Olfactory Function and Olfactory Disorders. / Riechen und Riechstörungen.

The sense of smell is important. This became especially clear to patients with infection-related olfactory loss during the SARS-CoV-2 pandemic. We react, for example, to the body odors of other humans. The sense of smell warns us of danger, and it allows us to perceive flavors when eating and drinking. In essence, this means quality of life. Therefore, anosmia must be taken seriously. Although olfactory receptor neurons are characterized by regenerative capacity, anosmia is relatively common with about 5 % of anosmic people in the general population. Olfactory disorders are classified according to their causes (e. g., infections of the upper respiratory tract, traumatic brain injury, chronic rhinosinusitis, age) with the resulting different therapeutic options and prognoses. Thorough history taking is therefore important. A wide variety of tools are available for diagnosis, ranging from short screening tests and detailed multidimensional test procedures to electrophysiological and imaging methods. Thus, quantitative olfactory disorders are easily assessable and traceable. For qualitative olfactory disorders such as parosmia, however, no objectifying diagnostic procedures are currently available. Therapeutic options for olfactory disorders are limited. Nevertheless, there are effective options consisting of olfactory training as well as various additive drug therapies. The consultation and the competent discussion with the patients are of major importance.

Future therapeutic strategies for olfactory disorders: electrical stimulation, stem cell therapy, and transplantation of olfactory epithelium-an overview.

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work.

Reliability and validity of a brief version of the Questionnaire of Olfactory Disorders (brief QOD) in patients with olfactory dysfunction.

BACKGROUND: The aim of this study was to determine the reliability and validity of the brief version of Questionnaire of Olfactory Disorders (brief QOD). METHODS: A total of 372 patients participated in this study. Olfactory function was examined using the Sniffin' Sticks test. The brief version of QOD, including 4 items concerning parosmia (QOD-P), 7 items concerning quality of life (QOD-QOL), and 3 visual analog scales to rate disease burden, awareness of the disorder and issues related to professional life (QOD-VAS), was used to assess subjective information on olfactory dysfunction. We evaluated the split-half reliability, internal consistency and validity of the brief QOD. RESULTS: The split-half reliability was 0.60 (QOD-P), 0.87 (QOD-QOL), and 0.66 (QOD-VAS), respectively. The Cronbach's coefficient was 0.63 (QOD-P), 0.87 (QOD-QOL), and 0.71 (QOD-VAS), respectively. Olfactory function was found to be associated with QOD-P, QOD-QOL and QOD-VAS. CONCLUSIONS: The brief QOD is a suitable scale for the assessment of subjective severity of olfactory dysfunction for purposes such as treatment counseling, disability assessment, treatment control, and research in patients with olfactory disorder.

Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients.

OBJECTIVES: We have previously shown that treatment with intranasal sodium citrate may be beneficial in post-infectious olfactory dysfunction. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. We also aimed to determine whether sodium citrate is beneficial in treating qualitative olfactory dysfunction. METHODS: We performed a prospective, controlled study. Patients applied intranasal sodium citrate solution to the right nasal cavity for 2 weeks. The left nasal cavity was untreated and, therefore, acted as an internal control. Monorhinal olfactory function was assessed using the "Sniffin' Sticks" composite 'TDI' score, before and after treatment. The presence of parosmia and phantosmia was also assessed. RESULTS: Overall, there was a significant increase in TDI after treatment (using the best of right and left sides). Treatment with sodium citrate did not significantly improve quantitative olfactory function, compared to control. The proportion of patients reporting parosmia did not change significantly after treatment. However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period. CONCLUSIONS: Treatment with intranasal sodium citrate for a period of 2 weeks does not appear to improve quantitative olfactory function in patients with post-infectious impairment, compared to control. It may, however, be beneficial in treating phantosmia, which should be further addressed in future work.

The complexity of surface acoustic wave fields used for microfluidic applications.

