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1.
Proc Natl Acad Sci U S A ; 119(13): e2119883119, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35312369

RESUMEN

SignificanceWe present a groundbreaking advance in completely nonprecious hydrogen fuel cell technologies achieving a record power density of 200 mW/cm2 with Ni@CNx anode and Co-Mn cathode. The 2-nm CNx coating weakens the O-binding energy, which effectively mitigates the undesirable surface oxidation during hydrogen oxidation reaction (HOR) polarization, leading to a stable fuel cell operation for Ni@CNx over 100 h at 200 mA/cm2, superior to a Ni nanoparticle counterpart. Ni@CNx exhibited a dramatically enhanced tolerance to CO relative to Pt/C, enabling the use of hydrogen gas with trace amounts of CO, critical for practical applications. The complete removal of precious metals in fuel cells lowers the catalyst cost to virtually negligible levels and marks a milestone for practical alkaline fuel cells.

2.
Chem Rev ; 122(6): 6117-6321, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35133808

RESUMEN

Hydrogen energy-based electrochemical energy conversion technologies offer the promise of enabling a transition of the global energy landscape from fossil fuels to renewable energy. Here, we present a comprehensive review of the fundamentals of electrocatalysis in alkaline media and applications in alkaline-based energy technologies, particularly alkaline fuel cells and water electrolyzers. Anion exchange (alkaline) membrane fuel cells (AEMFCs) enable the use of nonprecious electrocatalysts for the sluggish oxygen reduction reaction (ORR), relative to proton exchange membrane fuel cells (PEMFCs), which require Pt-based electrocatalysts. However, the hydrogen oxidation reaction (HOR) kinetics is significantly slower in alkaline media than in acidic media. Understanding these phenomena requires applying theoretical and experimental methods to unravel molecular-level thermodynamics and kinetics of hydrogen and oxygen electrocatalysis and, particularly, the proton-coupled electron transfer (PCET) process that takes place in a proton-deficient alkaline media. Extensive electrochemical and spectroscopic studies, on single-crystal Pt and metal oxides, have contributed to the development of activity descriptors, as well as the identification of the nature of active sites, and the rate-determining steps of the HOR and ORR. Among these, the structure and reactivity of interfacial water serve as key potential and pH-dependent kinetic factors that are helping elucidate the origins of the HOR and ORR activity differences in acids and bases. Additionally, deliberately modulating and controlling catalyst-support interactions have provided valuable insights for enhancing catalyst accessibility and durability during operation. The design and synthesis of highly conductive and durable alkaline membranes/ionomers have enabled AEMFCs to reach initial performance metrics equal to or higher than those of PEMFCs. We emphasize the importance of using membrane electrode assemblies (MEAs) to integrate the often separately pursued/optimized electrocatalyst/support and membranes/ionomer components. Operando/in situ methods, at multiscales, and ab initio simulations provide a mechanistic understanding of electron, ion, and mass transport at catalyst/ionomer/membrane interfaces and the necessary guidance to achieve fuel cell operation in air over thousands of hours. We hope that this Review will serve as a roadmap for advancing the scientific understanding of the fundamental factors governing electrochemical energy conversion in alkaline media with the ultimate goal of achieving ultralow Pt or precious-metal-free high-performance and durable alkaline fuel cells and related technologies.


Asunto(s)
Suministros de Energía Eléctrica , Protones , Hidrógeno/química , Oxígeno/química , Agua
3.
Crit Care Med ; 45(5): 806-813, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28221185

