Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...     

Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates.

High cytoplasmic expression of maspin was described in ovarian cancers of shorter survival rates. Until now, no relationship has been described between expression of maspin and sensitivity to cisplatin in ovarian cancers. This study aimed at examining the relationship between expression of maspin, detected by immunohistochemistry and clinical response to cisplatin in ovarian cancer cases as well as the in vitro sensitivity to cisplatin of 11 ovarian cancer cell lines. The analyzes were performed on 73 samples of ovarian cancer and on A2780P, A2780RCIS, CAOV-3, EFO 21, EFO 27, ES-2, Mdah 2774, OAW 42, OVCAR-3, PA-1, and SKOV-3 ovarian cancer cells. Cytoplasmic maspin expression in studied cells significantly correlated with cisplatin sensitivity. A significantly shorter overall survival and progression-free survival was associated with lower cytoplasmic maspin expression at first-look laparotomies and nuclear maspin expression and secondary cytoreductions. Higher nuclear maspin at first-look laparotomies expression was specific for cases of complete response. In the study, the elevated expression of maspin was shown to be typical for cisplatin-sensitive ovarian cancers.     

Mapping molecular networks using proteomics: a vision for patient-tailored combination therapy.

Mapping tumor cell protein networks in vivo will be critical for realizing the promise of patient-tailored molecular therapy. Cancer can be defined as a dysregulation or hyperactivity in the network of intracellular and extracellular signaling cascades. These protein signaling circuits are the ultimate targets of molecular therapy. Each patient's tumor may be driven by a distinct series of molecular pathogenic defects. Thus, for any single molecular targeted therapy, only a subset of cancer patients may respond. Individualization of therapy, which tailors a therapeutic regimen to a tumor molecular portrait, may be the solution to this dilemma. Until recently, the field lacked the technology for molecular profiling at the genomic and proteomic level. Emerging proteomic technology, used concomitantly with genomic analysis, promises to meet this need and bring to reality the clinical adoption of molecular stratification. The activation state of kinase-driven signal networks contains important information relative to cancer pathogenesis and therapeutic target selection. Proteomic technology offers a means to quantify the state of kinase pathways, and provides post-translational phosphorylation data not obtainable by gene arrays. Case studies using clinical research specimens are provided to show the feasibility of generating the critical information needed to individualize therapy. Such technology can reveal potential new pathway interconnections, including differences between primary and metastatic lesions. We provide a vision for individualized combinatorial therapy based on proteomic mapping of phosphorylation end points in clinical tissue material.     

Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia.

PURPOSE: Cloretazine (VNP40101M) is a novel sulfonylhydrazine alkylating agent with significant antileukemia activity. A phase I study of cloretazine combined with cytarabine (1-beta-d-arabinofuranosylcytosine, ara-C) was conducted in patients with refractory disease. DESIGN: Ara-C was given i.v. at a fixed dose of 1.5 gm/m(2)/d by continuous infusion for 4 days (patients ages <65 years at time of diagnosis) or 3 days (patients ages > or =65 years). Cloretazine was given i.v. over 15 to 60 minutes on day 2 at a starting dose of 200 mg/m(2), with escalation in 100 mg/m(2) increments in cohorts of three to six patients until a maximum tolerated dose was established. The DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT) was measured at baseline. RESULTS: Forty patients, including 32 with acute myeloid leukemia, received 47 courses of treatment. Complete responses were seen at cloretazine dose levels of > or =400 mg/m(2) in 10 of 37 (27%) evaluable patients, and in this patient subset, AGT activity was significantly lower in patients that responded to treatment than in patients who did not (P < or = 0.027). Dose-limiting toxicities (gastrointestinal and myelosuppression) were seen with 500 and 600 mg/m(2) of cloretazine combined with the 4-day ara-C schedule but not seen with the 3-day schedule. CONCLUSION: The recommended cloretazine dose schedule for future studies is 600 mg/m(2) combined with 1.5 gm/m(2)/d continuous infusion of ara-C for 3 days. The cloretazine and ara-C regimen has significant antileukemic activity. AGT activity may be a predictor of response to cloretazine.     

Right heart function in impaired left ventricular diastolic function: 2D speckle tracking echocardiography–based and Doppler tissue imaging–based analysis of right atrial and ventricular function

Aim

The aim of our study was to describe right atrial (RA) and right ventricular (RV) function, assessed by Doppler tissue imaging and 2D speckle tracking echocardiography (2DSTE), in women with signs of early impaired left ventricular diastolic function (DD).

Methods and Results

In a cross‐sectional trial, standard parameters of diastolic and right heart function were investigated in 438 women of the Berlin Female Risk Evaluation (BEFRI) study. In a subset of women, average peak systolic RA strain (RAS), as well as the average peak systolic RV strain of the free wall (RVS free wall) and of all RV segments (average RV strain; RVS Avg), was analyzed using 2DSTE. Compared to women with normal diastolic function (DD0), RAS, RVS free wall and RVS Avg were significantly reduced in DD (43.1% ± 11.9%, ?26.7% ± 5.6%, and ?23.3% ± 3.5% in DD0; vs 35.1% ± 10.4%, ?23.9% ± 5.5%, and ?20.6% ± 3.8% in DD; P < .01). Peak RV myocardial velocity (RV‐IVV) and acceleration during isovolumetric contraction (RV‐IVA) were markedly higher in DD (15.0 ± 3.9 cm/s and 3.1 ± 1.0 m/s² in DD vs 11.9 ± 3.2 cm/s and 2.8 ± 0.8 m/s² in DD0; P < .05). RAS and RV‐IVV were significantly associated with DD after adjustment to age, BMI, and left atrial strain in multivariate regression analysis.

Conclusion

Systolic right heart function is significantly altered in DD. DTI as well as 2DSTE constitute sensitive echocardiographic tools that enable the diagnosis of impaired right heart mechanics in early‐staged DD.     

Faszikuläre ventrikuläre Tachykardie bei einem 49-jährigen Patienten

We report a 49-year-old patient who presented with tachycardia in our emergency room. The 12-lead ECG showed a wide complex tachycardia with a heart rate of 234 beats per minute. After structural heart disease was excluded via echocardiography, coronary angiography and magnetic resonance imaging, an electrophysiological study was performed. During programmed ventricular stimulation, a fascicular tachycardia was induced, which was successfully treated by radiofrequency ablation. Fascicular ventricular tachycardia is a rare tachycardia that occurs in patients without structural heart disease. Radiofrequency ablation can be performed safely and shows a high success rate. Differential diagnoses of fascicular ventricular tachycardias are substrate-based ventricular tachycardia and supraventricular tachycardia.     

Brain temperature regulation in poor-grade subarachnoid hemorrhage patients – A multimodal neuromonitoring study

Elevated body temperature (T_core) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (T_brain) is usually higher than T_core. However, the implication of this difference (T_delta) remains unclear. We aimed to study factors associated with higher T_delta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of T_core, T_brain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. T_brain was tightly correlated with T_core (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (T_delta +0.18°C, IQR −0.01 – 0.37°C). A higher T_delta was associated with better metabolic state, indicated by lower CMD-glutamate (p = 0.003) and CMD-lactate (p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, T_delta was significantly lower (0°C, IQR −0.2 – 0.1; p < 0.001). A higher T_delta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that T_brain is associated with brain metabolic activity and exceeds T_core when mitochondrial function is preserved. Further studies are needed to understand how T_delta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH.