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1.
Health Aff (Millwood) ; 43(3): 318-326, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38437601

RESUMO

Nursing home ownership has become increasingly complicated, partly because of the growth of facilities owned by institutional investors such as private equity (PE) firms and real estate investment trusts (REITs). Although the ownership transparency and accountability of nursing homes have historically been poor, the Biden administration's nursing home reform plans released in 2022 included a series of data releases on ownership. However, our evaluation of the newly released data identified several gaps: One-third of PE and fewer than one-fifth of REIT investments identified in the proprietary Irving Levin Associates and S&P Capital IQ investment data were present in Centers for Medicare and Medicaid Services (CMS) publicly available ownership data. Similarly, we obtained different results when searching for the ten top common owners of nursing homes using CMS data and facility survey reports of chain ownership. Finally, ownership percentages were missing in the CMS data for 82.40 percent of owners in the top ten chains and 55.21 percent of owners across all US facilities. Although the new data represent an important step forward, we highlight additional steps to ensure that the data are timely, accurate, and responsive. Transparent ownership data are fundamental to understanding the adequacy of public payments to provide patient care, enable policy makers to make timely decisions, and evaluate nursing home quality.


Assuntos
Medicare , Propriedade , Idoso , Estados Unidos , Humanos , Centers for Medicare and Medicaid Services, U.S. , Casas de Saúde , Instituições de Cuidados Especializados de Enfermagem
2.
J Strength Cond Res ; 36(7): 1966-1971, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35510889

RESUMO

ABSTRACT: Stone, BL, Ashley, JD, Skinner, RM, Polanco, JP, Walters, MT, Schilling, BK, and Kellawan, JM. Effects of a short-term heat acclimation protocol in elite amateur boxers. J Strength Cond Res 36(7): 1966-1971, 2022-Boxing requires proficient technical and tactical skills coupled with high levels of physiological capacity. Although heat and humidity negatively affect acute exercise performance, short-term exercise training in hot and humid environments can lead to physiological adaptations that enhance exercise performance in both hot and thermoneutral conditions. In highly trained endurance athletes, exercise-induced acclimation can occur in as little as 5 days (known as short-term heat acclimation [STHA]). However, the impact of a 5-day heat acclimation (5-DayHA) in combat athletes, such as elite amateur boxers, is unknown. The aim of the present investigation was to determine whether a 5-DayHA improves aerobic performance in a thermoneutral environment and causes positive physiological adaptations in elite boxers. Seven elite amateur boxers underwent a 5-DayHA protocol, consisting of 60-minute exercise sessions in an environmental chamber at 32 °C and 70% relative humidity. Repeat sprint test (RST) evaluated aerobic performance in a thermoneutral environment 24 hours before and after the 5-DayHA. Presession and postsession hydration status (urine specific gravity) and body mass were assessed. After a 5-DayHA period, boxers significantly improved RST performance (13 ± 7 to 19 ± 7 sprints, d = 0.92, p = 0.03) but not pre-exercise hydration status (1.02 ± 0.01 to 1.01 ± 0.01, d = 0.82, p = 0.07). Therefore, these findings suggest 5-DayHA enhances aerobic performance in elite-level amateur boxers and may provide a viable training option for elite combat athletes.


Assuntos
Boxe , Temperatura Alta , Aclimatação/fisiologia , Atletas , Boxe/fisiologia , Exercício Físico/fisiologia , Humanos
3.
J Comp Eff Res ; 11(8): 563-574, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35593109

RESUMO

Aim: Among hospitalized patients, venous thromboembolism (VTE) is a preventable cause of morbidity and mortality. This study analyzed the effects of a large-scale adoption of a prompt response and education protocol to increase VTE prophylaxis adherence in the USA. Methods: A Markov model was developed that simulates outcomes and costs of delivering a VTE education bundle versus not, to hospitalized at-risk patients. Results: The education bundle could avert more than 134,000 VTEs, 552,000 hospital days and 19,000 deaths over 5 years. Patients could save 13 million hours in work absenteeism and travel time, valued at US$237 million. Total societal savings could amount to US$2.8 billion. In scenario analyses with assumed lower-effectiveness estimates, the bundle averts 16,000 VTEs, 67,000 hospital days and 2000 deaths. Conclusion: A nationwide rollout of an education bundle to reduce missed doses of prescribed prophylaxis could improve quality of care, resulting in a decline in VTEs and mortality.


