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2.
Nat Immunol ; 25(2): 282-293, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38172257

RESUMO

Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals.


Assuntos
Ceramidas , Proteínas de Ligação ao GTP , Animais , Humanos , Longevidade/genética , Células Endoteliais/metabolismo , Mamíferos/metabolismo
3.
J Clin Microbiol ; 61(3): e0079021, 2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36598247

RESUMO

Mycoplasma genitalium is an important sexually transmitted pathogen affecting both men and women. Its extremely slow growth in vitro and very demanding culture requirements necessitate the use of molecular-based diagnostic tests for its detection in clinical specimens. The recent availability of U.S. Food and Drug Administration (FDA)-cleared commercial molecular-based assays has enabled diagnostic testing to become more widely available in the United States and no longer limited to specialized reference laboratories. Advances in the knowledge of the epidemiology and clinical significance of M. genitalium as a human pathogen made possible by the availability of molecular-based testing have led to updated guidelines for diagnostic testing and treatment that have been published in various countries. This review summarizes the importance of M. genitalium as an agent of human disease, explains the necessity of obtaining a microbiological diagnosis, describes currently available diagnostic methods, and discusses how the emergence of antimicrobial resistance has complicated treatment alternatives and influenced the development of diagnostic tests for resistance detection, with an emphasis on developments over the past few years.


Assuntos
Infecções por Mycoplasma , Mycoplasma genitalium , Uretrite , Masculino , Humanos , Feminino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Mycoplasma genitalium/genética , Laboratórios , Farmacorresistência Bacteriana , Infecções por Mycoplasma/microbiologia , Macrolídeos , Uretrite/microbiologia
4.
Clin Exp Immunol ; 210(2): 91-103, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36208448

RESUMO

A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig®) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years). Seventy-five patients received 4462 infusions during up to 70 weeks of follow-up in the main study and 27 patients received 2777 infusions during up to 168 weeks of follow-up in the extension. In the main study, there were no serious bacterial infections (SBIs), and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5). One SBI was recorded in the extension, for an SBI rate of 0.02 (upper 99% CI 0.19). The annual rate of all infections over the duration of the extension study was 2.2 (95% CI 1.2, 3.9). Only 15.0% (1085) of 7239 infusions were associated with infusion site reactions (ISRs), leaving 85.0% (6153) of infusions without reactions. The majority of ISRs were mild and transient. ISR incidence decreased over time, from 36.9% to 16% during the main study and from 9% to 2.3% during the extension. The incidence of related systemic adverse events was 14.7% in the main study and 7.4% in the extension. In conclusion, this prospective, long-term study with cutaquig showed maintained efficacy and low rates of local and systemic adverse reactions in PID patients over up to 238 weeks of follow-up.


Assuntos
Infecções Bacterianas , Síndromes de Imunodeficiência , Humanos , Estudos Prospectivos , Infusões Subcutâneas , Síndromes de Imunodeficiência/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Resultado do Tratamento , Imunoglobulinas Intravenosas/uso terapêutico
5.
Microbiol Spectr ; 10(6): e0365422, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36314935

RESUMO

Here, we performed in vitro susceptibility testing on 10 Mycoplasma genitalium isolates against omadacycline, minocycline, tetracycline, doxycycline, moxifloxacin, levofloxacin, and azithromycin. Omadacycline was the most potent agent, with all MICs of ≤0.5 µg/mL. MICs were not affected by resistance to other agents, including resistance to other tetracycline class drugs. Omadacycline may be a potential treatment option for M. genitalium infection. IMPORTANCE There are very few clinical isolates of Mycoplasma genitalium available for in vitro susceptibility testing. We studied 10 isolates and determined that the new semisynthetic aminomethylcycline omadacycline is active against isolates that are resistant to tetracyclines, macrolides, and quinolones. These data suggest that clinical studies should be performed in order to see if omadacycline may be useful to treat urogenital infections caused by M. genitalium.


Assuntos
Infecções por Mycoplasma , Mycoplasma genitalium , Quinolonas , Humanos , Tetraciclina/farmacologia , Infecções por Mycoplasma/tratamento farmacológico , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Macrolídeos/farmacologia , Quinolonas/farmacologia , Quinolonas/uso terapêutico , Minociclina/farmacologia , Minociclina/uso terapêutico , Mitomicina/farmacologia , Mitomicina/uso terapêutico , Inibidores da Síntese de Proteínas/farmacologia
7.
N Engl J Med ; 386(24): 2295-2302, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35704481

RESUMO

Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αß T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.).


