RESUMEN
OBJECTIVE: The coronavirus disease-2019 (COVID-19) pandemic has strained all levels of healthcare and it is not known how chiropractic practitioners have responded to this crisis. The purpose of this report is to describe responses by a sample of chiropractors during the early stages of the COVID-19 pandemic. METHODS: We used a qualitative-constructivist design to understand chiropractic practice during the COVID-19 pandemic, as described by the participants. A sample of chiropractic practitioners (doctors of chiropractic, chiropractors) from various international locations were invited to participate. Each described the public health response to COVID-19 in their location and the actions that they took in their chiropractic practices from April 20 through May 4, 2020. A summary report was created from their responses and common themes were identified. RESULTS: Eighteen chiropractic practitioners representing 17 locations and 11 countries participated. A variety of practice environments were represented in this sample, including, solo practice, mobile practice, private hospital, US Veterans Administration health care, worksite health center, and group practice. They reported that they recognized and abided by changing governmental regulations. They observed their patients experience increased stress and mental health concerns resulting from the pandemic. They adopted innovative strategies, such as telehealth, to do outreach, communicate with, and provide care for patients. They abided by national and World Health Organization recommendations and they adopted creative strategies to maintain connectivity with patients through a people-centered, integrated, and collaborative approach. CONCLUSION: Although the chiropractors in this sample practiced in different cities and countries, their compliance with local regulations, concern for staff and patient safety, and people-centered responses were consistent. This sample covers all 7 World Federation of Chiropractic regions (ie, African, Asian, Eastern Mediterranean, European, Latin American, North American, and Pacific) and provides insights into measures taken by chiropractors during the early stages of the COVID-19 pandemic. This information may assist the chiropractic profession as it prepares for different scenarios as new evidence about this disease evolves.
Asunto(s)
Quiropráctica , Infecciones por Coronavirus/epidemiología , Control de Infecciones/organización & administración , Administración de Consultorio/organización & administración , Neumonía Viral/epidemiología , Betacoronavirus , COVID-19 , Regulación Gubernamental , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios , TelemedicinaRESUMEN
Objective: This study aimed to (1) collect and analyze statements about how to celebrate chiropractic in the present and roles that chiropractors may fulfill in the future, (2) identify if there was congruence among the themes between present and future statements, and (3) offer a model about the chiropractic profession that captures its complex relationships that encompass its interactions within microsystem, mesosystem, exosystem, and macrosystem levels. Methods: For this qualitative analysis, we used pattern and grounded theory approaches. A purposive sample of thought leaders in the chiropractic profession were invited to answer the following 2 open-ended questions: (1) envision the chiropractor of the future, and (2) recommendations on how to celebrate chiropractic. Information was collected during April 2023 using Survey Monkey. The information was entered into a spreadsheet and analyzed for topic clusters, which resulted in matching concepts with social-ecological themes. The themes between the responses to the 2 questions were analyzed for congruence. We used the Standards for Reporting Qualitative Research to report our findings. Results: Of the 54 experts invited, 32 (59%) participated. Authors represented 7 countries and have a median of 32 years of chiropractic experience, with a range of 5 to 51 years. Nineteen major topics in the future statements and 23 major topics in statements about celebrating chiropractic were combined in a model. The topics were presented using the 4 levels of the social-ecological framework. Individual (microsystem): chiropractors are competent, well-educated experts in spine and musculoskeletal care who apply evidence-based practices, which is a combination of the best available evidence, clinical expertise, and patient values. Interpersonal relationships (mesosystem): chiropractors serve the best interests of their patients, provide person-centered care, embrace diversity, equity, and inclusion, consider specific health needs and the health of the whole person. Community (exosystem): chiropractors provide care within integrated health care environments and in private practices, serve the best interests of the public through participation in their communities, participate through multidisciplinary collaboration with and within the health care system, and work together as a profession with a strong professional identity. Societal (macrosystem): chiropractors contribute to the greater good of society and participate on a global level in policy, leadership, and research. There was concordance between both the future envisioning statements and the present celebration recommendations, which suggest logical validity based on the congruence of these concepts. Conclusion: A sample of independent views, including the perceptions from a broad range of chiropractic thought leaders from various backgrounds, philosophies, diversity characteristics, and world regions, were assembled to create a comprehensive model of the chiropractic profession. The resulting model shows an array of intrinsic values and provides the roles that chiropractors may provide to serve patients and the public. This study offers insights into the roles that future chiropractors may fulfill and how these are congruent with present-day values. These core concepts and this novel model may have utility during dialogs about identity, applications regarding chiropractic in policy, practice, education, and research, and building positive relationships and collaborations.
