The unconditioned fear produced by morphine withdrawal is regulated by mu- and kappa-opioid receptors in the midbrain tectum

We have recently shown that morphine withdrawal sensitizes the neural substrates of fear in the midbrain tectum structures-the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC). In the present study, we investigated the role of mu- and kappa-opioid receptors in the mediation of these effects. Periadolescent rats chronically treated with morphine (10 mg/kg; s.c.) twice daily for 10 days were implanted with an electrode glued to a guide-cannula into the dPAG or the IC. Forty-eight hours after the interruption of this treatment, the effects of intra-dPAG or intra-IC microinjections of [D-Ala(2) N-Me-Phe(4) Gly(5)-ol]-enkephalin (DAMGO; 0.6 and 1 nmol/0.2 mu l) - a selective mu-receptor agonist - or nor-binaltorphimine (BNI; 2.5 and 5 mu g/0.2 mu l) - a selective K-receptor antagonist with tardive action - on the freezing and escape thresholds determined by electrical stimulation of the dPAG and the IC were examined. For both structures, morphine withdrawal produced pro-aversive effects. DAMGO and BNI had antiaversive effects when injected into the dPAG and IC of non-dependent rats. In morphine-withdrawn rats, only BNI continued to promote antiaversive effects in both structures. Whereas DAMGO lost its antiaversive efficacy when injected into the dPAG, only its highest dose promoted antiaversive effects in the IC of morphine-withdrawn rats, suggesting the development of an apparent tolerance. Thus, the enhanced reactivity of the midbrain tectum in morphine-withdrawn periadolescent rats may be due, at least partially, to an impairment of the inhibitory influence of mechanisms mediated by mu-receptors on the neural substrates of fear in this region. (C) 2009 Elsevier B.V. All rights reserved.

Use of the q-Gaussian mutation in evolutionary algorithms

This paper proposes the use of the q-Gaussian mutation with self-adaptation of the shape of the mutation distribution in evolutionary algorithms. The shape of the q-Gaussian mutation distribution is controlled by a real parameter q. In the proposed method, the real parameter q of the q-Gaussian mutation is encoded in the chromosome of individuals and hence is allowed to evolve during the evolutionary process. In order to test the new mutation operator, evolution strategy and evolutionary programming algorithms with self-adapted q-Gaussian mutation generated from anisotropic and isotropic distributions are presented. The theoretical analysis of the q-Gaussian mutation is also provided. In the experimental study, the q-Gaussian mutation is compared to Gaussian and Cauchy mutations in the optimization of a set of test functions. Experimental results show the efficiency of the proposed method of self-adapting the mutation distribution in evolutionary algorithms.

Effects of Self-Assembled Materials Prepared from V(2)O(5) for Lithium Ion Electroinsertion

Self-assembled materials consisting of V(2)O(5), polyallylamine (PAR) and silver nanoparticles (AgNPs) were obtained by the layer-by-layer (LbL) method, aiming at their application as electrodes for lithium-ion batteries and electrochromic devices. The method employed herein allowed for linear growth of visually homogeneous films composed of V(2)O(5), V(2)O(5)/PAH, and V(2)O(5)/PAH/AgNP with 15 bilayers. According to the Fourier transform infrared spectra, interaction between the oxygen atom of the vanadyl group and the amino group should be responsible for the growth of these films. This interaction also enabled establishment of an electrostatic shield between the lithium ions and the sites with higher negative charge, thereby raising the ionic mobility and consequently increasing the energy storage capacity and reducing the response time. According to the site-saturation model and the electrochemical and spectroelectrochemical results, the presence of PAH in the self-assembled host matrix decreased the number of V(2)O(5) electroactive sites. Thus, AgNPs were stabilized in PAR and inserted into the nanoarchitecture, so as to enhance the specific capacity. This should provide new conducting pathways and connect isolated V(2)O(5) particles in the host matrix. Therefore, new nanoarchitectures for specific interactions were formed spontaneously and chosen as examples in this work, aiming to demonstrate the potentiality of the adopted self-assembled method for enhancing the charge transport rate into the host matrices. The obtained materials displayed suitable properties for use as electrodes in lithium batteries and electrochromic devices.

