Therapeutic reactance as a predictor of outcome in the treatment of chronic depression

This study examined whether reactance would negatively influence treatment outcome in 347 patients diagnosed with chronic forms of depression and treated at 9 sites with either Nefazodone, cognitive-behavioral analysis system of psychotherapy (CBASP), or combination therapy. Contrary to our hypotheses, reactance positively predicted treatment outcome in CBASP on 2 of 4 scales. These effects were independent of the therapeutic alliance, which also positively predicted outcome. Reactance did not predict outcome in the groups receiving medication alone or in combination with CBASP. The findings suggest that reactance may be an asset in psychotherapy among chronically depressed individuals and that reactant patients can benefit from directive psychotherapy when therapists flexibly respond to perturbations in the therapeutic relationship. Results support the importance of Aptitude * Treatment interactions in psychotherapy outcome. The direction and significance of such interactions may vary with different forms of psychopathology.     

Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O ⁶-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.Key words: Neuroendocrine neoplasms, MGMT gene methylation, Methylation-specific PCR, Amplicon bisulfite sequencing, Temozolomide     

Compliance,Adherence and Concordance Differently Predict the Improvement of Uremic and Microbial Toxins in Chronic Kidney Disease on Low Protein Diet

Background. In medicine, “compliance” indicates that the patient complies with the prescriber’s recommendations, “adherence” means that “the patient matches the recommendations” and “concordance” means “therapeutic alliance” between patient and clinician. While a low protein diet (LPD) is a cornerstone treatment of chronic kidney disease (CKD), monitoring the actual performance of LPD is a challenge. Patients. Fifty-seven advanced CKD adult patients were enrolled and LPD prescribed. Compliance was evaluated through the normalized protein catabolic rate (nPCR), adherence by the dietitian by means of a 24-h dietary recall and concordance by the nephrologist during consultations. Traditional parameters as well as total p-Cresyl Sulphate (t-PCS), total Indoxyl Sulphate (t-IS) and Lipoprotein-associated phspholipase A₂ (Lp-PLA₂) were compared between adherent/not adherent and concordant/not concordant subjects at enrolment and after two months. Results. nPCR, blood urea nitrogen, cholesterol and triglycerides significantly decreased in all patients. t-PCS and t-IS decreased among adherent subjects. Lp-PLA₂, t-PCS, free-PCS and t-IS decreased among concordant subjects, while these increased in non-concordant ones. Conclusion. This study demonstrates that LPD may improve the control of traditional uremic toxins and atherogenic toxins in “adherent” and “concordant” patients. A comprehensive and multidisciplinary approach is needed to evaluate the compliance/adherence/concordance to LPD for optimizing nutritional interventions.     

What Is the Current Direction of the Research on Carotenoids and Human Health? An Overview of Registered Clinical Trials

Carotenoids have been the object of numerous observational, pre-clinical and interventional studies focused on elucidating their potential impacts on human health. However, the large heterogeneity among the trials, in terms of study duration and characteristics of participants, makes any conclusion difficult to draw. The present study aimed to explore the current carotenoid research trends by analyzing the characteristics of the registered clinical trials. A total of 193 registered trials on ClinicalTrials.gov and ISRCTN were included in the revision. Eighty-three studies were performed with foods, one-hundred-five with food supplements, and five with both. Among the foods tested, tomatoes and tomato-based foods, and eggs were the most studied. Lutein, lycopene, and astaxanthin were the most carotenoids investigated. Regarding the goals, 52 trials were focused on studying carotenoids’ bioavailability, and 140 studies investigated the effects of carotenoids on human health. The main topics included eye and cardiovascular health. Recently, the research has focused also on two new topics: cognitive function and carotenoid–gut microbiota interactions. However, the current research on carotenoids is still mostly focused on the bioavailability and metabolism of carotenoids from foods and food supplements. Within this context, the impacts/contributions of food technologies and the development of new carotenoid formulations are discussed. In addition, the research is still corroborating the previous findings on vision and cardiovascular health. Much attention has also been devoted to new research areas, such as the carotenoid–microbiota interactions, which could contribute to explaining the metabolism and the health effects of carotenoids; and the relation between carotenoids and cognitive function. However, for these topics the research is still only beginning, and further studies are need.     