RESUMEN
BACKGROUND: Open surgical trigger finger release has limited success and the risk of complications; however, percutaneous techniques offer a successful alternative. There is limited understanding of the success of percutaneous trigger finger release. OBJECTIVE: To prospectively evaluate the functional outcomes of patients with Green classification Grade 2 to 4 trigger finger treated with an ultrasound-guided microinvasive trigger finger release using a special 18-gauge needle with a blade at the tip. DESIGN: Prospective, case-series study. SETTING: This study took place at an academic institution by one sports medicine physician (R.E.C.) with subspecialty training and certification in musculoskeletal ultrasound. PATIENTS: Sixty patients (79 cases) met criteria and agreed to participate in this study; 19 patients had multiple fingers treated. Average patient age was 62.8 years (SD 10.2). Average trigger finger severity diagnosis was Grade 3. INTERVENTIONS: Patients were treated with an ultrasound-guided microinvasive trigger finger release using a special 18-gauge needle with a blade at the tip. MAIN OUTCOME MEASUREMENTS: Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), numerical rating scale (NRS), and Nirschl scores were captured preprocedure, at various time points, and at final follow-up. Changes between preprocedure and final follow-up were analyzed by paired t test (p < .05). Differences were also analyzed between finger, grade level, and gender by repeated measures analyses of variance (p < .05). RESULTS: No adverse events were documented perioperatively or postoperatively. Average follow-up time was 18.4 months (SD 4.6). At final follow-up, 100% of patients reported no recurrence of catching/locking, 97% had complete resolution of symptoms and significant improvement in QuickDASH scores, and 99% required no further treatment. All measurements showed a decrease in pain and symptoms over time. The improvements in QuickDASH score, NRS, and Nirschl scale and the resolution of mechanical symptoms were all statistically significant. CONCLUSIONS: Ultrasound-guided release using the 18-gauge needle with a blade provides significant functional improvement and full resolution of mechanical symptoms with minimal adverse events.
Asunto(s)
Trastorno del Dedo en Gatillo , Humanos , Persona de Mediana Edad , Agujas , Estudios Prospectivos , Resultado del Tratamiento , Trastorno del Dedo en Gatillo/diagnóstico por imagen , Trastorno del Dedo en Gatillo/cirugía , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: Trends over time in the incidence of ulnar collateral ligament (UCL) surgeries in National Collegiate Athletic Association Division I baseball players are currently unknown. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the trends in UCL surgeries over 3 years in Division I baseball programs. We hypothesized that surgical injuries would be consistently high over the course of the study. STUDY DESIGN: Descriptive epidemiology study. METHODS: Athletic trainers from Division I baseball programs were invited to participate in an electronic survey over 3 seasons. A total of 155 baseball programs agreed to participate in 2017, 294 programs participated in 2018, and 296 programs participated in 2019. After each of the 3 collegiate baseball seasons, the athletic trainer from each program entered anonymous, detailed descriptive data and surgical information on injured players into a secured database. RESULTS: During the 3 years of this study, 100% of the enrolled programs successfully completed the survey (155/155 in year 1, 294/294 in year 2, and 296/296 in year 3). This registry of 745 completed surveys over 3 years represented 25,587 player-years from Division I collegiate baseball. The percentage of programs with at least 1 UCL surgery during this time was 57% in 2017, 51% in 2018, and 49% in 2019. The majority of these players were pitchers (84% overall from the 3 years). Seniors underwent a significantly lower percentage of the UCL surgeries (8% in 2017, 10% in 2018, and 13% in 2019) than did underclassmen. Surgeries were performed most often in-season and least often during the preseason. A slight majority of players undergoing surgery originated from warm-weather states, but the number of these players was never significantly higher than was the number of players from cold-weather states. Most surgeries performed each year were UCL reconstruction, but the percentage of UCL repair with ligament augmentation increased each year (10% UCL repairs in 2017, 20% in 2018, and 25% in 2019). CONCLUSION: UCL injuries requiring surgery were found to be a major source of morbidity in Division I collegiate baseball, supporting our hypothesis. This study can serve as a baseline for tracking long-term trends in UCL surgeries in collegiate baseball.