RESUMEN

OBJECTIVE: This meta-analysis aimed to examine the impact of antipyretic therapy on mortality in critically ill septic adults. DATA SOURCES: Literature searches were implemented in Ovid Medline, Embase, Scopus, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, and ClinicalTrials.gov through February 2016. STUDY SELECTION: Inclusion criteria were observational or randomized studies of septic patients, evaluation of antipyretic treatment, mortality reported, and English-language version available. Studies were excluded if they enrolled pediatric patients, patients with neurologic injury, or healthy volunteers. Criteria were applied by two independent reviewers. DATA EXTRACTION: Two reviewers independently extracted data and evaluated methodologic quality. Outcomes included mortality, frequency of shock reversal, acquisition of nosocomial infections, and changes in body temperature, heart rate, and minute ventilation. Randomized and observational studies were analyzed separately. DATA SYNTHESIS: Eight randomized studies (1,507 patients) and eight observational studies (17,432 patients) were analyzed. Antipyretic therapy did not reduce 28-day/hospital mortality in the randomized studies (relative risk, 0.93; 95% CI, 0.77-1.13; I = 0.0%) or observational studies (odds ratio, 0.90; 95% CI, 0.54-1.51; I = 76.1%). Shock reversal (relative risk, 1.13; 95% CI, 0.68-1.90; I = 51.6%) and acquisition of nosocomial infections (relative risk, 1.13; 95% CI, 0.61-2.09; I = 61.0%) were also unchanged. Antipyretic therapy decreased body temperature (mean difference, -0.38°C; 95% CI, -0.63 to -0.13; I = 84.0%), but not heart rate or minute ventilation. CONCLUSIONS: Antipyretic treatment does not significantly improve 28-day/hospital mortality in adult patients with sepsis.


Asunto(s)
Enfermedad Crítica/mortalidad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Temperatura Corporal/efectos de los fármacos , Infección Hospitalaria/epidemiología , Mortalidad Hospitalaria , Humanos , Morgue , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/epidemiología
4.
Crit Care ; 20(1): 334, 2016 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-27760554

RESUMEN

BACKGROUND: Identifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Little data exists comparing the ability of the two most well-studied markers of sepsis-induced immunosuppression, human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-ɑ) production, to predict mortality and morbidity. The purpose of this study was to compare HLA-DR expression and LPS-induced TNF-ɑ production as predictors of 28-day mortality and acquisition of secondary infections in adult septic patients. METHODS: A single-center, prospective observational study of 83 adult septic patients admitted to a medical or surgical intensive care unit. Blood samples were collected at three time points during the septic course (days 1-2, days 3-4, and days 6-8 after sepsis diagnosis) and assayed for HLA-DR expression and LPS-induced TNF-ɑ production. A repeated measures mixed model analysis was used to compare values of these immunological markers among survivors and non-survivors and among those who did and did not develop a secondary infection. RESULTS: Twenty-five patients (30.1 %) died within 28 days of sepsis diagnosis. HLA-DR expression was significantly lower in non-survivors as compared to survivors on days 3-4 (p = 0.04) and days 6-8 (p = 0.002). The change in HLA-DR from days 1-2 to days 6-8 was also lower in non-survivors (p = 0.04). Median HLA-DR expression decreased from days 1-2 to days 3-4 in patients who developed secondary infections while it increased in those without secondary infections (p = 0.054). TNF-ɑ production did not differ between survivors and non-survivors or between patients who did and did not develop a secondary infection. CONCLUSIONS: Monocyte HLA-DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS-stimulated TNF-ɑ production in adult medical and surgical critically ill patients.


Asunto(s)
Antígenos HLA-DR/metabolismo , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Sepsis/mortalidad , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Enfermedad Crítica/epidemiología , Femenino , Antígenos HLA-DR/inmunología , Humanos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Missouri/epidemiología , Estudios Prospectivos , Sepsis/epidemiología , Estadísticas no Paramétricas , Sobrevivientes/estadística & datos numéricos , Factor de Necrosis Tumoral alfa/inmunología
5.
J Pediatr Gastroenterol Nutr ; 60(4): 544-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25419681

