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1.
J Am Pharm Assoc (2003) ; 63(3): 909-914, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36702735

RESUMO

BACKGROUND: Postdischarge follow-up in primary care is an opportunity for pharmacists to re-evaluate medication use in acute kidney injury (AKI) survivors. Of the emerging AKI survivor care models described in literature, only one involved a pharmacist with limited detail about the direct impact. OBJECTIVE: This study aimed to describe pharmacist contributions to a comprehensive postdischarge AKI survivorship program in primary care (the AKI in Care Transitions [ACT] program). METHODS: The ACT program was piloted from May to December of 2021 at Mayo Clinic as a bundled care strategy for patients who survived an episode of AKI and were discharged home without the need for hemodialysis. Patients received education and care coordination from nurses before discharge and later completed postdischarge laboratory assessment and clinician follow-up in primary care. During the follow-up encounter, patients completed a 30-minute comprehensive medication management visit with a pharmacist focusing on AKI survivorship considerations. Medication therapy recommendations were communicated to a collaborating primary care provider (PCP) before a separate 30-minute visit with the patient. PCPs had access to clinical decision support with evidence-based post-AKI care recommendations. Medication-related issues were summarized descriptively. RESULTS: Pharmacists made 28 medication therapy recommendations (median 3 per patient, interquartile range 2-3) and identified 14 medication discrepancies for the 11 patients who completed the pilot program, and 86% of the medication therapy recommendations were acted on by the PCP within 7 days. Six recommendations were made to initiate renoprotective medications, and 5 were acted on (83%). CONCLUSION: During the pilot phase of a multifaceted transitional care program for AKI survivors, pharmacists' successfully identified and addressed multiple medication therapy problems, including for renally active drugs. These results demonstrate the potential for pharmacist-provider collaborative visits in primary care to improve safe and effective medication use in AKI survivors.


Assuntos
Injúria Renal Aguda , Alta do Paciente , Humanos , Farmacêuticos , Assistência ao Convalescente , Sobreviventes , Injúria Renal Aguda/terapia , Hospitais
2.
Eur J Neurosci ; 52(1): 2705-2723, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31943448

RESUMO

Episodic memory involves the integration and recall of discrete events that include information about what happened, where it happened and when it occurred. Episodic memory function is critical to daily life, and its dysfunction is both a first identifiable indicator and an enduring core feature of cognitive decline in ageing and in neuropsychiatric disorders including Alzheimer's disease and schizophrenia. Available evidence from human studies suggests that biological sex and sex hormones modulate episodic memory function in health and disease. However, knowledge of how this occurs is constrained by the limited availability and underutilization of validated animal models in investigating hormone impacts on episodic-like memory function. Here, adult female, adult male and gonadally manipulated adult male rats were tested on the what-where-when episodic-like memory task to determine whether rats model human sex differences in episodic memory and how the hormonal milieu impacts episodic-like memory processes in this species. These studies revealed salient ways in which rats model human sex differences in episodic memory, including a male advantage in spatial episodic memory performance. They also identified domain-specific roles for oestrogens and androgens in modulating what, where and when discriminations in male rats that were unlike those engaged in corresponding novel object recognition and novel object location tasks. These studies thus identify rats and the what-where-when task as suitable for investigating the neuroendocrine bases of episodic-like memory, and provide new information about the unique contributions that sex and sex hormones make to this complex mnemonic process.


Assuntos
Doença de Alzheimer , Memória Episódica , Animais , Cognição , Feminino , Hormônios Esteroides Gonadais , Masculino , Rememoração Mental , Ratos
3.
Int J Mol Sci ; 21(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012921

RESUMO

Cerebral amyloid angiopathy (CAA) is the deposition of amyloid protein in the cerebral vasculature, a common feature in both aging and Alzheimer's disease (AD). However, the effects of environmental factors, particularly cognitive stimulation, social stimulation, and physical activity, on CAA pathology are poorly understood. These factors, delivered in the form of the environmental enrichment (EE) paradigm in rodents, have been shown to have beneficial effects on the brain and behavior in healthy aging and AD models. However, the relative importance of these subcomponents on CAA pathology has not been investigated. Therefore, we assessed the effects of EE, social enrichment (SOC), and cognitive enrichment (COG) compared to a control group that was single housed without enrichment (SIN) from 4 to 8 months of age in wild-type mice (WT) and Tg-SwDI mice, a transgenic mouse model of CAA that exhibits cognitive/behavioral deficits. The results show that individual facets of enrichment can affect an animal model of CAA, though the SOC and combined EE conditions are generally the most effective at producing physiological, cognitive/behavioral, and neuropathological changes, adding to a growing literature supporting the benefits of lifestyle interventions.


