Prevalence and factors associated with burnout among health professionals of a public hospital network during the COVID-19 pandemic.

Burnout is most commonly defined as a syndrome characterized by emotional exhaustion, cynicism, and ineffectiveness, which occurs in response to chronic stressors at work. It can adversely affect health workers' physical and mental health, and the quality of care provided. The COVID-19 pandemic increased stressors and could impact burnout prevalence in this group. There is a lack of information regarding the prevalence of burnout among hospital health workers in Brazil. A newer definition of burnout has been proposed that considers three different clinical profiles: the frenetic, underchallenged and worn-out subtypes. This differentiation could lead to interventions tailored for each subtype. The present study aimed to estimate the prevalence of burnout, its subtypes, and associated factors in workers of a public hospital network in Brazil, during the pandemic. A total of 143 randomly selected participants answered an online form that included sociodemographic and occupational items, and the Burnout Clinical Subtypes Questionnaire, a summarized version. This questionnaire evaluates three burnout dimensions (overload, lack of development, neglect) that can be used to discriminate the three burnout subtypes (frenetic, underchallenged, worn-out, respectively); higher scores indicate higher burnout levels. The prevalence of burnout was high (53.85%), similar to other studies during the pandemic. The most common subtypes were 'frenetic' (34.97%), characterized by increased efforts to meet work demands, to the point of neglecting personal needs, and 'lack of development' (23.78%), characterized by a sense that work is uninteresting and does not contribute to personal development, and a perfunctory behavior towards tasks. Age was associated with burnout: workers with less than 51 years presented higher levels of burnout. These findings indicate the need for effective interventions to prevent and/or treat burnout. The assessment of burnout subtypes can allow managers to better understand the processes affecting employees, and inform actions to improve workforce health.

Oncologic safety of immediate autologous fat grafting for reconstruction in breast-conserving surgery.

IMPORTANCE: Autologous fat grafting (AFG), or lipofilling, has been used for immediate reconstruction at the time of breast-conserving surgery in order to achieve a satisfactory cosmetic outcome in patients with breast cancer and an unfavorable tumor-to-breast volume ratio or unfavorable tumor location. However, the oncologic safety of this technique is still unclear. OBJECTIVE: To determine whether AFG performed simultaneously with breast-conserving surgery is associated with differences in local relapse rates and disease-free survival. DESIGN: Matched retrospective cohort study. SETTING: Tertiary referral center. PARTICIPANTS: Patients undergoing breast-conserving surgery with or without AFG between 2004 and 2016 were retrospectively enrolled and matched for age, staging, grade, tumor histology, and tumor immunohistochemical profile. MAIN OUTCOME(S) AND MEASURE(S): The cumulative incidence of locoregional recurrence (LRR) and disease-free survival were the primary end points, while distant recurrence and overall survival were the secondary end points. RESULTS: A total of 320 patients were followed. Cases were matched with controls at a 1:4 ratio. There was no difference in LRR or distant recurrence of breast cancer between the two groups. The annual LRR rate was 0.86% in patients who received immediate AFG vs. 0.7% in patients undergoing breast-conserving surgery alone (p ≥ 0.05). Number of lymph nodes was the sole independent risk factor for local recurrence (p = 0.045). No significant differences in disease-free survival rates were found between the groups. CONCLUSIONS AND RELEVANCE: At a mean follow-up of 5 years, no significant differences in locoregional recurrence rates were found between patients who received immediate AFG and those who underwent breast-conserving surgery alone. These findings corroborate previous research demonstrating the oncological safety of immediate AFG reconstruction, further suggesting that this technique as a safe, effective way to achieve optimal cosmetic outcomes in primary breast cancer surgery without jeopardizing oncologic outcomes.

