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1.
Prev Sci ; 25(1): 155-174, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37843761

RESUMEN

Parents of adolescents are faced with a variety of challenges related to their children's behavior and development. Behavioral parent training (BPT) programs may be effective strategies to mitigate adverse childhood experiences (ACEs) and other common behavioral problems in the adolescent period. Adolescence is the period following the onset of puberty and describes the transition from childhood to adulthood. Digital BPTs, including those delivered via the internet, downloaded digital content, text message, tablet, and video call, may present a unique opportunity to reach a broad audience of parents of adolescents by removing barriers to program accessibility (e.g., cost and transportation). We conducted a literature review to synthesize the existing evidence on digital BPTs for parents of adolescents. We described the digital BPTs, study designs, and evaluation and feasibility outcomes. A structured literature search identified studies meeting the following criteria for inclusion: (a) published between January 2000 and October 2022, (b) peer-reviewed, (c) available in English language, (d) study included a description of a digital BPT methodological approach, (e) study had to identify at least one parent or child behavioral outcome (e.g., parent-reported communication with their child) or feasibility outcome associated with the digital BPT, and (f) study included parents of adolescents aged 10-18 years. We extracted data on the characteristics of the study and demographic characteristics of participants, digital BPT, and evaluation and feasibility outcomes. Twenty-eight studies met inclusion criteria. Twenty-two unique digital BPTs were evaluated across the published studies. Thirteen digital BPTs (59.1%) were developed from or grounded by an identified theory. Six digital BPTs were freely accessible by the public, while the remaining 16 were available through study participation or purchase. One digital BPT was specifically tailored to parents of adolescents of a racial/ethnic minority group. Of the 16 studies that reported either parent or adolescent race/ethnicity, 10 consisted of more than 50% White parent or adolescent participants. Twenty-four (88.9%) studies provided evaluation data for the digital BPT. Fourteen studies (63.6%) employed a randomized control trial study design, and the remaining study designs included quasi-experimental (n = 2), mixed methods (n = 1), open trial (n = 3), case study (n = 1), pretest-posttest design (n = 1), and feasibility and acceptability trial (n = 2). All studies reported improvements in at least one parent-reported or adolescent-reported behavioral outcome or feasibility outcomes, with effect sizes (Cohen's d) ranging from small (e.g., 0.20-0.49) to very large (e.g., > 1.20). The findings of this review illustrate that technology may be a valuable way to deliver BPTs to parents of adolescents. However, few digital BPTs were developed for parents of adolescents from racial/ethnic minority groups, and many digital BPTs were not available without cost or participation in a research study. Considerations for future research are discussed.


Asunto(s)
Etnicidad , Grupos Minoritarios , Adolescente , Niño , Humanos , Comunicación , Lenguaje , Padres/educación , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
Transfusion ; 63(11): 2170-2178, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37864539

RESUMEN

BACKGROUND: Safe blood transfusion is an increasing priority in global health equity. The Global Health 2030 commission lists access to a safe blood supply as essential for all surgical and nonoperative patients. The objective of this study was to determine if Transfusion Camp, when modified through a collaborative partnership between experts in Canada and Rwanda, results in improved knowledge and confidence among trainees in a resource-limited setting in sub-Saharan Africa. METHODS: This prospective study took place at The University Teaching Hospital of Kigali in Rwanda. Participants were postgraduate medical trainees from departments where blood transfusion is frequent. Participants watched five prerecorded lectures and then attended a 5-hour team-based learning seminar to consolidate learning. Pre- and post-data were analyzed on transfusion knowledge and trainee confidence. A Rasch analysis investigated the performance of individual questions in assessing respondent knowledge. RESULTS: Of 31 trainees from surgery, anesthesia, internal medicine, and pediatrics invited to the course, 27 trainees attended the in-person team-based learning and 24 trainees completed the pre- and post-course analysis. Trainee knowledge assessment improved from (mean ± SD) 7.7/20 ± 1.95 to 10.4/20 ± 2.4 (p < .0001) and this knowledge was maintained by 12 trainees on a 3-month follow-up with a mean score of 9.3/20 ± 2.3. Trainees reported increased confidence in managing transfusion medicine-related patient issues. CONCLUSION: This pilot study demonstrated that Transfusion Camp education content modified to the local context can result in increased knowledge and confidence in managing transfusion-related issues. These results will inform future planning of Transfusion Camp in resource-limited settings.