Assuntos
Proteínas Amiloidogênicas/metabolismo , Angiopatia Amiloide Cerebral/psicologia , Exercício Físico/psicologia , Proteínas Amiloidogênicas/genética , Animais , Angiopatia Amiloide Cerebral/genética , Angiopatia Amiloide Cerebral/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório , Humanos , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos
4.
J Neuroinflammation ; 16(1): 144, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296239

RESUMO

BACKGROUND: Cardiovascular exercise (CVE) has been shown to be protective against cognitive decline in aging and the risk for dementias, including Alzheimer's Disease (AD). CVE has also been shown to have several beneficial effects on brain pathology and behavioral impairments in mouse models of AD; however, no studies have specifically examined the effects of CVE on cerebral amyloid angiopathy (CAA), which is the accumulation of amyloid-beta (Aß) in the cerebral vasculature. CAA may be uniquely susceptible to beneficial effects of CVE interventions due to the location and nature of the pathology. Alternatively, CVE may exacerbate CAA pathology, due to added stress on already compromised cerebral vasculature. METHODS: In the current study, we examined the effects of CVE over many months in mice, thereby modeling a lifelong commitment to CVE in humans. We assessed this voluntary CVE in Tg-SwDI mice, a transgenic mouse model of CAA that exhibits behavioral deficits, fibrillar vascular Aß pathology, and significant perivascular neuroinflammation. Various "doses" of exercise intervention (0 h ("Sedentary"), 1 h, 3 h, 12 h access to running wheel) were assessed from ~ 4 to 12 months of age for effects on physiology, behavior/cognitive performance, and pathology. RESULTS: The 12 h group performed the greatest volume of exercise, whereas the 1 h and 3 h groups showed high levels of exercise intensity, as defined by more frequent and longer duration running bouts. Tg-SwDI mice exhibited significant cerebral vascular Aß pathology and increased expression of pro-inflammatory cytokines as compared to WT controls. Tg-SwDI mice did not show motor dysfunction or altered levels of anxiety or sociability compared to WT controls, though Tg-SwDI animals did appear to exhibit a reduced tendency to explore novel environments. At all running levels, CAA pathology in Tg-SwDI mice was not significantly altered, but 12-h high-volume exercise showed increased insoluble Aß burden. However, CVE attenuated the expression of pro-inflammatory cytokines TNF-α and IL-6 and was generally effective at enhancing motor function and reducing anxiety-like behavior in Tg-SwDI mice, though alterations in learning and memory tasks were varied. CONCLUSIONS: Taken together, these results suggest that CAA can still develop regardless of a lifespan of substantial CVE, although downstream effects on neuroinflammation may be reduced and functional outcomes improved.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Angiopatia Amiloide Cerebral/patologia , Inflamação/patologia , Atividade Motora/fisiologia , Animais , Encéfalo/metabolismo , Angiopatia Amiloide Cerebral/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
5.
J Fish Biol ; 93(6): 1163-1170, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30306570

RESUMO

This study examined the usefulness of portable ultrasonography in accurately predicting pregnancy and fecundity in the bonnethead shark Sphyrna tiburo by comparing ultrasound-obtained data with those obtained from animal dissection, the gold standard for elasmobranch reproduction studies. Mature female S. tiburo (n = 66) were collected throughout the period of reproduction and examined via portable ultrasonography using two different ultrasound transducers (8-5 MHz linear array transducer and a 5.0-2.5 MHz curvilinear array transducer) to determine pregnancy status and fecundity. Ultrasound-derived data were compared with validated assessments of pregnancy and litter size obtained using animal dissection to determine the level of agreement between the two approaches. Overall, there was strong agreement (90.9%) between pregnancy determinations obtained using ultrasonography and dissection. However, the effectiveness of portable ultrasonography in accurately determining specific stages of maturity and pregnancy differed slightly between transducer types (linear = 61.3%; curvilinear = 88.9%). Measurements of fecundity also agreed well between ultrasonography and dissection and there were no significant differences between mean fecundity estimates obtained using the two methods. In general, portable ultrasonography was found to be a good alternative to lethal sampling and animal dissection in obtaining reproductive data critical for the management and conservation of elasmobranchs. Special attention should be given to factors that can influence the reliability of ultrasound-derived data such as transducer type, embryo size and sound wave interference due to gut contents.


