[2022 Update of the Austrian Society for Rheumatology and Rehabilitation nutrition and lifestyle recommendations for patients with gout and hyperuricemia]. / Empfehlungen der Österreichischen Gesellschaft für Rheumatologie und Rehabilitation zu Ernährung und Lebensstil bei Gicht und Hyperurikämie ­ Update 2022.

BACKGROUND: Gout is the most frequent inflammatory joint disease in the western world and has a proven genetic background. Additionally, lifestyle factors, such as increasing life expectation and standard of living, sufficient or excess nutrition and a growing prevalence of obesity in the population as well as e.g. alcohol consumption, contribute to the rising incidence of hyperuricemia and gout. Apart from an adequate medication, medical consultation on nutrition and lifestyle is an essential part of the management of gout patients, who have a high risk of internal comorbidities. OBJECTIVE: In 2015 the Austrian Society for Rheumatology and Rehabilitation (ÖGR) working group for osteoarthritis and crystal arthropathies published nutrition and lifestyle recommendations for patients with gout and hyperuricemia. Since then, a multitude of studies have been published addressing this topic, which necessitated an update. METHODS: First, the authors performed a hierarchical literature search to screen for the literature published since 2015. Considering references given in the first publication, the relevant literature was selected and the recommendations from 2015 were either kept as published, reformulated or recreated. Finally, the evidence level and the level of agreement for each recommendation were added by the authors. RESULTS: Based on this process, 10 recommendations were generated instead of the initial 9. As in the original publication, a graphical presentation with symbols was constructed to complement the written text. CONCLUSION: The ÖGR recommendations on nutrition and lifestyle for patients with gout and hyperuricemia were updated in accordance with the most recent relevant literature. These are supposed to serve as information and education material for patients and updated information for physicians.

NLRP inflammasomes and induced skin inflammation, barrier recovery and extended skin hydration.

OBJECTIVE: In vitro assays were designed to examine the release of active Caspase-1 (ACasp-1) from NLRP inflammasome-activated Normal Human Epidermal Keratinocytes (NHEK) employing a bioluminescent assay specific for measuring inflammasome-induced ACasp-1 expression. METHODS: Four anticipated exogenous activators of the NLRP inflammasome including: UVB, ATP, Nigericin and Urban Dust were examined. Follow-up studies examined the influence of extracellular application of three different natural blends of known anti-inflammatories, one a polysaccharide blend and the other two antioxidant blends, one oil-soluble the other water-soluble, to examine ACasp-1 inhibition. Clinical work using the same blend of polysaccharides employed at 3% in a moisturizing formulation was examined for skin barrier recovery, measured with TEWL over a 60-h time frame after tape stripping on 10 individuals, and extended moisturization, measured using corneometer conductance after a single product application out through a 48-h regression on 10 individuals. RESULTS: In vitro results indicated that two exogenous activators, 60 mJ cm-2 UVB and 5 mM ATP, worked to upregulate expression of ACasp-1 within a 20-h timeframe. Additional studies were conducted to examine the influence of three extracellularly applied active ingredient blends. A blend of polysaccharides demonstrated potential to inhibit ACasp-1 expression in both UVB- and ATP-activated skin cells. Oil-soluble and water-soluble antioxidant blends inhibited ACasp-1 expression in UVB-activated keratinocytes but not ATP-activated keratinocytes. Barrier disruption studies indicated that 3% of the polysaccharide blend accelerated barrier recovery in a 60-h time frame as measured by TEWL. Skin hydration studies showed an ability for the polysaccharide blend to show significant improvements in skin hydration out to 48 h after a single application vs. a moisturizing placebo. CONCLUSIONS: The role of the skin's innate immune response, controlled by NLRP inflammasomes, is beginning to be linked to numerous skin conditions including inflammaging. In this work, it was found that: (i) an in vitro assay could activate NHEKs to express NLRP inflammasome-induced ACasp-1 expression, (ii) Ingredient blends inhibited UVB and ATP-induced NLRP inflammasome-induced ACasp-1 expression, and (iii) skin barrier disruption improvements and extended skin hydration could be achieved with 3% of the polysaccharide blend.

