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2.
JAMA Netw Open ; 7(5): e2410721, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38753331

RESUMO

Importance: Preterm children are at risk for neurodevelopment impairments. Objective: To evaluate the effect of a music therapy (MT) intervention (parent-led, infant-directed singing) for premature children during the neonatal intensive care unit (NICU) stay and/or after hospital discharge on language development at 24 months' corrected age (CA). Design, Setting, and Participants: This predefined secondary analysis followed participants in the LongSTEP (Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and Their Caregivers) randomized clinical trial, which was conducted from August 2018 to April 2022 in 8 NICUs across 5 countries (Argentina, Colombia, Israel, Norway, and Poland) and included clinic follow-up visits and extended interventions after hospital discharge. Intervention: Participants were children born preterm (<35 weeks' gestation) and their parents. Participants were randomized at enrollment to MT with standard care (SC) or SC alone; they were randomized to MT or SC again at discharge. The MT was parent-led, infant-directed singing tailored to infant responses and supported by a music therapist and was provided 3 times weekly in the NICU and/or in 7 sessions across 6 months after discharge. The SC consisted of early intervention methods of medical, nursing, and social services, without MT. Main Outcome and Measures: Primary outcome was language development, as measured by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) language composite score, with the remaining BSID-III composite and subscale scores as the secondary outcomes. Group differences in treatment effects were assessed using linear mixed-effects models using all available data. Results: Of 206 participants (103 female infants [50%]; mean [SD] GA, 30.5 [2.7] weeks), 51 were randomized to MT and 53 to SC at enrollment; at discharge, 52 were randomized to MT and 50 to SC. A total of 112 (54%) were retained at the 24 months' CA follow-up. Most participants (79 [70%] to 93 [83%]) had BSID-III scores in the normal range (≥85). Mean differences for the language composite score were -2.36 (95% CI, -12.60 to 7.88; P = .65) for the MT at NICU with postdischarge SC group, 2.65 (95% CI, -7.94 to 13.23; P = .62) for the SC at NICU and postdischarge MT group, and -3.77 (95% CI, -13.97 to 6.43; P = .47) for the MT group at both NICU and postdischarge. There were no significant effects for cognitive or motor development. Conclusions and Relevance: This secondary analysis did not confirm an effect of parent-led, infant-directed singing on neurodevelopment in preterm children at 24 months' CA; wide CIs suggest, however, that potential effects cannot be excluded. Future research should determine the MT approaches, implementation time, and duration that are effective in targeting children at risk for neurodevelopmental impairments and introducing broader measurements for changes in brain development. Trial Registration: ClinicalTrials.gov Identifier: NCT03564184.


Assuntos
Recém-Nascido Prematuro , Musicoterapia , Humanos , Musicoterapia/métodos , Feminino , Masculino , Recém-Nascido , Lactente , Unidades de Terapia Intensiva Neonatal , Pré-Escolar , Desenvolvimento da Linguagem , Estudos Longitudinais , Desenvolvimento Infantil/fisiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Colômbia , Noruega , Israel
4.
Cancer Res Commun ; 2(4): 220-232, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-36187937

RESUMO

Ewing sarcoma is a fusion oncoprotein-driven primary bone tumor. A subset of patients (~10%) with Ewing sarcoma are known to harbor germline variants in a growing number of genes involved in DNA damage repair. We recently reported our discovery of a germline mutation in the DNA damage repair protein BARD1 (BRCA1-associated RING domain-1) in a patient with Ewing sarcoma. BARD1 is recruited to the site of DNA double stranded breaks via the poly(ADP-ribose) polymerase (PARP) protein and plays a critical role in DNA damage response pathways including homologous recombination. We thus questioned the impact of BARD1 loss on Ewing cell sensitivity to DNA damage and the Ewing sarcoma transcriptome. We demonstrate that PSaRC318 cells, a novel patient-derived cell line harboring a pathogenic BARD1 variant, are sensitive to PARP inhibition and by testing the effect of BARD1 depletion in additional Ewing sarcoma cell lines, we confirm that BARD1 loss enhances cell sensitivity to PARP inhibition plus radiation. Additionally, RNA-seq analysis revealed that loss of BARD1 results in the upregulation of GBP1 (guanylate-binding protein 1), a protein whose expression is associated with variable response to therapy depending on the adult carcinoma subtype examined. Here, we demonstrate that GBP1 contributes to the enhanced sensitivity of BARD1 deficient Ewing cells to DNA damage. Together, our findings demonstrate the impact of loss-of function mutations in DNA damage repair genes, such as BARD1, on Ewing sarcoma treatment response.


