Early microbial colonization is a relevant aspect in human health. Altered microbial colonization patterns have been linked to an increased risk of non-communicable diseases (NCDs). Advances in ...understanding host-microbe interactions highlight the pivotal role of maternal microbiota on infant health programming. This birth cohort is aimed to characterize the maternal microbes transferred to neonates during the first 1000 days of life, as well as to identify the potential host and environmental factors, such as gestational age, mode of delivery, maternal/infant diet, and exposure to antibiotics, which affect early microbial colonization.
MAMI is a prospective mother-infant birth cohort in the Spanish-Mediterranean area. Mothers were enrolled at the end of pregnancy and families were follow-up during the first years of life. Maternal-infant biological samples were collected at several time points from birth to 24 months of life. Clinical and anthropometric characteristics and dietary information is available. Specific qPCR and 16S rRNA gene sequencing as well as short chain fatty acid (SCFAs) profile would be obtained. Multivariable models will be used to identy associations between microbiota and clinical and anthropometric data controlling for confounders. MAMI would contribute to a better understanding of the interaction between diet, microbiota and host response in early life health programming, enabling new applications in the field of personalized nutrition and medicine.
The study is registered on the ClinicalTrial.gov platform NCT03552939. (June 12, 2018).
COVID-19 has caused more than 767 million cases and 6.94 million deaths up to June 2023 (https://covid19.who.int/), and these numbers could be significantly higher, potentially even three to four ...times the excess mortality associated with this disease 6–10. ...early during this pandemic (2020) 11–14, multiple studies began to recognize and understand that chronic consequences may occur in a significant proportion of patients 15,16, leading to various manifestations and affecting different systems and organs after the acute phase of the illness 17. According to this study, once the symptoms of prolonged COVID are established, they tend to remain stable and without much variation over time, the same can be said of those people who do not develop the condition immediately 37. According to the WHO, 10–20% of people infected by SARS-CoV-2 may go on to develop its symptoms (https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition). ...studies assessing the trajectories of the evolution of post-COVID-19 conditions in the long term are widely needed 43. Female sex, younger age, belonging to a an African-American, mixed ethnicity or another ethnic minority group, socioeconomic deprivation, smoking, high body mass index and the presence of a wide range of comorbidities were associated with increased risk of symptoms included in the WHO definition of long COVID-19, and they are statistically associated with SARS-CoV-2 infection reported 12 weeks or more after infection 48.
Purpose: To describe the microRNAs (miRNAs) involved in ocular hypertension (OHT) and open‐angle glaucoma (OAG) to develop miRNA‐based glaucoma diagnostic and therapeutic tools.
Methods: An ...analytical, observational, case–control study was performed in 42 volunteers of both sexes, aged 50 to 80 years, that were classified according to: suffering OHT (n = 20) or with the diagnosis of OAG (n = 20). All participants were interviewed for obtaining sociodemographic and personal/familial records, ophthalmologically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular‐genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. In addition, Gene information was set up from the DIANA‐TarBase v7, DIANA‐microT‐CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered.
Results: Mean age of participants was 61.1 ± 2.4 years (OHT subjects) and 64.5 ± 1.4 years (OAG patients). In this work we have investigated the delivering of intact miRNAs to target tissues by analysing the tear samples. We identified 95 miRNAs in tears of the OHT subjects and/or OAG patients. When comparing tears from both study groups, the differential expression profiling of eight miRNAs: miR‐26b‐5p, miR‐152‐3p, miR‐30 e‐5p, miR‐125b‐2‐5p, miR‐224‐5p, miR‐151a‐3p, miR‐1307‐3p, and miR‐27a‐3p was found. Also, the interaction networks of the above miRNAS were identified in HTO versus OAG.
Conclusions: We propose specific miRNAs and their target genes/signalling pathways as candidates for a better understanding of the molecular‐genetic bases of OAG.
Abstract
Objectives
To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain.
...Methods
Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids.
Results
Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid.
Conclusions
We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.
•Plasmodium berghei gametes fertilized and developed in vitro to ookinetes in a serum-free medium.•At least 75 proteins changed phosphorylation status during gametogenesis.•Phosphorylations of ...serine, threonine and tyrosine were found.•Proteins identified by mass spectrometry are involved in DNA synthesis, cytoskeleton and other processes.
Plasmodium gametogenesis within the mosquito midgut is a complex differentiation process involving signaling mediated by phosphorylation, which modulate metabolic routes and protein synthesis required to complete this development. However, the mechanisms leading to gametogenesis activation are poorly understood. We analyzed protein phosphorylation during Plasmodium berghei gametogenesis in vitro in serum-free medium using bidimensional electrophoresis (2-DE) combined with immunoblotting (IB) and antibodies specific to phosphorylated serine, threonine and tyrosine. Approximately 75 protein exhibited phosphorylation changes, of which 23 were identified by mass spectrometry. These included components of the cytoskeleton, heat shock proteins, and proteins involved in DNA synthesis and signaling pathways among others. Novel phosphorylation events support a role for these proteins during gametogenesis. The phosphorylation sites of six of the identified proteins, HSP70, WD40 repeat protein msi1, enolase, actin-1 and two isoforms of large subunit of ribonucleoside reductase were investigated using TiO2 phosphopeptides enrichment and tandem mass spectrometry. In addition, transient exposure to hydroxyurea, an inhibitor of ribonucleoside reductase, impaired male gametocytes exflagellation in a dose-dependent manner, and provides a resource for functional studies.
