Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion

We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 microm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti-major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE.     

The role of the clinical nurse specialist: problems and solutions

The clinical nurse specialist (CNS) is a generally untapped resource for the nurse executive. Although seen as an asset, the CNS may be considered an expensive and nonessential part of the department of nursing. The role is threatened with extinction not only because it is seen as dispensable in a time of cost restraint, but also because of problems in role implementation. We believe the CNS role is vital to the advancement of nursing practice and that the impact of the CNS on nursing practice has not reached its full potential. This paper summarizes the major problems inhibiting role development in the hospital setting and suggests solutions to the nurse executive for maximizing the role potential of the CNS.     

Relationship between intensive care unit-acquired weakness,fatigability and fatigue: What role for the central nervous system?

PurposeTo provide a comprehensive review of studies that have investigated fatigue in intensive care unit (ICU) survivors and questions the potential link between intensive care unit-acquired weakness (ICUAW), fatigability and fatigue. We also question whether the central nervous system (CNS) may be the link between these entities.Material and methodsA narrative review of the literature that investigated fatigue in ICU survivors and review of clinical trials enabling understanding of CNS alterations in response to ICU stays.ResultsFatigue is a pervasive and debilitating symptom in ICU survivors that can interfere with rehabilitation. Due to the complex pathophysiology of fatigue, more work is required to understand the roles of ICUAW and/or fatigability in fatigue to provide a more holistic understanding of this symptom. While muscle alterations have been well documented in ICU survivors, we believe that CNS alterations developing early during the ICU stay may play a role in fatigue.ConclusionsFatigue should be considered and treated in ICU survivors. The causes of fatigue are likely to be specific to the individual. Understanding the role that ICUAW and fatigability may have in fatigue would allow to tailor individual treatment to prevent this persistent symptom and improve quality of life.     

Imaging of vascular biology in the heart

The potential of molecular imaging in visualizing pathophysiologic processes underlying the development, progression, and regression of disease makes it a powerful tool for early detection, risk stratification, and tracking response to therapy. We have seen remarkable advances in molecular imaging of vascular diseases in recent years. To date, most studies have addressed the feasibility of molecular imaging in animal models of human disease, and translation into clinical practice is expected in the near future. Although there is a large body of literature, some groundbreaking, on cardiovascular molecular imaging going back to a decade ago, this review mainly focuses on recent advances in molecular imaging of vascular diseases of the heart.     

专科护士在护理专业中的角色和地位

对“专科护士”(CNS)的概念和执业标准 ,CNS的工作内容、角色作用和在实践中遇到的问题 ,以及CNS在护理专业发展中的意义作了简要的介绍和分析。CNS是在护理专业化进程中产生的 ,是高级临床护理工作者。在一些国家的卫生保健系统中 ,CNS活跃在各种护理服务场所 ,可有其专门的工作岗位和相应的岗位职责 ,为服务对象提供常规的医疗护理工作未能提供或未能系统地提供的专门化护理服务。多年来 ,CNS所做的工作体现了护理工作在卫生保健事业中的独特作用和价值 ,丰富了护理学知识体系 ,对护理学科的发展做出了贡献。我国CNS的培养和使用尚处于起步阶段 ,其发展是符合卫生保健事业的需求的 ,也给临床护士在专业上的发展展示了一个全新的领域     

A competency-based orientation program for the clinical nurse specialist

A factor affecting role development of the clinical nurse specialist (CNS) is the orientation process. Unless nursing service provides the structure for enhancing role development, frustration, nonacceptance, and even early termination of a qualified clinical nurse specialist may result. An orientation program provides the mechanism to guide the CNS through the introduction phase of the CNS role in the institution. Without such a program, the CNS may not acquire the fundamental understanding of the nursing department's service and educational philosophy.     

The Foundations for Chronic Low Back Pain Management may Start in Early Life. Exploring the Role of Caregiver Parental Leave on Future Low Back Pain in the Offspring

Chronic low back pain is difficult to treat and despite increased spending on health services, clinical outcomes for people with low back pain have not improved. Innovative, large scale initiatives seem necessary to stem the cost of low back pain. Psychological health contributes to the development and persistence of chronic low back pain and psychological interventions are important in the management of low back pain. Given the contribution of psychological health to low back pain development and management, it raises the question; can we support psychological health in later life by bolstering emotional development in early life, and reduce the burden of this common condition? Positive early life experiences, including those induced by extended paid parental leave, could bolster emotional development and support the psychological health necessary to manage low back pain in later life. We present the current state of evidence demonstrating the potential value of increasing support for parent-child relationships in early life to reduce the burden of low back pain in future generations. The current evidence is limited to cross-sectional associations, but strong preclinical data clearly shows the potential negative impacts of maternal separation on rodent pup health that compels consideration in human populations.PerspectiveThe benefits stemming from enhanced child development include stable emotional foundations, possibly improving psychological health and low back pain management in the future. This perspective raises questions for future studies – within the context of low back pain, what ingredients bolster stable psychological health? And are these ingredients influenced by parental leave?     