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Transplante de Rim , Síndrome Nefrótica , Osteocondrodisplasias , Doenças da Imunodeficiência Primária , Arteriosclerose/genética , Arteriosclerose/terapia , Rejeição de Enxerto/prevenção & controle , Humanos , Síndromes de Imunodeficiência/terapia , Rim/fisiologia , Transplante de Rim/efeitos adversos , Síndrome Nefrótica/genética , Síndrome Nefrótica/terapia , Osteocondrodisplasias/genética , Osteocondrodisplasias/terapia , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/terapia , Embolia Pulmonar/genética , Embolia Pulmonar/terapia , Condicionamento Pré-Transplante/métodos
8.
BMC Genomics ; 23(Suppl 4): 361, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546658

RESUMO

BACKGROUND: Accurate bacteria genome de novo assembly is fundamental to understand the evolution and pathogenesis of new bacteria species. The advent and popularity of Third-Generation Sequencing (TGS) enables assembly of bacteria genomes at an unprecedented speed. However, most current TGS assemblers were specifically designed for human or other species that do not have a circular genome. Besides, the repetitive DNA fragments in many bacterial genomes plus the high error rate of long sequencing data make it still very challenging to accurately assemble their genomes even with a relatively small genome size. Therefore, there is an urgent need for the development of an optimized method to address these issues. RESULTS: We developed B-assembler, which is capable of assembling bacterial genomes when there are only long reads or a combination of short and long reads. B-assembler takes advantage of the structural resolving power of long reads and the accuracy of short reads if applicable. It first selects and corrects the ultra-long reads to get an initial contig. Then, it collects the reads overlapping with the ends of the initial contig. This two-round assembling procedure along with optimized error correction enables a high-confidence and circularized genome assembly. Benchmarked on both synthetic and real sequencing data of several species of bacterium, the results show that both long-read-only and hybrid-read modes can accurately assemble circular bacterial genomes free of structural errors and have fewer small errors compared to other assemblers. CONCLUSIONS: B-assembler provides a better solution to bacterial genome assembly, which will facilitate downstream bacterial genome analysis.


Assuntos
Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Bactérias/genética , DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Análise de Sequência de DNA/métodos
9.
Anaerobe ; 75: 102532, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35122953

RESUMO

F. necrophorum, a gram-negative obligate anaerobe, causes pharyngotonsillitis, peritonsillar abscess and the Lemierre Syndrome as well as other significant infections. Clinical information on this bacterium has increased dramatically over the past 20 years, yet no standard guidance exists for treating these infections. While data support F. necrophorum as a cause of pharyngotonsillitis, no consensus exists on the clinical importance of these findings especially in the 15-30 age group. Similarly, recent data find this bacterium the most frequent and most likely to recur in peritonsillar abscess for that age group. Should this impact how we treat these patients? Finally, we have no studies of either antibiotics or anticoagulation for the Lemierre Syndrome. Thus, each physician making the diagnosis of the Lemierre Syndrome chooses antibiotics (and their duration) and whether or not to anticoagulate without guidance. Infectious disease specialists and hospitalists would benefit from consensus expert opinions based on reviewing data on these infections.


Assuntos
Doenças Transmissíveis , Infecções por Fusobacterium , Síndrome de Lemierre , Abscesso Peritonsilar , Tonsilite , Antibacterianos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Infecções por Fusobacterium/diagnóstico , Infecções por Fusobacterium/tratamento farmacológico , Infecções por Fusobacterium/microbiologia , Fusobacterium necrophorum , Humanos , Síndrome de Lemierre/diagnóstico , Síndrome de Lemierre/tratamento farmacológico , Síndrome de Lemierre/microbiologia , Abscesso Peritonsilar/diagnóstico , Abscesso Peritonsilar/tratamento farmacológico , Abscesso Peritonsilar/microbiologia , Tonsilite/microbiologia
10.
J Clin Immunol ; 41(8): 1804-1838, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34390440

RESUMO

Hyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers.


Assuntos
Candidíase Mucocutânea Crônica/genética , Síndrome de Job/genética , Adolescente , Adulto , Candidíase Mucocutânea Crônica/sangue , Criança , Pré-Escolar , Estudos de Coortes , Eczema/genética , Eosinofilia/genética , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Síndrome de Job/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
11.
Access Microbiol ; 3(4): 000221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151172

RESUMO

Mycoplasma salivarium is a common mycoplasma usually isolated from human oropharynx, particularly from individuals with periodontal disease. It is also among the more common mycoplasmal contaminants of eukaryotic cell cultures. Although M. salivarium has been isolated occasionally from abscesses and other sterile sites, to our knowledge, only three cases of septic arthritis have been documented in the past due to this organism, all in patients with humoral immunodeficiency. We now report a fourth case of septic polyarthritis in a patient with profound hypoimmunoglobulinemia who had experienced dental abscesses within the preceding 2 years. Our case highlights the importance of considering invasive mycoplasmal infection in hypogammaglobulinemic patients. It is likely of significance that the patient had suffered recurrent dental abscesses as a source of infection with M. salivarium .