Asunto(s)
Transfusión Sanguínea , Competencia Clínica , Humanos , Niño , Estudios Prospectivos , Rwanda , Proyectos Piloto , Estudios de Factibilidad
3.
Transfusion ; 63(11): 2159-2169, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37688306

RESUMEN

BACKGROUND: Due to few teaching faculty, resource-limited settings may lack the education curricula providers need for safe practice. As safe surgery becomes an increasing priority worldwide, it is essential to improve access to critical education content including in transfusion medicine. Transfusion Camp is a longitudinal curriculum, shown to increase knowledge in postgraduate trainees. The objective was to develop a sustainable bilateral partnership between Rwanda and Canada, and to integrate Transfusion Camp into the existing curriculum of the School of Medicine and Pharmacy at University of Rwanda. METHODS: A Transfusion Camp pilot course was initiated through collaboration of experts in Rwanda and Canada. Planning occurred over 6 months via online and in-person meetings. Canadian teaching faculty adapted course content via iterative discussion with Rwandan faculty. Final content was delivered through online pre-recorded lectures by Canadian Faculty, and in-person small-group seminars by Rwandan Faculty. Project feasibility was assessed through structured evaluation and informal debriefing. RESULTS: Twenty-seven postgraduate trainees were present for the pilot course, of whom 21 (78%) submitted evaluation forms. While the structure and content of the adapted Transfusion Camp curriculum were well-received, the majority of respondents indicated a preference for in-person rather than pre-recorded lectures. Debriefing determined that future courses should focus on continuing education initiatives aimed at physicians entering or already in independent practice. CONCLUSION: A partnership between universities and blood operators in high-resource and resource-limited countries results in a transfusion medicine curriculum that is locally applicable, multidisciplinary, and supportive of learning benefitting the learners and educators alike.


Asunto(s)
Medicina Transfusional , Humanos , Medicina Transfusional/educación , Rwanda , Configuración de Recursos Limitados , Canadá , Curriculum
4.
World J Surg Oncol ; 21(1): 379, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38044454

RESUMEN

BACKGROUND: Abdominally based free flaps are commonly used in breast reconstruction. A frequent complication is venous congestion, which might contribute to around 40% of flap failures. One way to deal with it is venous supercharging. The primary aim of this study was to investigate the scientific evidence for the effects of venous supercharging. METHODS: A systematic literature search was conducted in PubMed, CINAHL, Embase, and Cochrane library. The included articles were critically appraised, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: Thirty-six studies were included. Most studies had serious study limitations and problems with directness. Three studies report 'routine' use of venous supercharging and performed it prophylactically in patients who did not have clinical signs of venous congestion. Seventeen studies report on flap complications, of which one is a randomised controlled trial demonstrating statistically significant lower complication rates in the intervention group. The overall certainty of evidence for the effect of a venous supercharging on flap complications, length of hospital stay and operative time, in patients without clinical signs of venous congestion, is very low (GRADE ⊕ ⊕ ⊝ ⊝), and low on and surgical takebacks (GRADE ⊕ ⊕ ⊝ ⊝). Twenty-one studies presented data on strategies and overall certainty of evidence for using radiological findings, preoperative measurements, and clinical risk factors to make decisions on venous supercharging is very low (GRADE ⊕ ⊝ ⊝ ⊝). CONCLUSION: There is little scientific evidence for how to predict in which cases, without clinical signs of venous congestion, venous supercharging should be performed. The complication rate might be lower in patients in which a prophylactic venous anastomosis has been performed. TRIAL REGISTRATION: PROSPERO (CRD42022353591).


Asunto(s)
Hiperemia , Mamoplastia , Colgajo Perforante , Humanos , Hiperemia/etiología , Hiperemia/prevención & control , Hiperemia/cirugía , Colgajo Perforante/efectos adversos , Supervivencia de Injerto , Mamoplastia/efectos adversos , Venas/cirugía , Estudios Retrospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Air Med J ; 39(6): 512-515, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33228906

RESUMEN

The intubated and ventilated patient in austere and inaccessible environments requiring helicopter hoist extraction presents significant procedural and logistical challenges. This case report describes the use of a mechanical ventilator and visible advanced monitoring throughout the entirety of the patient journey from the prehospital scene to the hospital, including the period during hoist extraction as human external cargo.


