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2.
Circulation ; 148(6): 512-542, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37427418

RESUMO

Cardiovascular disease remains the leading cause of death and disability in the United States and globally. Disease burden continues to escalate despite technological advances associated with improved life expectancy and quality of life. As a result, longer life is associated with multiple chronic cardiovascular conditions. Clinical guidelines provide recommendations without considering prevalent scenarios of multimorbidity and health system complexities that affect practical adoption. The diversity of personal preferences, cultures, and lifestyles that make up one's social and environmental context is often overlooked in ongoing care planning for symptom management and health behavior support, hindering adoption and compromising patient outcomes, particularly in groups at high risk. The purpose of this scientific statement was to describe the characteristics and reported outcomes in existing person-centered care delivery models for selected cardiovascular conditions. We conducted a scoping review using Ovid MEDLINE, Embase.com, Web of Science, CINAHL Complete, Cochrane Central Register of Controlled Trials through Ovid, and ClinicalTrials.gov from 2010 to 2022. A range of study designs with a defined aim to systematically evaluate care delivery models for selected cardiovascular conditions were included. Models were selected on the basis of their stated use of evidence-based guidelines, clinical decision support tools, systematic evaluation processes, and inclusion of the patient's perspective in defining the plan of care. Findings reflected variation in methodological approach, outcome measures, and care processes used across models. Evidence to support optimal care delivery models remains limited by inconsistencies in approach, variation in reimbursement, and inability of health systems to meet the needs of patients with chronic, complex cardiovascular conditions.


Assuntos
Doenças Cardiovasculares , Qualidade de Vida , Humanos , Estados Unidos/epidemiologia , American Heart Association , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Atenção à Saúde , Cuidados Paliativos
3.
Emerg Infect Dis ; 29(7): 1386-1396, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37308158

RESUMO

Isolating and characterizing emerging SARS-CoV-2 variants is key to understanding virus pathogenesis. In this study, we isolated samples of the SARS-CoV-2 R.1 lineage, categorized as a variant under monitoring by the World Health Organization, and evaluated their sensitivity to neutralizing antibodies and type I interferons. We used convalescent serum samples from persons in Canada infected either with ancestral virus (wave 1) or the B.1.1.7 (Alpha) variant of concern (wave 3) for testing neutralization sensitivity. The R.1 isolates were potently neutralized by both the wave 1 and wave 3 convalescent serum samples, unlike the B.1.351 (Beta) variant of concern. Of note, the R.1 variant was significantly more resistant to type I interferons (IFN-α/ß) than was the ancestral isolate. Our study demonstrates that the R.1 variant retained sensitivity to neutralizing antibodies but evolved resistance to type I interferons. This critical driving force will influence the trajectory of the pandemic.


Assuntos
COVID-19 , Interferon Tipo I , Humanos , SARS-CoV-2/genética , Interferon Tipo I/genética , Anticorpos Neutralizantes , Soroterapia para COVID-19 , Canadá/epidemiologia , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus
4.
Gastroenterology ; 163(5): 1351-1363.e15, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35810781

RESUMO

BACKGROUND & AIMS: Genes and gluten are necessary but insufficient to cause celiac disease (CeD). Altered gut microbiota has been implicated as an additional risk factor. Variability in sampling site may confound interpretation and mechanistic insight, as CeD primarily affects the small intestine. Thus, we characterized CeD microbiota along the duodenum and in feces and verified functional impact in gnotobiotic mice. METHODS: We used 16S rRNA gene sequencing (Illumina) and predicted gene function (PICRUSt2) in duodenal biopsies (D1, D2 and D3), aspirates, and stool from patients with active CeD and controls. CeD alleles were determined in consented participants. A subset of duodenal samples stratified according to similar CeD risk genotypes (controls DQ2-/- or DQ2+/- and CeD DQ2+/-) were used for further analysis and to colonize germ-free mice for gluten metabolism studies. RESULTS: Microbiota composition and predicted function in CeD was largely determined by intestinal location. In the duodenum, but not stool, there was higher abundance of Escherichia coli (D1), Prevotella salivae (D2), and Neisseria (D3) in CeD vs controls. Predicted bacterial protease and peptidase genes were altered in CeD and impaired gluten degradation was detected only in mice colonized with CeD microbiota. CONCLUSIONS: Our results showed luminal and mucosal microbial niches along the gut in CeD. We identified novel microbial proteolytic pathways involved in gluten detoxification that are impaired in CeD but not in controls carrying DQ2, suggesting an association with active duodenal inflammation. Sampling site should be considered a confounding factor in microbiome studies in CeD.


