Dose optimization for cancer treatments with considerations for late-onset toxicities.

Given that novel anticancer therapies have different toxicity profiles and mechanisms of action, it is important to reconsider the current approaches for dose selection. In an effort to move away from considering the maximum tolerated dose as the optimal dose, the Food and Drug Administration Project Optimus points to the need of incorporating long-term toxicity evaluation, given that many of these novel agents lead to late-onset or cumulative toxicities and there are no guidelines on how to handle them. Numerous methods have been proposed to handle late-onset toxicities in dose-finding clinical trials. A summary and comparison of these methods are provided. Moreover, using PI3K inhibitors as a case study, we show how late-onset toxicity can be integrated into the dose-optimization strategy using current available approaches. We illustrate a re-design of this trial to compare the approach to those that only consider early toxicity outcomes and disregard late-onset toxicities. We also provide proposals going forward for dose optimization in early development of novel anticancer agents with considerations for late-onset toxicities.

The rs2018736 fibulin-5 polymorphism as a determinant for pelvic organ prolapse: a case-control study.

OBJECTIVE: Fibulin-5 is a connective tissue component and may play a role in pelvic organ prolapse (POP) pathogenesis. This study aimed to verify the association of the rs2018736 polymorphism of the fibulin-5 gene with POP in postmenopausal Brazilian women, and to determine the risk factors for POP. METHOD: This observational, cross-sectional, case-control study assessed postmenopausal women with advanced POP (stages III and IV) and control women (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences were analyzed by real-time reverse-transcriptase polymerase chain reaction. A logistic regression model was used with p < 0.05 for significance. RESULTS: A total of 565 participants were evaluated (325 POP and 240 control). The homozygous C allele of rs2018736 (CC) was protective against POP (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.91). Age (OR 1.09, 95% CI 1.05-1.13), number of pregnancies (OR 1.14, 95% CI 1.01-1.28), vaginal delivery (OR 5.32, 95% CI 2.58-11.01), forceps delivery (OR 3.34, 95% CI 1.72-6.47), weight of newborn (OR 1.0007, 95% CI 1.0002-1.0011), family history of POP (OR 2.35, 95% CI 1.24-4.44), hypertension (OR 1.74, 95% CI 1.01-3.00) and diabetes (OR 2.19, 95% CI 1.07-4.48)] were independent predictors for POP; cesarean (OR 0.02, 95% CI 0.005-0.09) was protective. CONCLUSION: The rs2018736-CC genotype of the fibulin-5 gene has a protective role against POP.

Association between the rs1036819 polymorphism of the ZFAT gene and pelvic organ prolapse: a case-control study.

INTRODUCTION AND HYPOTHESIS: The identification of risk factors for pelvic organ prolapse (POP) would contribute to planning prevention strategies. This study tests the hypothesis that the rs1036819 polymorphism in the ZFAT gene is associated with POP and investigates other risk factors for prolapse development. METHODS: A case-control study was carried out including 826 postmenopausal women divided into POP cases (stages III and IV) and controls (stages 0 and I), assessed by anamnesis, examination, and peripheral blood samples. DNA was extracted from blood and genotyped by real-time RT-PCR. We used logistic regression models for the association analyses of variables, with p < 0.05 for significance. RESULTS: Five hundred and sixty-eight women were evaluated (315 POP and 253 controls). The minor allele C was found in 19.3% of our sample and the genotype frequencies of AA, AC, and CC were similar in both groups. Age (OR 1.09, 95% CI 1.06-1.13), number of pregnancies (OR 1.23, 95% CI 1.08-1.41), history of one vaginal delivery (OR 3.39, 95% CI 1.38-8.33) or two or more (OR 2.51, 95% CI 1.04-6.07), weight of the largest newborn (OR 1.0001, 95% CI 1-1.001), and family history of POP (OR 2.27, 95% CI 1.24-4.13) were independent risk factors for POP, whereas one cesarean section (OR 0.48, 95% CI 0.27-0.88) or two or more (OR 0.14, 95% CI 0.05-0.38) were protective. CONCLUSIONS: No association was detected between the rs1036819 polymorphism of the ZFAT gene and advanced POP. Age, number of pregnancies, at least one vaginal delivery, weight of the newborn, and POP family history were independent risk factors for POP.

Visceral adiposity indices and cardiometabolic risk markers in patients with hypertension.

