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1.
Cell ; 184(19): 4939-4952.e15, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34508652

RESUMO

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.


Assuntos
COVID-19/epidemiologia , Epidemias , SARS-CoV-2/fisiologia , COVID-19/transmissão , Bases de Dados como Assunto , Surtos de Doenças , Humanos , Louisiana/epidemiologia , Filogenia , Fatores de Risco , SARS-CoV-2/classificação , Texas , Viagem , Estados Unidos/epidemiologia
2.
Clin Infect Dis ; 78(6): 1462-1472, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305378

RESUMO

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. RESULTS: Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. CONCLUSIONS: Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.


Assuntos
Antibacterianos , Clostridioides difficile , Infecções por Clostridium , Microbioma Gastrointestinal , Vancomicina , Humanos , Vancomicina/uso terapêutico , Vancomicina/efeitos adversos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Idoso , Clostridioides difficile/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Adulto , Resultado do Tratamento , Metaboloma/efeitos dos fármacos , Oxidiazóis/uso terapêutico , Oxidiazóis/efeitos adversos , Disbiose/induzido quimicamente , Benzimidazóis , Piridinas
3.
Clin Infect Dis ; 78(2): 248-258, 2024 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-37738153

RESUMO

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Acinetobacter baumannii/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Estudos Prospectivos , Testes de Sensibilidade Microbiana , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , beta-Lactamases/genética , Proteínas de Bactérias/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
4.
N Engl J Med ; 384(1): 20-30, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33332779

RESUMO

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Adulto , Idoso , COVID-19/etnologia , COVID-19/mortalidade , Progressão da Doença , Feminino , Hospitalização , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Taxa de Sobrevida
5.
J Neuroinflammation ; 21(1): 54, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383421

RESUMO

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by the aggregation of α-Synuclein (αSYN) building up intraneuronal inclusions termed Lewy pathology. Mounting evidence suggests that neuron-released αSYN aggregates could be central to microglial activation, which in turn mounts and orchestrates neuroinflammatory processes potentially harmful to neurons. Therefore, understanding the mechanisms that drive microglial cell activation, polarization and function in PD might have important therapeutic implications. Here, using primary microglia, we investigated the inflammatory potential of pure αSYN fibrils derived from PD patients. We further explored and characterized microglial cell responses to a chronic-type inflammatory stimulation combining PD patient-derived αSYN fibrils (FPD), Tumor necrosis factor-α (TNFα) and prostaglandin E2 (PGE2) (TPFPD). We showed that FPD hold stronger inflammatory potency than pure αSYN fibrils generated de novo. When combined with TNFα and PGE2, FPD polarizes microglia toward a particular functional phenotype departing from FPD-treated cells and featuring lower inflammatory cytokine and higher glutamate release. Whereas metabolomic studies showed that TPFPD-exposed microglia were closely related to classically activated M1 proinflammatory cells, notably with similar tricarboxylic acid cycle disruption, transcriptomic analysis revealed that TPFPD-activated microglia assume a unique molecular signature highlighting upregulation of genes involved in glutathione and iron metabolisms. In particular, TPFPD-specific upregulation of Slc7a11 (which encodes the cystine-glutamate antiporter xCT) was consistent with the increased glutamate response and cytotoxic activity of these cells toward midbrain dopaminergic neurons in vitro. Together, these data further extend the structure-pathological relationship of αSYN fibrillar polymorphs to their innate immune properties and demonstrate that PD-derived αSYN fibrils, TNFα and PGE2 act in concert to drive microglial cell activation toward a specific and highly neurotoxic chronic-type inflammatory phenotype characterized by robust glutamate release and iron retention.