RESUMEN
Baseball coaches often focus on the landing position of a pitcher's front foot as a key aspect of mechanics. Furthermore, controversy persists regarding positioning the rear foot on the first base or third base end of the rubber. The purpose of this study was to determine the effect of rear and front foot placement on pitching biomechanics. Our hypotheses were that there would be significant kinematic and kinetic differences associated with foot placement. This was a retrospective review including 144 healthy right-handed adult baseball pitchers divided into groups based on their rear and front foot placements: first base open (1B-Open), first base closed (1B-Closed), third base open (3B-Open), and third base closed (3B-Closed). Two-way ANOVAs detected no statistically significant main effects for kinetic variables but several for kinematic variables. Open pitchers had less shoulder abduction at the time of ball release and greater maximum shoulder internal rotation velocity in comparison with closed pitchers. They also had less forearm pronation at the time of ball release and greater maximum elbow extension velocity. Additional statistically significant results were found; however, low effect sizes may lessen the clinical significance of many of the results.
RESUMEN
BACKGROUND: There is limited literature regarding outcomes after operative treatment of displaced medial epicondyle avulsion fractures in adolescent athletes. Most studies have had a relatively small sample size and have not assessed return to play of the overhead athlete. PURPOSE: To examine return to play and outcomes of youth overhead athletes who underwent open reduction and internal fixation (ORIF) with screw fixation. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Charts and radiographs were queried between January 2003 and June 2018 for young overhead athletes (age, <17 years) who underwent ORIF for displaced medial epicondyle fracture. Patients with open fracture or concomitant injury were excluded. Radiographs from postoperative follow-up visits were examined for radiographic union. Eligible patients were asked to provide responses to the American Shoulder and Elbow Surgeons Standardized Assessment Elbow questionnaire and Kerlan-Jobe Orthopaedic Clinic questionnaires as well as questions regarding return to play. RESULTS: Overall, 29 patients were included in the study; the mean age at surgery was 14.7 years (range, 12.9-16.5 years). There were 25 baseball players, 3 football quarterbacks, and 1 tennis player. Of the 23 patients with available images at least 3 months after surgery, 96% demonstrated radiographic union at last follow-up. Imaging for the 1 patient with nonunion was taken 3 months after ORIF, and it is unknown if he eventually had union. All patients (100%) were successfully contacted to complete questionnaires at a mean follow-up of 4.8 years (range, 1.0-13.5 years). The mean KJOC score was 93.0, and the mean scores for the American Shoulder and Elbow Surgeons Elbow questionnaire were 8.9, 35.6, and 9.8 for pain, function, and satisfaction, respectively. One overhead athlete did not return to play, while the other 28 returned at a mean 7 months after surgery. No patient underwent revision ORIF, 1 underwent hardware removal, and 1 underwent ulnar nerve transposition. No players underwent ulnar collateral ligament reconstruction after primary ORIF of the medial epicondyle. CONCLUSION: ORIF of displaced medial epicondyle fractures is a reliable and successful procedure in adolescent overhead athletes with high demands, with relatively low risk of major complications, reinjury, or reoperation.
