RESUMO
BACKGROUND: US nursing homes (NHs) have struggled to overcome a historic pandemic that laid bare limitations in the number and clinical expertise of NH staff. PROBLEM: For nurse staffing, current regulations require only one registered nurse (RN) on duty 8 consecutive hours per day, 7 days per week, and one RN on call when a licensed practical/vocational nurse is on duty. There is no requirement for a degreed or licensed social worker, and advanced practice registered nurses (APRNs) in NHs cannot bill for services. APPROACH: It is time to establish regulation that mandates a 24-hour, 7-day-a-week, on-site RN presence at a minimum requirement of 1 hour per resident-day that is adjusted upward for greater resident acuity and complexity. Skilled social workers are needed to improve the quality of care, and barriers for APRN billing for services in NHs need to be removed. CONCLUSIONS: Coupling enhanced RN and social work requirements with access to APRNs can support staff and residents in NHs.
Assuntos
Prática Avançada de Enfermagem , Enfermeiras e Enfermeiros , Humanos , Missouri , Casas de Saúde , Admissão e Escalonamento de Pessoal , Serviço SocialRESUMO
Aging in place is a preferred and cost-effective living option for older adults. Research indicates that technology can assist with this goal. Information on consumer preferences will help in technology development to assist older adults to age in place. The study aim was to explore the perceptions and preferences of older adults and their family members about a fall risk assessment system. Using a qualitative approach, this study examined the perceptions, attitudes, and preferences of 13 older adults and five family members about their experience living with the fall risk assessment system during five points in time. Themes emerged in relation to preferences and expectations about the technology and how it fits into daily routines. We were able to capture changes that occurred over time for older adult participants. Results indicated that there was acceptance of the technology as participants adapted to it. Two themes were present across the five points in time-safety and usefulness. Five stages of acceptance emerged from the data from preinstallation to 2 years postinstallation. Identified themes, stages of acceptance, and design and development considerations are discussed.
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Acidentes por Quedas/prevenção & controle , Família/psicologia , Invenções/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Feminino , Humanos , Vida Independente , Masculino , Pesquisa Qualitativa , Medição de RiscoRESUMO
BACKGROUND: Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hind limb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. MATERIALS AND METHODS: VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young, healthy rats (Wistar Kyoto, WKY; lean Zucker rats, LZR) and rats with cardiovascular risk factors (spontaneously hypertensive [SHR]; obese Zucker rats [OZR]) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. RESULTS: VO measurement in WKY demonstrated the utility of this method to assess hind limb perfusion at rest and during calf muscle contraction. Although application to diseased models (OZR and SHR) demonstrated normal resting perfusion compared with contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. CONCLUSIONS: The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in preclinical rodent models.
Assuntos
Veia Femoral/fisiologia , Membro Posterior/irrigação sanguínea , Doença Arterial Periférica/diagnóstico por imagem , Animais , Estudos de Viabilidade , Artéria Femoral/cirurgia , Veia Femoral/diagnóstico por imagem , Membro Posterior/diagnóstico por imagem , Hiperemia , Ligadura , Losartan , Masculino , Contração Muscular , Ramipril , Ratos Endogâmicos WKY , UltrassonografiaRESUMO
The present study was undertaken to establish the role of NADPH oxidase (Nox) in impaired vascular compensation to arterial occlusion that occurs in the presence of risk factors associated with oxidative stress. Diet-induced obese (DIO) mice characterized by multiple comorbidities including diabetes and hyperlipidemia were used as a preclinical model. Arterial occlusion was induced by distal femoral artery ligation in lean and DIO mice. Proximal collateral arteries were identified as the site of major (â¼70%) vascular resistance to calf perfusion by distal arterial pressures, which decreased from â¼80 to â¼30 mmHg with ligation in both lean and DIO mice. Two weeks after ligation, significant vascular compensation occurred in lean but not DIO mice as evidenced by increased perfusion (147 ± 48% vs. 49 ± 29%) and collateral diameter (151 ± 30% vs. 44 ± 17%). Vascular mRNA expression of p22(phox), Nox2, Nox4, and p47(phox) were all increased in DIO mice. Treatment of DIO mice with either apocynin or Nox2ds-tat or with whole body ablation of either Nox2 or p47(phox) ameliorated the impairment in both collateral growth and hindlimb perfusion. Multiparametric flow cytometry analysis demonstrated elevated levels of circulating monocytes in DIO mice without impaired mobilization and demargination after femoral artery ligation. These results establish collateral resistance as the major limitation to calf perfusion in this preclinical model, demonstrate than monocyte mobilization and demarginatin is not suppressed, implicate Nox2-p47(phox) interactions in the impairment of vascular compensation to arterial occlusion in DIO mice, and suggest that selective Nox component suppression/inhibition may be effective as either primary or adjuvant therapy for claudicants.