Assuntos
Síndromes Neurotóxicas , Doença de Parkinson , Humanos , Doença de Parkinson/patologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Microglia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Sinais (Psicologia) , Inflamação/metabolismo , Neurônios Dopaminérgicos/patologia , Síndromes Neurotóxicas/metabolismo , Glutamatos/metabolismo , Ferro/metabolismo
6.
J Helminthol ; 98: e30, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584420

RESUMO

Six species of freshwater turtles dominate the Chaco-Pampa Plain in southern South America and their parasites have been relatively understudied, with most records concentrated in Brazil. Particularly in Argentina, there are only scattered records of parasites for most of the turtles that inhabit the region, leaving a large knowledge gap. The purpose of the present contribution is to increase the knowledge of the internal parasites of six species of freshwater turtles from Argentina, after 15 years of fieldwork, by providing new hosts and additional geographic records for many host-parasite relationships. Some molecular sequences of the studied parasites were provided as a tool for better species identification. We processed 433 stomach and fecal samples from live individuals and visceral and soft tissue samples from 54 dissected turtles collected from a wide range and different ecoregions. We found 6230 helminths belonging to 18 taxa (one cestode, 11 digeneans and six nematodes). Fourteen new parasite-host associations are reported here, and for the first time parasites are recorded for Phrynops williamsi. This work contributes significantly to the knowledge of the parasitofauna in freshwater turtles in Argentina, providing a detailed list of parasites present in each turtle species and reporting molecular characters for future studies.


Assuntos
Helmintos , Parasitos , Tartarugas , Animais , Tartarugas/parasitologia , Helmintos/genética , Água Doce , Brasil
7.
BMC Microbiol ; 23(1): 225, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596530

RESUMO

INTRODUCTION: Whole genome sequencing (WGS) of bacterial isolates can be used to identify antimicrobial resistance (AMR) genes. Previous studies have shown that genotype-based AMR has variable accuracy for predicting carbapenem resistance in carbapenem-resistant Enterobacterales (CRE); however, the majority of these studies used short-read platforms (e.g. Illumina) to generate sequence data. In this study, our objective was to determine whether Oxford Nanopore Technologies (ONT) long-read WGS would improve detection of carbapenem AMR genes with respect to short-read only WGS for nine clinical CRE samples. We measured the minimum inhibitory breakpoint (MIC) using two phenotype assays (MicroScan and ETEST) for six antibiotics, including two carbapenems (meropenem and ertapenem) and four non-carbapenems (gentamicin, ciprofloxacin, cefepime, and trimethoprim/sulfamethoxazole). We generated short-read data using the Illumina NextSeq and long-read data using the ONT MinION. Four assembly methods were compared: ONT-only assembly; ONT-only assembly plus short-read polish; ONT + short-read hybrid assembly plus short-read polish; short-read only assembly. RESULTS: Consistent with previous studies, our results suggest that the hybrid assembly produced the highest quality results as measured by gene completeness and contig circularization. However, ONT-only methods had minimal impact on the detection of AMR genes and plasmids compared to short-read methods, although, notably, differences in gene copy number differed between methods. All four assembly methods showed identical presence/absence of the blaKPC-2 carbapenemase gene for all samples. The two phenotype assays showed 100% concordant results for the non-carbapenems, but only 65% concordance for the two carbapenems. The presence/absence of AMR genes was 100% concordant with AMR phenotypes for all four non-carbapenem drugs, although only 22%-50% sensitivity for the carbapenems. CONCLUSIONS: Overall, these findings suggest that the lack of complete correspondence between CRE AMR genotype and phenotype for carbapenems, while concerning, is independent of sequencing platform/assembly method.


Assuntos
Antibacterianos , Carbapenêmicos , Fenótipo , Genótipo , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Ertapenem
8.
Parasitology ; 150(6): 498-504, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36892015

