Evaluation of Sézary cell marker expression and cell death behaviour upon in vitro treatment by flow cytometry in Sézary syndrome patients.

The diagnosis of Sézary syndrome (SS) relies on the identification of blood Sézary cells (SC) by different markers via flow cytometry. Treatment of SS is challenging since its pathogenesis is characterized by cell death resistance rather than hyperproliferation. In this study, we establish an integrated approach that considers both the expression of SC markers and sensitivity to cell death both spontaneously and upon in vitro treatment. Peripheral blood mononuclear cells were isolated from 20 SS patients and analysed for the SC markers CD7 and CD26 loss as well as CD158k and PD1 gain. The cells were then treated with different established and experimental therapies in vitro and cell death was measured. Spontaneous and therapeutically induced cell death were measured and correlated to cellular marker profiles. In the marker-positive cells, spontaneous cell death sensitivity was reduced. Different treatments in vitro managed to specifically induce cell death in the putative CTCL cell populations. Interestingly, a repeated analysis after 3 months of treatment revealed the CTCL cell death sensitivity to be restored by therapy. We propose this novel integrated approach comprising the evaluation of SC marker expression and analysis of cell death sensitivity upon treatment that can also enable a better therapy stratification.

Extensive retreat and re-advance of the West Antarctic Ice Sheet during the Holocene.

To predict the future contributions of the Antarctic ice sheets to sea-level rise, numerical models use reconstructions of past ice-sheet retreat after the Last Glacial Maximum to tune model parameters 1 . Reconstructions of the West Antarctic Ice Sheet have assumed that it retreated progressively throughout the Holocene epoch (the past 11,500 years or so)2-4. Here we show, however, that over this period the grounding line of the West Antarctic Ice Sheet (which marks the point at which it is no longer in contact with the ground and becomes a floating ice shelf) retreated several hundred kilometres inland of today's grounding line, before isostatic rebound caused it to re-advance to its present position. Our evidence includes, first, radiocarbon dating of sediment cores recovered from beneath the ice streams of the Ross Sea sector, indicating widespread Holocene marine exposure; and second, ice-penetrating radar observations of englacial structure in the Weddell Sea sector, indicating ice-shelf grounding. We explore the implications of these findings with an ice-sheet model. Modelled re-advance of the grounding line in the Holocene requires ice-shelf grounding caused by isostatic rebound. Our findings overturn the assumption of progressive retreat of the grounding line during the Holocene in West Antarctica, and corroborate previous suggestions of ice-sheet re-advance 5 . Rebound-driven stabilizing processes were apparently able to halt and reverse climate-initiated ice loss. Whether these processes can reverse present-day ice loss 6 on millennial timescales will depend on bedrock topography and mantle viscosity-parameters that are difficult to measure and to incorporate into ice-sheet models.

[Is the use of virtual reality in otorhinolaryngology teaching automatically positively rated by students? : A questionnaire-based evaluation among students]. / Wird der Einsatz der virtuellen Realität in der HNO-Heilkunde-Lehre von Studierenden automatisch positiv bewertet? : Eine Fragebogenevaluation bei Studierenden.

BACKGROUND: Analogous to the situation in other disciplines, digital ENT teaching made significant progress during the pandemic. Most ENT clinics nationwide were able to offer a complete virtual teaching program in time. Innovative teaching methods were also used early on. This was recognized in student teaching evaluations. Due to the expansion of virtual reality (VR) in medical teaching, even greater satisfaction should be expected through improved teaching quality. MATERIALS AND METHODS: Surveys were performed with students (n = 180) of the ENT block internship in the summer semester of 2023. The aim of the evaluation was to determine the students' satisfaction with and subjective effectiveness of the newly implemented VR digital teaching method for teaching ear anatomy and coniotomy. A survey was also carried out among resident physicians. RESULTS: The ENT teaching was perceived favorably by the students, with an average rating of 11.7 out of 15. The learning effectiveness and the value of VR in the ENT learning portfolio was evaluated varyingly by the students. The physicians' assessment was different, with a more positive perception. CONCLUSION: Virtual reality represents an innovative component in the teaching portfolio of otolaryngology. This new teaching method is viewed and accepted as a future-oriented tool. Remarkably, the physicians involved voted consistently positively, while the students gave more critical assessments and pointed out limitations in the individual and subjective areas. These findings are in contrast to the further development of innovative teaching methods demanded by student interest groups.

