Variance sum rule for entropy production.

Entropy production is the hallmark of nonequilibrium physics, quantifying irreversibility, dissipation, and the efficiency of energy transduction processes. Despite many efforts, its measurement at the nanoscale remains challenging. We introduce a variance sum rule (VSR) for displacement and force variances that permits us to measure the entropy production rate σ in nonequilibrium steady states. We first illustrate it for directly measurable forces, such as an active Brownian particle in an optical trap. We then apply the VSR to flickering experiments in human red blood cells. We find that σ is spatially heterogeneous with a finite correlation length, and its average value agrees with calorimetry measurements. The VSR paves the way to derive σ using force spectroscopy and time-resolved imaging in living and active matter.

Fluctuations of a membrane nanotube covered with an actin sleeve.

Many biological functions rely on the reshaping of cell membranes, in particular into nanotubes, which are covered in vivo by dynamic actin networks. Nanotubes are subject to thermal fluctuations, but the effect of these on cell functions is unknown. Here, we form nanotubes from liposomes using an optically trapped bead adhering to the liposome membrane. From the power spectral density of this bead, we study the nanotube fluctuations in the range of membrane tensions measured in vivo. We show that an actin sleeve covering the nanotube damps its high-frequency fluctuations because of the network viscoelasticity. Our work paves the way for further studies of the effect of nanotube fluctuations on cellular functions.

Actin modulates shape and mechanics of tubular membranes.

The actin cytoskeleton shapes cells and also organizes internal membranous compartments. In particular, it interacts with membranes for intracellular transport of material in mammalian cells, yeast, or plant cells. Tubular membrane intermediates, pulled along microtubule tracks, are formed during this process and destabilize into vesicles. While the role of actin in tubule destabilization through scission is suggested, literature also provides examples of actin-mediated stabilization of membranous structures. To directly address this apparent contradiction, we mimic the geometry of tubular intermediates with preformed membrane tubes. The growth of an actin sleeve at the tube surface is monitored spatiotemporally. Depending on network cohesiveness, actin is able to entirely stabilize or locally maintain membrane tubes under pulling. On a single tube, thicker portions correlate with the presence of actin. These structures relax over several minutes and may provide enough time and curvature geometries for other proteins to act on tube stability.

Biosynthetic vascular graft: a valuable alternative to traditional replacement materials for treatment of prosthetic aortic graft infection?

BACKGROUND AND AIMS: To report the experience of a tertiary vascular surgery center using Omniflow II® biosynthetic vascular grafts for treatment of prosthetic aortic graft infection. MATERIALS AND METHODS: Retrospective analysis of all patients with prosthetic graft infections who underwent in situ aortic reconstruction using Omniflow II® grafts or other conduits between March 2015 and May 2017. Early and late mortality, perioperative complications, and reinfection rate were analyzed. RESULTS: Sixteen patients (14 males, median age 68.5, range 57-89) with prosthetic aortic graft infection were treated at our center. Eight patients received an Omniflow II® biosynthetic graft, two patients silver-triclosan coated grafts, three patients bovine pericardial tube grafts, and three patients composite bovine pericardial tube grafts with Omniflow II® graft extensions. Perioperative complications occurred in seven patients (43.8%). Early mortality rate was 18.7% (n = 3). In addition, four patients died during follow-up after a median of 11 months (range 0-34 months). We did not observe any reinfections. Bypass grafts were patent in all patients. No major limb amputations were performed during follow-up. CONCLUSION: Treatment of prosthetic aortic graft infection with Omniflow II® vascular grafts is feasible. Graft material seems to have an excellent resistance to infection and might be a valuable alternative to traditional replacement materials. Especially long-term durability has to be continuously monitored and documented.

A comparison of tibial and peroneal venous and HePTFE bypasses in diabetics with critical limb ischemia.