The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS). We tested the hypothesis that melatonin use before and during the first cycle of ACBC is better than placebo at improving the DPMS function assessed by changes in the 0-10 Numerical Pain Scale (NPS) during the conditioned pain modulating task (CPM-task) (primary outcome). The effects of melatonin were evaluated in the following secondary endpoints: heat pain threshold (HPT), heat pain tolerance (HPTo), and neuroplasticity state assessed by serum brain-derived neurotrophic factor (BDNF), tropomyosin kinase receptor B, and S100B-protein and whether melatonin's effects on pain and neuroplasticity state are due more so to its impact on sleep quality. Methods: Thirty-six women, ages 18 to 75 years old, scheduled for their first cycle of ACBC were randomized to receive 20mg of oral melatonin (n = 18) or placebo (n = 18). The effect of treatment on the outcomes was analyzed by delta (Δ)-values (from pre to treatment end). Results: Multivariate analyses of covariance revealed that melatonin improved the function of the DPMS. The Δ-mean (SD) on the NPS (0-10) during the CPM-task in the placebo group was -1.91 [-1.81 (1.67) vs. -0.1 (1.61)], and in the melatonin group was -3.5 [-0.94 (1.61) vs. -2.29 (1.61)], and the mean difference (md) between treatment groups was 1.59 [(95% CI, 0.50 to 2.68). Melatonin's effect increased the HPTo and HPT while reducing the (Δ)-means of the serum neuroplasticity marker in placebo vs. melatonin. The Δ-BDNF is 1.87 (7.17) vs. -20.44 (17.17), respectively, and the md = 22.31 [(95% CI = 13.40 to 31.22)]; TrKB md = 0.61 [0.46 (0.17) vs. -0.15 (0.18); 95% CI = 0.49 to 0.73)] and S00B-protein md = -8.27[(2.89 (11.18) vs. -11.16 (9.75); 95% CI = -15.38 to -1.16)]. However, melatonin's effect on pain and the neuroplastic state are not due to its effect on sleep quality. Conclusions: These results suggest that oral melatonin, together with the first ACBC counteracts the dysfunction in the inhibitory DPMS and improves pain perception measures. Also, it shows that changes in the neuroplasticity state mediate the impact of melatonin on pain. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03205033.

Breast-Conserving Surgery with Immediate Autologous Fat Grafting Reconstruction: Oncologic Outcomes.

INTRODUCTION: Autologous fat grafting (AFG; lipofilling, lipografting) has been used in delayed breast reconstruction. Recently, it has also been investigated as an alternative for immediate reconstruction in patients submitted to breast-conserving surgery (BCS). Although good aesthetic results have been reported, the oncologic safety of the procedure remains under investigation. This article aims to assess oncologic outcomes of patients submitted to BCS with immediate AFG reconstruction. METHODS: This study consisted of 65 patients undergoing BCS with AFG between January 2010 and January 2017. They were closely followed after surgery for a median period of 40.8 months. Locoregional and systemic recurrences were the primary endpoints of this study. RESULTS: Ten patients developed cancer recurrence (15.4%). The median time for recurrence was 58.9 months. Only two patients presented locoregional recurrence (LRR) (3.07%). Five patients had systemic recurrence (7.69%), and three had both systemic and LRR (4.61%). Median disease-free survival (DFS) was 42.2 months, and overall survival (OV) was 44.3 months. Recurrences were significantly associated with the number of metastatic axillary lymph nodes detected. CONCLUSION: Oncologic outcomes of immediate AFG are similar to the results previously reported in BCS without AFG. Locoregional and systemic recurrences are associated with the presence of axillary metastases. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

TP53 p.Arg337His germline mutation prevalence in Southern Brazil: Further evidence for mutation testing in young breast cancer patients.

Premenopausal breast cancer (BC) is a core tumor of Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) Syndromes, predisposition disorders caused by germline mutations in TP53 gene. In the Southern and Southeastern regions of Brazil, a specific TP53 germline mutation, c.1010G>A (p.Arg337His), was identified at a population frequency of 0.3%, the highest value ever described for a TP53 germline variation. In Brazilian BC patients, carrier frequency can vary from 0.5% to 8.7%. The current study assessed carrier frequency by genotyping TP53 c.1010G>A in 2 BC groups: 1) 315 patients unselected for age of diagnosis and family history (FH) and 2) 239 patients diagnosed before 46 years and without Chompret criteria for LFS or LFL. One carrier was identified in group 1 (0.3%; CI 95% 0.1-1.76%) and six carriers in group 2 (2.5%; CI 95% 0.93-5.39%). The frequencies differed significantly between groups (p = 0.04). The mutation carrier frequency observed in group 2 could justify mutation testing in BC patients diagnosed before 46 years and without Chompret criteria for LFS or LFL. Further studies in larger samples of BC patients of different ages and regions of the country are necessary to provide more definitive TP53 p.Arg337His carrier frequencies in different scenarios.

Immediate reconstruction with autologous fat grafting: influence in breast cancerregional recurrence.

