Approach to the difficult transseptal: diathermy facilitated left atrial access

Percutaneous transseptal left atrial (LA) access is increasingly becoming a routine procedure in the electrophysiology and cardiac catheterisation laboratories. Our aim was to review an unselected large series of this procedure performed over a period of five years. We clinically characterised difficult cases and presented a method of safe and expeditious LA access. Overall, 543 transseptal punctures were performed. Of those, 10 were classified as difficult, with failure to access the LA in three or more attempts. In all 10 cases, surgical electrocautery was successfully used to facilitate needle puncture of the septum. All patients subsequently underwent an uncomplicated procedure. In conclusion, we describe a method to trouble-shoot the difficult transseptal access procedure, outlining the clinical characteristics, echocardiographic features and special precautions that need to be considered when utilising this method.     

In silico and in vitro metabolism of ribociclib: a mass spectrometric approach to bioactivation pathway elucidation and metabolite profiling

Ribociclib (RBC, Kisqali®) is a highly selective CDK4/6 inhibitor that has been approved for breast cancer therapy. Initially, prediction of susceptible sites of metabolism and reactivity pathways were performed by the StarDrop WhichP450™ module and the Xenosite web predictor tool, respectively. Later, in vitro metabolites and adducts of RBC were characterized from rat liver microsomes using LC-MS/MS. Subsequently, in silico data was used as a guide for the in vitro work. Finally, in silico toxicity assessment of RBC metabolites was carried out using DEREK software and structural modification was proposed to reduce their side effects and to validate the bioactivation pathway theory using the StarDrop DEREK module. In vitro phase I metabolic profiling of RBC was performed utilizing rat liver microsomes (RLMs). Generation of reactive metabolites was investigated using potassium cyanide (KCN) as a trapping nucleophile for the transient and reactive iminium intermediates to form a stable cyano adduct that can be identified and characterized using mass spectrometry. Nine phase I metabolites and one cyano adduct of RBC were characterized. The proposed metabolic pathways involved in generation of these metabolites are hydroxylation, oxidation and reduction. The reactive intermediate generation mechanism of RBC may provide an explanation of its adverse reactions. Aryl piperazine is considered a structural alert for toxicity as proposed by the DEREK report. We propose that the generation of only one reactive metabolite of RBC in a very small concentration is due to the decreased reactivity of the piperazine ring compared to previous reports of similar drugs. Docking analysis was performed for RBC and its proposed derivatives at the active site of the human CDK6 enzyme. Methyl-RBC exhibited the best ADMET and docking analysis and fewer side effects compared to RBC and fluoro-RBC. Further drug discovery studies can be conducted taking into account this concept allowing the development of new drugs with enhanced safety profiles that were confirmed by using StarDrop software. To the best of our knowledge, this is the first literature report of RBCin vitro metabolic profiling and structural characterization and toxicological properties of the generated metabolites.

Nine phase I metabolites and one product of KCN trapping of RBC were characterized. Aryl piperazine is considered a structural alert for toxicity as proposed by the DEREK report. Methyl-RBC exhibited less toxicity and more binding affinity to CDK6.     

Developmental changes in group climate in two types of group therapy for binge-eating disorder: A growth curve analysis

Abstract

The development of group climate across 16 sessions of group psychodynamic–interpersonal psychotherapy (GPIP) and group cognitive–behavioral therapy (GCBT) for 65 female treatment completers with binge-eating disorder (BED) was assessed. Engaged scale growth for GPIP patients varied across sessions and was best represented by a cubic growth curve. This suggested that GPIP progressed in definable phases that reflected a rupture and repair sequence of engaged group climate. For patients receiving GCBT, engaged, avoiding, and conflict scale growth was gradual and consistent (i.e., linear), indicating an increase in positive group climate across sessions. This likely reflected patients taking greater responsibility for treatment as suggested by the CBT model. Linear growth in engaged climate mediated the relationship between attachment anxiety and outcome in GPIP. A consistent increase in engaged group climate through the rupture and repair phase may be a necessary condition for successful treatment of BED patients with high attachment anxiety who receive GPIP.

