The effectiveness of an extra-curricular lecture for STI prevention and sexual education.

While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs.

Unique robotic vascular surgery procedures.

INTRODUCTION: Based on their experience with robot-assisted vascular surgery, the authors present some unique types of procedures they have performed in this area. METHODS: From November 2005 to February 2022, a total of 560 robotic vascular procedures were performed, of which 70 were orphan operations, corresponding to 12.5%. The most common was robotic decompression of the coeliac trunk (18 times) in Dunbar syndrome, followed by robotic repair of type II endoleak after stent graft implantation (15 times) and robotic repair of splenic artery aneurysm (11 times). Less common were isolated pelvic artery aneurysm surgery (8 times), aortic thromboenderectomy and abdominal aortic patch repair (8 times) and hybrid surgery (6 times). Completely unique are renal artery reconstruction (2 times), operation of internal mammary artery aneurysm (1 time) in a patient with Marfan syndrome and paracaval biopsy (1 time) in a cancer patient. RESULTS: In 3 cases (4.2%) the operation had to be converted to open surgery. Twice in the management of splenic artery aneurysm due to flat adhesions in the abdominal cavity and once in the endoleak operation, when due to the very fragile wall of the dilated and pulsating abdominal aortic aneurysm sac, we considered manipulation with robotic instruments to be highly risky. There was zero mortality in this cohort; one patient had to undergo laparoscopic diaphragm repair for diaphragmatic hernia at another institution after deliberation of the coeliac trunk and in one case open surgery was needed for persistent endoleak. CONCLUSION: The use of the robotic system can be beneficial also in less frequent procedures, offering the patients all the advantages of robotic surgery. However, the need of extensive experience in robotic surgery should be emphasized because these operations are rare and perfect anatomical knowledge of the area is necessary.

Surgical treatment of thoracoabdominal aortic pathology - retrospective study of 300 patients.

INTRODUCTION: Thoracoabdominal aortic surgery is a technically demanding and extensive treatment that has its place in the era of endovascular techniques. To ensure the best possible outcomes, it requires a well-coordinated team of surgeons, anaesthetists, intensive care physicians and other medical staff. METHODS: The authors present a series of 300 patients operated on between 1 January 2003 and 15 March 2022. Although the group included sporadic cases of severe obliterating involvement of the visceral aorta, patients with thoracoabdominal aortic aneurysms (TAAA) constituted the vast majority. All known organ preservation procedures were used during the operations. The thoraco-phreno-retroperitoneal approach was chosen in almost all TAAA cases; the thoraco-phreno-transperitoneal approach was used only in two reoperations. RESULTS: In this cohort, type II thoracoabdominal aneurysm according to Crawford classification was most common (33%). This was followed by type IV (32%), type III (15.3%), type I (8.7%), type V (6.7%) and other thoracoabdominal aortic procedures (4.3%). Thirty-day mortality rate was 9.6% (2019 - 6%, 2020 - 9.5%, 2021 - 3.8%) in this group; surgical postoperative complications occurred in 36 patients (12%). Neurological complications were reported in 16 cases (5.3%), of which postoperative paraplegia was noted 6 times (2%). Temporary postoperative dialysis due to renal insufficiency was performed in 19 patients (6.3%) and 4 patients (1.3%) have entered the chronic dialysis programme. In 67 patients (23.3%), temporary tracheostomy was done postoperatively due to prolonged withdrawal from the lung ventilator. CONCLUSION: Surgical treatment of the thoracoabdominal aorta is one of the most extensive procedures in vascular surgery and the mortality and morbidity rates still remain relatively high. A multidisciplinary approach, sufficient experience and a dedicated team are essential for a successful outcome of these highly specialised operations.

First ex vivo cultivation of human Demodex mites and evaluation of different drugs on mite proliferation.