Assuntos
Doença Celíaca , Microbioma Gastrointestinal , Camundongos , Animais , Doença Celíaca/complicações , RNA Ribossômico 16S/genética , Glutens/metabolismo , Peptídeo Hidrolases
5.
Brain Behav Immun ; 102: 266-278, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35259427

RESUMO

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood. As the intestinal microbiota profoundly influences host behaviour, we sought to determine whether the altered gut microbiota associated with intestinal inflammation contributes to the development of behavioural abnormalities. Using the dextran sulphate sodium (DSS) model of colitis, we characterized intestinal inflammation, behaviour (elevated plus maze and tail suspension test) and the composition of the microbiota in male mice. Cecal contents from colitic mice were transferred into germ-free (GF) or antibiotic (Abx)-treated mice, and behaviour was characterized in recipient mice. Gene expression was measured using qPCR. DSS colitis was characterized by a significant reduction in body weight and an increase in colonic inflammatory markers. These changes were accompanied by increased anxiety-like behaviour, an altered gut microbiota composition, and increased central Tnf expression. Transfer of the cecal matter from colitic mice induced similar behavioural changes in both GF and Abx-treated recipient mice, with no signs of colonic or neuroinflammation. Upon characterization of the microbiota in donor and recipient mice, specific taxa were found to be associated with behavioural changes, notably members of the Lachnospiraceae family. Behavioural abnormalities associated with intestinal inflammation are transmissible via transfer of cecal matter, suggesting that alterations in the composition of the gut microbiota play a key role in driving behavioural changes in colitis.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Microbiota , Animais , Colite/induzido quimicamente , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Circulation ; 141(22): e841-e863, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32349541

RESUMO

Heart failure is a clinical syndrome that affects >6.5 million Americans, with an estimated 550 000 new cases diagnosed each year. The complexity of heart failure management is compounded by the number of patients who experience adverse downstream effects of the social determinants of health (SDOH). These patients are less able to access care and more likely to experience poor heart failure outcomes over time. Many patients face additional challenges associated with the cost of complex, chronic illness management and must make difficult decisions about their own health, particularly when the costs of medications and healthcare appointments are at odds with basic food and housing needs. This scientific statement summarizes the SDOH and the current state of knowledge important to understanding their impact on patients with heart failure. Specifically, this document includes a definition of SDOH, provider competencies, and SDOH assessment tools and addresses the following questions: (1) What models or frameworks guide healthcare providers to address SDOH? (2) What are the SDOH affecting the delivery of care and the interventions addressing them that affect the care and outcomes of patients with heart failure? (3) What are the opportunities for healthcare providers to address the SDOH affecting the care of patients with heart failure? We also include a case study (Data Supplement) that highlights an interprofessional team effort to address and mitigate the effects of SDOH in an underserved patient with heart failure.


Assuntos
Atenção à Saúde , Insuficiência Cardíaca/terapia , Determinantes Sociais da Saúde , Escolaridade , Exposição Ambiental , Etnicidade , Insegurança Alimentar , Identidade de Gênero , Letramento em Saúde , Acessibilidade aos Serviços de Saúde , Disparidades nos Níveis de Saúde , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/epidemiologia , Humanos , Cobertura do Seguro , Grupos Minoritários , Modelos Teóricos , Preparações Farmacêuticas/provisão & distribuição , Pobreza , Grupos Raciais , Classe Social , Apoio Social , Desemprego , Populações Vulneráveis
7.
BMC Microbiol ; 21(1): 96, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784986

RESUMO

BACKGROUND: Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis - we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure. RESULTS: Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders - demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas. CONCLUSIONS: Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.


