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ABSTRACT:Coastal swamp forests fill ecological niches that provide valuable environmental services, yet their extent across coastal Louisiana has diminished from logging and saltwater intrusion. Previous reforestation attempts yielded mixed results, attributed to hydrological disturbances leaving regions of the coast vulnerable to environmental stress. Environmental conditions may be improving. In the Pontchartrain Estuary, the Caernarvon Freshwater Diversion (CFD) has pulsed Mississippi River water into lower estuary wetlands since 1991, and the Mississippi River Gulf Outlet Canal closure in 2009 lowered soil salinity further upstream in the estuary on the Maurepas Landbridge (MLB). However, how hydrological restoration impacts habitat restoration remains undocumented. The Pontchartrain Conservancy planted ~80,000 saplings from 2011–2021 in two regions (CFD, MLB) within the estuary. Species included Taxodium distichum (L.) Rich, Nyssa aquatica L., Nyssa sylvatica Marshal var. biflora, Acer rubrum L. var. drummondii (Hook. & Arn. ex Nutt.) Sarg., and Fraxinus pennsylvanica, though > 80% of the saplings planted were T. distichum. We assessed survival and growth for 7.3% of saplings. Survival differed between regions; survival was lower around the CFD (63%) and higher on the MLB (82%). Growth rates also differed; growth was higher in CFD (height: 0.18–0.69 m/yr; diameter 0.66–1.62 cm/yr) and lower in MLB (height: 0.00–0.44 m/yr; diameter 0.05–0.18 cm/yr). Growth varied temporally between areas, but trends were similar. Results indicate 1) hydrological restoration benefits coastal swamp reforestation, and 2) river water increased growth. As habitat restoration, including swamp reforestation, scales-up in Louisiana, these outcomes help resource managers and planners refine restoration goals and target areas to maximize restoration success.

Experiencing more stressful life events has been linked to higher levels of inflammation, but this association may depend on when in the lifespan the stressors occur. To address this knowledge gap, we tested two lifespan theories, the accumulation of risks and sensitive period models, by assessing the association between the total number of stressful events and their life stage occurrence on later-life C-reactive protein (CRP). We harmonized data across two cohort studies, maximizing variation in stressors reported across the lifespan. Participants (Ntotal = 7,952, 57.7% female, Mage = 69) from the Health and Retirement Study (HRS: n = 5,136, Mage = 70.6) and the English Longitudinal Study of Aging (ELSA: n = 2,816, Mage = 66.1) completed retrospective surveys of stressful life events and indicated what year(s) each event occurred and had blood drawn ∼4.5 years later. Stressful events were summed across the participants’ lifespans (age 0 to current age) and within childhood (0–17 years), young adulthood (18–39), midlife (40–59), and late adulthood (60+). In main effects models, more cumulative stressors (γ = .05, SE = .02, p = .012) and stressors in young adulthood (γ = .06, SE = .03, p = .037) were associated with higher levels of CRP. In models with all life stages together among adults age 65+ (n = 4,972), experiencing more stressors in midlife significantly predicted higher levels of CRP (γ = .08, SE = .04, p = .038). Our findings replicate prior evidence of an association between cumulative stressors and inflammation and extend this work by identifying stressors in young adulthood and midlife as potentially unique sensitive periods that predict higher levels of later-life inflammation.

ABSTRACTThis article analyses the positioning of mayors as intermediaries between global governance and local practices in small towns with no previous experience with immigration in the state of Brandenburg in eastern Germany between 2015 and 2017. To gain an empirical insight into the dynamics in these municipalities, the results of a study of eight towns are presented. The analytical focus is on how the redefinition of the mayors’ position took place and what the expectations, experiences and irritations were that accompanied the arrival of refugees. The article highlights how mayors governed civil society involvement and dealt with the (partly xenophobic) resident population. The mayors turned out to be glocal bureaucrats who mediated on an ad hoc basis and with unclear competences between global flows of people, local needs and nationally organized bureaucracies. Their integration in multilevel governance constellations was characterized by ambiguities. At the same time, the new situation of becoming (finally) a place of in-migration provoked minor cracks in a since long petrified institutional setting and in most places led to civil society engagement Social media acted as ‘fire accelerators’ by picking up a subliminal sense of discontent among the citizens and attributing this feeling to the arrival of the refugees.

