The operationalized psychodynamic diagnostics system. Clinical relevance, reliability and validity

In this paper, we present a multiaxial system for psychodynamic diagnosis, which has attained wide usage in Germany in the last 10 years. First we will discuss the 4 operationalized psychodynamic diagnostics (OPD) axes: illness experience and treatment assumptions, relationships, mental conflicts, and structure, then clinical applications will be outlined. Focus psychodynamic formulations can be employed both with inpatients and with outpatients. Studies show good reliability in a research context and acceptable reliability for clinical purposes. Validity will be separately summarized as content, criterion, and construct validity. Validity studies indicate good validity for the individual axes. Numerous studies on the OPD indicate areas of possible improvement, for example for clinical purposes the OPD should be more practically formulated

Riociguat: Mode of action and clinical development in pulmonary hypertension

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and the pivotal Phase III randomized clinical trials in PAH and CTEPH

Generación @

Si la adolescencia fue descubierta a finales del siglo XIX, y se democratizó en la primera mitad del XX, la segunda mitad del siglo ha presenciado la irrupción de la juventud, ya no como sujeto pasivo sino como actor protagonista en la escena pública

Low coordinate magnesium sulfide and selenide complexes

Funding: Authors thank the University of St Andrews and the EPSRC doctoral training grant (EP/N509759/1) for support. We gratefully acknowledge computational support via the EaStCHEM Research Computing Facility.The reactions of [{(iPrDipNacNac)Mg}2] 1 (iPrDipnacnac = HC(iPrCNDip)2) with Ph3P═O at 100 °C afforded the phosphinate complex [(iPrDipNacNac)Mg(OPPh3)(OPPh2)] 3 . Reactions of 1 with Ph3P═E (E = S, Se) proceeded rapidly at room temperature to low-coordinate chalcogenide complexes [{(iPrDipNacNac)Mg}2(μ-S)] 4 and [{(iPrDipNacNac)Mg}2(μ-Se)] 5 , respectively. Similarly, reactions of RNHC═S ((MeCNR)2C═S with R = Me, Et, or iPr) with 1 afforded NHC adducts of magnesium sulfide complexes, [{(iPrDipNacNac)Mg(RNHC)}(μ-S){Mg(iPrDipNacNac)}] 6 , that could alternatively be obtained by adding the appropriate RNHC to sulfide complex 4 . Complex 4 reacted with 1-adamantylazide (AdN3) to give [{(iPrDipNacNac)Mg}2(μ-SN3Ad)] 7 and can form various simple donor adducts in solution, of which [(iPrDipNacNac)Mg(OAd)}2(μ-S)] 8a (OAd = 2-adamantanone) was structurally characterized. The nature of the ionic Mg–E–Mg unit is described by solution and solid-state studies of the complexes and by DFT computational investigations.Publisher PDFPeer reviewe

Characteristics and treatment outcomes of 69 cases with early prosthetic joint infections of the hip and knee

Purpose: Early prosthetic joint infection (PJI) can be treated with an intensive surgical debridement and implant retention (DAIR) of the prosthesis if (1) the prosthesis is stable, (2) the pathogen is not a difficult-to-treat microorganism, (3) symptoms have lasted for <3weeks and (4) a sinus tract is absent. Methods: We retrospectively evaluated the treatment outcome of early PJI in the hip and knee in a single orthopaedic centre. An early PJI was defined as a prosthesis infection within 3months after primary implantation or revision surgery for a non-infectious cause. Results: We identified 69 patients with confirmed early PJI, with a median age of 71 (range 33-84) years. Only 64% presented with ≥2 acute signs of infection. The most commonly isolated bacteria were coagulase-negative staphylococci (38%) and Staphylococcus aureus (25%). Surgical procedures included DAIR (50 cases, 69%) and two-stage exchange (19 cases, 31%). At last follow-up, five ofremaining living 67 patients (7.5%) had a relapse of infection. The overall relapse-free survival of the prosthesis after 2 yearswas 92.3% (95% confidence interval 82-97%) with no significant difference between DAIR and exchange of prosthesis. Conclusion: Our data suggest that an early PJI should be treated with DAIR as a less invasive procedure whenever possible according to the established treatment algorithm