Objective: Arterial hypertension (AH) is a risk factor for cardiovascular diseases (CVD). We sought to evaluate the association between two adiposity indices (visceral adiposity index [VAI] and lipid accumulation product [LAP]) with traditional markers of cardiometabolic risk in hypertensive patients. Materials and methods: This is a cross-sectional study with 1,273 subjects with hypertension treated as outpatients at a university hospital. The VAI and LAP were calculated using formulas stratified by sex. Cardiometabolic risk variables were considered: overweight, risk for waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHA), and altered biochemical test values. The predictive effect of independent variables on outcomes was assessed by multivariate linear regression analysis. There was statistical significance when p ≤ 0.05. Results: Higher cardiometabolic risk (according to BMI, WHR, WHA, and altered biochemical parameters) was associated with higher values of VAI and LAP with statistical significance (p ≤ 0.05). The regression models used explained 30.7% and 10.5% of the changes in LAP and VAI, respectively. Conclusion: LAP and VAI are associated with cardiometabolic risk parameters in the individuals evaluated, suggesting that these indices can be used to screen for CVD risk in individuals with AH.

Visceral adiposity indices and cardiometabolic risk markers in patients with hypertension

Abstract Objective: Arterial hypertension (AH) is a risk factor for cardiovascular diseases (CVD). We sought to evaluate the association between two adiposity indices (visceral adiposity index [VAI] and lipid accumulation product [LAP]) with traditional markers of cardiometabolic risk in hypertensive patients. Materials and methods: This is a cross-sectional study with 1,273 subjects with hypertension treated as outpatients at a university hospital. The VAI and LAP were calculated using formulas stratified by sex. Cardiometabolic risk variables were considered: overweight, risk for waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHA), and altered biochemical test values. The predictive effect of independent variables on outcomes was assessed by multivariate linear regression analysis. There was statistical significance when p ≤ 0.05. Results: Higher cardiometabolic risk (according to BMI, WHR, WHA, and altered biochemical parameters) was associated with higher values of VAI and LAP with statistical significance (p ≤ 0.05). The regression models used explained 30.7% and 10.5% of the changes in LAP and VAI, respectively. Conclusion: LAP and VAI are associated with cardiometabolic risk parameters in the individuals evaluated, suggesting that these indices can be used to screen for CVD risk in individuals with AH.

Phase angle, muscle mass, and functionality in patients with Parkinson's disease.

OBJECTIVE: To evaluate the association of phase angle (PA) with clinical and nutritional aspects in patients with Parkinson's disease (PD) treated in an outpatient clinic in northeastern Brazil. METHODS: This is a case series study involving adults and the elderly with PD of both genders. We collected data such as stage, severity, and time of diagnosis of the disease, muscle strength, gait speed, and level of physical activity. We evaluated the nutritional status using body mass index, calf circumference, skeletal appendicular muscle mass index, and the presence of sarcopenia. We obtained the PA through the analysis by electrical bioimpedance. After obtaining the result of the division between reactance and resistance, with later transformation into degrees, we multiplied the result by 180/π. RESULTS: We evaluated 77 individuals with a mean age of 65.4 ± 8.9 years. 63.6% of them had reduced PA values and 19.7% of them had sarcopenia. Age (rho = - 0.423; p = < 0.001) was inversely correlated with PA. Skeletal appendicular muscle mass index (rho = 0.251; p = 0.028), pressure force (rho = 0.240; p = 0.035), and gait speed (rho = 0.323; p = 0.005) showed a direct correlation with age. When adjusted for confounding factors, only age remained associated with PA (p = 0.012). CONCLUSION: Most individuals had reduced PA, and only age was associated with this result. Aging is a risk factor for reducing muscle mass and physical disability in PD. Although this study indicates a relationship between PA, age, muscle mass, and functionality, further prospective studies are needed to confirm these findings.

