Campylobacter concisus Pseudo-Outbreak Caused by Improved Culture Conditions

An unusual increase in the number of Campylobacter concisus isolates found in stool cultures provoked an outbreak investigation at Bern University Hospital. No epidemiological links were found between the cases, and the Campylobacter isolates were clonally unrelated. A change in culture conditions to a hydrogen-rich atmosphere enhancing growth of C. concisus was deemed responsible for this pseudo-outbreak.     

Failure on voxilaprevir,velpatasvir, sofosbuvir and efficacy of rescue therapy

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BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma

Purpose BRAF ^V600E mutation represents the most common oncogenic event in sporadic papillary thyroid cancer (PTC). There are, however, significant discrepancies regarding the overall frequency, its prevalence in PTC‐variants, and its relationship with clinico‐pathological parameters of poor outcome. Moreover, the impact of BRAF^V600E mutants on tumour‐related patient's death has not been evaluated. Design We analysed, by PCR‐SSCP and/or PCR‐direct sequencing, exons 8, 10, 11 and 15 of BRAF in 113 tumour samples from 49 PTC‐patients. Matched lymph node metastases and/or distant metastases (DMs) were screened in 35 patients. Focal changes in the growth pattern or microscopic grade within the primary tumour (Pt) or the metastases were separately genotyped. Mutations at H‐, K‐, N‐ras and PIK3CA exons 9 and 20 were also investigated. For comparison with PTC cases, the BRAF and Ras mutational status was evaluated in 89 specimens obtained from 24 poorly differentiated thyroid carcinomas (PDCs) and 36 anaplastic thyroid carcinomas (ATCs). Results BRAF ^V600E was found in 13/16 classical PTCs (CL‐PTCs), 6/17 follicular variant PTCs (FV‐PTCs) and 8/16 mixed (papillary/follicular) PTCs (Mx‐PTCs), being significantly associated with CL‐PTCs (P = 0·015). BRAF^V600E segregated with metastatic PTC‐cells in 43% of the patients, but only one DM disclosed the mutation. PTC‐tumours featuring concurrent less‐differentiated foci were BRAF wild‐type in both components. Noteworthy, the frequency of BRAF mutations among PDCs and ATCs resulted considerably lower (16·6% and 25%, respectively) than in PTCs (55%). The prevalence of Ras mutations among PDCs and ATCs (46% and 36%, respectively) was, however, much higher than in PTCs (14%). Five (71%) of the patients who died of PTC displayed somatic mutations. Four of them had other gene alteration associated with BRAF^V600E and the only one that did not, BRAF^V600E was restricted to the Pt. The occurrence of BRAF^V600E associated with other genetic events was an independent predictor of DMs during follow‐up, recurrence and tumour‐related death. Remarkably, two PDCs (8·3%) and five ATCs (14%) revealed concurrent BRAF and Ras mutations. Conclusion BRAF ^V600E‘alone’ does not represent a marker for poor outcome, however, when associated with alterations in other genes identifies a subset of PTCs with increased risk of recurrence and decreased survival.     

Subclavian coronary steal syndrome: an obligatory common fate between subclavian artery,internal mammary graft and coronary circulation

The long-term patency of the left internal mammary artery (IMA) has made it the preferred conduit for myocardial revascularization. The proximal segment of the subclavian artery becomes functionally connected to the coronary circulation as a result of IMA implantation during coronary artery bypass surgery. The subclavian coronary steal syndrome results from stenosis in the left subclavian artery proximal to the IMA, compromising blood flow to the myocardium. We describe 7 patients, aged 55-75 years, 1.7-10.5 years after coronary bypass who presented with recurrent angina due to subclavian artery stenosis. The IMA graft was found open in each patient. A true steal mechanism was not demonstrated, casting doubt on the syndrome's traditional name. Angioplasty and stenting of the subclavian artery resulted in the immediate disappearance of angina and continuous benefit at a follow-up of 3-32 months. The subclavian coronary steal syndrome, although rare, is a severe condition readily treated by angioplasty and stenting.     

