Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity.

Spheroids resemble features of tissues and serve as model systems to study cell-cell and cell-ECM interactions in non-adhesive three-dimensional environments. Although it is generally accepted that mature spheroids resemble tissue properties very well, no studies relate different phases in the spheroid formation processes that contribute to tissue integrity. Tissue integrity involves the cellular processes adhesion formation, adhesion reinforcement, rearrangement as well as proliferation. They maintain the structure and function of tissues and, upon dysregulation, contribute to malignancy. We investigated spheroid formation dynamics in cell lines of different metastatic potential. We dissected spheroid formation into phases of aggregation, compaction and growth to identify the respective contributions of E-cadherin, actin, microtubules and FAK. E-cadherin, actin and microtubules drive the first two phases. Microtubules and FAK are involved in the proliferation phase. FAK activity correlates with the metastatic potential of the cells. A robust computational model based on a very large number of experiments reveals the temporal resolution of cell adhesion. Our results provide novel hypotheses to unveil the general mechanisms that contribute to tissue integrity.

Identifying the necrotic zone boundary in tumour spheroids with pair-correlation functions.

Automatic identification of the necrotic zone boundary is important in the assessment of treatments on in vitro tumour spheroids. This has been difficult especially when the difference in cell density between the necrotic and viable zones of a tumour spheroid is small. To help overcome this problem, we developed novel one-dimensional pair-correlation functions (PCFs) to provide quantitative estimates of the radial distance of the necrotic zone boundary from the centre of a tumour spheroid. We validate our approach on synthetic tumour spheroids in which the position of the necrotic zone boundary is known a priori It is then applied to nine real tumour spheroids imaged with light sheet-based fluorescence microscopy. PCF estimates of the necrotic zone boundary are compared with those of a human expert and an existing standard computational method.

Robust and automated three-dimensional segmentation of densely packed cell nuclei in different biological specimens with Lines-of-Sight decomposition.

BACKGROUND: Due to the large amount of data produced by advanced microscopy, automated image analysis is crucial in modern biology. Most applications require reliable cell nuclei segmentation. However, in many biological specimens cell nuclei are densely packed and appear to touch one another in the images. Therefore, a major difficulty of three-dimensional cell nuclei segmentation is the decomposition of cell nuclei that apparently touch each other. Current methods are highly adapted to a certain biological specimen or a specific microscope. They do not ensure similarly accurate segmentation performance, i.e. their robustness for different datasets is not guaranteed. Hence, these methods require elaborate adjustments to each dataset. RESULTS: We present an advanced three-dimensional cell nuclei segmentation algorithm that is accurate and robust. Our approach combines local adaptive pre-processing with decomposition based on Lines-of-Sight (LoS) to separate apparently touching cell nuclei into approximately convex parts. We demonstrate the superior performance of our algorithm using data from different specimens recorded with different microscopes. The three-dimensional images were recorded with confocal and light sheet-based fluorescence microscopes. The specimens are an early mouse embryo and two different cellular spheroids. We compared the segmentation accuracy of our algorithm with ground truth data for the test images and results from state-of-the-art methods. The analysis shows that our method is accurate throughout all test datasets (mean F-measure: 91%) whereas the other methods each failed for at least one dataset (F-measure≤69%). Furthermore, nuclei volume measurements are improved for LoS decomposition. The state-of-the-art methods required laborious adjustments of parameter values to achieve these results. Our LoS algorithm did not require parameter value adjustments. The accurate performance was achieved with one fixed set of parameter values. CONCLUSION: We developed a novel and fully automated three-dimensional cell nuclei segmentation method incorporating LoS decomposition. LoS are easily accessible features that ensure correct splitting of apparently touching cell nuclei independent of their shape, size or intensity. Our method showed superior performance compared to state-of-the-art methods, performing accurately for a variety of test images. Hence, our LoS approach can be readily applied to quantitative evaluation in drug testing, developmental and cell biology.

Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens junctions.

Cadherin interactions ensure the correct registry and anchorage of cells during tissue formation. Along the plasma membrane, cadherins form inter-junctional lattices via cis- and trans-dimerization. While structural studies have provided models for cadherin interactions, the molecular nature of cadherin binding in vivo remains unexplored. We undertook a multi-disciplinary approach combining live cell imaging of three-dimensional cell assemblies (spheroids) with a computational model to study the dynamics of N-cadherin interactions. Using a loss-of-function strategy, we demonstrate that each N-cadherin interface plays a distinct role in spheroid formation. We found that cis-dimerization is not a prerequisite for trans-interactions, but rather modulates trans-interfaces to ensure tissue stability. Using a model of N-cadherin junction dynamics, we show that the absence of cis-interactions results in low junction stability and loss of tissue integrity. By quantifying the binding and unbinding dynamics of the N-cadherin binding interfaces, we determined that mutating either interface results in a 10-fold increase in the dissociation constant. These findings provide new quantitative information on the steps driving cadherin intercellular adhesion and demonstrate the role of cis-interactions in junction stability.

Robotics and allied technologies in endoscopic surgery.

