[ADAPTHERA-Statewide cross-sectoral care network for patients with early rheumatoid arthritis shows sustained remission in standard care]. / ADAPTHERA ­ Landesweit transsektorales Versorgungsnetzwerk für Patienten mit früher rheumatoider Arthritis zeigt anhaltende Remissionen in der Regelversorgung.

BACKGROUND/OBJECTIVE: The majority of patients in Germany miss out on the necessity of early diagnosis and initiation of therapy for rheumatoid arthritis (RA) caused by considerable structural deficits in the health care system. The challenge is to reconcile the individual demand for the best possible therapy result with a sustainable expenditure of resources. METHODS: The cross-sectoral regional care network ADAPTHERA aims to improve early RA diagnosis and treatment in Rhineland-Palatinate. The retrospective triage analyses of suspected early onset RA patients was performed by tracing the selection process of all available enquiries (n = 1045). For analysis of the clinical course of the disease, a subset comprising 143 patients with a minimum observation time of 12 months (5 consecutive visits) was available. Clinical and laboratory parameters were collected quarter yearly, self-administered questionnaires were filled out and the treatment was adapted if necessary. RESULTS: A total of 454 patients were included. The mean waiting time was 23.9 (SD = 18) days. The mean observation period in the subcohort was 29.2 (SD = 12.7) months, with about 50% of the patients presenting within 3 months. Almost 75% of the patients were in remission after 2 years. A sustained remission could be described for 74.8% (6 months) and 53.5% (12 months), respectively. Especially patients with rapid remission induction benefited in terms of longer remissions (p = 0.03). A very early stage of the disease (VERA) was associated with a rarely necessary biologic therapy (p = 0.022). DISCUSSION: The approach of a supply network is not a panacea, but it might improve healthcare for patients with early onset RA. In order to minimize resource utilization, a pinpoint referral and accurate triage of potential cases are crucial.

[The regional network ADAPTHERA : Rheumatology care through coordinated cooperation: comprehensive, trans-sectoral, covering all health insurance. Initial results]. / Das landesweite Netzwerk ADAPTHERA : Erste Ergebnisse einer flächendeckenden, krankenkassenübergreifenden und transsektoralen rheumatologischen Versorgung.

The aim of the rheumatology network ADAPTHERA ("risk-adapted rheumatology therapy") is to achieve a comprehensive improvement in rheumatology care by coordinating treatment in a regional, trans-sectoral network. Accompanying biomedical research projects, training concepts, and the construction of a rheumatology register (gathering data and biomaterials) should furthermore ensure the stable and sustainable optimisation of care. In the pilot phase (2012-2015) the focus of the ADAPTHERA network, required as a "regional key project" within the framework of the Initiative on Health Economy of Rheinland-Palatinate (RL-P), Germany, was placed on the optimisation of the early diagnosis of rheumatoid arthritis, where it is well-known that there is a significant care deficit.Through the intensive, stable, and coordinated cooperation of all health care partners in the field of rheumatology (registered general practitioners and orthopaedic specialists, registered core rheumatologists as well as the Association of Rheumatology of RL-P) a unique regional, comprehensive offer with verifiable care optimisation has been established in RL-P. The network is supported by outstanding collaboration with the Association of Statutory Health Insurance Physicians and the self-help organisation Rheumatology League.The aims that were established at the start of the project will be achieved by the end of the pilot phase:- significant improvement in the early diagnosis of rheumatoid arthritis (an average of 23.7 days until diagnosis by rheumatologists)- access covering all health insurance (regardless of the particular scheme the patients belong to)- comprehensive (verifiable participation of general practitioners from all over RL-P)- data and biomaterials collection, established as a basis for biomarker research, and a rheumatology register for RL-P.

Floral diversity and pollination strategies of three rheophytic Schismatoglottideae (Araceae).

Homoplastic evolution of 'unique' morphological characteristics in the Schismatoglottideae - many previously used to define genera - prompted this study to compare morphology and function in connection with pollination biology for Aridarum nicolsonii, Phymatarum borneense and Schottarum sarikeense. Aridarum nicolsonii and P. borneense extrude pollen through a pair of horned thecae while S. sarikeense sheds pollen through a pair of pores on the thecae. Floral traits of spathe constriction, presence and movement of sterile structures on the spadix, the comparable role of horned thecae and thecae pores, the presence of stamen-associated calcium oxalate packages, and the timing of odour emission are discussed in the context of their roles in pollinator management. Pollinators for all investigated species were determined to be species of Colocasiomyia (Diptera: Drosophilidae).

