RESUMEN
Whereas prolonged static stretching (SS: >60-seconds per muscle) can increase range of motion (ROM) for up to 2-hours, it can also decrease maximal voluntary isometric contraction (MVIC) forces, countermovement (CMJ) and drop jump (DJ) heights, and muscle activation immediately after the stretching exercise. When an appropriate SS duration (<60-seconds per muscle) is incorporated into a dynamic warm-up, performance decrements are often trivial. However, there is a lack of studies that observed the effects of extensive SS (180-seconds) 2-hours prior to a dynamic warm-up. The objective was to investigate ROM and performance effects of prolonged SS, 2-hours prior to a traditional warm-up. This study investigated 9 female and 8 male healthy recreationally active, young adult participants on the effects of prolonged SS (180-seconds per muscle) of the quadriceps and hamstrings, 2-hours before a traditional warm-up compared to an active control condition on hip flexion ROM, knee extension and flexion MVIC forces, CMJ, DJ, and quadriceps and hamstrings electromyography (EMG). There were no significant changes in knee flexion/extension MVIC forces, EMG, CMJ, or DJ height. However, there was significant, small magnitude (p = 0.002) greater post-warm-up left hip flexion ROM (115.4° ± 17.2) than pre-SS (108.9° ± 17.13, Effect size [ES]: 0.28) and control post-warm-up (p = 0.05, ES: 0.31, 109.5° ± 20.55). Similarly, right hip flexion ROM (117.2° ± 16.5) also demonstrated significant small magnitude (p = 0.003) greater than the pre-SS (112.4° ± 18.4, ES: 0.22) and control post-warm-up (p = 0.046, ES: 0.33, 110.8° ± 20.5). Additionally, significant, large magnitude greater hip flexion ROM was observed with the women vs. men (ES: 1.29 - 1.34). Significant hip flexion ROM increases were not accompanied by significant changes in knee flexion/extension MVIC forces, EMG, or jump heights, suggesting that extensive SS can positively impact ROM without performance deficits when followed by a traditional warm-up, 2-hours after SS.
Asunto(s)
Rendimiento Atlético , Electromiografía , Músculos Isquiosurales , Contracción Isométrica , Ejercicios de Estiramiento Muscular , Rango del Movimiento Articular , Ejercicio de Calentamiento , Humanos , Masculino , Ejercicios de Estiramiento Muscular/fisiología , Femenino , Ejercicio de Calentamiento/fisiología , Adulto Joven , Músculos Isquiosurales/fisiología , Contracción Isométrica/fisiología , Rendimiento Atlético/fisiología , Músculo Cuádriceps/fisiología , Factores de Tiempo , Adulto , Rodilla/fisiologíaRESUMEN
Importance: In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists guidelines that recommended postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm. In response to increased wound hematomas without significant reduction in VTE using this protocol, a more selective risk-stratified approach was adopted in 2021. Objective: To evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol. Design, Setting, and Participants: Retrospective observational study of 17â¯489 patients who delivered at a single tertiary care center in the southeast US between January 1, 2016, and December 31, 2018 (original protocol), and between December 1, 2021, and May 31, 2023 (more selective protocol). Patients receiving outpatient anticoagulation for active VTE or high VTE risk during pregnancy were excluded. Exposure: Standard risk-stratified and more selective postpartum VTE chemoprophylaxis protocols. Main Outcomes and Measures: The primary outcome was clinical diagnosis of wound hematoma up to 6 weeks pos tpartum. The secondary outcome was new diagnosis of VTE up to 6 weeks post partum. We compared baseline characteristics and outcomes between groups and estimated adjusted odds ratios with 95% CIs of primary and secondary outcomes using the original protocol group as reference. Results: Of 17â¯489 patients included in the analysis, 12â¯430 (71%) were in the original protocol group and 5029 (29%) were in the more selective group. Rates of chemoprophylaxis decreased from 16% (original protocol) to 8% (more selective protocol). Patients in the more selective group were more likely to be older, be married, and have obesity or other comorbidities (hypertension, diabetes, cardiac disease). Compared with the original protocol, the more selective protocol was associated with a decrease in any wound hematoma (0.7% vs 0.3%; adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.67), specifically due to a lower rate of superficial wound hematomas (0.6% vs 0.3%; aOR, 0.43; 95% CI, 0.24-0.75). There was no significant increase in VTE or individual types of VTE (0.1% vs 0.1%; aOR, 0.40; 95% CI, 0.12-1.36). Conclusions and Relevance: A more selective risk-stratified approach to an enoxaparin thromboprophylaxis protocol for VTE was associated with decreased rates of wound hematomas without increased rates of postpartum VTE.