RESUMEN

OBJECTIVES: Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. METHODS: Rural Malawian children 6 to 59 months old with MAM, defined as a weight-for-height z score (WHZ) between -2 and -3, were provided supplementary feeding for a fixed duration of 12 weeks. The children were then studied for 12 months to assess long-term nutritional status, and compared with children initially treated only until they first reached WHZ > -2. RESULTS: Compared with children treated until they reached WHZ > -2, children treated for 12 weeks were more likely to remain well nourished (71% vs 63%, P = 0.0015) and maintain more normal anthropometric indices during 12 months of follow-up; there was also a trend towards lower rates of severe acute malnutrition (7% vs 10%, P = 0.067) and death (2% vs 4%, P = 0.082). Regression modeling showed that mid-upper arm circumference and WHZ at the end of supplementary feeding were the most important factors in predicting which children remained well nourished (P < 0.001 for each). CONCLUSIONS: The duration of supplementary feeding for children with MAM may not be as important as their anthropometry in terms of remaining well nourished after initial recovery. The presently accepted recovery criteria of WHZ of -2 may be insufficient for ensuring long-term nutritional health; consideration should be given to setting higher recovery criteria.


Asunto(s)
Fenómenos Fisiológicos Nutricionales del Lactante , Desnutrición/dietoterapia , Estado Nutricional , Enfermedad Aguda , Tamaño Corporal , Preescolar , Femenino , Humanos , Lactante , Malaui/epidemiología , Masculino , Desnutrición/mortalidad , Proyectos Piloto , Recurrencia , Valores de Referencia , Factores de Tiempo
6.
Food Nutr Bull ; 36(1 Suppl): S72-5, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25902618

RESUMEN

A pattern of changes in the microbiome composition have been observed in the normal maturation of the human gut. Perturbations from this pattern have been described in malnourished humans and reproduced in animal models of severe malnutrition. Treatment and prevention of malnutrition in the future may be more effective if the interventions not only restore body composition, but the composition of the microbiome as well.


Asunto(s)
Dieta , Desnutrición/dietoterapia , Desnutrición/microbiología , Microbiota/fisiología , Enfermedad Aguda , Adulto , Animales , Niño , Preescolar , Modelos Animales de Enfermedad , Ambiente , Heces/microbiología , Humanos , Lactante , Enfermedades Intestinales/inmunología , Enfermedades Intestinales/microbiología , Mucosa Intestinal/microbiología , Kwashiorkor/microbiología , Malaui , Desnutrición/prevención & control , Ratones , Microbiota/inmunología , Estudios en Gemelos como Asunto
7.
Clin Gastroenterol Hepatol ; 12(9): 1507-13.e1, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24462483

RESUMEN

BACKGROUND & AIMS: Environmental enteropathy (EE) is a subclinical condition among children in the developing world, characterized by T-cell infiltration of the small-bowel mucosa and diffuse villous atrophy. EE leads to macronutrient and micronutrient malabsorption and stunting, with a resultant increased risk for infection and reduced cognitive development. We tested the hypothesis that zinc and albendazole treatments would reduce the severity of EE in rural African children. METHODS: In a randomized, double-blind, placebo-controlled trial in rural southern Malawi, asymptomatic children, 1 to 3 years old and at high risk for EE, received either a single dose of albendazole, a 14-day course of 20 mg zinc sulfate, or a placebo. Subjects were given the dual-sugar absorption test, and the ratio of lactulose to mannitol (L:M) in urine was used to determine the severity of EE at baseline and 34 days after completion of the assigned regimen. The primary outcome was the change in the L:M. RESULTS: A complete set of urine samples was obtained from 222 of 234 children enrolled and analyzed. The mean baseline L:M was 0.32 ± 0.18 among all children and did not differ among groups (normal L:M range, <0.12). At the end of the study, the L:M ratio had increased more in the placebo group (0.12 ± 0.31) than in the zinc group (0.03 ± 0.20; P < .03) or the albendazole group (0.04 ± 0.22; P < .04). CONCLUSIONS: Treatment with zinc or albendazole protects against a significant increase in the L:M ratio, a biomarker for EE, in asymptomatic rural Malawian children. These findings could provide insight into the etiology and pathogenesis of EE. Clinicaltrials.gov Number: NCT01440608.


