A systematic review of factors influencing treatment adherence in chronic inflammatory skin disease – strategies for optimizing treatment outcome

Adherence describes how a patient follows a medical regime recommended by a healthcare provider. Poor treatment adherence represents a complex and challenging problem of international healthcare systems, as it has a substantial impact on clinical outcomes and patient safety and constitutes an important financial burden. Since it is one of the most common causes of treatment failure, it is extremely important for physicians to reliably distinguish between non‐adherence and non‐response. This systematic review aims to summarize the current literature on treatment adherence in dermatology, focusing on chronic inflammatory skin diseases such as psoriasis, atopic dermatitis and acne. A systematic literature search was performed using the PubMed Database, including articles from 2008 to 2018. Low treatment adherence is a multidimensional phenomenon defined by the interplay of numerous factors and should under no circumstances be considered as the patient's fault alone. Factors influencing treatment adherence in dermatology include patient characteristics and beliefs, treatment efficacy and duration, administration routes, disease chronicity and the disease itself. Moreover, the quality of the physician‐patient relationship including physician‐time available for the patient plays an important role. Understanding patients’ adherence patterns and the main drivers of non‐adherence creates opportunities to improve adherence in the future. Strategies to increase treatment adherence range from reminder programs to simplifying prescriptions or educational interventions. Absolute adherence to treatment may not be realistically achievable, but efforts need to be made to raise awareness in order to maximize adherence as far as possible

Psoriasis bei Dupilumab-behandeltem atopischem Ekzem

Dupilumab ist ein monoklonaler Antikörper, der an die gemeinsame α‑Kette des IL(Interleukin)-4- und IL-13-Rezeptors bindet und den Th(T-Helferzelle)2-Signalweg blockiert, der bei der Entstehung des atopischen Ekzems eine Schlüsselrolle spielt. Wir berichten über den Fall eines 40-jährigen Patienten, der nach 6 Wochen Dupilumab-Therapie eine histologisch gesicherte Psoriasis entwickelte. Das eigenmächtige, abrupte Absetzen der ungewöhnlichen, nicht leitliniengerechten oralen Steroidtherapie und die Blockade des Th2-Signalwegs durch Dupilumab dürften die entscheidenden Auslösefaktoren für die erstmalige Ausbildung der Psoriasis bei unserem Patienten gewesen sein

Once and Future Gulf of Mexico Ecosystem: Restoration Recommendations of an Expert Working Group

The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants—liquid and gaseous petroleum compounds plus chemical dispersants—poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these widely dispersed, highly bioavailable and toxic hydrocarbons and chemical dispersants on marine life from pelicans to salt marsh grasses and to deep-sea animals. As tragic as the DWH blowout was, it has stimulated public interest in protecting this economically, socially and environmentally critical region. The 2010 Mabus Report, commissioned by President Barack Obama and written by the secretary of the Navy, provides a blueprint for restoring the Gulf that is bold, visionary and strategic. It is clear that we need not only to repair the damage left behind by the oil but also to go well beyond that to restore the anthropogenically stressed and declining Gulf ecosystems to prosperity-sustaining levels of historic productivity. For this report, we assembled a team of leading scientists with expertise in coastal and marine ecosystems and with experience in their restoration to identify strategies and specific actions that will revitalize and sustain the Gulf coastal economy. Because the DWH spill intervened in ecosystems that are intimately interconnected and already under stress, and will remain stressed from global climate change, we argue that restoration of the Gulf must go beyond the traditional "in-place, in-kind" restoration approach that targets specific damaged habitats or species. A sustainable restoration of the Gulf of Mexico after DWH must: 1. Recognize that ecosystem resilience has been compromised by multiple human interventions predating the DWH spill; 2. Acknowledge that significant future environmental change is inevitable and must be factored into restoration plans and actions for them to be durable; 3. Treat the Gulf as a complex and interconnected network of ecosystems from shoreline to deep sea; and 4. Recognize that human and ecosystem productivity in the Gulf are interdependent, and that human needs from and effects on the Gulf must be integral to restoration planning. With these principles in mind, the authors provide the scientific basis for a sustainable restoration program along three themes: 1. Assess and repair damage from DWH and other stresses on the Gulf; 2. Protect existing habitats and populations; and 3. Integrate sustainable human use with ecological processes in the Gulf of Mexico. Under these themes, 15 historically informed, adaptive, ecosystem-based restoration actions are presented to recover Gulf resources and rebuild the resilience of its ecosystem. The vision that guides our recommendations fundamentally imbeds the restoration actions within the context of the changing environment so as to achieve resilience of resources, human communities and the economy into the indefinite future