Somatosensory control of precision grip during unpredictable pulling loads

In manipulating 'passive' objects, for which the physical properties are stable and therefore predictable, information essential for the adaptation of the motor output to the properties of the current object is principally based on 'anticipatory parameter control' using sensorimotor memories, i.e., an internal representation of the object's properties based on previous manipulative experiences. Somatosensory afferent signals only intervene intermittently according to an 'event driven' control policy. The present study is the first in a series concerning the control of precision grip when manipulating 'active' objects that exert unpredictable forces which cannot be adequately represented in a sensorimotor memory. Consequently, the manipulation may be more reliant on a moment-to-moment sensory control. Subjects who were prevented from seeing the hand used the precision grip to restrain a manipulandum with two parallel grip surfaces attached to a force motor which produced distally directed (pulling) loads tangential to the finger tips. The trapezoidal load profiles consisted of a loading phase (4 N/s), plateau phase and an unloading phase (4 N/s) returning the load force to zero. Three force amplitudes were delivered in an unpredictable sequence; 1 N, 2 N and 4 N. In addition, trials with higher load rate (32 N/s) at a low amplitude (0.7 N), were superimposed on various background loads. The movement of the manipulandum, the load forces and grip forces (normal to the grip surfaces) were recorded at each finger. The grip force automatically changed with the load force during the loading and unloading phases. However, the grip responses were initiated after a brief delay. The response to the loading phase was characterized by an initial fast force increase termed the 'catch-up' response, which apparently compensated for the response delay--the grip force adequately matched the current load demands by the end of the catch-up response. In ramps with longer lasting loading phases (amplitude greater than or equal to 2 N) the catch-up response was followed by a 'tracking' response, during which the grip force increased in parallel with load force and maintained an approximately constant force ratio that prevented frictional slips. The grip force during the hold phase was linearly related to the load force, with an intercept close to the grip force used prior to the loading. Likewise, the grip force responses evoked by the fast loadings superimposed on existing loads followed the same linear relationship.(ABSTRACT TRUNCATED AT 400 WORDS)     

Development and evaluation of a two-dimensional electrocutaneous cognitive feedback system for use in paraplegic standing

Fatigue of electrically activated paralysed muscles is a major factor limiting the duration of functional electrical stimulation (FES) supported paraplegic standing. Fatigue can be significantly delayed by changing the posture. Since paralysed individuals are deprived of proprio- and exteroception from the lower limbs they are not aware of the posture and loading of their paralysed legs. If suitable cognitive feedback (CF) information about posture in the sagittal and frontal planes is provided, they might be able to successfully exercise posture switching. A two-dimensional electrocutaneous CF system was developed. Relative limb loading and the location of the weighted centre of pressure were selected as informational variables. Discrete encoding schemes in the form of spatial and frequency codes were employed and the informational signals were divided into three sub-regions. The ability to correctly interpret the CF was investigated using one- and two-dimension tracking tests in three paralysed subjects, each of whom were studied over five consecutive days. All three subjects were able to use the CF in one-dimension tests. Two subjects could do the same also in two-dimension tests. The encoding scheme which was developed to communicate the selected biomechanical variables proved to be easily understood and thus appropriate for use in paraplegic standing.     