Immediate Locally Advanced Breast Cancer and Chest Wall Reconstruction: Surgical Planning and Reconstruction Strategies with Extended V-Y Latissimus Dorsi Myocutaneous Flap

Background: Surgical resection in locally advanced breast cancer produces large defects that may not be suitable for primary closure. Immediate reconstruction is controversial and presents a complicated scenario for breast surgeons and plastic surgeons. Methods: In this study, a different design was planned for the latissimus dorsi musculocutaneous flap with primary closure in V-Y for the correction of major lesions in the anterior chest wall. Twenty-five patients underwent immediate locally advanced breast cancer reconstruction with a V-Y latissimus dorsi musculocutaneous flap. This flap was raised from adjacent tissue located on the lateral and posterior thoracic region and presented a triangular shape whose base was the lateral aspect of the mastectomy wound. The technique was indicated in patients with large thoracic wounds. Results: Mean follow-up time was 16 months. Closure was obtained in the donor and recipient sites without the use of skin grafts or other more major procedures. Complications occurred in nine patients (36 percent), including dorsal wound dehiscence in five patients and seroma in three. All cases except one were treated by a conservative approach with a good result. No total flap loss was reported. All patients achieved a satisfactory thoracic reconstruction and adequate wound care. Conclusions: The V-Y latissimus dorsi musculocutaneous flap is a reliable technique for immediate locally advanced breast cancer reconstruction. The technique is advantageous because the V-Y design allows primary closure of the chest wound and donor defect. Success depends on patient selection, coordinated planning with the breast cancer surgeon, and careful intraoperative management. (Plast. Reconstr. Surg. 127: 2186, 2011.)

The Tessier Number 5 Facial Cleft: Surgical Strategies and Outcomes in Six Patients

The Tessier no. 5 facial cleft is an extremely rare congenital malformation. Only 26 cases have been described In the English-language literature. The cleft begins In the upper lip just medial to the oral commissure, extending across the cheek as a groove ending at the junction of the middle and lateral thirds of the lower eyelid. The bone Involvement usually Includes an alveolar cleft in the premolar region, extends across the maxilla lateral to the Infraorbital nerve, up to the infraorbital rim and orbital floor. The goals of the surgical procedure Include reconstructing the lower eyelid, repositioning the lateral canthus, closure of the labiomaxillary cleft, and restoration of the skeletal continuity (including the orbital floor defect) with bone grafts. We present six patients with the Tessier no. 5 facial cleft who have been treated in our combined centers and discuss the surgical options and difficulties faced in the reconstruction of this rare and challenging craniofacial malformation. To date, we have treated six patients (two with bilateral and four with unilateral clefts). Three of the patients with unilateral clefting had an associated no. 4 cleft and one patient with a bilateral cleft had an associated no. 3 cleft. This paper represents the largest series to date documenting surgery for patients with the Tessier no. 5 facial cleft.

Strategies for genetic model specification in the screening of genome-wide meta-analysis signals for further replication

Background Meta-analysis is increasingly being employed as a screening procedure in large-scale association studies to select promising variants for follow-up studies. However, standard methods for meta-analysis require the assumption of an underlying genetic model, which is typically unknown a priori. This drawback can introduce model misspecifications, causing power to be suboptimal, or the evaluation of multiple genetic models, which augments the number of false-positive associations, ultimately leading to waste of resources with fruitless replication studies. We used simulated meta-analyses of large genetic association studies to investigate naive strategies of genetic model specification to optimize screenings of genome-wide meta-analysis signals for further replication. Methods Different methods, meta-analytical models and strategies were compared in terms of power and type-I error. Simulations were carried out for a binary trait in a wide range of true genetic models, genome-wide thresholds, minor allele frequencies (MAFs), odds ratios and between-study heterogeneity (tau(2)). Results Among the investigated strategies, a simple Bonferroni-corrected approach that fits both multiplicative and recessive models was found to be optimal in most examined scenarios, reducing the likelihood of false discoveries and enhancing power in scenarios with small MAFs either in the presence or in absence of heterogeneity. Nonetheless, this strategy is sensitive to tau(2) whenever the susceptibility allele is common (MAF epsilon 30%), resulting in an increased number of false-positive associations compared with an analysis that considers only the multiplicative model. Conclusion Invoking a simple Bonferroni adjustment and testing for both multiplicative and recessive models is fast and an optimal strategy in large meta-analysis-based screenings. However, care must be taken when examined variants are common, where specification of a multiplicative model alone may be preferable.

Ten-Year Follow-Up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) A Randomized Controlled Clinical Trial of 3 Therapeutic Strategies for Multivessel Coronary Artery Disease