Asunto(s)
Anticoagulantes , Enoxaparina , Hematoma , Tromboembolia Venosa , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Tromboembolia Venosa/prevención & control , Adulto , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Enoxaparina/uso terapéutico , Medición de Riesgo , Hematoma/prevención & control , Protocolos Clínicos , Complicaciones Cardiovasculares del Embarazo/prevención & control , Guías de Práctica Clínica como AsuntoRESUMEN
Pressure injuries affect 13.1% to 45.5% of patients in the intensive care unit and lead to pain and discomfort for patients, burden on healthcare providers, and unnecessary cost to the health system. Turning and positioning systems offer improvements on usual care devices, however the evidence of the effectiveness of such systems is still emerging. We conducted an investigator initiated, prospective, single centre, two group, non-blinded, randomised controlled trial to determine the effectiveness of a system for turning and positioning intensive care unit patients, when compared to usual care turning and positioning devices, for preventing PIs. The trial was prematurely discontinued after enrolment of 78 participants due to COVID-19 pandemic related challenges and lower than expected enrolment rate. The study groups were comparable on baseline characteristics and adherence to the interventions was high. Four participants developed a PI (in the sacral, ischial tuberosity or buttock region), n = 2 each in the intervention and control group. Each participant developed one PI. As the trial is underpowered, these findings do not provide an indication of the clinical effectiveness of the interventions. There was no participant drop-out or withdrawal and there were no adverse events, device deficiencies, or adverse device effects identified or reported. The results of our study (in particular those pertaining to enrolment, intervention adherence and safety) provide considerations for future trials that seek to investigate how to prevent PIs among ICU patients.
Asunto(s)
COVID-19 , Úlcera por Presión , Humanos , COVID-19/prevención & control , Análisis de Costo-Efectividad , Úlcera por Presión/prevención & control , Pandemias , Estudios Prospectivos , Unidades de Cuidados Intensivos , HospitalesRESUMEN
OBJECTIVE: Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p-value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p-value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. STUDY DESIGN: A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p-values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p-value significance threshold of 0.005 versus be reinterpreted as "suggestive" (defined as p-value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. RESULTS: Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p <0.05 at the time of publication, 54.4% (n = 49) would maintain significant (p < 0.005), while 45.6% (n = 41) would become suggestive using the lower threshold. Most RCTs utilized a single (90.1%) versus composite (8.9%) primary outcome type, used an intent-to-treat analysis (73.3%), and studied a drug intervention (46.5%). Methodologically, 23.7% did not prespecify analysis type, 28.2% did not meet the pre-determined sample size, and 9.4% did not report an a priori sample size calculation. Studies maintaining significance were more likely to be international and report a funding source. CONCLUSION: Adopting a p-value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. KEY POINTS: · New p-value threshold results in reinterpretation of nearly half of RCT results in OB/Gyn literature.. · Highly variable methodological quality was identified.. · Reduced use of binary interpretations of significance is necessary..
Asunto(s)
Interpretación Estadística de Datos , Ginecología , Obstetricia , Ensayos Clínicos Controlados Aleatorios como Asunto , Publicaciones Periódicas como Asunto , Reproducibilidad de los Resultados , Estadística como AsuntoRESUMEN
Human cytomegalovirus (HCMV) enters cells through a complex pathway involving the interaction of multiple viral glycoproteins and cellular receptors. While HCMV clinical isolates enter a wide range of cell types, entry has historically been studied using a laboratory strain of virus that can only infect fibroblasts. Herein, we have constructed a HCMV reporter strain that contains GFP fused to the abundant tegument protein pp65 to allow for the direct visualization of virus attachment and entry. Furthermore, the UL131 gene of this strain was restored to clinical isolate sequence to expand our studies of entry into physiologically relevant epithelial cell types. Using the HCMV-GFP reporter virus, we developed an image-based assay and screened a library containing 65,000 compounds for the inhibition of virus entry into fibroblasts. In addition to assessing the effect on virus entry, automated image analysis provided information on compound toxicity and whether the compounds acted as attachment or post-attachment inhibitors. To identify therapeutically viable inhibitors capable of blocking entry in multiple cell types, the inhibitors were screened further for their ability to inhibit virus entry into epithelial cells. Compounds were identified that were able to inhibit virus entry into both cell types at either attachment or post-attachment steps.