In a previous study, an education bundle was designed to increase administration of medication to prevent blood clotting among hospitalized patients at risk of venous thromboembolism (VTE). The education bundle led to a decrease in patients missing those needed doses of medication. The current study estimates the economic impacts of a nationwide rollout of the education bundle for patients at risk of VTE. The results show that if the education bundle were rolled out nationally, it could result in 134,000 fewer VTEs, 552,000 fewer days spent in the hospital and 19,000 fewer deaths over 5 years. As a result of reduced medical care, less time off work, and informal caregiving needed, societal cost savings could be as much as US$2.8 billion.


Assuntos
Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Hospitalização , Humanos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle
4.
J Comp Eff Res ; 11(6): 399-409, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35187950

RESUMO

Aim: To estimate the economic impacts of increased use of specialty care infusion centers for treating adults experiencing vaso-occlusive crises. Methods: A Markov model is developed to estimate the impact of expanding use of specialty care infusion centers to treat vaso-occlusive crises compared to emergency department care. Results: Access to infusion centers for sickle cell disease could result in savings over US$1.9 billion in formal medical costs and over US$2 billion in societal costs, based on uptake assumptions over 10 years. Conclusion: Expansion of adult sickle cell disease centers across the nation could lead to considerably better economic outcomes in the form of reduced costs and hospital length of stay in addition to improved clinical outcomes as reported in the existing literature.


Specialty care centers for sickle cell disease crises offer improved care and patient experience over typical emergency department care. This paper is based on a recent study, which compared the treatment for sickle cell disease crises at specialty centers and emergency departments by estimating the potential economic impacts of expanded specialty care centers. We estimate the impacts of increased specialty care use on healthcare costs, caregiver time, patient time and employer absenteeism costs. When 35% of the USA adult population acquires access to a specialty sickle cell disease center, a total savings over US$1.9 billion can be obtained after 10 years.


Assuntos
Anemia Falciforme , Adulto , Anemia Falciforme/terapia , Serviço Hospitalar de Emergência , Humanos
5.
J Comp Eff Res ; 11(2): 67-77, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34747638

RESUMO

Aim: Analyze the impact of nationwide implementation of teledermatological care for psoriasis. Methods: Develop a Markov model that estimates the impact of telehealth technology for treatment of moderate-to-severe psoriasis on health and healthcare expenditures compared with in-person clinical care. Results: Lower medical costs by US$1.5 billion and total social costs of US$4.3 billion over 5 years. Patients save more than 67 million hours in work absenteeism and travel time, valued at US$598 million. Employers save US$1.2 billion over 5 years due to decreased employee absenteeism. Conclusion: National implementation of telehealth for psoriasis care has the potential to substantially reduce both formal healthcare costs and informal costs for families and patients, while maintaining equivalent clinical outcomes as traditional in-person care.


Lay abstract Recent innovations in telehealth (methods of accessing and managing healthcare using digital information and technologies, such as the computer or telephone) have allowed for convenient access to care for dermatology patients. A recent study found that psoriasis patients experienced similar quality of care outcomes when using telehealth services as they did when seeing a clinician in-person. This paper builds on previous work examining teledermatological care outcomes and aims to analyze the potential economic impacts of a nationwide implementation of telehealth for managing psoriasis. We model the impacts of healthcare utilization and costs, caregiver time loss, and work absenteeism costs between the telehealth and in-person care settings. These results produce cost savings to society of over US$4.3 billion over 5 years.


Assuntos
Efeitos Psicossociais da Doença , Dermatopatias , Doença Crônica , Análise Custo-Benefício , Custos de Cuidados de Saúde , Humanos , Dermatopatias/terapia
6.
Clin Neurol Neurosurg ; 200: 106371, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33307326