Assuntos
Adaptação Fisiológica , Circulação Colateral , Artéria Femoral/cirurgia , Glicoproteínas de Membrana/genética , NADPH Oxidases/genética , Neovascularização Fisiológica , Obesidade/metabolismo , RNA Mensageiro/metabolismo , Acetofenonas/farmacologia , Animais , Antioxidantes/farmacologia , Grupo dos Citocromos b/genética , Grupo dos Citocromos b/metabolismo , Membro Posterior/irrigação sanguínea , Ligadura , Glicoproteínas de Membrana/metabolismo , Camundongos , NADPH Oxidase 2 , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Estresse OxidativoRESUMO
Environmentally embedded (nonwearable) sensor technology is in continuous use in elder housing to monitor a new set of 'vital signs' that continuously measure the functional status of older adults, detect potential changes in health or functional status, and alert healthcare providers for early recognition and treatment of those changes. Older adult participants' respiration, pulse, and restlessness are monitored as they sleep. Gait speed, stride length, and stride time are calculated daily, and automatically assess for increasing fall risk. Activity levels are summarized and graphically displayed for easy interpretation. Falls are detected when they occur and alerts are sent immediately to healthcare providers, so time to rescue may be reduced. Automated health alerts are sent to healthcare staff, based on continuously running algorithms applied to the sensor data, days and weeks before typical signs or symptoms are detected by the person, family members, or healthcare providers. Discovering these new functional status 'vital signs', developing automated methods for interpreting them, and alerting others when changes occur have the potential to transform chronic illness management and facilitate aging in place through the end of life. Key findings of research in progress at the University of Missouri are discussed in this viewpoint article, as well as obstacles to widespread adoption.
Assuntos
Envelhecimento/fisiologia , Nível de Saúde , Monitorização Fisiológica/métodos , Acidentes por Quedas/prevenção & controle , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Tecnologia Biomédica/instrumentação , Tecnologia Biomédica/métodos , Tecnologia Biomédica/tendências , Feminino , Geriatria , Humanos , Masculino , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/tendências , Sinais VitaisAssuntos
Infecções por Coronavirus/prevenção & controle , Relações Interinstitucionais , Casas de Saúde/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Missouri/epidemiologia , Pneumonia Viral/epidemiologiaRESUMO
BACKGROUND: When planning the Aging in Place Initiative at TigerPlace, it was envisioned that advances in technology research had the potential to enable early intervention in health changes that could assist in proactive management of health for older adults and potentially reduce costs. PURPOSE: The purpose of this study was to compare length of stay (LOS) of residents living with environmentally embedded sensor systems since the development and implementation of automated health alerts at TigerPlace to LOS of those who are not living with sensor systems. Estimate potential savings of living with sensor systems. METHODS: LOS for residents living with and without sensors was measured over a span of 4.8 years since the implementation of sensor-generated health alerts. The group living with sensors (n = 52) had an average LOS of 1,557 days (4.3 years); the comparison group without sensors (n = 81) was 936 days (2.6 years); p = .0006. Groups were comparable based on admission age, gender, number of chronic illnesses, SF12 physical health, SF12 mental health, Geriatric Depression Scale (GDS), activities of daily living, independent