Assuntos
Azitromicina/farmacologia , Fibrose Cística/microbiologia , Microbiota/efeitos dos fármacos , Adulto , Antibacterianos , Feminino , Humanos , Masculino , RNA Ribossômico 16S/genética , Escarro
8.
Thorax ; 75(12): 1058-1064, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33139451

RESUMO

BACKGROUND: Inhaled tobramycin powder/solution (TIP/S) use has resulted in improved clinical outcomes in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa. However, TIP/S effect on the CF sputum microbiome has not been explored. We hypothesised that TIP/S has additional 'off-target' effects beyond merely P. aeruginosa and that baseline microbiome prior to initiation of therapy is associated with subsequent patient response. METHODS: We drew sputum samples from a prospectively collected biobank. Patients were included if they had one sputum sample in the 18 months before and after TIP/S. Bacterial 16S rRNA gene profiling was used to characterise the sputum microbiome. RESULTS: Forty-one patients met our inclusion criteria and 151 sputum samples were assessed. At baseline, median age was 30.4 years (IQR 24.2-35.2) and forced expiratory volume in 1 (FEV1) second was 57% predicted (IQR 44-74). Nineteen patients were defined a priori as responders having no net decrease in FEV1 in the year following TIP/S. No significant changes were observed in key microbiome metrics of alpha (within-sample) or beta (between-sample) diversity for samples collected before and after TIP/S. However, significant beta-diversity (Bray-Curtis) differences were noted at baseline between patients based on response status. Notably, responders were observed to have a higher abundance of Staphylococcus in pretherapy baseline samples. CONCLUSIONS: Our longitudinal study demonstrates that the sputum microbiome of patients with CF is relatively stable following inhaled tobramycin over many months. Intriguingly, our findings suggest that baseline microbiome may associate with patient response to TIP/S-suggesting the sputum microbiome could be used to personalise therapy.


Assuntos
Antibacterianos/farmacologia , Fibrose Cística/tratamento farmacológico , Microbiota/efeitos dos fármacos , Escarro/microbiologia , Tobramicina/farmacologia , Administração por Inalação , Adulto , Antibacterianos/administração & dosagem , Fibrose Cística/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Masculino , Pós , Pseudomonas/efeitos dos fármacos , Soluções , Staphylococcus/efeitos dos fármacos , Tobramicina/administração & dosagem , Resultado do Tratamento , Adulto Jovem
9.
J Surg Oncol ; 121(4): 630-637, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31957034

RESUMO

BACKGROUND AND OBJECTIVES: Limb salvage surgery remains the standard treatment in bone and soft tissue tumors. Toronto Extremity Salvage Score (TESS) is the most used quality of life measure. Our objective was to perform cross-cultural adaptation and validation in Italian, testing test-retest reliability, construct validity, and responsiveness. METHODS: We interviewed patients already treated for content validity. A total of 124 patients completed TESS and other questionnaires presurgery, at 3 months, 3 months + 2 weeks, and 6 months follow-up. We calculated intraclass correlation coefficients (ICCs) for reliability, associations with Pearson's r, and change over time with paired T tests. RESULTS: A new item regarding touch-screen devices was added to the upper extremity (UE) questionnaire. ICC resulted of 0.99 for lower extremity (LE) and 0.98 for UE patients, Pearson's r between TESS and Musculoskeletal Tumor Society was .66 and .64, EuroQol-5D-5L r was .62 and .61, and r between TESS and short form-36 physical function subscale was .76 and .71 for LE and UE groups, respectively. Paired T test results were statistically significant to detect change over time (0.03, 0.04, and 0.04 for LE groups and 0.03, 0.01, and 0.04 for UE groups). CONCLUSION: The Italian version of TESS can be used for the bone and soft tissue sarcoma population in clinical trials in Italy and with Italian speaking patients abroad to ensure patients' perspectives for efficacy and efficiency of treatments.