BACKGROUND: Demodex spp. mites are the most complex resident of the human skin microbiome. Although they are considered commensals, they can be pathophysiologically relevant in inflammatory skin diseases like rosacea. Until now, there is no culture system available for these mites except for using live vertebrate hosts. OBJECTIVES: Our aim was to establish an ex vivo culture of human Demodex mites and to characterize the sebogenesis-dependent mite density. METHODS: Demodex mites were cultivated in pilosebaceous units of human skin explants, called human organotypic skin explant culture (hOSEC). Furthermore, different sebogenesis-modifying additives were evaluated. Mites and mite survival were evaluated using light and fluorescence microscopy. RESULTS: After 90 days of incubation, living Demodex mites - including eggs, larvae and nymphs - were detected in the dissected skin samples. Incubation for 30 days with anabolic steroids (testosterone and trenbolone) as well as retinol and retinoic acid (isotretinoin) yielded a reduced mite density. CONCLUSIONS: With this technique, mites can be cultivated ex vivo for the first time, thereby establishing new ways to investigate Demodex spp. The sebostatic effect of isotretinoin might explain the mechanism of action in the off-label treatment of rosacea. We anticipate our findings to be the basis of an accelerated research on our most complex commensal, its life, biology and physiology.

Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.

Abdominal aortic aneurysm as an IgG4-related disease.

The objectives of this study were to evaluate patients with aortic abdominal aneurysm (AAA) with regard to immunoglobulin (Ig)G4-related disease (IgG4-RD). IgG4-RD represents a recently defined condition comprised of a collection of disorders characterized by IgG4 hypergammaglobulinemia, the presence of IgG4-positive plasma cells in organs affected with fibrotic or sclerotizing changes and typical histopathological features. It was identified as a possible cause of vasculitis in large vessels. Studies have been published on a possible association between inflammatory aortic or cardiovascular disease and IgG4-RD. We examined 114 patients with AAA requiring surgery in order to identify findings which are characteristic of IgG4-RD. Aneurysm samples from seven patients showed histopathological features consistent with IgG4-RD and the presence of IgG4+ plasma cells. Only two of these seven patients showed elevated IgG4 serum levels higher 1·35 g/l. In five of the patients, the concentration of serum IgG4 was lower than 1·20 g/l, with the number of IgG4+ plasma cells being higher than 50/high-power field. These findings were consistent with AAA being a heterogeneous group of inflammatory diseases with different pathogenesis.

Gene expression in patients with abdominal aortic aneurysm - more than immunological mechanisms involved.

Abdominal aortic aneurysm (AAA) is a serious condition of unclear pathogenesis and progression. Two samples were collected from 48 patients during AAA surgery. One sample was collected from the aneurysm, the other from the aneurysm proximal neck where the tissue did not exhibit any aneurysmal changes. Subsequently, gene expression profiles using microarrays (Illumina) were compared in RNA extracted from the samples. Overall, 2,185 genes were found to be upregulated and 2,100 downregulated; from which 158 genes had a different expression with FDR<0.05 (False Discovery Rate) and FC>/=2 (Fold Change). Of this number, 115 genes were over-expressed and 43 under-expressed. The analysis of the gene list based on their biological pathways revealed that the regulation of inflammation was mediated by chemokine and cytokine signaling pathways, the integrin signaling pathway, and T and B cell activation. Moreover, a change was identified in the expression of genes involved in both intercellular and intracellular signaling systems.

Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa.

BACKGROUND: Heterotrimeric G proteins are fundamental signaling proteins composed of three subunits, Gα and a Gßγ dimer. The role of Gα as a molecular switch is critical for transmitting and amplifying intracellular signaling cascades initiated by an activated G protein Coupled Receptor (GPCR). Despite their biochemical and therapeutic importance, the study of G protein evolution has been limited to the scope of a few model organisms. Furthermore, of the five primary Gα subfamilies, the underlying gene structure of only two families has been thoroughly investigated outside of Mammalia evolution. Therefore our understanding of Gα emergence and evolution across phylogeny remains incomplete. RESULTS: We have computationally identified the presence and absence of every Gα gene (GNA-) across all major branches of Deuterostomia and evaluated the conservation of the underlying exon-intron structures across these phylogenetic groups. We provide evidence of mutually exclusive exon inclusion through alternative splicing in specific lineages. Variations of splice site conservation and isoforms were found for several paralogs which coincide with conserved, putative motifs of DNA-/RNA-binding proteins. In addition to our curated gene annotations, within Primates, we identified 15 retrotranspositions, many of which have undergone pseudogenization. Most importantly, we find numerous deviations from previous findings regarding the presence and absence of individual GNA- genes, nuanced differences in phyla-specific gene copy numbers, novel paralog duplications and subsequent intron gain and loss events. CONCLUSIONS: Our curated annotations allow us to draw more accurate inferences regarding the emergence of all Gα family members across Metazoa and to present a new, updated theory of Gα evolution. Leveraging this, our results are critical for gaining new insights into the co-evolution of the Gα subunit and its many protein binding partners, especially therapeutically relevant G protein - GPCR signaling pathways which radiated in Vertebrata evolution.