Assuntos
Neoplasias Ósseas , Tumores Neuroectodérmicos Primitivos Periféricos , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Dano ao DNA/genética , Reparo do DNA/genética , Neoplasias Ósseas/genética , Poli(ADP-Ribose) Polimerases/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética , Proteínas de Ligação ao GTP/genética , Proteína BRCA1/genética
5.
Brain ; 145(3): 1052-1068, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-34529034

RESUMO

Social feedback can selectively enhance learning in diverse domains. Relevant neurocognitive mechanisms have been studied mainly in healthy persons, yielding correlational findings. Neurodegenerative lesion models, coupled with multimodal brain measures, can complement standard approaches by revealing direct multidimensional correlates of the phenomenon. To this end, we assessed socially reinforced and non-socially reinforced learning in 40 healthy participants as well as persons with behavioural variant frontotemporal dementia (n = 21), Parkinson's disease (n = 31) and Alzheimer's disease (n = 20). These conditions are typified by predominant deficits in social cognition, feedback-based learning and associative learning, respectively, although all three domains may be partly compromised in the other conditions. We combined a validated behavioural task with ongoing EEG signatures of implicit learning (medial frontal negativity) and offline MRI measures (voxel-based morphometry). In healthy participants, learning was facilitated by social feedback relative to non-social feedback. In comparison with controls, this effect was specifically impaired in behavioural variant frontotemporal dementia and Parkinson's disease, while unspecific learning deficits (across social and non-social conditions) were observed in Alzheimer's disease. EEG results showed increased medial frontal negativity in healthy controls during social feedback and learning. Such a modulation was selectively disrupted in behavioural variant frontotemporal dementia. Neuroanatomical results revealed extended temporo-parietal and fronto-limbic correlates of socially reinforced learning, with specific temporo-parietal associations in behavioural variant frontotemporal dementia and predominantly fronto-limbic regions in Alzheimer's disease. In contrast, non-socially reinforced learning was consistently linked to medial temporal/hippocampal regions. No associations with cortical volume were found in Parkinson's disease. Results are consistent with core social deficits in behavioural variant frontotemporal dementia, subtle disruptions in ongoing feedback-mechanisms and social processes in Parkinson's disease and generalized learning alterations in Alzheimer's disease. This multimodal approach highlights the impact of different neurodegenerative profiles on learning and social feedback. Our findings inform a promising theoretical and clinical agenda in the fields of social learning, socially reinforced learning and neurodegeneration.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Doenças Neurodegenerativas , Doença de Parkinson , Doença de Alzheimer/patologia , Encéfalo/patologia , Demência Frontotemporal/patologia , Humanos , Doenças Neurodegenerativas/patologia , Doença de Parkinson/patologia
7.
Front Cell Dev Biol ; 9: 759259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35111748

RESUMO

p21-Activated kinase-1 (Pak1) is frequently overexpressed and/or amplified in human breast cancer and is necessary for transformation of mammary epithelial cells. Here, we show that Pak1 interacts with and phosphorylates the Calcium/Calmodulin-dependent Protein Kinase II (CaMKII), and that pharmacological inhibition or depletion of Pak1 leads to diminished activity of CaMKII. We found a strong correlation between Pak1 and CaMKII expression in human breast cancer samples, and combined inhibition of Pak1 and CaMKII with small-molecule inhibitors was synergistic and induced apoptosis more potently in Her2 positive and triple negative breast cancer (TNBC) cells. Co-adminstration of Pak and CaMKII small-molecule inhibitors resulted in a dramatic reduction of proliferation and an increase in apoptosis in a 3D cell culture setting, as well as an impairment in migration and invasion of TNBC cells. Finally, mice bearing xenografts of TNBC cells showed a significant delay in tumor growth when treated with small-molecule inhibitors of Pak and CaMKII. These data delineate a signaling pathway from Pak1 to CaMKII that is required for efficient proliferation, migration and invasion of mammary epithelial cells, and suggest new therapeutic strategies in breast cancer.