Full-field swept-source optical coherence tomography (FF-SS-OCT) and laser Doppler holography (LDH) are two holographic imaging techniques presenting unique capabilities for ophthalmology. We report on interlaced FF-SS-OCT and LDH imaging with a single instrument. Effectively, retinal blood flow and pulsation could be quasi-simultaneously monitored. This instrument holds potential for a wide scope of ophthalmic applications.

Objective: To gather data about structural and procedural characteristics of patient rounds in the intensive care unit (ICU) setting. Design: A structured online survey was offered to members of two German intensive care medicine societies. Measurements and main results: Intensivists representing 390 German ICUs participated in this study (university hospitals 25%, tertiary hospitals 23%, secondary hospitals 36%, primary hospitals 16%). In 90% of participating ICUs, rounds were reported to take place in the morning and cover an average of 12 intensive care beds and 6 intermediate care beds within 60 min. With an estimated bed occupancy of 80%, this averaged to 4.3 min spent per patient during rounds. In 96% of ICUs, rounds were stated to include a bedside visit. On weekdays, 86% of the respondents reported holding a second ICU round with the attendance of a qualified decision-maker (e.g. board-certified intensivist). On weekends, 79% of the ICUs performed at least one round with a decision-maker per day. In 18%, only one ICU round per weekend was reported, mostly on Sundays. The highest-qualified decision-maker present during rounds on most ICUs was an ICU attending (57%). Residents (96%) and intensive care nurses (87%) were stated to be always or usually present during rounds. In contrast, physiotherapists, respiratory therapists or medical specialists such as pharmacists or microbiologist were not regular members of the rounding team on most ICUs. In the majority of cases, the participants reported examining the medical chart directly before or during the bedside visit (84%). An electronic patient data management system (PDMS) was available on 31% of ICUs. Daily goals were always (55%) or usually (39%) set during rounds. Conclusion: This survey gives a broad overview of the structure and processes of ICU rounds in different sized hospitals in Germany. Compared to other mostly Anglo-American studies, German ICU rounds appear to be shorter and less interdisciplinary.

The mechanistic target of rapamycin (mTOR) pathway is hyperactivated in cancer and neurological disorders. Rapalogs and mTOR kinase inhibitors (TORKi) have recently been applied to alleviate epileptic seizures in tuberous sclerosis complex (TSC). Herein, we describe a pharmacophore exploration to identify a highly potent, selective, brain penetrant TORKi. An extensive investigation of the morpholine ring engaging the mTOR solvent exposed region led to the discovery of PQR626 (8). 8displayed excellent brain penetration and was well-tolerated in mice. In mice with a conditionally inactivated Tsc1gene in glia, 8significantly reduced the loss of Tsc1-induced mortality at 50 mg/kg p.o. twice a day. 8overcomes the metabolic liabilities of PQR620 (52), the first-in-class brain penetrant TORKi showing efficacy in a TSC mouse model. The improved stability in human hepatocytes, excellent brain penetration, and efficacy in Tsc1GFAPCKO mice qualify 8as a potential therapeutic candidate for the treatment of neurological disorders.

Functional retinal imaging, especially of neuronal activity non-invasively in humans, is of tremendous interest. Although the activation of photoreceptor cells (PRCs) could be detected in humans, imaging the function of other retinal neurons had been so far hardly possible. Here, using phase-sensitive full-field swept-source optical coherence tomography (FF-SS-OCT), we show simultaneous imaging of the activation in the photoreceptor and ganglion cell layer/inner plexiform layer (GCL/IPL). The signals from the GCL/IPL are 10-fold smaller than those from the PRC and were detectable only using algorithms for suppression of motion artifacts and pulsatile blood flow in the retinal vessels. FF-SS-OCT with improved phase evaluation algorithms, therefore, allowed us to map functional connections between PRC and GCL/IPL, confirming previous ex vivo results. The demonstrated functional imaging of retinal neuronal layers can be a valuable tool in diagnostics and basic research.

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclinical characterization of compound 1(PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations. No off-target interactions were detected for 1in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1did not bind tubulin, which was observed for the structurally related 4(BKM120, buparlisib). Compound 1is orally available, crosses the blood–brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound’s safety profile, identifies 1as a clinical candidate with a broad application range in oncology, including treatment of brain tumors or CNS metastasis. Compound 1is currently in phase II clinical trials for advanced solid tumors and refractory lymphoma.