[Options for reconstruction after injuries in the head and neck region]. / Rekonstruktionsmöglichkeiten nach Verletzungen der Kopf-Hals-Region.

Reconstruction of lesions in the head and neck region must be both functionally and esthetically adequate, as the exposed anatomic position can easily lead to social stigmatization after injury. Distortion of symmetry, e.g., by a crooked nose, enophthalmos, or a (partial) amputation of the outer ear, is easily visible. On the other hand, limitations to nasal breathing and olfaction or diplopia may significantly reduce quality of life, and restoration of form and function continues to be challenging. This review discusses the treatment options for trauma of the external nose and the lateral midface, including the orbital floor and the auricle.

[Traumatology-an interdisciplinary task: exclusively for educational purposes?] / Traumatologie ­ eine interdisziplinäre Aufgabe: nur in der Lehre?

BACKGROUND: Traumatology of the head and neck region is not only a part of otorhinolaryngology, but also has a large overlap with neighboring disciplines of the head and neck region. In Freiburg, an interdisciplinary lecture on "ENT emergencies" was implemented in the 21/22 winter semester. The aim was to provide an even more realistic view on interdisciplinary patient care and to make evident the areas of intersection of four of the major head disciplines (otorhinolaryngology, neurosurgery, ophthalmology, and maxillofacial surgery). MATERIALS AND METHODS: A new, special lecture in otorhinolaryngology was implemented as part of the regular online lecture series accompanying the semester. With reference to the clinical care of ENT emergencies, possible overlaps with neighboring disciplines were identified and explained by the discipline representatives or discussed in front of and with the auditorium. At the end of the semester, all participating students (n = 173) were invited to evaluate the seminar using the survey tool "EvaSys" (EvaSys GmbH, Lüneburg, Germany). In total, 78 students participated in the evaluation process. RESULTS: The new lecture concept was very well accepted and immediately ranked top among the interdisciplinary lecture titles within the ENT lecture series. The clear communication of the term "interdisciplinarity" in the sense of a complementary clinical cooperation was also very successful and was appreciated accordingly by students during the evaluation process. CONCLUSION: Pragmatic presentation of ideal clinical patient care using an interdisciplinary approach is possible within the regular ENT lecture series. This realistic portrayal, beyond any technical and/or professional differences, is of great interest to students and is considered clinically relevant. Thus, interdisciplinary lectures provide a valuable tool to teach the fundamental values of clinical interdisciplinary management for the best possible patient care.

Electric Single-Molecule Hybridization Detector for Short DNA Fragments.

By combining DNA nanotechnology and high-bandwidth single-molecule detection in nanopipets, we demonstrate an electric, label-free hybridization sensor for short DNA sequences (<100 nucleotides). Such short fragments are known to occur as circulating cell-free DNA in various bodily fluids, such as blood plasma and saliva, and have been identified as disease markers for cancer and infectious diseases. To this end, we use as a model system an 88-mer target from the RV1910c gene in Mycobacterium tuberculosis, which is associated with antibiotic (isoniazid) resistance in TB. Upon binding to short probes attached to long carrier DNA, we show that resistive-pulse sensing in nanopipets is capable of identifying rather subtle structural differences, such as the hybridization state of the probes, in a statistically robust manner. With significant potential toward multiplexing and high-throughput analysis, our study points toward a new, single-molecule DNA-assay technology that is fast, easy to use, and compatible with point-of-care environments.

Testing the phenotype-linked fertility hypothesis in the presence and absence of inbreeding.