Assuntos
Fertilidade , Prenhez , Tubarões , Ultrassonografia Pré-Natal/veterinária , Animais , Feminino , Gravidez , Ultrassonografia Pré-Natal/métodos
6.
Neurobiol Learn Mem ; 137: 92-100, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27884756

RESUMO

Psychological stressors elicit the anticipation of homeostatic challenge, whereas physical stressors are direct threats to homeostasis. Many rodent models of stress include both types of stressors, yet deficits, like those reported for working memory, are often attributed to psychological stress. To empirically test whether intermittent psychological stressors, such as repeated threats, are solely sufficient to impair spatial working memory, we developed a novel rodent model of stress that is restricted to the anticipation of threat, and free of direct physical challenge. Adolescent male Sprague-Dawley rats were randomly assigned to control (CT) or stress (ST) housing conditions consisting of two tub cages, one with food and another with water, separated by a tunnel. Over three weeks (P31-P52), the ST group received random (probability of 0.25), simultaneous presentations of ferret odor, and abrupt lights, and sound at the center of the tunnel. Relative to the CT group, the ST group had consistently fewer tunnel crossings, consistent with avoidance of a psychological stressor. Both groups had similar body weights and crossed the tunnel more in the dark than light period. Three days after removal from the treatment conditions, spatial working memory was tested on the Barnes maze. The ST group displayed deficits in spatial working memory, including longer latencies to enter the goal box position, and a greater number of returns to incorrect holes, but no significant differences in speed. Memory can be affected by sleep disruption, and sleep can be affected by stress. Circadian activity patterns in the tunnels were similar across groups. Therefore, the data suggest that intermittent threats without physical stress are sufficient to impair spatial working memory in adolescence.


Assuntos
Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/fisiologia , Memória Espacial/fisiologia , Estresse Fisiológico/fisiologia , Estresse Psicológico/psicologia , Animais , Masculino , Odorantes , Ratos , Ratos Sprague-Dawley
7.
Minn Med ; 96(6): 49-51, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23862373

RESUMO

Many patients refuse blood or blood products because of religious beliefs or fear of complications. At Hennepin County Medical Center, a multidisciplinary team developed a Bloodless Surgery Medicine Guideline (BSMG) to help identify those who refuse blood products, guide medical decision-making, improve documentation of informed consent or refusal, and ensure continuity of care for patients. To our knowledge, this is the first documentation of a guideline for managing informed consent for or refusal of blood or blood products in trauma patients. This article discusses the development of and legal rationale for two key components of the BSMG: an informed consent/refusal algorithm and a blueprint for discussing the use of blood or blood components with patients and documenting their decisions.


Assuntos
Procedimentos Médicos e Cirúrgicos sem Sangue/legislação & jurisprudência , Autonomia Pessoal , Segurança/legislação & jurisprudência , Ferimentos e Lesões/cirurgia , Algoritmos , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Minnesota , Equipe de Assistência ao Paciente/legislação & jurisprudência , Recusa do Paciente ao Tratamento/legislação & jurisprudência
8.
Kidney Med ; 5(12): 100734, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37964784

RESUMO

Rationale & Objective: Innovative models are needed to address significant gaps in kidney care follow-up for acute kidney injury (AKI) survivors. Study Design: This quasi-experimental pilot study reports the feasibility of the AKI in Care Transitions (ACT) program, a multidisciplinary approach to AKI survivor care based in the primary care setting. Setting & Participants: The study included consenting adults with stage 3 AKI discharged home without dialysis. Interventions: The ACT intervention included predischarge education from nurses and coordinated postdischarge follow-up with a primary care provider and pharmacist within 14 days. ACT was implemented in phases (Usual Care, Education, ACT). Outcomes: The primary outcome was feasibility. Secondary outcomes included process and clinical outcomes. Results: In total, 46 of 110 eligible adults were enrolled. Education occurred in 18/18 and 14/15 participants in the Education and ACT groups, respectively. 30-day urine protein evaluation occurred in 15%, 28%, and 87% of the Usual Care, Education, and ACT groups, respectively (P < 0.001). Cumulative incidence of provider (primary care or nephrologist) and laboratory follow-up at 14 and 30 days was different across groups (14 days: Usual care 0%, Education 11%, ACT 73% [P < 0.01]; 30 days: 0%, 22%, and 73% [P < 0.01]). 30-day readmission rates were 23%, 44%, and 13% in the Usual Care, Education, and ACT groups, respectively (P = 0.13). Limitations: Patients were not randomly assigned to treatment groups. The sample size limited the ability to detect some differences or perform multivariable analysis. Conclusions: This study demonstrated the feasibility of multidisciplinary AKI survivor follow-up beginning in primary care. We observed a higher cumulative incidence of laboratory and provider follow-up in ACT participants. Trial Registration: ClinicalTrials.gov (NCT04505891). Plain-Language Summary: Abrupt loss of kidney function in hospitalized patients, acute kidney injury (AKI), increases the chances of long-term kidney disease and a worse health care experience for patients. One out of 3 people who experience AKI do not get the follow-up kidney care they need. We performed a pilot study to test whether a program that facilitates structured AKI follow-up in primary care called the AKI in Care Transitions (ACT) program was possible. ACT brings together the unique expertise of nurses, doctors, and pharmacists to look at the patient's kidney health plan from all angles. The study found that the ACT program was possible and led to more complete kidney care follow-up after discharge than the normal approach to care.