Making visible the contributions of the clinical nurse specialist

This paper reviews the knowledge gap regarding the contributions of the clinical nurse specialist (CNS) in Canada. As a first step to deal with this gap, we address how the CNS role has been conceptualized and studied in Canada. Because the CNS is a clinical leader with a primary focus on improving the quality of nursing and patient care, we propose the Spheres of Influence Model for studying the contributions of the CNS. This model directs attention to various research questions, which are illustrated with sample questions for each of the spheres of influence: the patient/client sphere, the nurses/nursing sphere and the organizations/health systems sphere. Examining the role through these spheres of influence may be a better way to illuminate the contributions of the CNS to health services and to the provision of excellent nursing care.     

SELDI-TOF-MS proteomics of breast cancer.

The detection, diagnosis, and management of breast cancer rely on an integrated approach using clinical history, physical examination, imaging, and histopathology. The discovery and validation of novel biomarkers will aid the physician in more effectively achieving this integration. This review discusses efforts in surface-enhanced laser desorption/ionization (SELDI)-based proteomics to address various clinical questions surrounding breast cancer, including diagnosis, monitoring, and stratification for treatment. Emphasis is placed on examining how study design and execution influence the discovery and validation process, which is critical to the proper development of potential clinical tests.     

Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS

The macrophage is well established as a target of HIV and simian immunodeficiency virus (SIV) infection and a major contributor to the neuropathogenesis of AIDS. However, the identification of distinct subpopulations of monocyte/macrophages that carry virus to the brain and that sustain infection within the central nervous system (CNS) has not been examined. We demonstrate that the perivascular macrophage and not the parenchymal microglia is the primary cell productively infected by SIV. We further demonstrate that although productive viral infection of the CNS occurs early, thereafter it is not easily detectable until terminal AIDS. The biology of perivascular macrophages, including their rate of turnover and replacement by peripheral blood monocytes, may explain the timing of neuroinvasion, disappearance, and reappearance of virus in the CNS, and questions the ability of the brain to function as a reservoir for productive infection by HIV/SIV.     

肝磁共振血流灌注成像及进展

近年来,随着硬件与软件技术的发展,灌注加权磁共振成像在肝脏疾病诊断中取得了一定的进步.作者根据近年的相关文献,就其基本原理与成像方法、成像技术、质量评价、对比剂、临床应用等作一综述.重点在于成像技术与临床应用以及未来有待解决的一些问题.     

Limbic seizures, kindling, and psychosis: a link between neurobiology and clinical psychiatry

This interplay between basic neurobiology and clinical psychiatry helps shape clinical thinking about behavioral disorders. At a basic science level, the potential exists for elucidating the functional anatomy and physiology of CNS regions involved in kindling. These studies should aid in understanding the basic mechanisms involved in this process, thus clarifying the processes involved in the associated behavioral changes. At a clinical level, improved techniques of CNS imaging such as provided by positron emission tomography should allow better elucidation of the functional anatomy related to specific psychiatric symptoms. By combining basic science and clinical research with careful clinical diagnosis and observation, we eventually should be able to understand many aspects of human psychopathology. Such understanding will lead to improved therapeutic strategies.     

Screening for breast cancer with MRI

Breast MRI has emerged as an extremely powerful tool in breast imaging. The use of breast MRI for cancer detection has the potential to change our current algorithms in the detection of breast cancer. By being able to detect cancer that is occult on conventional imaging, such as mammography and sonography, MRI can detect early breast cancer that was previously unseen by conventional imaging. This article reviews the experience of screening breast MRI in the high-risk population. It also reviews the limitations associated with its use. Before breast MRI can be used in the clinical setting, an ability to localize or biopsy MRI detected lesions that are occult on mammography and ultrasound is needed and must be available for these patients. Although the robustness of this technique has generated considerable enthusiasm, our perspective should be tempered by the fact that many questions remain unanswered regarding the use of breast MRI for screening in the nonhigh risk population as well as integration of breast MRI into clinical practice.     

