RESUMEN
Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.
Asunto(s)
Lentinula , Filogenia , Asia Oriental , TailandiaRESUMEN
BACKGROUND: Tuberculosis in the UK is more prevalent in people with social risk factors- e.g. previous incarceration, homelessness - and in migrants from TB endemic countries. The management of TB infection is part of TB elimination strategies, but is challenging to provide to socially excluded groups and the evidence base for effective interventions is small. METHODS: We evaluated a TB infection screening and treatment programme provided by a peer-led service (Find&Treat) working in inclusion health settings (e.g. homeless hostels) in London. IGRA (interferon-gamma release assay) testing and TB infection treatment were offered to eligible adults using a community-based model. The primary outcome was successful progression through the cascade of care. We also evaluated socio-demographic characteristics associated with a positive IGRA. RESULTS: 42/312 (13.5%) participants had a positive IGRA and no one had evidence of active TB. 35/42 completed a medical evaluation; 22 started treatment, and 17 completed treatment. Having a positive IGRA was associated with previous incarceration and being born outside of the UK. DISCUSSION: Provision of TB infection diagnosis and management to this socially excluded population has several challenges including maintaining people in care and drug-drug interactions. Peer-support workers provided this service safely and effectively with appropriate support. Further work to generate data to inform risks and benefits of treatment for TB infection in this group is needed to facilitate joint decision making.
Asunto(s)
Tuberculosis Latente , Tuberculosis , Adulto , Humanos , Prueba de Tuberculina , Londres/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Ensayos de Liberación de Interferón gammaRESUMEN
BACKGROUND: Cementless total knee arthroplasty (TKA) is the subject of renewed interest. Previous concerns about survivorship have been addressed and there is an appeal in terms of biological fixation and surgical efficiency. However, even surgeon advocates have concerns about the risk of marked subsidence when using this technology in older patients at risk for osteoporosis. METHODS: This was a retrospective analysis of 1,000 consecutive fully cementless mobile bearing TKAs performed at a single institution on women over 75 years of age who had postoperative and 1-year x-rays. The primary outcome was the incidence of subsidence. RESULTS: There were three asymptomatic cases with definite subsidence and change in alignment. In a fourth symptomatic case, the femoral component subsided into varus and the tibia into valgus, thus maintaining alignment which facilitated nonoperative treatment in a 92-year-old. Overall, at 1 year, there were two- liner revisions for infection without recurrence. Five patients had further surgery, of which three were washouts and two were for periprosthetic fractures sustained postoperatively within 1 year. Seven patients had further anesthesia, of which five were manipulations and two were nonrecurrent closed reductions for spinouts. CONCLUSION: Cementless TKA did not have a high risk of subsidence in this at-risk population. In the hands of experienced surgeons, these procedures can be used safely irrespective of bone quality.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios Retrospectivos , Prótesis de la Rodilla/efectos adversos , Tibia/cirugía , Radiografía , Reoperación , Resultado del TratamientoRESUMEN
Polar bear (Ursus maritimus) and brown bear (Ursus arctos) are recently diverged species that inhabit vastly differing habitats. Thus, analysis of the polar bear and brown bear genomes represents a unique opportunity to investigate the evolutionary mechanisms and genetic underpinnings of rapid ecological adaptation in mammals. Copy number (CN) differences in genomic regions between closely related species can underlie adaptive phenotypes and this form of genetic variation has not been explored in the context of polar bear evolution. Here, we analyzed the CN profiles of 17 polar bears, 9 brown bears, and 2 black bears (Ursus americanus). We identified an average of 318 genes per individual that showed evidence of CN variation (CNV). Nearly 200 genes displayed species-specific CN differences between polar bear and brown bear species. Principal component analysis of gene CN provides strong evidence that CNV evolved rapidly in the polar bear lineage and mainly resulted in CN loss. Olfactory receptors composed 47% of CN differentiated genes, with the majority of these genes being at lower CN in the polar bear. Additionally, we found significantly fewer copies of several genes involved in fatty acid metabolism as well as AMY1B, the salivary amylase-encoding gene in the polar bear. These results suggest that natural selection shaped patterns of CNV in response to the transition from an omnivorous to primarily carnivorous diet during polar bear evolution. Our analyses of CNV shed light on the genomic underpinnings of ecological adaptation during polar bear evolution.