Asunto(s)
Antivirales/aislamiento & purificación , Citomegalovirus/fisiología , Evaluación Preclínica de Medicamentos/métodos , Células Epiteliales/virología , Fibroblastos/virología , Virología/métodos , Internalización del Virus , Antivirales/farmacología , Citomegalovirus/efectos de los fármacos , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Coloración y Etiquetado/métodosRESUMEN
Human cytomegalovirus (CMV) is a large enveloped virus that encodes multiple glycoproteins required for virus-cell binding and fusion. To assess the binding properties of antibodies with target glycoprotein in a natural context of infection, we investigated the feasibility of using the surface plasmon resonance (SPR) technique for studying the direct binding of antibodies with CMV virions. Direct immobilization of whole virions to sensor surface and a surface regeneration procedure allowed for quantitative and reproducible measurements of binding affinity and binding kinetics of antibody-whole virion interactions. The conformational and functional integrity of viral particles was not compromised by the regeneration condition as evaluated with antibodies recognizing conformational epitopes and by electron microscopy. Binding of an irrelevant antibody was not observed, indicating the high specificity of the method. A panel of anti-gB antibodies was measured and the binding affinities correlated fairly well with those determined by ELISA. These data demonstrated that the interaction of anti-gB antibody with whole virion of large enveloped CMV can be quantitatively studied using SPR. This method has been successfully applied for screening and selection of anti-CMV antibodies and can be potentially extended to study antibody-glycoprotein interactions of other related herpesviruses.
Asunto(s)
Anticuerpos Antivirales/inmunología , Citomegalovirus/inmunología , Resonancia por Plasmón de Superficie/métodos , Proteínas del Envoltorio Viral/inmunología , Especificidad de Anticuerpos/inmunología , Citomegalovirus/ultraestructura , Ensayo de Inmunoadsorción Enzimática , Humanos , Cinética , Reproducibilidad de los Resultados , Propiedades de Superficie , Virión/ultraestructuraRESUMEN
Secondary bacterial infections that follow infection with influenza virus result in considerable morbidity and mortality in young children, the elderly, and immunocompromised individuals and may also significantly increase mortality in normal healthy adults during influenza pandemics. We herein describe a mouse model for investigating the interaction between influenza virus and the bacterium Haemophilus influenzae. Sequential infection with sublethal doses of influenza and H. influenzae resulted in synergy between the two pathogens and caused mortality in immunocompetent adult wild-type mice. Lethality was dependent on the interval between administration of the bacteria and virus, and bacterial growth was prolonged in the lungs of dual-infected mice, although influenza virus titers were unaffected. Dual infection induced severe damage to the airway epithelium and confluent pneumonia, similar to that observed in victims of the 1918 global influenza pandemic. Increased bronchial epithelial cell death was observed as early as 1 day after bacterial inoculation in the dual-infected mice. Studies using knockout mice indicated that lethality occurs via a mechanism that is not dependent on Fas, CCR2, CXCR3, interleukin-6, tumor necrosis factor, or Toll-like receptor-4 and does not require T or B cells. This model suggests that infection with virulent strains of influenza may predispose even immunocompetent individuals to severe illness on secondary infection with H. influenzae by a mechanism that involves innate immunity, but does not require tumor necrosis factor, interleukin-6, or signaling via Toll-like receptor-4.
