Concise Three Step Synthesis of the Bioactive Alkaloid Huajiaosimuline via a Zn(OTf)-Promoted Meinwald Rearrangement.

The synthesis of the biologically active alkaloid huajiaosimulne, isolated from the roots of Zanthoxylum simulans, is reported. The natural product was assembled from simple commercial reagents via initial domino Knoevenagel/oxa-6π-electrocyclization followed by epoxidation and an epoxide/ketone rearrangement promoted by Zn(OTf). In vitro cytotoxicity assays identified natural products huajiaosimuline and simulansine as moderate antiproliferative agents against murine colon cancer CT26 cells.

Fungal microbiota dynamics and its geographic, age and gender variability in patients with cystic fibrosis.

Objectives: In cystic fibrosis (CF), there is a predisposition to bronchial colonization by potentially pathogenic microorganisms, such as fungi. Our aims were to describe the dynamics of respiratory mycobiota in patients with CF and to evaluate the geographic, age and gender variability in its distribution.

Methods: Cohort study in which 45 patients with CF from four hospitals in three Spanish cities were followed up during a 1-year period, obtaining spontaneous sputum samples every 3 to 6 months.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.

Multilocus Genotyping of from Deceased Cuban AIDS Patients Using Formalin-Fixed and Paraffin-Embedded Tissues.

The results of the genotypic characterization of are described in lung tissue samples from 41 Cubans who died of AIDS with pneumocystosis between 1995 and 2008. Histological sections of the lung preserved as formalin-fixed and paraffin-embedded tissue were examined. PCR amplification and nucleotide sequencing of the two mitochondrial genes (large and small) of the pathogen allowed verification of a predominance of genotype 3 (85T/248C) of the large mitochondrial gene and genotype 3 (160A/196T) of the small mitochondrial gene over a period of 14 years (1995-2008).

Update on Dihydropteroate Synthase (DHPS) Mutations in .

A is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms.

Pneumocystis jirovecii among patients with cystic fibrosis and their household members.

Unlabelled: We conducted a pilot study of patients with cystic fibrosis (CF) to assess intra-family transmission of P. jirovecii and compare it with data on other prevalent pathogens such as P. aeruginosa and S.

Genetic Polymorphisms of Superoxide Dismutase Locus of in Spanish Population.

pneumonia remains a major opportunistic infection in immunocompromised patients worldwide. Colonization with has recently gained attention as an important issue for understanding the complete cycle of human infection. Superoxide Dismutase (SOD) gene could be a molecular target with high clinical relevance, but the epidemiological information about SOD genotypes distribution is scarce.

Changing Trends in the Epidemiology and Risk Factors of Pneumonia in Spain.

The information about the epidemiology of pneumonia (PcP) in Europe is scarce, and in Spain there are only data nationwide on patients with HIV infection. This study has been carried out with the aim of knowing in our country the current epidemiological spectrum and the risk factors of PcP. Observational, descriptive transversal study that included all patients admitted in Spain with diagnosis upon discharge of PcP registered in the National Health System's Hospital Discharge Records Database of Spain, between 2008 and 2012.

Airborne acquisition of Pneumocystis in bronchoscopy units: a hidden danger to healthcare workers.

The possible presence of Pneumocystis in a bronchoscopy unit of a tertiary-hospital was examined by detecting Pneumocystis-specific DNA by polymerase chain reaction in prospectively obtained samples of oropharyngeal wash from seven healthcare workers (HCWs) and air from three areas of the unit at different time points (baseline, days +15,+30,+60,+90 after initiation of the study). Positive samples were genotyped at two genetic loci: the mitochondrial large subunit ribosomal RNA (mtLSUrRNA) fragment by direct sequencing and the gene for dihydropteroate synthase (DHPS) by restriction fragment-length polymorphism. Pneumocystis DNA was identified in 13/24 samples from HCWs, in 4/14 air samples and also in two patients with Pneumocystis pneumonia (PcP) and another with a Pneumocystis-associated disease subjected to bronchoscopy on days +15 and +60 after initiation of the study.

Pneumocystis jirovecii infection in patients with acute interstitial pneumonia.

Objective: Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP.

Early Acquisition of Pneumocystis jirovecii Colonization and Potential Association With Respiratory Distress Syndrome in Preterm Newborn Infants.