Asunto(s)
Ambulancias Aéreas , Aeronaves , Humanos
6.
Stud Hist Philos Sci ; 78: 5-13, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31818419

RESUMEN

This paper provides an account of the 'use-value' of case-based research by showing how social scientists exploit cases, and case studies, in a variety of practices of inference and extension. The critical basis for making such extensions relies on the power of a case, or the account given of a case (the case-study account), to exemplify certain features of the social world in ways which prove valuable for further analysis: either of the same case, or in many domains beyond the original case study. Framing use-values in terms of exemplification compares favourably with understanding reasoning beyond the case either as a form of analogical reasoning or in taking cases as experimentable objects.

7.
J Intensive Care Med ; 33(1): 37-47, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27591199

RESUMEN

OBJECTIVE: Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. METHODS: This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. RESULTS: Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] µM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. CONCLUSIONS: Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.


Asunto(s)
Homocisteína/metabolismo , Mortalidad Hospitalaria , Metionina/metabolismo , S-Adenosilhomocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Sepsis/metabolismo , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Infecciones Relacionadas con Catéteres/metabolismo , Estudios de Cohortes , Femenino , Humanos , Infecciones Intraabdominales/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Infecciones del Sistema Respiratorio/metabolismo , Sepsis/mortalidad , Enfermedades Cutáneas Infecciosas/metabolismo , Infecciones Urinarias/metabolismo
8.
9.
Stud Hist Philos Sci ; 62: 86-97, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28583363

RESUMEN

This paper investigates the important role of narrative in social science case-based research. The focus is on the use of narrative in creating a productive ordering of the materials within such cases, and on how such ordering functions in relation to 'narrative explanation'. It argues that narrative ordering based on juxtaposition - using an analogy to certain genres of visual representation - is associated with creating and resolving puzzles in the research field. Analysis of several examples shows how the use of conceptual or theoretical resources within the narrative ordering of ingredients enables the narrative explanation of the case to be resituated at other sites, demonstrating how such explanations can attain scope without implying full generality.

10.
Br J Haematol ; 175(2): 318-330, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27432187

RESUMEN

Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the 'discoverability' of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family.


Asunto(s)
Anemia/diagnóstico , Anemia/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Biología Computacional/métodos , Manejo de la Enfermedad , Estudios de Asociación Genética , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Mutación , Polimorfismo de Nucleótido Simple , Enfermedades Raras , Reproducibilidad de los Resultados , Flujo de Trabajo
11.
J Natl Compr Canc Netw ; 14(6): 715-24, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27283164

RESUMEN

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment. They are intended to aid health care professionals who work with survivors of adult-onset cancer in the posttreatment period, including those in general oncology, specialty cancer survivor clinics, and primary care practices. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors. This article summarizes the NCCN Survivorship panel's discussions for the 2016 update of the guidelines regarding the management of anxiety, depression, posttraumatic stress disorder-related symptoms, and emotional distress in survivors.


Asunto(s)
Neoplasias/mortalidad , Humanos , Neoplasias/terapia , Tasa de Supervivencia
12.
Crit Care ; 20(1): 335, 2016 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-27765072

RESUMEN

BACKGROUND: Experimental studies demonstrate beneficial immunological and hemodynamic effects of estradiol in animal models of sepsis. This raises the question whether estradiol contributes to sex differences in the incidence and outcomes of sepsis in humans. Yet, total estradiol levels are elevated in sepsis patients, particularly nonsurvivors. Bioavailable estradiol concentrations have not previously been reported in septic patients. The bioavailable estradiol concentration accounts for aberrations in estradiol carrier protein concentrations that could produce discrepancies between total and bioavailable estradiol levels. We hypothesized that bioavailable estradiol levels are low in septic patients and sepsis nonsurvivors. METHODS: We conducted a combined case-control and prospective cohort study. Venous blood samples were obtained from 131 critically ill septic patients in the medical and surgical intensive care units at the University of Rochester Medical Center and 51 control subjects without acute illness. Serum bioavailable estradiol concentrations were calculated using measurements of total estradiol, sex hormone-binding globulin, and albumin. Comparisons were made between patients with severe sepsis and control subjects and between hospital survivors and nonsurvivors. Multivariable logistic regression analysis was also performed. RESULTS: Bioavailable estradiol concentrations were significantly higher in sepsis patients than in control subjects (211 [78-675] pM vs. 100 [78-142] pM, p < 0.01) and in sepsis nonsurvivors than in survivors (312 [164-918] pM vs. 167 [70-566] pM, p = 0.04). After adjustment for age and comorbidities, patients with bioavailable estradiol levels above the median value had significantly higher risk of hospital mortality (OR 4.27, 95 % CI 1.65-11.06, p = 0.003). Bioavailable estradiol levels were directly correlated with severity of illness and did not differ between men and women. CONCLUSIONS: Contrary to our hypothesis, bioavailable estradiol levels were elevated in sepsis patients, particularly nonsurvivors, and were independently associated with mortality. Whether estradiol's effects are harmful, beneficial, or neutral in septic patients remains unknown, but our findings raise caution about estradiol's therapeutic potential in this setting. Our findings do not provide an explanation for sex-based differences in sepsis incidence and outcomes.