Asunto(s)
Evolución Biológica , Dieta/veterinaria , Dosificación de Gen , Ursidae/genética , Adaptación Fisiológica/genética , Animales , Ecología , Dosificación de Gen/genética , MetagenómicaRESUMEN
PURPOSE: The aim of this study was to identify if experience in arthroscopy confers ambidexterity to the operator and the role of baseline characteristics in arthroscopic simulator performance. METHODS: A prospective comparative study was carried out across four regional Orthopaedic training centres. Participants were divided into novice, intermediate or experienced groups based on arthroscopic experience. Baseline demographics including age, sex, handedness, and gaming history were also collected. Following familiarisation with the procedure, participants were asked to complete a simulated task requiring bimanual control consisting of visualisation with camera control and manipulation of highlighted objects using a grasping instrument. One attempt using camera control and grasping accuracy per hand was performed by each participant, with scores for each hand collected for analysis. Performance scores for camera alignment, camera path length, grasper path length and grasping efficiency were collected. Time taken to completion was also noted for each attempt. RESULTS: Fifty-six participants were recruited to the study. A significant difference in grasping efficiency between groups in the dominant hand was demonstrated (p = 0.013). Novices demonstrated laterality with superior performance in grasping efficiency in the dominant hand (p = 0.001). No significant difference was noted between dominant and non-dominant hand performance in the experienced group. CONCLUSION: Arthroscopic simulation-based training is a valuable learning tool for orthopaedic training. This study demonstrated that experienced orthopaedic surgeons have a greater degree of ambidexterity than intermediate or novice groups, hypothesised by authors to be conferred through conventional orthopaedic training. Dedicated bimanual control tasks to reduce laterality in trainees should be incorporated in simulated surgical curricula. LEVEL OF EVIDENCE: III.
Asunto(s)
Ortopedia , Entrenamiento Simulado , Artroscopía/educación , Competencia Clínica , Simulación por Computador , Humanos , Ortopedia/educación , Estudios Prospectivos , Entrenamiento Simulado/métodos , Análisis y Desempeño de TareasRESUMEN
BACKGROUND: The current pandemic has impacted heavily on health systems, making unprecedented demands on resources, and forcing reconfiguration of services. Trauma and orthopaedic units have cancelled elective surgery, moved to virtual based clinics and have been forced to reconsider the provision of trauma. Our national elective orthopaedic centre has been re-designated as a trauma centre to allow tertiary centres re-direct triaged trauma. Many governments, as part of their COVID-19 management, have significantly restricted activity of the general population. We proposed that trauma patterns would change alongside these changes and maintaining existing standards of treatment would require dedicated planning and structures. METHODS: Referrals over a six-week period (March 15th to April 30th) were retrospectively reviewed. Data was collected directly from our referral database and a database populated. Analysis was performed to assess trauma volume, aetiology, and changes in trends. RESULTS: There were one hundred and fifty-nine referrals from three individual hospitals within the timeframe. Mean age of patient's referred was 55 (range17-92). Males accounted for 45% of cases. F&A injuries were the most common (32%), followed by H&W (28%), UL (17%), H&F (16%) and K&T (7%). In comparison to the corresponding time-period in 2019, trauma theatre activity reduced by almost one half (45.3%) CONCLUSION: The majority of trauma referred to our Dublin based centre during COVID-19 related population restrictions appears to be home based and trauma volumes have decreased. Significant reductions are apparent in work and sport related injuries suggestive of compliance with COVID-19 activity guidelines. Maintaining existing standards of treatment requires dedicated planning.
