Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans

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Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial

No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.The authors thank Gerard Carot-Sans, PhD, for providing medical writing support during the revisions of the subsequent drafts of the manuscript; the personnel from the Fights Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management; Eric Ubals (Pierce AB) and Òscar Palao (Opentic) for website and database management; Óscar Camps and OpenArms nongovernmental organization for nursing home operations; and Anna Valentí and the Hospital Germans Trias i Pujol Human Resources Department for telephone monitoring. We thank Consorci Sanitari del Maresme, Centre Sociosanitari El Carme, l'Hospital General de Granollers and occupational hazards department of Hospital Germans Trias i Pujol for their contribution with patient enrollment. We are very grateful to Marc Clotet and Natalia Sánchez who coordinated the JoEmCorono crowd-funding campaign. We thank the Hospital Germans Trias Pujol Institutional Review Board and the Spanish Agency of Medicines and Medical Devices for their prompt action for consideration and approvals to the protocol. Financial support. This work was mainly supported by the crowd-funding campaign JoEmCorono (https://www.yomecorono.com/) with contributions from more than 72 000 citizens and corporations. The study also received financial support from Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®). Foundation Dorneur partly funded lab equipment at Irsi-Caixa.Peer reviewe

The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa.

There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa

Avaliação das funções executivas em idosos acometidos por doenças crónico-degenerativas

Los avances en las condiciones de salud ha facilitado el aumento de la longevidad y por lo tanto una mayor esperanza de vida. Esta investigación se realizó con el objetivo de verificar la existencia de déficits en el desempeño de las funciones ejecutivas en pacientes ancianos con enfermedades crónicas a través de la prueba de clasificación de tarjetas de Wisconsin e investigar patologías asociadas (depresión y ansiedad) y sus implicaciones en la vida en los ancianos. Se estudiaron 30 ancianos hombres y mujeres, mayores de 60 años, diagnosticados con enfermedades crónicas degenerativas (Diabetes Mellitus y la hipertensión). El diseño fue un estudio cuantitativo y transversal, con los instrumentos: hoja de datos socio-demográficos, prueba Wisconsin Card (WCST), inventario de depresión de Beck (BDI-I), inventario de ansiedad de Beck (BAI) y la escala de depresión geriátrica (GDS). Los res uItad os in dican que los ancia nos ha n mostrad o dificultades en la realización de las tareas como descriptores de la WCST. En correlaciones altamente significativas entre la puntuación total de la GDS BAI (r = 0.667, P < 0,001), lo que significa que, en la medida en que los síntomas de ansiedad aumentan también aumenta los síntomas depresivos

Avaliação das funções executivas em idosos acometidos por doenças crônico-degenerativas

The advancement of health conditions has facilitated the increase in longevity and therefore a longer life expectancy. This research was conducted with the objective of verifying the existence of deficits in the performance of executive functions in elderly patients with chronic diseases through the Test Wisconsin Card Sorting, and to investigate associated pathologies (depression and anxiety) and their implications in the life the elderly. We studied 30 elderly men and women, aged over 60 years, diagnosed with (Diabetes Mellitus and Hypertension). The design was a quantitative and transversal study, with the instruments: socio-demographic data sheet, Test Wisconsin Card Sorting (WCST), Beck Depression Inventory (BDI-I), Beck Anxiety Inventory (BAI) and Depression Scale geriatric (GDS). The results indicate that the elderly have shown difficulties in performing the tasks as descriptors of the WCST. It is highly significant correlations between the total score of the GDS BAI (r = 0.667, p <0.001), which means that, inasmuch as the symptoms of anxiety increase also increases depressive symptoms.O avanço das condições de saúde vem propiciando o aumento da longevidade e conseqüentemente uma expectativa de vida maior. Esta pesquisa foi elaborada com o objetivo de verificar a existência de déficit no desempenho das Funções Executivas em idosos acometidos com doenças crônico-degenerativas através do Teste Wisconsin de Classificação de Cartas, bem como investigar patologias associadas (depressão e ansiedade) e suas implicações na vida dos idosos. Participaram do estudo 30 idosos de ambos os sexos, com idade igual ou superior a 60 anos, diagnosticados com doenças crônico-degenerativas (Diabetes Mellitus e Hipertensão Arterial). O delineamento foi de um estudo quantitativo e transversal, tendo como instrumentos: Ficha de Dados Sociodemográficos, Teste Wisconsin de Classificação de Cartas (WCST), Inventário de Depressão de Beck (BDI-I), Inventário de Ansiedade de Beck (BAI) e Escala de Depressão Geriátrica (GDS). Os resultados apontam que os idosos demonstraram dificuldades no desempenho das tarefas conforme descritores do WCST. Verifica-se correlações altamente significativas entre o total do escore do BAI com o GDS (r=0,667, p<0,001), o que significa que, na medida em que os sintomas de ansiedade aumentam, aumenta também os sintomas depressivos.Los avances en las condiciones de salud ha facilitado el aumento de la longevidad y por lo tanto una mayor esperanza de vida. Esta investigación se realizó con el objetivo de verificar la existencia de déficits en el desempeño de las funciones ejecutivas en pacientes ancianos con enfermedades crónicas a través de la prueba de clasificación de tarjetas de Wisconsin e investigar patologías asociadas (depresión y ansiedad) y sus implicaciones en la vida en los ancianos. Se estudiaron 30 ancianos hombres y mujeres, mayores de 60 años, diagnosticados con enfermedades crónicas degenerativas (Diabetes Mellitus y la hipertensión). El diseño fue un estudio cuantitativo y transversal, con los instrumentos: hoja de datos socio-demográficos, prueba Wisconsin Card (WCST), inventario de depresión de Beck (BDI-I), inventario de ansiedad de Beck (BAI) y la escala de depresión geriátrica (GDS). Los resultados indican que los ancianos han mostrado dificultades en la realización de las tareas como descriptores de la WCST. En correlaciones altamente significativas entre la puntuación total de la GDS BAI (r = 0.667, p < 0,001), lo que significa que, en la medida en que los síntomas de ansiedad aumentan también aumenta los síntomas depresivos

