Evaluation of the Suprafascial Thin ALT Flap in Foot and Ankle Reconstruction.

BACKGROUND: Distal lower extremity reconstruction can be challenging in terms of flap design. Bulky flaps result in limited mobility accompanied with the need of customized footwear. Raising the ALT-flap in a superficial fascial plane (thin ALT-flap) can be beneficial. This study evaluates thin ALT-flaps for lower distal extremity reconstruction. METHODS: In a retrospective study, patients that underwent microvascular extremity reconstruction at the level of the ankle and dorsal foot at the University of Freiburg from 2008-2018 were reviewed. RESULTS: 95 patients could be included in the study (35 perforator flaps, 8 fascia flaps and 54 muscle flaps).Among the perforator flaps, 21 ALT-flaps were elevated conventionally and 14 in the superficial fascial plane (thin ALT-flap). Among the conventional ALT-flaps, there was one flap loss (5%) and one successful revision (5%). 5(24%) flaps received secondary thinning. 57%(n = 12) were able to wear conventional footwear. There were 2(15%) successful revisions of thin ALT-flaps. 100% of thin ALT-flaps survived and 85%(n = 11) of the patients wore ordinary footwear after defect coverage.Among fascial flaps, 50%(n = 4) had to be revised with 2(25%) complete and 1 (13%) partial flap loss. All patients achieved mobility in ordinary shoes (n = 8).In muscle flaps, there were 7(13%) revisions and 5(9%) flap losses. 5(9%) flaps received secondary thinning. Only 33%(n = 18) were mobile in ordinary footwear. CONCLUSION: The thin ALT-flap is a save one-stage evolution for lower distal extremity reconstruction with a favorable flap survival rate. Compared with conventional ALT-flaps it might be beneficial in reducing the need for expensive custom fitted shoes and secondary thinning procedures.

[Association of Deployment and Tobacco Dependence among Soldiers]. / Zusammenhang von Auslandseinsätzen und Tabakabhängigkeit bei Soldaten.

OBJECTIVE: Smoking is a highly preventable risk factor. The present study investigates whether military operations abroad, as compared to deployment preparation, increase the risk of starting to smoke, enhance tobacco dependence and moderator variables can be identified on smoking behavior. METHOD: The study was conducted at 2 mechanized infantry battalions with N=264 soldiers. The task force completed a deployment in Afghanistan, the control group performed a deployment training. Assessments of tobacco dependence, posttraumatic symptoms, depression and stress were done before (t1) and after (t3) deployment. In addition, one assessment was done at mid-point (t2) during deployment and during the pre-deployment training, respectively. RESULTS: The prevalence rate of smoking soldiers was 56,4%. 51,1% (n=135) of all examined soldiers smoked more than 20 cigarettes per day. The results show a significant increase of tobacco dependence in the task force from t1 to t3 (p=0,040) as compared to the control group. For both groups, there was no increase in starting to smoke during the period of investigation (χ²<1; n. s.). Moderator variables on smoking were not found, but there was a significant increase in posttraumatic stress symptoms in the deployed group (p=0,006). CONCLUSIONS: Perhaps the increase in tobacco dependence in the experimental group can be attributed to the specific burdens of deployment. If high smoking rates were to be found also in other branches of the armed services, effective smoking cessation programs should be offered more widely.

Targeting C-Reactive Protein in Inflammatory Disease by Preventing Conformational Changes.

C-reactive protein (CRP) is a pentraxin that has long been employed as a marker of inflammation in clinical practice. Recent findings brought up the idea of CRP to be not only a systemic marker but also a mediator of inflammation. New studies focused on structural changes of the plasma protein, revealing the existence of two distinct protein conformations associated with opposed inflammatory properties. Native, pentameric CRP (pCRP) is considered to be the circulating precursor form of monomeric CRP (mCRP) that has been identified to be strongly proinflammatory. Recently, a dissociation mechanism of pCRP has been identified on activated platelets and activated/apoptotic cells associated with the amplification of the proinflammatory potential. Correspondingly, CRP deposits found in inflamed tissues have been identified to exhibit the monomeric conformation by using conformation-specific antibodies. Here we review the current literature on the causal role of the dissociation mechanism of pCRP and the genesis of mCRP for the amplification of the proinflammatory potential in inflammatory reactions such as atherosclerosis and ischemia/reperfusion injury. The chance to prevent the formation of proinflammatory mediators in ubiquitous inflammatory cascades has pushed therapeutic strategies by targeting pCRP dissociation in inflammation. In this respect, the development of clinically applicable derivatives of the palindromic compound 1,6-bis(phosphocholine)-hexane (1,6-bis PC) should be a major focus of future CRP research.