activities of daily living, and mini-mental status examination scores. Both groups, all residents living at TigerPlace since the implementation of health alerts, receive registered nurse (RN) care coordination as the standard of care. DISCUSSION: Results indicate that residents living with sensors were able to reside at TigerPlace 1.7 years longer than residents living without sensors, suggesting that proactive use of health alerts facilitates successful aging in place. Health alerts, generated by automated algorithms interpreting environmentally embedded sensor data, may enable care coordinators to assess and intervene on health status changes earlier than is possible in the absence of sensor-generated alerts. Comparison of LOS without sensors TigerPlace (2.6 years) with the national median in residential senior housing (1.8 years) may be attributable to the RN care coordination model at TigerPlace. Cost estimates comparing cost of living at TigerPlace with the sensor technology vs. nursing home reveal potential saving of about $30,000 per person. Potential cost savings to Medicaid funded nursing home (assuming the technology and care coordination were reimbursed) are estimated to be about $87,000 per person. CONCLUSIONS: Early alerts for potential health problems appear to enhance the current RN care coordination care delivery model at TigerPlace, increasing LOS for those living with sensors to nearly twice that of those who did not. Sensor technology with care coordination has cost saving potential for consumers and Medicaid.
Assuntos
Instituição de Longa Permanência para Idosos/economia , Vida Independente , Tempo de Internação/estatística & dados numéricos , Monitorização Ambulatorial/métodos , Telenfermagem/economia , Telenfermagem/instrumentação , Atividades Cotidianas , Idoso de 80 Anos ou mais , Redução de Custos , Feminino , Enfermagem Geriátrica , Humanos , Masculino , Missouri , Estudos Retrospectivos , Instituições de Cuidados Especializados de Enfermagem/economiaRESUMO
The role of NADPH oxidase (Nox) in both the promotion and impairment of compensatory collateral growth remains controversial because the specific Nox and reactive oxygen species involved are unclear. The aim of this study was to identify the primary Nox and reactive oxygen species associated with early stage compensatory collateral growth in young, healthy animals. Ligation of the feed arteries that form primary collateral pathways in rat mesentery and mouse hindlimb was used to assess the role of Nox during collateral growth. Changes in mesenteric collateral artery Nox mRNA expression determined by real-time PCR at 1, 3, and 7 days relative to same-animal control arteries suggested a role for Nox subunits Nox2 and p47(phox). Administration of apocynin or Nox2ds-tat suppressed collateral growth in both rat and mouse models, suggesting the Nox2/p47(phox) interaction was involved. Functional significance of p47(phox) expression was assessed by evaluation of collateral growth in rats administered p47(phox) small interfering RNA and in p47(phox-/-) mice. Diameter measurements of collateral mesenteric and gracilis arteries at 7 and 14 days, respectively, indicated no significant collateral growth compared with control rats or C57BL/6 mice. Chronic polyethylene glycol-conjugated catalase administration significantly suppressed collateral development in rats and mice, implying a requirement for H2O2. Taken together, these results suggest that Nox2, modulated at least in part by p47(phox), mediates early stage compensatory collateral development via a process dependent upon peroxide generation. These results have important implications for the use of antioxidants and the development of therapies for peripheral arterial disease.
Assuntos
Artérias/crescimento & desenvolvimento , Circulação Colateral/fisiologia , Glicoproteínas de Membrana/fisiologia , NADPH Oxidases/fisiologia , Neovascularização Fisiológica/fisiologia , Acetofenonas/farmacologia , Animais , Antioxidantes/farmacologia , Artérias/fisiologia , Circulação Colateral/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Masculino , Glicoproteínas de Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , NADPH Oxidase 2 , NADPH Oxidases/deficiência , NADPH Oxidases/efeitos dos fármacos , NADPH Oxidases/genética , Neovascularização Fisiológica/efeitos dos fármacos , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismoRESUMO
Older adults prefer to age in place, remaining in their home as their health care needs intensify. In a state evaluation of aging in place (AIP), the University of Missouri Sinclair School of Nursing and Americare System Inc, Sikeston, MO, developed an elder housing facility to be an ideal housing environment for older adults to test the AIP care delivery model. An evaluation of the first 4 years (2005-2008) of the AIP program at TigerPlace (n = 66) revealed that the program was effective in restoring health and maintaining independence while being cost-effective. Similar results evaluating the subsequent 4 years (2009-2012) of the program (N = 128) revealed positive health outcomes (fall risk, gait velocity, Functional Ambulation Profile, handgrips, Short-Form 12 Physical Health, Short-Form 12 Mental Health, and Geriatric Depression Scale); slightly negative activities of daily living, independent activities of daily living, and Mini-Mental State Examination; and positive cost-effectiveness results. Combined care and housing costs for any resident who was receiving additional care services and qualified for nursing home care (n = 44) was about $20,000 less per year per person than nursing home care. Importantly, residents continued to live in private apartments and were encouraged to be as independent as possible through the end of life.
Assuntos
Enfermagem Geriátrica/organização & administração , Instituição de Longa Permanência para Idosos/organização & administração , Vida Independente , Assistência de Longa Duração/organização & administração , Papel do Profissional de Enfermagem , Enfermeiras e Enfermeiros/organização & administração , Casas de Saúde/organização & administração , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Missouri , Avaliação de Programas e Projetos de SaúdeRESUMO
Previous investigations indicate that diminished functional expression of voltage-dependent K(+) (KV) channels impairs control of coronary blood flow in obesity/metabolic syndrome. The goal of this investigation was to test the hypothesis that KV channels are electromechanically coupled to CaV1.2 channels and that coronary microvascular dysfunction in obesity is related to subsequent increases in CaV1.2 channel activity. Initial studies revealed that inhibition of KV channels with 4-aminopyridine (4AP, 0.3 mM) increased intracellular [Ca(2+)], contracted isolated coronary arterioles and decreased coronary reactive hyperemia. These effects were reversed by blockade of CaV1.2 channels. Further studies in chronically instrumented Ossabaw swine showed that inhibition of CaV1.2 channels with nifedipine (10 µg/kg, iv) had no effect on coronary blood flow at rest or during exercise in lean swine. However, inhibition of CaV1.2 channels significantly increased coronary blood flow, conductance, and the balance between coronary flow and metabolism in obese swine (P < 0.05). These changes were associated with a ~50 % increase in inward CaV1.2 current and elevations in expression of the pore-forming subunit (α1c) of CaV1.2 channels in coronary smooth muscle cells from obese swine. Taken together, these findings indicate that electromechanical coupling between KV and CaV1.2 channels is involved in the regulation of coronary vasomotor tone and that increases in CaV1.2 channel activity contribute to coronary microvascular dysfunction in the setting of obesity.
Assuntos
Canais de Cálcio Tipo L/metabolismo , Circulação Coronária/fisiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Canais de Potássio/metabolismo , Animais , Hemodinâmica/fisiologia , SuínosRESUMO
Passive sensor networks were deployed in independent living apartments to monitor older adults in their home environments to detect signs of impending illness and alert clinicians so they can intervene and prevent or delay significant changes in health or functional status. A retrospective qualitative deductive content analysis was undertaken to refine health alerts to improve clinical relevance to clinicians as they use alerts in their normal workflow of routine care delivery to older adults. Clinicians completed written free-text boxes to describe actions taken (or not) as a result of each alert; they also rated the clinical significance (relevance) of each health alert on a scale of 1 to 5. Two samples of the clinician's written responses to the health alerts were analyzed after alert algorithms had been adjusted based on results of a pilot study using health alerts to enhance clinical decision-making. In the first sample, a total of 663 comments were generated by seven clinicians in response to 385 unique alerts; there are more comments than alerts because more than one clinician rated the same alert. The second sample had a total of 142 comments produced by three clinicians in response to 88 distinct alerts. The overall clinical relevance of the alerts, as judged by the content of the qualitative comments by clinicians for each alert, improved from 33.3% of the alerts in the first sample classified as clinically relevant to 43.2% in the second. The goal is to produce clinically relevant alerts that clinicians find useful in daily practice. The evaluation methods used are described to assist others as they consider building and iteratively refining health alerts to enhance clinical decision making.
Assuntos
Moradias Assistidas , Diagnóstico Precoce , Idoso , Nível de Saúde , HumanosRESUMO
Falls are a major problem in older adults. A continuous, unobtrusive, environmentally mounted (i.e., embedded into the environment and not worn by the individual), in-home monitoring system that automatically detects when falls have occurred or when the risk of falling is increasing could alert health care providers and family members to intervene to improve physical function or manage illnesses that may precipitate falls. Researchers at the University of Missouri Center for Eldercare and Rehabilitation Technology are testing such sensor systems for fall risk assessment (FRA) and detection in older adults' apartments in a senior living community. Initial results comparing ground truth (validated measures) of FRA data and GAITRite System parameters with data captured from Microsoft(®) Kinect and pulse-Doppler radar are reported.
Assuntos
Acidentes por Quedas , Medição de Risco , Medidas de Segurança , Idoso , Humanos , SegurançaRESUMO
Survivors of acute radiation exposure suffer from the delayed effects of acute radiation exposure (DEARE), a chronic condition affecting multiple organs, including lung, kidney, heart, gastrointestinal tract, eyes, and brain, and often causing cancer. While effective medical countermeasures (MCM) for the hematopoietic-acute radiation syndrome (H-ARS) have been identified and approved by the FDA, development of MCM for DEARE has not yet been successful. We previously documented residual bone marrow damage (RBMD) and progressive renal and cardiovascular DEARE in murine survivors of H-ARS, and significant survival efficacy of 16,16-dimethyl prostaglandin E2 (dmPGE2) given as a radioprotectant or radiomitigator for H-ARS. We now describe additional DEARE (physiological and neural function, progressive fur graying, ocular inflammation, and malignancy) developing after sub-threshold doses in our H-ARS model, and detailed analysis of the effects of dmPGE2 administered before (PGE-pre) or after (PGE-post) lethal total-body irradiation (TBI) on these DEARE. Administration of PGE-pre normalized the twofold reduction of white blood cells (WBC) and lymphocytes seen in vehicle-treated survivors (Veh), and increased the number of bone marrow (BM) cells, splenocytes, thymocytes, and phenotypically defined hematopoietic progenitor cells (HPC) and hematopoietic stem cells (HSC) to levels equivalent to those in non-irradiated age-matched controls. PGE-pre significantly protected HPC colony formation ex vivo by >twofold, long term-HSC in vivo engraftment potential up to ninefold, and significantly blunted TBI-induced myeloid skewing. Secondary transplantation documented continued production of LT-HSC with normal lineage differentiation. PGE-pre reduced development of DEARE cardiovascular pathologies and renal damage; prevented coronary artery rarefication, blunted progressive loss of coronary artery endothelia, reduced inflammation and coronary early senescence, and blunted radiation-induced increase in blood urea nitrogen (BUN). Ocular monocytes were significantly lower in PGE-pre mice, as was TBI-induced fur graying. Increased body weight and decreased frailty in male mice, and reduced incidence of thymic lymphoma were documented in PGE-pre mice. In assays measuring behavioral and cognitive functions, PGE-pre reduced anxiety in females, significantly blunted shock flinch response, and increased exploratory behavior in males. No effect of TBI was observed on memory in any group. PGE-post, despite significantly increasing 30-day survival in H-ARS and WBC and hematopoietic recovery, was not effective in reducing TBI-induced RBMD or any other DEARE. In summary, dmPGE2 administered as an H-ARS MCM before lethal TBI significantly increased 30-day survival and ameliorated RBMD and multi-organ and cognitive/behavioral DEARE to at least 12 months after TBI, whereas given after TBI, dmPGE2 enhances survival from H-ARS but has little impact on RBMD or other DEARE.
