RESUMEN
BACKGROUND: There has been a dramatic increase in the number of doctoral programs (PhD and DNP) that prepare nurse research scientists and advanced practitioners since establishment of the National Institute of Nursing Research (NINR) at the National Institutes of Health (NIH) in 1985. PURPOSE: The purpose of this report is to examine the historical context of federal research funding to schools/colleges of nursing to determine if the NINR/NIH budget is adequate. METHOD: Data were extracted from the NIH RePORT/ER database from 1993 to 2017. Additional data were obtained from the American Association of Colleges of Nursing. A return on investment analysis for four landmark nursing studies is included. FINDINGS: The percent of the NINR budget awarded to schools/colleges of nursing peaked in 2005; since 2011, more funding to schools/colleges of nursing was received from all other NIH institutes combined, compared to NINR. The return on investment for four nursing research studies, ranged from $1:$202 to $1:$1,206, and far exceeds the Standard and Poor's 500 Index (S&P 500) of 10%. DISCUSSION: Federal funding of nursing research is inadequate and a chokepoint relative to the number of doctoral programs. We suggest the NINR budget would need to increase at least fivefold to over $763 million to adequately fund nursing science. The impact of inadequate funding on the discipline is discussed.
Asunto(s)
Gobierno Federal , Financiación Gubernamental/estadística & datos numéricos , National Institutes of Health (U.S.)/economía , Investigación en Enfermería/economía , Apoyo a la Investigación como Asunto/estadística & datos numéricos , Presupuestos , Bases de Datos Factuales , Humanos , National Institute of Nursing Research (U.S.)/economía , Estados UnidosRESUMEN
CONTEXT: Acute postoperative pain remains inadequately assessed and managed. A valid instrument that assesses acute pain in sedated postanesthesia care unit (PACU) patients is needed. OBJECTIVES: Two behavioral pain assessment instruments, the NonVerbal Pain Scale Revised (NVPS-R) and Critical-care Pain Observation Tool (CPOT), were used to determine whether these instruments adequately assess acute pain in the PACU. METHODS: A crossover study design was used. The study was conducted in the Medical Services Administration at the Puerto Rico Medical Center. Upon PACU arrival, patient sedation levels were evaluated using the Richmond Agitation Sedation Scale. Acute pain was assessed using the CPOT (scored, 0 to 8) and the NVPS-R (scored, 0 to 10) at timepoints 0, 15, 30, 45, 60, 90, and 120 minutes. Descriptive statistics and mixed model regression analysis were used to compare pain score assessment between instruments. RESULTS: Clinically significant increases in vital signs and respiratory indicators using the NVPS-R were not seen in patients with significant pain at time 0, 15, and 120 minutes. The CPOT vocalization indicator was more frequent in patients with significant pain. CONCLUSIONS: Findings suggest that NVPS-R and CPOT can assess acute pain in sedated PACU patients. In patients with significant pain, the CPOT vocalization indicator was more consistent than physiological and respiratory indicators in detecting acute pain. Thus, our data do not support the exclusive use of vital sign indicators to assess acute pain, suggesting the superiority of the CPOT for the assessment of acute pain in sedated PACU patients.
Asunto(s)
Dolor Agudo/diagnóstico , Sedación Consciente , Dimensión del Dolor/métodos , Dolor Postoperatorio/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Sedación Consciente/métodos , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Distribución Aleatoria , Respiración , Factores de Tiempo , Conducta Verbal , Adulto JovenRESUMEN
BACKGROUND: A major feature of chronic wounds is the loss of tissue, with the exposure of dermal components preventing primary closure and leading to bacterial colonization. Bacterial colonization has been proposed as one of the common underlying pathologies present in chronic wounds. The objective of this exploratory study was to identify bacteria cultured from chronic venous leg ulcers and test for proteolytic activity that degrades matrix substrates. METHOD: Bacteria were isolated, cultured, and identified from six subjects (average age = 62.8 years) over 2-10 months under an approved protocol using swabs and microbiological culture media. Proteolytic activity against (a) gelatin, (b) an elastin substrate, and (c) a serine/trypsin-sensitive substrate was determined using a colorimetric plate assay with an ELISA plate reader and zymography. RESULTS: We identified 13 bacteria that expressed proteolytic activity against one or more of the tested substrates. Of these, six were Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Streptococcus agalactiae, Corynebacterium, and Streptococcus bovis) and seven were Gram-negative (Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Morganella morganii, Klebsiella pneumoniae, Bacteroides fragilis, and Serratia marcescens) organisms. Two of these, S. aureus and P. aeruginosa, are recognized wound pathogens. CONCLUSIONS: Multiple bacteria species isolated from colonized venous leg ulcers have the capacity to secrete proteases capable of degrading components of the extracellular matrix important for wound healing. Matrix degradation by bacteria may contribute to delays in tissue deposition and repair, suggesting that treatment of chronic wounds should include appropriate management of colonizing bacteria.