Checkpoint inhibitors have improved survival of metastatic melanoma. However, reliable biomarkers to predict response are still needed. Immunoglobulin G (IgG) antibody subclasses reflect immunocompetence in individuals and are known to be involved in essential functions in our immune system. This prospective study evaluated the association between serum IgG with its subclasses IgG1, IgG2, IgG3, and IgG4 and antitumor response according to RECIST 1.1. Serum samples from 49 patients were prospectively collected before the start of treatment with a checkpoint inhibitor. We observed a statistically significant association of baseline IgG2 with response to therapy (P=0.011). After defining optimal cutpoints, we found significant associations between total IgG (>9.66 g/L, P=0.038), IgG1 (>6.22 g/L, P=0.025), IgG2 (>2.42 g/L, P=0.019), and IgG3 (>0.21 g/L, P=0.034) with progression-free survival. Prolonged overall survival was associated with elevated IgG2 (>2.42 g/L, P=0.043). Together, these findings define total IgG and subclasses as predictors of clinical successful checkpoint inhibition in metastatic melanoma patients.

Accelerometers are useful in analyzing lying behavior in farm animals. The effect of the farrowing system on sow lying behavior has been studied around parturition, but not long-term. In a natural environment, sows increase activity 14 d post parturition, which we expected to be also evident in housed sows when they can move freely. The objective of this study was (1) to validate the methodology to automatically measure sow lying bouts and duration with accelerometers and (2) to apply it to crated and free-farrowing sows 24-h pre-parturition until weaning. We used videos with manual behavior coding as the gold standard for validation and calculated the agreement with an intraclass correlation coefficient (ICC), which was 0.30 (95% CI: −0.10 to 0.64) for the number of lying bouts. When transitional sitting bouts were excluded from the video dataset, the ICC for lying bouts increased to 0.86 (95% CI: 0.40 to 0.95). For lying duration, the ICC was 0.93 (95% CI: 0.26 to 0.98). We evaluated the effects of housing, day relative to parturition, and time of day on lying using the accelerometer data and linear mixed models. In crated sows, the number of lying bouts increased toward parturition, peaking at about five bouts per 6 h, and decreased to almost zero bouts after parturition. Then, it increased again (P= 0.001). In free-farrowing sows, the number of lying bouts gradually decreased from a high level towards parturition and was lowest after parturition. It remained constant, as in the crated sows, until day 15, when the number of bouts increased to eight bouts on day 20 (P= 0.001). Sows in both systems were lying almost all of the time between 18:00 and 00:00 hours and on all days (P= 0.001). The crated sows showed a very similar pattern in the other three-quarters of the day with a reduced lying time before parturition, a peak after parturition, reduced lying time from days 5 to 20, and an increase again towards weaning (P= 0.001). Free-farrowing sows had a similar pattern to the crated sows from 00:00 to 06:00 hours, but without the reduction in lying time from days 5 to 20. They showed an increase in lying time toward parturition, which remained constant with a final decrease toward weaning, especially during the day (P= 0.001). This study proves the accuracy of accelerometer-based sow lying behavior classification and shows that free-farrowing systems benefit lactating sows around parturition but also towards weaning in the nest-leaving phase by facilitating activity.This study demonstrates the feasibility of automatically measuring the lying behavior of sows using triaxial accelerometers. Long-term application from the day pre-parturition throughout the entire lactation period in two farrowing environments demonstrated the need for sows to move freely during the period associated with nest building and nest abandonment.We analyzed lying behavior of sows using sensors, focusing on crated versus free-farrowing sows from pre-parturition to weaning. Lying behavior varies in this time following the needs of the sow and her litter. In a natural environment, sows increase activity 14 d post parturition, which we expected to be also evident in housed sows when they are allowed to move freely. Validation with video data showed excellent agreement for duration and frequency of lying. In crated sows, the number of lying bouts peaked around parturition, decreased after parturition, and then gradually increased. In free-farrowing sows, lying down occurred less often before parturition, but increased by day 20 compared to crated sows. Both housing systems showed prolonged lying periods from 18:00 to 00:00 hours. Crated sows had reduced lying times before parturition and lied longest post-parturition, which decreased until day 5 and then increased toward weaning. Free-farrowing sows had similar nocturnal patterns but persistent lying times that increased prior to parturition and decreased prior to weaning. Overall, the study highlighted the accuracy of accelerometer-based lying behavior classification and showed that free-farrowing systems benefit lactating sows not only around parturition but also toward weaning, facilitating activity during the nest-leaving phase.