Assuntos
Síndrome Aguda da Radiação , Transplante de Células-Tronco Hematopoéticas , Feminino , Masculino , Animais , Camundongos , Dinoprostona/farmacologia , Síndrome Aguda da Radiação/tratamento farmacológico , Síndrome Aguda da Radiação/prevenção & controle , Síndrome Aguda da Radiação/etiologia , Medula Óssea/efeitos da radiação , Modelos Animais de Doenças , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Inflamação/patologia , Irradiação Corporal Total/efeitos adversos , Camundongos Endogâmicos C57BLRESUMO
Our team has developed a technological innovation that detects changes in health status that indicate impending acute illness or exacerbation of chronic illness before usual assessment methods or self-reports of illness. We successfully used this information in a 1-year prospective study to alert health care providers so they could readily assess the situation and initiate early treatment to improve functional independence. Intervention participants showed significant improvements (as compared with the control group) for the Short Physical Performance Battery gait speed score at Quarter 3 (p = 0.03), hand grip-left at Quarter 2 (p = 0.02), hand grip-right at Quarter 4 (p = 0.05), and the GAITRite functional ambulation profile score at Quarter 2 (p = 0.05). Technological methods such as these could be widely adopted in older adult housing, long-term care settings, and in private homes where older adults wish to remain independent for as long as possible.
Assuntos
Automação , Diagnóstico Precoce , Idoso , Humanos , Internet , Estudos Prospectivos , Estudos Retrospectivos , Interface Usuário-ComputadorRESUMO
A state-sponsored evaluation of aging in place (AIP) as an alternative to assisted living and nursing home has been underway in Missouri. Cost, physical, and mental health assessment data reveal the cost-effectiveness and positive health measures of AIP. Findings of the first four years of the AIP evaluation of two long-term care settings in Missouri with registered nurse care coordination are compared with national data for traditional long-term care. The combined care and housing cost for any resident who received care services beyond base services of AIP and who qualified for nursing home care has never approached or exceeded the cost of nursing home care at either location. Both mental health and physical health measures indicate the health restoration and independence effectiveness of the AIP model for long-term care.
Assuntos
Serviços de Assistência Domiciliar/organização & administração , Instituição de Longa Permanência para Idosos/organização & administração , Vida Independente , Casas de Saúde/organização & administração , Idoso , Idoso de 80 Anos ou mais , Comportamento do Consumidor , Feminino , Pesquisa sobre Serviços de Saúde , Nível de Saúde , Serviços de Assistência Domiciliar/economia , Instituição de Longa Permanência para Idosos/economia , Humanos , Tempo de Internação , Masculino , Modelos de Enfermagem , Casas de Saúde/economiaRESUMO
Medical countermeasures (MCMs) for hematopoietic acute radiation syndrome (H-ARS) should be evaluated in well-characterized animal models, with consideration of at-risk populations such as pediatrics. We have developed pediatric mouse models of H-ARS and delayed effects of acute radiation exposure (DEARE) for efficacy testing of MCMs against radiation. Male and female C57BL/6J mice aged 3, 4, 5, 6, 7 and 8 weeks old (±1 day) were characterized for baseline hematopoietic and gastrointestinal parameters, radiation response, efficacy of a known MCM, and DEARE at six and 12 months after total-body irradiation (TBI). Weanlings (age 3 weeks) were the most radiosensitive age group with an estimated LD50/30 of 712 cGy, while mice aged 4 to 8 weeks were more radioresistant with an estimated LD50/30 of 767-787 cGy. Female weanlings were more radiosensitive than males at 3 and 4 weeks old but became significantly more radioresistant after the pubertal age of 5 weeks. The most dramatic increase in body weight, RBC counts and intestinal circumference length occurred from 3 to 5 weeks of age. The established radiomitigator Neulasta® (pegfilgrastim) significantly increased 30-day survival in all age groups, validating these models for MCM efficacy testing. Analyses of DEARE among pediatric survivors revealed depressed weight gain in males six months post-TBI, and increased blood urea nitrogen at 12 months post-TBI which was more severe in females. Hematopoietic DEARE at six months post-TBI appeared to be less severe in survivors from the 3- and 4-week-old groups but was equally severe in all age groups by 12 months of age. Similar to our other acute radiation mouse models, there was no appreciable effect of Neulasta used as an H-ARS MCM on the severity of DEARE. In summary, these data characterize a pediatric mouse model useful for assessing the efficacy of MCMs against ARS and DEARE in children.