Assuntos
Neoplasias Ósseas/psicologia , Neoplasias Ósseas/cirurgia , Salvamento de Membro/psicologia , Osteossarcoma/psicologia , Osteossarcoma/cirurgia , Sarcoma/psicologia , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Comparação Transcultural , Extremidades/patologia , Extremidades/cirurgia , Feminino , Humanos , Itália , Idioma , Salvamento de Membro/métodos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/patologia , Qualidade de Vida , Reprodutibilidade dos Testes , Sarcoma/patologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Tradução , Adulto Jovem
10.
J Oncol Pharm Pract ; 26(7): 1715-1720, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32594844

RESUMO

The use of continuous-infusion in outpatient setting could be widely used in oncology and haematology care. Many times the lack of data stability about single drug or admixture of drugs, together with patient education and safety, make difficult the transition from inpatient to outpatient setting. Nowadays, this is a big challenge for hospital pharmacists, who must take into consideration the critical issues related to chemical and physical stability, besides microbiological one, in order to ensure high quality preparations and guarantee the safety and quality of care, to protect patients and their health. The aim of this article is to highlight the critical issues concerning the transition from inpatient to outpatient setting, with particular interest regarding chemotherapy protocols, which require preparation with long-term continuous-infusion.


Assuntos
Antineoplásicos/administração & dosagem , Farmacêuticos , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Estabilidade de Medicamentos , Humanos , Infusões Intravenosas , Pacientes Internados , Pacientes Ambulatoriais
11.
Eur J Orthop Surg Traumatol ; 30(7): 1171-1178, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32363558

RESUMO

PURPOSE: Chronic anterior ankle pain is a recognized and straightforward characteristic of anterior impingement syndrome. This retrospective study aims to evaluate outcomes, clinical and radiological results in patients affected by anterior ankle impingement, in a context of early osteoarthritis, and treated with mini-open anterior ankle arthrolysis, in the perspective to delay or avoid other demolitive surgical options, such as total ankle replacement and joint fusion. METHODS: In total, 49 patients (50 feet, mean age 45 years) undergone mini-open anterior ankle arthrolysis for anterior impingement, fulfilled inclusion criteria and gave their consent and have been enlisted in the study. Patients were retrospectively reviewed with AOFAS ankle-hindfoot score and SF-36 score at a minimum follow-up of 36 months. Statistical analysis was performed. RESULTS: A marked improvement was noticed in terms of preoperative clinical score (mean AOFAS score 47.32 ± 17.89) compared to follow-up clinical score (mean AOFAS score 70.66 ± 16.62; p < 0.005), and all of 8 SF-36 domains showed statistically improved (p < 0.05) from preoperative to follow-up. Statistical significance has been shown. CONCLUSIONS: It is possible to consider the mini-open anterior arthrolysis, thanks to the reduction of the painful symptomatology, a valid tool for procrastinating more invasive interventions such as arthrodesis or prosthetic replacement in patients with grade 1 or 2 of ankle osteoarthritis.


Assuntos
Tornozelo , Osteoartrite , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Seguimentos , Humanos , Recém-Nascido , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
12.
Eur J Orthop Surg Traumatol ; 30(7): 1179, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32583167

RESUMO

The original version of this article unfortunately contained a mistake. The spelling of the 'Francesco Ceccarelli' name was incorrect.