RESUMEN
OBJECTIVES: To determine whether increasing pitching distance for adult baseball pitchers would affect their upper extremity kinetics, full-body kinematics, and pitched ball kinematics (ball velocity, duration of ball flight, vertical and horizontal break, strike percentage). DESIGN: Controlled laboratory study. METHODS: Twenty-six collegiate baseball pitchers threw sets of five full-effort fastballs from three different pitching distances (18.44m, 19.05m, 19.41m) in a randomized order. Ball velocity, horizontal and vertical break, duration of ball flight, and strike percentage were computed by a ball tracking system, while pitching kinetics and kinematics were calculated with a 12-camera optical motion capture system. Repeated measures analysis of variance was utilized to detect significant differences among the three different pitching distances (p<0.05). RESULTS: No significant differences in pitching kinetics and kinematics were observed among the varying pitching distances. Ball velocity and strike percentage were also not significantly different among the pitching distances, however, the duration of ball flight and horizontal and vertical break significantly increased with pitching distance. CONCLUSIONS: Increasing pitching distance may not alter upper extremity kinetics, full-body kinematics, ball velocity or strike percentage in adult pitchers. However, as pitching distance increases the duration of ball flight and amount of horizontal and vertical break also increase. Increased ball flight duration could be an advantage for the hitter while increased ball break could help the pitcher. In conclusion, it is unlikely that moving the mound backwards would significantly affect pitching biomechanics and injury risk; however, the effects on pitching and hitting performance are unknown.
Asunto(s)
Béisbol/fisiología , Extremidad Superior/fisiología , Fenómenos Biomecánicos , Voluntarios Sanos , Humanos , Cinética , Adulto JovenRESUMEN
BACKGROUND: There is a lack of evidence regarding the success of ulnar collateral ligament (UCL) revision reconstruction. Understanding outcomes after UCL revision reconstruction is important in clinical decision making for overhead athletes. PURPOSE: To evaluate return to play and patient-reported outcomes after UCL revision reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All patients who underwent UCL revision reconstruction, attributed to retear of the ligament or pain, between June 2004 and July 2016 at 2 surgical centers were identified. Charts were reviewed for age, sex, date of primary and revision reconstruction, sport played, level of play, graft type, and complications. Patients were contacted by telephone to determine time to return to play, current level of participation, Conway score, Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow Score, and satisfaction. RESULTS: Of the 65 consecutive baseball players who underwent revision UCL reconstruction, 40 (62%) were contacted at a minimum 22 months after surgery. Of these, 38 (95%) were pitchers and 2 (5%) were position players. Time to return to throwing was 6.2 ± 2.3 months (mean ± SD), and the KJOC score was 74.2 ± 20.7. Based on the Conway score, 50% (20/40) had an excellent result, indicating a return to the previous competition level for at least 1 year, and 30% (12/40) had a good result, indicating a return to a lower level for at least 1 year. For those who were able to return to competition, it took 12.7 ± 3.6 months. In pitchers, 47% (18/38) returned to their previous competition levels for at least 1 year, with a KJOC score of 73.7 ± 21.1. Pitchers were able to return to throwing at 6.3 ± 2.3 months and competition at 12.8 ± 3.7 months. CONCLUSION: Only half of baseball players undergoing UCL revision reconstruction were able to return to their previous levels of competition. Outcomes for revision reconstructions are not as promising as primary procedures. Baseball players should be cautioned that they may not return to their previous levels of play after a revision reconstruction.