8.
Environ Entomol ; 49(5): 999-1011, 2020 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-32797186

RESUMO

The spotted lanternfly Lycorma delicatula (White) is an invasive insect spreading throughout southeast Asia and eastern North America. The rapid spread of this species is facilitated by the prevalence of its preferred host, tree of heaven (Ailanthus altissima (Mill.) Swingle), as well as its use of many other host plants. While the spotted lanternfly has been previously reported to use over 65 plant species, most of these reports are from Asia and may not be applicable in North America. Additionally, many of the known hosts have not been specified as feeding hosts or as egg laying substrates. To better understand the potential impacts of this invasive insect on natural and cultivated systems in North America, we reviewed records from published and unpublished results and observations of host plant use by spotted lanternfly. We aggregated 172 host plant records worldwide and found feeding behaviors associated with 103 plant taxa across 33 families and 17 orders, 20 of which were not previously known to be associated with SLF and 15 of which were not confirmed as feeding hosts. North American records account for 56 of these taxa which include native, cultivated, and nonnative species. As a result, the spotted lanternfly has the potential to impact a wide assortment of ecosystems throughout its potential range and its North American distribution may not be limited by the presence of tree of heaven.


Assuntos
Ailanthus , Hemípteros , Animais , Ecossistema , Insetos , América do Norte
9.
J Pediatr ; 226: 55-63.e2, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32681989

RESUMO

OBJECTIVES: To describe the clinical manifestations and outcomes of critically ill children with coronavirus disease-19 (COVID-19) in New York City. STUDY DESIGN: Retrospective observational study of children 1 month to 21 years admitted March 14 to May 2, 2020, to 9 New York City pediatric intensive care units (PICUs) with severe acute respiratory syndrome coronavirus 2 infection. RESULTS: Of 70 children admitted to PICUs, median age was 15 (IQR 9, 19) years; 61.4% male; 38.6% Hispanic; 32.9% black; and 74.3% with comorbidities. Fever (72.9%) and cough (71.4%) were the common presenting symptoms. Twelve patients (17%) met severe sepsis criteria; 14 (20%) required vasopressor support; 21 (30%) developed acute respiratory distress syndrome (ARDS); 9 (12.9%) met acute kidney injury criteria; 1 (1.4%) required renal-replacement therapy, and 2 (2.8%) had cardiac arrest. For treatment, 27 (38.6%) patients received hydroxychloroquine; 13 (18.6%) remdesivir; 23 (32.9%) corticosteroids; 3 (4.3%) tocilizumab; and 1 (1.4%) anakinra; no patient was given immunoglobulin or convalescent plasma. Forty-nine (70%) patients required respiratory support: 14 (20.0%) noninvasive mechanical ventilation, 20 (28.6%) invasive mechanical ventilation (IMV), 7 (10%) prone position, 2 (2.8%) inhaled nitric oxide, and 1 (1.4%) extracorporeal membrane oxygenation. Nine (45%) of the 20 patients requiring IMV were extubated by day 14 with median IMV duration of 218 (IQR 79, 310.4) hours. Presence of ARDS was significantly associated with duration of PICU and hospital stay, and lower probability of PICU and hospital discharge at hospital day 14 (P < .05 for all). CONCLUSIONS: Critically ill children with COVID-19 predominantly are adolescents, have comorbidities, and require some form of respiratory support. The presence of ARDS is significantly associated with prolonged PICU and hospital stay.