Background-This study compared the 10-year follow-up of percutaneous coronary intervention (PCI), coronary artery surgery (CABG), and medical treatment (MT) in patients with multivessel coronary artery disease, stable angina, and preserved ventricular function. Methods and Results-The primary end points were overall mortality, Q-wave myocardial infarction, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. At a single institution, 611 patients were randomly assigned to CABG (n = 203), PCI (n = 205), or MT (n = 203). The 10-year survival rates were 74.9% with CABG, 75.1% with PCI, and 69% with MT (P = 0.089). The 10-year rates of myocardial infarction were 10.3% with CABG, 13.3% with PCI, and 20.7% with MT (P < 0.010). The 10-year rates of additional revascularizations were 7.4% with CABG, 41.9% with PCI, and 39.4% with MT (P < 0.001). Relative to the composite end point, Cox regression analysis showed a higher incidence of primary events in MT than in CABG (hazard ratio 2.35, 95% confidence interval 1.78 to 3.11) and in PCI than in CABG (hazard ratio 1.85, 95% confidence interval 1.39 to 2.47). Furthermore, 10-year rates of freedom from angina were 64% with CABG, 59% with PCI, and 43% with MT (P < 0.001). Conclusions-Compared with CABG, MT was associated with a significantly higher incidence of subsequent myocardial infarction, a higher rate of additional revascularization, a higher incidence of cardiac death, and consequently a 2.29-fold increased risk of combined events. PCI was associated with an increased need for further revascularization, a higher incidence of myocardial infarction, and a 1.46-fold increased risk of combined events compared with CABG. Additionally, CABG was better than MT at eliminating anginal symptoms.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background-The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P = 0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P = 0.76). In the coronary artery bypass grafting stratum (n = 763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P = 0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P = 0.010) and cardiac death or MI (P = 0.03) were also less frequent. Reduction in MI (P = 0.001) and cardiac death/MI (P = 0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305. (Circulation. 2009;120:2529-2540.)

Human breast tumor slices: A model for identification of vitamin D regulated genes in the tumor microenvironment

While many studies have addressed the direct effects of 1 alpha,25(OH)(2)D(3) on breast cancer (BC) cells, stromal-epithelial interactions, which are important for the tumor development, have been largely ignored. In addition, high concentrations of the hormone, which cannot be attained in vivo, have been used. Our aim was to establish a more physiological breast cancer model, represented by BC tissue slices, which maintain epithelial-mesenchymal interactions, cultured with a relatively low 1 alpha,25(OH)(2)D(3) concentration, in order to evaluate the vitamin D pathway. Freshly excised human BC samples were sliced and cultured in complete culture media containing vehicle, 0.5 nM or 100 nM 1 alpha,25(OH)(2)D(3) for 24 h. BC slices remained viable for at least 24 h, as evaluated by preserved tissue morphology in hematoxylin and eosin (HE) stained sections and bromodeoxyuridine (BrdU) incorporation by 10% of tumor cells. VDR mRNA expression was detected in all samples and CYP24A1 mRNA expression was induced by 1 alpha,25(OH)(2)D(3) in both concentrations (but mainly with 100 nM). Our results indicate that the vitamin D signaling pathway is functional in BC slices, a model which preserves stromal-epithelial interactions and mimics in vivo conditions. (C) 2010 Elsevier Ltd. All rights reserved.

What needs to be done? Occupational therapy responsibilities and challenges regarding human rights

Background: Addressing human rights issues brings forth ethical and political responsibilities for occupational therapists and requires new epistemological and educational approaches. The way occupational therapists have faced these challenges has depended upon historical, cultural and social contexts. Aim and method: By means of literature review and historical analysis, this paper reflects on how occupational therapists have dealt with human matters issues and on the contemporary changes within the profession. Results and discussion: The paper portrays how Latin American occupational therapists have engaged in social transformation by choosing not to transform ethical and political problems into technical matters. Taking into account experiences and views from South Africa, Brazil and Chile, the paper outlines the importance of developing political literacy and interdisciplinary professional/postprofessional education to prepare the new generation of occupational therapists to engage in social transformation. Addressing issues of invisibility and lack of access to human rights, the paper reflects on the need of developing conceptual tools and strategies for change, and discusses the transformations being produced in contemporary occupational therapy. Conclusion: Occupational therapists and scientists need to be attentive to human rights issues. They also need to answer the call for interconnectedness in the present-day complex societies, and engage in networking and a cross-bordering dialogue. Nevertheless, although necessary and welcome, international cooperation requires a permanent exercise of cultural sensitivity, political awareness and self-awareness.