Asunto(s)
Matriz Extracelular/microbiología , Bacterias Gramnegativas/metabolismo , Bacterias Grampositivas/metabolismo , Tejido de Granulación/microbiología , Úlcera de la Pierna/microbiología , Piel/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Elastina/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Gelatina/metabolismo , Tejido de Granulación/metabolismo , Tejido de Granulación/patología , Humanos , Úlcera de la Pierna/metabolismo , Úlcera de la Pierna/patología , Masculino , Técnicas Microbiológicas , Persona de Mediana Edad , ProteolisisRESUMEN
Wound healing is the inherent ability of an organism to protect itself against injuries. Cumulative evidence indicates that the healing process patterns in part embryonic morphogenesis and may result in either organ regeneration or scarring, phenomena that are developmental stage- or age-dependent. Skin is the largest organ. Its morphogenesis and repair mechanisms have been studied extensively due not only to its anatomical location, which allows easy access and observation, but also to its captivating structure and vital function. Thus, this review will focus on using skin as a model organ to illustrate new insights into the mechanisms of wound healing that are developmentally regulated in mammals, with special emphasis on the role of the Wnt signaling pathway and its crosstalk with TGF-ß signaling. Relevant information from studies of other organs is discussed where it applies, and the clinical impact from such knowledge and emerging concepts on regenerative medicine are discussed in perspective.
Asunto(s)
Mamíferos/crecimiento & desarrollo , Morfogénesis/fisiología , Medicina Regenerativa/métodos , Fenómenos Fisiológicos de la Piel , Factores de Transcripción/metabolismo , Vía de Señalización Wnt/fisiología , Cicatrización de Heridas/fisiología , Factores de Edad , Animales , Humanos , Miofibroblastos/fisiología , Especificidad de la Especie , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: The use of Dakin's solution on open wounds remains controversial in clinical practice. Here we investigated the effect of Dakin's solution on collagen degradation and fibroblast migration using a dermal equivalent. MATERIALS AND METHODS: Acid solubilized or neutralized collagen was combined with four dilutions of Dakin's solution (0.5%, 0.25%, 0.125%, 0.0125%), with and without serum, at room temperature and 37 degrees C. Collagen degradation was examined at 0, 1, and 24 h using 8% SDS-page gels. Cell migration was determined using dermal equivalents where fibroblasts were incorporated into 3D collagen gels and exposed to Dakin's solution with and without serum. The cells were assessed for viability and cell migration at 24 and 48 h. RESULTS: Dakin's at 0.0125% resulted in little or no collagen degradation compared with a higher concentration of 0.5%, where collagen was either partially or completely degraded. Likewise, cell migration was completely inhibited at higher concentrations, while fibroblasts in a 3D matrix at 0.0125% were still able to migrate at 24 and 48 h, albeit in fewer numbers compared with controls. Serum had a protective effect for both collagen degradation and cell migration when added together with the Dakin's solutions. A time and temperature dependent effect was also noted, with longer contact and higher temperatures being more detrimental. CONCLUSIONS: Collagen degradation and fibroblast migration is affected by the concentration of Dakin's solution, the presence or absence of serum, time exposure and temperature. Use of Dakin's solution in clinical settings should take these findings into consideration in clinical practice.
Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Movimiento Celular/efectos de los fármacos , Colágeno/metabolismo , Fibroblastos/efectos de los fármacos , Bicarbonato de Sodio/administración & dosificación , Hipoclorito de Sodio/administración & dosificación , Células Cultivadas , Colágeno/efectos de los fármacos , Combinación de Medicamentos , Humanos , Suero , Temperatura , Factores de TiempoRESUMEN
Dynamic interactions between growth factors and extracellular matrix (ECM) are integral to wound healing. These interactions take several forms that may be categorized as direct or indirect. The ECM can directly bind to and release certain growth factors (e.g., heparan sulfate binding to fibroblast growth factor-2), which may serve to sequester and protect growth factors from degradation, and/or enhance their activity. Indirect interactions include binding of cells to ECM via integrins, which enables cells to respond to growth factors (e.g., integrin binding is necessary for vascular endothelial growth factor-induced angiogenesis) and can induce growth factor expression (adherence of monocytes to ECM stimulates synthesis of platelet-derived growth factor). Additionally, matrikines, or subcomponents of ECM molecules, can bind to cell surface receptors in the cytokine, chemokine, or growth factor families and stimulate cellular activities (e.g., tenascin-C and laminin bind to epidermal growth factor receptors, which enhances fibroblast migration). Growth factors such as transforming growth factor-beta also regulate the ECM by increasing the production of ECM components or enhancing synthesis of matrix degrading enzymes. Thus, the interactions between growth factors and ECM are bidirectional. This review explores these interactions, discusses how they are altered in difficult to heal or chronic wounds, and briefly considers treatment implications.
Asunto(s)
Matriz Extracelular/fisiología , Péptidos y Proteínas de Señalización Intercelular/fisiología , Cicatrización de Heridas/fisiología , Heridas y Lesiones/fisiopatología , Enfermedad Crónica , Colágeno/fisiología , Elastina/fisiología , Factor 2 de Crecimiento de Fibroblastos/fisiología , Fibroblastos/fisiología , Glicosaminoglicanos/fisiología , Humanos , Integrinas/fisiología , Péptidos y Proteínas de Señalización Intercelular/uso terapéutico , Metaloproteinasas de la Matriz/fisiología , Glicoproteínas de Membrana/fisiología , Osteonectina/fisiología , Receptores de Superficie Celular/fisiología , Trombospondinas/fisiología , Heridas y Lesiones/metabolismo , Heridas y Lesiones/terapiaRESUMEN
Chronic wounds expose the dermal matrix and underlying tissue to a diversity of microbes from the body and surrounding environment. We determined the microbial diversity of 19 chronic wounds using both molecular methods (sequence analysis of rRNA genes) and routine clinical culturing methods using swab samples. We identified 93 phylotypes in 2,653 rRNA clone sequences and found that compared with other environments, the microbial diversity of chronic wounds is relatively well characterized, i.e., 95% of sequences have > or =97% identity with known human commensals. In total, 75% of sequences belonged to four well-known wound-associated phylotypes: Staphylococcus (25%), Corynebacterium (20%), Clostridiales (18%), and Pseudomonas (12%). Approximately 0.5% of sequences (seven phylotypes) belonged to potentially new species. Individual wound samples contained four to 22 phylotypes, but in all wounds only a few (one to three) phylotypes were dominant. In more than half the wound specimens, polymerase chain reaction and culturing methods gave different diversity and dominance information about the microbes present. This exploratory study suggests that combining molecular and culturing methods provides a more complete characterization of the microbial diversity of chronic wounds, and can thereby expand our understanding of how microbiology impacts chronic wound pathology and healing.