Hazel leaves (Corylus avellana) fed to sheep resulted in decreased methane emissions without negatively affecting feed intake and were found to have antioxidant properties in vitro. The objective of this study was to evaluate effects of hazel leaves, rich in tannins, on blood antioxidant activity, cellular immune response, and heart beat parameters in sheep. Four experimental pellets were produced by mixing alfalfa and hazel leaves in different proportions, including alfalfa alone as a control, 30% and 60% of hazel leaves, the latter also with 3.8% polyethylene glycol (PEG). Six adult, nonpregnant, nonlactating female sheep (71 ± 5.7 kg of body weight) were allocated to 4 treatments in a 6 × 4 crossover design with four 18-d periods. The diet consisted of experimental pellets and ryegrass-dominated hay (ratio 80% to 20% in dry matter), resulting in hazel leaf proportions of approximately 0%, 25%, and 50% in the total diet. Blood samples were collected at the end of each period to determine plasma total phenol concentration and markers of oxidative status as well as peripheral blood mononuclear cells (PBMC) activation and proliferation response in vitro. Heart rate (HR) and HR variability parameters were measured for 2 consecutive days in each period, during different activities (i.e., eating pellets or hay, or lying). Treatments were compared with multiple comparisons and contrast analysis was used to test for linear and quadratic relations. Compared with control, feeding a high dosage of hazel leaves enhanced (P = 0.006) the plasma total antioxidant capacity, which linearly (P = 0.016) increased with increasing level of hazel leaves in the diet. The total phenol concentration and activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione reductase in the plasma were not different (P ≥ 0.23) among the treatments; however, the latter slightly increased linearly (P = 0.047) with increasing hazel leaves proportion. No differences were observed in the activation and proliferation of PBMC among treatments. The HR decreased linearly (P ≤ 0.009) during pellet eating and lying and the root mean square of successive differences of interbeat intervals (RMSSD) increased linearly (P = 0.037) when lying with increasing level of hazel leaves in the diet. In conclusion, our findings indicate that hazel leaves are a promising supplement to improve oxidative status with no effect on cellular immune response and cardiac stress level of sheep.

The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conformational restriction approach to explore a novel chemical space for the generation of TORKi. Structure–activity relationship (SAR) studies led to the identification of compound 12bwith a ∼450-fold selectivity for mTOR over class I PI3K isoforms. Pharmacokinetic studies in male Sprague Dawley rats highlighted a good exposure after oral dosing and a minimum brain penetration. CYP450 reactive phenotyping pointed out the high metabolic stability of 12b. These results identify the tricyclic pyrimido-pyrrolo-oxazine moiety as a novel scaffold for the development of highly selective mTOR inhibitors for cancer treatment.

Ausgehend von der These, dass Stadtentwicklungspolitik ein wesentlicher Bestandteil einer zunehmenden local governance of migrationist, untersucht dieser Beitrag die Schnittstellen zwischen migrationsbezogenen Politiken und migrantischen Handlungspraxen einerseits und Stadtentwicklungsstrategien andererseits. Es wird davon ausgegangen, dass europäische Städte in übergeordnete (supra)nationale Migrationsregime eingegliedert sind, die deren institutionelles Handeln im Umgang mit Migration beeinflussen. Der Vergleich zweier Städte in unterschiedlichen Migrationsregimen ermöglicht es, Gemeinsamkeiten und Unterschiede der Verbindung zwischen Migrations- und Stadtentwicklungsfragen, die sich trotz oder aufgrund der Einbindung in unterschiedliche Regime ergeben, herauszuarbeiten. Betrachtet werden Genua in Italien und Manchester in Großbritannien. Der Vergleich zeigt, dass sowohl Städte mit wenig institutionalisierten Migrationspolitiken als auch mit langjährigen migrationsbezogenen Politiken sich insbesondere auf zivilgesellschaftliche Akteure verlassen. Migration-led regenerationfindet statt, wird in den Regenerierungsstrategien jedoch nicht explizit thematisiert.