A Once and Future Gulf of Mexico Ecosystem: Restoration Recommendations of an Expert Working Group

The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants — liquid and gaseous petroleum compounds plus chemical dispersants — poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these widely dispersed, highly bioavailable and toxic hydrocarbons and chemical dispersants on marine life from pelicans to salt marsh grasses and to deep-sea animals. As tragic as the DWH blowout was, it has stimulated public interest in protecting this economically, socially and environmentally critical region. The 2010 Mabus Report, commissioned by President Barack Obama and written by the secretary of the Navy, provides a blueprint for restoring the Gulf that is bold, visionary and strategic. It is clear that we need not only to repair the damage left behind by the oil but also to go well beyond that to restore the anthropogenically stressed and declining Gulf ecosystems to prosperity-sustaining levels of historic productivity. For this report, we assembled a team of leading scientists with expertise in coastal and marine ecosystems and with experience in their restoration to identify strategies and specific actions that will revitalize and sustain the Gulf coastal economy. Because the DWH spill intervened in ecosystems that are intimately interconnected and already under stress, and will remain stressed from global climate change, we argue that restoration of the Gulf must go beyond the traditional “in-place, in-kind” restoration approach that targets specific damaged habitats or species. A sustainable restoration of the Gulf of Mexico after DWH must: 1. Recognize that ecosystem resilience has been compromised by multiple human interventions predating the DWH spill; 2. Acknowledge that significant future environmental change is inevitable and must be factored into restoration plans and actions for them to be durable; 3. Treat the Gulf as a complex and interconnected network of ecosystems from shoreline to deep sea; and 4. Recognize that human and ecosystem productivity in the Gulf are interdependent, and that human needs from and effects on the Gulf must be integral to restoration planning. With these principles in mind, we provide the scientific basis for a sustainable restoration program along three themes: 1. Assess and repair damage from DWH and other stresses on the Gulf; 2. Protect existing habitats and populations; and 3. Integrate sustainable human use with ecological processes in the Gulf of Mexico. Under these themes, 15 historically informed, adaptive, ecosystem-based restoration actions are presented to recover Gulf resources and rebuild the resilience of its ecosystem. The vision that guides our recommendations fundamentally imbeds the restoration actions within the context of the changing environment so as to achieve resilience of resources, human communities and the economy into the indefinite future

Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy

Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A*0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma

Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a

<p>Abstract</p> <p>Background</p> <p>X chromosome inactivation is the mechanism used in mammals to achieve dosage compensation of X-linked genes in XX females relative to XY males. Chromosome silencing is triggered in <it>cis </it>by expression of the non-coding RNA <it>Xist</it>. As such, correct regulation of the <it>Xist </it>gene promoter is required to establish appropriate X chromosome activity both in males and females. Studies to date have demonstrated co-transcription of an antisense RNA <it>Tsix </it>and low-level sense transcription prior to onset of X inactivation. The balance of sense and antisense RNA is important in determining the probability that a given <it>Xist </it>allele will be expressed, termed the X inactivation choice, when X inactivation commences.</p> <p>Results</p> <p>Here we investigate further the mechanism of <it>Xist </it>promoter regulation. We demonstrate that both sense and antisense transcription modulate <it>Xist </it>promoter DNA methylation in undifferentiated embryonic stem (ES) cells, suggesting a possible mechanistic basis for influencing X chromosome choice. Given the involvement of sense and antisense RNAs in promoter methylation, we investigate a possible role for the RNA interference (RNAi) pathway. We show that the <it>Xist </it>promoter is hypomethylated in ES cells deficient for the essential RNAi enzyme Dicer, but that this effect is probably a secondary consequence of reduced levels of <it>de novo </it>DNA methyltransferases in these cells. Consistent with this we find that Dicer-deficient XY and XX embryos show appropriate <it>Xist </it>expression patterns, indicating that Xist gene regulation has not been perturbed.</p> <p>Conclusion</p> <p>We conclude that <it>Xist </it>promoter methylation prior to the onset of random X chromosome inactivation is influenced by relative levels of sense and antisense transcription but that this probably occurs independent of the RNAi pathway. We discuss the implications for this data in terms of understanding <it>Xist </it>gene regulation and X chromosome choice in random X chromosome inactivation.</p