Direct determination of large spin-torque nonadiabaticity in vortex core dynamics.

We use a pump-probe photoemission electron microscopy technique to image the displacement of vortex cores in Permalloy discs due to the spin-torque effect during current pulse injection. Exploiting the distinctly different symmetries of the spin torques and the Oersted-field torque with respect to the vortex spin structure we determine the torques unambiguously, and we quantify the amplitude of the strongly debated nonadiabatic spin torque. The nonadiabaticity parameter is found to be ß=0.15±0.07, which is more than an order of magnitude larger than the damping constant α, pointing to strong nonadiabatic transport across the high magnetization gradient vortex spin structures.

Genetic variation of inbreeding depression among floral and fitness traits in Silene nutans.

The magnitude and variation of inbreeding depression (ID) within populations is important for the evolution and maintenance of mixed mating systems. We studied ID and its genetic variation in a range of floral and fitness traits in a small and large population of the perennial herb Silene nutans, using controlled pollinations in a fully factorial North Carolina II design. Floral traits and early fitness traits, that is seed mass and germination rate, were not much affected by inbreeding (delta<0.2). In contrast, 'late' fitness traits and multiplicative fitness suffered severely from inbreeding (delta>0.4). Lack of genetic correlations indicated that ID in floral, early and late traits is genetically decoupled. There was a trend that the smaller population was less affected by ID than the large one, although the differences were not significant for most traits. Hence, evidence for purging of deleterious alleles remains inconclusive in this study. Genetic variation in ID among paternal families was statistically significant in most floral and all seed traits, but not in late fitness traits. However, some paternal families had delta<0.5, even in the multiplicative fitness measure that suffered most from ID (delta=0.74), suggesting that the mixed mating system of S. nutans might be evolutionary stable.

Time-related changes of the intestinal morphology of Atlantic salmon, Salmo salar L., at two different soybean meal inclusion levels.

Abstract Soybean meal (SBM) induces enteritis in the distal intestine of Atlantic salmon. The present study assesses the effects of SBM concentrations on the kinetics of the enteritis process. Fish of 300 g, kept at 12 degrees C, were fed diets with different SBM inclusions: 0%, 10% and 20% SBM for 57 days. Samples of the distal intestine of five fish per treatment were taken for histological and electron microscopical analysis. A semi-quantitative scoring system was used to assess the degree of the morphological changes induced by SBM feeding in the distal intestinal epithelium. The first signs of enteritis appeared earlier in the salmon fed the 20SBM diet than in those fed the 10SBM diet. Thereafter, the condition increased steadily, displaying no signs of recovery. Furthermore, at the lower concentration, the process marking the onset of enteritis began more gradually than at the higher concentration and it displayed a tendency to stabilize after 13-20 days of continuous feeding. Electron microscopy indicated that the endocytosis process was hampered at day 3 of 20SBM and at 7 days of 10SBM. Furthermore, a strong reduction of microvilli was already evident after 7 days of 20SBM feeding, thus indicating a decreased uptake capacity of the distal enterocytes. In addition, transformation and migration of eosinophilic granulocytes was observed, which, in combination with the lysozyme C immunoreactivity supports their protective role during the inflammatory process in the distal gut of Atlantic salmon. It can be concluded that the severity of enteritis and its kinetics are concentration-dependent, showing no signs of recovery during feeding with diets containing SBM.

Use of solid phosphorus fractionation data to evaluate phosphorus release from waste activated sludge.

Waste activated sludge (WAS) can become an important source of phosphorus (P). P speciation was examined under anaerobic conditions, with different pH (4, 6 and 8) and temperatures (10, 20 and 35 °C). Aqueous P was measured and an extraction protocol was used to find three solid phosphorus fractions. A pH of 4 and a temperature of 35 °C gave a maximum of 51% of total P solubilized in 22 days with 50% of total P solubilized in 7 days. Batch tests indicate that little pH depression is needed to release non-apatite inorganic P (including microbial polyphosphate), while a pH of 4 rather than 6 will release more apatite inorganic P, and that organic P is relatively more difficult to release from WAS. Fractionation analysis of P in WAS can aid in design of more efficient methods for P recovery from WAS.

Optimized procedures for generating an enhanced, near physiological 2D culture system from porcine intestinal organoids.