Asunto(s)
Accidentes Domésticos/tendencias , COVID-19 , Heridas y Lesiones/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/prevención & control , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Pandemias , Derivación y Consulta , Estudios Retrospectivos , Centros Traumatológicos/tendencias , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/etiología , Adulto JovenRESUMEN
INTRODUCTION: With the emergence of the 2019 novel coronavirus and its resulting pandemic status in March 2020 all routine elective orthopaedic surgery was cancelled in our institution. The developing picture in Italy, of acute hospitals becoming overwhelmed with treating patients suffering with severe and life-threatening symptoms from the disease, prompted the orthopaedic surgeons to formulate a plan to transfer trauma patients requiring surgery to the elective hospital to unburden the acute hospital system. METHODS: Under the threat of this pandemic; protocols and algorithms were established for referral, acceptance and care of trauma patients from acute hospitals in the region. Each day, as new guidance on COVID-19 emerged, our process and algorithms were adjusted to reflect pertinent change. RESULTS: The screening of all patients referred, worked well in keeping our hospital "COVID-free" with respect to patients undergoing operations. An upward trend in cases referred reflected the decreased capacity in the acute hospitals due to rising cases of COVID-19 within the hospital network. During the first 7 weeks of the pandemic 308 operations were performed, (31.1% upper limb, 33.4% lower limb, 4.1% spine, 14.1% urgent elective, 17.4% plastic surgery cases). Regular review and audit of the activity in the hospital as well as communication with the referring teams enabled appropriate planning to accommodate the increase in case-mix as the need arose. DISCUSSION: This paper details the steps that were taken in planning for such a change in management specific to the orthopaedic surgery setting and the lessons learnt during this process. The success of the development of this pathway was facilitated by clear communication channels, flexibility to adapt to changing process and feedback from all stakeholders. The implementation of this pathway allowed the unburdening of acute hospitals dealing with the pandemic that was steadily reducing access to operating theatres and anaesthetic resources.
Asunto(s)
COVID-19/epidemiología , Gestión del Cambio , Procedimientos Ortopédicos , Derivación y Consulta/organización & administración , Heridas y Lesiones/cirugía , Algoritmos , Procedimientos Quirúrgicos Electivos , Humanos , Irlanda , Transferencia de Pacientes , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/epidemiologíaRESUMEN
Tempeh is a fermented food made of mainly soybeans and is a nutritious, affordable, and sustainable functional source of protein. Globally, tempeh is a widely accepted fermented product. Although there is a growing body of literature on tempeh, most research has focused on unfermented soybeans, thus the impact of tempeh fermentation on biological properties of soybeans has been largely left scattered. The objective of this review is to summarize the literature of tempeh fermentation over the past 60 years. A search of articles on tempeh published from 1960 to 2020 was performed using the Cochrane Library, Web of Science, EBSCOhost FSTA database, and Google Scholar. References from identified articles were reviewed for additional sources. In total, 321 papers were selected for this review, of which 64 papers were related to the health benefits of tempeh. This review concluded that sufficient evidence exists in the literature supporting tempeh fermentation as a low-cost, health-promoting, and sustainable food processing technology to produce protein-rich foods using various beans, legumes, and grains. This comprehensive review suggests further studies are needed on tempeh fermentation and its impact on human health; research and standardization of nonsoy tempeh; assessment of food safety-improving modification in tempeh production system; and initiatives supporting the sourcing of local ingredients in tempeh production.
Asunto(s)
Alimentos de Soja , Costos y Análisis de Costo , Fermentación , Humanos , Rhizopus , Glycine maxRESUMEN
BACKGROUND: HCV infection disproportionately affects underserved populations such as homeless individuals, people who inject drugs and prison populations. Peer advocacy can enable active engagement with healthcare services and increase the likelihood of favourable treatment outcomes. OBJECTIVES: This observational study aims to assess the burden of disease in these underserved populations and describe the role of peer support in linking these individuals to specialist treatment services. METHODS: Services were identified if they had a high proportion of individuals with risk factors for HCV, such as injecting drug use or homelessness. Individuals were screened for HCV using point-of-care tests and a portable FibroScan. All positive cases received peer support for linkage to specialist care. Information was gathered on risk factors, demographics and follow-up information regarding linkage to care and treatment outcomes. RESULTS: A total of 461 individuals were screened, of which 197 (42.7%) were chronically infected with HCV. Referral was made to secondary care for 176 (89.3%) and all received peer support, with 104 (52.8%) individuals engaged with treatment centres. Of these, 89 (85.6%) started treatment and 76 (85.4%) had a favourable outcome. Factors associated with not being approved for treatment were recent homelessness, younger age and current crack cocaine injecting. CONCLUSIONS: Highly trained peer support workers working as part of a specialist outreach clinical team help to identify a high proportion of individuals exposed to HCV, achieve high rates of engagement with treatment services and maintain high rates of treatment success amongst a population with complex needs.