9.
Medsurg Nurs ; 21(6): 378-82, 384, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23477032

RESUMO

The assessment of a program to promote appropriate knowledge and behaviors related to vancomycin and aminoglycoside administration by direct-care nurses working on the intensive care and a medical-surgical unit of one regional medical center is reported.


Assuntos
Aminoglicosídeos/administração & dosagem , Antibacterianos/administração & dosagem , Vancomicina/administração & dosagem , Adulto , Aminoglicosídeos/farmacocinética , Antibacterianos/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vancomicina/farmacocinética , Adulto Jovem
10.
Front Med (Lausanne) ; 9: 826169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35733861

RESUMO

Background: Meaningful patient centered outcomes of critical illness such as functional status, cognition and mental health are studied using validated measurement tools that may often be impractical outside the research setting. The Electronic health record (EHR) contains a plethora of information pertaining to these domains. We sought to determine how feasible and reliable it is to assess meaningful patient centered outcomes from the EHR. Methods: Two independent investigators reviewed EHR of a random sample of ICU patients looking at documented assessments of trajectory of functional status, cognition, and mental health. Cohen's kappa was used to measure agreement between 2 reviewers. Post ICU health in these domains 12 month after admission was compared to pre- ICU health in the 12 months prior to assess qualitatively whether a patient's condition was "better," "unchanged" or "worse." Days alive and out of hospital/health care facility was a secondary outcome. Results: Thirty six of the 41 randomly selected patients (88%) survived critical illness. EHR contained sufficient information to determine the difference in health status before and after critical illness in most survivors (86%). Decline in functional status (36%), cognition (11%), and mental health (11%) following ICU admission was observed compared to premorbid baseline. Agreement between reviewers was excellent (kappa ranging from 0.966 to 1). Eighteen patients (44%) remained home after discharge from hospital and rehabilitation during the 12- month follow up. Conclusion: We demonstrated the feasibility and reliability of assessing the trajectory of changes in functional status, cognition, and selected mental health outcomes from EHR of critically ill patients. If validated in a larger, representative sample, these outcomes could be used alongside survival in quality improvement studies and pragmatic clinical trials.

11.
BMJ Open ; 12(12): e064017, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460332

RESUMO

INTRODUCTION: Anaemia is highly prevalent in critical illness and is associated with impaired outcomes during and after hospitalisation. However, the impact of interventions designed to attenuate or treat anaemia during critical illness on post-hospitalisation haemoglobin recovery and functional outcomes is unclear. METHODS AND ANALYSIS: The Practical Anemia Bundle for Sustained Blood Recovery (PABST-BR) clinical trial is a pragmatic, open-label, parallel group, single-centre, randomised clinical trial assessing the impact of a multifaceted anaemia prevention and treatment strategy versus standard care for improvement of haemoglobin concentrations and functional outcomes after critical illness. The intervention, which will be delivered early in critical illness for those with moderate-to-severe anaemia (ie, haemoglobin <100 g/L), includes three components: (1) optimised phlebotomy, (2) clinical decision support and (3) pharmacological anaemia treatment directed at the underlying aetiology of anaemia. In-person assessments will occur at 1 and 3 months post-hospitalisation for laboratory evaluations and multidimensional functional outcome assessments. The primary outcome is differences in haemoglobin concentrations between groups, with secondary endpoints of anaemia-related fatigue, physical function, cognition, mental health, quality of life, phlebotomy volumes and frequency, transfusions, readmissions and mortality through 1-year post-hospitalisation. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Mayo Clinic in Minnesota, USA. A Data Safety Monitoring Plan has been created in accordance with the policies of the Institutional Review Board and the study funder, the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). The study will comply with NIH data sharing and dissemination policies. Results will be presented at national and international meetings and published in peer-reviewed journals. Designing and testing strategies to optimise haemoglobin recovery and improve functional outcomes after critical illness remain important research gaps. The PABST-BR trial will inform the development of a larger multicentre clinical trial. TRIAL REGISTRATION NUMBER: NCT05167734.


