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Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilaxglyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes. Citation: Tan YP, Bishop-Hurley SL, Shivas RG, et al. 2022. Fungal Planet description sheets: 1436-1477. Persoonia 49: 261-350. https://doi.org/10.3767/persoonia.2022.49.08.
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The phylogeny and taxonomy of powdery mildews, belonging to the genus Erysiphe, on Lonicera species throughout the world are examined and discussed. Phylogenetic analyses revealed that sequences retrieved from Erysiphe lonicerae, a widespread powdery mildew species distributed in the Northern Hemisphere on a wide range of Lonicera spp., constitutes a complex of two separate species, viz., E. lonicerae (s. str.) and Erysiphe ehrenbergii comb. nov. Erysiphe lonicerae occurs on Lonicera spp. belonging to Lonicera subgen. Lonicera (= subgen. Caprifolium and subgen. Periclymenum), as well as L. japonica. Erysiphe ehrenbergii comb. nov. occurs on Lonicera spp. of Lonicera subgen. Chamaecerasus. Phylogenetic and morphological analyses have also revealed that Microsphaera caprifoliacearum (≡ Erysiphe caprifoliacearum) should be reduced to synonymy with E. lonicerae (s. str.). Additionally, Erysiphe lonicerina sp. nov. on Lonicera japonica in Japan is described and the new name Erysiphe flexibilis, based on Microsphaera lonicerae var. flexuosa, is introduced. The phylogeny of Erysiphe ehrenbergii and E. lonicerae as well as other Erysiphe species on honeysuckle is discussed, and a survey of all species, including a key to the species concerned, is provided. Citation: Bradshaw M, Braun U, Götz M, Takamatsu S (2020). Taxonomy and phylogeny of the Erysiphe lonicerae complex (Helotiales, Erysiphaceae) on Lonicera spp. Fungal Systematics and Evolution 7: 49-65. doi: 10.3114/fuse.2021.07.03.
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BACKGROUND: Emerging evidence implicates the gut microbiota in central nervous system functioning via its effects on inflammation, the hypothalamic-pituitary axis, and/or neurotransmission. Our understanding of the cellular underpinnings of the brain-gut relationship is based almost exclusively on animal models with some small-scale human studies. This study examined the relationship between the gut microbiota and psychiatric symptom severity and treatment response among inpatients with serious mental illness. METHOD: We collected data from adult inpatients (N = 111). Measures of diagnoses, suicide severity, trauma, depression, and anxiety were collected shortly after admission, while self-collected fecal swabs were collected early in the course of hospitalization and processed using 16S rRNA gene sequencing and whole genome shotgun sequencing methods. RESULTS: Results indicate that depression and anxiety severity shortly after admission were negatively associated with bacterial richness and alpha diversity. Additional analyses revealed a number of bacterial taxa associated with depression and anxiety severity. Gut microbiota richness and alpha diversity early in the course of hospitalization was a significant predictor of depression remission at discharge. CONCLUSIONS: This study is among the first to demonstrate a gut microbiota relationship with symptom severity among psychiatric inpatients as well as a relationship to remission of depression post-treatment. These findings are consistent with animal models and limited human studies as well as with the broader literature implicating inflammation in the pathophysiology of depression. These findings offer the foundation for further studies of novel therapeutic approaches to the treatment, prevention of, or recurrence of serious mental illness.