RESUMO

Haemosporidia (Apicomplexa, Haemosporida) are protozoa that infect vertebrate blood cells and are transmitted by vectors. Among vertebrates, birds possess the greatest diversity of haemosporidia, historically placed in 3 genera: Haemoproteus, Leucocytozoon and Plasmodium, the causative agent of avian malaria. In South America, existing data on haemosporidia are spatially and temporally dispersed, so increased surveillance is needed to improve the determination and diagnosis of these parasites. During the non-breeding season in 2020 and 2021, 60 common terns (Sterna hirundo) were captured and bled as part of ongoing research on the population health of migratory birds on the Argentinian Atlantic coast. Blood samples and blood smears were obtained. Fifty-eight samples were screened for Plasmodium, Haemoproteus and Leucocytozoon, as well as for Babesia parasites by nested polymerase chain reaction and by microscopic examination of smears. Two positive samples for Plasmodium were found. The cytochrome b lineages detected in the present study are found for the first time, and are close to Plasmodium lineages found in other bird orders. The low prevalence (3.6%) of haemoparasites found in this research was similar to those reported for previous studies on seabirds, including Charadriiformes. Our findings provide new information about the distribution and prevalence of haemosporidian parasites from charadriiforms in the southernmost part of South America, which remains understudied.


Assuntos
Doenças das Aves , Charadriiformes , Haemosporida , Malária Aviária , Parasitos , Plasmodium , Infecções Protozoárias em Animais , Animais , Malária Aviária/epidemiologia , Malária Aviária/parasitologia , Doenças das Aves/epidemiologia , Doenças das Aves/parasitologia , Plasmodium/genética , Haemosporida/genética , Aves/parasitologia , América do Sul/epidemiologia , Prevalência , Filogenia , Infecções Protozoárias em Animais/epidemiologia , Infecções Protozoárias em Animais/parasitologia
9.
Parasitol Res ; 123(1): 61, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38112785

RESUMO

Species of the genus Contracaecum (Family Anisakidae) exhibit a broad host and geographical distribution, parasitizing aquatic organisms such as piscivorous birds and mammals as their definitive hosts. Several Contracaecum species have been reported parasitizing cormorants (Family: Phalacrocoracidae) in South America. The objective of this study was to highlight phylogenetic relationships between Contracaecum species parasitizing cormorants based on both molecular analyses and the papillae arrangement on the male tail. Some Contracaecum species parasitizing Red-legged cormorants from the Ría Deseado (RD), and other nematodes parasitizing eight Neotropic cormorants from San Miguel del Monte lagoon (SMML), Argentina, were collected and analyzed. Both morphological and phylogenetic analyses allowed us to recognize two species: Contracaecum chubutensis parasitizing Phalacrocorax gaimardi, and Contracaecum australe parasitic in Phalacrocorax brasilianus. According to the obtained sequences (mtDNA cox2, ITS1, ITS2, and SSrRNA), Contracaecum sp. parasitizing P. gaimardi exhibited concordance with the previously reported C. chubutensis parasitizing P. atriceps from Bahía Bustamante, Chubut province. Likewise, Contracaecum sp. isolates parasitizing P. brasilianus showed concordance with C. australe from Chile. Besides, the papillae arrangement on the male tail allowed us to understand the interspecific and genetic relationships between the Contracaecum species. The analyses confirm that C. chubutensis specimens parasitizing P. gaimardi from RD present a new host record for the species, whereas, those C. australe specimens parasitizing P. brasilianus from SMML provide a new geographical record for the species and the extension of its distribution range. Present results also confirm the inland and marine distribution of C. australe and C. chubutensis, respectively.


Assuntos
Ascaridoidea , Doenças das Aves , Animais , Masculino , Argentina , Doenças das Aves/parasitologia , Aves/parasitologia , Chile , Filogenia
10.
An Acad Bras Cienc ; 95(2): e20201392, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255125