Asunto(s)
Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Grupo Paritario , Apoyo Social , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , Consumidores de Drogas/estadística & datos numéricos , Europa (Continente)/epidemiología , Femenino , Hepatitis C/diagnóstico , Personas con Mala Vivienda/estadística & datos numéricos , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Sistemas de Atención de Punto , Práctica de Salud Pública , Marginación Social , Adulto JovenRESUMEN
INTRODUCTION: The increasing incidence of acetabular fractures in the elderly and the fracture complexity seen in this cohort represents one of the greatest challenges faced by trauma orthopaedic surgeons today. There are no formal guidelines of best practice in the treatment of these patients. Management options vary from non-operative, acute ORIF, and/or total joint replacement. Although surgical intervention allows for earlier mobilization and avoidance of the complications of prolonged bedrest, the patients ability to tolerate what is often major surgery is always of concern. This is in stark contrast to intracapsular hip fractures, (a fracture within the same joint), where acute surgery is recommended in virtually all cases. OBJECTIVES: This study was undertaken to evaluate the peri-operative outcomes for geriatric patients undergoing acetabular ORIF and hemiarthroplasty to assess if there is a significant difference in early outcome parameters. DESIGN: This is a retrospective case-control study. SETTING: This study was performed in the National Centre for Pelvic and Acetabular surgery. PATIENTS: 42 age- and sex-matched patients with comparable ASA grades were included in each arm of the study. Patient selection in the acetabular ORIF group was consecutive patients managed operatively in the centre during the period 2010-2015. The selection for the hemiarthroplasty group was by random selection of age- and sex-matched patients undergoing hemiarthroplasty during the same period. MAIN OUTCOME MEASUREMENTS: The primary outcomes that were proposed prior to the study being performed was perioperative mortality and post-op complications. Secondary outcomes were operating times, blood loss and need for ICU admission. RESULTS: A significant difference between the two cohorts was observed with operative times, blood loss, need for transfusion, and need for ICU admission, all higher in the acetabular ORIF group. There was no significant difference in mortality or post-op infection. CONCLUSIONS: Our paper supports the concept that acute ORIF of acetabular fractures, with appropriate peri-operative support, can be undertaken safely. There is no difference in the major peri-operative outcomes of mortality or infection when compared with hip fracture patients requiring hemiarthroplasty.
Asunto(s)
Acetábulo/lesiones , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Reducción Abierta , Acetábulo/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Fracturas Óseas/mortalidad , Hemiartroplastia , Fracturas de Cadera/mortalidad , Fracturas de Cadera/cirugía , Humanos , Masculino , Análisis por Apareamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Aspergillus fumigatus, a ubiquitous human fungal pathogen, produces asexual spores (conidia), which are the main mode of propagation, survival and infection of this human pathogen. In this study, we present the molecular characterization of a novel regulator of conidiogenesis and conidial survival called MybA because the predicted protein contains a Myb DNA binding motif. Cellular localization of the MybA::Gfp fusion and immunoprecipitation of the MybA::Gfp or MybA::3xHa protein showed that MybA is localized to the nucleus. RNA sequencing data and a uidA reporter assay indicated that the MybA protein functions upstream of wetA, vosA and velB, the key regulators involved in conidial maturation. The deletion of mybA resulted in a very significant reduction in the number and viability of conidia. As a consequence, the ΔmybA strain has a reduced virulence in an experimental murine model of aspergillosis. RNA-sequencing and biochemical studies of the ΔmybA strain suggested that MybA protein controls the expression of enzymes involved in trehalose biosynthesis as well as other cell wall and membrane-associated proteins and ROS scavenging enzymes. In summary, MybA protein is a new key regulator of conidiogenesis and conidial maturation and survival, and plays a crucial role in propagation and virulence of A. fumigatus.