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Microbioma Gastrointestinal , Adulto , Animales , Ansiedad , Trastornos de Ansiedad , Microbioma Gastrointestinal/genética , Humanos , ARN Ribosómico 16S/genética , Resultado del TratamientoRESUMEN
AIM: The objective of this study was to assess the impact of a simulation workshop on self-efficacy towards teaching for nurse educators in India. Additionally, we sought to revise and validate a tool to measure self-efficacy in teaching for use with a global audience. BACKGROUND: Simulation is an evidence-based teaching and learning method and is increasingly used in nursing education globally. INTRODUCTION: As new technology and teaching methods such as simulation continue to evolve, it is important for new as well as experienced nurse educators globally to have confidence in their teaching skills and abilities. METHODS: The study included (1) instrument revision, and measures of reliability and validation, (2) an 8-h faculty development workshop intervention on simulation, (3) pre- and post-survey of self-efficacy among nurse educators, and (4) investigation of relationship between faculty socio-demographics and degree of self-efficacy. RESULTS: The modified tool showed internal consistency (r = 0.98) and was validated by international faculty experts. There were significant improvements in total self-efficacy (P < 0.001) and subscale scores among nurse educators after the simulation workshop intervention when compared to pre-survey results. No significant relationships were found between socio-demographic variables and degree of self-efficacy. DISCUSSION: Strong self-efficacy in teaching among nurse educators is crucial for effective learning to occur. CONCLUSIONS AND IMPLICATIONS FOR NURSING: Results indicated the simulation workshop was effective in significantly improving self-efficacy towards teaching for nurse educators using an internationally validated tool. IMPLICATIONS FOR NURSING POLICY: The Minister of Health in India recently called for improvements in nursing education. Introducing nursing education on simulation as a teaching method in India and globally to improve self-efficacy among teachers is an example of a strategy towards meeting this call.
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Educación en Enfermería , Docentes de Enfermería/educación , Docentes de Enfermería/psicología , Autoeficacia , Entrenamiento Simulado , Formación del Profesorado , Adulto , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
An important histological difference between normal, uninjured dermis and scar tissue such as that found in keloid scars is the pattern (morphological architecture) in which the collagen is deposited and arranged. In the uninjured dermis, collagen bundle architecture appears randomly organized (or in a basket weave formation), whereas in pathological conditions such as keloid scar tissue, collagen bundles are often found in whorls or in a hypotrophic scar collagen is more densely packed in a parallel configuration. In the case of skin, a scar disables the dermis, leaving it weaker, stiff and with a loss of optimal functionality. The absence of objective and quantifiable assessments of collagen orientation is a major bottleneck in monitoring progression of scar therapeutics. In this article, a novel quantitative approach for analyzing collagen orientation is reported. The methodology is demonstrated using collagen produced by cells in a model scar environment and examines collagen remodeling post-TGFß stimulation in vitro. The method is shown to be reliable and effective in identifying significant coherency differences in the collagen deposited by human keloid scar cells. The technique is also compared for analysing collagen architecture in rat sections of normal, scarred skin and tendon tissue. Results demonstrate that the proposed computational method provides a fast and robust way of analyzing collagen orientation in a manner surpassing existing methods. This study establishes this methodology as a preliminary means of monitoring in vitro and in tissue treatment modalities which are expected to alter collagen morphology.
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BACKGROUND: Natalizumab (NTZ), a monoclonal antibody to human α4ß1/ß7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8â weeks 5â days. METHODS: A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4â weeks 3â days to 6â weeks 6â days; late extended dosing (LED; n=274) every 7â weeks to 8â weeks 5â days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4â weeks. RESULTS: 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort. CONCLUSIONS: Dosing intervals up to 8â weeks 5â days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.
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Leucoencefalopatía Multifocal Progresiva/inducido químicamente , Leucoencefalopatía Multifocal Progresiva/prevención & control , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/administración & dosificación , Natalizumab/uso terapéutico , Adulto , Esquema de Medicación , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Natalizumab/efectos adversos , Neuroimagen , Recurrencia , Estudios RetrospectivosRESUMEN
Cell behavior is tightly coupled to the properties of the extracellular matrix (ECM) to which they attach. Fibronectin (Fn) forms a supermolecular, fibrillar component of the ECM that is prominent during development, wound healing and the progression of numerous diseases. This indicates that Fn has an important function in controlling cell behavior during dynamic events in vivo. The multiscale architecture of Fn molecules assembled into these fibers determines the ligand density of cell adhesion sites on the surface of the Fn fiber, Fn fiber porosity for cell signaling molecules such as growth factors, the mechanical stiffness of the Fn matrix and the adhesivity of Fn for its numerous soluble ligands. These parameters are altered by mechanical strain applied to the ECM. Recent efforts have attempted to link the molecular properties of Fn with bulk properties of Fn matrix fibers. Studies of isolated Fn fibers have helped to characterize the fiber's material properties and, in combination with models of Fn molecular behavior in the fibers, have begun to provide insights into the Fn molecular arrangement and intermolecular adhesions within the fibers. A review of these studies allows the development of an understanding of the mechanobiological functions of Fn.