The phenotype-linked fertility hypothesis suggests that females can judge male fertility by inspecting male phenotypic traits. This is because male sexually selected traits might correlate with sperm quality if both are sensitive to factors that influence male condition. A recent meta-analysis found little support for this hypothesis, suggesting little or no shared condition dependence. However, we recently reported that in captive zebra finches (Taeniopygia guttata) inbreeding had detrimental effects both on phenotypic traits and on measures of sperm quality, implying that variation in inbreeding could induce positive covariance between indicator traits and sperm quality. Therefore, we here assess empirically the average strength of correlations between phenotypic traits (courtship rate, beak colour, tarsus length) and measures of sperm quality (proportion of functional sperm, sperm velocity, sperm length) in populations of only outbred individuals and in mixed populations consisting of inbreds (F = 0.25) and outbreds (F = 0). As expected, phenotype sperm-trait correlations were stronger when the population contained a mix of inbred and outbred individuals. We also found unexpected heterogeneity between our two study populations, with correlations being considerably stronger in a domesticated population than in a recently wild-derived population. Correlations ranged from essentially zero among outbred-only wild-derived birds (mean Fisher's Zr ± SE = 0.03 ± 0.10) to moderately strong among domesticated birds of mixed inbreeding status (Zr ± SE = 0.38 ± 0.08). Our results suggest that, under some conditions, the phenotype-linked fertility hypothesis might apply.

Ionic liquids for metal extraction from chalcopyrite: solid, liquid and gas phase studies.

We studied leaching of Cu and Fe from naturally occurring chalcopyrite ore using aqueous solutions of ionic liquids (ILs) based on imidazolium and ethylammonium cations and hydrogensulfate, nitrate, acetate or dicyanamide anions. Liquid, solid and gas phases of the leaching systems were characterised. We have shown that nonoxidative leaching is greatly dependant not only on temperature and pH, but on the anion species of the IL. Solutions of 1-butylimidazolium hydrogen sulfate exhibited the best leaching performance among hydrogen sulphate ILs. We have suggested that the formation of an oxide layer in some ILs may be responsible for a reduced leaching ability. The analysis of the gas phase showed the production of CO2 and CS2 in all leached samples. Our results suggested that the CS2 produced upon leaching could be responsible for decreasing the sulfur, but not oxide, layer on the surface of chalcopyrite samples and therefore more efficient leaching. This is the first study, to our knowledge, to provide a systematic comparison of the leaching performance of ILs composed of different anions and cations and without added oxidants.

[Basis for the treatment of eczematous diseases in otorhinolaryngology]. / Grundlage der Behandlung ekzematöser Erkrankungen im HNO-Bereich.

According to Coombs and Gell, cell-mediated immune responses belong to type IV reactions and are borne mainly by T lymphocytes. The eliciting allergens are usually so-called haptens. Haptens are substances which develop to whole antigens only by binding to protein carriers. In otorhinolaryngology, delayed allergic hypersensitivities are apparent mainly as contact eczemata. Facial dermatitis, auricle and ear canal eczema as well as perioral eczema belong to the most common forms of contact dermatitis in ENT patients. The patient's medical history and morphology of the eczema give a strong indication for a proper diagnosis. Verification is carried out by patch test according to the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF, The Association of the Scientific Medical Societies in Germany) guidelines. Hereby the most widespread contact allergens are tested in a so-called "standard block", which can be reduced to an individualized allergen spectrum, based on medical history. For therapy, allergen avoidance is the most important measure which should also be applied prophylactically. Moreover, antiinflammatory treatment of the contact eczema is carried out with tapering topical corticosteroids. Depending on the patient's age, location and severity of the contact eczema, newer class II or III preparations should be chosen. Skin care preparations are helpful to reduce corticosteroid consumption and are indicated additionally after the acute phase treatment. An important differential diagnosis of contact eczema is atopic dermatitis. Whilst contact dermatitis experiences healing by avoiding the triggering noxious agent, genetically determined atopic dermatitis shows a chronic, recurrent course. In addition to topical corticosteroids, calcineurin inhibitors have been approved for treatment of atopic eczema. In all eczema diseases, regular skin care is a necessary measure which contributes mainly to barrier repair.