Asunto(s)
Aspergillus fumigatus/genética , Esporas Fúngicas/genética , Aspergilosis/microbiología , Aspergillus fumigatus/metabolismo , Pared Celular/metabolismo , Proteínas Fúngicas/metabolismo , Eliminación de Gen , Regulación Fúngica de la Expresión Génica/genética , Humanos , Proteínas de la Membrana/metabolismo , Eliminación de Secuencia , Factores de Transcripción/metabolismo , Virulencia/genéticaRESUMEN
Tandemly repeated ribosomal DNA (rDNA) arrays are among the most evolutionary dynamic loci of eukaryotic genomes. The loci code for essential cellular components, yet exhibit extensive copy number (CN) variation within and between species. CN might be partly determined by the requirement of dosage balance between the 5S and 45S rDNA arrays. The arrays are nonhomologous, physically unlinked in mammals, and encode functionally interdependent RNA components of the ribosome. Here we show that the 5S and 45S rDNA arrays exhibit concerted CN variation (cCNV). Despite 5S and 45S rDNA elements residing on different chromosomes and lacking sequence similarity, cCNV between these loci is strong, evolutionarily conserved in humans and mice, and manifested across individual genotypes in natural populations and pedigrees. Finally, we observe that bisphenol A induces rapid and parallel modulation of 5S and 45S rDNA CN. Our observations reveal a novel mode of genome variation, indicate that natural selection contributed to the evolution and conservation of cCNV, and support the hypothesis that 5S CN is partly determined by the requirement of dosage balance with the 45S rDNA array. We suggest that human disease variation might be traced to disrupted rDNA dosage balance in the genome.
Asunto(s)
Variaciones en el Número de Copia de ADN/genética , ADN Ribosómico/genética , Genoma/genética , Animales , Compuestos de Bencidrilo/toxicidad , Cromosomas Humanos Par 1/genética , Variaciones en el Número de Copia de ADN/efectos de los fármacos , Femenino , Sitios Genéticos , Genoma Humano/genética , Genotipo , Humanos , Masculino , Ratones , Linaje , Fenoles/toxicidad , Polimorfismo de Nucleótido Simple/genética , ARN Ribosómico/genética , ARN Ribosómico 5S/genéticaRESUMEN
This study compares energy spectra of the multiple electron beams of individual radiotherapy machines, as well as the sets of spectra across multiple matched machines. Also, energy spectrum metrics are compared with central-axis percent depth-dose (PDD) metrics. METHODS: A lightweight, permanent magnet spectrometer was used to measure energy spectra for seven electron beams (7-20 MeV) on six matched Elekta Infinity accelerators with the MLCi2 treatment head. PDD measurements in the distal falloff region provided R50 and R80-20 metrics in Plastic Water® , which correlated with energy spectrum metrics, peak mean energy (PME) and full-width at half maximum (FWHM). RESULTS: Visual inspection of energy spectra and their metrics showed whether beams on single machines were properly tuned, i.e., FWHM is expected to increase and peak height decrease monotonically with increased PME. Also, PME spacings are expected to be approximately equal for 7-13 MeV beams (0.5-cm R90 spacing) and for 13-16 MeV beams (1.0-cm R90 spacing). Most machines failed these expectations, presumably due to tolerances for initial beam matching (0.05 cm in R90 ; 0.10 cm in R80-20 ) and ongoing quality assurance (0.2 cm in R50 ). Also, comparison of energy spectra or metrics for a single beam energy (six machines) showed outlying spectra. These variations in energy spectra provided ample data spread for correlating PME and FWHM with PDD metrics. Least-squares fits showed that R50 and R80-20 varied linearly and supralinearly with PME, respectively; however, both suggested a secondary dependence on FWHM. Hence, PME and FWHM could serve as surrogates for R50 and R80-20 for beam tuning by the accelerator engineer, possibly being more sensitive (e.g., 0.1 cm in R80-20 corresponded to 2.0 MeV in FWHM). CONCLUSIONS: Results of this study suggest a lightweight, permanent magnet spectrometer could be a useful beam-tuning instrument for the accelerator engineer to (a) match electron beams prior to beam commissioning, (b) tune electron beams for the duration of their clinical use, and (c) provide estimates of PDD metrics following machine maintenance. However, a real-time version of the spectrometer is needed to be practical.
Asunto(s)
Electrones , Método de Montecarlo , Neoplasias/radioterapia , Aceleradores de Partículas/instrumentación , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodosRESUMEN
Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFNγ to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNγ-treated cells and improved survival in mice with postinfluenza pneumococcal pneumonia. Transcription factor analysis also indicated a role for transcription factor E-box (TFEB) in MARCO recovery. Overexpression of TFEB in THP-1 cells led to marked increases in MARCO. The ability of Akt activation to increase MARCO expression in IFNγ-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in postinfluenza bacterial pneumonia.