An empirical model of the Baltic Sea reveals the importance of social dynamics for ecological regime shifts

Regime shifts triggered by human activities and environmental changes have led to significant ecological and socioeconomic consequences in marine and terrestrial ecosystems worldwide. Ecological processes and feedbacks associated with regime shifts have received considerable attention, but human individual and collective behavior is rarely treated as an integrated component of such shifts. Here, we used generalized modeling to develop a coupled social–ecological model that integrated rich social and ecological data to investigate the role of social dynamics in the 1980s Baltic Sea cod boom and collapse. We showed that psychological, economic, and regulatory aspects of fisher decision making, in addition to ecological interactions, contributed both to the temporary persistence of the cod boom and to its subsequent collapse. These features of the social–ecological system also would have limited the effectiveness of stronger fishery regulations. Our results provide quantitative, empirical evidence that incorporating social dynamics into models of natural resources is critical for understanding how resources can be managed sustainably. We also show that generalized modeling, which is well-suited to collaborative model development and does not require detailed specification of causal relationships between system variables, can help tackle the complexities involved in creating and analyzing social–ecological models.In recent decades, the world’s biological and physical systems have experienced dramatic change (1, 2). Many marine ecosystems, for example, have undergone abrupt changes known as regime shifts (3, 4). In one prominent case, the Baltic cod fishery suddenly changed in the 1980s from historically high cod biomass and catches (henceforth the “cod boom”) to a sprat-dominant ecosystem with low cod abundance (5–8). This collapse, generally understood to have been precipitated by deteriorating environmental conditions and overfishing (7), had substantial negative socioeconomic impact on Baltic Sea fisheries, including among others the small-scale coastal fishery (9).Ecological analyses of regime shifts, such as of the Baltic cod fishery (10), can capture the complex interplay of ecological and physical processes and drivers that trigger the shift. Numerous studies, however, have shown that understanding individual and collective human behavior is also critical for managing natural resources (11, 12) such as marine ecosystems (13, 14). Social–ecological system research responds to the need to incorporate humans as part of ecosystems by treating natural resource use as arising from linked systems of humans and nature, so-called social–ecological systems. Social–ecological system dynamics result from feedback loops involving biophysical processes, human behavior, and institutional processes within given social and biophysical contexts (15). Formal, quantitative analyses of the contributions of the social and biophysical subsystems to a social–ecological system’s dynamics are rare, however, because knowledge of social–ecological systems is often partial and spread over multiple disciplines (16).Here, we tested the influence of social dynamics on a regime shift in a marine ecosystem using a formal modeling framework. Specifically, we investigated the significance of fisher decision making, as influenced by psychological, economic, and regulatory factors, on the 1980s boom and collapse of the Eastern Baltic cod stock. In a significant advance for natural resource modeling, and for social–ecological modeling more generally, use of the generalized modeling approach (17, 18) enabled us to empirically parameterize, dynamically model, and analyze the qualitative social and ecological dynamics of the Baltic cod fishery at comparable levels of detail and without detailed specification of causal relationships. The Baltic cod fishery was selected because the ecological dynamics during the cod boom and collapse have been well-studied (10, 19, 20), and information about fisher behavior and institutional settings, such as regulation and subsidy policy, is available. Additionally, the cod boom and collapse are qualitatively distinct features of the social–ecological system’s dynamics that are amenable to the concepts and methods of dynamical systems theory (21), such as stability.     

Gradient Spin Echo (GraSE) imaging for fast myocardial T2 mapping

Background

Quantitative Cardiovascular Magnetic Resonance (CMR) techniques have gained high interest in CMR research. Myocardial T2 mapping is thought to be helpful in diagnosis of acute myocardial conditions associated with myocardial edema. In this study we aimed to establish a technique for myocardial T2 mapping based on gradient-spin-echo (GraSE) imaging.

Methods

The local ethics committee approved this prospective study. Written informed consent was obtained from all subjects prior to CMR. A modified GraSE sequence allowing for myocardial T2 mapping in a single breath-hold per slice using ECG-triggered acquisition of a black blood multi-echo series was developed at 1.5 Tesla. Myocardial T2 relaxation time (T2-RT) was determined by maximum likelihood estimation from magnitude phased-array multi-echo data. Four GraSE sequence variants with varying number of acquired echoes and resolution were evaluated in-vitro and in 20 healthy volunteers. Inter-study reproducibility was assessed in a subset of five volunteers. The sequence with the best overall performance was further evaluated by assessment of intra- and inter-observer agreement in all volunteers, and then implemented into the clinical CMR protocol of five patients with acute myocardial injury (myocarditis, takotsubo cardiomyopathy and myocardial infarction).

