una u otra forma tiene una influencia tanto psicológica como económica, predispone a la madre a embarazo de alto riesgo y a un parto pretérmino. Así lo demuestra el presente estudio ya que 40 (66.7 por ciento) de las 60 madres presentaban una inestabilidad civil, de las cuales 30 (50 por ciento) eran madres solteras, 15 en el ambulatorio y otras 15 en el tradicional. 3. El nivel socioeconómico de las madres muestra un predominio en ambos métodos de la condición de regulares ingresos económicos