Asunto(s)
Enfermedad Crítica/mortalidad , Estradiol/sangre , Mortalidad Hospitalaria/tendencias , Choque Séptico/sangre , Choque Séptico/mortalidad , Anciano , Disponibilidad Biológica , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Choque Séptico/diagnóstico
13.
Biochim Biophys Acta ; 1842(4): 573-83, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24440361

RESUMEN

Over the last decade, there has been a growing interest in the use of interventions that target the intestinal microbiota as a treatment approach for asthma. This study is aimed at exploring the therapeutic effects of long-term treatment with a combination of Bifidobacterium breve with non-digestible oligosaccharides on airway inflammation and remodeling. A murine ovalbumin-induced chronic asthma model was used. Pulmonary airway inflammation; mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; expression of Foxp3 in blood Th cells; in vitro T cell activation; mast cell degranulation; and airway remodeling were examined. The combination of B. breve with non-digestible oligosaccharides suppressed pulmonary airway inflammation; reduced T cell activation and mast cell degranulation; modulated expression of pattern recognition receptors, cytokines and transcription factors; and reduced airway remodeling. The treatment induced regulatory T cell responses, as shown by increased Il10 and Foxp3 transcription in lung tissue, and augmented Foxp3 protein expression in blood CD4+CD25+Foxp3+ T cells. This specific combination of beneficial bacteria with non-digestible oligosaccharides has strong anti-inflammatory properties, possibly via the induction of a regulatory T cell response, resulting in reduced airway remodeling and, therefore, may be beneficial in the treatment of chronic inflammation in allergic asthma.


Asunto(s)
Asma/tratamiento farmacológico , Bifidobacterium , Oligosacáridos/uso terapéutico , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Animales , Asma/inmunología , Enfermedad Crónica , Citocinas/genética , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead/análisis , Masculino , Mastocitos/fisiología , Ratones , Ratones Endogámicos BALB C , ARN Mensajero/análisis , Receptores de Reconocimiento de Patrones/genética , Células Th2/inmunología
14.
Mol Ther ; 22(1): 52-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23863881

RESUMEN

The occurrence of clonal perturbations and leukemia in patients transplanted with gamma-retroviral (RV) vector-transduced autologous hematopoietic stem and progenitor cells (HSPCs) has stimulated extensive investigation, demonstrating that proviral insertions may perturb adjacent proto-oncogene expression. Although enhancer-deleted lentiviruses are less likely to result in insertional oncogenesis, there is evidence that they may perturb transcript splicing, and one patient with a benign clonal expansion of lentivirally transduced HPSC has been reported. The rhesus macaque model provides an opportunity for informative long-term analysis to ask whether transduction impacts on long-term HSPC properties. We used two techniques to examine whether lentivirally transduced HSPCs from eight rhesus macaques transplanted 1-13.5 years previously are perturbed at a population level, comparing telomere length as a measure of replicative history and gene expression profile of vector positive versus vector negative cells. There were no differences in telomere lengths between sorted GFP+ and GFP- blood cells, suggesting that lentiviral (LV) transduction did not globally disrupt replicative patterns. Bone marrow GFP+ and GF- CD34+ cells showed no differences in gene expression using unsupervised and principal component analysis. These studies did not uncover any global long-term perturbation of proliferation, differentiation, or other important functional parameters of transduced HSPCs in the rhesus macaque model.