RESUMO

Ecto and endoparasites of four species of coastal birds, Haematopus ater, Larus dominicanus, Leucophaeus scoresbii (Charadriiformes), and Lophonetta specularioides (Anseriformes), are reported from Puerto Deseado on the Patagonian coast, Argentina. Only H. ater was infested with lice (Phthiraptera), belonging to 2 species (Ischnocera, Amblycera). A total of 19 helminth species were found parasitizing the coastal birds studied: 4 cestodes (1 Tetrabothriidae, 3 Cyclophyllidea); 11 trematodes (2 Gymnophallidae, 3 Microphallidae, 2 Notocotylidae, 1 Philophthalmidae, 2 Renicolidae, 1 Schistosomatidae); 3 nematodes (1 Anisakidae, 2 Acuariidae); and 1 acanthocephalan (Polymorphidae). Although some isolated records have been previously reported for these birds, the present work provides a parasitofauna study for H. ater, L. scoresbii, and L. specularioides for the first time. Endoparasites reflected the feeding habits of the birds; the parasite assemblage of L. dominicanus was the richest, indicating their wide prey spectrum and the diversity of the habitats frequented. A great species richness of trematodes, whose life cycles are partially known, suggests that L. specularioides feeds upon crustaceans and small bivalves. The blackish oystercatcher H. ater preys upon the limpet Nacella magellanica which hosts two larval trematodes corresponding to the adults found parasitizing it.


Assuntos
Charadriiformes , Iscnóceros , Nematoides , Trematódeos , Animais , Aves/parasitologia , Charadriiformes/parasitologia , Oceano Atlântico
11.
Environ Microbiol ; 24(5): 2259-2269, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35102659

RESUMO

Dissolved organic phosphorus (DOP) is a critical nutritional resource for marine microbial communities. However, the relative bioavailability of different types of DOP, such as phosphomonoesters (P-O-C) and phosphoanhydrides (P-O-P), is poorly understood. Here we assess the utilization of these P sources by a representative bacterial copiotroph, Ruegeria pomeroyi DSS-3. All DOP sources supported equivalent growth by R. pomeroyi, and all DOP hydrolysis rates were upregulated under phosphorus depletion (-P). A long-chain polyphosphate (45polyP) showed the lowest hydrolysis rate of all DOP substrates tested, including tripolyphosphate (3polyP). Yet the upregulation of 45polyP hydrolysis under -P was greater than any other substrate analyzed. Proteomics revealed three common P acquisition enzymes potentially involved in polyphosphate utilization, including two alkaline phosphatases, PhoD and PhoX, and one 5'-nucleotidase (5'-NT). Results from DOP substrate competition experiments show that these enzymes likely have broad substrate specificities, including chain length-dependent reactivity toward polyphosphate. These results confirm that DOP, including polyP, are bioavailable nutritional P sources for R. pomeroyi, and possibly other marine heterotrophic bacteria. Furthermore, the chain-length dependent mechanisms, rates and regulation of polyP hydrolysis suggest that these processes may influence the composition of DOP and the overall recycling of nutrients within marine dissolved organic matter.


Assuntos
Matéria Orgânica Dissolvida , Rhodobacteraceae , Fósforo/metabolismo , Polifosfatos/metabolismo , Rhodobacteraceae/metabolismo
12.
Am J Hum Biol ; 34(11): e23713, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34914157

RESUMO

OBJECTIVE: Cytomegalovirus (CMV) infection is associated with age-related chronic disease, and co-infection with Epstein-Barr virus (EBV) may compound disease risk. We aimed to assess the frequency of CMV infection and its relationship with age among EBV seropositive individuals in an Indigenous Amazonian population. METHODS: We report concentrations of CMV and EBV antibodies in dried blood spot samples collected from 157 EBV positive Shuar participants aged 15-86 years (60.5% female) to assess CMV infection rate. We used logistic and linear regression models to examine associations among CMV, EBV, and age, adjusting for sex, geographic region, and body mass index. RESULTS: Nearly two-thirds (63.1%) of EBV seropositive participants were also CMV seropositive. A 1-year increase in age was associated with 3.4% higher odds of CMV infection (OR [95% CI]: 1.034 [1.009-1.064], p = .012), but CMV antibody concentration was not significantly associated with age or EBV antibody concentration among co-infected individuals. CONCLUSIONS: Herpesvirus-related immunosenescence may be important to understanding chronic disease risk among Shuar. Future studies should further explore the role of co-infection in shaping age-related changes in immune function.