13.
Regul Toxicol Pharmacol ; 109: 104477, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586681

RESUMO

Four years on since the last cross sector workshop, experience of the practical application and interpretation of several non-animal assays that contribute to the predictive identification of skin sensitisers has begun to accumulate. Non-animal methods used for hazard assessments increasingly are contributing to the potency sub-categorisation for regulatory purposes. However, workshop participants generally supported the view that there remained a pressing need to build confidence in how information from multiple methods can be combined for classification, sub-categorisation and potency assessment. Furthermore, the practical experience gained over the last few years, highlighted the overall high potential value of using the newly validated methods and testing strategies, but also that limitations for certain substance/product classes may become evident with further use as had been the case with other new regulatory methods. As the available information increases, review of the data and collated experience could further determine strengths and limitations leading to more confidence in their use. Finally, the need for a substantial and universally accepted dataset of non-sensitisers and substances of different sensitising potencies, based on combined human and in vivo animal data for validation of methods and test strategies was re-emphasised.


Assuntos
Alternativas aos Testes com Animais , Congressos como Assunto , Projetos de Pesquisa/normas , Pele/efeitos dos fármacos , Testes de Toxicidade/normas , Conjuntos de Dados como Assunto , Europa (Continente) , Pele/imunologia , Testes Cutâneos/métodos , Testes Cutâneos/normas
14.
BMC Med Educ ; 19(1): 276, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340808

RESUMO

BACKGROUND: Cooperative interdisciplinary patient care is a modern healthcare necessity. While various medical and surgical disciplines have independent educational requirements, a system-wide simulation-based curriculum composed of different disciplines provides a unique forum to observe the effect of interdisciplinary simulation-based education (IDSE). Our hypothesis: IDSE positively affects intern outlook and attitudes towards other medical disciplines. METHODS: Using an established interdisciplinary simulation curriculum designed for first year interns, we explored the relative effect of IDSE on between-discipline intern attitudes in a convergent, parallel, mixed-methods study. Data sources included novel pre-post anonymous survey measurements (10-point Likert scale), focus groups, direct observations, and reflective field notes. This quasi-experimental pilot study was conducted at an academic, tertiary care medical center with two cohorts of interns: one exposed to IDSE and one exposed to an independent within-discipline simulation curriculum. RESULTS: IDSE exposed interns demonstrated statistically significant improvements when comparing mean pre-test and post-test score differences in five of seven areas: perceived interdisciplinary collegiality ([Formula: see text] = 0.855; p = 0.0002), respect (x̅ = 0.436; p = 0.0312), work interactions ([Formula: see text] = 0.691; p = 0.0069), perceived interdisciplinary attitudes (x̅ = 0.764; p = 0.0031), and comfort in interdisciplinary learning (x̅ = 1.164; p < 0.0001). There were no changes in interdisciplinary viewpoints observed among non-IDSE interns. IDSE interns were comfortable when learning with interns of different disciplines and believed others viewed their discipline positively compared to non-IDSE interns. Qualitative data uncovered the following themes related to the impact of IDSE including: 1) Relationship building, 2) Communication openness, 3) Attitude shifting, and 4) Enhanced learner experience. CONCLUSIONS: IDSE positively influenced intern outlook on and attitudes towards other medical disciplines. This unique learning environment provided interns an opportunity to learn clinical case management while learning about, from, and with each other; subsequently breaking traditional discipline-specific stereotypes and improving interdisciplinary relations. Future explicit focus on IDSE offers opportunity to improve interdisciplinary interactions and patient care.


Assuntos
Estudos Interdisciplinares , Internato e Residência , Treinamento por Simulação , Currículo , Grupos Focais , Projetos Piloto
15.
J Foot Ankle Surg ; 58(2): 203-207, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30658957

RESUMO

The aim of our study is a retrospective analysis of the 2 most common surgical treatments of symptomatic juvenile flat foot: different arthroereisis techniques. Exosinotarsal arthroereisis with metallic screw and endosinotarsal with bioabsorbable devices were compared. In total, 402 feet were examined for a median follow-up of 130 months. Only symptomatic (plantar or calcaneus pain), flexible, and idiopathic flat feet were included in our study. Congenital (fibrous/bone tarsal coalitions), neurologic, and posttraumatic flat feet were excluded. During clinical examination, the feet were categorized according to the Viladot classification, which took into consideration the plantar impression: only grades 3 and 4 were included (complete medial longitudinal arch collapse). Evaluation was determined by taking into consideration 3 parameters: clinical evaluation, pain, and variation of the radiologic angles. No statistical differences were found between the 2 techniques; the choice can be determined mostly by the surgeon's preference.