12.
J Exp Med ; 218(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33951726

RESUMO

The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. PU.1 deficiency fatally arrests lymphopoiesis and myelopoiesis in mice, but human congenital PU.1 disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients lacked circulating B cells and possessed few conventional dendritic cells. Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation. Patient SPI1 mutations encoded destabilized PU.1 proteins unable to nuclear localize or bind target DNA. In PU.1-haploinsufficient pro-B cell lines, euchromatin was less accessible to nonpioneer TFs critical for B cell development, and gene expression patterns associated with the pro- to pre-B cell transition were undermined. Our findings molecularly describe a novel form of agammaglobulinemia and underscore PU.1's critical, dose-dependent role as a hematopoietic euchromatin gatekeeper.


Assuntos
Agamaglobulinemia/genética , Cromatina/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Adolescente , Adulto , Linfócitos B/fisiologia , Diferenciação Celular/genética , Linhagem Celular , Criança , Pré-Escolar , Células Dendríticas/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Células HEK293 , Hematopoese/genética , Células-Tronco Hematopoéticas/fisiologia , Humanos , Lactente , Linfopoese/genética , Masculino , Mutação/genética , Células Precursoras de Linfócitos B/fisiologia , Células-Tronco/fisiologia , Adulto Jovem
13.
N Engl J Med ; 384(17): 1613-1622, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33838625

RESUMO

BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue. METHODS: We conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement of up to four intratumoral catheters. The following day, they received G207 (107 or 108 plaque-forming units) by controlled-rate infusion over a period of 6 hours. Cohorts 3 and 4 received radiation (5 Gy) to the gross tumor volume within 24 hours after G207 administration. Viral shedding from saliva, conjunctiva, and blood was assessed by culture and polymerase-chain-reaction assay. Matched pre- and post-treatment tissue samples were examined for tumor-infiltrating lymphocytes by immunohistologic analysis. RESULTS: Twelve patients 7 to 18 years of age with high-grade glioma received G207. No dose-limiting toxic effects or serious adverse events were attributed to G207 by the investigators. Twenty grade 1 adverse events were possibly related to G207. No virus shedding was detected. Radiographic, neuropathological, or clinical responses were seen in 11 patients. The median overall survival was 12.2 months (95% confidence interval, 8.0 to 16.4); as of June 5, 2020, a total of 4 of 11 patients were still alive 18 months after G207 treatment. G207 markedly increased the number of tumor-infiltrating lymphocytes. CONCLUSIONS: Intratumoral G207 alone and with radiation had an acceptable adverse-event profile with evidence of responses in patients with recurrent or progressive pediatric high-grade glioma. G207 converted immunologically "cold" tumors to "hot." (Supported by the Food and Drug Administration and others; ClinicalTrials.gov number, NCT02457845.).


Assuntos
Neoplasias Encefálicas/terapia , Glioma/terapia , Terapia Viral Oncolítica , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/radioterapia , Humanos , Estimativa de Kaplan-Meier , Células Matadoras Naturais , Contagem de Leucócitos , Masculino , Terapia Viral Oncolítica/efeitos adversos , Linfócitos T
14.
Front Immunol ; 12: 796065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35003119

RESUMO

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.


Assuntos
Granuloma/imunologia , Inflamação/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Vírus da Rubéola/fisiologia , Rubéola (Sarampo Alemão)/imunologia , Idoso , Antígenos Virais/metabolismo , Estudos de Coortes , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Doenças Genéticas Inatas , Transplante de Células-Tronco Hematopoéticas , Humanos , Imuno-Histoquímica , Síndromes de Imunodeficiência , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-1/antagonistas & inibidores , Rubéola (Sarampo Alemão)/complicações , Células Th2/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
16.
Front Microbiol ; 11: 585524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193233

RESUMO

Mycoplasma genitalium is an important etiologic agent of non-gonococcal urethritis (NGU), known for chronicity and multidrug resistance, in which biofilms may play an integral role. In some bacterial species capable of forming biofilms, extracellular polymeric substances (EPS) composed of poly-N-acetylglucosamine (PNAG) are a crucial component of the matrix. Monosaccharide analysis of M. genitalium strains revealed high abundance of GlcNAc, suggesting a biofilm-specific EPS. Chromatograms also showed high concentrations of galactose and glucose as observed in other mycoplasma species. Fluorescence microscopy of M. genitalium biofilms utilizing fluor-coupled lectins revealed differential staining of biofilm structures. Scanning electron microscopy (SEM) showed increasing maturation over time of bacterial "towers" seen in biofilm development. As seen with Mycoplasma pneumoniae, organisms within fully mature M. genitalium biofilms exhibited loss of cell polarization. Bacteria associated with disrupted biofilms exhibited decreased dose-dependent viability after treatment with antibiotics compared to bacteria with intact biofilms. In addition, growth index analysis demonstrated decreases in metabolism in cultures with disrupted biofilms with antibiotic treatment. Taken together, these data suggest that M. genitalium biofilms are a contributing factor in antibiotic resistance.