Ameliorating spatial neglect with non-invasive brain stimulation: from pathophysiological concepts to novel treatment strategies.

Neglect is a multifaceted, complex syndrome, in which patients fail to detect or respond to stimuli or parts thereof located contralesionally. Non-invasive brain stimulation by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) may not only be useful as diagnostic research tools to explore the pathophysiology of neglect, but also for ameliorating its symptoms. Current approaches for modulating neglect non-invasively are mainly based on the neurophysiological concept of interhemispheric inhibition, which suggests a pathological overactivation of the contralesional hemisphere due to reduced inhibitory influences from the lesioned one. Within this framework, non-invasive brain stimulation mainly aims to inhibit the contralesional hemisphere to allow for rebalancing the system. However, facilitatory protocols for enhancing the ipsilesional neural circuitry might also prove useful. In this review, we discuss the contribution of non-invasive brain stimulation to current pathological concepts of neglect, the promising results of the proof-of-principle studies currently available as well as the specific aspects to be systematically investigated before broader clinical trials may eventually suggest a routine clinical application.

Conventional and novel modes of exine patterning in members of the Araceae--the consequence of ecological paradigm shifts?

In the family Araceae, the members of all subfamilies except Aroideae follow the conventional mode of exine formation pattern, which conforms with the textbook view of sporoderm stratification and chemistry (sporopollenin ektexine formed before the endexine). Only members of the subfamily Aroideae show a quite uncommon mode of exine formation pattern, with an endexine formed prior to the nonsporopollenin, polysaccharidic outer exine layer. The intine is formed simultaneously with this non-sporopollenin layer. From the differing timetable and especially from the different origin it is concluded that this outer exine layer is not homologous to the angiosperm ektexine. The fundamental question, why members of the Aroideae lack an elaborated sporopollenin ektexine, is discussed in terms of functionality of the nonsporopollenin outer exine layer. It seems that a major change in aroid evolution took place at the point when the family phylogenetically and ecologically shifted from bisexual (most subfamilies) to unisexual flowers (Aroideae only). The hypothesis is that ephemeral spathes and the absence of sporopollenin are the consequence of an adaptive syndrome for a short pollination time window in many members of the Aroideae, with short-lived pollen, an energetically not costly pollen wall, rapid germination of pollen tube, and brief receptivity of stigma.

N,N',N"-triferuloylspermidine, a new UV absorbing polyamine derivative from pollen of Hippeastrum x hortorum.

A new hydroxycinnamoyl polyamine derivative, N,N',N"-triferuloylspermidine (= (E)-N-(4-aminobutyl) -3,3',3"-tris(4-hydroxy-3-methoxyphenyl)-N,N',N"- (butane-1,4-diyl)tris [prop-2-enamide]) (1) was detected in the H2O/MeOH extract of pollen from Hippeastrum x hortorum. The compound was identified by on-line-coupled high-performance liquid chromatography and atmospheric-pressure chemical-ionization mass spectrometry (HPLC-UV(DAD)/APCI-MS and MS/MS). The structure was proven by comparing the HPLC/MS data after UV-induced (E) <==> (Z) photoisomerization and catalytic hydrogenation of the natural compound and the synthetic reference compound. This is the first report of a triferuloylspermidine in nature.

Cutting edge: Stat6-dependent substrate depletion regulates nitric oxide production.

The cytokines IL-4 and IL-13 inhibit the production of NO from activated macrophages through an unresolved molecular mechanism. We show here that IL-4 and IL-13 regulate NO production through depletion of arginine, the substrate of inducible NO synthase (iNOS). Inhibition of NO production from murine macrophages stimulated with LPS and IFN-gamma by IL-4 or IL-13 was dependent on Stat6, cell density in the cultures, and pretreatment for at least 6 h. IL-4/IL-13 did not interfere with the expression or activity of iNOS but up-regulated arginase I (the liver isoform of arginase) in a Stat6-dependent manner. Addition of exogenous arginine completely restored NO production in IL-4-treated macrophages. Furthermore, impaired killing of the intracellular pathogen Toxoplasma gondii in IL-4-treated macrophages was overcome by supplementing L-arginine. The simple system of regulated substrate competition between arginase and iNOS has implications for understanding the physiological regulation of NO production.