Asunto(s)
Expresión Génica , Vectores Genéticos/genética , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/metabolismo , Lentivirus/genética , Telómero , Transducción Genética , Animales , Antígenos CD34/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Leucocitos Mononucleares/metabolismo , Macaca mulatta , Transcriptoma , Transgenes
15.
Gut ; 63(4): 578-87, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23525573

RESUMEN

OBJECTIVE: Proline-glycine-proline (PGP) has been shown to have chemotactic effects on neutrophils via CXCR2 in several lung diseases. PGP is derived from collagen by the combined action of matrix metalloproteinase (MMP) 8 and/or MMP9 and prolyl endopeptidase (PE). We investigated the role of PGP in inflammatory bowel disease (IBD). DESIGN: In intestinal tissue from patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis, MMP8, MMP9 and PE were evaluated by ELISA, immunoblot and immunohistochemistry. Peripheral blood polymorphonuclear cell (PMN) supernatants were also analysed accordingly and incubated with collagen to assess PGP generation ex vivo. PGP levels were measured by mass spectrometry, and PGP neutralisation was achieved with a PGP antagonist and PGP antibodies. RESULTS: In the intestine of patients with IBD, MMP8 and MMP9 levels were elevated, while PE was expressed at similar levels to control tissue. PGP levels were increased in intestinal tissue of patients with IBD. Similar results were obtained in intestine from DSS-treated mice. PMN supernatants from patients with IBD were far more capable of generating PGP from collagen ex vivo than healthy controls. Furthermore, PGP neutralisation during DSS-induced colitis led to a significant reduction in neutrophil infiltration in the intestine. CONCLUSIONS: The proteolytic cascade that generates PGP from collagen, as well as the tripeptide itself, is present in the intestine of patients with IBD and mice with DSS-induced colitis. PGP neutralisation in DSS-treated mice showed the importance of PGP-guided neutrophilic infiltration in the intestine and indicates a vicious circle in neutrophilic inflammation in IBD.


Asunto(s)
Colágeno/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Infiltración Neutrófila/fisiología , Adolescente , Adulto , Anciano , Animales , Niño , Modelos Animales de Enfermedad , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/fisiopatología , Mucosa Intestinal/metabolismo , Intestinos/enzimología , Intestinos/fisiopatología , Masculino , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Prolil Oligopeptidasas , Serina Endopeptidasas/metabolismo , Adulto Joven
16.
Biochim Biophys Acta ; 1832(12): 2162-72, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23851050

RESUMEN

Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), contribute to the development of intestinal inflammatory diseases, like inflammatory bowel disease (IBD). Supporting investigations of the underlying mechanisms of IBD, this study provides an extensive PRR expression survey together with T-cell associated factors along the murine colon during experimental colitis. 8-12 week-old C57BL/6 mice were treated with dextran sodium sulfate (DSS) to induce colitis. The mRNA expression levels of Tlr1-9, Nod1, Nod2, T cell subset-associated master transcription factors and cytokines were determined using qPCR. The expression of TLR2, 4, 5 and 6 was determined with immunohistochemistry. Th1 and Th17 associated responses were quantified in the mesenteric lymph nodes (mLNs) using flow cytometry. In DSS treated mice, the mRNA expression of the majority of PRRs was increased relative to healthy controls and correlated with the degree of inflammation. The exceptions were Tlr1 and Tlr5, which displayed unchanged and down-regulated transcription, respectively. Furthermore, in healthy animals, there was increased transcription of Tlr2, 3 and 5 near the caecum as opposed the region near the rectum. Within the inflamed regions, the mRNA expression of Th1-, Th17- and regulatory T-cell associated cytokines was enhanced, while there was no change for Th2-associated cytokines. In agreement with the mRNA expression, enhanced IFNγ and IL-17 producing cells were observed in stimulated mLNs. This study provides an extensive expression survey of PRRs along the colon during the acute colitis and shows that the induced inflammation is characterized by a Th1- and IL-17 mediated cytokine response.


Asunto(s)
Colitis/patología , Regulación de la Expresión Génica , Proteína Adaptadora de Señalización NOD1/genética , Proteína Adaptadora de Señalización NOD2/genética , Receptores de Reconocimiento de Patrones/genética , Linfocitos T Reguladores/inmunología , Receptores Toll-Like/genética , Transcripción Genética , Enfermedad Aguda , Animales , Western Blotting , Colitis/inducido químicamente , Colitis/genética , Citocinas/inmunología , Citocinas/metabolismo , Sulfato de Dextran/toxicidad , Femenino , Citometría de Flujo , Técnicas para Inmunoenzimas , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Interleucina-17/inmunología , Interleucina-17/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína Adaptadora de Señalización NOD1/metabolismo , Proteína Adaptadora de Señalización NOD2/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Reconocimiento de Patrones/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores/metabolismo , Células TH1/inmunología , Células TH1/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Receptores Toll-Like/metabolismo
17.
Br J Haematol ; 164(3): 414-21, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24422725