Objective: to evaluate local and systemic recurrence of breast cancer in patients submitted to autologous fat grafting in the immediate reconstruction after conservative surgery for breast cancer. Methods: this is a historical cohort study comparing 167 patients submitted to conservative surgery without reconstruction (conservative surgery group) with 27 patients submitted to conservative treatment with immediate graft reconstruction, following the Coleman's technique (lipofilling group). All patients had invasive carcinoma and were operated by a single surgeon from 2004 to 2011. The postoperative follow-up time was 36 months. Results: the overall incidence of local recurrence was 2.4%. No patient in the lipofilling group had local recurrence during the study period. For systemic recurrence, the rates obtained were 3.7% (one patient) for the fat grafting group and 1.8% (three patients) for the conservative surgery group without reconstruction. Conclusion: there was no significant difference for local or systemic recurrence in the groups studied. Immediate autologous fat grafting appears to be a safe procedure.

Objtivo: avaliar recorrência local e sistêmica do câncer de mama em pacientes submetidas ao enxerto autólogo de gordura na reconstrução imediata após cirurgia conservadora para o câncer de mama. Métodos: estudo de coorte histórica em que foram comparadas 167 pacientes submetidas à cirurgia conservadora sem reconstrução com 27 pacientes submetidas ao tratamento conservador com reconstrução imediata do enxerto, seguindo técnica de Coleman. Todas as pacientes eram portadoras de carcinoma invasor e foram operadas por um único cirurgião, no período de 2004 a 2011. O tempo de acompanhamento pós-operatório foi 36 meses. Resultados: a incidência global de recidiva local foi 2,4%. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (uma paciente) para o grupo lipoenxertia e 1,8% (três pacientes) para grupo da cirurgia conservadora sem reconstrução. Conclusão: não houve diferença significativa para recorrência local ou sistêmica nos grupos estudados. O enxerto autólogo imediato de gordura parece ser um procedimento seguro.

Immediate reconstruction with autologous fat grafting: influence in breast cancerregional recurrence / Reconstrução imediata com enxerto autólogo de gordura: influência na recorrência local de câncer de mama

ABSTRACT Objective: to evaluate local and systemic recurrence of breast cancer in patients submitted to autologous fat grafting in the immediate reconstruction after conservative surgery for breast cancer. Methods: this is a historical cohort study comparing 167 patients submitted to conservative surgery without reconstruction (conservative surgery group) with 27 patients submitted to conservative treatment with immediate graft reconstruction, following the Coleman's technique (lipofilling group). All patients had invasive carcinoma and were operated by a single surgeon from 2004 to 2011. The postoperative follow-up time was 36 months. Results: the overall incidence of local recurrence was 2.4%. No patient in the lipofilling group had local recurrence during the study period. For systemic recurrence, the rates obtained were 3.7% (one patient) for the fat grafting group and 1.8% (three patients) for the conservative surgery group without reconstruction. Conclusion: there was no significant difference for local or systemic recurrence in the groups studied. Immediate autologous fat grafting appears to be a safe procedure.

RESUMO Objetivo: avaliar recorrência local e sistêmica do câncer de mama em pacientes submetidas ao enxerto autólogo de gordura na reconstrução imediata após cirurgia conservadora para o câncer de mama. Métodos: estudo de coorte histórica em que foram comparadas 167 pacientes submetidas à cirurgia conservadora sem reconstrução com 27 pacientes submetidas ao tratamento conservador com reconstrução imediata do enxerto, seguindo técnica de Coleman. Todas as pacientes eram portadoras de carcinoma invasor e foram operadas por um único cirurgião, no período de 2004 a 2011. O tempo de acompanhamento pós-operatório foi 36 meses. Resultados: a incidência global de recidiva local foi 2,4%. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (uma paciente) para o grupo lipoenxertia e 1,8% (três pacientes) para grupo da cirurgia conservadora sem reconstrução. Conclusão: não houve diferença significativa para recorrência local ou sistêmica nos grupos estudados. O enxerto autólogo imediato de gordura parece ser um procedimento seguro.

Água e saúde: bens públicos da humanidade / Water and health: public goods of humanity

O desenvolvimento sustentável foi mais divulgado após a Rio-92. Nesse encontro foi criado o Dia Mundial da Água, celebrado anualmente. Em 2001, pela OMS, tivemos “Água para Saúde”, que afirma que ambos são “bens públicos da humanidade”. Em 2015, pelo PNUD, “Água e Desenvolvimento Sustentável” mostra que é uma constante associar água, saúde e desenvolvimento e comparar suas propostas aos Objetivos de Desenvolvimento do Milênio (ODM). Consideramos que os rumos globais, na atualidade, colocam em debate a propriedade privada no século XXI.

Sustainable development was more widespread after Rio-92. This meeting was created World Water Day, celebrated annually. In 2001, the WHO had “Water for estudos avançados 29(84), 2015147Health” which states that both are “public goods of humanity”. In 2015, UNDP, “Water and Sustainable Development” shows that it is a constant associate water, health and development and compare their proposals to the Millennium Development Goals (MDGs). We believe that the actual global debate puts in question the private property in the XXI century.