Asunto(s)
Infecciones Bacterianas/microbiología , Técnicas de Tipificación Bacteriana/métodos , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ARN/métodos , Infección de Heridas/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Técnicas de Tipificación Bacteriana/normas , Enfermedad Crónica , Infecciones por Clostridium/microbiología , Comorbilidad , Infecciones por Corynebacterium/microbiología , Femenino , Variación Genética/genética , Humanos , Masculino , Persona de Mediana Edad , Mississippi/epidemiología , Montana/epidemiología , Filogenia , Reacción en Cadena de la Polimerasa/normas , Infecciones por Pseudomonas/microbiología , ARN Bacteriano/análisis , ARN Bacteriano/genética , Análisis de Secuencia de ARN/normas , Infecciones Estafilocócicas/microbiología , Infección de Heridas/diagnóstico , Infección de Heridas/epidemiologíaRESUMEN
Keloids are tumor-like skin scars that grow as a result of the aberrant healing of skin injuries, with no effective treatment. We provide new evidence that both overexpression of plasminogen activator inhibitor-1 (PAI-1) and elevated collagen accumulation are intrinsic features of keloid fibroblasts and that these characteristics are causally linked. Using seven strains each of early passage normal and keloid fibroblasts, the keloid strains exhibited inherently elevated collagen accumulation and PAI-1 expression in serum-free, 0.1% ITS+ culture; larger increases in these parameters occurred when cells were cultured in 3% serum. To demonstrate a causal relationship between PAI-1 overexpression and collagen accumulation, normal fibroblasts were infected with PAI-1-expressing adenovirus. Such cells exhibited a two- to fourfold increase in the accumulation of newly synthesized collagen in a viral dose-dependent fashion in both monolayers and fibrin gel, provisional matrix-like cultures. Three different PAI-1-targeted small interfering RNAs, alone or in combination, produced greater than an 80% PAI-1 knockdown and reduced collagen accumulation in PAI-1-overexpressing normal or keloid fibroblasts. A vitronectin-binding mutant of PAI-1 was equipotent with wild-type PAI-1 in inducing collagen accumulation, whereas a complete protease inhibitor mutant retained approximately 50% activity. Thus, PAI-1 may use more than its protease inhibitory activity to control keloid collagen accumulation. PAI-1-targeted interventions, such as small interfering RNA and lentiviral short hairpin RNA-containing microRNA sequence suppression reported here, may have therapeutic utility in the prevention of keloid scarring.
Asunto(s)
Adenoviridae/genética , Colágeno/metabolismo , Fibroblastos/patología , Queloide/patología , Inhibidor 1 de Activador Plasminogénico/metabolismo , ARN Interferente Pequeño/metabolismo , Supresión Genética , Adolescente , Adulto , Anciano , Células Cultivadas , Colágeno/biosíntesis , Femenino , Fibroblastos/metabolismo , Fibroblastos/virología , Humanos , Queloide/metabolismo , Masculino , Persona de Mediana Edad , Mutación/genética , Transducción GenéticaRESUMEN
Acceleration of the wound healing process by using angiogenic peptides has been demonstrated previously. Here we used select laminin-111 peptides, A13 and C16, from the laminin alpha1 and gamma1 chain, respectively, to test whether they are able to stimulate wound healing in a rat full thickness wound model. The 12-mer peptides C16 and A13 are highly angiogenic and bind to integrins alphavbeta3 and alpha5beta1. We show that A13 increases wound re-epithelialization as much as 17% over controls by day 4 and C16 increases coverage by 11%. Contraction of the treated wounds was increased as much as 11% for A13 and 8% for C16 at day 4. No differences were observed at day 7 with either peptide. The peptides also stimulated fibroblast migration in Boyden chamber assays. A13 increased cell migration as much as 2.4-fold on uncoated filters and as much as 16-fold on collagen type IV-coated filters over negative controls. Similarly, C16 also stimulated migration 1.8-fold on uncoated filters and as much as 12-fold on collagen-coated filters. A13 and C16 significantly decreased expression of the pro and active forms of matrix metalloproteinase 2 in foreskin fibroblasts indicating their role in collagen accumulation. We conclude that small bioactive angiogenic peptides can promote dermal wound healing and may offer a new class of stable and chemically manipulable therapeutics for wound healing.