Assuntos
COVID-19/diagnóstico , Adolescente , Antivirais/uso terapêutico , COVID-19/epidemiologia , COVID-19/terapia , Criança , Pré-Escolar , Terapia Combinada , Comorbidade , Cuidados Críticos/métodos , Estado Terminal , Feminino , Seguimentos , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Masculino , Cidade de Nova Iorque/epidemiologia , Terapia Respiratória/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Environ Int ; 136: 105443, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31927465

RESUMO

Increasing amounts of anthropogenic debris enter the ocean because of mismanagement in coastal communities and, despite a global ban on deliberate dumping, also from vessels, endangering wildlife. Assessing marine plastic pollution directly is challenging, and an alternative is to use seabirds as bioindicators. Our analyses of long time-series (26-years) revealed substantial variation in the amount, characteristics and origin of marine debris (mainly macroplastics and mesoplastics, and excluding fishing gear) associated with seabirds at South Georgia, and, for two species, long-term increases in incidence since 1994. Annual debris recovery rates (items per capita) were 14 × higher in wandering albatrosses Diomedea exulans, and 6 × higher in grey-headed albatrosses Thalassarche chrysostoma and giant petrels Macronectes spp., than in black-browed albatrosses T. melanophris, partly related to differences in egestion (regurgitation), which clears items from the proventriculus. Although some debris types were common in all species, wandering albatrosses and giant petrels ingested higher proportions that were food-related or generic wrapping, gloves, clear or mixed colour, and packaged in South America. This was highly likely to originate from vessels, including the large South American fishing fleets with which they overlap. Debris associated with the two smaller albatrosses was more commonly shorter, rigid (miscellaneous plastic and bottle/tube caps), and packaged in East Asia. Grey-headed albatrosses are exposed to large and increasing amounts of user plastics transported from coastal South America in the Subantarctic Current, or discarded from vessels and circulating in the South Atlantic Gyre, whereas the lower debris ingestion by black-browed albatrosses suggests that plastic pollution in Antarctic waters remains relatively low. Current plastic loads in our study species seem unlikely to have an impact at the population level, but the results nevertheless affirm that marine plastics are a major, trans-boundary animal-welfare and environmental issue that needs to be addressed by much-improved waste-management practices and compliance-monitoring both on land and on vessels in the south Atlantic.


Assuntos
Aves , Monitoramento Ambiental , Plásticos , Animais , Regiões Antárticas , Oceano Atlântico , América do Sul , Resíduos
11.
J Glob Oncol ; 4: 1-14, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30085895

RESUMO

Purpose The global burden of cancer is slated to reach 21.4 million new cases in 2030 alone, and the majority of those cases occur in under-resourced settings. Formidable changes to health care delivery systems must occur to meet this demand. Although significant policy advances have been made and documented at the international level, less is known about the efforts to create national systems to combat cancer in such settings. Methods With case reports and data from authors who are clinicians and policymakers in three financially constrained countries in different regions of the world-Guatemala, Rwanda, and Vietnam, we examined cancer care programs to identify principles that lead to robust care delivery platforms as well as challenges faced in each setting. Results The findings demonstrate that successful programs derive from equitably constructed and durable interventions focused on advancement of local clinical capacity and the prioritization of geographic and financial accessibility. In addition, a committed local response to the increasing cancer burden facilitates engagement of partners who become vital catalysts for launching treatment cascades. Also, clinical education in each setting was buttressed by international expertise, which aided both professional development and retention of staff. Conclusion All three countries demonstrate that excellent cancer care can and should be provided to all, including those who are impoverished or marginalized, without acceptance of a double standard. In this article, we call on governments and program leaders to report on successes and challenges in their own settings to allow for informed progression toward the 2025 global policy goals.