Genome-wide differentiation in closely related populations: the roles of selection and geographic isolation.

Population divergence in geographic isolation is due to a combination of factors. Natural and sexual selection may be important in shaping patterns of population differentiation, a pattern referred to as 'isolation by adaptation' (IBA). IBA can be complementary to the well-known pattern of 'isolation by distance' (IBD), in which the divergence of closely related populations (via any evolutionary process) is associated with geographic isolation. The barn swallow Hirundo rustica complex comprises six closely related subspecies, where divergent sexual selection is associated with phenotypic differentiation among allopatric populations. To investigate the relative contributions of selection and geographic distance to genome-wide differentiation, we compared genotypic and phenotypic variation from 350 barn swallows sampled across eight populations (28 pairwise comparisons) from four different subspecies. We report a draft whole-genome sequence for H. rustica, to which we aligned a set of 9493 single nucleotide polymorphisms (SNPs). Using statistical approaches to control for spatial autocorrelation of phenotypic variables and geographic distance, we find that divergence in traits related to migratory behaviour and sexual signalling, as well as geographic distance, together explain over 70% of genome-wide divergence among populations. Controlling for IBD, we find 42% of genomewide divergence is attributable to IBA through pairwise differences in traits related to migratory behaviour and sexual signalling alone. By (i) combining these results with prior studies of how selection shapes morphological differentiation and (ii) accounting for spatial autocorrelation, we infer that morphological adaptation plays a large role in shaping population-level differentiation in this group of closely related populations.

Phenotypic differentiation is associated with divergent sexual selection among closely related barn swallow populations.

Sexual selection plays a key role in the diversification of numerous animal clades and may accelerate trait divergence during speciation. However, much of our understanding of this process comes from phylogenetic comparative studies, which rely on surrogate measures such as dimorphism that may not represent selection in wild populations. In this study, we assess sexual selection pressures for multiple male visual signals across four barn swallow (Hirundo rustica) populations. Our sample encompassed 2400 linear km and two described subspecies: European H. r. rustica (in the Czech Republic and Romania) and eastern Mediterranean H. r. transitiva (in Israel), as well as a potential area of contact (in Turkey). We demonstrate significant phenotypic differentiation in four sexual signalling axes, despite very low-level genomic divergence and no comparable divergence in an ecological trait. Moreover, the direction of phenotypic divergence is consistent with differences in sexual selection pressures among subspecies. Thus, H. r. transitiva, which have the darkest ventral plumage of any population, experience directional selection for darker plumage. Similarly, H. r. rustica, which have the longest tail feathers of any population, experience directional selection for elongated tail feathers and disruptive selection for ventral plumage saturation. These results suggest that sexual selection is the primary driver of phenotypic differentiation in this species. Our findings add to growing evidence of phenotypic divergence with gene flow. However, to our knowledge, this is the first study to relate direct measures of the strength and targets of sexual selection to phenotypic divergence among closely related wild populations.

Thermally stable and efficient polymer solar cells based on a novel donor-acceptor copolymer.

We report high photovoltaic performance of a novel donor-acceptor (D-A) conjugated polymer poly[2,6[4,8-bis(2-ethyl-hexyl)benzo[1,2-b;4,5-b']dithiophene-co-2,5-thiophene-co-4,7[5,6-bis-octyloxy-benzo[1,2,5]thiadiazole]-co-2,5-thiophene] (PBDTTBTZT) in bulk heterojunctions with [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM). A power conversion efficiency (PCE) of more than 7% is obtained for optimized charge-extracting electrodes. Upon application of thermal stress via annealing, a superior thermal stability is demonstrated as compared to poly[N-9″-hepta-decanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT).