Asunto(s)
Albendazol/administración & dosificación , Enfermedades Ambientales/tratamiento farmacológico , Enfermedades Ambientales/prevención & control , Fármacos Gastrointestinales/administración & dosificación , Enfermedades Intestinales/tratamiento farmacológico , Enfermedades Intestinales/prevención & control , Zinc/administración & dosificación , Enfermedades Asintomáticas , Preescolar , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Lactante , Absorción Intestinal/efectos de los fármacos , Lactulosa/análisis , Malaui , Masculino , Manitol/análisis , Placebos/administración & dosificación , Resultado del Tratamiento , Orina/química
8.
J Urban Health ; 90(5): 888-901, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23192386

RESUMEN

The Representation of Health Professionals on Governing Boards of Health Care Organizations in New York City. The heightened importance of processes and outcomes of care-including their impact on health care organizations' (HCOs) financial health-translate into greater accountability for clinical performance on the part of HCO leaders, including their boards, during an era of health care reform. Quality and safety of care are now fiduciary responsibilities of HCO board members. The participation of health professionals on HCO governing bodies may be an asset to HCO governing boards because of their deep knowledge of clinical problems, best practices, quality indicators, and other issues related to the safety and quality of care. And yet, the sparse data that exist indicate that physicians comprise more than 20 % of the governing board members of hospitals while less than 5 % are nurses and no data exist on other health professionals. The purpose of this two-phased study is to examine health professionals' representations on HCOs-specifically hospitals, home care agencies, nursing homes, and federally qualified health centers-in New York City. Through a survey of these organizations, phase 1 of the study found that 93 % of hospitals had physicians on their governing boards, compared with 26 % with nurses, 7 % with dentists, and 4 % with social workers or psychologists. The overrepresentation of physicians declined with the other HCOs. Only 38 % of home care agencies had physicians on their governing boards, 29 % had nurses, and 24 % had social workers. Phase 2 focused on the barriers to the appointment of health professionals to governing boards of HCOs and the strategies to address these barriers. Sixteen health care leaders in the region were interviewed in this qualitative study. Barriers included invisibility of health professionals other than physicians; concerns about "special interests"; lack of financial resources for donations to the organization; and lack of knowledge and skills with regard to board governance, especially financial matters. Strategies included developing an infrastructure for preparing and getting appointed various health professionals, mentoring, and developing a personal plan of action for appointments.


Asunto(s)
Consejo Directivo/organización & administración , Administración de Instituciones de Salud/estadística & datos numéricos , Personal de Salud/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Humanos , Capacitación en Servicio , Mentores , Ciudad de Nueva York , Servicio Social/estadística & datos numéricos
9.
BMC Cardiovasc Disord ; 13: 31, 2013 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-23617744

RESUMEN

BACKGROUND: Atrial fibrillation (AF) is an independent risk factor for stroke and a significant predictor of mortality. Evidence-based guidelines for stroke prevention in AF recommend antithrombotic therapy corresponding to the risk of stroke. In practice, many patients with AF do not receive the appropriate antithrombotic therapy and are left either unprotected or inadequately protected against stroke. The purpose of the Global Anticoagulant Registry in the FIELD (GARFIELD) is to determine the real-life management and outcomes of patients newly diagnosed with non-valvular AF. METHODS/DESIGN: GARFIELD is an observational, international registry of newly diagnosed AF patients with at least one additional investigator-defined risk factor for stroke. The aim is to enrol 55,000 patients at more than 1000 centres in 50 countries worldwide. Enrolment will take place in five independent, sequential, prospective cohorts; the first cohort includes a retrospective validation cohort. Each cohort will be followed up for 2 years. The UK stands to be a significant contributor to GARFIELD, aiming to enrol 4,582 patients, and reflecting the care environment in which patients with AF are managed. The UK protocol will also focus on better understanding the validity of the two main stroke risk scores (CHADS2 and CHA2DS2VASC) and the HAS-BLED bleeding risk score, in the context of a diverse patient population. DISCUSSION: The GARFIELD registry will describe how therapeutic strategies, patient care, and clinical outcomes evolve over time. This study will provide UK-specific comprehensive data that will allow a range of evaluations both at a national level and in relation to global data and contribute to a better understanding of AF management in the UK. TRIAL REGISTRATION: ClinicalTrial.gov: NCT01090362.


Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Servicios Preventivos de Salud/métodos , Proyectos de Investigación , Accidente Cerebrovascular/prevención & control , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Adhesión a Directriz , Hemorragia/inducido químicamente , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Selección de Paciente , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Estudios Prospectivos , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Reino Unido/epidemiología
10.
BMC Cardiovasc Disord ; 13: 16, 2013 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-23497371

RESUMEN

BACKGROUND: Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence.Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure. METHODS/DESIGN: Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires. DISCUSSION: The primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3-6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting. TRIAL REGISTRATION: ISRCTN73819751.


Asunto(s)
Anticoagulantes/administración & dosificación , Síndrome Postrombótico/prevención & control , Proyectos de Investigación , Tromboembolia Venosa/prevención & control , Warfarina/administración & dosificación , Administración Oral , Biomarcadores/sangre , Protocolos Clínicos , Esquema de Medicación , Inglaterra , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Síndrome Postrombótico/sangre , Síndrome Postrombótico/diagnóstico , Síndrome Postrombótico/etiología , Atención Primaria de Salud , Calidad de Vida , Prevención Secundaria , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/sangre , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/diagnóstico
11.
Cureus ; 15(6): e40906, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37492806

RESUMEN

Spontaneous coronary artery dissection (SCAD) is a condition primarily seen in young women and is characterized by non-atherosclerotic arterial damage. It can occur with or without conventional risk factors for coronary heart disease and is often associated with chronic inflammatory conditions. Here, we present a unique instance of a 67-year-old woman without known risk factors who developed sudden onset chest pain in the setting of an asymptomatic coronavirus 2019 (COVID-19) infection three weeks earlier. Subsequent evaluation revealed SCAD in the distal left anterior descending (LAD) artery.

12.
Chest ; 161(1): e23-e28, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35000713

RESUMEN

CASE PRESENTATION: A 55-year-old woman with a medical history of hereditary hemorrhagic telangiectasia (HHT) complicated by recurrent nosebleeds, severe blood loss anemia, hepatic arterial-venous malformation (AVM), pulmonary hypertension, and severe tricuspid regurgitation presented to the HHT specialty clinic with acute hypoxic respiratory failure (new 3-L O2 requirement), weight gain, and volume overload. She was directly admitted to the pulmonary hypertension unit of our hospital. She had two recent admissions for similar symptoms thought to be due to worsening pulmonary arterial hypertension. In prior admissions, she had undergone right heart catheterization demonstrating mild pulmonary hypertension (pulmonary arterial pressure, 29 mm Hg, cardiac output by Fick 5.76, and cardiac index 3.22, mildly elevated pulmonary vascular resistance to 5.5 woods units). She would undergo diuresis with symptomatic improvement; however, after discharge she would rapidly develop recurrent heart failure symptoms. She reported compliance with guideline-directed medications, diuretics, and dietary restrictions and was still suffering severe symptoms. Notably she had previously elevated liver enzymes concerning for cirrhosis and had begun a workup to evaluate for causes of cirrhosis; she had a history of mild alcohol use, negative hepatitis viral serology, and no known history of liver disease.