Zusammenfassung

Entwicklung von Veränderungen im Gruppenklima bei zwei Arten von Gruppentherapie für Essstörungen: Eine Wachstumskurven-Analyse

Es wurde die Entwicklung des Gruppenklimaklimas über 16 Sitzungen bei psychodynamisch - interpersoneller Gruppentherapie (psychodynamic-interpersonal psychotherapy [GPIP]) und kognitiv-verhaltensmässiger Gruppentherapie (group cognitive-behavioral therapy [GCBT]) eingeschätzt. An der Untersuchung nahmen 65 Frauen mit Essanfallstörungen, die die Behandlung auch zu Ende geführt haben, teil. Der Zuwachs der Engagement-Skala variierte für GPIP-Patienten und ließ sich am besten mit Hilfe einer kubischen Wachstumskurve wiedergeben. Das legt für das engagierte Gruppenklima das Fortschreiten vom GPIP-Patienten mit einer Phasensequenz von Einbrüchen und ihrer Wiederherstellung nahe. Für GCBT-Patienten war der Anstieg der Skalen für engagiertes, vermeidendes und konflikthaftes Gruppenklima graduell und konsistent (d. h. linear) und wies insgesamt auf einen kontinuierlichen Anstieg des positiven Gruppenklimas über die Sitzungen hin. Das spiegelt wahrscheinlich die größere Verantwortung der Patienten für die Behandlung, wie sie nach dem CBT-Modell angenommen wird, wider. Ein linearer Anstieg des engagierten Gruppenklimas, über die Phasen von Einbrüchen und Wiederherstellung hinweg, könnte eine notwendige Bedingung für eine erfolgreiche Behandlung von Essanfallstörungs-Patienten mit hoher Bindungsangst unter der GPIP Bedingung sein.

Résumé

Changements du climat dans le groupe dans deux types de thérapies de groupe pour le binge-eating?: une analyse par courbe de croissance

Le développement du climat dans le groupe était évalué à travers 16 séances de psychothérapie de groupe psychodynamique–interpersonnelle (GCBT) et de thérapie de groupe cognitivo–comportementale (GCBT) pour 65 femmes avec un trouble de binge–eating (BED) ayant terminé le traitement. La croissance sur l’échelle d'engagement des patients en GPIP variait à travers les séances et était le mieux représentée par une courbe de croissance cubique. Ceci suggère que la GPIP progressait par phases définies reflétant une séquence de rupture et de réparation du climat d'engagement du groupe. Pour les patients en GCBT, la croissance des échelles d'engagement, d’évitement et de conflit était graduel et consistant (linéaire), indiquant une augmentation du climat de groupe positif à travers les séances. Ceci pourrait refléter une plus grande prise de responsabilité par les patients pour leur traitement, comme suggéré par le modèle CBT. La croissance linéaire du climat engagé était médiatrice de la relation entre l'anxiété d'attachement et l'issue en GPIP. Une augmentation consistante du climat d'engagement dans le groupe dans la phase de rupture et de réparation pourrait être une condition nécessaire pour un traitement réussi de patients BED avec une haute anxiété d'attachement qui bénéficient d'une GPIP.

Resumen

Cambios en el clima grupal en dos tipos de terapia para la bulimia: análisis de la curva de crecimiento

Se evaluó el desarrollo del clima grupal a lo largo de 16 sesiones de una psicoterapia grupal psicodinámica-interpersonal (GPIP) y de otra grupal cognitivo-comportamental (GCBT) de sesenta y cinco mujeres que completaron su tratamiento para desorden bulímico (BED). El crecimiento de la escala comprometida para pacientes GPIP varió a través de las sesiones y se lo representó mejor por medio de una curva de crecimiento cúbico. Esto sugiere que la GPIP progresó en fases definibles que reflejaron una secuencia de ruptura y reparación del clima comprometido grupal. Para los pacientes que recibieron GCBT, el crecimiento en las escalas comprometida, evitativa y conflictiva fue gradual y consistente (esto es, lineal), lo que indica un aumento en el clima positivo grupal a lo largo de las sesiones. Probablemente, esto fue reflejo de que los pacientes tomaron su tratamiento con mayor responsabilidad, según lo sugiere el modelo CBT. Un crecimiento lineal en el clima comprometido medió entre la ansiedad de apego y el resultado en GPIP. Un aumento consistente en el clima grupal comprometido a través de las fases de ruptura y reparación puede ser una condición necesaria para un tratamiento exitoso con GPIP de pacientes BED con gran ansiedad de apego.