Endoscopic surgery was developed in the 1970s and 1980s, with initial work conducted by pioneering surgeons. After the development of laparoscopic cholecystectomy, the breakthrough of endoscopic surgery had a great effect on all surgical specialties. Starting with rather simple procedures, such as cholecystectomy, a rapid progression toward more complex procedures, such as reflux or colonic surgery, took place. It was realized at this time that the existing endoscopic instruments allowed only a limited preciseness when performing the procedures, and part of the information from inside the abdominal cavity was not available to the surgeon. This prompted a discussion with engineers concerning the development of more advanced technologies to give those performing endoscopic surgery the same quality of information and manipulation that surgeons have when performing open surgery. These qualities include (1) instruments and manipulators that allow surgical action under endoscopic control with all degrees of freedom; (2) devices that provide surgeons with tactile feedback; and (3) vision systems that provide surgeons with the same quality of visual information as with open surgery, namely, high resolution, excellent color quality, precise spatial information, and a constant clear view for optimal surgical action. At the end of 1999, some of the aforementioned quality concepts found their way into the surgical routine, but most of the concepts are still being developed. Another decade will pass before endoscopic surgery procedures will be closer to the technological goals.

Perceptual and cognitive factors governing performance in comparative arrival-time judgments.

Four experiments were conducted to investigate factors affecting relative arrival-time judgments in the transverse plane. Across experiments, results indicated an overreliance on relative distance information. The levels of relative velocity and distance used in the arrival-time task were proved discriminable, and performance in both relative velocity and distance judgments predicted performance in the relative arrival-time task. Despite the distance bias, an attempt to integrate relative velocity and distance information was also evidenced. The distance bias appears to have resulted from resource limitations on the concurrent processing of relative velocity and distance information, causing relative velocity information to become resource limited. The final experiment assessed the stability of performance in each of the tasks over time and provided evidence of individual differences in the ability to coordinate information from multiple sources.

Changes in DSM-III-R axis II diagnoses following treatment of obsessive-compulsive disorder.

Seventeen patients with obsessive-compulsive disorder and concomitant personality disorders were treated with pharmacologic and/or behavioral therapy and reassessed after 4 months. Nine of the 10 patients who responded to treatment for obsessive-compulsive disorder no longer met criteria for a personality disorder. Of the seven nonresponders, five continued to meet criteria for a personality disorder.

Stimulus complexity effects in visual comparisons: the effects of practice and learning context.

This study examined visual comparison performance for 6-24-point random polygon stimuli (Cooper & Podgorny, 1976). Stimulus complexity effects decreased with practice, consistent with Bethell-Fox and Shepard (1988). A difficult discrimination context produced greater complexity effects than an easy discrimination context, consistent with Folk and Luce (1987). The difficult discrimination context also led to more stimulus-specific learning and diminished stimulus complexity effects. Increased stimulus learning resulted in continued skill acquisition, better transfer, and less performance disruption when the task context was equated for all Ss. It is argued that improvements in performance in a perceptual comparison task are not solely a function of the amount of practice provided in responding to particular stimuli. The context in which responses are elicited is equally important and must be accommodated in theories of skill acquisition.

Hemisphere differences for components of mental rotation.

The hemispheric functional lateralization of components of mental rotation performance was investigated. Twenty right-handed males were presented with rotated alphanumerics and unfamiliar characters in the left or right visual field. Subjects decided if the laterally presented stimulus was identical to or a mirror image of a center standard stimulus. Reaction time and errors were measured. Previous mental rotation findings were replicated and the visual field variable produced significant effects for both dependent measures. An overall right visual field advantage was observed in the latency data, suggesting a left hemisphere superiority for at least one component process of the task. A significant interaction in the error data showed that alphanumerics produced less errors in the right visual field than in the left visual field, consistent with a left hemisphere superiority for processing verbal symbolic material. No such hemispheric difference in accuracy was found for unfamiliar characters.

MSH/ACTH4-10 influences on the CAR in human subjects: a negative finding.

Twenty normal, male, paid volunteers were randomly assigned to MSH/ACTH4-10 or diluent control groups. Following a subcutaneous injection of either 30 mg MSH/ACTH4-10 or diluent, all subjects were placed in an active conditioned avoidance response situation where they learned to avoid a painful electric shock by pressing a key during a safe interval between a warning signal (light) and shock onset. MSH/ACTH4-10 did not influence any parameter of the acquisition or extinction process. The between subjects' variability of autonomic variables was significantly less for the MSH/ACTH4-10 group. Results indicate that inhibition of extinction of conditioned avoidance responding does not generalize across species from rat to man.

Alternative behavioral approaches to the treatment of homosexuality.

Radical changes in attitudes toward homosexuality in American society are integrated into a new perspective for the therapist confronted by a client who engages in homosexual behavior. The traditional mandatory attempt to eradicate homosexual behavior has been expanded into three options, any one of which may be pursued by the therapist at the client's request: (1) modification of homosexual in favor of heterosexual behavior, (2) enhancement of homosexual behavior, and (3) ignoring of homosexual behavior if it is functionally unrelated to the presenting symptoms. Therapists' negative attitudes toward clients who engage in homosexual behavior are such as to abrogate expanded options and may results in therapeutic efforts at modification of homosexual behavior in defiance of the client's expressed wishes. Contrary to current professional belief, careful analysis and the use of appropriate techniques such as systematic desensitization, orgasmic reconditioning, and training in heterosocial skills generally obviate the necessity for aversive procedures in those instances where homosexual behavior is to be modified in favor of heterosexual behavior. Three case histories are presented illustrating the use of each of the expanded options described above.