Assuntos
Neoplasias/terapia , Adolescente , Adulto , Idoso , Pré-Escolar , Atenção à Saúde , Feminino , Guatemala , Humanos , Masculino , Pessoa de Meia-Idade , Ruanda , Vietnã , Adulto Jovem
12.
J Cell Biochem ; 119(10): 8204-8219, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29923217

RESUMO

Osteoblast differentiation is controlled by transcription factor RUNX2 which temporally activates or represses several bone-related genes, including those encoding extracellular matrix proteins or factors that control cell-cell, and cell-matrix interactions. Cell-cell communication in the many skeletal pericellular micro-niches is critical for bone development and involves paracrine secretion of growth factors and morphogens. This paracrine signaling is in part regulated by "A Disintegrin And Metalloproteinase" (ADAM) proteins. These cell membrane-associated metalloproteinases support proteolytic release ("shedding") of protein ectodomains residing at the cell surface. We analyzed microarray and RNA-sequencing data for Adam genes and show that Adam17, Adam10, and Adam9 are stimulated during BMP2 mediated induction of osteogenic differentiation and are robustly expressed in human osteoblastic cells. ADAM17, which was initially identified as a tumor necrosis factor alpha (TNFα) converting enzyme also called (TACE), regulates TNFα-signaling pathway, which inhibits osteoblast differentiation. We demonstrate that Adam17 expression is suppressed by RUNX2 during osteoblast differentiation through the proximal Adam17 promoter region (-0.4 kb) containing two functional RUNX2 binding motifs. Adam17 downregulation during osteoblast differentiation is paralleled by increased RUNX2 expression, cytoplasmic-nuclear translocation and enhanced binding to the Adam17 proximal promoter. Forced expression of Adam17 reduces Runx2 and Alpl expression, indicating that Adam17 may negatively modulate osteoblast differentiation. These findings suggest a novel regulatory mechanism involving a reciprocal Runx2-Adam17 negative feedback loop to regulate progression through osteoblast differentiation. Our results suggest that RUNX2 may control paracrine signaling through regulation of ectodomain shedding at the cell surface of osteoblasts by directly suppressing Adam17 expression.


Assuntos
Proteína ADAM17/genética , Proteína Morfogenética Óssea 2/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Retroalimentação Fisiológica , Osteoblastos/metabolismo , Osteogênese/genética , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Proteína ADAM17/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Sítios de Ligação , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Linhagem Celular , Linhagem Celular Tumoral , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteoblastos/citologia , Comunicação Parácrina/genética , Regiões Promotoras Genéticas , Ligação Proteica , Ratos , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
13.
Front Vet Sci ; 5: 345, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30723722

RESUMO

Dogs' abilities to respond to concentrations of odorant molecules are generally deemed superior to electronic sensors. This sensitivity has been used traditionally in many areas; but is a more recent innovation within the medical field. As a bio-detection sensor for human diseases such as cancer and infections, dogs often need to detect volatile organic compounds in bodily fluids such as urine and blood. Although the limits of olfactory sensitivity in dogs have been studied since the 1960s, there is a gap in our knowledge concerning these limits in relation to the concentration of odorants presented in a fluid phase. Therefore, the aim of this study was to estimate olfactory detection thresholds to an inert substance, amyl acetate presented in a liquid phase. Ten dogs were trained in a "Go/No go" single scent-detection task using an eight-choice carousel apparatus. They were trained to respond to the presence of solutions of amyl acetate diluted to varying degrees in mineral oil by sitting in front of the positive sample, and not responding to the 7 other control samples. Training and testing took place in an indoor room with the same handler throughout using a food reward. After 30 weeks of training, using a forward chaining technique, dogs were tested for their sensitivity. The handler did not assist the dog during the search and was blind to the concentration of amyl acetate tested and the position of the target in the carousel. The global olfactory threshold trend for each dog was estimated by fitting a least-squares logistic curve to the association between the proportion of true positives and amyl acetate concentration. Results show an olfactory detection threshold for fluid mixtures ranging from 40 parts per billion to 1.5 parts per trillion. There was considerable inter-dog difference in sensitivity, even though all dogs were trained in the same way and worked without the assistance of the handler. This variation highlights factors to be considered in future work assessing olfactory detection performance by dogs.

14.
BMJ Open ; 5(9): e008689, 2015 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-26399574

RESUMO

INTRODUCTION: Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. METHODS AND ANALYSIS: A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. ETHICS AND DISSEMINATION: Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987.