Asunto(s)
Béisbol , Ligamento Colateral Cubital , Ligamentos Colaterales , Articulación del Codo , Reconstrucción del Ligamento Colateral Cubital , Ligamento Colateral Cubital/cirugía , Ligamentos Colaterales/cirugía , Codo , Articulación del Codo/cirugía , HumanosRESUMEN
In today's competitive health care recruitment environment, one of the most cost-effective and successful recruitment strategies is alumni or "boomerang" recruitment. A proven business model, alumni recruitment is just beginning to be used in a significant way in the health care arena. The cost to recruit alumni is much lower than for those in the general workforce and the alumni population is a known quantity. Alumni will assimilate much more easily into your corporate culture, will need less orientation and onboarding, and will be more productive.
Asunto(s)
Selección de Personal/métodos , Humanos , Internet , Apoyo Social , Estados UnidosRESUMEN
A combination of factors has diluted the recruitment experience and created a confluence of elements similar to a perfect storm. Recruitment has morphed from a high-touch experience to a high-tech process. Though we can't go back to those halcyon pre-Internet days, we do need to find a better approach than our current technology-based, fragmented recruitment process. The ideal recruitment scenario would be a marriage of high tech and high touch. We must drive the technology, not let the technology dictate our process.
Asunto(s)
Internet/organización & administración , Relaciones Interprofesionales , Solicitud de Empleo , Enfermeras Administradoras , Personal de Enfermería , Selección de Personal/organización & administración , Actitud del Personal de Salud , Humanos , Entrevistas como Asunto/métodos , Enfermeras Administradoras/organización & administración , Enfermeras Administradoras/psicología , Personal de Enfermería/psicología , Personal de Enfermería/provisión & distribuciónRESUMEN
OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase insert domain receptor (KDR), which is currently being evaluated in clinical studies. OSI-930 selectively inhibits Kit and KDR with similar potency in intact cells and also inhibits these targets in vivo following oral dosing. We have investigated the relationships between the potency observed in cell-based assays in vitro, the plasma exposure levels achieved following oral dosing, the time course of target inhibition in vivo, and antitumor activity of OSI-930 in tumor xenograft models. In the mutant Kit-expressing HMC-1 xenograft model, prolonged inhibition of Kit was achieved at oral doses between 10 and 50 mg/kg and this dose range was associated with antitumor activity. Similarly, prolonged inhibition of wild-type Kit in the NCI-H526 xenograft model was observed at oral doses of 100 to 200 mg/kg, which was the dose level associated with significant antitumor activity in this model as well as in the majority of other xenograft models tested. The data suggest that antitumor activity of OSI-930 in mouse xenograft models is observed at dose levels that maintain a significant level of inhibition of the molecular targets of OSI-930 for a prolonged period. Furthermore, pharmacokinetic evaluation of the plasma exposure levels of OSI-930 at these effective dose levels provides an estimate of the target plasma concentrations that may be required to achieve prolonged inhibition of Kit and KDR in humans and which would therefore be expected to yield a therapeutic benefit in future clinical evaluations of OSI-930.
Asunto(s)
Leucemia de Mastocitos/terapia , Proteínas Proto-Oncogénicas c-kit/fisiología , Quinolinas/farmacología , Tiofenos/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Administración Oral , Animales , Femenino , Humanos , Leucemia de Mastocitos/patología , Ratones , Ratones Desnudos , Quinolinas/administración & dosificación , Quinolinas/farmacocinética , Tiofenos/administración & dosificación , Tiofenos/farmacocinética , Trasplante Heterólogo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/fisiologíaRESUMEN
A consortium of international organizations convened a first-ever Global Health Care Workforce Conference to discuss the worldwide shortages of health care workers and the migration patterns of health care workers from developing nations to the first world. Over 300 participants from 47 countries, including one-third from developing countries, discussed a variety of critical issues ranging from global immigration, recruitment, economics, to partnerships. Results, recommendations, and actionable items generated from the conference, as well as ways to put these ideas into practice, will be critical for sustaining and improving world health and the plight and numbers of health care providers.
Asunto(s)
Personal Profesional Extranjero , Salud Global , Planificación en Salud , Enfermería , Administración de Personal , Economía de la Enfermería , Emigración e Inmigración , Personal Profesional Extranjero/provisión & distribución , Humanos , Cooperación Internacional , Recursos HumanosRESUMEN
In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes.