Using surface acoustic waves (SAW) for the agitation and manipulation of fluids and immersed particles or cells in lab-on-a-chip systems has been state of the art for several years. Basic tasks comprise fluid mixing, atomization of liquids as well as sorting and separation (or trapping) of particles and cells, e.g. in so-called acoustic tweezers. Even though the fundamental principles governing SAW excitation and propagation on anisotropic, piezoelectric substrates are well-investigated, the complexity of wave field effects including SAW diffraction, refraction and interference cannot be comprehensively simulated at this point of time with sufficient accuracy. However, the design of microfluidic actuators relies on a profound knowledge of SAW propagation, including superposition of multiple SAWs, to achieve the predestined functionality of the devices. Here, we present extensive experimental results of high-resolution analysis of the lateral distribution of the complex displacement amplitude, i.e. the wave field, alongside with the electrical S-parameters of the generating transducers. These measurements were carried out and are compared in setups utilizing travelling SAW (tSAW) excited by single interdigital transducer (IDT), standing SAW generated between two IDTs (1DsSAW, 1D acoustic tweezers) and between two pairs of IDTs (2DsSAW, 2D acoustic tweezers) with different angular alignment in respect to pure Rayleigh mode propagation directions and other practically relevant orientations. For these basic configurations, typically used to drive SAW-based microfluidics, the influence of common SAW phenomena including beam steering, coupling coefficient dispersion and diffraction on the resultant wave field is investigated. The results show how tailoring of the acoustic conditions, based on profound knowledge of the physical effects, can be achieved to finally realize a desired behavior of a SAW-based microacoustic-fluidic system.

Stateful Three-Input Logic with Memristive Switches.

Memristive switches are able to act as both storage and computing elements, which make them an excellent candidate for beyond-CMOS computing. In this paper, multi-input memristive switch logic is proposed, which enables the function X OR (Y NOR Z) to be performed in a single-step with three memristive switches. This ORNOR logic gate increases the capabilities of memristive switches, improving the overall system efficiency of a memristive switch-based computing architecture. Additionally, a computing system architecture and clocking scheme are proposed to further utilize memristive switching for computation. The system architecture is based on a design where multiple computational function blocks are interconnected and controlled by a master clock that synchronizes system data processing and transfer. The clocking steps to perform a full adder with the ORNOR gate are presented along with simulation results using a physics-based model. The full adder function block is integrated into the system architecture to realize a 64-bit full adder, which is also demonstrated through simulation.

Pitfalls in interpretation of large registry data on hernia repair.

Since more and more hernia registries are being created and the number of patients included is increasing, knowledge of potential pitfalls in interpretation of registry data has to be known and dealt with. This invited commentary is to discuss some of these topics. The aim is to present and discuss the main shortcoming of register-based studies and how to deal with these problems, to contribute to more validated results and eventually improved surgical outcomes.

The incidence of incisional hernia after aortic aneurysm is not higher than after benign colorectal interventions: A retrospective control-matched cohort study.

BACKGROUND: Abdominal aortic aneurysms (AAA) have most probably an inflammatory origin, whereby the elastica is the layer actually involved. In the past, collagen weackness was supposed to be the shared cause of both, AAA and incisional hernias. Since the development of new techniques of closure of the abdominal wall over the last decade, collagen deficency seems to play only a secondary etiologic role. OBJECTIVES: The aim of the study was to investigate whether the incidence of incisional hernia following laparotomy due to AAA differs from that of colorectal interventions. MATERIAL AND METHODS: This was a retrospective control matched cohort study. After screening of 403 patients with colorectal interventions and 96 patients with AAA, 27 and 72 patients, respectively were included. The match criteria for inclusion of patients with colorectal interventions were: age, benign underlying disease and median xiphopubic laparotomy. The primary endpoint was the incidence of an incisional hernia. The secondary endpoints were the risk profile, length of stay in the intensive care unit and postoperative complications. Data analysis was carried in the consecutive collective from 2006 to 2008. RESULTS: In the group with AAA the mean follow-up was 34.5±18.1 months and in the group with colorectal interventions 35.7±21.4 months. The incidence of incisional hernias showed no significant differences between the two groups. In the AAA group 10 patients (13.8%) developed an incisional hernia in contrast to 7 patients in the colorectal intervention group (25.9%). CONCLUSIONS: In our collective patients with AAA did not show an increased incidence of incisional hernia in comparison to patients with colorectal interventions with comparable size of the laparotomy access and age. The quality of closure of the abdominal wall seems to be an important factor for the prevention of incisional hernia.

Identification of the ectoenzyme CD38 as a marker of committed preadipocytes.