Assuntos
Anemia , Estado Terminal , Estados Unidos , Humanos , Estado Terminal/terapia , Qualidade de Vida , Anemia/terapia , Flebotomia , Coração , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Can J Kidney Health Dis ; 9: 20543581221081258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35284082

RESUMO

Background: Acute kidney injury (AKI) survivors are at heightened risk for poor short- and long-term health outcomes. Even among those who recover after an AKI episode, the risk for chronic kidney disease is 4- to 6-fold higher than in patients without AKI, underscoring the importance of identifying methods to improve AKI survivorship. Objective: The purpose of this report was to describe the development and feasibility of a novel multidisciplinary approach to caring for AKI survivors at care transitions (ACT). Design: Observational process improvement initiative. Setting: Single academic medical center in the United States. Patients: The studied population was adults with stage 3 AKI not discharging on dialysis who were established with a primary care provider (PCP) at our institution. Methods: An electronic health record tool was developed prior to implementation to identify AKI survivors. The ACT program encompassed engaging patients in the hospital, delivering education by nephrology-trained nurses before discharge, completing recommended laboratory testing after discharge, and conducting structured kidney-focused follow-up with a pharmacist and a PCP within 7 to 14 days after discharge. Patients could be referred for nephrology evaluation at the discretion of the PCP. Results: Preliminary data demonstrated that most AKI survivors of interest could be identified, educated, and followed up with this model. This strategy appeared feasible, scalable, and maximized the unique expertise of each member of the multidisciplinary team. Limitations: Small sample size, future assessment of process, clinical, and patient-reported outcomes needed. Conclusions: The multidisciplinary ACT workflow supported by clinical decision support was feasible and addressed gaps in existing care transition models. Team-based care delivery in primary care appears to be a mechanism to extend the capacity for kidney health monitoring for AKI survivors.


Contexte: Les patients qui survivent à un épisode d'insuffisance rénale aiguë (IRA) courent un risque plus élevé de mauvais résultats cliniques à court et à long terme. Même chez les patients qui se rétablissent, le risque de progression vers l'insuffisance rénale chronique (IRC) demeure de quatre à six fois plus élevé que chez les patients n'ayant jamais eu d'épisode d'IRA. Il est donc essentiel d'identifier des méthodes permettant d'améliorer la survie à un épisode d'IRA. Objectif: L'objectif de cette étude était de décrire l'élaboration et la faisabilité d'une nouvelle approche multidisciplinaire pour la prise en charge des survivants d'un épisode d'IRA en transition de soins (Approche multidisciplinaire en Transition de Soins­AmTS). Type d'étude: Initiative d'amélioration des processus menée par observation. Cadre: Un seul centre médical universitaire aux États-Unis. Sujets: La population étudiée était constituée d'adultes atteints d'IRA de stade 3 sans traitements de dialyse à leur sortie et qui avaient été mis en contact avec un fournisseur de soins primaires (FSP) dans l'établissement. Méthodologie: Avant la mise en œuvre de l'intervention, un outil de dossier de santé électronique a été développé pour identifier les survivants à un épisode d'IRA. Le programme de l'AmTS comprenait la participation des patients pendant leur séjour à l'hôpital, une formation donnée par des infirmières formées en néphrologie avant le congé, les tests de laboratoire recommandés après la sortie de l'hôpital et un suivi structuré axé sur la santé rénale avec un pharmacien et un FSP dans les 7 à 14 jours suivant la sortie de l'hôpital. Il a été laissé à la discrétion des FSP d'aiguiller ou non leurs patients pour une évaluation en néphrologie. Résultats: Des données préliminaires ont démontré qu'il était possible d'identifier, d'informer et d'assurer le suivi de la plupart des sujets d'intérêt (des survivants à un épisode d'IRA) avec ce modèle. Cette stratégie a semblé réalisable, évolutive et apte à optimiser l'expertise individuelle des membres de l'équipe multidisciplinaire. Limites: Faible taille de l'échantillon; une évaluation future du processus, des résultats cliniques et des résultats rapportés par les patients est nécessaire. Conclusion: Le processus de cette AmTS soutenue par une aide à la prise de décision clinique s'est avéré réalisable et a permis de combler les lacunes des modèles de transition des soins existants. Dans le contexte des soins primaires, la prestation de soins en équipe semble être un mécanisme permettant d'étendre la capacité de surveillance de la santé rénale des survivants à un épisode d'IRA.