OBJECTIF: des dosages in vitro ont été conçus afin d'examiner la libération de caspase-1 (ACasp-1) active, à partir de kératinocytes épidermiques humains normaux (Normal Human Epidermal Keratinocytes, NHEK) activés via l'inflammasome NLRP, en utilisant un dosage par bioluminescence spécifique mesurant l'expression de l'ACasp-1 induite par l'inflammasome. MÉTHODES: quatre activateurs exogènes présumés de l'inflammasome NLRP : UVB, ATP, nigéricine et poussière urbaine, ont été examinés. Des études de suivi ont examiné l'influence de l'application extracellulaire de trois différents mélanges naturels d'anti-inflammatoires connus, l'un étant un mélange de polysaccharides et les deux autres des mélanges d'antioxydants, l'un soluble dans l'huile et l'autre dans l'eau, pour analyser l'inhibition de l'ACasp-1. Une étude clinique utilisant le même mélange de polysaccharides à 3 % dans une formulation hydratante, a analysé la récupération de la barrière cutanée, mesurée par la perte d'eau transépidermique (Trans Epidermal Water Loss, TEWL) sur une période de 60 h après prélèvement au moyen de ruban adhésif sur 10 personnes, ainsi que l'étendue de l'hydratation, par la mesure de la conductance à l'aide d'un cornéomètre après une seule application du produit au moyen d'une régression de 48 h, sur 10 personnes également. RÉSULTATS: les résultats in vitro ont indiqué que deux des activateurs exogènes, les UVB à 60 mJ/cm−2 et l'ATP à 5 mM, régulaient positivement l'expression de l'ACasp-1 sur une période de 20 h. D'autres études ont été menées pour examiner l'influence de trois mélanges de principes actifs appliqués de manière extracellulaire. Un mélange de polysaccharides a démontré un potentiel d'inhibition de l'expression de l'ACasp 1 dans les cellules cutanées activées par les UVB et par l'ATP. Les mélanges antioxydants solubles dans l'huile et dans l'eau ont inhibé l'expression de l'ACasp-1 dans les kératinocytes activés par les UVB mais pas dans les kératinocytes activés par l'ATP. Les études sur la perturbation de la barrière cutanée ont indiqué que le mélange de polysaccharide à 3 % accélérait la récupération de la barrière cutanée, dans un délai de 60 h telle que mesurée par le TEWL. Des études sur l'hydratation de la peau ont mis en évidence la capacité du mélange de polysaccharides à améliorer de manière significative l'hydratation de la peau jusqu'à 48 h après une seule application par rapport à un placebo de produit hydratant. CONCLUSIONS: le rôle de la réponse immunitaire innée de la peau, qui est contrôlée par les inflammasomes NLRP, commence à être associé à de nombreuses pathologies cutanées dont le phénomène inflammatoire. Il a été constaté, dans ce travail, que: (i) un dosage in vitro pouvait activer les NHEK permettant l'expression de l'ACasp-1 induite par l'inflammasome NLRP, (ii) les mélanges d'ingrédients inhibaient l'expression de l'ACasp-1 induite par les UVB et l'ATP via l'inflammasome NLRP, et (iii) des améliorations de la perturbation de la barrière cutanée ainsi qu'une hydratation prolongée de la peau pouvaient être obtenues avec un mélange de polysaccharides à 3%.

Ultrafast energy relaxation in single light-harvesting complexes.

Energy relaxation in light-harvesting complexes has been extensively studied by various ultrafast spectroscopic techniques, the fastest processes being in the sub-100-fs range. At the same time, much slower dynamics have been observed in individual complexes by single-molecule fluorescence spectroscopy (SMS). In this work, we use a pump-probe-type SMS technique to observe the ultrafast energy relaxation in single light-harvesting complexes LH2 of purple bacteria. After excitation at 800 nm, the measured relaxation time distribution of multiple complexes has a peak at 95 fs and is asymmetric, with a tail at slower relaxation times. When tuning the excitation wavelength, the distribution changes in both its shape and position. The observed behavior agrees with what is to be expected from the LH2 excited states structure. As we show by a Redfield theory calculation of the relaxation times, the distribution shape corresponds to the expected effect of Gaussian disorder of the pigment transition energies. By repeatedly measuring few individual complexes for minutes, we find that complexes sample the relaxation time distribution on a timescale of seconds. Furthermore, by comparing the distribution from a single long-lived complex with the whole ensemble, we demonstrate that, regarding the relaxation times, the ensemble can be considered ergodic. Our findings thus agree with the commonly used notion of an ensemble of identical LH2 complexes experiencing slow random fluctuations.