OBJECTIVE: In this study we analyzed the outcome of tibial and peroneal venous and heparin-bonded expanded polytetrafluoroethylene (HePTFE) bypasses in diabetics with critical limb ischemia (CLI). We aimed to verify our hypothesis that HePTFE grafts will achieve acceptable 1-year patency and limb salvage results in patients who lack an adequate vein. METHODS: We conducted a retrospective analysis for all diabetics who underwent tibial bypass surgery in our department between October 2007 and October 2012. The study includes 97 grafts. All these patients were not suited for an endovascular therapy. We used autologous veins in 56 cases (Vein-Group) and HePTFE grafts in 41 cases (HePTFE-Group). Study endpoints were primary and secondary patency, limb salvage, and survival at 2 years postoperatively. RESULTS: Risk factors and indications were similar in both groups. The comparison between HePTFE- and Vein-Group showed significantly different patency rates. At 2 years, primary patency was 39.3% in HePTFE-Group vs. 78.5% in Vein-Group (P = .003) and secondary patency was 47.4% vs. 81.9% (P = .002). Limb salvage at 2 years was 79.3% vs. 87.4% (P = .073) and survival was 64.6% vs. 62.9% (P = .593) at the 2-year mark, with no significant differences. 30-days mortality, graft occlusion and major amputation rate showed no significant differences, either. CONCLUSIONS: This study shows that HePTFE bypasses are a viable option for diabetics undergoing tibial bypass surgery when no adequate vein is available.

Fluctuations of a membrane nanotube revealed by high-resolution force measurements.

Pulling membrane nanotubes from liposomes presents a powerful method to gain access to membrane mechanics. Here we extend classical optical tweezers studies to infer membrane nanotube dynamics with high spatial and temporal resolution. We first validate our force measurement setup by accurately measuring the bending modulus of EPC membrane in tube pulling experiments. Then we record the position signal of a trapped bead when it is connected, or not, to a tube. We derive the fluctuation spectrum of these signals and find that the presence of a membrane nanotube induces higher fluctuations, especially at low frequencies (10-1000 Hz). We analyse these spectra by taking into account the peristaltic modes of nanotube fluctuations. This analysis provides a new experimental framework for a quantitative study of the fluctuations of nanotubular membrane structures that are present in living cells, and now classically used for in vitro biomimetic approaches.

Cell-sized liposome doublets reveal active tension build-up driven by acto-myosin dynamics.

Cells modulate their shape to fulfill specific functions, mediated by the cell cortex, a thin actin shell bound to the plasma membrane. Myosin motor activity, together with actin dynamics, contributes to cortical tension. Here, we examine the individual contributions of actin polymerization and myosin activity to tension increase with a non-invasive method. Cell-sized liposome doublets are covered with either a stabilized actin cortex of preformed actin filaments, or a dynamic branched actin network polymerizing at the membrane. The addition of myosin II minifilaments in both cases triggers a change in doublet shape that is unambiguously related to a tension increase. Preformed actin filaments allow us to evaluate the effect of myosin alone while, with dynamic actin cortices, we examine the synergy of actin polymerization and myosin motors in driving shape changes. Our assay paves the way for a quantification of tension changes triggered by various actin-associated proteins in a cell-sized system.

The impact of infrainguinal endovascular interventions on the results of subsequent femoro-tibial bypass procedures: a retrospective cohort study.

BACKGROUND: Endovascular recanalization has become the accepted first-line treatment strategy for most lower extremity arterial occlusions, especially in patients with critical limb ischemia (Rutherford 4-6). Prior endovascular interventions have been described as risk factors for the outcome of subsequent lower extremity bypass surgery. The effect on subsequent tibial and peroneal bypasses is controversial. We analyzed the impact of prior endovascular lower extremity revascularization procedures on the short- and mid-term results of femoro-tibial and femoro-peroneal bypasses. METHODS: A retrospective analysis was conducted of all patients who had undergone tibial or peroneal bypass surgery after prior endovascular interventions (PEI-Group, n=40) of the same extremity in our department from October 2007 to October 2012. We compared this group with a group of patients who had received a tibial or peroneal bypass as primary revascularization procedure (BF-Group, n=93) during the same period of time because primary endovascular therapy had been deemed unfeasible in those cases. Indication in all cases was critical limb ischemia; the median age was 78 years (range 50-90 years), 45.1% were diabetics, and 42.9% were female. The graft material was autologous vein in 80 cases and HePTFE in 53 cases. Endpoints of the analysis were primary and secondary patency rates, limb salvage and survival at 2 years postoperatively. RESULTS: At 2 years overall primary patency was 68.4%, secondary patency was 69.5%, limb salvage was 83.6% and survival was 62.6%. Primary patency for the BF-Group was 74.3% vs. 55.1% for the PEI-Group (P=.310) at 2 years; secondary patency was 74.6% vs. 59.1% (P=.268). Prior endovascular intervention did not have any significant effects on limb salvage (83.7% vs. 83.6%; P=.470) or survival rates (61.0% vs. 65.0%; P=.258) at the 2-year mark, either. There were no significant differences in graft occlusion, death and major amputation rates within the first 30 postoperative days. Except for male gender, there were no significant differences in risk factors and indications between the two groups. CONCLUSIONS: Prior endovascular intervention of femoro-tibial vessels does not have a negative impact on the outcome of subsequent tibial or peroneal bypass surgery in patients with critical limb ischemia.