Global Roles of Ssn6 in Tup1- and Nrg1-dependent Gene Regulation in the Fungal Pathogen, Candida albicans

In budding yeast, Tup1 and Ssn6/Cyc8 form a corepressor that regulates a large number of genes. This Tup1-Ssn6 corepressor appears to be conserved from yeast to man. In the pathogenic fungus Candida albicans, Tup1 regulates cellular morphogenesis, phenotypic switching, and metabolism, but the role of Ssn6 remains unclear. We show that there are clear differences in the morphological and invasive phenotypes of C. albicans ssn6 and tup1 mutants. Unlike Tup1, Ssn6 depletion promoted morphological events reminiscent of phenotypic switching rather than filamentous growth. Transcript profiling revealed minimal overlap between the Ssn6 and Tup1 regulons. Hypha-specific genes, which are repressed by Tup1 and Nrg1, were not derepressed in ssn6 cells under the conditions studied. In contrast, the phase specific gene WH11 was derepressed in ssn6 cells, but not in tup1 or nrg1 cells. Hence Ssn6 and Tup1 play distinct roles in C. albicans. Nevertheless, both Ssn6 and Tup1 were required for the Nrg1-mediated repression of an artificial NRE promoter, and lexA-Nrg1 mediated repression in the C. albicans one-hybrid system. These observations are explained in models that are generally consistent with the Tup1-Ssn6 paradigm in budding yeast

Rectal Colonization and Nosocomial Transmission of Carbapenem-Resistant <i>Acinetobacter baumannii </i>in an Intensive Care Unit, Southwest Nigeria

BACKGROUND: Acinetobacter baumannii are of major human health importance because they cause life-threatening nosocomial infections and often are highly resistant to antimicrobials. Specific multidrug-resistant A. baumannii lineages are implicated in hospital outbreaks globally. We retrospectively investigated a suspected outbreak of carbapenem-resistant A. baumannii (CRAB) colonizing patients in an intensive care unit (ICU) of a tertiary hospital in Southwest Nigeria where genomic surveillance of Acinetobacter has hitherto not been conducted. METHODS: A prospective observational study was conducted among all patients admitted to the ICU between August 2017 and June 2018. Acinetobacter species were isolated from rectal swabs and verified phenotypically with the Biomerieux Vitek 2 system. Whole genome sequencing (WGS) was performed on the Illumina platform to characterize isolates from a suspected outbreak during the study period. Phylogenetic analysis, multilocus sequence typing, and antimicrobial resistance gene prediction were carried out in silico. RESULTS: Acinetobacter isolates belonging to the A. baumannii complex were recovered from 20 (18.5%) ICU patients. Single nucleotide polymorphism (SNP) analysis and epidemiological information revealed a putative outbreak clone comprising seven CRAB strains belonging to the globally disseminated international clone (IC) 2. These isolates had ≤2 SNP differences, identical antimicrobial resistance and virulence genes, and were all ST1114/1841. CONCLUSION: We report a carbapenem-resistant IC2 A. baumannii clone causing an outbreak in an ICU in Nigeria. The study findings underscore the need to strengthen the capacity to detect A. baumannii in human clinical samples in Nigeria and assess which interventions can effectively mitigate CRAB transmission in Nigerian hospital settings

Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread

EuSCAPE Working Group: Portugal - Manuela Caniça, Vera ManageiroPublic health interventions to control the current epidemic of carbapenem-resistant Klebsiella pneumoniae rely on a comprehensive understanding of its emergence and spread over a wide range of geographical scales. We analysed the genome sequences and epidemiological data of >1,700 K. pneumoniae samples isolated from patients in 244 hospitals in 32 countries during the European Survey of Carbapenemase-Producing Enterobacteriaceae. We demonstrate that carbapenemase acquisition is the main cause of carbapenem resistance and that it occurred across diverse phylogenetic backgrounds. However, 477 of 682 (69.9%) carbapenemase-positive isolates are concentrated in four clonal lineages, sequence types 11, 15, 101, 258/512 and their derivatives. Combined analysis of the genetic and geographic distances between isolates with different β-lactam resistance determinants suggests that the propensity of K. pneumoniae to spread in hospital environments correlates with the degree of resistance and that carbapenemase-positive isolates have the highest transmissibility. Indeed, we found that over half of the hospitals that contributed carbapenemase-positive isolates probably experienced within-hospital transmission, and interhospital spread is far more frequent within, rather than between, countries. Finally, we propose a value of 21 for the number of single nucleotide polymorphisms that optimizes the discrimination of hospital clusters and detail the international spread of the successful epidemic lineage, ST258/512.This work was funded by The Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Wellcome (grant nos. 098051 and 099202) and the NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance (NIHR 16/136/111). The EuSCAPE project was funded by ECDC through a specific framework contract (ECDC/2012/055) following an open call for tender (OJ/25/04/2012-PROC/2012/036).info:eu-repo/semantics/publishedVersio

Hydroxychloroquine Alone or in Combination with Cobicistat-Boosted Darunavir for Treatment of Mild COVID-19: A Cluster-Randomized Clinical Trial

Background: No therapeutics have yet been proven effective for the treatment of mild-illness caused by SARS-CoV-2. We assessed the efficacy and safety of hydroxychloroquine (HCQ) alone or in combination with cobicistat-boosted darunavir (DRVc) for treating patients with mild Covid-19. Methods: We conducted a randomized, prospective, controlled, open-label trial in three health regions of Catalonia. After confirmation of a case of Covid-19 disease, we enumerated on a list a ring of the case and all their contacts and randomly assigned the ring to either control or intervention arm on a 1:1 ratio. Here we present the methods concerning eligible index cases, which involved non-hospitalized adult patients with recently confirmed SARS-CoV-2 infection and less than seven days of symptoms. Patients were assigned to receive HCQ (800 mg on day 1, followed by 400 mg once daily for six days) in combination with DRVc (800 mg/150 mg tablets, once daily for seven days) or no antiviral treatment. The protocol was adapted during the course of the trial to use HCQ alone after findings of no benefit of the protease inhibitor lopinavir-ritonavir. Study outcomes were the reduction of viral RNA load in nasopharyngeal swabs and time to clinical improvement within 28 days of follow-up in the per-protocol population. Adverse events were assessed up to 28 days. Findings: Between Mar 17 and Apr 28, 2020, 353 Covid-19 patients met the criteria for the per-protocol analysis: 165 in the control arm and 142 in the intervention arm. The median time from symptom onset to treatment start was 3 days (IQR 2–4). The per-protocol analysis revealed no significant differences in the mean reduction of viral load in nasopharyngeal swabs at day-3 compared to baseline between the control group (-1·28 Log 10 copies/mL, SD 1·68) and the intervention group (-1·47, SD 1·50); difference -0·18 [95% CI -0.59 to 0·22]. The same pattern was observed at day-7 and -14 after treatment. Time to complete alleviation of symptoms was similar in both groups (22 vs. 20·5 days, p = 0·37). Adverse events included self-limited nausea and diarrhea. Twenty patients required hospitalization, all due to Covid-19 progression. No patients died during the study. Interpretation: In patients with mild Covid-19, no benefit was observed with HCQ alone or in combination with DRVc beyond the usual care. Future testing of other agents in randomized trials may help to identify other drugs that provide a treatment benefit.Crowdfunding campaign YoMeCorono (https://www.yomecorono.com/), Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®).N