RESUMO

BACKGROUND AND PURPOSE: The Dawn and Extend Intra-Arterial (IA) acute stroke intervention trials have proven the benefit of thrombectomy in a select group of patients up to 24 h since their last known well time (LKWT) or time of symptom onset. Following the issuance of new treatment guidelines for large vessel occlusion strokes, we reviewed the paradigm shift effect on transfers for possible thrombectomy in a rural state. HYPOTHESIS: Extended time window for thrombectomy increases the need for better identification of potential transfers for thrombectomy in rural states with few hospitals capable of 24/7 interventional thrombectomy. METHODS: We analyzed all transfers to a comprehensive stroke center (CSC) from January to December 2018 which were specifically transferred for possible further intervention. This time period was selected in accordance with the change in American Heart Association (AHA) guidelines for extended time windows in mechanical thrombectomy (MT) care. RESULTS: A total of 132 patients were transferred for possible thrombectomy and advanced imaging. Thirty-four % patients underwent diagnostic angiogram with 33% patients having successful MT. Of the excluded patients 19% had large core infarcts by the time they arrived at hub hospital, 1.5% had hemorrhagic conversion, 32% had stroke without treatable occlusion not amenable for thrombectomy or cortical strokes on follow-up imaging, and 13.5% did not have stroke or LVO on follow-up imaging. CONCLUSION: Since the AHA's change in time window guidelines for mechanical thrombectomies, there has been an increased effort in identifying good candidates with computerized tomography angiography (CTA). To avoid undue burden on stroke systems of care, CTA identification of these patients at the spoke hospitals is key along with timely transport to appropriate thrombectomy capable sites. Given the rural nature of this state along with limited resources, selection of patients is a practical issue, especially for avoiding futile transfers, which might be true for large areas of the USA.


Assuntos
Isquemia Encefálica/cirurgia , Angiografia por Tomografia Computadorizada/tendências , Transferência de Pacientes/tendências , Acidente Vascular Cerebral/cirurgia , Trombectomia/tendências , Tempo para o Tratamento/tendências , Adulto , Idoso , Isquemia Encefálica/diagnóstico por imagem , Estudos de Coortes , Angiografia por Tomografia Computadorizada/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transferência de Pacientes/métodos , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Trombectomia/métodos , Triagem/métodos , Triagem/tendências
7.
J Vasc Interv Radiol ; 30(8): 1244-1250.e1, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31349978

RESUMO

PURPOSE: This randomized, placebo-controlled, double-blind, dose-escalation acute ischemic stroke trial was designed to demonstrate maximum tolerated dose, characterize adverse events (AEs), and explore clinical outcomes when intravenous dodecafluoropentane emulsion (DDFPe) was used as neuroprotection. METHODS: Acute ischemic stroke patients (n = 24) with National Institutes of Health Stroke Scale (NIHSS) score of 2-20 were randomized to either 3 doses of intravenous DDFPe or placebo, 1 every 90 minutes, starting within 12 hours of symptom onset. Doses were given without affecting standard stroke care. Each of the 3 dose cohorts included 8 patients, with 2 receiving placebo and 6 receiving DDFPe. Primary outcomes were serious adverse events (SAEs), AEs, NIHSS score, and modified Rankin Score (mRS). RESULTS: No dose-limiting toxicities were encountered, and no maximum tolerated dose was defined. One unrelated delayed death occurred in a DDFPe patient, and another occurred in the placebo group. Group SAEs and AEs were similar in incidence and severity. Early initiation of DDFPe treatment resulted in better NIHSS score response than late initiation (P = .03). Thirty- and 90-day mRS after high-dose therapy suggested clinical improvement (P = .01 and P = .03, respectively). However, the significance of differences in clinical outcomes was limited by small patient numbers and differences in stroke severity between cohorts. CONCLUSIONS: Intravenous DDFPe appears to be safe at all doses tested. Clinical improvements in NIHSS score and mRS were significant but compromised by small sample size.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fluorocarbonos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Acidente Vascular Cerebral/terapia , Administração Intravenosa , Arkansas , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Avaliação da Deficiência , Método Duplo-Cego , Esquema de Medicação , Feminino , Fluorocarbonos/efeitos adversos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
8.
Fed Pract ; 36(Suppl 2): S11-S13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30983856

RESUMO

Hepatitis C virus-associated porphyria cutanea tarda can result from viral-induced inhibition of uroporphyrinogen decarboxylase and the subsequent accumulation of uroporphyrins and associated metabolites in urine.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30868141