Increase in electron scattering length in PEDOT:PSS by a triflic acid post-processing.

ABSTRACT: A stringent limitation in many optoelectronic devices, such as solar cells and light emitting diodes, is the intrinsic need for a transparent electrode. Uniting relevant aspects, indium tin oxide (ITO) is often the material of choice, however, alternatives are sought and being in particular found in conductive polymers. In this work, we present a novel doping strategy to arrive at highly conducting polymeric material based on poly-3,4-ethylenedioxythiophene (PEDOT). Based on commercial high conductivity PEDOT:PSS (Clevios PH 1000), and a post processing with aqueous triflic acid delivers a material that is both transparent and of low resistivity (5.23 × 10-4 Ω cm). Furthermore, this material retains its conductive character over a large temperature range, indicating metallic behaviour. This is further supported by positive magnetoconductance effects at low temperatures (1.8-10 K) and extended mean free paths of the conduction electrons are observed-evidencing for a metallic state in this polymer.

[The da Vinci robot in the field of vascular surgery]. / Uplatnení robotického systému da Vinci v cévní chirurgii.

INTRODUCTION: The aim of this study was to evaluate the clinical experience with 379 robot-assisted vascular procedures performed from November 2005 to December 2016 at our institution. METHODS: A total of 366 cases (96.6%) were successfully completed using the robotic surgical systems da Vinci Standard and da Vinci Xi. RESULTS: Conversion was necessary in 13 patients (3.4%). The 30-day mortality was 0.26% and 2 (0.5%) late prosthetic infections occurred. CONCLUSIONS: From a practical point of view, the greatest advantage of robot-assisted procedures has been the speed and relative simplicity of vascular anastomosis construction. Our experience with robot-assisted surgery has demonstrated the safety and feasibility of this technique in different areas of vascular surgery.Key words: robotic vascular surgery aortic and non-aortic surgery.

Ground-State Cooling of a Mechanical Oscillator by Interference in Andreev Reflection.

We study the ground-state cooling of a mechanical oscillator linearly coupled to the charge of a quantum dot inserted between a normal metal and a superconducting contact. Such a system can be realized, e.g., by a suspended carbon nanotube quantum dot with a capacitive coupling to a gate contact. Focusing on the subgap transport regime, we analyze the inelastic Andreev reflections which drive the resonator to a nonequilibrium state. For small coupling, we obtain that vibration-assisted reflections can occur through two distinct interference paths. The interference determines the ratio between the rates of absorption and emission of vibrational energy quanta. We show that ground-state cooling of the mechanical oscillator can be achieved for many of the oscillator's modes simultaneously or for single modes selectively, depending on the experimentally tunable coupling to the superconductor.

Robot assisted Aortic and Non-aortic Vascular Operations.

BACKGROUND: The aim of this study was to evaluate the clinical experience with 310 robot assisted vascular procedures. The da Vinci system has been used by a variety of disciplines for laparoscopic procedures but the use of robots in vascular surgery is still relatively uncommon. METHODS: From November 2005 to May 2014, 310 robot assisted vascular operations were performed. Two hundred and twenty four patients were prospectively evaluated for occlusive disease, 61 patients for abdominal aortic aneurysm, four for a common iliac artery aneurysm, four for a splenic artery aneurysm, one for a internal mammary artery aneurysm, and after the unsuccessful endovascular treatment five for hybrid procedures, two patients for median arcuate ligament release and nine for endoleak II treatment post EVAR. Among these patients, 224 underwent robotic occlusive disease treatment (Group I), 65 robotic aorto-iliac aneurysm surgery (Group II) and 21 other robotic procedures (Group III). RESULTS: A total of 298 cases (96.1%) were successfully completed robotically. In 10 patients (3.2%) conversion was necessary. The 30 day mortality was 0.3%, and two (0.6%) late prosthetic infections were seen. Targeted Group I and Group II patients were compared. Robotic ilio-femoral bypass, aorto-femoral bypass, or aorto-iliac thrombo-endarterectomy with prosthetic patch (Group I) required an operative time of 194 (range, 127-315) minutes and robotic aorto-iliac aneurysm surgery (Group II), 253 (range, 185-360) minutes. The mean aortic cross clamping time was 37 minutes in Group I and 93 minutes in Group II. The mean blood loss was more significant in Group II (1,210 mL) than in Group I (320 mL). CONCLUSION: From a practical point of view, the greatest advantage of the robot assisted procedure has been the speed and relative simplicity of construction of the vascular anastomosis. This experience with robot assisted laparoscopic surgery has demonstrated the feasibility of this technique in different areas of vascular surgery.