Assuntos
Coinfecção , Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Feminino , Humanos , Masculino , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Citomegalovirus , Coinfecção/epidemiologia , Coinfecção/complicações , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/complicações , Anticorpos Antivirais
13.
Mycoses ; 65(2): 186-198, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34888961

RESUMO

BACKGROUND: Isavuconazole, administered as isavuconazonium sulfate (ISAVUSULF), is a broad-spectrum triazole agent for the treatment of invasive fungal disease. In phase 3 studies, ISAVUSULF showed comparable efficacy to voriconazole and amphotericin B for the treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM), respectively. OBJECTIVES: The objective of this study is to determine all-cause mortality and safety outcomes among adults with IM and/or IA non-fumigatus (nf) treated with ISAVUSULF or other antifungal therapies (AFT). PATIENTS AND METHODS: This multicentre, non-interventional registry enrolled patients aged ≥18 years with IM or IA-nf who received systemic AFT from January 2016 to November 2018. Patients received primary ISAVUSULF, non-primary ISAVUSULF, or other AFT, as monotherapy or combination therapy. The primary end point was all-cause mortality at Days 42 and 84; safety outcomes were adverse drug reactions (ADRs) to ISAVUSULF. RESULTS: Of 204 patients enrolled, 74 received primary ISAVUSULF, 30 non-primary ISAVUSULF, and 100 other AFT. All-cause mortality through Day 42 was numerically lower in the non-primary ISAVUSULF group than in the primary ISAVUSULF and other AFT groups, for patients with IM (20.0% vs. 33.3% and 41.3%, respectively) or IA-nf (0% vs. 14.8% and 17.8%, respectively). All-cause mortality tended to be lower with combination therapy than with monotherapy, except for patients with IM receiving primary ISAVUSULF. Of 111 patients receiving ISAVUSULF, 14 (12.6%) reported ADRs, of whom three (2.7%) developed serious ADRs. There were no drug-related deaths. CONCLUSIONS: This study supports the effectiveness and tolerability of ISAVUSULF in clinical practice. Further research is required to confirm the value of ISAVUSULF combination therapy over monotherapy.


Assuntos
Antifúngicos , Aspergilose , Infecções Fúngicas Invasivas , Mucormicose , Adulto , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Mucormicose/tratamento farmacológico , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Sistema de Registros , Triazóis/efeitos adversos , Triazóis/uso terapêutico
14.
Proc Natl Acad Sci U S A ; 116(33): 16448-16453, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31346083

RESUMO

Reactive oxygen species (ROS) like superoxide drive rapid transformations of carbon and metals in aquatic systems and play dynamic roles in biological health, signaling, and defense across a diversity of cell types. In phytoplankton, however, the ecophysiological role(s) of extracellular superoxide production has remained elusive. Here, the mechanism and function of extracellular superoxide production by the marine diatom Thalassiosira oceanica are described. Extracellular superoxide production in T. oceanica exudates was coupled to the oxidation of NADPH. A putative NADPH-oxidizing flavoenzyme with predicted transmembrane domains and high sequence similarity to glutathione reductase (GR) was implicated in this process. GR was also linked to extracellular superoxide production by whole cells via quenching by the flavoenzyme inhibitor diphenylene iodonium (DPI) and oxidized glutathione, the preferred electron acceptor of GR. Extracellular superoxide production followed a typical photosynthesis-irradiance curve and increased by 30% above the saturation irradiance of photosynthesis, while DPI significantly impaired the efficiency of photosystem II under a wide range of light levels. Together, these results suggest that extracellular superoxide production is a byproduct of a transplasma membrane electron transport system that serves to balance the cellular redox state through the recycling of photosynthetic NADPH. This photoprotective function may be widespread, consistent with the presence of putative homologs to T. oceanica GR in other representative marine phytoplankton and ocean metagenomes. Given predicted climate-driven shifts in global surface ocean light regimes and phytoplankton community-level photoacclimation, these results provide implications for future ocean redox balance, ecological functioning, and coupled biogeochemical transformations of carbon and metals.