You'll feel better in the morning: slow wave activity and overnight mood regulation in interepisode bipolar disorder.

BACKGROUND: Sleep disturbances are prominent correlates of acute mood episodes and inadequate recovery in bipolar disorder (BD), yet the mechanistic relationship between sleep physiology and mood remains poorly understood. Using a series of pre-sleep mood inductions and overnight sleep recording, this study examined the relationship between overnight mood regulation and a marker of sleep intensity (non-rapid eye movement sleep slow wave activity; NREM SWA) during the interepisode phase of BD. METHODS: Adults with interepisode BD type 1 (BD; n = 20) and healthy adult controls (CTL; n = 23) slept in the laboratory for a screening night, a neutral mood induction night (baseline), a happy mood induction night, and a sad mood induction night. NREM SWA (0.75-4.75 Hz) was derived from overnight sleep EEG recordings. Overnight mood regulation was evaluated using an affect grid pleasantness rating post-mood induction (pre-sleep) and the next morning. RESULTS: Overnight mood regulation did not differ between groups following the sad or happy inductions. SWA did not significantly change for either group on the sad induction night compared with baseline. In BD only, SWA on the sad night was related to impaired overnight negative mood regulation. On the happy induction night, SWA increased relative to baseline in both groups, though SWA was not related to overnight mood regulation for either group. CONCLUSIONS: These findings indicate that SWA disruption may play a role in sustaining negative mood state from the previous night in interepisode BD. However, positive mood state could enhance SWA in bipolar patients and healthy adults.

Disentangling sex allocation in a viviparous reptile with temperature-dependent sex determination: a multifactorial approach.

Females are predicted to alter sex allocation when ecological, physiological and behavioural variables have different consequences on the fitness of male and female offspring. Traditionally, tests of sex allocation have examined single causative factors, often ignoring possible interactions between multiple factors. Here, we used a multifactorial approach to examine sex allocation in the viviparous skink, Niveoscincus ocellatus. We integrated a 16-year observational field study with a manipulative laboratory experiment to explore whether the effects of the maternal thermal environment interact with the resources available to females for reproduction to affect sex allocation decisions. We found strong effects of temperature on sex allocation in the field, with females born in warm conditions and males in cold conditions; however, this was not replicated in the laboratory. In contrast, we found no effect of female resource availability on sex allocation, either independently, or in interaction with temperature. These results corresponded with an overall lack of an effect of resource availability on any of the life history traits that we predicted would mediate the benefits of differential sex allocation in this system, suggesting that selection for sex allocation in response to resource availability may be relatively weak. Combined, these results suggest that temperature may be the predominant factor driving sex allocation in this system.

Acute Gouty Knee Arthritis: Ultrasound Findings Compared With Dual-Energy CT Findings.

OBJECTIVE: The purpose of this study was to compare findings of ultrasound (US) with dual-energy CT (DECT) findings in patients presenting with suspected gouty knee arthritis. SUBJECTS AND METHODS: This prospective study included 65 patients (52 men and 13 women; median age, 61.7 years [range, 38-87 years]) with an initial clinical diagnosis of acute gouty knee arthritis who underwent DECT performed using a 128-MDCT scanner and US performed using a 5-18-MHz transducer. Both intra- and extraarticular findings obtained using each modality were tabulated. RESULTS: DECT identified gout as the final diagnosis for 52 of 65 patients (80.0%). An alternative diagnosis was confirmed for the remaining 13 patients. US detected gout in 31 of 52 patients (sensitivity, 59.6%) and produced findings negative for gout in seven of 13 patients (specificity, 53.8%). The double contour sign on US was positive for gout in 23 of 52 patients (44.2%) and negative in 12 of 13 patients (92.3%). Extraarticular urate deposition was identified by DECT in 44 of 52 patients, compared with identification by US in 11 of 52 patients (p < 0.001). CONCLUSION: The sensitivity of US for the diagnosis of gouty knee arthritis is limited, particularly with respect to extraarticular urate deposition. The double contour sign is the single most valuable sign for the assessment of gouty knee arthritis by US.

Timing and predictors of severe rotavirus gastroenteritis among unvaccinated infants in low- and middle-income countries.