An important practical limitation of the three-dimensional geometry of stem-cell derived intestinal organoids is that it prevents easy access to the apical epithelium for testing food components, microorganisms, bioactive and toxic compounds. To this end, we here report on a new robust method for generating confluent intestinal cell monolayers from single-cell suspensions of enzymatically-dissociated porcine organoids using modified culture conditions. With this method, cell seeding densities can be standardised, overcoming problems with methods based on mechanical dissociation of organoids. Confluent monolayers formed tight junctions with high transepithelial electrical resistance in three days and could be used in experiments for up to two weeks. Multilineage differentiation of ileal stem cells was demonstrated by immunohistochemistry and RT-qPCR of cell-specific transcripts, also unequivocally confirming the controversial existence of Paneth-like cells in the porcine small intestine. The method described here is useful to standardize primary epithelial monolayer formation from intestinal organoids and allows rapid and robust studies of intestinal physiology.

Standardized microgel beads as elastic cell mechanical probes.

Cell mechanical measurements are gaining increasing interest in biological and biomedical studies. However, there are no standardized calibration particles available that permit the cross-comparison of different measurement techniques operating at different stresses and time-scales. Here we present the rational design, production, and comprehensive characterization of poly-acrylamide (PAAm) microgel beads mimicking size and overall mechanics of biological cells. We produced mono-disperse beads at rates of 20-60 kHz by means of a microfluidic droplet generator, where the pre-gel composition was adjusted to tune the beads' elasticity in the range of cell and tissue relevant mechanical properties. We verified bead homogeneity by optical diffraction tomography and Brillouin microscopy. Consistent elastic behavior of microgel beads at different shear rates was confirmed by AFM-enabled nanoindentation and real-time deformability cytometry (RT-DC). The remaining inherent variability in elastic modulus was rationalized using polymer theory and effectively reduced by sorting based on forward-scattering using conventional flow cytometry. Our results show that PAAm microgel beads can be standardized as mechanical probes, to serve not only for validation and calibration of cell mechanical measurements, but also as cell-scale stress sensors.

Circulating Tumor Cells: Fluid Surrogates of Solid Tumors.

Evaluation of circulating tumor cells (CTCs) has demonstrated clinical validity as a prognostic tool based on enumeration, but since the introduction of this tool to the clinic in 2004, further clinical utility and widespread adoption have been limited. However, immense efforts have been undertaken to further the understanding of the mechanisms behind the biology and kinetics of these rare cells, and progress continues toward better applicability in the clinic. This review describes recent advances within the field, with a particular focus on understanding the biological significance of CTCs, and summarizes emerging methods for identifying, isolating, and interrogating the cells that may provide technical advantages allowing for the discovery of more specific clinical applications. Included is an atlas of high-definition images of CTCs from various cancer types, including uncommon CTCs captured only by broadly inclusive nonenrichment techniques.

Critical phenomena of a hybrid phase transition in cluster merging dynamics.

Recently, a hybrid percolation transition (HPT) that exhibits both a discontinuous transition and critical behavior at the same transition point has been observed in diverse complex systems. While the HPT induced by avalanche dynamics has been studied extensively, the HPT induced by cluster merging dynamics (HPT-CMD) has received little attention. Here, we aim to develop a theoretical framework for the HPT-CMD. We find that two correlation-length exponents are necessary for characterizing the giant cluster and finite clusters separately. The conventional formula of the fractal dimension in terms of the critical exponents is not valid. Neither the giant nor finite clusters are fractals, but they have fractal boundaries. A finite-size scaling method for the HPT-CMD is also introduced.

Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: a forgotten pearl.

Histopathology of bone marrow (BM) biopsies plays a crucial role in the interdisciplinary approach to diagnosis and classification of chronic myeloproliferative disorders (CMPDs). Based on careful clinicopathologic studies, BM features are critical determinants that help to predict overall prognosis, to detect complications such as progression to myelofibrosis and blast crisis, and to assess therapy-related changes. A systematic evaluation of BM histopathology allows an objective identification of cases of (true) essential thrombocythemia (ET) and their separation from (false) ET, which often is the prodromal stage of chronic idiopathic myelofibrosis (CIMF). By follow-up examinations that include BM biopsies, the progression of the disease process is unveiled, which is especially important for patients with initial (early) polycythemia vera and prefibrotic CIMF that may require a different therapeutic approach than the full-blown stages. In conclusion, BM biopsy should be considered as major diagnostic tool for evaluation and follow-up of patients enrolled in prospective studies.

Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM: The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS: This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS: Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.

[A 29-year-old man with Takayasu's arteritis]. / Ein 29-jähriger Patient mit dem Bild einer Takayasu-Arteriitis.