13.
Dev Psychobiol ; 53(5): 456-65, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21678393

RESUMO

Fifty years ago, Mark Rosenzweig and coworkers described environmental effects on brain chemistry and gross brain weight. William Greenough then used stereological tools, electron microscopy, and the Golgi stain to demonstrate that enrichment led to dendritic growth and synapse addition. Together these forms of plasticity accounted for cortical expansion and a reduction in cell density. In parallel with other investigators, Greenough demonstrated that these effects were not limited to the rodent, the cortex, or development, but instead generalize to many species, brain regions, and life stages. Studies of the anatomical effects of enrichment foreshadowed the recent empirical evidence for cortical volumetric increases after environmental experience and training in humans. Since research in humans is limited to regional effects, the analysis of the cellular and synaptic effects of enrichment, and their contribution to volumetric increases can inform us of the potential cellular and subcellular plasticity the leads to volume change in humans.


Assuntos
Encéfalo/anatomia & histologia , Fibras Nervosas Amielínicas/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia , Animais , Encéfalo/fisiologia , Humanos , Tamanho do Órgão/fisiologia , Ratos
14.
Front Neurol ; 11: 942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041964

RESUMO

Episodic memory deficits are among the earliest appearing and most commonly occurring examples of cognitive impairment in Parkinson's disease (PD). These enduring features can also predict a clinical course of rapid motor decline, significant cognitive deterioration, and the development of PD-related dementia. The lack of effective means to treat these deficits underscores the need to better understand their neurobiological bases. The prominent sex differences that characterize episodic memory in health, aging and in schizophrenia and Alzheimer's disease suggest that neuroendocrine factors may also influence episodic memory dysfunction in PD. However, while sex differences have been well-documented for many facets of PD, sex differences in, and sex hormone influences on associated episodic memory impairments have been less extensively studied and have never been examined in preclinical PD models. Accordingly, we paired bilateral neostriatal 6-hydroxydopamine (6-OHDA) lesions with behavioral testing using the What-Where-When Episodic-Like Memory (ELM) Task in adult rats to first determine whether episodic-like memory is impaired in this model. We further compared outcomes in gonadally intact female and male subjects, and in male rats that had undergone gonadectomy-with and without hormone replacement, to determine whether biological sex and/or sex hormones influenced the expression of dopamine lesioned-induced memory deficits. These studies showed that 6-OHDA lesions profoundly impaired recall for all memory domains in male and female rats. They also showed that in males, circulating gonadal hormones powerfully modulated the negative impacts of 6-OHDA lesions on What, Where, and When discriminations in domain-specific ways. Specifically, the absence of androgens was shown to fully attenuate 6-OHDA lesion-induced deficits in ELM for "Where" and to partially protect against lesion-induced deficits in ELM for "What." In sum, these findings show that 6-OHDA lesions in rats recapitulate the vulnerability of episodic memory seen in early PD. Together with similar evidence recently obtained for spatial working memory, the present findings also showed that diminished androgen levels provide powerful, highly selective protections against the harmful effects that 6-OHDA lesions have on memory functions in male rats.

15.
J Alzheimers Dis ; 73(1): 359-374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31796673

RESUMO

Exercise has been shown to be protective against the risk of dementias, including Alzheimer's disease (AD). Intervention studies have demonstrated its ability to mitigate cognitive and behavioral impairments and reduce disease in both humans and animals. However, information is lacking in regard to the volume and intensity, as well as timing of exercise onset with respect to disease stage, which produces optimal benefits. Here, utilizing the Tg2576 mouse, a model of AD-like parenchymal amyloid pathology and cognitive impairment, we sought to understand the effects of different lengths of daily access to a running wheel on advanced stage disease. This study is the first to determine the benefits of long-term exercise (4 months of voluntary running) and different periods of daily access to a running wheel (0 h, 1 h, 3 h, and 12 h running wheel access) beginning in 14-month-old Tg2576 mice, an age with significant amyloid pathology. We found that exercising Tg2576 animals showed lower levels of some aspects of AD pathology and reduced behavioral dysfunction compared to sedentary Tg2576 animals. High intensity exercise, rather than high volume exercise, was generally most beneficial in reducing amyloid pathology. Our results suggest that engaging in vigorous exercise programs, even after living a sedentary life, may lead to a measurable reduction in AD pathology and preservation of some cognitive abilities.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/metabolismo , Condicionamento Físico Animal , Corrida , Envelhecimento/patologia , Envelhecimento/psicologia , Animais , Cognição , Treinamento Intervalado de Alta Intensidade , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Desempenho Psicomotor , Comportamento Sedentário , Interação Social , Análise de Sobrevida
16.
J Crit Care ; 52: 166-171, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31078997