Asunto(s)
Malformaciones Arteriovenosas/fisiopatología , Gasto Cardíaco Elevado/diagnóstico , Insuficiencia Cardíaca/diagnóstico , Hígado/irrigación sanguínea , Telangiectasia Hemorrágica Hereditaria/fisiopatología , Insuficiencia de la Válvula Tricúspide/fisiopatología , Malformaciones Arteriovenosas/complicaciones , Cateterismo Cardíaco , Gasto Cardíaco Elevado/etiología , Gasto Cardíaco Elevado/fisiopatología , Ecocardiografía , Ecocardiografía Doppler en Color , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Arteria Hepática/anomalías , Venas Hepáticas/anomalías , Humanos , Persona de Mediana Edad , Vena Porta/anomalías , Hipertensión Arterial Pulmonar , Radiografía Torácica , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia/congénito , Insuficiencia de la Válvula Tricúspide/complicaciones , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/fisiopatología
13.
Front Microbiol ; 13: 936083, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35935217

RESUMEN

Escherichia coli and Enterococcus faecalis have been implicated as important players in human gut health that have been associated with the onset of inflammatory bowel disease (IBD). Bacteriophage (phage) therapy has been used for decades to target pathogens as an alternative to antibiotics, but the ability of phage to shape complex bacterial consortia in the lower gastrointestinal tract is not clearly understood. We administered a cocktail of six phages (either viable or heat-inactivated) targeting pro-inflammatory Escherichia coli LF82 and Enterococcus faecalis OG1RF as members of a defined community in both a continuous fermenter and a murine colitis model. The two target strains were members of a six species simplified human microbiome consortium (SIHUMI-6). In a 72-h continuous fermentation, the phage cocktail caused a 1.1 and 1.5 log (log10 genome copies/mL) reduction in E. faecalis and E. coli numbers, respectively. This interaction was accompanied by changes in the numbers of other SIHUMI-6 members, with an increase of Lactiplantibacillus plantarum (1.7 log) and Faecalibacterium prausnitzii (1.8 log). However, in germ-free mice colonized by the same bacterial consortium, the same phage cocktail administered twice a week over nine weeks did not cause a significant reduction of the target strains. Mice treated with active or inactive phage had similar levels of pro-inflammatory cytokines (IFN-y/IL12p40) in unstimulated colorectal colonic strip cultures. However, histology scores of the murine lower GIT (cecum and distal colon) were lower in the viable phage-treated mice, suggesting that the phage cocktail did influence the functionality of the SIHUMI-6 consortium. For this study, we conclude that the observed potential of phages to reduce host populations in in vitro models did not translate to a similar outcome in an in vivo setting, with this effect likely brought about by the reduction of phage numbers during transit of the mouse GIT.

14.
Fam Pract ; 28(2): 134-40, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21068191

RESUMEN

BACKGROUND: Research related to service requirements for anticoagulation management has focussed on clinical and health economic outcomes and paid little attention to the impact of treatment and service delivery on patients' quality of life. This was the first large UK study to evaluate the effect of patient self-management (PSM) of oral anticoagulation on treatment-related quality of life (TRQoL) and anxiety in comparison with routine care (RC) and to explore the effect of level of therapeutic control on TRQoL and anxiety across and within each model of care. METHODS: A quantitative survey, set in primary care in the West Midlands. The subjects were 517 randomized controlled trial participants, 242 receiving PSM and 275 RC. Postal questionnaires at baseline and 12 months comprised the State Trait Anxiety Inventory and a treatment-specific measure of positive (satisfaction and self-efficacy) and negative aspects (daily hassles, strained social network and psychological distress) of TRQoL. Change in anxiety and TRQoL scores were compared between PSM and RC. Subgroup analysis was based upon level of therapeutic control (high, medium and low). RESULTS: Overall, 83% (n = 202) PSM and 55% (n = 161) RC patients contributed data. Anxiety scores were similar in both groups. PSM demonstrated greater improvement in self-efficacy than RC across the study period. A statistically significant between-group difference (PSM versus RC) in the self-efficacy also existed in subgroups with medium and high levels of therapeutic control. CONCLUSIONS: PSM is not associated with increased anxiety and has a positive effect upon some aspects of TRQoL compared to RC.