To describe the experience of treatment with baricitinib (BARI) and/or tocilizumab (TCZ), in monotherapy or combined, in patients admitted for interstitial pneumonia secondary to COVID19, and for 30 ...days after discharge.
Medical records of patients admitted with COVID19 and IP with PaO2/FiO2<300, treated with BARI and/or TCZ, and compared with patients who did not, were retrospectively reviewed.
Sixty patients were included; 43 (72%) are males, mean age 67 (SD: 14) years (<50 years: 17%; 51–70: 30%; >70: 53%), with 8.5 (SD: 1) days of symptoms. Sixteen (27%) patients required ICU (94% in <70 years). Fifteen (25%) patients died, 67% in >70 years; 11 (18%) patients died in the first 15 days of admission and 4 (7%) between days 16 to 30. Twenty-three (38%) patients received BARI, 12 (52%) monotherapy (Group 1), during 6 (SD: 2.6) days on average, none required ICU and 2 (17%) died. Thirty-one (52%) patients received TCZ, 20 (33%) as monotherapy (Group 2), 16 (52%) patients required ICU and 4 (20%) died. In the 11 (18%) patients who received BARI (2.8 SD: 2.5 days average) and TCZ combined (Group 3), 3 (27%) required ICU and died. There were no severe side effects in BARI or TCZ patients. In the 17 (28%) patients who received neither BARI nor TCZ (Group 4), none required ICU and 6 (35%) died. Mean (SD) PaO2/FiO2 at admission between groups was respectively: 167 (82.3), 221 (114.9), 236 (82.3), 276 (83.2).
Treatment with BARI and TCZ did not cause serious side effects. They could be considered early in patients with NI secondary to COVID19 and impaired PaO2/PaFi.
Describir la experiencia con baricitinib (BARI) y/o tocilizumab (TCZ), en monoterapia o combinados en pacientes ingresados por neumonía intersticial (NI) por COVID-19 y durante los 30 días después del alta.
Se revisaron retrospectivamente las historias clínicas de los pacientes ingresados por COVID-19 y NI, con PaO2/FiO2<300, tratados con BARI y/o TCZ y se compararon con pacientes que no los recibieron.
Se incluyeron 60 pacientes; 43 (72%) varones, edad media 67 (DE: 14) años (< 50 años: 17%; 51-70: 30%; > 70: 53%), y 8,5 (DE: 1) días de síntomas. Dieciséis (27%) ingresaron en la unidad de cuidados intensivos (UCI) (94% < 70 años). Quince (25%) fallecieron (67% > 70 años); 11 (18%) de ellos en los primeros 15 días del ingreso y cuatro (7%) entre los días 16 y 30. Veintitrés (38%) pacientes recibieron BARI, 12 (52%) en monoterapia (Grupo 1), durante seis (DE: 2.6) días de promedio, ninguno de ellos ingresó en UCI y dos (17%) fallecieron. Treinta y un (52%) pacientes recibieron una dosis de TCZ, 20 (33%) en monoterapia (Grupo 2), 16 (52%) ingresaron en UCI y cuatro (20%) fallecieron. Entre los 11 (18%) pacientes que recibieron BARI (2,8 DE: 2,5 días de promedio) y TCZ combinados (Grupo 3), tres (27%) ingresaron en UCI y fallecieron. No hubo efectos secundarios graves entre los que recibieron BARI y/o TCZ. Entre los 17 (28%) pacientes que no recibieron ni BARI ni TCZ (Grupo 4), ninguno ingresó en UCI y seis (35%) fallecieron. La PaO2/FiO2 media (DE) al ingreso entre los grupos fue respectivamente: 167 (82,3), 221 (114,9), 236 (82,3), 276 (83,2).
El tratamiento con BARI y TCZ no provocó efectos secundarios graves. Podrían considerarse precozmente en pacientes con NI secundaria a COVID-19 y deterioro de PaO2/PaFi.