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Fibronectinas/química , Fibronectinas/metabolismo , Animales , Matriz Extracelular/metabolismo , Fibronectinas/biosíntesis , Humanos , Ligandos , Mecanotransducción Celular , Estrés Mecánico , Relación Estructura-ActividadRESUMEN
BACKGROUND: Although enamel matrix derivative (EMD) has demonstrated the ability to promote angiogenesis and osteogenesis both in vitro and in vivo, the specific elements within the EMD compound responsible for these effects remain unknown. METHODS: Nine different protein pools from a commercially produced EMD were collected based on molecular weight. Six of these pools, along with the complete EMD unfractionated compound and positive and negative controls, were tested for their ability to induce bone formation in a calvarial induction assay. Immunocytochemistry of phosphorylated SMAD1/5/8 (phospho-SMAD), osterix, and vascular endothelial growth factor A (VEGF-A) was carried out at selected time points. Finally, proteomic analysis was completed to determine the specific protein-peptide content of the various osteoinductive pools. RESULTS: One of the lower-molecular-weight pools tested, pool 7, showed bone induction responses significantly greater than those of the other pools and the complete EMD compound and was concentration dependent. Dynamic bone formation rate analysis demonstrated that pool 7 was optimally active at the 5- to 10-µg concentration. It was demonstrated that EMD and pool 7 induced phospho-SMAD, osterix, and VEGF-A, which is indicative of increased bone morphogenetic protein (BMP) signaling. Proteomic composition analysis demonstrated that pool 7 had the highest concentration of the biologically active amelogenin-leucine-rich amelogenin peptide and ameloblastin 17-kDa peptides. CONCLUSIONS: These studies demonstrate that the low-molecular-weight protein pools (7 to 17 kDa) within EMD have greater osteoinductive potential than the commercially available complete EMD compound and that the mechanism of action, in part, is through increased BMP signaling and increased osterix and VEGF-A. With this information, selected components of EMD can now be formulated for optimal osteo- and angio-genesis.
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Proteínas del Esmalte Dental/análisis , Amelogenina/análisis , Animales , Proteínas Morfogenéticas Óseas/efectos de los fármacos , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Proteínas del Esmalte Dental/fisiología , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Espectrometría de Masas , Ratones , Modelos Animales , Peso Molecular , Osteogénesis/efectos de los fármacos , Hueso Parietal/efectos de los fármacos , Periostio/efectos de los fármacos , Proteoma/análisis , Proteína Smad1/análisis , Proteína Smad1/farmacología , Proteína Smad5/análisis , Proteína Smad5/farmacología , Proteína Smad8/análisis , Proteína Smad8/farmacología , Factor de Transcripción Sp7 , Factores de Transcripción/análisis , Factores de Transcripción/farmacología , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/farmacologíaRESUMEN
BACKGROUND: Necrotizing ulcerative gingivitis (NUG) is a periodontal disease characterized by pain, bleeding, and necrosis of interdental papillae. This series details treatment of four cases, followed by a discussion of the disease. CASE DESCRIPTION: Four patients presented to four practitioners for treatment of severe gingival pain, each eventually being diagnosed with NUG. All patients in this series were successfully treated using accepted protocols, and though each was different with regard to presenting signs and symptoms, all responded similarly to treatment. Similar to the patients described in this series, NUG cases in general can present with varying degrees of involvement from barely-noticeable to starkly severe. CLINICAL IMPLICATIONS: The most severe cases of NUG are often more destructive in appearance than those most commonly seen in textbooks, while in the mildest cases the appearance can almost be mistaken for health.
