Redox ratio of mitochondria as an indicator for the response of photodynamic therapy

The effect of photodynamic therapy (PDT) treatment on the metabolic state of tumor mitochondria is investigated by imaging of tumor redox status. PDT is performed using the photosensitizer pyropheophorbide-2-deoxyglucosamide (Pyro-2DG), which utilizes the glucose import pathway. It is found that Pyro-2DG-induced PDT resulting in a highly oxidized state of tumor mitochondria. This is determined from the redox ratio changes derived from the intrinsic oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) [i.e., reduced nicotinamide adenine dinucleotide (NADH)] fluorescence signals observed using a cryoimager. Thus, the redox ratio is a sensitive indicator for providing reliable and informative measurements of PDT-induced tissue damage. In the PDT treated region of the tumor, highly oxidized flavoprotein and diminishing NADH fluorescence is detected, suggesting that flavoprotein and NADH are oxidized by singlet oxygen produced in the photosensitization process.     

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9–14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9–14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.     

Comparative efficacy,speed, and adverse effects of three PTSD treatments: exposure therapy,EMDR, and relaxation training

The authors examined the efficacy, speed, and incidence of symptom worsening for 3 treatments of posttraumatic stress disorder (PTSD): prolonged exposure, relaxation training, or eye movement desensitization and reprocessing (EMDR; N = 60). Treaments did not differ in attrition, in the incidence of symptom worsening, or in their effects on numbing and hyperarousal symptoms. Compared with EMDR and relaxation training, exposure therapy (a) produced significantly larger reductions in avoidance and reexperiencing symptoms, (b) tended to be faster at reducing avoidance, and (c) tended to yield a greater proportion of participants who no longer met criteria for PTSD after treatment. EMDR and relaxation did not differ from one another in speed or efficacy.     

Evidence for Classically Conditioned Fatigue Responses in Patients Receiving Chemotherapy Treatment for Breast Cancer

Fatigue is the most common side effect of chemotherapy for cancer. Not yet explored is the possibility that patients may develop conditioned fatigue responses to clinic cues as a result of the repeated pairing of the clinic environment (conditioned stimulus) with infusions of chemotherapy (unconditioned stimulus) that cause fatigue (unconditioned response). As a first critical test of this possibility, breast cancer patients (N = 82) were studied across their first four cycles of chemotherapy. Consistent with conditioning: (1) fatigue levels in the clinic environment significantly increased with repeated pairings of the clinic environment and chemotherapy administration; (2) fatigue responses in the clinic environment prior to the fourth infusion (CR) were predicted by patients’ previous experiences of post-infusion fatigue (UR) above and beyond effects of concurrent emotional distress. These results provide the first evidence in the literature that fatigue can be conditioned. Additional research is warranted to determine the clinical importance of this source of fatigue in chemotherapy patients.     

Vitamin D receptor FokI genotype influences bone mineral density response to strength training, but not aerobic training

To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50-81 years old) were studied before and after approximately 5-6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD (P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD (P = 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT.     

Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen

We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1/2 mediated activation of the hemagglutinin peptide-specific T cell line IP-12-7, as assessed by IL-2 production. Efficient presentation was dependent on the binding of the constructs to CR1/2, implying that receptor-mediated endocytosis is responsible for the effect. Cross-linkage of CR1/2 or CD19 by mAb did not increase the extent of T cell activation. However, when CR1/2 was co-ligated with the BCR--using either polyclonal goat anti-mouse IgG or recombinant protein LA--the antigen concentration required to activate T cells decreased by two orders of magnitude. Moreover, this enhancement was selective for the antigen included in these complexes and did not affect the presentation of a free peptide or of antigen bound to CR1/2 excluded from the complexes. These results suggest that B cells may bind various C3d-coated antigens at a time, but only the one which reacts with the BCR will be processed with high efficiency. This mechanism may ensure the specificity of cognate T cell help.     

Computational simulations of mitral regurgitation quantification using the flow convergence method: Comparison of hemispheric and hemielliptic formulae

Mitral regurgitation results from the incomplete closure of the mitral valve, and the noninvasive diagnosis of this disease remains an important clinical goal. In this study, steady flow computer simulations were used to evaluate flow convergence method for flow rate estimation. The hemispheric and hemielliptic formulae were compared for accuracy in the presence of complicating factors such, as ventricular confinement, orifice shape, and aortic outflow. Results showed that in the absence of aortic outflow and ventricular confinement, there was a plateau zone where the hemispheric formula approximated the true flow rate, independent of orifice shape. However, in the presence of complicating factors such as aortic outflow and ventricular confinement, there was no clear zone where the hemispheric formula could be applied. The hemielliptic formula, however, worked in, all cases, regardless of chamber size or magnitude of aortic outflow. Therefore, application of the hemielliptic formula shold be considered in future clinical studies.     

Cognitive imagery and physiological feedback relaxation protocols applied to clinically tense young adults: a comparison of state, trait, and physiological effects

Examined changes in targeted and general tension behaviors as well as reductions in physiological tension associated with cognitive imagery and electromyographic biofeedback relaxation procedures. Three groups of 15 female college students participated. During three weekly sessions each person received either guided cognitive imagery relaxation, frontalis muscle feedback relaxation, or a self-rest control procedure. The Anxiety Differential was administered before and after each session, while frontalis EMG, heart rate, and skin temperature were monitored continuously. A second Temperament Analysis was administered after the final session. The imagery procedure was associated with moderate reductions in physiological tension and significant reductions in state anxiety and three tension-related personality dimensions. Self-rest persons displayed lesser reductions in general tension with little physiological change. While biofeedback persons showed the largest reductions in physiological tension, they displayed only small and variable changes in state anxiety and personality dimensions. The data raise continued questions about the application of physiologically based operant relaxation procedures and support the use of cognitively mediated protocols for the treatment of specific or general anxiety behaviors.     

Heterotypic adhesion-induced mast cell activation: biologic relevance in the inflammatory context

In addition to being a major effector cell in the elicitation of allergic inflammation, mast cells have been found to be activated in various T cell-mediated inflammatory processes and to reside in close physical proximity to T cells. Such observations have led investigators to propose a functional relationship between these two cell populations. In this regard, we have recently reported that murine and human mast cells can be activated to both release granule-associated mediators, such as histamine and matrix metalloproteinase-9 (MMP-9), and to produce several cytokines (i.e. TNF-alpha, IL-4 and IL-6) upon physical contact, which is adhesion molecule mediated, with activated T cells. This cascade of events, whereby mast cells are activated by T cells to release certain mediators which are known to be essential for leukocyte extravasation and recruitment to affected sites, points to an important immunoregulatory function of mast cells within the context of T cell-mediated inflammatory processes.