Resumo

Mudanças no ambiente de grupo em dois tipos de terapia de grupo para a perturbação de ingestão alimentar compulsiva: uma análise da curva de crescimento

Foi avaliado o desenvolvimento de atmosfera de grupo durante 16 sessões de psicoterapia interpessoal psicodinâmica de grupo (PIPG) e terapia cognitivo-comportamental de grupo (TCCG) no tratamento de 65 mulheres que completaram o tratamento para a perturbação de ingestão alimentar compulsiva (PIAC). O aumento na escala do envolvimento em pacientes com PIPG variou ao longo das sessões e era melhor descrito por uma curva de crescimento cúbica. Isto sugere que a PIPG progrediu em fases definidas que reflectem a ruptura e restauram a sequência da atmosfera de envolvimento do grupo. Para os pacientes que receberam TCCG, a elevação nas escalas de envolvimento, evitamento e conflito foi gradual e consistente (i.e. linear), indicando um aumento positivo no ambiente do grupo ao longo das sessões. Isto parece reflectir que os pacientes tomam maiores responsabilidades no tratamento tal como é sugerido no modelo cognitivo-comportamental. O crescimento linear no envolvimento mediava a relação entre a vinculação ansiosa e o resultado da PIPG. Um aumento consistente no envolvimento do ambiente de grupo ao longo da ruptura e fase de reconciliação poderá ser necessário para o sucesso no tratamento de pacientes com BED, com elevada vinculação ansiosa, que recebem PIPG.

Sommario

Cambiamenti nel clima di gruppo in due tipi di terapia di gruppo per il binge-eating disorder: un'analisi della curva crescente

E’ stato valutato lo sviluppo del clima di gruppo mediante 16 sedute di psicoterapia di gruppo psicodinamico-interpersonale (GPIP) e di terapia di gruppo cognitivo-comportamentale (GCBT) per 65 donne con binge-eating disorder (BED) che hanno terminato il trattamento.

La crescita nelle scale impiegate per i pazienti GPIP è variata tra le sedute ed è stata al meglio rappresentata da una curva di crescita cubica. Ciò ha suggerito che il GPIP è progredito in fasi determinabili che hanno riflettuto una sequenza di rottura e riparazione del clima di gruppo instaurato.

Per i pazienti che hanno ricevuto la GCBT, la crescita nelle scale di adesione, evitamento e conflitto è stata graduale e consistente (lineare), indicando un incremento nel positivo clima di gruppo attraverso le sedute. Ciò probabilmente ha rispecchiato i pazienti che hanno assunto la maggiore responsabilità per il trattamento, come suggerito dal modello CBT.

La crescita lineare nel clima instaurato ha mediato la relazione tra ansia d'attaccamento ed esito nel GPIP. Un incremento consistente nel clima di gruppo instaurato attraverso la fase di rottura e riparazione potrebbe essere una condizione necessaria per un trattamento di successo dei pazienti con BED con alta ansia d'attaccamento che ricevono GPIP.

     

Developmental Trajectories of Delinquent and Aggressive Behavior: Evidence for Differential Heritability

Child Psychiatry & Human Development - The developmental course of antisocial behavior is often described in terms of qualitatively distinct trajectories. However, the genetic etiology of...     

Investigation of the Microstructure and Compressibility of Biodegradable Fe-Mn-Cu/W/Co Nanostructured Alloy Powders Synthesized by Mechanical Alloying

In this research work, the nanostructured Fe-Mn (BM0), Fe-Mn-Cu (BM1), Fe-Mn-W (BM2), and Fe-Mn-Co (BM3) biodegradable alloys were successfully synthesized using mechanical alloying. The microstructure of the synthesized alloys was examined using XRD, SEM equipped with EDS, and HRTEM techniques. The results obtained based on these techniques confirmed the development of nanostructured BM0, BM1, BM2, and BM3 alloys and homogenous solid solutions with an even elemental dispersion. The compressibility of the synthesized alloys was investigated experimentally and empirically in the as-milled conditions and after applying a stress relief treatment (150 °C for 1 h). The load applied for compaction experiments ranged from 25–1100 MPa with a rate of 1 mm/min. According to the experimentation performed in the current study, the relative density of the as-milled BM0, BM1, BM2, and BM3 alloys was 72.90% and 71.64%, 72.32%, and 72.03%, respectively. After applying the stress relief treatment, the density was observed to increase to 75.23%, 77.10%, 72.65%, and 72.86% for BM0-S, BM1-S, BM2-S and BM3-S samples, respectively. A number of compaction models were tested to identify the optimum models for predicting the compressibility behavior of nanostructured Fe-Mn, Fe-Mn-Cu, Fe-Mn-W, and Fe-Mn-Co alloys in the as-milled and stress-relieved conditions.