CYP3A4*22 is related to increased plasma levels of 4-hydroxytamoxifen and partially compensates for reduced CYP2D6 activation of tamoxifen.

AIM: To evaluate the impact of CYP3A4*22 in the formation of endoxifen (EDF) and hydroxytamoxifen (HTF), under different CYP2D6 genotypic backgrounds. MATERIALS & METHODS: 178 patients were enrolled in the study. CYP2D6 and CYP3A4 genotyping and tamoxifen (TAM) and metabolites quantification were performed. RESULTS: EDF concentrations were lower in poor (2.77 ng ml(-1)) and CYP2D6 intermediate metabolizers (5.84 ng ml(-1)), comparing to functional group (EM-F) (10.67 ng ml(-1), p < 0.001). HTF and TAM levels were respectively 47 and 53% higher in CYP3A4*22 carriers compared with *1/*1 patients in the whole group. Patients with impaired CYP2D6 metabolism and carriers of CYP3A4*22 had EDF levels comparable to CYP2D6 EM-F group (9.06 and 10.67 ng ml(-1), p = 0.247). CONCLUSION: The presence of CYP3A4*22 might compensate the reduction of EDF concentrations related to CYP2D6 inactivity, especially due to increased HTF concentrations.

Influence of CYP2D6 and CYP3A4 Phenotypes, Drug Interactions, and Vitamin D Status on Tamoxifen Biotransformation.

OBJECTIVE: In view of the large variability on therapeutic response and the multiple factors associated to tamoxifen (TAM) metabolic activation, this study aimed to evaluate the effect of CYP2D6 and CYP3A4 phenotypes, drug interactions, and vitamin D exposure on TAM metabolism in a group of breast cancer patients. METHODS: Trough blood samples were collected from 116 patients. TAM and metabolites endoxifen (EDF), N-desmethyltamoxifen, and 4-hydroxytamoxifen (HTF) were measured in plasma by liquid chromatography-tandem mass spectrometry. CYP2D6 and CYP3A4 phenotyping were obtained according to [dextromethorphan]/[dextrorphan] and [omeprazole]/[omeprazole sulfone] metabolic ratios, measured by high-performance liquid chromatography in plasma collected 3 hours after oral administration of 33 mg of dextromethorphan and 20 mg of omeprazole. Vitamin D3 was measured in plasma by high-performance liquid chromatography-ultraviolet. Data on concomitant use of drug considered as CYP2D6 and CYP3A4 inhibitor or inducer and vitamin D supplementation were recorded. RESULTS: About 20% of patients had reduced CYP2D6 metabolic activity and 7% CYP3A4 impaired metabolism. EDF levels diminished proportionally to the reduction of CYP2D6 metabolic activity (poor metabolizer 2.79 ng·mL, intermediate metabolizer (IM) 5.36 ng·mL, and extensive metabolizer 10.65 ng·mL, P < 0.01). Median plasma levels of TAM (161.50 ng·mL) and HTF (1.32 ng·mL) in CYP2D6 IM/CYP3A4 poor metabolizer patients were higher (P < 0.05) than those from CYP2D6 IM/CYP3A4 extensive metabolizer patients (122.07 ng·mL and 0.61 ng·mL, respectively). Seasons contributed to the interpatient variability of EDF and HTF levels; summer concentrations were 24% and 42% higher compared with winter. Vitamin D3 was not associated to CYP3A4 metabolic activity, indicating that other mechanisms might be involved in the relation between TAM metabolism and vitamin D exposure. CONCLUSIONS: CYP3A4 contributes to the bioactivation of TAM through formation of HTF and becomes increasingly important in case of reduced or absent CYP2D6 activity. EDF and HTF exposure were associated to seasonal variations, with considerable higher plasma concentrations during summer.

Immediate Reconstruction with Autologous fat Transfer Following Breast-Conserving Surgery.

