CycleGAN-Based Image to Image Translation for Realistic Surgical Training Phantoms.

Training in surgery is essential for surgeons to develop skill and dexterity. Physical training phantoms provide excellent haptic feedback and tissue properties for stitching and operating with authentic instruments and are easily available. However, they lack realistic traits and fail to reflect the complex environment of a surgical scene. Generative Adversarial Networks can be used for image-to-image translation, addressing the lack of realism in physical phantoms, by mapping patterns from the intraoperative domain onto the video stream captured during training with these surgical simulators. This work aims to achieve a successful I2I translation, from intra-operatory mitral valve surgery images onto a surgical simulator, using the CycleGAN model. Different experiments are performed - comparing the Mean Square Error Loss with the Binary Cross Entropy Loss; validating the Fréchet Inception Distance as a training and image quality metric; and studying the impact of input variability on the model performance. Differences between MSE and BCE are modest, with MSE being marginally more robust. The FID score proves to be very useful in identifying the best training epochs for the CycleGAN I2I translation architecture. Carefully selecting the input images can have a great impact in the end results. Using less style variability and input images with good feature details and clearly defined characteristics enables the network to achieve better results.Clinical Relevance- This work further contributes for the domain of realistic surgical training, successfully generating fake intra operatory images from a surgical simulator of the cardiac mitral valve.

Investigation of cutaneous penetration properties of stearic acid loaded to dendritic core-multi-shell (CMS) nanocarriers.

Dendritic core-multi shell (CMS) particles are polymer based systems consisting of a dendritic polar polyglycerol polymer core surrounded by a two-layer shell of nonpolar C18 alkyl chains and hydrophilic polyethylene glycol. Belonging to nanotransport systems (NTS) they allow the transport and storage of molecules with different chemical characters. Their amphipihilic character CMS-NTS permits good solubility in aqueous and organic solutions. We showed by multifrequency electron paramagnetic resonance (EPR) spectroscopy that spin-labeled 5-doxyl stearic acid (5DSA) can be loaded into the CMS-NTS. Furthermore, the release of 5DSA from the carrier into the stratum corneum of porcine skin was monitored ex vivo by EPR spectroscopy. Additionally, the penetration of the CMS-NTS into the skin was analyzed by fluorescence microscopy using indocarbocyanine (ICC) covalently bound to the nanocarrier. Thereby, no transport into the viable skin was observed, whereas the CMS-NTS had penetrated into the hair follicles down to a depth of 340 µm ± 82 µm. Thus, it could be shown that the combined application of fluorescence microscopy and multi-frequency EPR spectroscopy can be an efficient tool for investigating the loading of spin labeled drugs to nanocarrier systems, drug release and penetration into the skin as well as the localization of the NTS in the skin.

Review article: Associations between Helicobacter pylori and obesity--an ecological study.

BACKGROUND: There is emerging debate over the effect of Helicobacter pylori infection on body mass index (BMI). A recent study demonstrated that individuals who underwent H. pylori eradication developed significant weight gain as compared to subjects with untreated H. pylori colonisation. AIM: To elucidate the association between H. pylori colonisation and the prevalence of overweight and obesity in developed countries. METHODS: The literature was searched for publications reporting data on H. pylori prevalence rates and obesity prevalence rates. Studies selected reported H. pylori prevalence in random population samples with sample sizes of more than 100 subjects in developed countries (GDP >25,000 US$/person/year). Corresponding BMI distributions for corresponding countries and regions were identified. Nonparametric tests were used to compare the association between H. pylori and overweight and obesity rates. RESULTS: Forty-nine studies with data from 10 European countries, Japan, the US and Australia were identified. The mean H. pylori rate was 44.1% (range 17-75%), the mean rates for obesity and overweight were 46.6 (± 16)% and 14.2 (± 8.9)%. The rate of obesity and overweight were inversely and significantly (r = 0.29, P < 0.001) correlated with the prevalence of H. pylori infection. CONCLUSIONS: There is an inverse correlation between H. pylori prevalence and rate of overweight/obesity in countries of the developed world. Thus, the gradual decrease of the H. pylori colonisation that has been observed in recent decades (or factors associated with decrease of) could be causally related to the obesity endemic observed in the Western world.