Background: Pneumocystis pneumonia is a well-recognized lung disease of premature and malnourished babies. Even though serologic studies have shown that children are exposed to Pneumocystis jirovecii early in life, the epidemiology of human P. jirovecii infection and the host-microorganism relationship in infancy remain poorly understood.

High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia.

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children.

High prevalence of Pneumocystis jirovecii colonization among HIV-positive patients in southern Brazil.

A high prevalence of Pneumocystis jirovecii colonization was observed in patients positive for the human immunodeficiency virus (HIV) admitted to a tertiary hospital in southern Brazil between August 2012 and December 2012. Amplification of the mitochondrial large subunit ribosomal RNA gene in oropharyngeal samples through nested polymerase chain reaction identified P. jirovecii colonization in 26 of 58 (44.

High prevalence of Pneumocystis jirovecii colonization in Brazilian cystic fibrosis patients.

A high rate of Pneumocystis jirovecii colonization was observed in Brazilian cystic fibrosis (CF) patients (13 out of 34; 38.2%) who underwent bronchoscopy between March 2006 and August 2009 at the Hospital de Clinicas de Porto Alegre, Brazil. Bronchoalveolar lavage samples were collected from these patients and studied by nested PCR amplification of the mitochondrial gene coding for the large subunit ribosomal RNA (mtLSUrDNA).

Low genetic diversity of Pneumocystis jirovecii among Cuban population based on two-locus mitochondrial typing.

Genotypes of two different loci of the Pneumocystis jirovecii mitochondrial gene were studied in specimens from a total of 75 Pneumocystis pneumonia patients in Spain, France and Cuba. A new genotype of the mitochondrial small subunit rRNA gene of P. jirovecii (160A/196T) was identified, which was revealed to be the most common in these three countries, especially in Cuba where its proportion reached 93.

Pneumocystis jirovecii colonization in patients treated with infliximab.

Background: Infliximab, a chimeric antitumour necrosis factor (TNF) monoclonal antibody, has become an established effective therapy for inflammatory rheumatic disease. However, TNF is a critical factor in host defence, and the suppression of its biological activity may be associated with the increased risk of opportunistic infections. The frequent use of infliximab in clinical practice has identified Pneumocystis jirovecii pneumonia (PcP) as a serious complication.

Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized individuals and Pneumocystis pneumonia patients from Spain.

Cotrimoxazole, an association of trimethoprim and sulfamethoxazole, and dapsone, are mainstays for the prophylaxis and treatment of Pneumocystis pneumonia (PcP). The inability to culture Pneumocystis prevents routine susceptibility testing and detection of drug resistance. Instead, molecular techniques have been used to detect Pneumocystis jiroveci dihydropteroate synthase (DHPS) mutations that cause sulfa resistance in other microorganisms.

Pneumocystis jirovecii and cystic fibrosis.

Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and worldwide distribution that causes pneumonia in immunosuppressed individuals. The development of sensitive molecular techniques has led to the recognition of a colonization or carrier state of P. jirovecii, in which low levels of the organism are detected in persons who do not have pneumonia.

Metagenomic analysis of bronchoalveolar lavage samples from patients with idiopathic interstitial pneumonia and its antagonic relation with Pneumocystis jirovecii colonization.

Idiopathic interstitial pneumonias are interstitial lung diseases of unknown etiology which prognosis is usually fatal. Microbiota associated to bronchoalveolar lavage from 20 patients with negative bacterial cultures was explored by 16S-rDNA PCR-DGGE, showing a clearly negative relation among the presence of P. jirovecii and bacterial colonization.

Geographical variation in serological responses to recombinant Pneumocystis jirovecii major surface glycoprotein antigens.

The use of recombinant fragments of the major surface glycoprotein (Msg) of Pneumocystis jirovecii has proven useful for studying serological immune responses of blood donors and human immunodeficiency virus (HIV)-positive (HIV(+)) patients. Here, we have used ELISA to measure antibody titres to Msg fragments (MsgA, MsgB, MsgC1, MsgC3, MsgC8 and MsgC9) in sera isolated in the USA (n=200) and Spain (n=326), to determine whether geographical location affects serological responses to these antigens. Blood donors from Seville exhibited a significantly greater antibody titre to MsgC8, and significantly lower responses to MsgC3 and MsgC9, than did Cincinnati (USA) donors.