Recent advances in clinical trial design considerations in Thera“nostics”

Theranostics in drug development is an evolving framework, known as combining ‘thera’ (a therapeutic drug) with ‘nostics’ (a diagnostic imaging drug) and with the latter being mostly used to select patient for evaluation of safety and efficacy of an investigational therapeutics. However, when a diagnostic imaging drug is still investigational, patient selection performance of a nostics imaging has not been demonstrated. Clinical trials conducted to assess the effect of an investigational therapeutics in a theranostics setting may focus only on the therapeutics development and not necessarily require definitive truth standard or reference standard to also assess patient selection performance of an investigational diagnostic imaging drug.We propose an In-Parallel with Leveraging development pathway in view of current practice of theranostics for a nostics imaging development. We rationalize minimum statistical metrics necessary for patient selection to allow for rigors of a nostics or diagnostics imaging drug development. We highlight tangible benefits with newer design considerations. We articulate potential indications of a nostics development including prognostic, predictive and treatment response monitoring in addition to patient selection. We further articulate potential additional clinical utilities of risk stratification and clinical management. To take full advantage and the likely payoff in the benefit of leveraging, a group sequential design or an adaptive design for the therapeutic trial is highly encouraged.     

Neonatal CNS infection and inflammation caused by Ureaplasma species: rare or relevant?

Colonization with Ureaplasma species has been associated with adverse pregnancy outcome, and perinatal transmission has been implicated in the development of bronchopulmonary dysplasia in preterm neonates. Little is known about Ureaplasma-mediated infection and inflammation of the CNS in neonates. Controversy remains concerning its incidence and implication in the pathogenesis of neonatal brain injury. In vivo and in vitro data are limited. Despite improving care options for extremely immature preterm infants, relevant complications remain. Systematic knowledge of ureaplasmal infection may be of great benefit. This review aims to summarize pathogenic mechanisms, clinical data and diagnostic pitfalls. Studies in preterm and term neonates are critically discussed with regard to their limitations. Clinical questions concerning therapy or prophylaxis are posed. We conclude that ureaplasmas may be true pathogens, especially in preterm neonates, and may cause CNS inflammation in a complex interplay of host susceptibility, serovar pathogenicity and gestational age-dependent CNS vulnerability.     

光学成像技术在乳腺病变诊断中的应用及进展

光学成像技术是近年来发展的一种新的功能成像技术。该技术通过对组织血红蛋白浓度及血氧饱和度的测量,反映肿块内部代谢状况,从而为乳腺病变的诊断和鉴别诊断提供重要信息,具有很高的临床应用价值。本文就光学成像技术的发展及其在乳腺病变诊断中的应用与最新研究进展进行综述。     

Bone-marrow micrometastases in patients with brain metastases from epithelial cell tumours

Carcinoma that has metastasized to the central nervous system (CNS) poses a particular clinical problem regarding confirmation of the diagnosis and subsequent management. Prior to excision, thorough evaluation for coexisting systemic disease is essential, but current imaging techniques are limited by their spatial resolution and under-stage many patients. We evaluated the potential utility of bone-marrow evaluation for micrometastatic cells in patients with CNS metastasis. Bone-marrow aspirates were examined for cytokeratin-positive cells in 12 consecutive patients who presented with symptomatic space-occupying lesions of the CNS. These patients had previously undergone surgical excision of either gastrointestinal or breast cancers. All twelve had micrometastases in their bone marrow at the time of presentation with the CNS disease and all had a fatal outcome within 13 months. In nine of the 12 patients, bone-marrow micrometastases were the only evidence for systemic spread. Three patients had elevated serum tumour markers and two of these had radiologically detectable recurrence elsewhere. Bone-marrow micrometastases indicate concurrent systemic involvement and a poor prognosis. The results suggest that bone-marrow evaluation for systemic spread is a useful diagnostic adjunct and should be performed before considering diagnostic biopsy or excision.     

Cysticercosis of temporalis muscle: an unusual cause of temporal headaches. A case report

Cysticercosis is a common parasitic infection caused by encysted larvae of the helminth Taenia solium (pork tapeworm). The central nervous system (CNS) is the most important primary site of infection and the disease can present with solitary or multiple space occupying lesions. Less common presentations in the CNS include the racemose variety with macroscopic groups of cysticerci in the subarachnoid space giving the appearance of a cluster of grapes and basal or ventricular cysticercosis causing obstructive hydrocephalus. Involvement of other organs: skeletal muscle, eyes, myocardium and the lungs has also been reported. Cases of cysticercosis presenting as isolated muscle mass (pseudotumours) without involvement of the CNS have also been recently described in the literature. We present a case of a 43-year-old woman who complained of subacute onset of left temporal pain and headache. Magnetic resonance imaging (MRI) showed characteristic imaging findings suggestive of cysticercosis of the temporalis muscle.     

Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury

Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.