RESUMEN

Since the first description of subcutaneous protein C concentrate as treatment for severe protein C deficiency in 1996, further cases have been reported but there is no uniform approach to this form of treatment. In order to assess the safety and effectiveness of subcutaneous protein C concentrate and suggest recommendations for future use, patients who had received subcutaneous protein C concentrate were identified from the literature, by contacting the manufacturers and by personal communication. Treatment details were available from 14 cases. Apart from one case where the infusion interval was inadvertently increased, no thrombotic events occurred even when doses were subsequently reduced. Initially, a trough protein C level of >0·25 iu/ml should be aimed for. Subsequently, a smaller dose of subcutaneous protein C concentrate, especially if taken with an oral anticoagulant, may be protective maintenance treatment. The treatment was well tolerated with few side effects. Subcutaneous protein C concentrate on its own or combined with an oral anticoagulant appears to be safe and effective as maintenance treatment of severe protein C deficiency. A major advantage is the avoidance of central venous access devices. The incidence of neurodevelopmental handicap was high with blindness affecting the majority of patients.


Asunto(s)
Deficiencia de Proteína C/tratamiento farmacológico , Proteína C/administración & dosificación , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Infusiones Subcutáneas , Masculino , Persona de Mediana Edad , Proteína C/efectos adversos , Proteína C/metabolismo , Deficiencia de Proteína C/sangre , Resultado del Tratamiento , Adulto Joven
18.
Respir Res ; 15: 46, 2014 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-24735374

RESUMEN

BACKGROUND: Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma. METHODS: To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined. RESULTS: Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells. CONCLUSION: These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.


Asunto(s)
Asma/tratamiento farmacológico , Bifidobacterium , Budesonida/uso terapéutico , Modelos Animales de Enfermedad , Lacticaseibacillus rhamnosus , Neumonía/tratamiento farmacológico , Animales , Antiinflamatorios/uso terapéutico , Asma/microbiología , Asma/patología , Enfermedad Crónica , Masculino , Ratones , Ratones Endogámicos BALB C , Neumonía/microbiología , Neumonía/patología , Resultado del Tratamiento
19.
J Natl Compr Canc Netw ; 12(12): 1681-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25505209

RESUMEN

The number of cancer survivors will be increasing over the next decade. Caring for this burgeoning population will place demands on oncologists and primary care providers to meet the needs of the expected large numbers of new patients as the baby-boom generation ages. Many will live beyond 5 years and possibly for decades after diagnosis. Patients experience many transitions depending on the type and stage of cancer, its treatment, and the long-term or late effects they have from the disease and its treatment. The Institute of Medicine's report, "From Cancer Patient to Cancer Survivor: Lost in Transition," recommends that patients be provided with a summary of their cancer treatment and follow-up care plan (ie, survivorship care plan [SCP]), including recommendations on healthy lifestyle behaviors and resources to promote self-care. This plan should be shared with the patient's other health care providers, including the primary care provider. This will facilitate communication among providers and with the patient, which is a key component to quality care. The American College of Surgeons Commission on Cancer has also made providing SCPs to patients at completion of treatment a quality standard. Barriers to providing SCPs have been identified and include lack of time, reimbursement, and knowledge of late treatment effects and current guidelines. Survivorship guidelines are being developed by professional organizations that may be useful for providers. This article provides some practical tools that address these recommendations to help providers and patients with transitions along the cancer trajectory.


Asunto(s)
Neoplasias/epidemiología , Tasa de Supervivencia , Sobrevivientes/psicología , Humanos , Neoplasias/psicología , Planificación de Atención al Paciente , Relaciones Médico-Paciente , Encuestas y Cuestionarios , Estados Unidos
20.
J Natl Compr Canc Netw ; 12(11): 1526-31, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25361799

RESUMEN

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment. This portion of the guidelines describes recommendations regarding screening for the effects of cancer and its treatment. The panel created a sample screening tool, specifically for use in combination with the NCCN Guidelines for Survivorship, to guide providers to topics that require more in-depth assessment. Effective screening and assessment can help providers deliver necessary and comprehensive survivorship care.


Asunto(s)
Neoplasias/diagnóstico , Neoplasias/mortalidad , Detección Precoz del Cáncer/métodos , Humanos , Neoplasias/terapia , Tasa de Supervivencia , Sobrevivientes
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