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Antiinfecciosos Locales/uso terapéutico , Profilaxis Dental , Gingivitis Ulcerosa Necrotizante/diagnóstico , Adulto , Gingivitis Ulcerosa Necrotizante/terapia , Humanos , Masculino , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Cognitive impairment secondary to frontal lobe atrophy exists in 40-60% of Amyotrophic Lateral Sclerosis (ALS) cases. We aimed to determine the prevalence of frontal-lobe mediated behavioral impairment in (ALS) and to ascertain its relationship to cognitive impairment. METHODS: Two-hundred and twenty five patients diagnosed with sporadic ALS were evaluated for behavioral dysfunction using the Frontal Systems Behavior Scale (FrSBe), a validated measure used to examine frontal-lobe mediated behaviors, specifically apathy, executive dysfunction and disinhibition; a total behavior score is also provided. Additionally, a subset of patients also underwent a comprehensive neuropsychological evaluation. RESULTS: Changes in the total FrSBe scores were observed in 24.4% of the patients and 39.6% of the patients had impairment in at least one behavioral domain with symptoms of Apathy being the most common (31.1%). Cognitively impaired ALS patients had worse total (P = 0.05) and apathy scores (P < 0.01); however, behavioral dysfunction was also present in 16% of the cognitively intact patients. Half of the behaviorally intact patients exhibited cognitive impairment. Significant correlations were observed for performance on certain neuropsychological tests (Animal fluency, Block Design, Logical Memory I and Verbal Series Attention Test) and severity of behavioral dysfunction on certain FrSBe sub scores. CONCLUSIONS: Frontal-lobe mediated behavioral dysfunction appears to be common in ALS. Cognitively impaired ALS patients had greater behavioral dysfunction. Recognition of behavioral and cognitive dysfunction may assist health-care providers and care-givers recognize changes in decision-making capacity and treatment compliance of patients with ALS.
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Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/psicología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Lóbulo Frontal/fisiopatología , Adulto , Anciano , Comorbilidad , Toma de Decisiones/fisiología , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
Ventilatory depression is a significant risk associated with the use of opioids. We assessed whether opioid-induced ventilatory depression can be selectively antagonized by an ampakine without reduction of analgesia. In 16 healthy men, after a single oral dose of 1,500 mg of the ampakine CX717, a target concentration of 100 ng/ml alfentanil decreased the respiratory frequency by only 2.9 +/- 33.4% as compared with 25.6 +/- 27.9% during placebo coadministration (P < 0.01).Blood oxygenation and the ventilatory response to hypercapnic challenge also showed significantly smaller decreases with CX717 than with placebo. In contrast, CX717 did not affect alfentanil-induced analgesia in either electrical or heat-based experimental models of pain. Both ventilatory depression and analgesia were reversed with 1.6 mg of naloxone. These results support the use of ampakines as selective antidotes in humans to counter opioid-induced ventilatory depression without affecting opioid-mediated analgesia.
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Alfentanilo/efectos adversos , Analgésicos Opioides/efectos adversos , Isoxazoles/farmacología , Dolor/tratamiento farmacológico , Insuficiencia Respiratoria/prevención & control , Administración Oral , Adulto , Alfentanilo/farmacología , Analgésicos Opioides/farmacología , Estudios Cruzados , Método Doble Ciego , Humanos , Hipercapnia/fisiopatología , Masculino , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Oxígeno/sangre , Insuficiencia Respiratoria/inducido químicamente , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to compare the incidence of nausea and vomiting in patients with acute pain treated with morphine along with prophylactic metoclopramide or placebo. METHOD: A randomised controlled trial was carried out on patients requiring morphine for acute pain in the emergency department (ED) setting. Children under the age of 12, patients who had been vomiting or had already received prehospital analgesia, and those unable to give consent were excluded. All patients were given either metoclopramide (10 mg) or placebo (normal saline) followed by intravenous morphine. Pain scores (measured on a visual analogue scale) before and after morphine administration, all incidents of nausea or vomiting, the dose of morphine, and the patients' demographic data were recorded. Fisher's exact test was used for comparing the two groups of patients. RESULTS: A total of 259 patients were recruited. There were 123 patients in the metoclopramide group (age range 15-94 years; median age 53) and 136 patients in the placebo group (age range 17-93 years; median age 52.5). The overall incidence of nausea and vomiting in the whole study population was 2.7%, (1.6% in the metoclopramide group and 3.7% in the placebo group). The difference between the two groups was not statistically significant (Fisher's exact test = 0.451; p = 0.3; z-test statistic = 1.02; 95% CI -6% to 2%). CONCLUSION: When intravenous morphine is administered for acute pain, the overall incidence of nausea and vomiting is low, regardless of whether these patients are given prophylactic metoclopramide or not.