RESUMO

INTRODUCTION: Delays in recognizing stroke during pre-hospital emergency medical system (EMS) care may affect triage and transport time to an appropriate stroke ready hospital and may preclude patients from receiving time dependent treatment. All EMS transports in a large urban area in the stroke belt were evaluated for transport destinations, triage and transport time and stroke recognition following distribution ofan educational training video to local EMS services. HYPOTHESIS: Following video training, local paramedics will improve stroke recognition and shorten triage and transport time to appropriate stroke centers of care. METHODS: A training module (<10 min) containing a stroke triage scenario, instruction on the Cincinnati Prehospital Stroke Score (CPSS) and the Los Angeles Prehospital Stroke Score (LAPSS) and 'where to transport' stroke patients was distributed and viewed by 96 paramedics. Data was collected from February to October 2016. Stroke recognition was determined from one primary stroke center (PSC) hospital's confirmation of EMS delivered patients (Site A). Yearly stroke recognition percentages of 44% from Site A in 2014 were used as baseline. RESULTS: A total of 34,833 emergency 911 response transports were made with a total of 502 (1.4%) suspected strokes identified by paramedics. Median [IQR] triage and transport time for stroke transports was 33 [27-41] min. The PSC hospitals received a 5% increase in stroke transports and non-specific care facilities decreased by 7%. From 8,554 transports to site A (PSC) confirmed strokes totalled 107 transports with 139 suspected strokes by paramedics. Of these transports, 60 were correctly identified by paramedics (positive predictive value of 43%, sensitivity of 56%). By the second month following training, recognition percentages increased from baseline to 64%. At five months, percentages of correct stroke identification had dropped to 36%. CONCLUSION: Video based training improved stroke recognition by an additional 19%, but continual monthly or quarterly training is recommended for maintenance of increased stroke recognition.

11.
J Orthop Res ; 35(1): 183-192, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26990453

RESUMO

Current convex tethering techniques for treatment of scoliosis have centered on anterior convex staples or polypropylene tethers. We hypothesized that an allograft tendon tether inserted via the costo-transverse foramen would correct an established spinal deformity. In the pilot study, six 8-week-old pigs underwent allograft tendon tethering via the costo-transverse foreman or sham to test the strength of the transplanted tendon to retard spine growth. After 4 months, spinal deformity in three planes was induced in all animals with allograft tendons. In the treatment study, the allograft tendon tether was used to treat established scoliosis in 11 8-week-old pigs (spinal deformity > 50°). Once the deformity was observed (4 months) animals were assigned to either no treatment group or allograft tendon tether group and progression assessed by monthly radiographs. At final follow-up, coronal Cobb angle and maximum vertebral axial rotation of the treatment group was significantly smaller than the non-treatment group, whereas sagittal kyphosis of the treatment group was significantly larger than the non-treatment group. In sum, a significant correction was achieved using a unilateral allograft tendon spinal tether, suggesting that an allograft tendon tethering approach may represent a novel fusion-less procedure to correct idiopathic scoliosis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:183-192, 2017.


Assuntos
Escoliose/cirurgia , Tendões/transplante , Aloenxertos , Animais , Projetos Piloto , Suínos
12.
AAPS J ; 19(2): 520-526, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28028728

RESUMO

IV injection of dodecafluoropentane emulsion (DDFPe) increases oxygen transportation and reduces brain infarct volume in a rabbit stroke model. Tissue distribution of the parent perfluorocarbon dodecafluoropentane (DDFP) is unknown but is critical to understanding the mechanism by which DDFPe is effective in treating ischemia and for determining safe dosing. Previous studies showed a DDFP blood half-life of <2 min yet therapeutic effects lasted >90 min after injection. We describe DDFP distribution in brain, kidney, liver, spleen, and lung following nine dosing regimens in New Zealand White (NZW) rabbits. Single and multi-dose schedules were administered to NZW rabbits (n = 27). A single DDFPe dose (0.6 ml/kg) group was sacrificed 2 min after dosing and eight multi-dose groups (4 doses of 0.3 or 0.6 ml/kg and 15 doses of 0.1, 0.3, or 0.6) were sacrificed 90 min after final injections. Tissues were flash frozen and analyzed with headspace sampling/GC-MS. DDFP brain concentration increased with increasing dose in the 15 dose groups (4.70, 8.34, and 14.3 µg/g) and indicative of linear pharmacokinetics within this dose range. The DDFP lung concentration was not reflective of increasing dose or dose frequency. The total clearance of DDFP was consistent with previous reports showing 98% of DDFP is cleared within 2 h of administration.


