Hypoxia-ischemia induces an inflammatory response in the immature central nervous system that may be important for development of brain injury. Recent data implicate that chemoattractant cytokines, chemokines, are involved in the recruitment of immune cells. The aim was to study alpha- and beta-chemokines in relation to the temporal activation of inflammatory cells after hypoxia-ischemia in immature rats. Hypoxia-ischemia was induced in 7-day-old rats (left carotid artery occlusion + 7.7% oxygen). The pups were decapitated at different times after the insult. Immunohistochemistry was used for evaluation of the inflammatory cell response and RT-PCR to analyze the cytokine mRNA and chemokine mRNA expression. A distinct interleukin-1beta and tumor necrosis factor-alpha cytokine expression was found 0-24 h after hypoxia-ischemia that was accompanied by induction of alpha-chemokines (growth related gene and macrophage inflammatory protein-2). In the next phase, the beta2-integrin expression was increased (12 h and onward) and neutrophils transiently invaded the vessels and tissue in the infarct region. The mRNA induction for the beta-chemokines macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and RANTES preceded the expression of markers for lymphocytes [cluster of differentiation (CD)4, CD8], microglia/macrophages (MHC I), and natural killer cells in the infarct area. The activation of microglia/macrophages, CD4 lymphocytes, and astroglia persisted up to at least 42 d of postnatal age implicating a chronic component of immunoinflammatory activation. The expression of mRNA for alpha- and beta-chemokines preceded the appearance of immune cells suggesting that these molecules may have a role in the inflammatory response to insults in the immature central nervous system.

No abstract

No abstract

BackgroundImplementing the value-based healthcare concept (VBHC) is a growing management trend in Swedish healthcare organizations. The aim of this study is to explore how representatives of four pilot project teams experienced implementing VBHC in a large Swedish University Hospital over a period of 2 years. The project teams started their work in October 2013.MethodsAn explorative and qualitative design was used, with interviews as the data collection method. All the participants in the four pilot project teams were individually interviewed three times, with interviews starting in March 2014 and ending in November 2015. All the interviews were transcribed and analyzed using qualitative analysis.ResultsValue for the patients was experienced as the fundamental drive for implementing VBHC. However, multiple understandings of what value for patients’ means existed in parallel. The teams received guidance from consultants during the first 3 months. There were pros and cons to the consultant’s guidance. This period included intensive work identifying outcome measurements based on patients’ and professionals’ perspectives, with less interest devoted to measuring costs. The implementation process, which both gave and took energy, developed over time and included interventions. In due course it provided insights to the teams about the complexity of healthcare. The necessity of coordination, cooperation and working together inter-departmentally was critical.ConclusionsHealthcare organizations implementing VBHC will benefit from emphasizing value for patients, in line with the intrinsic drive in healthcare, as well as managing the process of implementation on the basis of understanding the complexities of healthcare. Paying attention to the patients’ voice is a most important concern and is also a key towards increased engagement from physicians and care providers for improvement work.