This study explores the technical viability of autologous fat grafting for immediate partial breast reconstruction following the primary conservative surgery for breast cancer; restoring volume, shape, and symmetry to the treated breast. We analyze the impact in relation to mammographic follow-up and the subjective degree of satisfaction with esthetic results and although we didn't have any local failure during the observation period; we understand that is too early for any kind of conclusion. From June of 2010 to July of 2011, 20 patients were selected for breast-conserving surgery (BCS) with partial breast reconstruction with autologous fat grafting performed during the same operation by the same medical team. The fat graft was injected in the subcutaneous and intraglandular breast tissue around the resected area. We performed an overcorrection, predicting a resorbing of about 30-50% of the volume grafted. All patients received the literature-based recommendations for breast cancer treatment with complementary radiotherapy. The follow-up period after the completion of radiotherapy ranged from 13 to 29 months. The average volume grafted was 121 cc and it was 2.1 times larger than the resected volume. The esthetic scores were considered very good or good in the majority of cases. Mammograms were taken every 6 months after radiotherapy and only one patient had a mammogram classified as BI-RADS 3, suggesting fat necrosis. The remaining patients were classified as BI-RADS 2. Immediate autologous fat grafting is a promising technique for partial breast reconstruction after BCS. It is associated with high patient and physician satisfaction. It is an alternative for reconstruction of small- and medium-sized breasts. This technique has the advantage that enables the reconstruction of defects in areas difficult to repair, particularly in the upper inner quadrants. It also may reduce the need for major glandular or myocutaneous flaps mobilization.

Standardization of sodium metabisulfite solution concentrations and immersion time for farmed shrimp Litopenaeus vannamei / Padronização da concentração da solução de metabissulfito de sódio e do tempo de imersão para camarão cultivado Litopenaeus vannamei

Sodium metabisulfite is the main additive used in the prevention of melanosis in shrimp; however, it has currently been employed with great variation in concentration by producers. Thus, the aim of the present study was to determine the correlation between the concentration of the sodium metabisulfite solution and immersion time of the whole shrimp to obtain the concentration of sulfur dioxide (SO2) in the edible muscle of farmed shrimp (Litopenaeus vannamei) in accordance with the limit established by law. For this, solutions of sodium metabisulfite at different concentrations (1%, 2 %, 3 %, 4% and 5%) were prepared and samples of L. vannamei shrimp (100g) were immersed during 10, 20 or 30 minutes at temperature of 7°C. For all treatment assayed the concentration of SO2 was determined in the edible muscle of farmed shrimp (L. vannamei). The results show that for the conditions used in this study, the correlations were linear, with significant increase (P<0.05) in the SO2 concentration in the edible muscle of shrimps both increasing sodium metabisulfite concentration as increasing immersion times, suggesting the immersion of shrimps in a 3% solution for a time of 13 minutes in order to obtain SO2 concentration of 100ppm in its edible muscle in accordance with Brazilian legislation.

O metabissulfito de sódio é o principal aditivo usado na prevenção da melanose em camarão, porém, atualmente, é empregado com grande variação de suas concentrações pelos produtores. Assim, o objetivo deste estudo foi determinar a correlação entre a concentração da solução de metabissulfito de sódio e do tempo de imersão do camarão inteiro para obter a concentração final de dióxido de enxofre (SO2) no músculo comestível de camarão cultivado (Litopenaeus vannamei), de acordo com os limites estabelecidos pela legislação. Para isso, foram preparadas soluções de metabissulfito de sódio em diferentes concentrações (1%, 2%, 3%, 4% e 5%); e amostras de camarão L. vannamei (100g) foram imersas durante 10, 20 e 30 minutos à temperatura de 7ºC. Para todos os tratamentos, foram realizadas análises da concentração de SO2 no músculo comestível do camarão cultivado (L. vannamei). Os resultados demonstraram que, para as condições empregadas nesta pesquisa, as correlações encontradas foram lineares, ocorrendo um aumento significativo (P<0,05) nos teores de SO2 no músculo comestível do camarão, tanto com o aumento da concentração das soluções de metabissulfito de sódio, quanto com o aumento no tempo de imersão, sendo possível sugerir a imersão dos camarões em solução a 3% por um tempo de 13 minutos, de forma a se obter, em seu músculo comestível, a concentração de 100ppm de SO2, de acordo com o recomendado pela legislação brasileira.

Ultra-high performance liquid chromatography tandem mass spectrometric method for the determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots--development, validation and clinical application during breast cancer adjuvant therapy.