Asunto(s)
Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/inmunología , Rabia/prevención & control , Vacunación , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , Voluntarios Sanos , Humanos , Inyecciones Intradérmicas , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Vacunas Antirrábicas/efectos adversos , Vacunación/efectos adversos , Vacunación/métodos , Adulto JovenRESUMEN
OSI-7836 (4'-thio-beta-D-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell death. This hypothesis has been examined by measuring and comparing the incorporation of ara-C, OSI-7836, and gemcitabine (dFdC) into DNA of cultured cells and by investigating the role of deoxycytidine kinase in OSI-7836 toxicity. We report here additional studies in which the role of cell cycling on OSI-7836 toxicity was investigated and incorporation of OSI-7836 into DNA of xenograft tumors measured. The role of the cell cycle was examined by comparing the toxicity of OSI-7836 in A549 NSCLC cells that were either in log phase growth or had reached confluence. A novel validated LC-MS/MS assay was developed to quantify the concentrations of OSI-7836 in DNA from Calu-6 and H460 human tumor xenografts in mice. Results showed that apoptosis induced by OSI-7836 was markedly greater in cycling cells than in confluent non-cycling cells despite only a modest increase in intracellular OSI-7836 triphosphate concentration. The LC-MS/MS assay developed to measure OSI-7836 incorporation into DNA had an on-column detection limit of 0.25 fmol, a quantification limit of 0.5 fmol, and a sensitivity of approximately 0.1 pmol OSI-7836/micromol dThy. Concentrations of OSI-7836 in splenic DNA (0.4 pmol OSI-7836/micromol dThy) averaged fivefold less than the average concentration in Calu-6 and H460 xenograft DNA (3.0 pmol OSI-7836/micromol dThy) following a 400 mg/kg dose of OSI-7836. Concentrations of OSI-7836 in Calu-6 tumor DNA isolated 24 h following a dose of 400, 1000, or 1600 mg OSI-7836/kg were approximately 1.3, 1 and 1.3 pmol OSI-7836/micromol dThy, respectively. Concentrations of OSI-7836 in DNA from H460 and Calu-6 xenografts did not appear to increase during repeated administration of 400 mg OSI-7836/kg on days 1, 4, 7, and 10. The majority of OSI-7836 in DNA from Calu-6 and H460 tumors of mice dosed with 1600 mg/kg was located at internal nucleotide linkages, similar to dFdC and ara-C. In conclusion, cell cycling studies supported the hypothesis that OSI-7836 cytotoxicity is dependent upon DNA synthesis. A validated LC-MS/MS assay was developed that could quantify OSI-7836 in DNA from tissues. The assay was used to show that OSI-7836 was incorporated in internal linkages in tumor DNA in a manner that was dose-independent at the doses tested and did not appear to accumulate during repeated dosing. The results suggest that if DNA incorporation is a toxic event, the relationships between administered dose, DNA incorporation, and toxicity are complex.
Asunto(s)
Antineoplásicos/metabolismo , Arabinonucleósidos/metabolismo , ADN de Neoplasias/metabolismo , Animales , Ciclo Celular , Replicación del ADN , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Trasplante de Neoplasias , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
Many of the closing comments that respondents shared revisited areas of concern and optimism about the nursing profession and men's place within it. Emphasis was placed on the need to recruit more men and minorities into the profession, confront stereotypes, and improve the general awareness and knowledge of what the profession has to offer to all its members. Just as in the student survey, we were struck by how articulate and passionate respondents were about nursing. Countless respondents indicated that nursing was a 'calling'; that they especially enjoyed 'making a difference' and how unique nursing is for that reason. We also appreciated the humor and self-confidenc they demonstrated about the reality of being a minority in the profession, and their 'just do it' mindset.