BACKGROUND/OBJECTIVES: Characterisation of the adipocyte cellular lineage is required for a better understanding of white adipose tissue homoeostasis and expansion. Although several studies have focused on the phenotype of the most immature adipocyte progenitors, very few tools exist to identify committed cells. In haematopoiesis, the CD38 ectoenzyme is largely used to delineate various stages of stem cell lineage commitment. We hypothesise that this marker could be used to identify committed preadipocytes. METHODS: Complementary strategies including flow cytometry, cell-sorting approaches, immunohistochemistry and primary cultures of murine adipose progenitors isolated from different fat pads of control or high-fat diet exposed C57BL/6 J mice were used to determine the molecular expression profile, proliferative and differentiation potentials of adipose progenitors expressing the CD38 molecule. RESULTS: We demonstrate here that a subpopulation of CD45- CD31- CD34+ adipose progenitors express the cell surface protein CD38. Using a cell-sorting approach, we found that native CD45- CD31- CD34+ CD38+ (CD38+) adipose cells expressed lower CD34 mRNA and protein levels and higher levels of adipogenic genes such as Pparg, aP2, Lpl and Cd36 than did the CD45- CD31- CD34+ CD38- (CD38-) population. When cultivated, CD38+ cells displayed reduced proliferative potential, assessed by BrdU incorporation and colony-forming unit assays, and greater adipogenic potential. In vitro, both CD38 mRNA and protein levels were increased during adipogenesis and CD38- cells converted into CD38+ cells when committed to the adipogenic differentiation programme. We also found that obesity development was associated with an increase in the number of CD38+ adipose progenitors, this effect being more pronounced in intra-abdominal than in subcutaneous fat, suggesting a higher rate of adipocyte commitment in visceral depots. CONCLUSIONS: Together, these data demonstrate that CD38 represents a new marker that identifies committed preadipocytes as CD45- CD31- CD34low CD38+ cells.

Risk-adjusted procedure tailoring leads to uniformly low complication rates in ventral and incisional hernia repair: a propensity score analysis and internal validation of classification criteria.

BACKGROUND: The usual approach in hernia surgery is to select the ideal repair method independent of the patient's characteristics. In the present study, we change the approach to ask which technique is best for the individual patient`s risk profile. For this, two criteria are important: does the patient need reconstruction of the abdominal wall? or does he or she need treatment of symptoms without being exposed to unnecessarily high perioperative risks? METHODS: In a heuristic selection procedure, 486 consecutive patients were classified according to their characteristics as low-risk or high-risk for postoperative complications. Low-risk patients preferentially underwent open abdominal wall reconstruction with mesh (MFR + mesh), high-risk patients mainly a bridging-mesh procedure, either by laparoscopic (Lap.-IPOM) or open approach (Open-IPOM). Primary outcome was the incidence of postoperative complications. Secondary outcome was the recurrence-free interval. The propensity score was used for covariate adjustment analyzing recurrence rate as well as postoperative complications using Cox regression and logistic regression, respectively. RESULTS: Comparison of all surgical procedures showed risk factors had no independent influence on occurrence of complications (p = 0.110). Hernial gap width was an independent factor for occurrence of complications (p = 0.002). Propensity score adjustment revealed Lap.-IPOM to have a significantly higher recurrence rate than MFR + mesh (HR 2.367, 95% CI 1.123-4.957, p = 0.024). Three or more risk factors were protective against recurrence (HR 0.454, 95% CI 0.221-0.924, p = 0.030). In the univariate Cox regression analysis for recurrence, age >50 years was a protective prognostic factor (HR 0.412, 95% CI 0.245-0.702, p = 0.002). CONCLUSIONS: The classification criteria applied were internally validated. The heuristic algorithm ensured that patients at high-risk of complications did not have a higher perioperative complication rate than patients at low-risk.

SET kinetics of electrochemical metallization cells: influence of counter-electrodes in SiO2/Ag based systems.

The counter-electrode material in resistively switching electrochemical metallization cells (ECMs) is a crucial factor influencing the nucleation of conductive filaments, the equilibrium electrode potentials, and kinetics in the devices, and hence the overall switching characteristics. Here, we demonstrate the influence of the counter-electrode (CE) material on the SET events and the importance of appropriate choice and combination of materials. The counter-electrode material influences the counter-electrode processes at the CE/insulator interface and consequently determines the metal ion concentration in the cells. We measured the switching kinetics for SiO2/Ag based ECM cells using different counter-electrode materials with different electrocatalytic activities towards water reduction, namely platinum, ruthenium, and iridium oxide, as well as titanium nitride and tantalum. The experimental results are fitted using a physical simulation model and are analysed for the limiting factors for fast SET kinetics.

Compact SAW aerosol generator.

In this work, we discuss and demonstrate the principle features of surface acoustic wave (SAW) aerosol generation, based on the properties of the fluid supply, the acoustic wave field and the acoustowetting phenomena. Furthermore, we demonstrate a compact SAW-based aerosol generator amenable to mass production fabricated using simple techniques including photolithography, computerized numerical control (CNC) milling and printed circuit board (PCB) manufacturing. Using this device, we present comprehensive experimental results exploring the complexity of the acoustic atomization process and the influence of fluid supply position and geometry, SAW power and fluid flow rate on the device functionality. These factors in turn influence the droplet size distribution, measured here, that is important for applications including liquid chromatography, pulmonary therapies, thin film deposition and olfactory displays.