Asunto(s)
Modelos Animales de Enfermedad , Infecciones por Haemophilus/mortalidad , Haemophilus influenzae/fisiología , Virus de la Influenza A/fisiología , Infecciones por Orthomyxoviridae/mortalidad , Inmunidad Adaptativa/fisiología , Animales , Células Cultivadas , Perros , Infecciones por Haemophilus/complicaciones , Infecciones por Haemophilus/patología , Infecciones por Haemophilus/virología , Humanos , Pulmón/patología , Pulmón/virología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infecciones por Orthomyxoviridae/complicaciones , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/virología , Sobreinfección/inmunología , Sobreinfección/mortalidad , Sobreinfección/patología , Sobreinfección/virología , Carga ViralRESUMEN
CD4 T cells are not essential for primary clearance of replicating murine gammaherpesvirus 68 (MHV-68) but are required for effective long-term control. The virus reactivates in the lungs of major histocompatibility complex class II-deficient (CII-/-) mice that lack functional CD4 T cells. CD40 ligand (CD40L) is upregulated on activated CD4 T cells, and it is thought that CD40-CD40L interactions are an important component of CD4 T-cell help. Our previous studies have shown that agonistic antibodies to CD40 can substitute for CD4 T-cell function in the long-term control of MHV-68. In the present study, we sought to identify the CD40-positive cell type mediating this effect. To address this question, we adoptively transferred MHV-68 peptide-pulsed CII(-/-) dendritic cells (DC) that had been treated with an agonistic antibody to CD40 into MHV-68-infected CII(-/-) recipients. Viral reactivation was significantly lower in mice injected with anti-CD40-treated DC than in those injected with control DC or in mice that did not receive any DC. However, in similar experiments with B cells, anti-CD40 treatment had no effect. We also investigated the requirement for CD40 expression on T cells by adoptive transfer of T cells from CD40(+/+) or CD40(-/-) mice into T-cell-deficient recipients that were subsequently infected with MHV-68. The results showed that CD40 expression on T cells is not necessary for preventing viral reactivation. Taken together, our data suggest that CD40 engagement on DC, but not on T or B cells, is essential for effective long-term control of MHV-68.
Asunto(s)
Linfocitos B/inmunología , Antígenos CD40/inmunología , Células Dendríticas/inmunología , Rhadinovirus/inmunología , Traslado Adoptivo , Animales , Anticuerpos Antivirales/sangre , Femenino , Pulmón/virología , Ratones , Ratones Noqueados , Linfocitos T/inmunología , Ensayo de Placa Viral , Activación Viral/inmunologíaRESUMEN
CD4 T cells are dispensable for acute control of murine gammaherpesvirus 68 (MHV-68) but are necessary for effective long-term control of the virus by CD8 T cells. In contrast, protein kinase C theta (PKCtheta) is not essential for either acute or long-term viral control. However, we found that while either CD4 or CD8 T cells could mediate the clearance of MHV-68 from the lungs of PKCtheta(+/+) mice, PKCtheta(-/-) mice depleted of either subset failed to clear the virus. These data suggest that there are two alternative pathways for MHV-68 clearance, one dependent on CD4 T cells and the other on PKCtheta. Protection mediated by the latter appears to be short-lived. These observations may help to explain the differential requirement for PKCtheta in various models of CD8 T-cell activation and differences in the costimulatory requirements for acute and long-term viral control.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Isoenzimas/fisiología , Proteína Quinasa C/fisiología , Rhadinovirus/inmunología , Animales , Movimiento Celular , Citotoxicidad Inmunológica , Interferón gamma/biosíntesis , Pulmón/inmunología , Ratones , Proteína Quinasa C-thetaRESUMEN
Neutrophils traffic to the lungs in large numbers during influenza virus infection. Although the ability of these cells to respond to numerous chemotactic stimuli has been described in other systems, the chemokine receptors mediating recruitment of neutrophils to the lungs during influenza virus infection and the role of this cell type in viral clearance are currently undefined. In the present study, we used CXCR2(/) mice to investigate the role of the chemokine receptor CXCR2 in neutrophil recruitment to the lungs during influenza virus infection and to determine the role of neutrophils in viral clearance. We infected CXCR2(/) or wild-type mice with influenza and assessed the level of inflammation, the cellular composition of the inflammatory infiltrate, and viral titers in the lungs. Absence of CXCR2 ablated neutrophil recruitment to the lungs, but had no effect on peak viral titers or on the kinetics of viral clearance. Thus, it appears that CXCR2 is the major receptor mediating neutrophil trafficking to the lung during influenza virus infection, but that neutrophils do not play an essential role in viral clearance.