Assuntos
Bandagens , Cateterismo Periférico , Cateteres de Demora , Protocolos Clínicos , Falha de Equipamento , Hospitalização , Adesivos , Administração Intravenosa , Adulto , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/efeitos adversos , Análise Custo-Benefício , Infecção Hospitalar/etiologia , Humanos , Infusões Intravenosas , Flebite/etiologia , Poliuretanos , Projetos de Pesquisa , Resultado do Tratamento
15.
mBio ; 5(6): e01721, 2014 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-25370488

RESUMO

UNLABELLED: For centuries, cholera has been one of the most feared diseases. The causative agent Vibrio cholerae is a waterborne Gram-negative enteric pathogen eliciting a severe watery diarrheal disease. In October 2010, the seventh pandemic reached Haiti, a country that had not experienced cholera for more than a century. By using whole-genome sequence typing and mapping strategies of 116 serotype O1 strains from global sources, including 44 Haitian genomes, we present a detailed reconstructed evolutionary history of the seventh pandemic with a focus on the Haitian outbreak. We catalogued subtle genomic alterations at the nucleotide level in the genome core and architectural rearrangements from whole-genome map comparisons. Isolates closely related to the Haitian isolates caused several recent outbreaks in southern Asia. This study provides evidence for a single-source introduction of cholera from Nepal into Haiti followed by rapid, extensive, and continued clonal expansion. The phylogeographic patterns in both southern Asia and Haiti argue for the rapid dissemination of V. cholerae across the landscape necessitating real-time surveillance efforts to complement the whole-genome epidemiological analysis. As eradication efforts move forward, phylogeographic knowledge will be important for identifying persistent sources and monitoring success at regional levels. The results of molecular and epidemiological analyses of this outbreak suggest that an indigenous Haitian source of V. cholerae is unlikely and that an indigenous source has not contributed to the genomic evolution of this clade. IMPORTANCE: In this genomic epidemiology study, we have applied high-resolution whole-genome-based sequence typing methodologies on a comprehensive set of genome sequences that have become available in the aftermath of the Haitian cholera epidemic. These sequence resources enabled us to reassess the degree of genomic heterogeneity within the Vibrio cholerae O1 serotype and to refine boundaries and evolutionary relationships. The established phylogenomic framework showed how outbreak isolates fit into the global phylogeographic patterns compared to a comprehensive globally and temporally diverse strain collection and provides strong molecular evidence that points to a nonindigenous source of the 2010 Haitian cholera outbreak and refines epidemiological standards used in outbreak investigations for outbreak inclusion/exclusion following the concept of genomic epidemiology. The generated phylogenomic data have major public health relevance in translating sequence-based information to assist in future diagnostic, epidemiological, surveillance, and forensic studies of cholera.


Assuntos
Cólera/epidemiologia , Cólera/microbiologia , Epidemias , Genoma Bacteriano , Tipagem Molecular , Vibrio cholerae O1/classificação , Vibrio cholerae O1/genética , Cólera/transmissão , Genótipo , Haiti/epidemiologia , Epidemiologia Molecular , Nepal , Filogeografia , Análise de Sequência de DNA , Vibrio cholerae O1/isolamento & purificação
16.
PLoS One ; 9(7): e102952, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25068801

RESUMO

Sustainable forest conservation strategies should be based on local as well as landscape-scale forest resource use data. Using ecological and sociological techniques, we test the hypotheses that (1) forest resource use differs between ethnic and socioeconomic indigenous groups and (2) that this difference results in differing spatial patterns of resource use, with implications for forest diversity and for conservation planning. In the North Rupununi Guyana, three adjacent indigenous communities (differing in their indigenous/immigrant balance) were recorded using 73 animal and 164 plant species (plus several unidentified ethno-species). Farm sites formed important foci for most forest based activities and ex-farm sites supported similar floristic diversity to surrounding forest. Resource usage differences between communities could be attributed to socio-cultural drivers, e.g. mammal meat consumption and the use of the fruits from the palm tree A. maripa were higher in more traditional households. When extracting household construction timber, lower income groups created small scattered felling sites akin to tree fall gaps whereas higher income groups created larger gaps. Lower income (indigenous) households tended to clear larger but more contained sites for farming while mixed or non-Amerindian household tended to clear smaller but more widely dispersed farm sites. These variations resulted in different patterns of forest disturbance originating from agriculture and timber extraction.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Florestas , Árvores , Animais , Ecossistema , Geografia , Guiana , Humanos
17.
Emerg Infect Dis ; 20(3): 364-71, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24565502