A LC-MSMS method for the simultaneous determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots samples was developed and validated. The method employs an ultrasound-assisted liquid extraction and a reversed phase separation in an Acquity(®) C18 column (150×2.1 mm, 1.7 µm). Mobile phase was a mixture of formic acid 0.1% (v/v) pH 2.7 and acetonitrile (gradient from 60:40 to 50:50, v/v). Total analytical run time was 8 min. Precision assays showed CV % lower than 10.75% and accuracy in the range 94.5 to 110.3%. Mean analytes recoveries from DBS ranged from 40% to 92%. The method was successfully applied to 91 paired clinical DBS and plasma samples. Dried blood spots concentrations were highly correlated to plasma, with rs>0.83 (P<0.01). Median estimated plasma concentrations after hematocrit and partition factor adjustment were: TAM 123.3 ng mL(-1); NDT 267.9 ng mL(-1), EDF 10.0 ng mL(-1) and HTF 1.3 ng mL(-1,) representing in average 98 to 104% of the actually measured concentrations. The DBS method was able to identify 96% of patients with plasma EDF concentrations below the clinical threshold related to better prognosis (5.9 ng mL(-1)). The procedure has adequate analytical performance and can be an efficient tool to optimize adjuvant breast cancer treatment, especially in resource limited settings.

Development, validation and clinical application of a HPLC-FL method for CYP2D6 phenotyping in South Brazilian breast cancer patients.

OBJECTIVE: To develop and validate a method for determination of dextromethorphan (DMT) and dextrorphan (DTP) in plasma samples using HPLC-FL and to apply it to CYP2D6 phenotyping of a population from the South of Brazil. METHODS: Samples were prepared by hydrolysis and liquid-liquid extraction. Analysis was conducted in a reversed phase column, with isocratic elution and fluorescence detection. One hundred and forty patients being treated with tamoxifen were given 30 mg of dextromethorphan and their CYP2D6 phenotypes were determined on the basis of [DMT]/[DTP] metabolic ratios in plasma samples collected after 3h. RESULTS: Total chromatography running time was 12 min. Precision (CV%) was below 9.7% and accuracy was between 92.1 and 106.9%. The lower limits of quantification were 1 ng mL(-1) for DMT and 10 ng mL(-1) for DTP. Mean extraction yield of analytes was 86.6%. Mean age of patients was 55.7 years. Phenotype frequencies were as follows: 7.1% poor metabolizers, 13.6% intermediate metabolizers, 77.1% extensive metabolizers and 2.1 ultra-rapid metabolizers. Metabolic ratios for patients on strong (n=11) and weak (n=16) CYP2D6 activity inhibitors were different from each other and also different from ratios for patients not taking enzyme inhibitors (n=113). CONCLUSIONS: A sensitive method for determination of dextromethorphan and its metabolite in plasma samples was developed and successfully applied, providing evidence of the impact that CYP2D6 inhibitors have on the enzyme's metabolic capacity.

Highly focalised thermotherapy using a ferrimagnetic cement in the treatment of a melanoma mouse model by low temperature hyperthermia.

PURPOSE: Evaluation of the effectiveness of highly focalised thermotherapy (HFT) in a melanoma mouse model, using a ferrimagnetic cement (FC) and repeated low hyperthermia treatments. MATERIALS AND METHODS: A melanoma mouse model was induced with B16F10 cells in C57BL6 mice. The FC, injected into the tumour, was used as the magnetic vehicle for HFT. FC location within the tumour was assessed by radiography and its capability to generate heat, when exposed to an external high frequency magnetic field (HFMF), monitored by thermal camera. The HFT treatment consisted of three HFMF exposures, with 48-h intervals, each one lasting 30 min, with a 5-6°C tumour temperature increase. At the end of the experiment, FC samples were characterised by scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS). The presence of iron contents was analysed in the tumour, lungs, liver and spleen. Histological evaluation and immunohistochemical staining for caspase-3 were performed. Tumour growth was monitored during the experiment. RESULTS: Surface analysis showed FC stabilisation within the tumour, and iron was absent. The thermal camera confirmed the localised temperature increase in the tumour. HFT treatments inhibited the tumour growth by ∼70% compared to controls. This was due to cell destruction by necrosis and apoptosis. CONCLUSIONS: The HFT, using the FC, proved to be a minimally invasive technique that statistically inhibited tumour growth. Results suggested that this methodology seems to be a promising technique for the treatment of solid tumours, allowing repeated low hyperthermia treatments, which can be easier and less traumatic than other hyperthermia techniques.

