A multi-modal treatment program for childhood trauma recovery:Women Recovering from Abuse Program (WRAP).

This article describes the Women Recovering from Abuse Program (WRAP), an outpatient day-hospital program for women suffering from the sequelae of childhood abuse. WRAP was conceived in 1998 by clinicians who advocated for its development based on a growing need to provide women who had experienced childhood trauma an alternative to an inpatient program. WRAP draws from a Stage 1 treatment approach to address chronic interpersonal trauma and dissociation by incorporating psychopharmacology, individual and group psychotherapy. The program is structured into two phases: a preparatory Building Resources Group (BRG) and an intensive multimodal segment comprised of seven types of group therapy. Each group is described in terms of the treatment rationale and its structure and process. Two research studies to date support the effectiveness of WRAP.     

PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide

Plasmatic levels of PDGF-AB, TGFbeta1, and bFGF are increased in patients with essential thrombocythemia (ET) while intraplatelet levels are low for PDGF, normal for TGFbeta, and elevated for bFGF. To evaluate the contribution of gene expression to the dysregulated cytokine levels, we studied platelet PDGF-A, PDGF-B, TGFbeta1, and bFGF mRNA in ET patients before and during anagrelide treatment. We found decreased PDGF-A and PDGF-B, increased TGFbeta1, and normal bFGF mRNA levels. During treatment, mRNA levels remained decreased for PDGF-A, were increased for PDGF-B and normal for TGFbeta1. In untreated patients, protein expression of PDGF paralleled its mRNA levels while different patterns of RNA and protein were found for TGFbeta1 and bFGF.     

What Do Medical Students Do and Want When Caring for “Difficult Patients”?

Phenomenon: Medical students, like physicians, experience negative emotions such as frustration when interacting with some patients, and many of these interactions occur for the first time during clinical clerkships. Students receive preclinical training in the social and behavioral sciences, often including learning about “difficult patient” interactions, yet little is known about their desire for training during clinical education. We explored students’ strategies in these difficult clinical interactions, whether they felt prepared by the curriculum, and what support they would have liked. These data inform proposed strategies for supporting clinical learning. Approach: We interviewed 4th-year students about interactions with patients toward whom they felt negative emotions and sought to identify strategies and supports needed in these interactions. Interviews ended when theoretical sufficiency was achieved. We used qualitative content analysis to organize strategies into themes about areas benefiting from curricular supports. We mapped students’ desired curricular support examples to cognitive apprenticeship teaching methods—modeling, coaching, reflection, scaffolding, exploration, and articulation—and aligned them with traditional pedagogical techniques. Findings: We interviewed 26 medical students (44 volunteered/180 invited). Their strategies formed five themes: finding empathy (with a subtheme of focusing on social determinants of health), using learned communication approaches, anticipating challenging interactions, seeking support, and considering it an opportunity for more responsibility. Students described ideal clinical teaching, including postinteraction debriefs with an emphasis on validating their emotional reactions and challenges. Students mentioned all cognitive apprenticeship teaching methods, most prominently modeling (observing supervisors in such interactions) and supported oral reflection. They also identified a need for faculty and resident development to enact these teaching methods. Insights: Although students use some learned strategies in interactions in which they feel negative emotions toward patients, they desire more preparation and support during their clinical rotations. Their desires map to traditional pedagogical techniques and to methods of cognitive apprenticeship. Our findings point to the need to use these techniques to enhance clinical learning for students who experience emotionally challenging patient interactions.     

A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood–brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80^®-coated poly-l-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-l-lactid acid nanoparticles (5 mg/kg), a saline solution of tacrine (5 mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine–lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.     

Characterization and physical stability of fast-dissolving microparticles containing nifedipine.

The suitability of a poly(sodium methacrylate, methyl methacrylate) (NaPMM), a novel mucoadhesive material, to prepare fast-dissolving microparticles containing nifedipine (NIF) in the range of 25-75% w/w was verified. Microparticles made of a low-viscosity hydroxypropylmethylcellulose (HPMC), were also prepared to compare the NIF release profile and bioadhesive properties. The release test was carried out in oversaturation conditions. The physical state of microparticles was also investigated. The formulation stability was evaluated over a 3-month period in long-term and accelerated conditions. The presence of amorphous NIF within freshly prepared microparticles was attributed to interactions between the drug and both polymers. NaPMM conferred to microparticles suitable mucoadhesive properties and significantly increased NIF dissolution rate in comparison to HPMC. Nevertheless, NIF apparent solubilities obtained by NaPMM microparticles were lower than those obtained by the HPMC set. After 3-month storage in the case of HPMC microparticles, NIF dissolution rate and supersaturation degree significantly decreased due to drug crystallization. As far as NaPMM microparticles are concerned, neither NIF dissolution rate nor apparent solubility significantly changed.     

Coherent X-ray diffraction from collagenous soft tissues

Coherent X-ray diffraction has been applied in the imaging of inorganic materials with great success. However, its application to biological specimens has been limited to some notable exceptions, due to the induced radiation damage and the extended nature of biological samples, the last limiting the application of most part of the phasing algorithms. X-ray ptychography, still under development, is a good candidate to overcome such difficulties and become a powerful imaging method for biology. We describe herein the feasibility of applying ptychography to the imaging of biological specimens, in particular collagen rich samples. We report here speckles in diffraction patterns from soft animal tissue, obtained with an optimized small angle X-ray setup that exploits the natural coherence of the beam. By phasing these patterns, dark field images of collagen within tendon, skin, bone, or cornea will eventually be obtained with a resolution of 60–70 nm. We present simulations of the contrast mechanism in collagen based on atomic force microscope images of the samples. Simulations confirmed the ‘speckled’ nature of the obtained diffraction patterns. Once inverted, the patterns will show the disposition and orientation of the fibers within the tissue, by enhancing the phase contrast between protein and no protein regions of the sample. Our work affords the application of the most innovative coherent X-ray diffraction tools to the study of biological specimens, and this approach will have a significant impact in biology and medicine because it overcomes many of the limits of current microscopy techniques.