Assuntos
Diatomáceas/metabolismo , Fotossíntese/genética , Complexo de Proteína do Fotossistema II/metabolismo , Superóxidos/metabolismo , Carbono/metabolismo , Diatomáceas/genética , Transporte de Elétrons/genética , NADP/genética , NADP/metabolismo , Oxirredução , Complexo de Proteína do Fotossistema II/genética , Fitoplâncton/genética , Fitoplâncton/metabolismo , Espécies Reativas de Oxigênio/metabolismo
15.
An Acad Bras Cienc ; 94(suppl 3): e20211430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417611

RESUMO

Digeneans are common parasites of small mammals. Dicrocoeliidae is a family with a cosmopolitan distribution, with 18 genera previously recorded from mammals in the Americas, six of them parasitizing rodents in Argentina. In this study, an updated compilation is provided of Dicrocoeliidae from rodents in the Americas. Also, a new Platynosomoides species is described parasitizing the cricetid rodent Akodon montensis of the Atlantic Forest in Argentina. Digital repositories were used to search for Dicrocoeliidae from rodents in the Americas. Rodents were collected in four localities of the Atlantic Forest, Argentina. Digeneans were removed from the rodent's bile duct, and conventional studies were used for the morphological description. A total of 15 Dicrocoeliidae species were found parasitizing 18 rodent species from eight countries in the Americas. The new species of Platynosomoides from Akodon montensis differs from the other two species of genus by the size of body, testes, ovary, cecum length and position and length of the vitelline bands. Dicrocoeliidae show growing diversity, and the compilation of species in a rodent host base allows a clearer comparison and identification of new taxa in the future.


Assuntos
Dicrocoeliidae , Doenças dos Roedores , Trematódeos , Animais , Feminino , Roedores , Argentina , Doenças dos Roedores/parasitologia , Sigmodontinae , Arvicolinae
16.
Emerg Infect Dis ; 27(1)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33171096

RESUMO

By using paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined point prevalence and seroprevalence in Louisiana, USA, during the second phase of reopening. Infections were highly variable by race and ethnicity, work environment, and ZIP code. Census-weighted seroprevalence was 3.6%, and point prevalence was 3.0%.


Assuntos
COVID-19/sangue , COVID-19/epidemiologia , Grupos Raciais , SARS-CoV-2 , Fatores Socioeconômicos , Local de Trabalho , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Louisiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Adulto Jovem
17.
BMC Vet Res ; 17(1): 376, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872547

RESUMO

BACKGROUND: This study aimed to measure the length of metacarpal and metatarsal bones in five Iranian sheep breeds and to correlate the length of the bones with ungula measurements. Thoracic and pelvic limbs of 2-year-old, previously untrimmed, pastured Afshari, Moghani, Kurdi, Makoui, and Lori-Bakhtiari ewes, (n = 20 ewes per breed) were collected after slaughter. The following lengths were recorded in the metacarpal and metatarsal bones: from the margo proximalis lateralis to the lateral (L1) and medial (D1) cartilago physialis; from the margo proximalis lateralis to the margo abaxialis of the lateral (L2) and medial (D2) caput; from the cartilago physialis lateralis to the margo abaxialis of the lateral caput (X1); from the cartilago physialis medialis to the margo distalis of the caput ridge (X2) and from the margo axialis of cartilago physialis to the margo axialis of the lateral caput (X3). Additionally, measurements of the ungula including pars dorsalis length, pars mobilis lateralis and medialis height, pars dorsalis height to the ground and to the solea cornea, thickness of the solea in the pars dorsalis, pars mobilis lateralis and medialis, solea cornea length and angulus dorsalis were recorded in the medial and lateral digits of the thoracic and pelvic limbs. Data on length of the metatarsal and metacarpal bones were analysed using mixed model equations while Pearson correlations were calculated between metacarpal and metatarsal bones and ungula measurements. RESULTS: Lori- Bakhtiari and Moghani ewes had greater L1, L2, and D1 and D2 while X1, X2 and X3 was greater in Kurdi ewes (P < 0.05). Measurements such as L1, L2, D1 and D2 were greater in the metatarsal than in metacarpal bones (P < 0.05) and the opposite was observed for X1, X2 and X3 (P < 0.05). No asymmetry was observed between the lateral and medial measurements (P > 0.05). Low to moderate correlations were observed between bone and ungula measurements (P < 0.05). CONCLUSION: Under the conditions of this study, differences in metacarpal and metatarsal bone measurements were observed between breeds but no asymmetry was observed between lateral and medial bones. Results indicate an association between metacarpal and metatarsal bones ungula measurements. This could provide baseline information for the development and/or improvement of current ungula health protocols in the studied sheep breeds.