Processamento de biscoitos adicionados de óleo de buriti(Mauritia flexuosa L): uma alternativa para o consumo de alimentos fontes de vitamina A na merenda escolar / Making cookies with buriti oil Mauritia flexuosa l: an alternative source of dietary vitamin A in school meals

OBJETIVO: Este trabalho teve como objetivo desenvolver biscoitos tipo cookie adicionado de óleo de buriti a fim de se analisarem sua aceitação sensorial e seu valor nutricional, visando a sua utilização na merenda escolar, bem como avaliar o consumo de alimentos fontes de vitamina A por escolares. MÉTODOS: Uma formulação-controle (15% de óleo de soja) e duas formulações experimentais (7,5% e 15% de óleo de buriti) foram produzidas e avaliadas quanto à composição centesimal, conteúdo de vitamina A e aceitação sensorial, testada por 201 escolares. Avaliou-se também o consumo de alimentos fontes de vitamina A por esses escolares mediante questionário semiquantitativo contendo 28 alimentos considerados fontes da referida vitamina. RESULTADOS: O biscoito elaborado com 15% de óleo de buriti obteve boa aceitação, e apresenta maior percentual de proteínas, de minerais e de vitamina A, podendo ser considerado fonte deste último nutriente. Observou-se uma maior frequência de consumo de alimentos com baixo teor de vitamina A, como também uma menor frequência de consumo dos frutos da região Nordeste. CONCLUSÃO: Os biscoitos adicionados de óleo de buriti podem ser uma alternativa de inclusão de alimentos fontes de vitamina A na dieta de escolares, no entanto o consumo de frutas e hortaliças fontes dessa vitamina deve ser estimulado, tendo em vista que os escolares consomem pouca variedade de alimentos fontes dessa vitamina, o que aumenta o risco de deficiência a longo prazo.

OBJECTIVE: The objective of this study was to make cookies with buriti oil for school meals and analyze their acceptance and nutritional content. The study also assessed schoolchildren's dietary vitamin A intake. METHODS: A control batch was made using 15% soybean oil and two batches were made using 7.5% and 15% buriti oil, respectively. The following were then assessed: centesimal composition, vitamin A content and acceptance by 201 children. Consumption of vitamin A by these children was also investigated using a semiquantitative questionnaire listing 28 good dietary sources of vitamin A. RESULTS: The cookie containing 15% buriti oil was well accepted and presented higher protein, mineral and vitamin A contents, so it may be considered a source of vitamin A. Consumption of foods with low vitamin A content was high and intake frequency of fruits from the Brazilian northeast was low. CONCLUSION: Cookies containing buriti oil may be an alternative source of dietary vitamin A in school meals. However, the consumption of fruits and vegetables with this vitamin should also be encouraged since schoolchildren consume a small variety of dietary sources of vitamin A, which increases their long-term susceptibility to vitamin A deficiency.

Sexual function and chemotherapy in postmenopausal women with breast cancer.

BACKGROUND: This cross-sectional, nested cohort study assessed Female Sexual Function Index (FSFI) scores in postmenopausal women with breast cancer receiving primary chemotherapy. METHODS: The FSFI questionnaire was administered to 24 postmenopausal women one month after diagnosis of breast cancer (post-diagnosis group) and one month after completion of the first cycle of primary anthracyclin-based chemotherapy (post-chemotherapy group). Scores were compared to those of 24 healthy postmenopausal women seeking routine gynecological care (control group). All patients were sexually active at the time of enrollment. Mean age was 57.29 ± 11.82 years in the breast cancer group and 52.58 ± 7.19 years in the control group. RESULTS: Scores in all domains of the FSFI instrument were significantly lower in the post-diagnosis group than in controls (-41.3%, p < 0.001). A further major reduction in FSFI scores was evident on completion of one cycle of primary chemotherapy (down 46.7% from post-diagnosis scores, p < 0.003), again in all domains. Six patients (25%) ceased all sexual relations, in a significant change from baseline (p < 0.001). After one chemotherapy cycle, a further five patients ceased sexual activity, for a total of 11 (45.8%) participants--a borderline significant difference (p = 0.063). CONCLUSION: The present study shows that female sexual function as assessed by the FSFI declines significantly at two distinct points in time: upon diagnosis of breast cancer and after administration of systemic chemotherapy.

Avaliação sensorial de filés do camarão marinho (Litopenaeus vannameII) Liofilizados / Sensory evaluation of steaks marine shrimp (Litopenaeus vannameII) Lyophilized

O objetivo desse estudo foi avaliar a aceitação do filé do camarão marinho (Litopenaeus vannameii) liofilizado, sob o enfoque da analise sensorial de testes. Foram preparados dois produtos: (1) camarão in natura e (2) camarão liofilizado previamente reidratado, cozido em molho de tomate. Foi também avaliada a intenção de compra, utilizando-se uma escala hedônica de 5 pontos, variando de certamente compraria e certamente não compraria. Os resultados foram submetidos ao teste estatístico t de Student. Na avaliação da interatividade entre os atributos sensoriais e a intenção de compra desenvolveu-se a ACP – Análise de Componentes Principais. As notas médias para o camarão não liofilizado e liofilizado para cada atributo avaliado situaram-se acima de 7 e não apresentaram diferença significativa ao nível de 5%. A intenção de compra resultou em valores iguais a 4,1, não havendo, também, diferença significante. Os testes comprovam que o produto desenvolvido é uma nova e rentável alternativa para o mercado brasileiro carente de novidades produzidas a partir do camarão.