Necrosis of the leg after intraarterial drug injection.

Inadvertent intraarterial injections in the context of drug abuse can cause damage to the vascular system. The clinical picture depends on the drug properties and ranges from partial ischemia to necrosis of the affected extremity. There are no current evidence-based guidelines regarding the management of intraarterial drug injections. In many cases the concept of solving vasospasm after injection is based on the use of intraarterial application of prostaglandins. We report a case in which a mixture of drugs was injected into the left femoral artery. The patient arrived 24 hours later with ischemia of the left leg at our emergency department. Angiography showed that there was no blood flowing in the leg. Despite intraarterial application of vasodilatators, regional neurolysis and thrombolyis with urokinase major amputation was unavoidable. The outcome after inadvertent injection depends on certain drug properties and the delay between injection and the beginning of therapy.

Two-point phase correlations of a one-dimensional bosonic Josephson junction.

We realize a one-dimensional Josephson junction using quantum degenerate Bose gases in a tunable double well potential on an atom chip. Matter wave interferometry gives direct access to the relative phase field, which reflects the interplay of thermally driven fluctuations and phase locking due to tunneling. The thermal equilibrium state is characterized by probing the full statistical distribution function of the two-point phase correlation. Comparison to a stochastic model allows us to measure the coupling strength and temperature and hence a full characterization of the system.

[Virtual tissue. Quaoaring]. / Virtuelles Gewebe. Quaoaring.

Virtual tissue can be generated by employing various methods. First steps en route to virtual tissue may encompass the generation of virtual cells. One such approach termed Quaoaring was applied to produce artificial erythrocytes and these were both discocyte and echinocyte in shape. The results were subsequently compared with data gleaned from scanning electron microscopy and atomic force microscopy. Quaoaring has, however, proved to be unsuccessful in creating convincing objects, particularly those which should be echinocytic in appearance.

Towards noninvasive molecular fluorescence imaging of the human brain.

Fluorescence molecular brain imaging is a new modality allowing the detection of specific contrast agents down to very low concentration ranges (picomolar) in disease models. Here we demonstrate a first noninvasive application of fluorescence imaging in the human brain, where concentrations down to about 100 nM of a nonspecific dye were detected. We argue that due to its high sensitivity, optical molecular imaging of the brain is feasible, which - together with its bedside applicability - makes it a promising technique for use in patients.

Guiding neuronal growth with light.

Control over neuronal growth is a fundamental objective in neuroscience, cell biology, developmental biology, biophysics, and biomedicine and is particularly important for the formation of neural circuits in vitro, as well as nerve regeneration in vivo [Zeck, G. & Fromherz, P. (2001) Proc. Natl. Acad. Sci. USA 98, 10457-10462]. We have shown experimentally that we can use weak optical forces to guide the direction taken by the leading edge, or growth cone, of a nerve cell. In actively extending growth cones, a laser spot is placed in front of a specific area of the nerve's leading edge, enhancing growth into the beam focus and resulting in guided neuronal turns as well as enhanced growth. The power of our laser is chosen so that the resulting gradient forces are sufficiently powerful to bias the actin polymerization-driven lamellipodia extension, but too weak to hold and move the growth cone. We are therefore using light to control a natural biological process, in sharp contrast to the established technique of optical tweezers [Ashkin, A. (1970) Phys. Rev. Lett. 24, 156-159; Ashkin, A. & Dziedzic, J. M. (1987) Science 235, 1517-1520], which uses large optical forces to manipulate entire structures. Our results therefore open an avenue to controlling neuronal growth in vitro and in vivo with a simple, noncontact technique.

Cell volume kinetics of adherent epithelial cells measured by laser scanning reflection microscopy: determination of water permeability changes of renal principal cells.