Ground-state cooling of a carbon nanomechanical resonator by spin-polarized current.

We study the nonequilibrium steady state of a mechanical resonator in the quantum regime realized by a suspended carbon nanotube quantum dot in contact with two ferromagnets. Because of the spin-orbit interaction and/or an external magnetic field gradient, the spin on the dot couples directly to the flexural eigenmodes. Accordingly, the nanomechanical motion induces inelastic spin flips of the tunneling electrons. A spin-polarized current at finite bias voltage causes either heating or active cooling of the mechanical modes. We show that maximal cooling is achieved at resonant transport when the energy splitting between two dot levels of opposite spin equals the vibrational frequency. Even for weak electron-resonator coupling and moderate polarizations we can achieve ground-state cooling with a temperature of the leads, for instance, of T = 10 ω.

A sensitive and robust method for automated on-line monitoring of enzymatic activities in water and water resources.

The realisation of a novel concept for automated on-line monitoring of enzymatic activities in water was successfully demonstrated by long-term field testing at two remote Austrian ground water resources. The ß-D-glucuronidase (GLUC) activity was selected as a representative enzymatic model parameter for the on-line determination. But the device can be adapted for any enzymatic reaction with diagnostic relevance for microbial water quality monitoring, as demonstrated for the ß-D-galactosidase activity. Automated filtration of volumes up to 5 litres supports sensitive quantification of enzymatic activities. Internet-based data transfer, using internal control parameters for verification and a dynamic determination of the limit of quantification, enabled robust enzymatic on-line monitoring during a 2-year period. A proportion of 5,313 out of 5,506 GLUC activity measurements (96.5%) could be positively verified. Hydrological (discharge, gauge, turbidity, temperature, pH, electric conductivity, spectral absorbance coefficient at 254 nm) as well as microbiological parameters (Escherichia coli, coliforms) were concurrently determined to characterise the investigated ground water resources. The enzymatic on-line measurements closely reflected the different hydrological conditions and contamination patterns of the test sites. Contrary to expectations, GLUC did not qualify as a proxy-parameter for the occurrence of cultivation-based E. coli contamination and warrants further detailed investigations on its indication capacity as a rapid means for microbial faecal pollution detection in such aquatic habitats. Microbial on-line monitoring is likely to become more important in the future, complementing existing surveillance strategies for water safety management. Further perspectives on the application of such analytical on-line technologies, such as their connection with event-triggered sampling and standardised diagnostics, are discussed.

[Comparison of different electrocardiographic techniques for the detection of arrhythmias in horses]. / Vergleichende Untersuchung von elektrokardiographischen Techniken zur Diagnostik von Herzrhythmusstörungen beim Pferd.

OBJECTIVE: The aim of the study was to extend the range of the electrocardiographic examination in horses, evaluating the practicability of special electrocardiographic techniques (exercise- and Holter-ECG) and comparing these with more common techniques (resting-ECG) in equine medicine. MATERIAL AND METHODS: Electrocardiographic examination (resting-ECG for 1 minute, exercise-ECG and Holter-ECG) was performed in 20 horses without any clinical or echocardiographic findings and in 80 patients with abnormal findings (valvular regurgitation and/or atrial fibrillation). RESULTS: In comparison with the resting-ECG, the exercise-ECG demonstrated more atrial and ventricular premature beats, while the Holter-ECG had a higher detection rate of 2nd degree atrioventricular or sinuatrial blocks, and of ventricular and atrial premature depolarisations (p < 0.001). In comparison to the exercise-ECG, the Holter-ECG registered more 2nd degree atrioventricular blocks (p < 0.001) and ventricular (p < 0.001) or atrial premature contractions (p < 0.01). Atrial fibrillation was detected in every recorded ECG-type, but Holter-ECG provided additional information. Three of 16 horses with atrial fibrillation had R-on-T-episodes during Holter-monitoring. In addition to more common findings in the ECG, Holter-monitoring detected a 2nd degree atrioventricular block associated with an adjacent ventricular escape beat in a horse without any clinical or echocardiographic findings. An accelerated idioventricular rhythm was identified in a horse without any clinical or echocardiographic findings and in a horse with mitral valve insufficiency. CONCLUSION AND CLINICAL RELEVANCE: The Holter-ECG is a useful tool in the evaluation of heart disease and could supply additional information when compared to the usual diagnostic electrocardiographic procedures used in horses. Exercise-ECG should not be replaced by Holter-ECG, however, Holter-EGC can provide additional diagnostic value.