Asunto(s)
Selección de Profesión , Satisfacción en el Trabajo , Enfermeros/provisión & distribución , Encuestas de Atención de la Salud , Humanos , Masculino , Estados UnidosRESUMEN
The tumor-suppressive activity of FOXP3 has been observed in tumor initiation, but the underlying mechanism still remains largely unknown. Here, we identified a FOXP3-microRNA-146 (miR-146)-NF-κB axis in vitro and in vivo in prostate cancer cells. We observed that FOXP3 dramatically induced the expression of miR-146a/b, which contributed to transcriptional inhibition of IRAK1 and TRAF6, in prostate cancer cell lines. Tissue-specific deletion of Foxp3 in mouse prostate caused a significant reduction of miR-146a and upregulation of NF-κB activation. In addition, prostatic intraepithelial neoplasia lesions were observed in miR-146a-mutant mice as well as in Foxp3-mutant mice. Notably, the NF-κB inhibitor bortezomib inhibited cell proliferation and induced apoptosis in prostate epithelial cells, attenuating prostatic intraepithelial neoplasia formation in Foxp3-mutant mice. Our data suggest that the FOXP3-miR-146-NF-κB axis has a functional role during tumor initiation in prostate cancer. Targeting the miR-146-NF-κB axis may provide a new therapeutic approach for prostate cancers with FOXP3 defects.
Asunto(s)
Ácidos Borónicos/uso terapéutico , Transformación Celular Neoplásica/genética , Factores de Transcripción Forkhead/fisiología , MicroARNs/fisiología , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Pirazinas/uso terapéutico , Animales , Bortezomib , Células Cultivadas , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Transgénicos , Lesiones Precancerosas/patología , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/patología , Transducción de Señal/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OSI-211 (liposomal lurtotecan), was evaluated using several different dose schedules (1mg/kg, d1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) in severe combined immunodeficient (SCID) mouse models of acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) with early treatment (ET, days 6-8) or late treatment (LT, days 15-19), examining early and advanced disease, respectively. Due to the aggressive nature of the Molt-4 model, the ET and LT were accelerated to day 3 or 4 and day 8 post-implant, respectively. For each model, 2 x 10(7) (KBM-3B) or 1 x 10(7) (Molt-4, HL-60 and CEM) leukemia cells were injected intravenously into the tail vein. Each control and test group consisted of eight animals. All three schedules (1mg/kg qd1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) increased the life span of OSI-211 treated animals in each model, with a tendency toward improved efficacy with the 6 mg/kg d1, 8 schedule. As a result, the activity of the 6 mg/kg d1, 8 schedule is detailed for each model. ET significantly (P<0.005) increased survival in the KBM-3B model with 86% long-term survivors (LTS). Using PRC analysis, human beta-globin gene sequences in one or several tissues were amplified in all but 3 LTS, suggesting minimal residual disease in 26 of the 29 LTS. LT also significantly (P<0.005) improved average life span in the KBM-3B model, with an average ILS=196+/-11% and one LTS. Treatment of HL-60 leukemia animals significantly (P<0.005) increased life span, with an ILS=213+/-9% and two LTS for ET, and with an ILS=219+/-4% and no LTS for LT. Treatment of Molt-4 animals, the most aggressive leukemia model tested, significantly (P<0.005) increased life span, with an average ILS=181+/-3% and no LTS for ET and an average ILS=172+/-1% with no LTS for LT. In the CEM model, ET resulted in a significantly (P<0.005) improved ILS=244+/-24% with one LTS. In comparison to OSI-211, treatment with DaunoXome, the liposomal formulation of daunorubicin, a drug with clinical efficacy in AML and ALL, had no effect on survival in the KBM-3B, nor Molt-4 A4 leukemia models when administered at its maximum or near maximum tolerated doses of 3mg/kg d1, 8. These data demonstrate that OSI-211 has potent antileukemia activity in preclinical SCID mouse AML and ALL leukemia models, supporting the clinical investigation of OSI-211 for hematological malignancies.