RESUMO

Three recently sequenced strains isolated from patients during an outbreak of Mycobacterium abscessus subsp. massiliense infections at a cystic fibrosis center in the United States were compared with 6 strains from an outbreak at a cystic fibrosis center in the United Kingdom and worldwide strains. Strains from the 2 cystic fibrosis outbreaks showed high-level relatedness with each other and major-level relatedness with strains that caused soft tissue infections during an epidemic in Brazil. We identified unique single-nucleotide polymorphisms in cystic fibrosis and soft tissue outbreak strains, separate single-nucleotide polymorphisms only in cystic fibrosis outbreak strains, and unique genomic traits for each subset of isolates. Our findings highlight the necessity of identifying M. abscessus to the subspecies level and screening all cystic fibrosis isolates for relatedness to these outbreak strains. We propose 2 diagnostic strategies that use partial sequencing of rpoB and secA1 genes and a multilocus sequence typing protocol.


Assuntos
Surtos de Doenças , Infecções por Mycobacterium/epidemiologia , Mycobacterium/isolamento & purificação , Brasil , Fibrose Cística/complicações , Genoma Bacteriano , Humanos , Tipagem de Sequências Multilocus , Mycobacterium/classificação , Mycobacterium/genética , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/microbiologia , Filogenia , Polimorfismo de Nucleotídeo Único , Reino Unido , Estados Unidos
18.
Dement. neuropsychol ; 7(2): 143-150, jun. 2013. tab
Artigo em Inglês | LILACS | ID: lil-677953

RESUMO

FTD is a unique condition which manifests with a range of behavioural symptoms, marked dysfunction in activities of daily living ADL and increased levels of carer burden as compared to carers of other dementias. No efficacious pharmacological interventions to treat FTD currently exist, and research on pharmacological symptom management isvariable. The few studies on non-pharmacological interventions in FTD focus on either the carer or the patients? symptoms, and lack methodological rigour. This paper reviews and discusses current studies utilising non-pharmacological approaches, exposing the clear need for more rigorous methodologies to be applied in this . Finally, a successful randomised controlled trial helped reduce behaviours of concern in dementia, and through implementing participation in tailored activities, the FTD-specific Tailored Activities Program TAP is presented. Crucially, this protocol has scope to target both the person with FTD and their carer. This paper highlights that studies in this area would help to elucidate the potential for using activities to reduce characteristic behaviours in FTD, improving quality of life and the caregiving experience in FTD.


A DFT é uma condição única que se manifesta por uma variedade de sintomas, principalmente em atividades da vida diária (AVD) e aumento da carga sobre os cuidadores em comparação aos cuidadores de outras demências. Não existe nenhuma intervenção farmacológica para tratamento da DFT até o momento e pesquisas sobre o manejo farmacológico dos sintomas são variáveis. Os poucos estudos em intervenção não farmacológica em DFT focam nos cuidadores ou emsintomas dos pacientes, faltando rigor metodológico. Este artigo revisa e discute os estudos atuais que utilizam abordagem não farmacológica, o que expõe a clara necessidade para metodologias mais rigorosas a serem aplicadas neste campo. Finalmente, um ensaio clinico randomizado bem sucedido ajudou na redução de comportamentos em demência, através da implementação da participação em atividades ajustadas, é apresentado o FTD-specific Tailored Activities Program (TAP). Este protocolo visa abordar tanto o paciente com DFT quanto seu cuidador. Este manuscrito evidencia que pesquisas dentro desta area ajudariam a elucidar o potencial em usar estas atividades para redução dos comportamentos característicos em DFt, melhorando a qualidade de vida e experiências dos cuidadores em DFT.