Asunto(s)
Anticoagulantes/uso terapéutico , Ansiedad/terapia , Calidad de Vida , Autocuidado/psicología , Administración Oral , Humanos , Encuestas y Cuestionarios , Resultado del Tratamiento
15.
Viruses ; 13(4)2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33920965

RESUMEN

Antibiotic-resistant pathogens are increasingly more prevalent and problematic. Traditional antibiotics are no longer a viable option for dealing with these multidrug-resistant microbes and so new approaches are needed. Bacteriophage-derived proteins such as endolysins could offer one effective solution. Endolysins are bacteriophage-encoded peptidoglycan hydrolases that act to lyse bacterial cells by targeting their cell's wall, particularly in Gram-positive bacteria due to their naturally exposed peptidoglycan layer. These lytic enzymes have received much interest from the scientific community in recent years for their specificity, mode of action, potential for engineering, and lack of resistance mechanisms. Over the past decade, a renewed interest in endolysin therapy has led to a number of successful applications. Recombinant endolysins have been shown to be effective against prominent pathogens such as MRSA, Listeria monocytogenes, Staphylococcus strains in biofilm formation, and Pseudomonas aeruginosa. Endolysins have also been studied in combination with other antimicrobials, giving a synergistic effect. Although endolysin therapy comes with some regulatory and logistical hurdles, the future looks promising, with the emergence of engineered "next-generation" lysins. This review will focus on the likelihood that endolysins will become a viable new antimicrobial therapy and the challenges that may have to be overcome along the way.


Asunto(s)
Endopeptidasas/uso terapéutico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Terapia de Fagos/métodos , Animales , Bacteriófagos/enzimología , Pared Celular/metabolismo , Humanos , Peptidoglicano/metabolismo
16.
J Occup Environ Med ; 62(7): e355-e369, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32730040

RESUMEN

: On May 17, 2019, the US Centers for Disease Control and Prevention and National Tuberculosis Controllers Association issued new Recommendations for Tuberculosis Screening, Testing, and Treatment of Health Care Personnel, United States, 2019, updating the health care personnel-related sections of the Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005. This companion document offers the collective effort and experience of occupational health, infectious disease, and public health experts from major academic and public health institutions across the United States and expands on each section of the 2019 recommendations to provide clarifications, explanations, and considerations that go beyond the 2019 recommendations to answer questions that may arise and to offer strategies for implementation.


Asunto(s)
Transmisión de Enfermedad Infecciosa/prevención & control , Personal de Salud/normas , Tuberculosis/diagnóstico , Tuberculosis/terapia , Comités Consultivos/organización & administración , Comités Consultivos/normas , Centers for Disease Control and Prevention, U.S./normas , Humanos , Control de Infecciones/normas , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/prevención & control , Tuberculosis Latente/terapia , Tuberculosis Latente/transmisión , Tamizaje Masivo/normas , Mycobacterium tuberculosis/aislamiento & purificación , Salud Laboral/normas , Medición de Riesgo , Sociedades Médicas/normas , Tuberculosis/prevención & control , Tuberculosis/transmisión , Estados Unidos
17.
J Phys Chem Lett ; 10(15): 4266-4272, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31287706

RESUMEN

At widths below 10 nm, armchair graphene nanoribbons become semiconductors. One promising route to synthesize nanoribbons is chemical vapor deposition (CVD) of hydrocarbons on Ge(001), and synthesis from seeds reduces nanoribbon polydispersity. In this contribution, we advance the seed-initiated synthesis of nanoribbons and explore the impact of seed size and nanoribbon spacing on growth kinetics. Periodic arrays of graphene seeds are lithographically patterned and etched to reduce their diameter. The viability of initiating synthesis from sub-5 nm seeds is demonstrated, and the pitch between nanoribbons is reduced from 500 to 50 nm to show that crowding effects do not perturb nanoribbon growth kinetics. The invariance of kinetics with pitch in combination with density functional theory (DFT) calculations indicate that (1) the growth species for synthesis has a diffusion length of ≪50 nm and/or (2) the kinetics are strongly attachment-limited. These results demonstrate that seed-initiated synthesis on Ge(001) is a promising route for creating dense arrays of armchair graphene nanoribbons for semiconductor electronics applications.