Assuntos
Encéfalo/metabolismo , Fluorocarbonos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluorocarbonos/farmacocinética , Cromatografia Gasosa-Espectrometria de Massas/métodos , Injeções Intravenosas , Masculino , Fármacos Neuroprotetores/farmacocinética , Coelhos , Distribuição Tecidual
13.
Mol Neurobiol ; 54(6): 4764-4770, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27501802

RESUMO

Dodecafluoropentane emulsion (DDFPe), an advanced oxygen transport drug, given IV at 90-min intervals maintains viability in the penumbra during cerebral ischemia in the standard rabbit anterior stroke model (STND). This study investigated shortened dosage schedules of DDFPe in nonstandard posterior (NSTND) strokes following occlusions of the posterior cerebral arteries. DDFPe given at shortened schedules of 30 or 60-min injection intervals will reduce neurological deficits, percent stroke volume (%SV), and serum glutamate levels in NSTND ischemic strokes. New Zealand White rabbits (N = 26) were randomly placed into three groups: A (n = 9) controls given saline injections every 60 min, B (n = 9) 2 % DDFPe given IV every 30 min, and C (n = 8) DDFPe every 60 min. Injections began 1 h after embolization. Groups were subdivided into STND and NSTND based on angiographically verified embolization of the cerebral arteries. Neurological assessments and blood samples were done at 0.5-1-h intervals. Rabbits were euthanized at 7 h following embolization. Stained brain slices were measured for %SV. The 30 and 60-min subgroups did not differ and were combined as DDFPe-STND or DDFPe-NSTND groups. In the DDFPe-STND stroke group, the %SV, neurological assessment scores (NAS), and serum glutamate were decreased vs. STND controls (p = 0.0016, 0.008, and 0.016, respectively). In the DDFPe-NSTND stroke group, %SV, NAS, and serum glutamate did not differ statistically compared to NSTND controls (p = 0.82, 0.097, and 0.06, respectively). More frequent dosage schedules provided no additional improvement. In anterior strokes, DDFPe improves recovery but not in the more severe NSTND strokes.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Fluorocarbonos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Angiografia , Animais , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Feminino , Glutamatos/sangue , Masculino , Coelhos , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações
14.
World J Orthop ; 7(8): 467-74, 2016 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-27622146

RESUMO

AIM: To test antibiotic-loaded coating for efficacy in reducing bacterial biofilm and development of osteomyelitis in an orthopaedic model of implant infection. METHODS: Phosphatidylcholine coatings loaded with 25% vancomycin were applied to washed and sterilized titanium wires 20 mm in length. A 10 mm segment was removed from rabbit radius (total = 9; 5 coated, 4 uncoated), and the segment was injected with 1 × 10(6) colony forming units (CFUs) of Staphylococcus aureus (UAMS-1 strain). Titanium wires were inserted through the intramedullary canal of the removed segment and into the proximal radial segment and the segment was placed back into the defect. After 7 d, limbs were removed, X-rayed, swabbed for tissue contamination. Wires were removed and processed to determine attached CFUs. Tissue was swabbed and streaked on agar plates to determine bacteriological score. RESULTS: Antibiotic-loaded coatings resulted in significantly reduced biofilm formation (4.7 fold reduction in CFUs; P < 0.001) on titanium wires and reduced bacteriological score in surrounding tissue (4.0 ± 0 for uncoated, 1.25 ± 0.5 for coated; P = 0.01). Swelling and pus formation was evident in uncoated controls at the 7 d time point both visually and radiographically, but not in antibiotic-loaded coatings. CONCLUSION: Active antibiotic was released from coated implants and significantly reduced signs of osteomyelitic symptoms. Implant coatings were well tolerated in bone. Further studies with additional control groups and longer time periods are warranted. Antibiotic-loaded phosphatidylcholine coatings applied at the point of care could prevent implant-associated infection in orthopaedic defects.