Results

In-vitro studies revealed the need for well defined sequence settings to obtain accurate T2-RT measurements with GraSE. An optimized 6-echo GraSE sequence yielded an excellent agreement with the gold standard Carr-Purcell-Meiboom-Gill sequence. Global myocardial T2 relaxation times in healthy volunteers was 52.2 ± 2.0 ms (mean ± standard deviation). Mean difference between repeated examinations (n = 5) was −0.02 ms with 95% limits of agreement (LoA) of [−4.7; 4.7] ms. Intra-reader and inter-reader agreement was excellent with mean differences of −0.1 ms, 95% LoA = [−1.3; 1.2] ms and 0.1 ms, 95% LoA = [−1.5; 1.6] ms, respectively (n = 20). In patients with acute myocardial injury global myocardial T2-RTs were prolonged (mean: 61.3 ± 6.7 ms).

Conclusion

Using an optimized GraSE sequence CMR allows for robust, reliable, fast myocardial T2 mapping and quantitative tissue characterization. Clinically, the GraSE-based T2-mapping has the potential to complement qualitative CMR in patients with acute myocardial injuries.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-015-0127-z) contains supplementary material, which is available to authorized users.     

Gum arabic promotes rat jejunal sodium and water absorption from oral rehydration solutions in two models of diarrhea

BACKGROUND & AIMS: We have shown that addition of gum arabic (GA) to a 90 mmol/L sodium-111 mmol/L glucose oral rehydration solution (ORS) enhances its effectiveness for water and electrolyte absorption in normal rats. The present study extends these observations on GA in ORS to two rat models of diarrheal disease. METHODS: Juvenile rats were either treated for 1 week with magnesium citrate-phenolphthalein to produce chronic osmotic-secretory diarrhea or luminally exposed to 10 mmol/L theophylline to induce jejunal secretion. In both models jejunal perfusion was used to assess absorption. RESULTS: Addition of 2.5 or 5.0 g/L GA to ORS increased roughly twofold absorption of sodium, potassium, and water in the model of chronic osmotic-secretory diarrhea. Rats perfused with GA-supplemented ORS showed an expansion of the basolateral intercellular spaces between villus absorptive epithelial cells and the lamina propria, reflecting enhanced water and sodium absorption. Similarly, addition of 2.5, 5.0, or 10.0 g/L GA to the ORS neutralized theophylline-induced abolition of net sodium and potassium absorption and reversed water and glucose malabsorption. CONCLUSIONS: These experimental studies in models of diarrhea suggest that GA may be a useful additive to ORS for the potentiation of water and electrolyte absorption. (Gastroenterology 1997 Jun;112(6):1979-85)     

Separation and analysis of subcellular organelles in a human promyelocytic leukemia cell line, HL-60: application to the study of myeloid lysosomal enzyme synthesis and processing

We describe a system for analysis of the intracellular pathways in the biosynthesis and packaging of functionally important proteins in human myeloid cells. The human promyelocytic cell line HL-60 was used since peripheral blood neutrophils are terminally differentiated and do not actively synthesize protein. Cells were disrupted by nitrogen cavitation and subcellular organelles in postnuclear supernatant separated on a discontinuous gradient of Percoll modified to resolve organelles important in protein synthesis. This Percoll gradient separated azurophilic granules from less dense organelles and partially separated the less dense organelles from one another. Approximate densities of organelles identified by electron microscopy and by biochemical markers are azurophilic granules, 1.102 g/mL; endoplasmic reticulum, 1.039 g/mL; Golgi apparatus, 1.032 g/mL; and plasma membrane, 1.027 g/mL. We validated the utility of this method of subcellular fractionation by examining intracellular transport of myeloperoxidase, a myeloid lysosomal enzyme present in azurophilic granules. The subunits of mature myeloperoxidase (molecular weight [mol wt] = 59,000 and 13,500) cosediment with biochemical markers for lysosomes, whereas the large-mol wt (89,000) precursor forms cosediments with biochemical markers of less dense organelles. Within the limits of assay sensitivity, the 89,000-mol wt precursor is enzymatically inactive and has no spectral evidence for a heme group, suggesting that precursors of myeloperoxidase may undergo proteolytic maturation in a prelysosomal compartment with concomitant incorporation of a heme group and acquisition of enzymatic activity. This system of analysis should be suitable for the identification, subcellular localization, and maturational analysis of other myeloid lysosomal enzymes as well as functionally important membrane proteins.