Computational adaptive optics (CAO) is emerging as a viable alternative to hardware-based adaptive optics—in particular when applied to optical coherence tomography of the retina. For this technique, algorithms are required that detect wavefront errors precisely and quickly. Here we propose an extension of the frequently used subaperture image correlation. By applying this algorithm iteratively and, more importantly, comparing each subaperture not to the central subaperture but to several randomly selected apertures, we improved aberration correction. Since these modifications only slightly increase the run time of the correction, we believe this method can become the algorithm of choice for many CAO applications.

This study sought to evaluate the performance of cervical digital photography as an alternative to colposcopy.

The phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is frequently overactivated in cancer, and drives cell growth, proliferation, survival, and metastasis. Here, we report a structure–activity relationship study, which led to the discovery of a drug-like adenosine 5′-triphosphate-site PI3K/mTOR kinase inhibitor: (S)-4-(difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530, compound 6), which qualifies as a clinical candidate due to its potency and specificity for PI3K and mTOR kinases, and its pharmacokinetic properties, including brain penetration. Compound 6showed excellent selectivity over a wide panel of kinases and an excellent selectivity against unrelated receptor enzymes and ion channels. Moreover, compound 6prevented cell growth in a cancer cell line panel. The preclinical in vivo characterization of compound 6in an OVCAR-3 xenograft model demonstrated good oral bioavailability, excellent brain penetration, and efficacy. Initial toxicity studies in rats and dogs qualify 6for further development as a therapeutic agent in oncology.

Two-dimensional nanomembranes are promising materials for filtration or separation by providing the basis for controlled and rapid transport between two compartments. The polymerization by UV light of diacetylene-containing lipids at an interface produces free-standing 2D nanomembranes. Here, we analyzed in situthe nanomembrane formation of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DiynePC) and 1-palmitoyl-2-(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (PTPE) on germanium using light-induced infrared difference spectroscopy with attenuated total reflection to obtain insights into the kinetics and mechanism of the polymerization process. Our interpretation is supported by atomic force microscopy and density functional theory. Formation of the polymer network is evidenced by changes in the frequency of C═O stretches acting as infrared probes. However, spectral and kinetic analysis revealed a biphasic process in the monolayer. In both phases, losses in signal of CH2stretches are observed which are not in agreement with the accepted mechanism of chain propagation for diacetylene polymerization. These signals are dominant in the second phase and are assigned to termination reactions with some contributions from intramolecular consecutive reactions. This finding now provides a spectroscopic measure for the identity and integrity of the nanomembrane complementary to microscopic analysis. We deduce that limited 2D mobility on the solid support promotes intramolecular termination, leading to smaller domains.

In optical coherence tomography (OCT), lateral motion is determined either by speckle tracking or by multi-aperture Doppler OCT. Here we show that both methods may provide incorrect results because, outside the focal plane, non-uniform axial motion is misinterpreted as lateral motion. First, we demonstrate the existence of this artifact by means of a simulation for speckle tracking. Then the physical origin of the artifact and its mathematical relation to defocus and axial motion are explained. It is shown that speckle tracking and multi-aperture Doppler OCT are equally affected by the artifact, which has a considerable effect, even for a defocus of less than one Rayleigh length.

Mechanistic target of rapamycin (mTOR) promotes cell proliferation, growth, and survival and is overactivated in many tumors and central nervous system disorders. PQR620 (3) is a novel, potent, selective, and brain penetrable inhibitor of mTORC1/2 kinase. PQR620 (3) showed excellent selectivity for mTOR over PI3K and protein kinases and efficiently prevented cancer cell growth in a 66 cancer cell line panel. In C57BL/6J and Sprague–Dawley mice, maximum concentration (Cmax) in plasma and brain was reached after 30 min, with a half-life (t1/2) > 5 h. In an ovarian carcinoma mouse xenograft model (OVCAR-3), daily dosing of PQR620 (3) inhibited tumor growth significantly. Moreover, PQR620 (3) attenuated epileptic seizures in a tuberous sclerosis complex (TSC) mouse model. In conclusion, PQR620 (3) inhibits mTOR kinase potently and selectively, shows antitumor effects in vitro and in vivo, and promises advantages in CNS indications due to its brain/plasma distribution ratio.