16.
J Orthop Res ; 34(10): 1716-1724, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26867804

RESUMO

The majority of Osteosarcoma (OS) patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. These protocols include distraction osteogenesis (DO), which is characterized by direct new bone formation. Cisplatin (CDP) is extensively used for OS chemotherapy and recent studies, using a mouse DO model, have demonstrated that CDP has profound negative effects on bone repair. Recent oncological therapeutic strategies are based on the use of standard cytotoxic drugs plus an assortment of biologic agents. Here we demonstrate that the previously reported CDP-associated inhibition of bone repair can be modulated by the administration of a small molecule p53 inducer (nutlin-3). The effects of nutlin-3 on CDP osteotoxicity were studied using both pre- and post-operative treatment models. In both cases the addition of nutlin-3, bracketing CDP exposure, demonstrated robust and significant bone sparing activity (p < 0.01-0.001). In addition the combination of nutlin-3 and CDP induced equivalent OS tumor killing in a xenograft model. Collectively, these results demonstrate that the induction of p53 peri-operatively protects bone healing from the toxic effects of CDP, while maintaining OS toxicity. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1716-1724, 2016.


Assuntos
Antineoplásicos/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Cisplatino/uso terapêutico , Imidazóis/uso terapêutico , Osteossarcoma/tratamento farmacológico , Piperazinas/uso terapêutico , Animais , Feminino , Humanos , Imidazóis/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Osteogênese por Distração , Osteossarcoma/cirurgia , Piperazinas/farmacologia , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Infect Immun ; 82(10): 4292-306, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25069985

RESUMO

The Lyme disease spirochete, Borrelia burgdorferi, occupies both a tick vector and mammalian host in nature. Considering the unique enzootic life cycle of B. burgdorferi, it is not surprising that a large proportion of its genome is composed of hypothetical proteins not found in other bacterial pathogens. bb0238 encodes a conserved hypothetical protein of unknown function that is predicted to contain a tetratricopeptide repeat (TPR) domain, a structural motif responsible for mediating protein-protein interactions. To evaluate the role of bb0238 during mammalian infection, a bb0238-deficient mutant was constructed. The bb0238 mutant was attenuated in mice infected via needle inoculation, and complementation of bb0238 expression restored infectivity to wild-type levels. bb0238 expression does not change in response to varying culture conditions, and thus, it appears to be constitutively expressed under in vitro conditions. bb0238 is expressed in murine tissues during infection, though there was no significant change in expression levels among different tissue types. Localization studies indicate that BB0238 is associated with the inner membrane of the spirochete and is therefore unlikely to promote interaction with host ligands during infection. B. burgdorferi clones containing point mutations in conserved residues of the putative TPR motif of BB0238 demonstrated attenuation in mice that was comparable to that in the bb0238 deletion mutant, suggesting that BB0238 may contain a functional TPR domain.


Assuntos
Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/patogenicidade , Doença de Lyme/microbiologia , Fatores de Virulência/metabolismo , Animais , Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Análise Mutacional de DNA , Modelos Animais de Doenças , Feminino , Deleção de Genes , Teste de Complementação Genética , Camundongos , Camundongos Endogâmicos C3H , Mutação Puntual , Ratos Sprague-Dawley , Fatores de Virulência/genética
20.
J Biomater Appl ; 29(4): 514-23, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24854984

RESUMO

We demonstrate that coating calcium sulfate with deacetylated chitosan enhances the elution profile of daptomycin by prolonging the period during which high concentrations of antibiotic are released. Coatings reduced initial bolus release of daptomycin by a factor of 10 to approximately 1000 µg/ml, and levels remained above 100 µg/ml for up to 10 days. Chitosan-coated and uncoated calcium sulfate implants with and without 15% daptomycin were evaluated in an experimental model of staphylococcal osteomyelitis through bacteriology scores, radiology, histopathology, and Gram staining. Significant reduction in bacteriology scores was observed for implants containing daptomycin and coated with chitosan compared with all the other groups. We confirm that the use of chitosan-coated calcium sulfate beads for local antibiotic delivery can be correlated with an improved therapeutic outcome following surgical debridement in the treatment of chronic osteomyelitis.


Assuntos
Antibacterianos/administração & dosagem , Quitosana/química , Osteomielite/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Sulfato de Cálcio/química , Doença Crônica , Materiais Revestidos Biocompatíveis/química , Daptomicina/administração & dosagem , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Masculino , Teste de Materiais , Osteomielite/microbiologia , Polimetil Metacrilato/química , Infecções Relacionadas à Prótese/microbiologia , Coelhos , Infecções Estafilocócicas/microbiologia
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