Asunto(s)
Resistencia a la Enfermedad , Factores Inmunológicos/farmacología , Gripe Humana/complicaciones , Neumonía Bacteriana/etiología , Neumonía Bacteriana/inmunología , Receptores Inmunológicos/metabolismo , Animales , Secuencia de Bases , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Líquido del Lavado Bronquioalveolar , Catequina/análogos & derivados , Catequina/farmacología , Línea Celular , Citocinas/metabolismo , Interacciones Huésped-Patógeno/inmunología , Humanos , Interferón gamma/farmacología , Isotiocianatos/farmacología , Quinasas Quinasa Quinasa PAM/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Infecciones por Orthomyxoviridae/complicaciones , Fagocitosis/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Inmunológicos/genética , Análisis de Secuencia de ARN , Transducción de Señal , Staphylococcus aureus/efectos de los fármacos , Sulfóxidos , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Copy number variants (CNVs) are a class of structural variants (SVs) and are defined as fragments of DNA that are present at variable copy number in comparison with a reference genome. Recent advances in bioinformatics methodologies and sequencing technologies have enabled the high-resolution quantification of genome-wide CNVs. In pathogenic fungi SVs have been shown to alter gene expression, influence host specificity, and drive fungicide resistance, but little attention has focused specifically on CNVs. Using publicly available sequencing data, we identified 90 isolates across 212 Cryptococcus gattii genomes that belong to the VGII subgroups responsible for the recent deadly outbreaks in the North American Pacific Northwest. We generated CNV profiles for each sample to investigate the prevalence and function of CNV in C. gattii. RESULTS: We identified eight genetic clusters among publicly available Illumina whole genome sequence data from 212 C. gattii isolates through population structure analysis. Three clusters represent the VGIIa, VGIIb, and VGIIc subgroups from the North American Pacific Northwest. CNV was bioinformatically predicted and affected ~300-400 Kilobases (Kb) of the C. gattii VGII subgroup genomes. Sixty-seven loci, encompassing 58 genes, showed highly divergent patterns of copy number variation between VGII subgroups. Analysis of PFam domains within divergent CN variable genes revealed enrichment of protein domains associated with transport, cell wall organization and external encapsulating structure. CONCLUSIONS: CNVs may contribute to pathological and phenotypic differences observed between the C. gattii VGIIa, VGIIb, and VGIIc subpopulations. Genes overlapping with population differentiated CNVs were enriched for several virulence related functional terms. These results uncover novel candidate genes to examine the genetic and functional underpinnings of C. gattii pathogenicity.
Asunto(s)
Criptococosis/epidemiología , Criptococosis/microbiología , Cryptococcus gattii/genética , Variaciones en el Número de Copia de ADN , Variación Genética , Genoma Bacteriano , Biología Computacional/métodos , Cryptococcus gattii/clasificación , Bases de Datos de Ácidos Nucleicos , Brotes de Enfermedades , Ontología de Genes , Sitios Genéticos , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Noroeste de Estados Unidos/epidemiologíaRESUMEN
The purpose of this work was to evaluate differences in dose resulting from the use of copper aperture inserts compared to lead-alloy (Cerrobend) aperture inserts for electron beam therapy. Specifically, this study examines if copper aperture inserts can be used clinically with the same commissioning data measured using lead-alloy aperture inserts. The copper inserts were acquired from .decimal, LLC and matching lead-alloy, Cerrobend inserts were constructed in-house for 32 com-binations of nine square insert field sizes (2 × 2 to 20 × 20 cm2) and five applicator sizes (6 × 6 to 25 × 25 cm2). Percent depth-dose and off-axis relative dose profiles were measured using an electron diode in water for select copper and Cerrobend inserts for a subset of applicators (6 × 6, 10 × 10, 25 × 25 cm2) and energies (6, 12, 20 MeV) at 100 and 110 cm source-to-surface distances (SSD) on a Varian Clinac 21EX accelerator. Dose outputs were measured for all field size-insert combina-tions and five available energies (6-20 MeV) at 100 cm SSD and for a smaller subset at 110 cm SSD. Using these data, 2D planar absolute dose distributions were generated and compared. Criteria for agreement were ± 2% of maximum dose or 1 mm distance-to-agreement for 99% of points. A gamma analysis of the beam dosimetry showed 94 of 96 combinations of insert size, applicator, energy, and SSD were within the 2%/1 mm criteria for > 99% of points. Outside the field, copper inserts showed less bremsstrahlung dose under the insert compared to Cerrobend (greatest difference was 2.5% at 20 MeV and 100 cm SSD). This effect was most prominent at the highest energies for combinations of large applicators with small field sizes, causing some