Response of Mouse Lung Air-Blood Barrier to X-Irradiation: Ultrastructural and Stereological Analysis

Male mice of the Balb/c strain were exposed, at an age of three months, to a single dose of 10 or 20 Gy on the right hemithorax. At 3, 4, 6, 9 and 12 months after exposure, lungs were processed for electron microscopy following a standardized procedure in order to allow stereological analysis. By this method, the arithmetical mean thickness and, the air-blood barrier mean thickness in the lung parenchyma was shown to increase quickly with time by oedemization and fibrinization of the septal space. The ratio endothelium/epithelium surfaces (Sr/SF) gradually decreased by reduction of both surfaces but this was more marked for Si. The endothelium and epithelium were both highly damaged. Quantitative results indicate that damage to the epithelial cells and mainly to type II, appear at the same time as damage to the endothelium. From the time lapse quantitation it is not possible to determine which one plays the predominant role in the radiation pneumonitis. The strong reaction of the basement membrane and mainly of the interstitial cells could play a decisive role in the evolution of the illness

An open platform for personal health record apps with platform-level privacy protection

One of the main barriers to the adoption of Personal Health Records (PHR) systems is their closed nature. It has been argued in the literature that this barrier can be overcome by introducing an open market of substitutable PHR apps. The requirements introduced by such an open market on the underlying platform have also been derived. In this paper, we argue that MyPHRMachines, a cloud-based PHR platform recently developed by the authors, satisfies these requirements better than its alternatives. The MyPHRMachines platform leverages Virtual Machines as flexible and secure execution sandboxes for health apps. MyPHRMachines does not prevent pushing hospital- or patient-generated data to one of its instances, nor does it prevent patients from sharing data with their trusted caregivers. External software developers have minimal barriers to contribute innovative apps to the platform, since apps are only required to avoid pushing patient data outside a MyPHRMachines cloud. We demonstrate the potential of MyPHRMachines by presenting two externally contributed apps. Both apps provide functionality going beyond the state-of-the-art in their application domain, while they did not require any specific MyPHRMachines platform extension

Tracebook : a dynamic checklist support system

It has recently been demonstrated that checklist scan enable significant improvements to patient safety. However, their clinical acceptance is significantly lower than expected. This is due to the lack of good support systems. Specifically, support systems are too static: this holds for paper-based support as well as for electronic systems that digitize paper-based support naively. Both approaches are independent from clinical process and clinical context. In this paper, we propose a process-oriented and context-aware dynamic checklist support system: Tracebook. This system supports the execution of complex clinical processes and rules involving data from Electronic Medical Record systems. Workflow activities and forms are specific to individual patients based on clinical rules and they are dispatched to the right user automatically based on a process model. Besides describing the Tracebook functionality in general, this paper demonstrates the support system specifically on an example application that we are preparing for a controlled clinical evaluation. At last we discuss the difference between Tracebook and other support systems which also rely on a checklist format

DCCSS:a meta-model for dynamic clinical checklist support systems

Clinical safety checklists receive much research attention since they can reduce medical errors and improve patient safety. Computerized checklist support systems are also being developed actively. Such systems should individualize checklists based on information from the patient’s medical record while also considering the context of the clinical workflows. Unfortunately, the form definitions, database queries and workflow definitions related to dynamic checklists are too often hard-coded in the source code of the support systems. This increases the cognitive effort for the clinical stakeholders in the design process, it complicates the sharing of dynamic checklist definitions as well as the interoperability with other information systems. In this paper, we address these issues by contributing the DCCSS meta-model which enables the model-based development of dynamic checklist support systems. DCCSS was designed as an incremental extension of standard meta-models, which enables the reuse of generic model editors in a novel setting. In particular, DCCSS integrates the Business Process Model and Notation (BPMN) and the Guideline Interchange Format (GLIF), which represent best of breed languages for clinical workflow modeling and clinical rule modeling respectively. We also demonstrate one of the use cases where DCCSS has already been applied in a clinical setting

Frozen section analysis of sentinel lymph nodes in patients with breast cancer does not impair the probability to detect lymph node metastases

Intra-operative frozen section analysis (FS analysis) of sentinel lymph nodes (SLNs) in patients with breast cancer can prevent a second operation for axillary lymph node dissection. In contrast, loss of tissue during FS analysis may impair the probability to detect lymph node metastases. To determine the effect of tissue loss on the probability of detection of metastases, dimensions and tissue loss resulting from intra-operative frozen section analysis were measured for 21 SLNs. In a mathematical model, the influence of tissue loss on the probability to detect metastases was calculated in relation to SLN size for various pathology protocols: an American, a widely used European, the extensive ‘Milan’ and the Dutch protocol. For median-sized SLN 11 × 8 × 5 mm (length × width × height), FS analysis led to a median loss of 680 μm (13.6%) of the height of the SLN. Irrespective of SLN size or used pathology protocol, the probability of detecting 2 mm metastases remained unchanged or even increased (0–12.8%). Moreover, the probability to detect 0.2 mm metastases increased for the majority of tested combinations of SLN size, tissue loss and used protocol. Only when combining maximum tissue loss and smallest SLN size in the Dutch protocol, or when applying the extensive Milan protocol on a median-sized SLN, the probability to detect 0.2 mm metastases decreased by 2.7% and 14.3%, respectively. Contrary to ‘common knowledge’, doing FS analysis of SLNs does not impair the probability to detect lymph node metastases