SAW-based fluid atomization using mass-producible chip devices.

Surface acoustic wave (SAW)-based fluid atomizers are ideally suited to generate micrometer-sized droplets without any moving parts or nozzles. Versatile application fields can be found for instance in biomedical, aerosol or thin film technology, including medical inhalators or particle deposition for advanced surface treatment. Such atomizers also show great potential for on-chip integration and can lead to economic production of hand-held and even disposable devices, with either a single functionality or integrated in more complex superior systems. However, this potential was limited in the past by fluid supply mechanisms inadequate for mass production, accuracy and reliability. In this work, we briefly discuss existing fluid supply methods and demonstrate a straightforward new approach suited for reliable and cost-effective mass-scale manufacturing of SAW atomizer chips. Our approach is based on a fluid supply at the boundary of the acoustic beam via SU-8 microchannels produced by a novel one-layer/double-exposure photolithography method. Using this technique, we demonstrate precise and stable fluid atomization with almost ideal aerosol plume geometry from a dynamically stabilized thin fluid film. Additionally, we demonstrate the possibility of in situ altering the droplet size distribution by controlling the amount of fluid available in the active region of the chip.

[Impact of acute normovolemic hemodilution on primary hemostasis]. / Einfluss der akuten normovolämischen Hämodilution auf die primäre Hämostase.

BACKGROUND: Acute normovolemic hemodilution (ANH) is performed with the intention to reduce the requirement for allogeneic blood transfusions. After preoperative withdrawal of whole blood, corresponding amounts of crystalloids and/or colloids are infused to maintain normovolemia. The main benefit of ANH is the availability of whole blood containing red blood cells, clotting factors and platelets for reinfusion after removal during the dilution process. Until retransfusion whole blood components are stored at the patient's bedside in the operating theatre. AIM: It was the aim of the present investigation to analyze potential changes in ex vivo induced platelet aggregation in stored blood components. MATERIAL AND METHODS: After obtaining approval 15 patients undergoing complex cardiac surgery were enrolled into this prospective observational study. Acute normovolemic hemodilution (ANH) was routinely performed in this collective based on institutional standards. Besides analyses of pH and plasma concentrations of ionized calcium and hemoglobin, hematological analyses included aggregometric measurements using multiple electrode aggregometry (MEA, Multiplate®, Roche, Grenzach, Germany). Ex vivo platelet aggregation was induced using arachidonic acid (ASPI test), as well as thrombin receptor activating peptide (TRAP test) and adenosine diphosphate (ADP test). Laboratory analyses were performed before beginning ANH (baseline), as well as immediately (T1), 30 min (T2), 60 min (T3), 90 min (T4), 120 min (T5), 150 min (T6) and 180 min (T7) after beginning of storage. The areas under the aggregation curves (AUC) in the MEA were defined as primary (ASPI test) and secondary endpoints (ADP test, TRAP test). RESULTS: As compared to baseline, arachidonic acid induced platelet aggregation was significantly reduced at T1 [77 U (68/94 U) vs. 53 U (25/86 U), p = 0.003] and each consecutive measuring point. As compared to T1 (begin of storage), arachidonic acid induced platelet aggregation was significantly reduced at T4 [26 U (14/54 U); p = 0.002], T5 [30 U (21/36 U); p = 0.007], T6 [25 U (17/40 U); p = 0.004] and T7 [28 U (17/39 U); p < 0.001]. The extent of ex vivo induced platelet aggregation in the TRAP test and ADP test remained unchanged during the study period. The pH as well as the concentrations of ionized calcium and hemoglobin remained unchanged in the blood component during storage. CONCLUSION: The results of the present study indicate that disturbances of platelet aggregation may occur during storage of whole blood components prepared for the purpose of ANH. Further investigations are needed to analyze whether the observed phenomena are of hemostatic relevance.

Compact modeling of CRS devices based on ECM cells for memory, logic and neuromorphic applications.