gamma analysis failures. Inside the field, more electrons scattered from the collimator edge of copper compared to Cerrobend, resulting in an increased dose at the field edge for copper at shallow depths (greatest increase was 1% at 20 MeV and 100 cm SSD). Dose differences decreased as the SSD increased, with no gamma failures at 110 cm SSD. Inserts for field sizes ≥ 6 × 6 cm2 at any energy, or for small fields (≤ 4 × 4 cm2) at energies < 20 MeV, showed dosimetric differences less than 2%/1 mm for more than 99% of points. All areas of comparison criteria failures were from lower out-of-field dose under copper inserts due to a reduction in bremsstrahlung production, which is clinically beneficial in reducing dose to healthy tissue outside of the planned treatment volume. All field size-applicator size-energy combinations passed 3%/1 mm criteria for 100% of points. Therefore, it should be clinically acceptable to utilize copper insets with dose distributions measured with Cerrobend inserts for treatment planning dose calculations and monitor unit calculations.
Asunto(s)
Aleaciones/química , Cobre/química , Electrones , Plomo/química , Fantasmas de Imagen , Humanos , Método de Montecarlo , Aceleradores de Partículas , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
AIM: To estimate cost-effectiveness of botulinum toxin therapy for axillary hyperhidrosis compared to the standard surgical intervention of endoscopic thoracic sympathectomy (ETS). METHODS: The validated dermatology life quality index questionnaire was given to patients attending for treatment over a 4 month period, to assess their quality of life (QoL) over the preceding week (n = 44). Follow-up was performed 4-6 weeks later by telephone using the same questionnaire to validate the effectiveness of the treatment. The duration of effect of the botulinum toxin treatment was also recorded and this data was used as the basis for cost effectiveness analysis. Using HIPE data, the baseline cost for single intervention using botulinum toxin and ETS was retrieved. Using figures provided by HIPE and expert opinion of the costs of complications, a stochastic model for 10,000 patients was used to evaluate the total costs for ETS including the complications. RESULTS: The results from the QoL analysis show that botulinum toxin therapy is a successful therapy for improvement of symptoms. It was revealed that the mean interval before recurrence of original symptoms after botulinum toxin therapy was 5.6 months. The baseline cost for both treatments are 389 for botulinum toxin and 9389 for uncomplicated ETS. The stochastic model yields a mean cost of 11,390 for ETS including complications. CONCLUSIONS: Treatments reached cost equivalence after 13.3 years. However, given the efficacy of the botulinum toxin therapy and the low risk we propose that botulinum toxin therapy for hyperhidrosis should be considered the gold standard.
Asunto(s)
Toxinas Botulínicas/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Hiperhidrosis/tratamiento farmacológico , Hiperhidrosis/cirugía , Calidad de Vida , Simpatectomía , Toracoscopía , Adulto , Axila , Toxinas Botulínicas/economía , Fármacos Dermatológicos/economía , Femenino , Estudios de Seguimiento , Humanos , Hiperhidrosis/diagnóstico , Hiperhidrosis/economía , Masculino , Satisfacción del Paciente , Proyectos Piloto , Estudios Retrospectivos , Escocia , Encuestas y Cuestionarios , Simpatectomía/economía , Toracoscopía/economía , Toracoscopía/métodos , Resultado del TratamientoRESUMEN
Malaria morbidity and mortality caused by both Plasmodium falciparum and Plasmodium vivax extend well beyond the African continent, and although P. vivax causes between 80 and 300 million severe cases each year, vivax transmission remains poorly understood. Plasmodium parasites are transmitted by Anopheles mosquitoes, and the critical site of interaction between parasite and host is at the mosquito's luminal midgut brush border. Although the genome of the "model" African P. falciparum vector, Anopheles gambiae, has been sequenced, evolutionary divergence limits its utility as a reference across anophelines, especially non-sequenced P. vivax vectors such as Anopheles albimanus. Clearly, technologies and platforms that bridge this substantial scientific gap are required in order to provide public health scientists with key transcriptomic and proteomic information that could spur the development of novel interventions to combat this disease. To our knowledge, no approaches have been published that address this issue. To bolster our understanding of P. vivax-An. albimanus midgut interactions, we developed an integrated bioinformatic-hybrid RNA-Seq-LC-MS/MS approach involving An. albimanus transcriptome (15,764 contigs) and luminal midgut subproteome (9,445 proteins) assembly, which, when used with our custom Diptera protein database (685,078 sequences), facilitated a comparative proteomic analysis of the midgut brush borders of two important malaria vectors, An. gambiae and An. albimanus.