A long winter for the Red Queen: rethinking the evolution of seasonal migration

This paper advances an hypothesis that the primary adaptive driver of seasonal migration is maintenance of site fidelity to familiar breeding locations. We argue that seasonal migration is therefore principally an adaptation for geographic persistence when confronted with seasonality – analogous to hibernation, freeze tolerance, or other organismal adaptations to cyclically fluctuating environments. These ideas stand in contrast to traditional views that bird migration evolved as an adaptive dispersal strategy for exploiting new breeding areas and avoiding competitors. Our synthesis is supported by a large body of research on avian breeding biology that demonstrates the reproductive benefits of breeding‐site fidelity. Conceptualizing migration as an adaptation for persistence places new emphasis on understanding the evolutionary trade‐offs between migratory behaviour and other adaptations to fluctuating environments both within and across species. Seasonality‐induced departures from breeding areas, coupled with the reproductive benefits of maintaining breeding‐site fidelity, also provide a mechanism for explaining the evolution of migration that is agnostic to the geographic origin of migratory lineages (i.e. temperate or tropical). Thus, our framework reconciles much of the conflict in previous research on the historical biogeography of migratory species. Although migratory behaviour and geographic range change fluidly and rapidly in many populations, we argue that the loss of plasticity for migration via canalization is an overlooked aspect of the evolutionary dynamics of migration and helps explain the idiosyncratic distributions and migratory routes of long‐distance migrants. Our synthesis, which revolves around the insight that migratory organisms travel long distances simply to stay in the same place, provides a necessary evolutionary context for understanding historical biogeographic patterns in migratory lineages as well as the ecological dynamics of migratory connectivity between breeding and non‐breeding locations.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149253/1/brv12476.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149253/2/brv12476_am.pd

Migration Patterns, Use of Stopover Areas, and Austral Summer Movements of Swainson\u27s Hawks

From 1995 to 1998, we tracked movements of adult Swainson’s Hawks (Buteo swainsoni), using satellite telemetry to characterize migration, important stopover areas, and movements in the austral summer. We tagged 46 hawks from July to September on their nesting grounds in seven U.S. states and two Canadian provinces. Swainson’s Hawks followed three basic routes south on a broad front, converged along the east coast of central Mexico, and followed a concentrated corridor to a communal area in central Argentina for the austral summer. North of 20°N, southward and northward tracks differed little for individuals from east of the continental divide but differed greatly (up to 1700 km) for individuals from west of the continental divide. Hawks left the breeding grounds mid-August to mid-October; departure dates did not differ by location, year, or sex. Southbound migration lasted 42 to 98 days, northbound migration 51 to 82 days. Southbound, 36% of the Swainson’s Hawks departed the nesting grounds nearly 3 weeks earlier than the other radio-marked hawks and made stopovers 9.0–26.0 days long in seven separate areas, mainly in the southern Great Plains, southern Arizona and New Mexico, and northcentral Mexico. The birds stayed in their nonbreeding range for 76 to 128 days. All used a core area in central Argentina within 23% of the 738 800-km2 austral summer range, where they frequently moved long distances (up to 1600 km). Conservation of Swainson’s Hawks must be an international effort that considers habitats used during nesting and non-nesting seasons, including migration stopovers

Dissecting the First Transcriptional Divergence During Human Embryonic Development

The trophoblast cell lineage is specified early at the blastocyst stage, leading to the emergence of the trophectoderm and the pluripotent cells of the inner cell mass. Using a double mRNA amplification technique and a comparison with transcriptome data on pluripotent stem cells, placenta, germinal and adult tissues, we report here some essential molecular features of the human mural trophectoderm. In addition to genes known for their role in placenta (CGA, PGF, ALPPL2 and ABCG2), human trophectoderm also strongly expressed Laminins, such as LAMA1, and the GAGE Cancer/Testis genes. The very high level of ABCG2 expression in trophectoderm, 7.9-fold higher than in placenta, suggests a major role of this gene in shielding the very early embryo from xenobiotics. Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression. A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta. The induction of this network could be recapitulated in an in vitro trophoblast differentiation model