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Analgésicos Opioides/efectos adversos , Antieméticos/uso terapéutico , Metoclopramida/uso terapéutico , Morfina/efectos adversos , Dolor/prevención & control , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Dimensión del Dolor , Vómitos/inducido químicamenteRESUMEN
The perception of natural scenes relies on the integration of pre-existing knowledge with the immediate results of attentional processing, and what can be remembered from a scene depends in turn on how that scene is perceived and understood. However, there are conflicting results in the literature as to whether people are more likely to remember those objects that are consistent with the scene or those that are not. Moreover, whether any discrepancy between the likelihood of remembering schema-consistent or schema-inconsistent objects should be attributed to the schematic effects on attention or on memory remains unclear. To address this issue, the current study attempted to directly manipulate attention allocation by requiring participants to look at (i) schema-consistent objects, (ii) schema-inconsistent objects, or (iii) to share attention equally across both. Regardless of the differential allocation of attention or object fixation, schema-consistent objects were better recalled whereas recognition was independent of schema-consistency, but depended on task instruction. These results suggest that attention is important both for remembering low-level object properties, and information whose retrieval is not supported by the currently active schema. Specific knowledge of the scenes being viewed can result in the recall of non-fixated objects, but without such knowledge attention is required to encode sufficient detail for subsequent recognition. Our results demonstrate therefore that attention is not critical for the retrieval of objects that are consistent with a scene's schematic content.
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Atención/fisiología , Memoria/fisiología , Reconocimiento Visual de Modelos/fisiología , Movimientos Oculares/fisiología , HumanosRESUMEN
OBJECTIVE: To investigate the prevalence and nature of cognitive changes associated with sporadic amyotrophic lateral sclerosis (ALS) using a large scale study. METHODS: Consecutive patients with sporadic ALS (n = 279) underwent comprehensive neurologic evaluation and neuropsychological testing. Testing data from normal controls (n = 129) were used for classification and comparison purposes. RESULTS: On non-motor, non-speed-dependent tasks, 51% of patients with ALS had evidence of cognitive impairment compared to 5% of controls. Cluster analysis suggested four patient subgroups: 49% intact, 32% with mild impairment, 13% with moderate impairment, and 6% with severe impairment. Forty-one patients (15%) met criteria for frontotemporal dementia (FTD). ALS patient subgroups, excluding the intact group, performed significantly lower on tests of executive function and memory than normal controls. Patients with more severe disease also had deficits in confrontation naming. Although memory function declined with increasing severity of overall cognitive impairment, only two patients had the severe memory loss typical of Alzheimer disease. Cognitive impairment was correlated with clinical measures of word-finding, phrase length, and motor programming. Cognitive impairment was not correlated with depression scores or severity or duration of motor or bulbar symptoms. Patients with bulbar vs limb-onset ALS were not different in either level of impairment or pattern of performance. CONCLUSIONS: These data confirm the presence of cognitive impairment in 50% of patients with ALS and particularly implicate executive dysfunction and mild memory decline in the disease process. More severe impairment occurs in a subset of patients with ALS and has features consistent with FTD.
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Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/psicología , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/psicología , Desempeño Psicomotor/fisiología , Adulto , Factores de Edad , Anciano , Esclerosis Amiotrófica Lateral/fisiopatología , Encéfalo/patología , Encéfalo/fisiopatología , Comorbilidad , Estudios Transversales , Demencia/epidemiología , Demencia/psicología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Escolaridad , Femenino , Humanos , Masculino , Trastornos de la Memoria/epidemiología , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Pruebas Neuropsicológicas , PrevalenciaRESUMEN
The botulinum neurotoxins (BoNTs) are category A biothreat agents which have been the focus of intensive efforts to develop vaccines and antibody-based prophylaxis and treatment. Such approaches must take into account the extensive BoNT sequence variability; the seven BoNT serotypes differ by up to 70% at the amino acid level. Here, we have analyzed 49 complete published sequences of BoNTs and show that all toxins also exhibit variability within serotypes ranging between 2.6 and 31.6%. To determine the impact of such sequence differences on immune recognition, we studied the binding and neutralization capacity of six BoNT serotype A (BoNT/A) monoclonal antibodies (MAbs) to BoNT/A1 and BoNT/A2, which differ by 10% at the amino acid level. While all six MAbs bound BoNT/A1 with high affinity, three of the six MAbs showed a marked reduction in binding affinity of 500- to more than 1,000-fold to BoNT/A2 toxin. Binding results predicted in vivo toxin neutralization; MAbs or MAb combinations that potently neutralized A1 toxin but did not bind A2 toxin had minimal neutralizing capacity for A2 toxin. This was most striking for a combination of three binding domain MAbs which together neutralized >40,000 mouse 50% lethal doses (LD(50)s) of A1 toxin but less than 500 LD(50)s of A2 toxin. Combining three MAbs which bound both A1 and A2 toxins potently neutralized both toxins. We conclude that sequence variability exists within all toxin serotypes, and this impacts monoclonal antibody binding and neutralization. Such subtype sequence variability must be accounted for when generating and evaluating diagnostic and therapeutic antibodies.
