Predicting Patient Status in Chronic Thromboembolic Pulmonary Hypertension Using a Biophysical Model.

Chronic thromboembolic pulmonary hypertension (CTEPH) involves abnormally high blood pressure in the pulmonary vessels and is associated with small vessel vasculopathy and pre-capillary proximal occlusions. Management of CTEPH disease is challenging, therefore accurate diagnosis is crucial in ensuring effective treatment and improved patient outcomes. The treatment of choice for CTEPH is pulmonary endarterectomy, which is an invasive surgical intervention to remove thrombi. Following PEA, a number of patients experience poor outcomes or worse-than-expected improvements, which may indicate that they have significant small vessel disease. A method that can predict the extent of distal remodelling may provide useful clinical information to plan appropriate CTEPH patient treatment. Here, a novel biophysical modelling approach has been developed to estimate and quantify the extent of distal remodelling. This method includes a combination of mathematical modelling and computed tomography pulmonary angiography to first model the geometry of the pulmonary arteries and to identify the under-perfused regions in CTEPH. The geometric model is then used alongside haemodynamic measurements from right heart catheterisation to predict distal remodelling. In this study, the method is tested and validated using synthetically generated remodelling data. Then, a preliminary application of this technique to patient data is shown to demonstrate the potential of the approach for use in the clinical setting.Clinical relevance- Patient-specific modelling can help provide useful information regarding the extent of distal vasculopathy on a per-patient basis, which remains challenging. Physicians can be unsure of outcomes following pulmonary endarterectomy. Therefore, the predictive aspect of the patient's response to surgery can help with clinical decision-making.

Gadoxetic acid in hepatocellular carcinoma and liver metastases: pearls and pitfalls.

Gadoxetic disodium (Primovist) is a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent with increasing popularity with its unique dual dynamic and excretory properties in focal liver lesion detection and characterisation. In-depth knowledge of its diagnostic utility and pitfalls in hepatocellular carcinoma (HCC) and liver metastases is crucial in facilitating clinical management. The current article reviews the pearls and pitfalls in these aspects with highlights from the latest research evidence. Pearls for common usage of Primovist in HCC includes detection of precursor cancer lesions in cirrhotic patients. Hepatobiliary phase hypointensity precedes arterial phase hyperenhancement (APHE) in hepatocarcinogenesis. Hepatobiliary phase hypointense nodules without APHE can represent early or progressed hepatocellular carcinoma (HCC) and high-grade dysplastic nodules. In addition, Primovist is useful to differentiate HCC from pseudolesions. Pitfalls in diagnosing HCC include transient tachypnoea in the arterial phase, rare hepatobiliary phase hyperintense HCC, and decompensated liver cirrhosis compromising image quality. Primovist is currently the most sensitive technique in diagnosing liver metastases before curative hepatic resection. Other patterns of enhancement of liver metastases, "disappearing" liver metastases are important pitfalls. Radiologists should be aware of the diagnostic utility, limitations, and potential pitfalls for the common usage of hepatobiliary specific contrast agent in liver MRI.

Metacognitive-Focused Occupational Therapy for Substance Abuse in Medical-Social Service Collaboration: a Case Report.

We describe a 26-year-old man who underwent Metacognitive-Focused Occupational Therapy for his substance abuse problems.

The many facets of neuropathic arthropathy.

Neuropathic arthropathy, also known as Charcot arthropathy, refers to progressive and occasionally rapid joint destruction that results from underlying disorders of the nervous system. This pictorial essay aims to illustrate various radiologic findings in neuropathic arthropathy using various examples in the upper and lower limbs and in the spine. Pearls for radiologic diagnosis, clinical differential considerations and possible complications are discussed individually for each joint. MR imaging techniques for differentiating infection and neuropathic arthropathy are explained with examples. Management issues are outlined.

High-throughput screening of microchip-synthesized genes in programmable double-emulsion droplets.

The rapid advances in synthetic biology and biotechnology are increasingly demanding high-throughput screening technology, such as screening of the functionalities of synthetic genes for optimization of protein expression. Compartmentalization of single cells in water-in-oil (W/O) emulsion droplets allows screening of a vast number of individualized assays, and recent advances in automated microfluidic devices further help realize the potential of droplet technology for high-throughput screening. However these single-emulsion droplets are incompatible with aqueous phase analysis and the inner droplet environment cannot easily communicate with the external phase. We present a high-throughput, miniaturized screening platform for microchip-synthesized genes using microfluidics-generated water-in-oil-in-water (W/O/W) double emulsion (DE) droplets that overcome these limitations. Synthetic gene variants of fluorescent proteins are synthesized with a custom-built microarray inkjet synthesizer, which are then screened for expression in Escherichia coli (E. coli) cells. Bacteria bearing individual fluorescent gene variants are encapsulated as single cells into DE droplets where fluorescence signals are enhanced by 100 times within 24 h of proliferation. Enrichment of functionally-correct genes by employing an error correction method is demonstrated by screening DE droplets containing fluorescent clones of bacteria with the red fluorescent protein (rfp) gene. Permeation of isopropyl ß-d-1-thiogalactopyranoside (IPTG) through the thin oil layer from the external solution initiates target gene expression. The induced expression of the synthetic fluorescent proteins from at least ∼100 bacteria per droplet generates detectable fluorescence signals to enable fluorescence-activated cell sorting (FACS) of the intact droplets. This technology obviates time- and labor-intensive cell culture typically required in conventional bulk experiment.

Adherent-invasive Escherichia coli induce claudin-2 expression and barrier defect in CEABAC10 mice and Crohn's disease patients.

BACKGROUND: Abnormal expression of CEACAM6 observed on the ileal epithelium in Crohn's disease (CD) patients allows adherent-invasive Escherichia coli (AIEC) to colonize gut mucosa. Since intestinal permeability is significantly increased in CD patients, we aimed at investigating whether and how AIEC alter barrier function. METHODS: Tissue microarray was performed on ileal biopsies from CD patients in quiescent and active phases. CEABAC10 or wildtype mice were orally challenged with 10(9) bacteria. Intestinal permeability was assessed by measuring 4 kDa dextran-FITC flux in serum, barrier integrity was analyzed using biotin tracer experiment, and claudin-2 protein immunostaining. Bacterial translocation was analyzed in Ussing chambers. RESULTS: Pore-forming tight junction protein claudin-2 is strongly expressed in the ileum of 51% patients in quiescent phase and in 49% of the patients with active CD. Infection of CEABAC10 transgenic mice expressing human CEACAMs with AIEC, but not with nonpathogenic E. coli, led to a significant 3.0-fold increase in intestinal permeability and to disruption of mucosal integrity in a type 1 pili-dependent mechanism. This is consistent with the claudin-2 abnormal expression at the plasma membrane of intestinal epithelial cells observed in AIEC-infected CEABAC10 mice. AIEC bacteria were able to translocate through CEABAC10 intestinal mucosa. CONCLUSIONS: These findings strongly support the hypothesis that AIEC type 1 pili-mediated interaction with CEACAM6 abnormally expressed in the quiescent phase of CD may disrupt intestinal barrier integrity before the onset of inflammation. Thus, therapeutic targeting claudin-2 induced by AIEC infection could be a new clinical strategy for preserving intestinal barrier function in CD patients.