The water channel aquaporin-2 (AQP2), a key component of the antidiuretic machinery in the kidney, is rapidly regulated by the antidiuretic hormone vasopressin. The hormone exerts its action by inducing a translocation of AQP2 from intracellular vesicles to the cell membrane. This step requires the elevation of intracellular cyclic AMP. We describe here a new method, laser scanning reflection microscopy (LSRM), suitable for determining cellular osmotic water permeability coefficient changes in primary cultured inner medullary collecting duct (IMCD) cells. The recording of vertical-reflection-mode x-z-scan section areas of unstained, living IMCD cells proved useful and valid for the investigation of osmotic water permeability changes. The time-dependent increases of reflection-mode x-z-scan section areas of swelling cells were fitted to a single-exponential equation. The analysis of the time constants of these processes indicates a twofold increase in osmotic water permeability of IMCD cells after treatment of the cells both with forskolin, a cyclic AMP-elevating agent, and with Clostridium difficile toxin B, an inhibitor of Rho proteins that leads to depolymerization of F-actin-containing stress fibers. This indicates that both agents lead to the functional insertion of AQP2 into the cell membrane. Thus, we have established a new functional assay for the study of the regulation of the water permeability at the cellular level.

[New possibilities in the diagnosis and documentation using 3D power doppler ultrasound with carcinoma of the floor of the mouth as illustration]. / Neue Möglichkeiten in Diagnostik und Bilddokumentation mit 3D Power Doppler-Ultraschall am Beispiel von Mundbodenkarzinomen.

AIM: To evaluate a novel 3D power Doppler ultrasound-technique (3D PDUS) in the diagnosis and documentation of tumours of the floor of the mouth. METHOD: 22 patients with tumours of the floor of the mouth (2 T1-, 5 T2-, 6 T3- and 9 T4-carcinomas) prospectively underwent conventional grey-scale ultrasound combined with power Doppler ultrasound and 3D PDUS (3-Scape). All examinations were performed with the "Sonoline Elegra Advanced" in combination with a 7.5 MHz transducer. Two independent observers compared the results regarding clear tumour margins, midline crossing, infiltration of the mylohyoid muscle, infrahyoidal tumour, contact to the mandible, contact to major vessels (such as the lingual, submental and/or facial artery), intra- and peritumoural vascularisation and judged the value of the 3D reconstruction method for documentation purpose. RESULTS: All parameters relevant for therapy could be gathered from the 3D data (agreement: 98.2%) almost without loss of information; results of both observers were identical (kappa value: 1.0). In the comparison to conventional ultrasound, 3D PDUS also allows for the reconstruction of axial images of the floor of the mouth similar to CT-images, and a 3D image of tumour vascularisation can be obtained. Acquisition and reconstruction of the 3D data only takes a couple of minutes. CONCLUSIONS: "3-Scape" is a novel easy-to-perform method allowing the complete acquisition of 3D data of the entire floor of the mouth, and providing the possibility to digitally store and/or transfer examination results without loss of information. Reconstruction of ultrasound-images in any desirable plane and/or as a 3D presentation is possible. Thus, in the future, additional software will facilitate the determination of the volume and the degree of vascularisation of tumours.

[Comparative studies of sinus floor elevation with autologous or allogeneic bone tissue]. / Vergleichende Untersuchungen zur Sinusbodenelevation mit autogenem oder allogenem Knochengewebe.

In 63 patients, 82 elevations of the maxillary sinus were performed. As augmentation, materials autografts from the iliac crest (combined with alveolar ridge augmentations in 16 sinus lifts) were transplanted in 39 cases and osteoinductive, allogeneic bone powder (AAA bone (autolyzed, antigen-extracted, allogeneic bone): n = 8, DFDBA (demineralized freeze-dried bone allograft) and/or Grafton (demineralized bone matrix gel): n = 35) were used in 43 cases. Some 4-6 months after implantation, osteoinductive, allogeneic (demineralized) bone implants showed radio-opaque areas as an equivalent of bone formation. Histological examinations revealed that osteoinductive implants were completely transformed into patients' own bone tissue. The average augmentation height after autograft transplantations was 14 (+/- 3) mm in comparison with 9 (+/- 3) mm after allograft implantations. Histologically as well as radiologically no differences of the bone quality could be determined between the two augmentation materials. Endoscopic controls showed, in both groups, nonirritated mucous membranes. On an average 2 endosseous implants (Bone Lock or ITI-screw implants) were inserted into the augmentated maxillary sinus floors in both groups. No osseointegration was achieved in 4 out of 67 dental implants when bone autografts were used and in 2 out of 74 dental implants of the allogeneic bone group. Patients with bone autografts suffered from postoperative complaints on an average of 19 (+/- 9) days (without consideration of 2 patients with postoperative complaints persisting for more than 90 days). The average postoperative complaints of recipients of allogeneic bone implants continued for 3 (+/- 5) days. The 13 patients who underwent an ambulant sinus lift procedure with allogeneic bone powder were already symptom-free several hours after the operation. Under critical consideration of all investigated parameters, osteoinductive bone implants are preferable to iliac bone autografts for maxillary sinus augmentations in those cases in which no additional alveolar ridge augmentation is required.