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Anticuerpos Antibacterianos/metabolismo , Sitios de Unión de Anticuerpos , Toxinas Botulínicas Tipo A/genética , Clostridium botulinum/clasificación , Animales , Anticuerpos Monoclonales/metabolismo , Secuencia de Bases , Toxinas Botulínicas Tipo A/antagonistas & inhibidores , Toxinas Botulínicas Tipo A/inmunología , Clostridium botulinum/inmunología , Variación Genética , Ratones , Estructura Terciaria de Proteína , Análisis de Secuencia de ADN , SerotipificaciónRESUMEN
Covert shifts of attention have been shown to improve detection and discrimination thresholds for a range of visual stimuli. Although there is some evidence to suggest that the allocation of attention to a particular region of interest occurs in a retinotopic frame of reference, the importance of an allocentric, or object-based, framework has gained widespread empirical support. The current experiment investigates the nature of the spatial representation in which covert shifts of attention occur in response to a reflexive prime. Primes and targets were presented in four conditions designed to vary systematically the validity of the spatial relationship between the prime and target in egocentric or allocentric coordinate frameworks. A significant advantage, in terms of reaction time and correct identification, was found for targets located in positions previously primed in an egocentric (but not allocentric) framework whereas there was no advantage for locations primed in an allocentric (but not egocentric) framework. These results suggest that the allocation of covert spatial attention within an egocentric framework may be more important than previously thought.
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Atención/fisiología , Orientación/fisiología , Percepción Espacial/fisiología , Humanos , Estimulación Luminosa/métodos , Tiempo de Reacción/fisiologíaRESUMEN
Clostridium botulinum comprises a diverse assemblage of clostridia that have the common property of producing a distinctive protein neurotoxin (BoNT) of similar pharmacological activity and extraordinary potency. BoNTs are produced in culture as molecular complexes consisting of BoNT, hemagglutinin (HA) and associated subcomponent proteins, nontoxic nonhemagglutinin (NTNH), and RNA. The genes encoding the protein components reside as a cluster on the chromosome, on bacteriophages, or on plasmids depending on the C. botulinum serotype. A gene BotR coding for a regulatory protein has been detected in toxin gene clusters from certain strains, as well as ORFs coding for uncharacterized components. The gene encoding TeNT is located on a large plasmid, and expression of the structural gene is controlled by the regulatory gene, TetR, located immediately upstream of the TeNT structural gene. TeNT is not known to be assembled into a protein/nucleic acid complex in culture. Cellular synthesis of BoNT and TeNT have been demonstrated to be positively regulated by the homologous proteins, BotR/A and TetR. Evidence suggests that negative regulatory factors and general control cascades such as those involved in nitrogen regulation and carbon catabolite repression also regulate synthesis of BoNTs. Neurotoxigenic clostridia have attracted considerable attention from scientists and clinicians during the past decade, and many excellent reviews are available on various aspects of these organisms and their neurotoxins. However, certain areas have not been well-studied, including metabolic regulation of toxin formation and genetic tools to study neurotoxigenic clostridia. These topics are the focus of this review.