Endovascular treatment of infected aortic aneurysms.

OBJECTIVE: To report on the short- and long-term outcomes of patients with primary infected aortic aneurysm (IAA) treated by stent graft (SG) in two centers. MATERIAL AND METHOD: Over a period of 15 years, 32 patients with IAA underwent endovascular treatment. None had undergone previous aortic surgery. The causal relationship was gastrointestinal infection in 9 patients (28%), endovascular diagnostic/therapeutic procedures/resuscitation in 6 (19%), wound infection after previous surgeries in 5 (16%), urinary infection in 4 (13%), urology or gastroenterology procedures in 3 (9%), pancreatitis in 2 (6%), endocarditis in 1 (3%) and phlebitis in 1 (3%) patient. We implanted 11 bifurcated, 10 tubular thoracic, 4 aorto-uni-iliac, 4 tubular abdominal and 1 iliac SG. Two other surgeries were hybrid procedures. RESULTS: The etiological agent was identified in 28 (88%) patients. Twenty-six (81%) patients survived the 30-day postoperative period. Sixteen (50%) survived to 1-year follow-up and 13 (40.6%) survived to 3-year follow-up. Three patients have survived for less than 1 year and a further 3 for less than 3 years, so far. Among patients with aneurysms situated in central parts of the thoracic and infrarenal aorta there was a better death/survival ratio than among patients with a proximal or distal aneurysm location. CONCLUSION: The implantation of a SG may be an alternative to open surgery in selected groups of patients with primary IAA. Aneurysms of the central part of the thoracic or abdominal aorta have a more favorable prognosis with endovascular treatment.

Hidden treasures in unspliced EST data.

Several classes of exclusively--or at least predominantly--unspliced non-coding RNAs have been described in the last years, including totally and partially intronic transcripts and long intergenic RNAs. Functionally, they appear to be involved in regulating gene expression, at least in part by associating with the chromatin. Intron-less transcripts have received little attention, even though recent findings indicate that intron-less protein-coding genes have several features that set them apart from the more abundant and much better understood spliced mRNAs. Even less is known about unspliced non-coding transcripts. Thus we systematically analyze the distribution of unspliced ESTs in the human genome. These form a large source of transcriptomic data that is almost always excluded from detailed studies. Most unspliced ESTs appear in clusters overlapping, or located in the close vicinity of, annotated RefSeq genes. Partially intronic unspliced ESTs show complex patterns of overlap with the intron/exon structure of the RefSeq gene. Distinctive patterns of CAGE tags indicate that a large class of unspliced EST clusters is forming long extensions of 3'UTRs, at least several hundreds of which probably appear also as independent 3'UTR-associated RNAs.

Current trends in the diagnosis of vascular prosthesis infection.

Early diagnosis of an infected vascular prosthesis, a potentially life-threatening disease, is a precondition of adequate treatment. The most frequently used diagnostic imaging method is computer tomography. Non-acute infections caused by low grade agents may pose a challenge with ambiguous CT-images and other ancillary imaging methods are used for these cases, each offering different levels of diagnostic sensitivity. These methods come from the fields of radiology (magnetic resonance imaging - MRI) and nuclear medicine studies using labelled leukocytes (111In or 99mTc HMPAO), 99mTc labelled antigranulocyte antibodies, 67Ga-citrate or labelled antibiotics (99mTc-ciprofloxacin) or avidin in combination with 111In-biotin. Positron emission tomography (PET) or hybrid PET/CT using 18F-FDG are becoming increasingly popular. The authors of this review article point out the diagnostic potential of the different methods and current trends, including the possibilities of microbiological demonstration of the agent, as well as their potential position in the diagnostic algorithm.