[Oral rehabilitation of tumor patients with endosseous implants. Implant success with special reference to peri-implant tissue]. / Orale Rehabilitation von Tumorpatienten mit enossalen Implantaten. Implantationserfolg unter besonderer Berücksichtigung der periimplantären Gewebe.

In a prospective study, the influence of the status of the peri-implant hard and soft tissues on the success of enosseous dental implants in tumor patients was assessed. Out of 59 tumor patients with 261 implants, treated between July 1988 and August 1996, a pool of 23 patients with 99 implants provided with dentures for at least 1 year was obtained. Eighteen of these patients suffered from a squamous cell carcinoma of the oral cavity. Seventeen patients underwent preoperative radiation (40 Gy). A total of 68 out of 99 implants were inserted into autologous bone transplanted to reconstruct the mandible. In order to assess the peri-implant hard and soft tissues, the Hygiene Index, the Sulcus Bleeding Index, the Gingiva Index, the pocket-probing depth. the peri-implant bone resorption, and the periotest were used. The results in the tumor patients were compared with the results in a pool of nontumor patients. Tumor patients had significantly worse periimplant parameters than nontumor patients. The peri-implant pocket-probing depth proved to have significant influence on the success rate. The overall success rate was 77.8%.

Controlled local delivery of tetracycline HCl in the treatment of periimplant mucosal hyperplasia and mucositis. A controlled case series.

The purpose of this controlled case series was to assess the adjunctive efficacy of controlled topical tetracycline HCl application in the treatment of infection associated periimplant mucositis or mucosal hyperplasia. Eight patients with at least 2 endosseous implants showing clinical signs of periimplant mucosal hyperplasia or mucositis were enrolled. All implants received supra- and subgingival scaling, with half of the implants receiving adjunctive controlled local delivery of tetracycline HCl (test). Control implants did not receive any other therapy aside from scaling. Clinical parameters were assessed at baseline, 4, and 12 weeks. Scaling plus controlled local delivery of tetracycline HCl markedly reduced periimplant mucosal hyperplasia in 4 of 5 test implants and demonstrated a trend towards a reduction of bleeding on probing scores. Scaling alone had no effect on mucosal hyperplasia in the 2 control implants presenting with this condition nor bleeding on probing scores. In both groups, plaque index scores were slightly reduced at 4 weeks but returned to baseline values at 12 weeks, whereas pocket probing depths, clinical attachment levels, and probing bone levels remained unchanged during the course of the trial. The observed trends suggest that scaling plus controlled local delivery of tetracycline HCl may have beneficial effects. Randomized controlled trials employing a sample size high enough to reach sufficient statistical power are needed to definitively assess the efficacy of controlled local tetracycline HCl delivery on periimplant diseases.

Significant reversibility of alcoholic brain shrinkage within 3 weeks of abstinence.

Chronic alcoholism is often associated with brain shrinkage or atrophy. During recent years, it has been demonstrated that this shrinkage is, at least in part, reversible when abstinence is maintained. There are different hypotheses concerning the mechanisms for this reversibility, but many questions are still open. Especially the time conditions for these reversible changes are subject of discussion. Twenty-eight male patients with severe alcohol dependence were investigated in a computed tomographic study at the beginning of abstinence and 3 weeks later. Planimetric evaluation of 5 selected slices revealed a significant decrease in liquor areas and an increase of brain volume. The densitometric analysis showed an increase in brain tissue density. In a multiple regression approach it was shown that the reversibility was mostly influenced by the age of the patients. Our results support neither the hypothesis of an increase in brain water as the most important principle for reversibility in alcoholic brain shrinkage nor the hypothesis of augmented dendritic growth. Other mechanisms like reduced (during chronic intoxication) and normalized (during abstinence) cerebral hemoperfusion have to be considered as possible mechanisms for the reversibility of alcoholic brain shrinkage.