Assuntos
Implantes Absorvíveis , Parafusos Ósseos , Pé Chato/cirurgia , Osteotomia/métodos , Articulação Talocalcânea/cirurgia , Adolescente , Estudos de Coortes , Feminino , Pé Chato/diagnóstico por imagem , Humanos , Masculino , Procedimentos Ortopédicos/métodos , Radiografia/métodos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Articulação Talocalcânea/diagnóstico por imagem , Resultado do Tratamento
16.
Am J Physiol Gastrointest Liver Physiol ; 315(3): G420-G431, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29848021

RESUMO

Crohn's disease (CD), characterized by discontinuous intestinal injury and inflammation, has been associated with changes in luminal microbial composition and impaired barrier function. The relationships between visual features of intestinal injury, permeability, and the mucosa-associated microbiota are unclear. Individuals undergoing routine colonoscopy (controls) and patients with CD were evaluated by clinical parameters and confocal laser scanning endomicroscopic colonoscopy (CLE). Patients with CD were categorized as either CD with no injury (CD-NI) or CD with injury (CD-I). Colonic biopsies were taken from adjacent matched sites in all individuals, and CLE images from these sites were analyzed for vascular permeability. Microbial composition was evaluated by 16S rRNA gene sequencing of the V3 region, and the mycome was identified through internal transcribed spacer 2 sequencing. Subgroup analyses were performed for histology, paracellular permeability (Ussing chamber), and encroachment of bacteria (fluorescent in situ hybridization). CD-I patients showed an altered microbial community compared with both controls and CD-NI patients, with enrichment in Escherichia and a decrease in Firmicutes, including Lachnospira, Faecalibacterium, and Blautia. In CD-I patients, bacterial encroachment to host epithelial cells was greater in sites of injury than in matched biopsy sites. Biopsies from sites of injury also demonstrated greater vascular and paracellular permeability. Overall, CD-I patients showed an altered mucosal microbial community compared with CD-NI patients and controls. Matched biopsy samples in CD-I patients revealed that sites of injury, identified endoscopically, are characterized by increased encroachment of bacteria to host epithelial cells, associated with increased paracellular and vascular permeability, which may drive inflammation in CD. NEW & NOTEWORTHY Patients with Crohn's disease (CD) with areas of colonic injury have an altered microbial community compared with patients who have no endoscopic evidence of injury or active disease. Although matched biopsies from patients with colonic injury show no differences in the mucosa-associated microbiota, injured sites are associated with increased permeability and increased encroachment. Our results support the notion that dysbiotic communities within patients with colonic injury cause or permit disruption of the mucosal and endothelial layers in CD.


Assuntos
Colo , Doença de Crohn , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Mucosa Intestinal , Intestinos , RNA Ribossômico 16S/genética , Biópsia/métodos , Colo/microbiologia , Colo/patologia , Colonoscopia/métodos , Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Doença de Crohn/patologia , Feminino , Humanos , Inflamação/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Intestinos/patologia , Intestinos/fisiopatologia , Masculino , Pessoa de Meia-Idade
17.
Respir Res ; 19(1): 245, 2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30526610

RESUMO

BACKGROUND: Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. METHODS: We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. RESULTS: We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2-4) and 6 days (stool; IQR 4.25-6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = - 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). CONCLUSIONS: The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01782755 . Registered February 4 2013.