Delays in rotavirus vaccine schedule could improve performance in low- and middle-income countries (LMICs). However, delaying the first dose could be detrimental if infants experience severe rotavirus gastroenteritis (RVGE) early in life. Our objective was to describe the timing and predictors of severe RVGE in unvaccinated children in LMICs. We analysed the placebo arms from two clinical trials (cohort 1: NCT00241644; cohort 2: NCT00362648). We estimated the rate, cumulative incidence (per 1000 infants) and age distribution of severe RVGE episodes. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between baseline factors and severe RVGE. Cumulative incidence at 6 months of age was 23/1000 (95% CI 15-30) in cohort 1 and 6/1000 (95% CI 3-8) in cohort 2. Early antibiotic use (compared with no use) was associated with 2.03 (95% CI 1.18-3.48) and 1.41 (95% CI 0.80-2.51) times the rate of severe RVGE in cohorts 1 and 2, respectively. The cumulative incidence of severe RVGE was low at 6 months of age, suggesting that a 4-week delay in the vaccination schedule may not result in a large number of severe RVGE episodes prior to vaccine receipt.

Light-harvesting Complexes (LHCs) Cluster Spontaneously in Membrane Environment Leading to Shortening of Their Excited State Lifetimes.

The light reactions of photosynthesis, which include light-harvesting and charge separation, take place in the amphiphilic environment of the thylakoid membrane. The light-harvesting complex II (LHCII) is the main responsible for light absorption in plants and green algae and is involved in photoprotective mechanisms that regulate the amount of excited states in the membrane. The dual function of LHCII has been extensively studied in detergent micelles, but recent results have indicated that the properties of this complex differ in a lipid environment. In this work we checked these suggestions by studying LHCII in liposomes. By combining bulk and single molecule measurements, we monitored the fluorescence characteristics of liposomes containing single complexes up to densely packed proteoliposomes. We show that the natural lipid environment per se does not alter the properties of LHCII, which for single complexes remain very similar to that in detergent. However, we show that LHCII has the strong tendency to cluster in the membrane and that protein interactions and the extent of crowding modulate the lifetimes of the excited state in the membrane. Finally, the presence of LHCII monomers at low concentrations of complexes per liposome is discussed.

Dynamic quenching in single photosystem II supercomplexes.

Photosystem II (PSII) is a huge pigment-protein supercomplex responsible for the primary steps of photosynthesis in green plants. Its light-harvesting antenna exhibits efficient transfer of the absorbed excitation energy to the reaction center and also contains a well-regulated protection mechanism against over-excitation in strong light conditions. The latter is based on conformational changes in antenna complexes that open up excitation decay channels resulting in considerable fluorescence quenching. Meanwhile, fluorescence blinking, observed in single antennas, is likely caused by a similar mechanism. Thus the question arises whether this effect is also present in and relevant to the native supramolecular organization of a fully assembled PSII. To further investigate energy transfer and quenching in single PSII, we performed single-molecule experiments on PSII supercomplexes at 5 °C. Analysis of the fluorescence intensity and mean lifetime allowed us to distinguish detached antennas and specifically analyze PSII supercomplexes. The average fluorescence lifetime in PSII of about 100-150 ps, measured under our extreme excitation conditions, is surprisingly similar to published ensemble lifetime data of photochemical quenching in PSII of a similar size. In our case, this lifetime is nevertheless caused by either one or multiple quenched antennas or by a quencher in the reaction center. The observed reversible light-induced changes in fluorescence intensity on a millisecond timescale are reminiscent of blinking subunits. Our results therefore directly illustrate how environmental control over a fluctuating antenna can regulate light-harvesting in plant photosynthesis.

The role of exciton delocalization in the major photosynthetic light-harvesting antenna of plants.

In the major peripheral plant light-harvesting complex LHCII, excitation energy is transferred between chlorophylls along an energetic cascade before it is transmitted further into the photosynthetic assembly to be converted into chemical energy. The efficiency of these energy transfer processes involves a complicated interplay of pigment-protein structural reorganization and protein dynamic disorder, and the system must stay robust within the fluctuating protein environment. The final, lowest energy site has been proposed to exist within a trimeric excitonically coupled chlorophyll (Chl) cluster, comprising Chls a610-a611-a612. We studied an LHCII monomer with a site-specific mutation resulting in the loss of Chls a611and a612, and find that this mutant exhibits two predominant overlapping fluorescence bands. From a combination of bulk measurements, single-molecule fluorescence characterization, and modeling, we propose the two fluorescence bands originate from differing conditions of exciton delocalization and localization realized in the mutant. Disruption of the excitonically coupled terminal emitter Chl trimer results in an increased sensitivity of the excited state energy landscape to the disorder induced by the protein conformations. Consequently, the mutant demonstrates a loss of energy transfer efficiency. On the contrary, in the wild-type complex, the strong resonance coupling and correspondingly high degree of excitation delocalization within the Chls a610-a611-a612 cluster dampens the influence of the environment and ensures optimal communication with neighboring pigments. These results indicate that the terminal emitter trimer is thus an essential design principle for maintaining the efficient light-harvesting function of LHCII in the presence of protein disorder.