Kawasaki disease is a self-limiting acute vasculitis that affects small and medium-sized vessels, and is the most common cause of acquired heart disease in children in our environment. Up to 25% of ...untreated patients develop coronary aneurysms. It is suspected that an infectious agent may be the trigger of the disease, but the causative agent is still unknown. Based on the previous evidence, recommendations are proposed for the diagnosis, treatment of acute disease, and the long-term management of these patients, in order to unify criteria. The diagnosis must be quick, based on easy-to-use algorithms and with the support of complementary tests. This document includes the indication of available imaging techniques, as well as the planning of cardiological examinations based on the initial involvement. Intravenous immunoglobulin is the basis of the initial treatment. The role of corticosteroids is still controversial, but there are studies that support its use as adjuvant treatment. A multidisciplinary working group has developed a scheme with different treatment guidelines depending on the risk factors at diagnosis, the patient's clinical situation, and response to previous treatment, including indications for thromboprophylaxis in patients with coronary involvement. The stratification of risk for long-term treatment is essential, as well as the recommendations on the procedures based on the initial cardiological involvement and its progression. Patients with coronary aneurysms require continuous and uninterrupted cardiological monitoring for life. Resumen: La enfermedad de Kawasaki es una vasculitis aguda autolimitada que afecta a vasos de pequeño y mediano calibre y es la causa más común de enfermedad cardiaca adquirida en niños en nuestro medio. Hasta un 25% de pacientes no tratados desarrollan aneurismas coronarios. Se sospecha que un agente infeccioso puede ser el desencadenante de la enfermedad, pero aún se desconoce el agente causal. En base a la evidencia previa, se proponen recomendaciones para el diagnóstico, tratamiento de la enfermedad aguda y manejo a largo plazo de estos pacientes, con el fin de unificar criterios. El diagnóstico debe ser rápido, basado en algoritmos de fácil manejo y con el apoyo de pruebas complementarias. Este documento recoge la indicación de las técnicas de imagen disponibles, así como la planificación de las revisiones cardiológicas en función de la afectación inicial. La inmunoglobulina intravenosa es la base del tratamiento inicial. El papel de los corticoides aún es controvertido, pero cada vez hay más estudios que avalan su uso como tratamiento adyuvante. Un equipo multidisciplinar ha elaborado un esquema con diferentes pautas de tratamiento en función de los factores de riesgo al diagnóstico, situación clínica del paciente y respuesta al tratamiento previo, incluyendo indicaciones sobre tromboprofilaxis en pacientes con afectación coronaria. La estratificación del riesgo para el tratamiento a largo plazo es esencial, así como las recomendaciones acerca del proceder en función de la afectación cardiológica inicial y su evolución. Los pacientes con aneurismas coronarios requieren un seguimiento cardiológico continuo e ininterrumpido de por vida.
Kawasaki disease is a self-limiting acute vasculitis that affects small and medium-sized vessels, and is the most common cause of acquired heart disease in children in our environment. Up to 25% of ...untreated patients develop coronary aneurysms. It is suspected that an infectious agent may be the trigger of the disease, but the causative agent is still unknown. Based on the previous evidence, recommendations are proposed for the diagnosis, treatment of acute disease, and the long-term management of these patients, in order to unify criteria. The diagnosis must be quick, based on easy-to-use algorithms and with the support of complementary tests. This document includes the indication of available imaging techniques, as well as the planning of cardiological examinations based on the initial involvement. Intravenous immunoglobulin is the basis of the initial treatment. The role of corticosteroids is still controversial, but there are studies that support its use as adjuvant treatment. A multidisciplinary working group has developed a scheme with different treatment guidelines depending on the risk factors at diagnosis, the patient's clinical situation, and response to previous treatment, including indications for thromboprophylaxis in patients with coronary involvement. The stratification of risk for long-term treatment is essential, as well as the recommendations on the procedures based on the initial cardiological involvement and its progression. Patients with coronary aneurysms require continuous and uninterrupted cardiological monitoring for life.
La enfermedad de Kawasaki es una vasculitis aguda autolimitada que afecta a vasos de pequeño y mediano calibre y es la causa más común de enfermedad cardiaca adquirida en niños en nuestro medio. Hasta un 25% de pacientes no tratados desarrollan aneurismas coronarios. Se sospecha que un agente infeccioso puede ser el desencadenante de la enfermedad, pero aún se desconoce el agente causal. En base a la evidencia previa, se proponen recomendaciones para el diagnóstico, tratamiento de la enfermedad aguda y manejo a largo plazo de estos pacientes, con el fin de unificar criterios. El diagnóstico debe ser rápido, basado en algoritmos de fácil manejo y con el apoyo de pruebas complementarias. Este documento recoge la indicación de las técnicas de imagen disponibles, así como la planificación de las revisiones cardiológicas en función de la afectación inicial. La inmunoglobulina intravenosa es la base del tratamiento inicial. El papel de los corticoides aún es controvertido, pero cada vez hay más estudios que avalan su uso como tratamiento adyuvante. Un equipo multidisciplinar ha elaborado un esquema con diferentes pautas de tratamiento en función de los factores de riesgo al diagnóstico, situación clínica del paciente y respuesta al tratamiento previo, incluyendo indicaciones sobre tromboprofilaxis en pacientes con afectación coronaria. La estratificación del riesgo para el tratamiento a largo plazo es esencial, así como las recomendaciones acerca del proceder en función de la afectación cardiológica inicial y su evolución. Los pacientes con aneurismas coronarios requieren un seguimiento cardiológico continuo e ininterrumpido de por vida.
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