Assessment of Occupational Genotoxic Risk among Brazilian Hairdressers

Objectives: To evaluate the genotoxic risk to hairdressers exposed daily to chemical substances such as hair dyes, waving and straightening preparations and manicurists` products by the Comet assay test (single-cell gel electrophoresis). Methods: The Comet assay was performed on blood samples from 69 female hairdressers (36.4 +/- 10.7 years old) currently employed in 21 different beauty institutes in Sao Paulo, Brazil, and on 55 female control blood donors (32.6 +/- 10.0 years old) from the Sao Paulo University Clinical Hospital blood bank. All the control subjects had occupations other than hairdresser. Comet assays were performed by evaluating 100 blood lymphocytes per individual and graded by visual score according to comet tail length. Results: The hairdressers showed a higher frequency of DNA damage revealed by Comet Score (159.8 +/- 71) when compared to the control group (125.4 +/- 64.1), and the difference was statistically significant by the Student`s t-test (P = 0.005). Multiple regression analysis showed that in addition to the hairdressers` profession, tobacco use contributed to the higher frequency of cells with comets (P < 0.05). Conclusions: The observed DNA damage could be associated with the hairdressers` occupational environment, where different chemicals are chronically manipulated and inhaled. Considering that this profession in many countries, including Brazil, is not officially regulated, more attention should focus on these professionals not only by legislative bodies but also by multidisciplinary teams able to develop and implement risk prevention and control strategies for chemical, physical and biological agents to which hairdressers are exposed.

Can Mobile Units Improve the Strategies for Cervical Cancer Prevention?

Cervical cancer is a serious public health problem in women in developing countries because of absence or ineffectiveness of screening programs. Several biases to access medical care and inequity of public health system in a continental country like Brazil limit the implementation of adequate programs to appropriately prevent the cervical cancer. Therefore, the aim of this study was to evaluate the results of applying the mobile unit (MU) for cervical cancer screening. From May 2003 to May 2004, a cervical cancer screening was offered to women aged 20-69 years, residing in 19 municipal districts of the Barretos county region, in Sao Paulo. Out of the 9,560 examination available, 2,964 (31%) women underwent screening. The medium distance traveled by the MU was 45 km. The medium time spent by women in the MU for completion of the questionnaire and doing the exam was 20 minutes. It was observed that 17.0% of women screened had never had the test or had not had it repeated within the last 3 years. The negative response was more common among women aged 20 to 29 years and 60 to 69 years and among women with less schooling and lower socio-economic income (P < 0.05). MU can significantly overcome the chronic deficiency of public health system accessibility offering opportunity to these women to participate in screening programs. Diagn. Cytopathol. 2010;38:727-730. (C) 2009 Wiley-Liss, Inc.

Prevalence of Erectile Dysfunction as Defined by the International Index of Erectile Function (IIEF) and Self-Reported Erectile Dysfunction in a Sample of Brazilian Men Who Consider Themselves Healthy

A cross-sectional study was carried out with 288 male blood donors, aged between 40 and 60 years old, with the aim of comparing the prevalence of erectile dysfunction (ED) as defined by the International Index of Erectile Function (IIEF) and that resulting from the simple questioning of the presence of ED. Socio-demographic, clinical, and behavioral factors that are associated with the presence of ED were considered. Erectile dysfunction prevalence in the IIEF was 31.9%, while self-reported ED prevalence was 3.1%. The factors associated to ED, as reported by the IIEF were: professional inactivity, suspected depression and/or anxiety, reduced sexual desired, and self-reported ED.

Validity of the self reporting questionnaire-20 in epidemiological studies with older adults

This study examined the validity of the self-reporting questionnaire (SRQ-20) in a population-based survey with older adults in Sao Paulo, Brazil. The study sample consisted of 2,008 individuals aged 65 years or more who were living in an economically disadvantaged area of the city. The geriatric mental state (GMS) was used as the gold standard for the assessment of common mental disorders (CMD). The optimal SRQ-20 threshold for case definition was 4/5 (sensitivity = 76.1%, specificity = 74.6%, area under ROC curve = 0.82). Women, older participants and those with lower income were more likely to be misclassified by the questionnaire. The inclusion of older persons with dementia or psychosis did not change the ability of the SRQ-20 to identify cases of CMD. The SRQ-20 may be a useful instrument to be used in large epidemiological studies in resource-poor settings for the identification of cases of depression and anxiety in later life. The performance of the SRQ-20 among older adults was similar to that observed with the adult population in Brazil.

Modelling the control strategies against dengue in Singapore

Notified cases of dengue infections in Singapore reached historical highs in 2004 (9459 cases) and 2005 (13 817 cases) and the reason for such all increase is still to be established. We apply a mathematical model for dengue infection that takes into account the seasonal variation in incidence, characteristic of dengue fever, and which mimics the 2004-2005 epidemics in Singapore. We simulated a set of possible control strategies and confirmed the intuitive belief that killing adult mosquitoes is the most effective strategy to control an ongoing epidemic. On the other hand, the control of immature forms was very efficient ill preventing the resurgence of dengue epidemics. Since the control of immature forms allows the reduction of adulticide, it seems that the best strategy is to combine both adulticide and larvicide control measures during an outbreak, followed by the maintenance of larvicide methods after the epidemic has subsided. In addition, the model showed that the mixed strategy of adulticide and larvicide methods introduced by the government seems to be very effective in reducing the number of cases in the first weeks after the start of control.