Attitudinal barriers to participation in oncology clinical trials: factor analysis and correlates of barriers.

Patient participation in cancer clinical trials is low. Little is known about attitudinal barriers to participation, particularly among patients who may be offered a trial during an imminent initial oncology consult. The aims of the present study were to confirm the presence of proposed subscales of a recently developed cancer clinical trial attitudinal barriers measure, describe the most common cancer clinical trials attitudinal barriers, and evaluate socio-demographic, medical and financial factors associated with attitudinal barriers. A total of 1256 patients completed a survey assessing demographic factors, perceived financial burden, prior trial participation and attitudinal barriers to clinical trials participation. Results of a factor analysis did not confirm the presence of the proposed four attitudinal barriers subscale/factors. Rather, a single factor represented the best fit to the data. The most highly-rated barriers were fear of side-effects, worry about health insurance and efficacy concerns. Results suggested that less educated patients, patients with non-metastatic disease, patients with no previous oncology clinical trial participation, and patients reporting greater perceived financial burden from cancer care were associated with higher barriers. These patients may need extra attention in terms of decisional support. Overall, patients with fewer personal resources (education, financial issues) report more attitudinal barriers and should be targeted for additional decisional support.

Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study.

The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.

Haemosporidian parasites of a European passerine wintering in South Asia: diversity, mixed infections and effect on host condition.

We studied haemosporidian parasites in the scarlet rosefinch Carpodacus erythrinus in a small isolated semicolony during an eight-year period using molecular methods of parasite detection. The scarlet rosefinch is an interesting model of parasite host species. It winters in South Asia which represents a rare exception among European passerines. Males express yellow to red carotenoid-based plumage ornament which is a good predictor of male reproductive success. In 240 blood samples originating from 199 adult individuals, the total parasite prevalence reached 60%. Prevalence varied among years from 36 to 81% in Haemoproteus, 8 to 22% in Plasmodium, and 0 to 14% in Leucocytozoon. Twenty parasite lineages were detected (Haemoproteus: 5 lineages, Plasmodium: 10 lineages, and Leucocytozoon: 5 lineages). Among them, the Haemoproteus ROFI2 lineage, which is a host-specific parasite lineage of the scarlet rosefinch, was the most frequently found. Parasite lineages showed varying degree of lineage specificity. While Haemoproteus lineages detected in the scarlet rosefinch have relatively narrow host breadth restricted mainly to Fringillidae family, Leucocytozoon and Plasmodium lineages generally showed wider host range. The presence of some parasite lineages hitherto detected in sedentary European passerines (SISKIN1, CCF3, BT2) or in Culicoides biting midges at the same locality (ROFI1) suggest local transmission. On the contrary, lineages LK05 and FANTAIL1 that were previously reported exclusively from Asian hosts imply parasite transmission at the scarlet rosefinch wintering sites in South Asia. Mixed infections were found in 17% of infected samples and comprised mainly the most frequent lineages. The pattern of concomitant infections seemed to be rather random and matched expected levels based on lineage frequencies. Between-year comparisons revealed that in a majority of the repeatedly captured individual hosts the infection status remained unchanged (individuals stayed uninfected or possessed the same parasite lineages). However, 16 gains and 8 losses of lineages were also reported. We have not found any effect of haemosporidians on male carotenoid ornament expression or host body mass.

COVID-19 and chronic rhinosinusitis: management and comorbidity - what have we learned?

INTRODUCTION: Approximately 5%-12% of the population worldwide suffer from chronic rhinosinusitis (CRS). CRS is defined as a chronic respiratory disease and is considered to be a risk factor for COVID-19 patients. AREAS COVERED: A non-systematic literature research was conducted on COVID-19 and treatment options for CRSwNP. The latest international publications in medical databases, international guidelines, and the internet were reviewed. Since there were no publications on all aspects of this topic during the pandemic, we included our own experience in this report. Based on the conducted literature research in addition to our previously reported experience, we discuss the treatment of CRSwNP during the COVID-19 pandemic and what can be taken for future pandemics. EXPERT OPINION: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Indications for surgical treatment of CRS should be critically evaluated and reserved for patients with complications and those with no other treatment options. For this purpose, COVID-19 status should be known if possible and, in case of unclear status (emergency), using appropriate personal protective equipment. Systemic corticosteroids should be avoided were possible. Biological treatment should be continued under careful monitoring in uninfected patients and should be temporarily interrupted during COVID-19 infection.