Hypersomnia subtypes, sleep and relapse in bipolar disorder.

BACKGROUND: Though poorly defined, hypersomnia is associated with negative health outcomes and new-onset and recurrence of psychiatric illness. Lack of definition impedes generalizability across studies. The present research clarifies hypersomnia diagnoses in bipolar disorder by exploring possible subgroups and their relationship to prospective sleep data and relapse into mood episodes. METHOD: A community sample of 159 adults (aged 18-70 years) with bipolar spectrum diagnoses, euthymic at study entry, was included. Self-report inventories and clinician-administered interviews determined features of hypersomnia. Participants completed sleep diaries and wore wrist actigraphs at home to obtain prospective sleep data. Approximately 7 months later, psychiatric status was reassessed. Factor analysis and latent profile analysis explored empirical groupings within hypersomnia diagnoses. RESULTS: Factor analyses confirmed two separate subtypes of hypersomnia ('long sleep' and 'excessive sleepiness') that were uncorrelated. Latent profile analyses suggested a four-class solution, with 'long sleep' and 'excessive sleepiness' again representing two separate classes. Prospective sleep data suggested that the sleep of 'long sleepers' is characterized by a long time in bed, not long sleep duration. Longitudinal assessment suggested that 'excessive sleepiness' at baseline predicted mania/hypomania relapse. CONCLUSIONS: This study is the largest of hypersomnia to include objective sleep measurement, and refines our understanding of classification, characterization and associated morbidity. Hypersomnia appears to be comprised of two separate subgroups: long sleep and excessive sleepiness. Long sleep is characterized primarily by long bedrest duration. Excessive sleepiness is not associated with longer sleep or bedrest, but predicts relapse to mania/hypomania. Understanding these entities has important research and treatment implications.

Singlet-triplet annihilation in single LHCII complexes.

In light harvesting complex II (LHCII) of higher plants and green algae, carotenoids (Cars) have an important function to quench chlorophyll (Chl) triplet states and therefore avoid the production of harmful singlet oxygen. The resulting Car triplet states lead to a non-linear self-quenching mechanism called singlet-triplet (S-T) annihilation that strongly depends on the excitation density. In this work we investigated the fluorescence decay kinetics of single immobilized LHCIIs at room temperature and found a two-exponential decay with a slow (3.5 ns) and a fast (35 ps) component. The relative amplitude fraction of the fast component increases with increasing excitation intensity, and the resulting decrease in the fluorescence quantum yield suggests annihilation effects. Modulation of the excitation pattern by means of an acousto-optic modulator (AOM) furthermore allowed us to resolve the time-dependent accumulation and decay rate (∼7 µs) of the quenching species. Inspired by singlet-singlet (S-S) annihilation studies, we developed a stochastic model and then successfully applied it to describe and explain all the experimentally observed steady-state and time-dependent kinetics. That allowed us to distinctively identify the quenching mechanism as S-T annihilation. Quantitative fitting resulted in a conclusive set of parameters validating our interpretation of the experimental results. The obtained stochastic model can be generalized to describe S-T annihilation in small molecular aggregates where the equilibration time of excitations is much faster than the annihilation-free singlet excited state lifetime.

[Austrian nutrition and lifestyle recommendations for gout and hyperuricemia]. / Österreichische Ernährungs- und Lebensstilempfehlungen bei Gicht und Hyperurikämie.