Daily intake of a formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection

The salutary characteristics of the tomato are normally related to its content of carotenoids, especially lycopene, and other antioxidants. Our purpose was to verify whether the daily intake of a beverage prototype called Lyc-o-Mato((R)) containing a natural tomato extract (Lyc-o-Mato((R)) oleoresin 6 %) was able to modify plasma and lymphocyte carotenoid concentrations, particularly those of lycopene, phytoene, phytofluene and beta-carotene, and to evaluate whether this intake was sufficient to improve protection against DNA damage in lymphocytes. In a double-blind, cross-over study, twenty-six healthy subjects consumed 250 ml of the drink daily, providing about 6 mg lycopene, 4 mg phytoene, 3 mg phytofluene, 1 mg beta-carotene and 1.8 mg alpha-tocopherol, or a placebo drink. Treatments were separated by a wash-out period. Plasma and lymphocyte carotenoid and alpha-tocopherol concentrations were determined by HPLC, and DNA damage by the comet assay. After 26 d of consumption of the drink, plasma carotenoid levels increased significantly: concentrations of lycopene were 1.7-fold higher (P<0.0001); of phytofluene were 1.6-fold higher (P<0.0001); of phytoene were doubled (P<0.0005); of beta-carotene were 1.3-fold higher (P<0.05). Lymphocyte carotenoid concentrations also increased significantly: that of lycopene doubled (P<0.001); that of phytofluene was 1.8-fold higher (P<0.005); that of phytoene was 2.6-fold higher (P<0.005); that of beta-carotene was 1.5-fold higher (P<0.01). In contrast, the alpha-tocopherol concentration remained nearly constant. The intake of the tomato drink significantly reduced (by about 42 %) DNA damage (P<0.0001) in lymphocytes subjected to oxidative stress. In conclusion, the present study supports the fact that a low intake of carotenoids from tomato products improves cell antioxidant protection.     

Comparison of lutein bioavailability from vegetables and supplement

Lutein is a carotenoid present in dark green leafy vegetables and it may be involved in the prevention of several diseases related to oxidative stress. The aim of this study was to evaluate bioavailability of lutein from different food sources (150 g spinach and 200 g broccoli) and a supplement in oil (300 mg VEGEX), all providing about 9 mg lutein. Eight healthy females were instructed to eat a low-carotenoid diet for the period of experimentation. On three different occasions, three weeks apart, volunteers ate the lutein sources together with 10 g olive oil and 40 g bread. Blood samples were collected just before eating, every two hours for 12 hours, and at 24, 32, 56, 80 and 104 hours. Lutein concentration increased significantly after six to eight hours and peaked after 10-12 hours, with the highest concentration reached after VEGEX intake. Lutein concentration remained significantly elevated for up to 80 hours (VEGEX and spinach). On the whole, our results suggest that the intake of one single dose of lutein from different sources is able to bring about a significant plasma response in the short term.     

Fuzzy logic and logistic regression in the decision making for parathyroid scintigraphy study

OBJECTIVE: To develop and compare two mathematical models, the first one based on logistic regression and the second one on fuzzy sets theory, aiming at defining a laboratory testing-based measure of indication for submitting patients to parathyroid scintigraphy. METHODS: One-hundred and ninety-four patients with serum calcium and parathyroid hormone available were identified from the data registry of parathyroid scintigraphy of a diagnostic laboratory in S?o Paulo, Southern Brazil, in the period between January 2000 and December 2004. The logistic regression model was developed using SPSS and the fuzzy model was developed using MatLab software programs. The performances of both models were compared using ROC curves. RESULTS: The performance of both models were statistically different (p=0.026). The area under the ROC curves were 0.862 (95% CI: 0.811-0.913) for the logistic regression model and 0.887 (95% CI: 0.840-0.933) for the fuzzy model. The latter had the advantage of allowing to making decisions based on parathyroid hormone information within a non-discriminating range of calcium values. CONCLUSIONS: The mathematical model based on fuzzy sets theory seemed to be more useful than the logistic model in the decision making for scintigraphy indication. However, inferences can be made only regarding model comparison and not for parathyroid scintigraphy itself since the data analyzed was not representative of any population.