Fluorescence Dequenching Makes Haem-Free Soluble Guanylate Cyclase Detectable in Living Cells

In cardiovascular disease, the protective NO/sGC/cGMP signalling-pathway is impaired due to a decreased pool of NO-sensitive haem-containing sGC accompanied by a reciprocal increase in NO-insensitive haem-free sGC. However, no direct method to detect cellular haem-free sGC other than its activation by the new therapeutic class of haem mimetics, such as BAY 58-2667, is available. Here we show that fluorescence dequenching, based on the interaction of the optical active prosthetic haem group and the attached biarsenical fluorophor FlAsH can be used to detect changes in cellular sGC haem status. The partly overlap of the emission spectrum of haem and FlAsH allows energy transfer from the fluorophore to the haem which reduces the intensity of FlAsH fluorescence. Loss of the prosthetic group, e.g. by oxidative stress or by replacement with the haem mimetic BAY 58-2667, prevented the energy transfer resulting in increased fluorescence. Haem loss was corroborated by an observed decrease in NO-induced sGC activity, reduced sGC protein levels, and an increased effect of BAY 58-2667. The use of a haem-free sGC mutant and a biarsenical dye that was not quenched by haem as controls further validated that the increase in fluorescence was due to the loss of the prosthetic haem group. The present approach is based on the cellular expression of an engineered sGC variant limiting is applicability to recombinant expression systems. Nevertheless, it allows to monitor sGC's redox regulation in living cells and future enhancements might be able to extend this approach to in vivo conditions

The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols

It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme. Like NO, HNO activation appears to occur via interaction with the regulatory ferrous heme on sGC. Somewhat unexpectedly, HNO does not activate the ferric form of the enzyme. Finally, HNO-mediated cysteine thiol modification appears to also affect enzyme activity leading to inhibition. Thus, sGC activity can be regulated by HNO via interactions at both the regulatory heme and cysteine thiols

Reflecting on loss in Papua New Guinea

This article takes up the conundrum of conducting anthropological fieldwork with people who claim that they have 'lost their culture,' as is the case with Suau people in the Massim region of Papua New Guinea. But rather than claiming culture loss as a process of dispossession, Suau claim it as a consequence of their own attempts to engage with colonial interests. Suau appear to have responded to missionization and their close proximity to the colonial-era capital by jettisoning many of the practices characteristic of Massim societies, now identified as 'kastom.' The rejection of kastom in order to facilitate their relations with Europeans during colonialism, followed by the mourning for kastom after independence, both invite consideration of a kind of reflexivity that requires action based on the presumed perspective of another

Normal and abnormal NHC coordination in cationic hydride iodide complexes of aluminium

We thank the University of St Andrews and the EPSRC UK National Mass Spectrometry Facility (NMSF) at Swansea University.The mixed N-heterocyclic carbene (NHC) complexes NHCAlHxI3-x, where NHC is IDip or IMes ((HCNAr)2C:, Ar = 2,6-iPr2C6H3 = Dip (IDip); or 2,4,6-Me3C6H2 = Mes (IMes)), x = 1 or 2, were either prepared from NHCAlH3 and NHCAlI3 or by halogenation of NHCAlH3 with MeI. Reaction of [(IDip)AlHxI3-x], with x = 0-3, with another equivalent of a IDip afforded either fluxional equilibria in benzene solution for x = 0, no reaction for x = 3, or the new mixed normal-abnormal NHC-coordinated ionic complexes [(IDip)AlH2(aIDip)]I ( 9 ) and [(IDip)AlHI(aIDip)]I ( 10 ), where aIDip is the abnormal IDip carbene tautomer bonded through its 4-position. The molecular structures of 9 and 10 were determined and show slightly shorter Al–C(aIDip) than Al–C(IDip) distances. In addition, a complex containing [(IDip)AlI2(aIDip)]I ( 11 ) was structurally characterized though could not intentionally be synthesised. Possible formation mechanisms for 9 - 11 are discussed and the normal and abnormal IDip coordination to the aluminium(III) centre is believed to occur for steric reasons.PostprintPeer reviewe