Assuntos
Ossos Metacarpais , Ossos do Metatarso , Ovinos/anatomia & histologia , Animais , Cruzamento , Feminino , Irã (Geográfico) , Ossos Metacarpais/anatomia & histologia , Ossos do Metatarso/anatomia & histologia
18.
Parasitol Res ; 120(5): 1637-1648, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33712928

RESUMO

Two species of intestinal Capillariidae were hitherto known from the Neotropic cormorant Phalacrocorax brasilianus, Baruscapillaria spiculata (Freitas, 1933), and Baruscapillaria appendiculata (Freitas, 1933). The original descriptions are very short and brief, and further reports of both species are scarce and/or confusing. This paper provides a morphological redescription and molecular characterization, based on the partial 18S rDNA gene, of B. spiculata specimens parasitizing the Neotropic cormorant in two continental lagoons from Buenos Aires province, Argentina. Both morphological and morphometrical differences between B. spiculata and B. appendiculata are highlighted on the examination of available type material. Additionally, two previous reports of B. appendiculata from Mexico and Brazil are discussed. A phylogenetic analysis conducted on specimens of B. spiculata and 46 other capillariid isolates available from the GenBank demonstrated a sister-taxon relationship between our specimens and the type species of Baruscapillaria. But, at the same time, significant genetic distances between both taxa showed an interesting variability of the genus Baruscapillaria. The probable division of this genus into multiple genera could probably be confirmed through integrative studies including more species.


Assuntos
Doenças das Aves/parasitologia , Aves/parasitologia , Nematoides/classificação , Infecções por Nematoides/veterinária , Animais , Argentina , DNA de Helmintos/genética , Feminino , Variação Genética , Masculino , Nematoides/citologia , Nematoides/genética , Infecções por Nematoides/parasitologia , Filogenia , RNA Ribossômico 18S/genética
19.
An Acad Bras Cienc ; 93(3): e20191577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34231755

RESUMO

The aim of this communication was to establish if Enterobacterales associated with gulls in Argentina harbored antimicrobial resistance (AMR) genes. We analyzed cloacal swabs in two contrasting areas: Ensenada, Buenos Aires province (26 Larus dominicanus and 22 Chroicocephalus maculipennis) and Puerto Madryn, Chubut province (20 L. dominicanus). In Ensenada, bla CTX-M and mcr-1 genes, were isolated from both gull species, whereas in the Puerto Madryn, only bla CTX-M gene was found. We report for the first time C. maculipennis as carrier of AMR. The finding of AMR in wildlife constitutes a useful tool in evaluating the anthropogenic impact on environmental health.


Assuntos
Charadriiformes , Animais , Antibacterianos/farmacologia , Argentina , Farmacorresistência Bacteriana/genética , América do Sul
20.
Emerg Infect Dis ; 26(11): 2766-2769, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32731911

RESUMO

Using a novel recruitment method and paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined seroprevalence in a racially diverse municipality in Louisiana, USA. Infections were highly variable by ZIP code and differed by race/ethnicity. Overall census-weighted seroprevalence was 6.9%, and the calculated infection fatality ratio was 1.63%.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , RNA Viral/sangue , Adulto , Idoso , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Louisiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , SARS-CoV-2 , Estudos Soroepidemiológicos
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