Enhancement of skin radical scavenging activity and stratum corneum lipids after the application of a hyperforin-rich cream.

Hyperforin is well-known for its anti-inflammatory, anti-tumor, anti-bacterial, and antioxidant properties. The application of a hyperforin-rich verum cream could strengthen the skin barrier function by reducing radical formation and stabilizing stratum corneum lipids. Here, it was investigated whether topical treatment with a hyperforin-rich cream increases the radical protection of the skin during VIS/NIR irradiation. Skin lipid profile was investigated applying HPTLC on skin lipid extracts. Furthermore, the absorption- and scattering coefficients, which influence radical formation, were determined. 11 volunteers were included in this study. After a single cream application, VIS/NIR-induced radical formation could be completely inhibited by both verum and placebo showing an immediate protection. After an application period of 4weeks, radical formation could be significantly reduced by 45% following placebo application and 78% after verum application showing a long-term protection. Furthermore, the skin lipids in both verum and placebo groups increased directly after a single cream application but only significantly for ceramide [AP], [NP1], and squalene. After long-term cream application, concentration of cholesterol and the ceramides increased, but no significance was observed. These results indicate that regular application of the hyperforin-rich cream can reduce radical formation and can stabilize skin lipids, which are responsible for the barrier function.

Ultraviolet radiation and nanoparticle induced intracellular free radicals generation measured in human keratinocytes by electron paramagnetic resonance spectroscopy.

BACKGROUND: Several nanoparticle-based formulations used in cosmetics and dermatology are exposed to sunlight once applied to the skin. Therefore, it is important to study possible synergistic effects of nanoparticles and ultraviolet radiation. METHODS: Electron paramagnetic resonance spectroscopy (EPR) was used to detect intracellular free radicals induced by ultraviolet B (UVB) radiation and amorphous silica nanoparticle and to evaluate the influence of nanoparticle surface chemistry on particle cytotoxicity toward HaCaT cells. Uncoated titanium dioxide nanoparticles served as positive control. In addition, particle intracellular uptake, viability, and induction of interleukin-6 were measured. RESULTS: We found that photo-activated titanium dioxide particles induced a significant amount of intracellular free radicals. On the contrary, no intracellular free radicals were generated by the investigated silica nanoparticles in the dark as well as under UVB radiation. However, under UVB exposure, the non-functionalized silica nanoparticles altered the release of IL-6. At the same concentrations, the amino-functionalized silica nanoparticles had no influence on UVB-induced IL-6 release. CONCLUSION: EPR spectroscopy is a useful technique to measure nanoparticle-induced intracellular free radicals. Non-toxic concentrations of silica particles enhanced the toxicity of UVB radiation. This synergistic effect was not mediated by particle-generated free radicals and correlated with particle surface charge and intracellular distribution.

[Long-term results after multiple trauma with ISS ≥ 25. Outcome and predictors of quality of life]. / Langzeitergebnisse nach Polytrauma mit ISS ≥25. Outcome und Prädiktoren der Lebensqualität.

BACKGROUND: The survival chances of multiple trauma patients have continually improved over the last decades; therefore, it is often not a question of whether a patient survives a severe accident but rather how the patient survives. METHODS: In a retrospective study 127 patients were questioned regarding quality of life and health and possible influencing factors using the POLO chart an average of 70 months after suffering severe trauma (ISS Ø 35.6). RESULTS: The quality of life of severely injured patients is significantly reduced compared with the normal population even years after the trauma. In addition to four pretraumatic factors (older age, female gender, low education and previous illnesses) four posttraumatic variables (difficulties with authorities/institutions and unemployment as a consequence of the accident, long duration and subjectively inadequate treatment in hospital) were identified that have a negative impact on long-term quality of life. CONCLUSIONS: The self-reported quality of life after multiple trauma no longer permanently achieves the original level despite extensive rehabilitation measures. Post-traumatic factors have a greater impact on the long-term quality of life than the injury severity. A long-term care and specialized rehabilitation services are needed to improve outcome further.