17.
Aust Vet J ; 98(12): 602-609, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33063857

RESUMO

The Australian goat meat industry has grown significantly in the last decade, with the value of exports nearly tripling. However, because carcase weight has remained constant over this time, the drivers of industry growth are price and supply. Animal health and reproduction are key factors contributing to supply and productivity, yet limitations to production management are poorly understood, hampering advice for effective intervention. This exploratory study aims to provide insights into the animal health and reproductive management practices and perceptions among meat goat producers in Australia. To achieve this aim, 20 producers, located in New South Wales, Queensland, Western Australia and Victoria, operating under different production systems were interviewed. The results of this study suggest that animal health management could be improved and that producers perceive a lack of relevant and species-specific information available to help them make informed decisions. Reproductive management and records varied greatly across producers interviewed. Kid loss was identified as an issue, with a 28% estimated average (6%-47% range) of losses from kidding until weaning. Producers identified predation, doe nutrition and mismothering as the biggest contributors to kid loss, with the majority of losses occurring within a week of birth. All producers believed management could minimise kid loss. This study highlights the importance of improving reproductive rates among goat enterprises and provides new information on the current practices within the Australian meat goat industry. This may assist the development of appropriate strategies for improving health and reproductive management and delivery of advice to producers.


Assuntos
Cabras , Carne , Criação de Animais Domésticos , Animais , New South Wales , Queensland , Vitória , Austrália Ocidental
18.
J Clin Microbiol ; 58(10)2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32817226

RESUMO

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Genótipo , Humanos , Macrolídeos/farmacologia , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Estados Unidos/epidemiologia
19.
Sci Rep ; 10(1): 10093, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572105

RESUMO

Temporally short X-ray pulses are an indispensable tool for the study of electron transitions close to the Fermi energy and structural changes in molecules undergoing chemical reactions which take place on a time-scale of hundreds of femtoseconds. The time resolution of experiments at 3rd generation light sources which produce intense synchrotron radiation is limited fundamentally by the electron-bunch length in the range of tens of picoseconds. Here we propose a new scheme for the generation of intense and coherent sub-femtoseconds soft X-ray pulses in storage rings by applying the Echo-Enabled Harmonic Generation (EEHG) method. Many issues for obtaining the EEHG structure such as two modulators and a radiator are solved by a paradigm shift in an achromatic storage ring cell. Numerical demonstration of the feasibility of the scheme for the BESSY II beam parameters is presented.

20.
J Clin Microbiol ; 58(6)2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32269102

RESUMO

We evaluated six commercial molecular tests targeting Mycoplasma pneumoniae, namely, the BioFire FilmArray respiratory panel (RP), the Meridian Alethia Mycoplasma Direct, the GenMark ePlex respiratory pathogen panel (RPP), the Luminex NxTAG RPP, the ELITech ELITe InGenius Mycoplasma MGB research use only (RUO) PCR, and the SpeeDx Resistance Plus MP assays. Laboratory-developed PCR assays at the University of Alabama at Birmingham and the Centers for Disease Control and Prevention were used as reference standards. Among 428 specimens, 212 were designated confirmed positives for M. pneumoniae The highest clinical sensitivities were found with the InGenius PCR (99.5%) and the FilmArray RP (98.1%). The Resistance Plus MP identified 93.3% of the confirmed-positive specimens, whereas 83.6, 64.6, and 55.7% were identified by the ePlex RPP, NxTAG RPP, and Mycoplasma Direct assays, respectively. There was no significant difference between the sensitivity of the reference methods and that of the FilmArray RP and InGenius assays, but the remaining four assays detected significantly fewer positive specimens (P < 0.05). Specificities of all assays were 99.5 to 100%. The Resistance Plus MP assay detected macrolide resistance in 27/33 specimens, resulting in a sensitivity of 81.8%. This study provides the first large-scale comparison of commercial molecular assays for detection of M. pneumoniae in the United States and identified clear differences among their performance. Additional studies are necessary to explore the impact of various test performances on patient outcome.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Humanos , Macrolídeos/farmacologia , Mycoplasma pneumoniae/genética , Patologia Molecular , Pneumonia por Mycoplasma/diagnóstico
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