Dynamic physics-based models of resistive switching devices are of great interest for the realization of complex circuits required for memory, logic and neuromorphic applications. Here, we apply such a model of an electrochemical metallization (ECM) cell to complementary resistive switches (CRSs), which are favorable devices to realize ultra-dense passive crossbar arrays. Since a CRS consists of two resistive switching devices, it is straightforward to apply the dynamic ECM model for CRS simulation with MATLAB and SPICE, enabling study of the device behavior in terms of sweep rate and series resistance variations. Furthermore, typical memory access operations as well as basic implication logic operations can be analyzed, revealing requirements for proper spike and level read operations. This basic understanding facilitates applications of massively parallel computing paradigms required for neuromorphic applications.

Delayed coalescence of droplets with miscible liquids: Lubrication and phase field theories.

Mixing of droplets with a body of different liquids shows an interesting behavior for small contact angles at solid substrate. The droplets interact with each other, a liquid exchange appears between the approaching drops owing to surface tension gradients at the droplets interface. But the drops remain separated for some seconds (up to minutes), until the merging into a single drop occurs (Langmuir 24, 6395 (2008)). We investigate this phenomenon using lubrication approximation and phase field approach. For both methods, 2D quantitative computer simulations for delayed fusion of perfectly miscible thin liquid films/droplets with low contact angles are reported.

Preparation of CNT-copper matrix composite films.

Copper matrix composite thin films reinforced with multiwall carbon nanotubes (CNT-Cu-MC) have been processed by electroplating on conducting or insulating underlayers on oxidized (100)Si substrates using iron catalyst particles. The nanotubes were grown by thermal or plasma enhanced catalytic CVD process. Enhanced interfacial strength to copper was achieved after covering the CNTs by plasma enhanced atomic layer deposition (PEALD) of a thin Ta-N or Ta-N/Zr-O interlayer. For copper plating a conventional copper electrolyte with additives (Ethone) was applied. The density of CNTs and their growth determine primarily the quality of the composite films. A sufficient dispersion of CNTs in the copper matrix and homogeneous copper plating were obtained for low density of CNTs. The CNT reinforcement changes the microstructure and electrical properties of electroplated copper films. The resistivity of the Cu films increases by multiwall CNT reinforcement as a result of changed microstructure.

[Evaluation of clinical trials following an approval from a research ethics committee]. / Evaluation von Forschungsvorhaben nach einem positiven Votum einer Ethikkommission.

BACKGROUND AND OBJECTIVE: According to the Medical Association's professional code of conduct a consultation of the responsible ethics committee has to be undertaken prior to biomedical research. Up to date there has been no systematic analysis of published results after an approval from the research ethics committee of the Medical Association Westfalen-Lippe. A measure for the importance are publications of concluded trials. This work presents a comprehensive collection and evaluation of clinical trials that were approved in 1996. METHODS: Clinical trials that were approved by the ethics committee in the year 1996 were analysed concerning their publication parameters, if results have been reported to the ethics committee, the design of the study and their funding. Publications were found by database mining in the Internet sources "Pubmed" and "ISI Web of Knowledge". RESULTS: 70 % out of the 99 approved clinical trials were published as specified in the initial proposal, whereas in 2 % only aspects of the proposal were published. In 21 % of the cases only publications in closely related subjects could be identified. 7 % however remained unpublished. Of these studies 63 % were designed as mono centre study and 37 % as multi centre studies. The time from approval of the study until publication was 46 months (median value). Furthermore the analysis revealed, that 45 % of the studies were funded by industry. CONCLUSION: This work represents an unprecedented and detailed analysis of the clinical studies approved by a German ethics committee. In the course of this work a comprehensive catalogue with criteria to facilitate a collection and tracking mechanism was established. This should enable the ethics committee to comply with their new duties. A great amount of the clinical trials were presented in publications to the scientific community.

Interaction between two quantitative trait loci affects fetal haemoglobin expression.

The biological mechanisms controlling complex quantitative traits are likely to be affected by interactions between genetic factors, sometimes referred to as epistasis. The identification of interacting loci through genetic analyse faces many challenges, and few examples of replicated findings of interaction exist for humans and model system organisms. The replication of an interaction, or the non-independence, of two quantitative trait loci (QTL) affecting the developmental switch from the expression of fetal to adult haemoglobin is reported here. Fetal haemoglobin expression in adults is a highly heritable, yet complex, phenotype. Using a sample of 874 dizygotic twin pairs of European descent, we found linkage to a QTL on chromosome 8 to be conditional on the twin pairs' genotypes at a polymorphism in the beta-globin complex; an interaction originally identified in a large Asian Indian kindred. The beta-globin polymorphism has been previously shown to be associated with fetal haemoglobin levels in adults. This study reports the first known replication of a genetic interaction between QTLs influencing a complex human trait.