Influence of dietary carotenoids on radical scavenging capacity of the skin and skin lipids.

Nutrition rich in carotenoids is well known to prevent cell damage, premature skin aging, and skin cancer. Cutaneous carotenoids can be enriched in the skin by nutrition and topically applied antioxidants have shown an increase in radical protection after VIS/NIR irradiation. In this paper, it was investigated whether orally administered carotenoids increase the radical scavenging activity and the radical protection of the skin using in vivo electron paramagnetic resonance spectroscopy and the skin lipid profile was investigated applying HPTLC on skin lipid extracts. Furthermore, in vivo Raman resonance spectroscopy was used to measure the cutaneous carotenoid concentration. A double blind placebo controlled clinical study was performed with 24 healthy volunteers, who have shown a slow but significant and effective increase in cutaneous carotenoids in the verum group. The enhancement in carotenoids increases the radical scavenging activity of the skin and provides a significant protection against stress induced radical formation. Furthermore, the skin lipids in the verum group increased compared to the placebo group but only significantly for ceramide [NS]. These results indicate that a supplementation with dietary products containing carotenoids in physiological concentrations can protect the skin against reactive oxygen species and could avoid premature skin aging and other radical associated skin diseases.

Encapsulated curcumin results in prolonged curcumin activity in vitro and radical scavenging activity ex vivo on skin after UVB-irradiation.

The phytochemical curcumin possesses antioxidant activity; however, it becomes unstable after being exposed to light or heat or loses activity during storage. This is especially important when curcumin is applied to the skin within a cosmetic or pharmaceutical formulation, since sun exposure is unavoidable. This drawback can be directly addressed by encapsulation of curcumin in photo-stable nanospheres. Therefore, curcumin was encapsulated into nanoparticles consisting of ethyl cellulose and/or methyl cellulose. Nanoparticles were subjected to processing conditions commonly used in industry, for example, temperature and pressure and thus retained their morphology. Furthermore, sun exposure resulted in the protection of curcumin by nanoparticles, whereas non-encapsulated curcumin degraded completely. Determination of the radical protection factor resulted in similar antioxidant activity of encapsulated and non-encapsulated curcumin indicating that curcumin maintains its antioxidant activity. Application of lotions containing curcumin or curcumin nanoparticles to the skin and subsequent UVB-irradiation resulted in less radical formation compared to lotion application only. Moreover, radical formation was even less after nanoparticle application compared to free curcumin. Nanoencapsulation protects curcumin from photo degradation and can therefore prolong the antioxidant activity of curcumin.

In vivo methods for the analysis of the penetration of topically applied substances in and through the skin barrier.

The efficacy of a drug is characterized by its action mechanism and its ability to pass the skin barrier. In this article, different methods are discussed, which permit this penetration process to be analysed non-invasively. Providing qualitative and quantitative information, tape stripping is one of the oldest procedures for penetration studies. Although single cell layers of corneocytes are removed from the skin surface, this procedure is considered as non-invasive and is applicable exclusively to the stratum corneum. Recently, optical and spectroscopic methods have been used to investigate the penetration process. Fluorescence-labelled drugs can be easily detected in the skin by laser scanning microscopy. This method has the disadvantage that the dye labelling changes the molecular structures of the drug and consequently might influence the penetration properties. The penetration process of non-fluorescent substances can be analysed by Raman spectroscopy, electron paramagnetic resonance, CARS and multiphoton microscopic measurements. Using these methods, the concentration of the topically applied formulations in different depths of the stratum corneum can be detected by moving the laser focus from the skin surface deeper into the stratum corneum. The advantages and disadvantages of these methods will be discussed in this article.