BACKGROUND: Gout is the most common inflammatory arthropathy in the Western world. This is mainly due to the high socioeconomic status, sufficient even superfluous nutrition, overweight and alcohol consumption. Despite adequate medication, information and advice on nutrition and lifestyle are one of the cornerstones in the management of these patients. OBJECTIVE: The aim was to provide recommendations on nutrition and lifestyle in cases of gout and hyperuricemia by a group of rheumatologists, based on a review of the most recent literature. MATERIALS AND METHODS: The study group for osteoarthritis and crystal arthropathies of the Austrian Society for Rheumatology and Rehabilitation (ÖGR) carried out a literature search on this topic. The selected papers were listed according to the level of evidence. RESULTS: Based on this literature search nine recommendations were generated and modified via a Delphi approach: four red "don'ts" concerning nutrition and beverages to be avoided, three green "do's" concerning favorable food as well as two blue general lifestyle recommendations. The format of the recommendations is a two-page leaflet with the list of recommendations, level of evidence, strength of recommendation and literature citations on the front page and a colored icon presentation of food and beverages in a circle, matching the colors of the written recommendations, on the reverse. CONCLUSION: For the first time in Austria, nine recommendations on nutrition, beverages and lifestyle for patients with gout and hyperuricemia were defined for everyday practice, as education material for patients and updated information for physicians.

[DRESS syndrome following sulfasalazine treatment]. / DRESS-Syndrom nach Sulfasalazintherapie.

A female patient developed systemic rash, lung edema, electrocardiogram (ECG) abnormalities and fulminant hepatitis with partial liver failure 4 weeks after the start of sulfasalazine treatment. Peripheral T-cell activation, a positive PCR test for human herpesvirus (HHV) 6 as well as eosinophilia in bronchial lavage and a differential blood count were also present. After initiation of systemic corticosteroid therapy and cessation of accompanying medication the clinical symptoms and abnormal laboratory test levels were gradually resolved. A DRESS syndrome (drug rash with eosinophilia and systemic symptoms) was confirmed in accordance with the diagnostic criteria.

Molecularly imprinted polymers as synthetic receptors for the QCM-D-based detection of L-nicotine in diluted saliva and urine samples.

Molecularly imprinted polymers (MIPs) are synthetic receptors that are able to specifically bind their target molecules in complex samples, making them a versatile tool in biosensor technology. The combination of MIPs as a recognition element with quartz crystal microbalances (QCM-D with dissipation monitoring) gives a straightforward and sensitive device, which can simultaneously measure frequency and dissipation changes. In this work, bulk-polymerized L-nicotine MIPs were used to test the feasibility of L-nicotine detection in saliva and urine samples. First, L-nicotine-spiked saliva and urine were measured after dilution in demineralized water and 0.1× phosphate-buffered saline solution for proof-of-concept purposes. L-nicotine could indeed be detected specifically in the biologically relevant micromolar concentration range. After successfully testing on spiked samples, saliva was analyzed, which was collected during chewing of either nicotine tablets with different concentrations or of smokeless tobacco. The MIPs in combination with QCM-D were able to distinguish clearly between these samples: This proves the functioning of the concept with saliva, which mediates the oral uptake of nicotine as an alternative to the consumption of cigarettes.

Heat-transfer-based detection of L-nicotine, histamine, and serotonin using molecularly imprinted polymers as biomimetic receptors.

In this work, we will present a novel approach for the detection of small molecules with molecularly imprinted polymer (MIP)-type receptors. This heat-transfer method (HTM) is based on the change in heat-transfer resistance imposed upon binding of target molecules to the MIP nanocavities. Simultaneously with that technique, the impedance is measured to validate the results. For proof-of-principle purposes, aluminum electrodes are functionalized with MIP particles, and L-nicotine measurements are performed in phosphate-buffered saline solutions. To determine if this could be extended to other templates, histamine and serotonin samples in buffer solutions are also studied. The developed sensor platform is proven to be specific for a variety of target molecules, which is in agreement with impedance spectroscopy reference tests. In addition, detection limits in the nanomolar range could be achieved, which is well within the physiologically relevant concentration regime. These limits are comparable to impedance spectroscopy, which is considered one of the state-of-the-art techniques for the analysis of small molecules with MIPs. As a first demonstration of the applicability in biological samples, measurements are performed on saliva samples spiked with L-nicotine. In summary, the combination of MIPs with HTM as a novel readout technique enables fast and low-cost measurements in buffer solutions with the possibility of extending to biological samples.

Efficacy of a novel treatment serum in the improvement of photodamaged skin.