Acute and long-term effects of hyperthermia in B16-F10 melanoma cells.

OBJECTIVE: Hyperthermia uses exogenous heat induction as a cancer therapy. This work addresses the acute and long-term effects of hyperthermia in the highly metastatic melanoma cell line B16-F10. MATERIALS AND METHODS: Melanoma cells were submitted to one heat treatment, 45°C for 30 min, and thereafter were kept at 37°C for an additional period of 14 days. Cultures maintained at 37°C were used as control. Cultures were assessed for the heat shock reaction. RESULTS: Immediately after the heat shock, cells began a process of fast degradation, and, in the first 24 h, cultures showed decreased viability, alterations in cell morphology and F-actin cytoskeleton organization, significant reduction in the number of adherent cells, most of them in a process of late apoptosis, and an altered gene expression profile. A follow-up of two weeks after heat exposure showed that viability and number of adherent cells remained very low, with a high percentage of early apoptotic cells. Still, heat-treated cultures maintained a low but relatively constant population of cells in S and G(2)/M phases for a long period after heat exposure, evidencing the presence of metabolically active cells. CONCLUSION: The melanoma cell line B16-F10 is susceptible to one hyperthermia treatment at 45°C, with significant induced acute and long-term effects. However, a low but apparently stable percentage of metabolically active cells survived long after heat exposure.

Degradação de α-Tocoferol, retinol e ácido ascórbico durante processamento e armazenamento de rações para camarão / α-Tocopherol, retinol and ascorbic acid degradation during the processing and storage of shrimp food

O cultivo de camarão marinho é um setor de grande viabilidade econômica, principalmente na região Nordeste. Entretanto, a alimentação dos camarões é responsável pelo maior custo no cultivo desses crustáceos, a ração deve ser nutricionalmente eficiente, sendo indispensável a presença das vitaminas que são substâncias fundamentais para o funcionamento do organismo animal, e sua falta resulta frequentemente em crescimento e desenvolvimento deficiente. O retinol, -tocoferol e o ácido ascórbico são vitaminas que atuam em diversos processos metabólicos. São indispensáveis em rações animais porque são antioxidantes que auxiliam os animais contra o estresse oxidativo. Objetivou-se, neste trabalho, avaliar as perdas das vitaminas durante o processamento das dietas e no período de armazenagem. Foram formuladas oito dietas isoprotéicas com diferentes níveis de vitamina A, E e C que foram processadas com temperatura de até 80ºC. Após a fabricação e depois de 60 dias de armazenagem foram analisadas e quantificadas as vitaminas a fim de descobrir as perdas durante o processamento e após estocagem. Constatou-se que a vitamina A, que foi adicionada na dieta, foi perdida em até 99,56 por cento. Já a vitamina E perdeu no máximo 93,5 por cento e a vitamina C com 70 por cento de perda, durante o processamento. Durante o período de armazenagem as perdas foram menores. Pode-se concluir que as vitaminas são extremamente sensíveis aos fatores que atuam durante a manufatura das dietas, ocasionando perdas consideráveis de vitaminas.

The farming of marine shrimp is a sector of great economic viability, mainly in the Northeast region of Brazil. However, feeding is responsible for the major cost in the farming of these crustaceans, so the food must be nutritiously efficient, since it is essential to the presence of vitamins which are vital substances to the functioning of the animal's organism where its lack frequently results in deficient growth and development. Retinol, -tocopherol, and ascorbic acid are vitamins that act in several metabolic processes, therefore they are indispensable in animal food due to their antioxidant effects that protect these animals against oxidative stress. The objective of this study was to evaluate the vitamin losses during the diet processing and in the storage period. Eight isoproteic diets were formulated with different levels of vitamin A, E and C that were processed with temperatures up to 70º C. After the production and 60 days of storage, the vitamins were analyzed and quantified in order to discover the losses during the processing and post-storage. It was observed that the vitamin A suffered loss of up to 99.56 percent, vitamin E had its maximum loss value of 93.5 percent and vitamin C with 70 percent of loss, during the processing. During the storage period the losses were lower. It can be concluded that the vitamins are extremely sensitive to the factors that occur during the production and food storage, causing considerable vitamin losses.