Nanostructured lipid carriers as nitroxide depot system measured by electron paramagnetic resonance spectroscopy.

Various nanometer scaled transport systems are used in pharmaceutics and cosmetics to increase penetration or storage of actives. Nanostructured lipid carriers (NLCs) are efficient drug delivery systems for dermatological applications. Electron paramagnetic resonance (EPR) spectroscopy was used for the determination of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) distribution within the carrier and to investigate the dynamics of skin penetration. Results of ex vivo penetration of porcine skin and in vivo data - forearm of human volunteers - are compared and discussed to previously obtained results with invasomes under comparable conditions. W-band measurements show 35% of TEMPO associated with the lipid compartments of the NLC. Application of TEMPO loaded NLC to skin ex vivo increases the observation time by 12min showing a stabilisation of the nitroxide radical. Moreover, stabilisation is also seen with data generated in vivo. Thus, same as invasomes NLCs are a suitable slow release depot system.

Stabilization of reactive nitroxides using invasomes to allow prolonged electron paramagnetic resonance measurements.

The detection of the antioxidative capacity of the skin is of great practical relevance since free radicals are involved in many skin damaging processes, including aging and inflammation. The nitroxide TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl) in combination with electron paramagnetic resonance spectroscopy was found suitable for measuring the antioxidative capacity since its reaction with reducing agents is considerably fast. Yet, in order to achieve longer measurement times, e.g. in inflammatory skin diseases, the stabilizing effect of an invasome (ultraflexible vesicle/liposome) suspension with TEMPO was investigated ex vivo on porcine skin and in vivo on human skin. Invasomes increased the measurement time ex vivo 2-fold and the reduction was significantly slowed down in vivo, which is due to membrane-associated and therefore protected TEMPO. Furthermore, TEMPO accumulation in the membrane phase as well as the decreasing polarity of the ultimate surroundings of TEMPO during skin penetration explains the stabilizing effect. Thus, an invasome suspension with TEMPO exhibits stabilizing effects ex vivo and in vivo.

Skin penetration enhancement of core-multishell nanotransporters and invasomes measured by electron paramagnetic resonance spectroscopy.

In order to cross the skin barrier several techniques and carrier systems were developed to increase skin penetration of topical dermatics and to reduce systemic adverse effects by avoiding systemic application. Ultra-flexible vesicles, e.g. invasomes and core-multishell (CMS) nanotransporters are efficient drug delivery systems for dermatological applications. Electron paramagnetic resonance (EPR) spectroscopic techniques were used for the determination of localization and distribution of the spin label 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA; logP=-1.7) within the carrier systems and the ability of the carriers to promote penetration of PCA into the skin. The results show an exclusive localization of PCA in the hydrophilic compartments of the invasome dispersion and the CMS nanotransporter solution. PCA penetration was enhanced 2.5 fold for CMS and 1.9 fold for invasomes compared to PCA solution. Investigation of penetration depth by step-wise removal of the stratum corneum by tape stripping revealed deepest PCA penetration for invasomes. UV-irradiation of PCA-exposed skin samples revealed that the spin label is still reactive. In conclusion novel polymer-based CMS nanotransporters and invasomes can favor the penetration of PCA or hydrophilic drugs. This offers possibilities for e.g. improved photodynamic therapy.

A 13-nation population survey of upper gastrointestinal symptoms: prevalence of symptoms and socioeconomic factors.