Asunto(s)
Proteínas Angiogénicas/farmacología , Laminina/química , Neovascularización Fisiológica/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Proteínas Angiogénicas/química , Proteínas Angiogénicas/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Células Cultivadas , Colágeno Tipo IV/metabolismo , Relación Dosis-Respuesta a Droga , Endotelio/efectos de los fármacos , Endotelio/metabolismo , Endotelio/fisiología , Endotelio Vascular/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/fisiología , Humanos , Integrina alfa5beta1/metabolismo , Integrina alfaVbeta3/metabolismo , Laminina/fisiología , Metaloproteinasa 2 de la Matriz/metabolismo , Neovascularización Fisiológica/fisiología , Ratas , Piel/citología , Factores de Tiempo , Venas Umbilicales/citología , Cicatrización de Heridas/fisiologíaRESUMEN
When a sheep loses its tail, it cannot regenerate it in the manner of lizards. On the other hand, it is possible to clone mammals from somatic cells, showing that a complete developmental program is intact in a wounded sheep's tail the same way it is in a lizard. Thus, there is a requirement for more than only the presence of the entire genetic code in somatic cells for regenerative abilities. Thoughts like this have motivated us to assemble more than just a factographic synopsis on tissue regeneration. As a model, we review skin wound healing in chronological order, and when possible, we use that overview as a framework to point out possible mechanisms of how damaged tissues can restore their original structure. This article postulates the existence of tissue structural memory as a complex distributed homeostatic mechanism. We support such an idea by referring to an extremely fragmented literature base, trying to synthesize a broad picture of important principles of how tissues and organs may store information about their own structure for the purposes of regeneration. Selected developmental, surgical, and tissue engineering aspects are presented and discussed in the light of recent findings in the field. When a sheep loses its tail, it cannot regenerate it in the manner of lizards. On the other hand, it is possible to clone mammals from somatic cells, showing that a complete developmental program is intact in a wounded sheep's tail the same way it is in a lizard. Thus, there is a requirement for more than only the presence of the entire genetic code in somatic cells for regenerative abilities. Thoughts like this have motivated us to assemble more than just a factographic synopsis on tissue regeneration. As a model, we review skin wound healing in chronological order, and when possible, we use that overview as a framework to point out possible mechanisms of how damaged tissues can restore their original structure. This article postulates the existence of tissue structural memory as a complex distributed homeostatic mechanism. We support such an idea by referring to an extremely fragmented literature base, trying to synthesize a broad picture of important principles of how tissues and organs may store information about their own structure for the purposes of regeneration. Selected developmental, surgical, and tissue engineering aspects are presented and discussed in the light of recent findings in the field.
Asunto(s)
Regeneración/genética , Fenómenos Fisiológicos de la Piel/genética , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Desarrollo Embrionario/genética , Desarrollo Embrionario/fisiología , Humanos , Modelos Biológicos , Regeneración/fisiología , Piel/lesiones , Piel/patología , Cicatrización de Heridas/genética , Cicatrización de Heridas/fisiologíaRESUMEN
 Evidence-based choices for treating burns in children are not well defined. Skin substitutes and contemporary dressings offer potential advantages over traditional treatment with topical antimicrobial agents in treating partial-thickness burns. Newer treatment modalities may reduce morbidity, financial burdens, and scarring by accelerating healing. Reports of pediatric burn management from 1997 to 2007 were reviewed to compare agent performance with outcome measures such as healing time, pain moderation, cosmetic results, and hospital costs. Transcyte™ (Smith & Nephew, London), Biobrane® (Bertek Pharmaceuticals Inc, Morgantown, WV), beta-glucan collagen, and Mepitel® (Mölnlycke, Göteborg, Sweden) have been reported as superior to silver sulfadiazine (SSD) in achieving faster healing times and decreased pain in pediatric patients. Initial reports describing the outcomes achieved with these new agents indicate that they may offer clinical advantages in the treatment of partial-thickness burns in children. Increased costs of the new products appeared to be offset by decreases in hospital stay, nursing care time and pain medications. The existing literature is not conclusive, and prospective trials with standardized outcome measures are needed to better define the role of these agents. .
RESUMEN
Open skin wounds are colonized with bacteria, and optimal wound care is required to prevent progression to infection. Intact skin normally provides protection from external environmental assaults. Disruption of the skin or tissue creating an open skin wound can result in infection, dehydration, hypothermia, scarring, compromised immunity, and changes in body image. Biofilms and bacterial genomics are areas of intense scientific investigation in the face of the emerging threat of bacterial resistance. Optimal wound care to prevent progression from colonization to infection remains the foundation of good clinical practice. On the basis of wound conditions, cleansing, debridement, measures to increase oxygenation and perfusion, adequate nutrition, and appropriate use of topical agents and antibiotics, when indicated, are the keys to managing open skin wounds. This article provides a targeted review of normal skin flora, wound healing, prevention of skin infection, colonization versus infection, biofilms, genomics and infectious disease, and management of open skin wounds.