Die Differenzialdiagnostik zystischer Läsionen des Skeletts ist vielfältig. Neben dem Patientenalter liefern Lokalisation und radiologisches Erscheinungsbild wichtige Informationen zur näheren Eingrenzung. Beim wachsenden Patienten sind die juvenile sowie die aneurysmatische Knochenzyste 2 häufige Entitäten. Zur Unterscheidung ist der Zysteninhalt wegweisend. Während juvenile Knochenzysten mit klarer Flüssigkeit gefüllt sind, ist der Inhalt aneurysmatischer Zysten blutig mit soliden Anteilen. Hinsichtlich der Progredienz weisen aneurysmatische Knochenzysten eine höhere Aktivität auf als solitäre Knochenzysten. Therapeutisch kommt bei juvenilen Knochenzysten die Kürettage inklusive Auffüllung mit Knochenersatzstoffen häufig zur Anwendung. Bei der aneurysmatischen Knochenzyste werden zusätzlich Adjuvanzien eingesetzt. Zur Auffüllung bietet sich Knochenzement an. Dies dient sowohl der Rezidivprophylaxe als auch der erleichterten Rezidiverkennung. Sowohl die juvenile als auch die aneurysmatische Knochenzyste zeigen häufig Rezidive. The differential diagnosis of cystic lesions of the skeleton is multifarious. Besides patient age, the localization and radiologic morphology provide important information for a closer differentiation. Juvenile and aneurysmal bone cysts represent two frequent entities in growing patients. The fluid content of the cysts helps in distinguishing between juvenile and aneurysmal bone cysts. Whereas juvenile bone cysts contain clear fluid, the content of aneurysmal bone cysts consists of blood combined with solid tissue. With respect to progression, aneurysmal bone cysts show a higher activity than solitary bone cysts. The treatment of juvenile bone cysts usually consists of curettage including filling with bone replacement material. For aneurysmal bone cysts the additional use of adjuvants is recommended. Bone cement is preferably used for filling. It shows favorable properties for prophylaxis of recurrence and facilitates the recognition of relapses. Both juvenile and aneurysmal bone cysts often show recurrences.

Cold atmospheric plasma (CAP) interacting with tumor cells, and finally, leading to selective cell death has opened new horizons in cancer therapy. Despite significant progress in modern cancer treatment using immunologic and targeted therapies melanoma and glioblastoma (GBM) presenting as brain metastases or primary tumor with poor prognosis are still a therapeutic challenge. The aim of this paper was to evaluate the potential of CAP (indirect treatment) in combination with the chemotherapeutics bleomycin, paclitaxel, and dacarbazine to inhibit proliferation on human melanoma and GBM cells in vitro. Cell lines of mouse melanoma (B16) were exposed for 1, 4, 12, 24, and 48 h, and of human melanoma (A375) and GBM (A172) for 24 h to bleomycin, dacarbazine, and paclitaxel together with plasma activated phosphate buffered saline. Directly after exposure, cell proliferation after single (CAP and chemotherapeutic) or combined (CAP plus chemotherapeutic) treatment was assessed by cytotoxicity assay. Indirect CAP treatment of cell lines of GBM and melanoma was followed by a strong reduction of proliferation most prominent after 24 and 48 h exposure. With all drugs maximal reduction was achieved when drug-CAP combinations were used. Combination with CAP treating B16 melanoma cells reached 98% (48 h, combined with paclitaxel), A375 melanoma cells 82% (24 h, combined with bleomycin), and GBM cells 96% (24 h, combined with paclitaxel). The combination of chemotherapy with CAP as indirect treatment may be beneficial in therapy of melanoma and GBM by enhanced tumor reduction and less drug toxicity of chemotherapeutics.

Psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) are both chronic, inflammatory conditions that result in a substantial burden of disease and reduced quality of life for patients. Patient involvement in developing optimal disease management strategies, including defining appropriate goals, therapies, and treatment options, as well as in setting policy priorities and agendas, is key. A working group of patient organization representatives and rheumatologists explored what patients consider to be unmet needs, important treatment gaps, and future priorities in PsA and AxSpA management. Reducing pain and fatigue, and improving physical and social functioning and work productivity were identified as important treatment goals for patients. Although the major treatment target for both PsA and AxSpA is remission, with low/minimal disease activity an alternative target for patients with established or long-standing disease, the meaning of remission from the patient’s perspective needs to be explored further as it may differ considerably from the physician’s perspective. Key recommendations from the working group to tackle unmet needs included reducing time to diagnosis, increasing patient and physician disease awareness, focusing on patients’ priorities for treatment goals, and improving patient–physician communication. By addressing these key action points moving forward, the hope is that outcomes will continue to improve for patients with PsA and AxSpA.