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Toxinas Botulínicas/toxicidad , Clostridium botulinum/metabolismo , Neurotoxinas/toxicidad , Animales , Toxinas Botulínicas/biosíntesis , Clostridium botulinum/genética , Genoma Bacteriano , Humanos , Neurotoxinas/biosíntesis , TransfecciónRESUMEN
The partially edentulous adult offers a unique and problem-rich resource as a basis for a case-based learning scenario in clinical dentistry in the field of planning oral rehabilitation. However, there is little resource material available to help students negotiate the territory between diagnosis and treatment options of discrete conditions and treatment sequencing once decisions have been made. To address the educational void surrounding the teaching and learning of oral rehabilitation strategies, the authors have developed a CD-ROM 'Interactive Learning in Dentistry: Decision making in the oral rehabilitation of the partially edentulous adult'. The disc emphasises the distinction between 'doing' and 'planning to do' in the decision-making process. After using the disc the students should be able to apply a generic framework to formulate a custom oral rehabilitation plan for their own patient. The disc was evaluated by final-year students from the Faculty of Dentistry, University of Sydney. Response to the program was essentially positive and comments from students have impacted on further development.
Asunto(s)
Instrucción por Computador , Educación en Odontología/métodos , Arcada Parcialmente Edéntula/rehabilitación , Aprendizaje Basado en Problemas , Prostodoncia/educación , Adulto , CD-ROM , Toma de Decisiones , Humanos , Rehabilitación Bucal , Evaluación de Programas y Proyectos de Salud , Programas Informáticos , Encuestas y CuestionariosRESUMEN
BACKGROUND/OBJECTIVE: Subantimicrobial dose doxycycline (SDD 20 mg bid) plus scaling and root planing (SRP) significantly improved clinical attachment level (CAL) and reduced probing depth (PD) compared with placebo plus SRP in a double-blind, placebo-controlled, multicenter study of patients with adult periodontitis (AP). In a study conducted as a follow-up, the post-treatment effects of SDD were assessed in patients who completed the SRP study. METHODS: The SRP study was a 9-month, active-treatment study and the follow-up was a 3-month, no-treatment study. In the SRP study, tooth sites in qualifying quadrants were scaled and root planed and patients were randomized to receive twice daily SDD 20 mg or placebo. In the follow-up, patients received no study drug; investigators and patients remained blinded to the previous treatment group assignments. Efficacy measures included the change in CAL and PD from baseline values determined at the start of the SRP study in tooth sites stratified by baseline PD (i.e., 0-3 mm, 4-6 mm, > or =7 mm). Safety was evaluated using adverse event data and the results of clinical laboratory tests, oral pathology examinations, and microbiological assessments. RESULTS: Within each disease stratum, the incremental improvements in PD and CAL demonstrated in the SDD group over 9 months of active treatment were maintained through 3 additional months of no treatment. Treatment cessation did not result in an accelerated regression of periodontal health. No differences in the incidence of adverse events (including those related to infection) or laboratory or microbiological parameters were noted between the SDD group and the placebo group. CONCLUSIONS: The administration of SDD 20 mg bid for a period of up to 9 months is not associated with rebound effects or delayed or negative after-effects for a 3-month period after cessation of therapy.
Asunto(s)
Antibacterianos/uso terapéutico , Raspado Dental/métodos , Doxiciclina/uso terapéutico , Periodontitis/terapia , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Doxiciclina/administración & dosificación , Doxiciclina/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Metaloproteinasas de la Matriz/efectos de los fármacos , Persona de Mediana Edad , Índice Periodontal , Periodontitis/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Aplanamiento de la Raíz/métodos , Resultado del TratamientoRESUMEN
The ability of ascorbic acid to induce browning of (+)-catechin in a model wine system has been studied. A significant increase in absorbance at 440 nm was observed over 14 days when ascorbic acid was incubated at 45 degrees C with (+)-catechin in a model wine base. The onset of browning was delayed for about 2 days, although the length of the lag period was dependent on the amount of molecular oxygen in the headspace of the reaction system. The lag period was not observed when a preoxidized solution of ascorbic acid was used, suggesting that a product of ascorbic acid oxidation is responsible for the onset of browning. Hydrogen peroxide, when added directly to (+)-catechin in the model system, was not capable of producing the same degree of browning as that generated by ascorbic acid. Liquid chromotography evidence is presented to show that different reaction products are produced by ascorbic acid and hydrogen peroxide.