Assuntos
Síndrome Aguda da Radiação/tratamento farmacológico , Filgrastim/farmacologia , Sistema Hematopoético/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Síndrome Aguda da Radiação/etiologia , Síndrome Aguda da Radiação/fisiopatologia , Animais , Modelos Animais de Doenças , Sistema Hematopoético/fisiopatologia , Sistema Hematopoético/efeitos da radiação , Humanos , Camundongos , Pediatria , Tolerância a Radiação/efeitos da radiação , Irradiação Corporal Total/efeitos adversosRESUMO
Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.
Assuntos
Arteriopatias Oclusivas/fisiopatologia , Circulação Colateral/fisiologia , Doenças Vasculares Periféricas/fisiopatologia , Animais , Arteriopatias Oclusivas/patologia , Modelos Animais de Doenças , Extremidades/irrigação sanguínea , Hemodinâmica , Humanos , Ligadura , Camundongos , Doenças Vasculares Periféricas/patologia , Ratos , Suínos , Porco Miniatura , Vasodilatação/fisiologiaRESUMO
Aging is a major risk factor for the development of cardiovascular diseases, including arterial occlusive disease. Oxidant stress increases with age, and may be a significant factor contributing to vascular dysfunction and disease. We have shown that aging and hypertension impair collateral growth, the natural compensatory response to arterial occlusive disease, and that antioxidants restore collateral growth in young hypertensive rats. The aim of this study was to test the hypothesis that oxidant stress mediates collateral growth impairment in nondiseased, aged rats. Ileal arteries were induced to become collaterals via ligation of adjacent arteries. Growth was assessed at 7 days by repeated in vivo measurements and comparison to same-animal control arteries. Collateral diameter enlargement did not occur in aged rats, but luminal expansion was stimulated by pretreatment with tempol. Co-administration of L-NAME with tempol prevented tempol-mediated collateral development. Expression of p22(phox) mRNA was increased in aged versus young rat arteries, suggesting NAD(P)H oxidase as a source of reactive oxygen species. Treatment with apocynin increased collateral growth capacity, whether administered prior to, or 7 days following, arterial ligation. The results suggest that antioxidant treatment may be useful in promoting collateral growth to compensate for age-related arterial occlusive disease.
Assuntos
Acetofenonas/farmacologia , Envelhecimento , Antioxidantes/farmacologia , Circulação Colateral/efeitos dos fármacos , Óxidos N-Cíclicos/farmacologia , Íleo/irrigação sanguínea , Oclusão Vascular Mesentérica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fatores Etários , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Ligadura , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/crescimento & desenvolvimento , Artérias Mesentéricas/cirurgia , Oclusão Vascular Mesentérica/metabolismo , Oclusão Vascular Mesentérica/fisiopatologia , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos WKY , Ratos Wistar , Marcadores de SpinRESUMO
Technology offers potential solutions to the pending crisis of healthcare for older adults, while healthcare workers are in short supply. Technology can enable remote monitoring of individuals and early detection of potential problems, so that early interventions can help older adults remain as healthy and independent as possible. Research is under way with passive monitoring technology in senior housing that is finding patterns in the data that can enhance nurse care coordination through early illness detection. With early detection, interventions can be more effective and reduce hospitalization and other healthcare expenses. Case studies are presented, and implications are discussed.