Asunto(s)
Anopheles/genética , Biología Computacional , Proteínas de Insectos/análisis , Insectos Vectores/genética , Proteoma/análisis , ARN/análisis , Secuencia de Aminoácidos , Animales , Anopheles/parasitología , Cromatografía Liquida , Bases de Datos de Proteínas , Interacciones Huésped-Parásitos , Humanos , Proteínas de Insectos/química , Insectos Vectores/parasitología , Malaria/parasitología , Microvellosidades , Plasmodium falciparum , Plasmodium vivax , Proteómica , Espectrometría de Masas en Tándem , TranscriptomaRESUMEN
Accurate beam data acquisition during commissioning is essential for modeling the treatment planning system and dose calculation in radiotherapy. Although currently several commercial scanning systems are available, there is no report that compared the differences among the systems because most institutions do not acquire several scanning systems due to the high cost, storage space, and infrequent usage. In this report, we demonstrate the intra- and intervariability of beam profiles measured with four commercial scanning systems. During a recent educational and training workshop, four different vendors of beam scanning water phantoms were invited to demonstrate the operation and data collection of their systems. Systems were set up utilizing vendor-recommended protocols and were operated with a senior physicist, who was assigned as an instructor along with vendor. During the training sessions, each group was asked to measure beam parameters, and the intravariability in percent depth dose (PDD). At the end of the day, the profile of one linear accelerator was measured with each system to evaluate intervariability. Relatively very small (SD < 0.12%) intervariability in PDD was observed among four systems at a region deeper than peak (1.5 cm). All systems showed almost identical profiles. At the area within 80% of radiation field, the average, and maximum differences were within ± 0.35% and 0.80%, respectively, compared to arbitrarily chosen IBA system as reference. In the penumbrae region, the distance to agreement (DTA) of the region where dose difference exceed ± 1% was less than 1 mm. Repeated PDD measurement showed small intravariability with SD < 0.5%, although large SD was observed in the buildup region. All four water phantom scanning systems demonstrated adequate accuracy for beam data collection (i.e., within 1% of dose difference or 1 mm of DTA among each other). It is concluded that every system is capable of acquiring accurate beam. Thus the selection of a water scanning system should be based on institutional comfort, personal preference of software and hardware, and financial consideration.
Asunto(s)
Aceleradores de Partículas/instrumentación , Aceleradores de Partículas/normas , Fantasmas de Imagen , Radiometría/métodos , Radiometría/normas , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Fotones , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/normas , Programas Informáticos , AguaRESUMEN
In 2009, Mary Bird Perkins Cancer Center (MBPCC) established a Radiation Oncology Physics Residency Program to provide opportunities for medical physics residency training to MS and PhD graduates of the CAMPEP-accredited Louisiana State University (LSU)-MBPCC Medical Physics Graduate Program. The LSU-MBPCC Program graduates approximately six students yearly, which equates to a need for up to twelve residency positions in a two-year program. To address this need for residency positions, MBPCC has expanded its Program by developing a Consortium consisting of partnerships with medical physics groups located at other nearby clinical institutions. The consortium model offers the residents exposure to a broader range of procedures, technology, and faculty than available at the individual institutions. The Consortium institutions have shown a great deal of support from their medical physics groups and administrations in developing these partnerships. Details of these partnerships are specified within affiliation agreements between MBPCC and each participating institution. All partner sites began resident training in 2011. The Consortium is a network of for-profit, nonprofit, academic, community, and private entities. We feel that these types of collaborative endeavors will be required nationally to reach the number of residency positions needed to meet the 2014 ABR certification requirements and to maintain graduate medical physics training programs.