Soft tissue angiofibroma: Clinicopathologic, immunohistochemical and molecular analysis of 14 cases

Soft tissue angiofibroma is rare and has characteristic histomorphological and genetic features. For diagnostic purposes, there are no specific antibodies available. Fourteen lesions (6 females, 8 males; age range 7‐67 years) of the lower extremities (12) and trunk (2) were investigated by immunohistochemistry, including for the first time NCOA2. NCOA2 was also tested in a control group of other spindle cell lesions. The known fusion‐genes (AHRR‐NCOA2 and GTF2I‐NCOA2) were examined using RT‐PCR in order to evaluate their diagnostic value. Cases in which no fusion gene was detected were additionally analysed by RNA sequencing. All cases tested showed nuclear expression of NCOA2. However, this was not specific since other spindle cell neoplasms also expressed this marker in a high percentage of cases. Other variably positive markers were EMA, SMA, desmin and CD34. STAT6 was negative in the cases tested. By RT‐PCR for the most frequently observed fusions, an AHRR‐NCOA2 fusion transcript was found in 9/14 cases. GTF2I‐NCOA2 was not detected in the remaining cases (n = 3). RNA sequencing revealed three additional positive cases; two harbored a AHRR‐NCOA2 fusion and one case a novel GAB1‐ABL1 fusion. Two cases failed molecular analysis due to poor RNA quality. In conclusion, the AHRR‐NCOA2 fusion is a frequent finding in soft tissue angiofibroma, while GTF2I‐NCOA2 seems to be a rare genetic event. For the first time, we report a GAB1‐ABL1 fusion in a soft tissue angiofibroma of a child. Nuclear expression of NCOA2 is not discriminating when compared with other spindle cell neoplasms

Endemic and emerging acute virus infections in Indonesia: an overview of the past decade and implications for the future

Being the largest archipelago country in the world, with a tropical climate and a unique flora and fauna, Indonesia habitats one of the most diverse biome in the world. These characteristics make Indonesia a popular travel destination, with tourism numbers increasing yearly. These characteristics also facilitate the transmission of zoonosis and provide ideal living and breading circumstances for arthropods, known vectors for viral diseases. A review of the past 10 years of literature, reports of the Ministry of Health, Republic of Indonesia and ProMED-mail shows a significant increase in dengue infection incidence. Furthermore, chikungunya, Japanese encephalitis and rabies are proven to be endemic in Indonesia. The combination of cohort studies, governmental data and ProMED-mail reveals an integrated overview for those working in travel medicine and public health, focusing on both endemic and emerging acute virus infections. This review summarizes the epidemiology of acute virus infections in Indonesia, including outbreak reports, as well as public health response measurements and their potential or efficacy. Knowledge about human behavio

Proteoglycan 4 modulates osteogenic smooth muscle cell differentiation during vascular remodeling and intimal calcification

Calcification is a prominent feature of late-stage atherosclerosis, but the mechanisms driving this process are unclear. Using a biobank of carotid endarterectomies, we recently showed that Proteoglycan 4 (PRG4) is a key molecular signature of calcified plaques, expressed in smooth muscle cell (SMC) rich regions. Here, we aimed to unravel the PRG4 role in vascular remodeling and intimal calcification. PRG4 expression in human carotid endarterectomies correlated with calcification assessed by preoperative computed tomographies. PRG4 localized to SMCs in early intimal thickening, while in advanced lesions it was found in the extracellular matrix, surrounding macro-calcifications. In experimental models, Prg4 was upregulated in SMCs from partially ligated ApoE(-/-) mice and rat carotid intimal hyperplasia, correlating with osteogenic markers and TGFb1. Furthermore, PRG4 was enriched in cells positive for chondrogenic marker SOX9 and around plaque calcifications in ApoE(-/-) mice on warfarin. In vitro, PRG4 was induced in SMCs by IFNg, TGFb1 and calcifying medium, while SMC markers were repressed under calcifying conditions. Silencing experiments showed that PRG4 expression was driven by transcription factors SMAD3 and SOX9. Functionally, the addition of recombinant human PRG4 increased ectopic SMC calcification, while arresting cell migration and proliferation. Mechanistically, it suppressed endogenous PRG4, SMAD3 and SOX9, and restored SMC markers' expression. PRG4 modulates SMC function and osteogenic phenotype during intimal remodeling and macro-calcification in response to TGFb1 signaling, SMAD3 and SOX9 activation. The effects of PRG4 on SMC phenotype and calcification suggest its role in atherosclerotic plaque stability, warranting further investigations.Vascular Surger