Assuntos
Humanos , Ensaio Clínico , Ensaio Clínico Controlado Aleatório , Demência Frontotemporal
19.
Pathog Dis ; 68(2): 39-43, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23661595

RESUMO

Helicobacter pylori, inhabitant of the gastric mucosa of over half of the world population, with decreasing prevalence in the U.S., has been associated with a variety of gastric pathologies. However, the majority of H. pylori-infected individuals remain asymptomatic, and negative correlations between H. pylori and allergic diseases have been reported. Comprehensive genome characterization of H. pylori populations from different human host backgrounds including healthy individuals provides the exciting potential to generate new insights into the open question whether human health outcome is associated with specific H. pylori genotypes or dependent on other environmental factors. We report the genome sequences of 65 H. pylori isolates from individuals with gastric cancer, preneoplastic lesions, peptic ulcer disease, gastritis, and from asymptomatic adults. Isolates were collected from multiple locations in North America (USA and Canada) as well as from Columbia and Japan. The availability of these H. pylori genome sequences from individuals with distinct clinical presentations provides the research community with a resource for detailed investigations into genetic elements that correlate either positively or negatively with the epidemiology, human host adaptation, and gastric pathogenesis and will aid in the characterization of strains that may favor the development of specific pathology, including gastric cancer.


Assuntos
DNA Bacteriano/química , DNA Bacteriano/genética , Genoma Bacteriano , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Análise de Sequência de DNA , Adulto , Doenças Assintomáticas , Análise por Conglomerados , Colômbia , Gastrite/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Japão , Dados de Sequência Molecular , América do Norte , Úlcera Péptica/microbiologia , Filogenia , Neoplasias Gástricas/microbiologia
20.
Dement Neuropsychol ; 7(2): 143-150, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-29213832

RESUMO

FTD is a unique condition which manifests with a range of behavioural symptoms, marked dysfunction in activities of daily living (ADL) and increased levels of carer burden as compared to carers of other dementias. No efficacious pharmacological interventions to treat FTD currently exist, and research on pharmacological symptom management is variable. The few studies on non-pharmacological interventions in FTD focus on either the carer or the patients' symptoms, and lack methodological rigour. This paper reviews and discusses current studies utilising non-pharmacological approaches, exposing the clear need for more rigorous methodologies to be applied in this field. Finally, a successful randomised controlled trial helped reduce behaviours of concern in dementia, and through implementing participation in tailored activities, the FTD-specific Tailored Activities Program (TAP) is presented. Crucially, this protocol has scope to target both the person with FTD and their carer. This paper highlights that studies in this area would help to elucidate the potential for using activities to reduce characteristic behaviours in FTD, improving quality of life and the caregiving experience in FTD.


A DFT é uma condição única que se manifesta por uma variedade de sintomas, principalmente em atividades da vida diária (AVD) e aumento da carga sobre os cuidadores em comparação aos cuidadores de outras demências. Não existe nenhuma intervenção farmacológica para tratamento da DFT até o momento e pesquisas sobre o manejo farmacológico dos sintomas são variáveis. Os poucos estudos em intervenção não farmacológica em DFT focam nos cuidadores ou em sintomas dos pacientes, faltando rigor metodológico. Este artigo revisa e discute os estudos atuais que utilizam abordagem não farmacológica, o que expõe a clara necessidade para metodologias mais rigorosas a serem aplicadas neste campo. Finalmente, um ensaio clinico randomizado bem sucedido ajudou na redução de comportamentos em demência, através da implementação da participação em atividades ajustadas, é apresentado o FTD-specific Tailored Activities Program (TAP). Este protocolo visa abordar tanto o paciente com DFT quanto seu cuidador. Este manuscrito evidencia que pesquisas dentro desta area ajudariam a elucidar o potencial em usar estas atividades para redução dos comportamentos característicos em DFt, melhorando a qualidade de vida e experiências dos cuidadores em DFT.

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