[Initial experience with transoral robotic surgery using the da Vinci® surgical system]. / Erste Erfahrung in der transoralen Roboterchirurgie mit dem da-Vinci®-Chirurgiesystem.

Transoral robotic surgery (TORS) can be considered an extension of transoral microscopic laser surgery. The microscope is replaced by an endoscope that provides the surgeon with a three-dimensional view of the surgical field. The surgeon operates from a console that controls the arms of the patient cart. These arms hold miniaturized surgical instruments that are transorally inserted into the patient, enabling tumor resection. Exposure is ensured by various mouth gags. The use of various endoscopes (0°, 30°), a work radius of 540° for instruments, and a zoom function provides significant advantages over the common transoral laser techniques. With this article we report our first experience with this technique and believe that it may provide significant advantages. However, thorough clinical testing in Germany is required before conclusions can be drawn.

Do the cardiovascular risk profile and the degree of arterial wall calcification influence the performance of MDCT angiography of lower extremity arteries?

OBJECTIVES: To retrospectively assess the influence of arterial wall calcifications on the accuracy of run-off computed tomographic angiography (CTA) and to analyse whether cardiovascular risk factors are predictors of compromising calcifications. METHODS: In 200 consecutive patients who underwent run-off CTA, calcifications were assessed in pelvic, thigh and calf arteries using a four-point scale. Fifty-nine patients with digital subtraction angiography (DSA) were assessed by both techniques to estimate a threshold of compromising calcifications, defined as a decrease of sensitivity, specificity, PPV or NPV below the lower 95% confidence interval of overall results. Regression analysis was performed to investigate a potential relationship between compromising calcifications and presence of cardiovascular risk factors, advanced patient age and severe peripheral arterial disease (PAD). RESULTS: The highest Ca(++)-score was chosen as the cut-off for the regression analysis, as a relevant decrease of specificity (0.91; overall: 0.95) above the knee and of sensitivity (0.66; overall: 0.83), specificity (0.65; overall: 0.93), positive predictive value (PPV) and negative predictive value (NPV) below the knee was observed. In the pelvic and thigh arteries, severe PAD (Fontaine Stage >or=III) showed the highest odds ratio for compromising calcifications (2.9), followed by diabetes mellitus (2.4), renal failure (2.1) and smoking (1.7). In the calf, renal failure (12.2) and diabetes mellitus (3.3) were the strongest predictors. CONCLUSIONS: Patients with diabetes and renal failure should be considered as candidates for alternative vessel imaging in order to avoid inconclusive examination results.

Electrically induced structure formation and pattern transfer

The wavelength of light represents a fundamental technological barrier to the production of increasingly smaller features on integrated circuits. New technologies that allow the replication of patterns on scales less than 100 nm need to be developed if increases in computing power are to continue at the present rate. Here we report a simple electrostatic technique that creates and replicates lateral structures in polymer films on a submicrometre length scale. Our method is based on the fact that dielectric media experience a force in an electric field gradient. Strong field gradients can produce forces that overcome the surface tension in thin liquid films, inducing an instability that features a characteristic hexagonal order. In our experiments, pattern formation takes place in polymer films at elevated temperatures, and is fixed by cooling the sample to room temperature. The application of a laterally varying electric field causes the instability to be focused in the direction of the highest electric field. This results in the replication of a topographically structured electrode. We report patterns with lateral dimensions of 140 nm, but the extension of the technique to pattern replication on scales smaller than 100 nm seems feasible.