In a model of cerebral hypoxia-ischemia in the immature rat, widespread brain injury is produced in the ipsilateral hemisphere, whereas the contralateral hemisphere is left undamaged. Previously, we found that calpains were equally translocated to cellular membranes (a prerequisite for protease activation) in the ipsilateral and contralateral hemispheres. However, activation, as judged by degradation of fodrin, occurred only in the ipsilateral hemisphere. In this study we demonstrate that calpastatin, the specific, endogenous inhibitor protein to calpain, is up-regulated in response to hypoxia and may be responsible for the halted calpain activation in the contralateral hemisphere. Concomitantly, extensive degradation of calpastatin occurred in the ipsilateral hemisphere, as demonstrated by the appearance of a membrane-bound 50-kDa calpastatin breakdown product. The calpastatin breakdown product accumulated in the synaptosomal fraction, displaying a peak 24 h post-insult, but was not detectable in the cytosolic fraction. The degradation of calpastatin was blocked by administration of CX295, a calpain inhibitor, indicating that calpastatin acts as a suicide substrate to calpain during hypoxia-ischemia. In summary, calpastatin was up-regulated in areas that remain undamaged and degraded in areas where excessive activation of calpains and infarction occurs.Hypoxic-ischemic brain damage is an important contributor to long term neurological sequelae in term and pre-term infants (1-3). The intracellular calcium concentration increases during anoxia/ischemia (4) followed by a secondary phase of cellular calcium overload simultaneous with or slightly preceding development of hypoxic-ischemic neuronal damage (5, 6). Activation of calcium-dependent enzymes is considered to be an early feature in this process (7). Calpains (EC 3.4.22.17) are calciumactivated, nonlysosomal, neutral cysteine proteases proposed to participate in many important intracellular processes, such as turnover of cytoskeletal proteins and regulation of kinase activity and transcription factors (8, 9). The activity of calpains is strictly regulated by calcium concentrations and interaction with calpastatin (the endogenous inhibitor protein), membrane phospholipids, and a multitude of other factors. The ubiquitous distribution of calpains and the complex regulation of their activity indicate that these proteases play important roles under both physiological and pathological conditions. Calpain activation, as judged by the appearance of specific fodrin (10) (also called brain spectrin (11)) breakdown products (FBDP) 1 has previously been demonstrated in adult (12-16) and neonatal (17, 18) models of ischemia and hypoxia. Activation of calpains and selective degradation of preferred substrates precede neuronal degeneration, indicating that these proteases are activated during hypoxia-ischemia (HI) and in the early phase of reperfusion after HI, preceding neuronal death (12, 13, 16 -19). In vivo administration of inhibitors of calpain activity has been sho...

PurposeDisasters and major incidents demand a multidisciplinary management. Recent experiences from terrorist attacks worldwide have resulted in a search for better assessment of the needs, resources, and knowledge in the medical and non-medical management of these incidents and also actualized the need for collaboration between civilian and military healthcare. The aim of this study was to evaluate the impact of the civilian–military collaboration in a Swedish context with the main focus on its non-medical management.MethodAn exercise, simulating a foreign military attack centrally on Swedish soil, was designed, initiated, and conducted by a team consisting of civilian and military staff. Data were collected prospectively and evaluated by an expert team.ResultsSpecific practical and technical issues were presented in collaboration between civilian and military staffs. In addition, shortcomings in decision-making, follow-up, communication, and collaboration due to prominent lack of training and exercising the tasks and positions in all managerial levels of the hospital were identified.ConclusionCurrent social and political unrests and terror attacks worldwide necessitate civilian–military collaboration. Such collaboration, however, needs to be synchronized and adjusted to avoid preventable medical and non-medical consequences. Simulation exercises might be one important source to improve such collaboration.

TAF and LAF remove bacteria more efficiently from the air than TMA, especially close to the wound and at the instrument table. Like LAF, the new TAF ventilation system maintained very low levels of cfu in the air, but TAF used substantially less energy and provided a more comfortable working environment than LAF. This enables energy savings with preserved air quality.

Purpose The aim of this study has been to explore learning experiences from the two first years of the implementation of value-based healthcare (VBHC) at a large Swedish University Hospital. Design/methodology/approach An explorative design was used in this study. Individual open-ended interviews were carried out with 19 members from four teams implementing VBHC. Qualitative analysis was used to analyse the verbatim transcripts of the interviews. Findings Three main themes pinpointing learning experiences emerged through the analysis: resource allocation to support implementation, anchoring to create engagement and dedicated, development-oriented leadership with power of decision. Resource allocation included the need to set aside time and administrative resources and also the need to adjust essential IT-systems. The work of anchoring to create engagement involved both patients and staff and was found to be a never-ending task calling for deep commitment. The hospital top management's explicit decision to implement VBHC facilitated the implementation process, but the team leaders' lack of explicit management mandate was experienced as obstructing the process. The development process contributed not only to single-loop learning but also to double-loop learning. Originality/value Learning experiences drawn from implementing VBHC have not been studied before, and thus the results of this study could be of importance to managers and administrators wanting to implement this concept in their respective organizations.