RESUMO

PURPOSE: Over a third of critical illness survivors manifest significant psychocognitive impairments following discharge from the intensive care unit (ICU). It is not known which patient populations are at highest risk or if assessment at ICU discharge can guide outpatient treatment prioritization. MATERIALS AND METHODS: Prospective single center study in an academic medical center encompassing six types of ICUs assessed prevalence of psychocognitive morbidity based on ICU type and associations between initial and 3 month follow-up evaluation. Adult patients with >48 h ICU stays completed the Hospital Anxiety and Depression Scale (HADS), Impact of Events Scale-Revised (IES-R), and Montreal Cognitive Assessment-Blind (MoCA-blind). RESULTS: Of 299 patients who underwent initial assessment, 174 (58%) completed follow-up. Length of stay, MoCA-Blind, HADS-A/D and IES-R scores were similar across ICUs. Most commonly observed impairment in-hospital was cognitive (58%) followed by anxiety (45%), acute stress (39%) and depression (37%). There were significant correlations between in-hospital and follow-up psychocognitive outcomes. CONCLUSIONS: There was no significant difference in impairment by ICU type. Significant correlation between the initial assessment and follow-up scores suggests that early screening of high risk patients may identify those at greatest risk of sustained morbidity and facilitate timely intervention.


Assuntos
Transtornos de Ansiedade/etiologia , Transtornos Cognitivos/etiologia , Estado Terminal/psicologia , Transtorno Depressivo/etiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Centros Médicos Acadêmicos , Idoso , Cuidados Críticos , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Morbidade , Alta do Paciente/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Sobreviventes/psicologia
17.
Physiol Behav ; 194: 218-232, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29879399

RESUMO

Cardiovascular exercise (CVE) is associated with healthy aging and reduced risk of disease in humans, with similar benefits seen in animals. Most rodent studies, however, have used shorter intervention periods of a few weeks to a few months, begging questions as to the effects of longer-term, or even life-long, exercise. Additionally, most animal studies have utilized a single exercise treatment group - usually unlimited running wheel access - resulting in large volumes of exercise that are not clinically relevant. It is therefore incumbent to determine the physiological and cognitive/behavioral effects of a range of exercise intensities and volumes over a long-term period that model a lifelong commitment to CVE. In the current study, C57/Bl6 mice remained sedentary or were allowed either 1, 3, or 12 h of access to a running wheel per day, 5 days/weeks, beginning at 3.5-4 months of age. Following an eight-month intervention period, animals underwent a battery of behavioral testing, then euthanized and blood and tissue were collected. Longer access to a running wheel resulted in greater volume and higher running speed, but more breaks in running. All exercise groups showed similarly reduced body weight, increased muscle mass, improved motor function on the rotarod, and reduced anxiety in the open field. While all exercise groups showed increased food intake, this was greatest in the 12 h group but did not differ between 1 h and 3 h mice. While exercise dose-dependently increased working memory performance in the y-maze, the 1 h and 12 h groups showed the largest changes in the mass of many organs, as well as alterations in several behaviors including social interaction, novel object recognition, and Barnes maze performance. These findings suggest that long-term exercise has widespread effects on physiology, behavior, and cognition, which vary by "dose" and measure, and that even relatively small amounts of daily exercise can provide benefits.


Assuntos
Corrida/fisiologia , Corrida/psicologia , Animais , Ansiedade/fisiopatologia , Ansiedade/terapia , Peso Corporal , Cognição , Feminino , Masculino , Memória , Camundongos Endogâmicos C57BL , Músculo Esquelético/anatomia & histologia , Tamanho do Órgão , Comportamento Sedentário , Comportamento Social , Fatores de Tempo , Volição
18.
Peptides ; 28(5): 1120-4, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17337094

RESUMO

The neuropeptide galanin and galanin receptors are widespread throughout cortical, limbic and midbrain areas implicated in reward, learning/memory, pain, drinking and feeding. While many studies have shown that galanin produces a variety of presynaptic and post-synaptic responses, work studying the effects of galanin on neural activation is limited. The present study examined patterns of c-Fos immunoreactivity resulting from intracerebroventricular administration of galanin versus saline injection in awake rats. An initial comprehensive qualitative survey was conducted to identify regions of high c-Fos expression followed up with quantitative analysis. Galanin induced a significant increase in c-Fos levels relative to saline-treated controls in dorsomedial hypothalamus and in the central nucleus of the amygdala. This pattern of activation was also produced by galanin receptor type 1 agonist M617. The present findings confirm that galanin upregulates c-Fos activation in hypothalamic nuclei, and supports roles for galanin in central amygdala-mediated regulation of stress-responses, food intake, and Pavlovian conditioning.


Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Núcleo Hipotalâmico Dorsomedial/efeitos dos fármacos , Galanina/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptor Tipo 1 de Galanina/agonistas , Tonsila do Cerebelo/metabolismo , Análise de Variância , Animais , Núcleo Hipotalâmico Dorsomedial/metabolismo , Galanina/administração & dosagem , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Ratos , Ratos Sprague-Dawley
19.
J Interv Card Electrophysiol ; 50(1): 117-124, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28844107

RESUMO

PURPOSE: Cardiovascular implantable electronic device infection (CIEDI) rates are rising. To improve outcomes, our institution developed an online care process model (CPM) and a specialized inpatient heart rhythm service (HRS). METHODS: This retrospective review compared hospital length of stay (LOS), mortality, and times to subspecialty consultation and procedures before and after CPM and HRS availability. RESULTS: CPM use was associated with shortened time to surgical consultation (median 2 days post-CPM vs. 3 days pre-CPM, p = 0.0152), pocket closure (median 4 vs. 5 days, p < 0.0001), and days to new CIED implant (median 7 vs. 8 days, p = 0.0126). Post-HRS patients were more likely to have a surgical consultation (OR 7.01, 95% CI 1.56-31.5, p = 0.011) and shortened time to pocket closure (coefficient - 2.21 days, 95% CI - 3.33 to - 1.09, p < 0.001), compared to pre-HRS. CONCLUSIONS: The CPM and HRS were associated with favorable outcomes, but further integration of CPM features into hospital workflow is needed.


Assuntos
Eletrofisiologia Cardíaca , Desfibriladores Implantáveis/efeitos adversos , Pacientes Internados , Marca-Passo Artificial/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Cardiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/fisiopatologia , Estudos Retrospectivos , Análise de Sobrevida
20.
J Comp Neurol ; 498(3): 363-74, 2006 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-16871536

RESUMO

Individuals with clinical disorders associated with elevated plasma glucocorticoids, such as major depressive disorder and Cushing's syndrome, are reported to have smaller hippocampal volume. To understand how the hippocampus responds at the cellular and subcellular levels to glucocorticoids and how such changes are related to volume measures, we have undertaken a comprehensive study of glucocorticoid effects on hippocampal CA3 volume and identified elements in the neuropil including astrocytic volume and cell and synapse number and size. Male Sprague-Dawley rats were injected with corticosterone (40 mg/kg), the primary glucocorticoid in rodents, or vehicle for 60 days. The CA3 was further subdivided so that the two-thirds of CA3 (nearest the dentate gyrus) previously shown to be vulnerable to corticosterone could be analyzed as two separate subfields. Corticosterone had no effect on neuropil volume or glial volume in the proximal subfield but caused a strong tendency for astrocytic processes to make up a larger proportion of the tissue and for volume of tissue made of constituents other than glial cells (primarily neuronal processes) to be smaller in the middle subfield. Within the neuropil, there were no cellular or subcellular profiles that indicated degeneration, suggesting that corticosterone does not cause prolonged damage. Corticosterone did not reduce cell number or cell or nonperforated synapse size but did cause a pronounced loss of synapses. This loss occurred in both subfields and, therefore, was independent of volume loss. Together, the findings suggest that volume measures can underestimate corticosterone effects on neural structure.


Assuntos
Atrofia/fisiopatologia , Glucocorticoides/metabolismo , Hipocampo/patologia , Degeneração Neural/fisiopatologia , Neurônios/patologia , Neurópilo/patologia , Sinapses/patologia , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Atrofia/induzido quimicamente , Contagem de Células , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Doença Crônica , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/fisiopatologia , Modelos Animais de Doenças , Gliose/induzido quimicamente , Gliose/fisiopatologia , Glucocorticoides/efeitos adversos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Degeneração Neural/induzido quimicamente , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurópilo/efeitos dos fármacos , Neurópilo/metabolismo , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/fisiopatologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologia , Ratos , Ratos Sprague-Dawley , Estresse Fisiológico/complicações , Estresse Fisiológico/fisiopatologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Regulação para Cima/fisiologia
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