18.
Nanoscale ; 11(11): 4864-4875, 2019 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-30821309

RESUMEN

Chemical vapor deposition of CH4 on Ge(001) can enable anisotropic growth of narrow, semiconducting graphene nanoribbons with predominately smooth armchair edges and high-performance charge transport properties. However, such nanoribbons are not aligned in one direction but instead grow perpendicularly, which is not optimal for integration into high-performance electronics. Here, it is demonstrated that vicinal Ge(001) substrates can be used to synthesize armchair nanoribbons, of which ∼90% are aligned within ±1.5° perpendicular to the miscut. When the growth rate is slow, graphene crystals evolve as nanoribbons. However, as the growth rate increases, the uphill and downhill crystal edges evolve asymmetrically. This asymmetry is consistent with stronger binding between the downhill edge and the Ge surface, for example due to different edge termination as shown by density functional theory calculations. By tailoring growth rate and time, nanoribbons with sub-10 nm widths that exhibit excellent charge transport characteristics, including simultaneous high on-state conductance of 8.0 µS and a high on/off conductance ratio of 570 in field-effect transistors, are achieved. Large-area alignment of semiconducting ribbons with promising charge transport properties is an important step towards understanding the anisotropic nanoribbon growth and integrating these materials into scalable, future semiconductor technologies.

19.
Lancet ; 370(9586): 493-503, 2007 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-17693178

RESUMEN

BACKGROUND: Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation, but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown. We assessed whether warfarin reduced risk of major stroke, arterial embolism, or other intracranial haemorrhage compared with aspirin in elderly patients. METHODS: 973 patients aged 75 years or over (mean age 81.5 years, SD 4.2) with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (target international normalised ratio 2-3) or aspirin (75 mg per day). Follow-up was for a mean of 2.7 years (SD 1.2). The primary endpoint was fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN89345269. FINDINGS: There were 24 primary events (21 strokes, two other intracranial haemorrhages, and one systemic embolus) in people assigned to warfarin and 48 primary events (44 strokes, one other intracranial haemorrhage, and three systemic emboli) in people assigned to aspirin (yearly risk 1.8%vs 3.8%, relative risk 0.48, 95% CI 0.28-0.80, p=0.003; absolute yearly risk reduction 2%, 95% CI 0.7-3.2). Yearly risk of extracranial haemorrhage was 1.4% (warfarin) versus 1.6% (aspirin) (relative risk 0.87, 0.43-1.73; absolute risk reduction 0.2%, -0.7 to 1.2). INTERPRETATION: These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient decides that the benefits are not worth the inconvenience.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/prevención & control , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Relación Normalizada Internacional , Masculino , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/clasificación , Accidente Cerebrovascular/etiología
20.
Am J Trop Med Hyg ; 99(4): 867-874, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29987998

RESUMEN

We used whole-genome sequencing to investigate a tuberculosis outbreak involving U.S.-born persons in the prison system and both U.S.- and foreign-born persons in the community in Florida over a 7-year period (2009-2015). Genotyping by spacer oligonucleotide typing and 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat suggested that the outbreak might be clonal in origin. However, contact tracing could not link the two populations. Through a multidisciplinary approach, we showed that the cluster involved distinct bacterial transmission networks segregated by country of birth. The source strain is of foreign origin and circulated in the local Florida community for more than 20 years before introduction into the prison system. We also identified novel transmission links involving foreign and U.S.-born cases not discovered during contact investigation. Our data highlight the potential for spread of strains originating from outside the United States into U.S. "high-risk" populations, such as prisoners, with subsequent movement back to the general community.


Asunto(s)
Brotes de Enfermedades , Genoma Bacteriano , Mycobacterium tuberculosis/genética , Prisioneros , Tuberculosis Pulmonar/epidemiología , Adulto , Infecciones Comunitarias Adquiridas , Trazado de Contacto , Emigrantes e Inmigrantes , Femenino , Florida/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia , Prisiones , Secuencias Repetidas en Tándem , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/transmisión , Secuenciación Completa del Genoma
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