We report on a 29-year-old male patient with collapse and recurrent vertigo. Physical examination showed a bruit of the left common carotid artery on auscultation and a pulselessness of both arms. The diagnosis of Takayasu's arteritis was based on the results of duplex sonography, MRI and angiography (stenosis and occlusion of extracranial arteries). Laboratory results did not reveal any specific changes. Combined treatment with prednisolone and azathioprine was initiated. After 12 days we saw an improvement of duplexsonographical and laboratory findings. Takayasu's disease should be considered as a differential diagnosis in patients with stenosis and occlusions of the aortic arch and its main branches (e.g. pulselessness). MRI is a valuable method in detection of wall abnormalities of the aorta, its branches and other large arteries.

The 2016 revision of WHO classification of myeloproliferative neoplasms: Clinical and molecular advances.

Clinical evidence supports the need of changing the diagnostic criteria of the 2008 updated WHO classification for polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In JAK2-mutated patients who show characteristic bone marrow (BM) morphology, clinical studies demonstrated that a hemoglobin level of 16.5g/dL in men and 16.0g/dl for women or a hematocrit value of 49% in men and 48% in women are the optimal cut off levels for distinguishing JAK2-mutated ET from "masked/prodromal" PV. Therefore BM morphology was upgraded to a major diagnostic criterion. Regarding ET the key issue was to improve standardization of prominent BM features enhancing differentiation between "true" ET and prefibrotic/early primary myelofibrosis (prePMF). These two entities have shown a different epidemiology and clinical outcomes. Concerning prePMF a more explicit clinical characterization of minor criteria is mandated for an improved distinction from ET and overt PMF and accurate diagnosis and outcome prediction.

Clinical impact of bone marrow morphology for the diagnosis of essential thrombocythemia: comparison between the BCSH and the WHO criteria.

Essential thrombocythemia (ET) is currently diagnosed either by the British Committee of Standards in Haematology (BCSH) criteria that are predominantly based on exclusion and not necessarily on bone marrow (BM) morphology, or the World Health Organization (WHO) criteria that require BM examination as essential criterion. We studied the morphological and clinical features in patients diagnosed according either to the BCSH (n=238) or the WHO guidelines (n=232). The BCSH-defined ET cohort was re-evaluated by applying the WHO classification. At presentation, patients of the BCSH group showed significantly higher values of serum lactate dehydrogenase and had palpable splenomegaly more frequently. Following the WHO criteria, the re-evaluation of the BCSH-diagnosed ET cohort displayed a heterogeneous population with 141 (59.2%) ET, 77 (32.4%) prefibrotic primary myelofibrosis (prePMF), 16 (6.7%) polycythemia vera and 4 (1.7%) primary myelofibrosis. Contrasting WHO-confirmed ET, the BCSH cohort revealed a significant worsening of fibrosis-free survival and prognosis. As demonstrated by the clinical data and different outcomes between WHO-diagnosed ET and prePMF, these adverse features were generated by the inadvertent inclusion of prePMF to the BCSH group. Taken together, the diagnosis of ET without a scrutinized examination of BM biopsy specimens will generate a heterogeneous cohort of patients impairing an appropriate clinical management.

Effect of temperature on membrane fluidity and calcium conductance of the excitable ciliary membrane from Paramecium.

Fluorescence anisotropy and average fluorescence lifetime of diphenylhexatriene were measured in artificial lipid membrane vesicles. Within the temperature range investigated (15-52 degrees C) both parameters correlate and can be used interchangeably to measure membrane fluidity. Fluorescence anisotropy of DPH in membrane vesicles of cilia from the protozoan Paramecium tetraurelia decreased slightly from 5 to 37 degrees C, yet, no phase transition was observed. An estimated flow activation energy of approx. 2 kcal/mol indicated that the ciliary membrane is very rigid and not readily susceptible to environmental stimuli. The ciliary membrane contains two domains of different membrane fluidity as indicated by two distinct fluorescence lifetimes of diphenylhexatriene of 7.9 and 12.4 ns, respectively. Ca2+ flux into ciliary membrane vesicles of Paramecium as measured with the Ca2+ indicator dye arsenazo III showed a nonlinear temperature dependency from 5 to 35 degrees C with a minimum around 15 degrees C and increasing flux rates at higher and lower temperatures. The fraction of vesicles permeable for Ca2+ remained unaffected by temperature. The differences in temperature dependency of Ca2+ conductance and membrane fluidity indicate that the Ca2+ permeability of the ciliary membrane is a membrane property which is not directly affected by the fluidity of its lipid environment.