A novel treatment serum formulated to target multiple pathways in the anti-ageing cascade was tested both in vitro and in clinical settings. In vitro testing was performed to assess the ability to stimulate key proteins and genes fundamental to the anti-ageing cascade. The antioxidant potential of the formulation was studied in a UV-irradiation clinical study. A 12-week, open-label, single-centre study was conducted to determine whether this uniquely formulated topical treatment serum could improve visible signs of facial photodamage. Clinical evaluations showed statistically significant reductions in fine wrinkles and coarse wrinkles and improvements in skin texture, tone and radiance starting at week 4 with continued improvements at weeks 8 and 12. Subject self-assessments confirmed that the beneficial effects of the treatment serum were readily observed by the users. The treatment serum was well tolerated with no treatment-related adverse events reported during the 12-week study. Use of this novel treatment serum produced significant improvements in the visible signs of facial photodamage.

High volume retrograde portography for better discrimination of the portal vein during TIPS procedure.

Background: Imaging of the portal vein prior to puncture for TIPS is essential. Purpose: With this study, we examined a modified retrograde portography with regard to the reliable representation of the portal vein. Material and Methods: Prospective evaluation of 65 TIPS interventions with regard to the delimitation of the portal vein and the exact parameters of retrograde portography such as catheter diameter and contrast medium volume per injection. Results: Retrograde portographies with a large-lumen catheter (10 F) and a large contrast medium volume (40 mL) were performed in 35/63 patients with significantly better delineation of the portal vein than when using 5 F catheters with 10 mL contrast medium. Conclusion: The so-called high volume retrograde portography leads to better delimitation of the portal vein during TIPS application.

The effect of dichloroacetate on health- and lifespan in C. elegans.

Aging is associated with increased vulnerability to chronic, degenerative diseases and death. Strategies for promoting healthspan without necessarily affecting lifespan or aging rate have gained much interest. The mitochondrial free radical theory of aging suggests that mitochondria and, in particular, age-dependent mitochondrial decline play a central role in aging, making compounds that affect mitochondrial function a possible strategy for the modulation of healthspan and possibly the aging rate. Here we tested such a "metabolic tuning" approach in nematodes using the mitochondrial modulator dichloroacetate (DCA). We explored DCA as a proof-of-principle compound to alter mitochondrial parameters in wild-type animals and tested whether this approach is suitable for reducing reactive oxygen species (ROS) production and for improving organismal health- and lifespan. In parallel, we addressed the potential problem of operator bias by running both unblinded and blinded lifespan studies. We found that DCA treatment (1) increased ATP levels without elevating oxidative protein damage and (2) reduced ROS production in adult C. elegans. DCA treatment also significantly prolonged nematode health- and lifespan, but did not strongly impact mortality doubling time. Operator blinding resulted in considerably smaller lifespan-extending effects of DCA. Our data illustrate the promise of a "metabolic tuning" intervention strategy, emphasize the importance of mitochondria in nematode aging and highlight operator bias as a potential confounder in lifespan studies.

Contrast-enhanced ultrasonography for the detection of joint vascularity in arthritis--subjective grading versus computer-aided objective quantification.

PURPOSE: To compare joint inflammation assessment using subjective grading of power Doppler ultrasonography (PDUS) and contrast-enhanced ultrasonography (CEUS) versus computer-aided objective CEUS quantification. MATERIALS AND METHODS: 37 joints of 28 patients with arthritis of different etiologies underwent B-mode ultrasonography, PDUS, and CEUS using a second-generation contrast agent. Synovial thickness, extent of vascularized pannus and intensity of vascularization were included in a 4-point PDUS and CEUS grading system. Subjective CEUS and PDUS scores were compared to computer-aided objective CEUS quantification using Qontrast® software for the calculation of the signal intensity (SI) and the ratio of SI for contrast enhancement. RESULTS: The interobserver agreement for subjective scoring was good to excellent (κ = 0.8 - 1.0; P < 0.0001). Computer-aided objective CEUS quantification correlated statistically significantly with subjective CEUS (P < 0.001) and PDUS grading (P < 0.05). The Qontrast® SI ratio correlated with subjective CEUS (P < 0.02) and PDUS grading (P < 0.03). Clinical activity did not correlate with vascularity or synovial thickening (P = N. S.) and no correlation between synovial thickening and vascularity extent could be found, neither using PDUS nor CEUS (P = N. S.). CONCLUSION: Both subjective CEUS grading and objective CEUS quantification are valuable for assessing joint vascularity in arthritis and computer-aided CEUS quantification may be a suitable objective tool for therapy follow-up in arthritis.