BACKGROUND: Previous data collected in separate studies using various different survey instruments have suggested some variability in the prevalence of symptoms between nations. However, there is a lack of studies which assess and compare the prevalence of upper gastrointestinal symptoms contemporaneously in various countries using a uniform, standardised method. AIM: To determine the prevalence of upper gastrointestinal (UGI) symptoms in 13 European countries, and the association between socioeconomic factors and symptoms using a standardised method. METHODS: A representative age- and gender-stratified sample of 23,163 subjects (aged 18-69 years) was surveyed. RESULTS: The prevalence of UGI symptoms was 38%. UGI symptoms were most prevalent in Hungary [45%, 95% confidence interval (CI): 42.2-48.4] and lowest in the Netherlands (24%, 95% CI: 21.0-26.2). UGI symptoms were more prevalent in women (39%, 95% CI: 38.4-39.6) vs. men (37%, 95% CI: 36.4-37.6). Heartburn (24%, 95% CI: 23.4-24.6) and acidic reflux (14%, 95% CI: 13.6-14.4) were most common. With age, the prevalence of UGI symptoms decreased (e.g. 18-29 years: 43%, 95% CI: 41.4-44.3 vs. 50-69 years: 33%, 95% CI: 32.3-34.4); in contrast, the frequency of symptom episodes/year increased with age (e.g. 18-29 years: 11.3 episodes per years, 95% CI: 10.5-12.1 vs. 50-69 years: 21.8, 95% CI: 20.7-22.9). Socioeconomic status as measured by gross domestic product was inversely associated with symptoms and in total, socioeconomic factors, gender, body mass index, smoking habits and alcohol consumption explained 83% of the variance of UGI symptoms. CONCLUSIONS: There are marked differences in the country specific prevalence of upper gastrointestinal complaints. Socioeconomic factors are closely associated with the prevalence of upper gastrointestinal symptoms.

Comparative study of carotenoids, catalase and radical formation in human and animal skin.

Animal skin is widely used in dermatological free radical research. Porcine ear skin is a well-studied substitute for human skin. The use of bovine udder skin is rare but its high carotenoid content makes it particularly appropriate for studying the redox state of the skin. Yet, information on the suitability of animal skin for the study of external hazard effects on the redox state of human skin has been lacking. In this study, we investigated the activity of the antioxidant enzyme catalase and the carotenoid content defining the redox status as well as UV-induced radical formation of human, porcine ear and bovine udder skin ex vivo. In human skin only low levels of radical formation were detected following UV irradiation, whereas bovine skin contains the highest amount of carotenoids but the lowest amount of catalase. Porcine ear skin does not exhibit a carotenoid signal but its catalase activity is close to human skin. Therefore, radical formation can neither be correlated to the amount of catalase nor to the amount of carotenoids in the skin. All skin types can be used for electron paramagnetic resonance-based detection of radicals, but porcine skin was found to be the most suitable type.

[Health economic impact of heart failure: An analysis of the nationwide German database]. / Gesundheitsökonomische Bedeutung der Herzinsuffizienz: Analyse bundesweiter Daten.

BACKGROUND AND AIMS: Patients with congestive heart failure represent a significant amount of the total annual cost of the health care system. Because of a lack of studies on the economic health cost of the related health care, including all cost generating factors, we analysed in detail characteristics of these patients and the costs created by their care. METHOD: Data were retrieved from the German Bureau of Health Statistics for the year 2002 relating to congestive heart failure (Code I50) including other factors (e. g. co-morbidities, ambulatory and hospital care and choice of the doctor). The data were from more than 2 million patients, from 350 insurance companies, the Federal Employees Insurance and the German Institute for Medical Informatics and Documentation. A total of 86 193 patients with congestive heart failure had been recorded. RESULTS: More women than men were recorded as having congestive heart failure (66 vs. 34 %). The various health insurance companies paid 2.3 times more for patients with than without congestive heart failure. Nearly three quarters of the cost for these patients (72 %) resulted from in-patient care. Moreover, costs for drugs were three times higher (1073 Euro vs. 366 Euro). CONCLUSIONS: This analysis clearly demonstrates the increased costs incurred for patients with congestive heart failure. It should serve as a reference base for better assessing future innovations, such as telemedicine, for their effects in different sectors of health care.