The main products of the low molecular mass fraction in the venom of the spider Latrodectus menavodi.

The low molecular mass fraction of the venom of the spider Latrodectus menavodi, a black widow spider domiciled in Madagascar, was analyzed with HPLC combined with electrospray mass spectrometry as lyophilized powder and as freshly milked liquid venom. The main components were found to be the purine derivatives adenosine (1), guanosine (2), inosine (3), and 2,4,6-trihydroxypurine (4). Compounds 1-3 are known as components of spider or snake venoms, but they have never been found previously in the venom of the species Latrodectus, whereas compound 4 has not previously been found in any spider venoms. The lyophilized and unlyophilized venoms were found to have identical composition.

Antimicrobial activities of secondary metabolites produced by endophytic fungi from Spondias mombin.

We performed a search for bioactive compounds produced by fungal endophytes from Spondias mombin (Anacardiaceae). Culture broth extracts of Guignardia sp., Phomopsis sp. and Pestalotiopsis guepinii were separated by chromatographic methods and tested for biological activities. The crude extracts of these endophytes were tested against fourteen organisms, including actinomycetes, Gram-negative and Gram-positive bacteria, yeast, and filamentous fungi. All fungal extracts inhibited actinomycete growth. Guignardia sp. was also active against Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae, Geotrichum sp., and Penicillium canadensis. Culture extracts of P. guepinii were active against S. cerevisae, while strains of Phomopsis sp. showed a pronounced antifungal effect against Cladosporium elatum, Mycotypha sp. and S. cerevisae.

Three New Tazettine-Type Alkaloids from Galanthus gracilis and Galanthus plicatus Subsp. byzantinus.

Three new tazettine-type alkaloids were isolated from two different GALANTHUS species of Turkish origin. (+)-Isotazettinol and (+)-3- O-demethylmacronine are obtained from G. GRACILIS, while (+)-3- O-demethyl-3-epimacronine is found in G. PLICATUS subsp. BYZANTINUS. The known base, trispheridine, is reported for the first time in GALANTHUS genus.

Indole Alkaloids from Alstonia angustifolia.

From the stem bark of ALSTONIA ANGUSTIFOLIA, eleven alkaloids were isolated. Seven of them are known ones: echitamine ( 1), N(b)-demethylechitamine ( 2), pseudoakuammigine ( 3), tubotaiwine ( 5), akuammicine ( 6), N(b)-beta-methylantirhine ( 12), and N(b)-methylakuammidine ( 13). The four others, pseudoakuammigine N-oxide ( 4), akuammicine N-oxide ( 7), N(b)-demethylalstogustine ( 8), and N(b)-demethylalstogustine N-oxide ( 11), are new alkaloids. Their structures were determined by means of spectroscopic analysis and chemical correlation with known alkaloids.

The spermine alkaloids of Chaenorhinum minus.

The spermine alkaloids O-methylorantine ( 1), orantine ( 2), ephedradine B ( 3), ephedradine C ( 4), and chaenorpine ( 5) were isolated from CHAENORHINUM MINUS.

The Alkaloids of Melodinus acutiflorus. Rhyzicine N-Oxide.

From the leaves of MELODINUS ACUTIFLORUS a new alkaloid, rhazicine N-oxide ( 2), and two known compounds, deacetylakuammiline ( 3) and 16- EPI-rhazinaline ( 4) were isolated. The structure of 2 was determined by spectral analysis and chemical correlation with rhazicine ( 1).

Conversion of nitroheptane to dihydrojasmone.

The synthesis of dihydrojasmone ( 4) from 1-nitroheptane via 5-nitro-2-undecanone is described. It is not necessary to transform the second nitro to a ketone group to give 2,5-undecadione. A direct transformation procedure is given.

[Contributions to the Structure of Hypercratine, another Alkaloid of Ruspolia hypercrateriformis.]. / Zur Struktur von Hypercratin, einem weiteren Alkaloid aus Ruspolia hypercrateriformis*

Besides the known pyrrolidine alkaloids ruspolinone ( 1), norruspolinone ( 2), and norruspoline ( 3) the "bispyrrolidine" alkaloid hypercratine was isolated from the roots of RUSPOLIA HYPERCRATERIFORMIS M. R. (Acanthaceae). After chemical and spectroscopic analysis of the new compound, structure 4 is suggested.