Assuntos
Disbiose/microbiologia , Disbiose/mortalidade , Fenômenos Microbiológicos , Respiração Artificial/efeitos adversos , Respiração Artificial/mortalidade , Idoso , Estado Terminal/epidemiologia , Estado Terminal/terapia , Disbiose/etiologia , Feminino , Humanos , Unidades de Terapia Intensiva/tendências , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
18.
Soft Matter ; 14(7): 1080-1087, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29372225

RESUMO

For magnetite spherical nanoparticles, the orientation of the dipole moment in the crystal does not affect the morphology of either zero field or field induced structures. For non-spherical particles however, an interplay between particle shape and direction of the magnetic moment can give rise to unusual behaviors, in particular when the moment is not aligned along a particle symmetry axis. Here we disclose for the first time the unique magnetic properties of hematite cubic particles and show the exact orientation of the cubes' dipole moment. Using a combination of experiments and computer simulations, we show that dipolar hematite cubes self-organize into dipolar chains with morphologies remarkably different from those of spheres, and demonstrate that the emergence of these structures is driven by competing anisotropic interactions caused by the particles' shape anisotropy and their fixed dipole moment. Furthermore, we have analytically identified a specific interplay between energy, and entropy at the microscopic level and found that an unorthodox entropic contribution mediates the organization of particles into the kinked nature of the dipolar chains.

19.
Proc Natl Acad Sci U S A ; 112(17): 5286-90, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25870301

RESUMO

Guiding the self-assembly of materials by controlling the shape of the individual particle constituents is a powerful approach to material design. We show that colloidal silica superballs crystallize into canted phases in the presence of depletants. Some of these phases are consistent with the so-called "Λ1" lattice that was recently predicted as the densest packing of superdisks. As the size of the depletant is reduced, however, we observe a transition to a square phase. The differences in these entropically stabilized phases result from an interplay between the size of the depletants and the fine structure of the superball shape. We find qualitative agreement of our experimental results both with a phase diagram computed on the basis of the volume accessible to the depletants and with simulations. By using a mixture of depletants, one of which is thermosensitive, we induce solid-to-solid phase transitions between square and canted structures. The use of depletant size to leverage fine features of the shape of particles in driving their self-assembly demonstrates a general and powerful mechanism for engineering novel materials.

20.
Euro Surveill ; 23(13)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29616614

RESUMO

Background and aimEpidemiology of human non-typhoid salmonellosis is characterised by recurrent emergence of new clones of the pathogen over time. Some clonal lines of Salmonella have shaped epidemiology of the disease at global level, as happened for serotype Enteritidis or, more recently, for Salmonella 4,[5],12:i:-, a monophasic variant of serotype Typhimurium. The same clonal behaviour is recognisable at sub-serotype level where single outbreaks or more generalised epidemics are attributable to defined clones. The aim of this study was to understand the dynamics of a clone of Salmonella 4,[5],12:i:- over a 3-year period (2012-15) in a province of Northern Italy where the clone caused a large outbreak in 2013. Furthermore, the role of candidate outbreak sources was investigated and the accuracy of multilocus variable-number tandem repeat analysis (MLVA) was evaluated. Methods: we retrospectively investigated the outbreak through whole genome sequencing (WGS) and further monitored the outbreak clone for 2 years after its conclusion. Results: The study showed the transient nature of the clone in the population, possibly as a consequence of its occasional expansion in a food-processing facility. We demonstrated that important weaknesses characterise conventional typing methods applied to clonal pathogens such as Salmonella 4,[5],12:i:-, namely lack of accuracy for MLVA and inadequate resolution power for PFGE to be reliably used for clone tracking. Conclusions: The study provided evidence for the remarkable prevention potential of whole genome sequencing used as a routine tool in systems that integrate human, food and animal surveillance.


Assuntos
DNA Bacteriano/genética , Surtos de Doenças , Doenças Endêmicas , Repetições Minissatélites/genética , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Salmonella/genética , Salmonella/isolamento & purificação , Técnicas de Tipagem Bacteriana/métodos , Eletroforese em Gel de Campo Pulsado , Humanos , Itália/epidemiologia , Epidemiologia Molecular , Tipagem Molecular/métodos , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Salmonella/classificação , Infecções por Salmonella/diagnóstico , Sequenciamento Completo do Genoma
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