Predictors for long-term adherence to vaginal pessary in pelvic organ prolapse: a prospective study.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the rate of adherence to pessary treatment for pelvic organ prolapse (POP), to identify factors associated with long-term (longer than 1 year) use of vaginal pessaries in Brazilian women with POP and its impact on quality of life (QoL). METHODS: A prospective observational study assessed 247 consecutive women candidates for a pessary to manage symptomatic POP. Patients were fitted with a ring pessary and follow-up visits were performed at 1, 6, and 12 months. Pessary complications and reasons for discontinuation were recorded. Prolapse Quality of Life Questionnaire (P-QoL) was applied at baseline and after 1 year of treatment. We used a logistic regression model for the analyses, with p < 0.05 for significance. RESULTS: A total of 236 women were included in the study, of whom 110 (46.6%) maintained the pessary treatment for longer than 12 months. The main reason for pessary discontinuation was the patient opting for surgery (50.8%). Vulvovaginitis was the main long-term complication (44.5%), followed by vaginal ulceration (16.4%) and urinary urgency (10%). No prior hysterectomy (OR = 2.26; 95% CI 1.19-4.31), vaginal estrogen use (OR = 1.94; 95% CI 1.06-3.52), and mean age (OR = 1.03; 95% CI 1.01-1.06) were variables associated with long-term use of vaginal pessary (p < 0.05 for all). Total P-QoL score significantly changed with pessary use (519.1 at baseline and 260 after 12-month treatment, p < 0.00). CONCLUSIONS: Our study suggests that no prior hysterectomy, the local estrogen therapy, and age might be factors associated with use of a ring vaginal pessary for longer than 1 year. Long-term pessary users had a significant improvement in their quality of life.

Nanoparticle-Assisted Nuclear Relaxation-Based Detection of Oligonucleotides.

Nuclear relaxation-based techniques rely on the capability of paramagnetic center to affect the transverse relaxation time (T2) of the water protons. These changes are sensitive to the microenvironment of the paramagnetic center, which can be used to detect a variety of targets. In this work, we present an "on-off" oligonucleotide detection scheme in aqueous solutions, which uses gadolinium phthalocyanine (GdTcPc)-grafted silica nanoparticles as the paramagnetic centers. A probe oligonucleotide strand was conjugated to the GdTcPc to act as a recognition element. In the presence of the target oligonucleotide, which was complementary to the probe, an increase in the ΔT2 value, which was measured by subtracting the characteristic T2 value of the background solution from that of the sample using a benchtop relaxometer, was observed. The magnitude of this increase was proportional to the target oligonucleotide concentration. A linear range was obtained from 30 to 140 nM, with a detection limit of 15 nM. The developed nuclear relaxation-based detection scheme is shown to be a simple, fast, and selective method to detect oligonucleotide and could be useful in point-of-care diagnostic applications.

Detection of Sortase A and Identification of Its Inhibitors by Paramagnetic Nanoparticle-Assisted Nuclear Relaxation.

Sortase A is a virulence factor responsible for the attachment of surface proteins to Staphylococcus aureus and other Gram-positive bacteria. Inhibitors of this enzyme are potential anti-infective agents. Herein, a new highly selective magnetic relaxation-based method for screening potential sortase A inhibitors is described. A 13-amino acid-long peptide substrate of sortase A is conjugated to SiO2-EDTA-Gd NPs. In the presence of sortase A, the LPXTG motif on the peptide strand is cleaved resulting in a shortened peptide as well as a reduced water T2 value whose magnitude is dependent on the concentration of sortase A. The detection limit is determined to be 76 pM. In contrast, the presence of sortase A inhibitors causes the T2 to remain at a higher value. The proposed method is used to characterize inhibition of sortase A by curcumin and 4-(hydroxymercuri)benzoic acid with an IC50 value of 12.9 ± 1.6 µM and 130 ± 1.76 µM, respectively. Furthermore, this method was successfully applied to detect sortase A activity in bacterial suspensions. The feasibility to screen different inhibitors in Escherichia coli and S. aureus suspensions was demonstrated. This method is fast and potentially useful to rapidly screen possible inhibitors of sortase A in bacterial suspensions, thereby aiding in the development of antibacterial agents targeting Gram-positive bacteria.

Would the Recommended Dose Have Been Different Using Novel Dose-Finding Designs? Comparing Dose-Finding Designs in Published Trials.

Simulation studies have shown that novel designs such as the continual reassessment method and the Bayesian optimal interval (BOIN) design outperform the 3 + 3 design by recommending the maximum tolerated dose (MTD) more often, using less patients, and allotting more patients to the MTD. However, it is not clear whether these novel designs would have yielded different results in the context of real-world dose-finding trials. This is a commonly mentioned reason for the continuous use of 3 + 3 designs for oncology trials, with investigators considering simulation studies not sufficiently convincing to warrant the additional design complexity of novel designs. METHODS: We randomly sampled 60 published dose-finding trials to obtain 22 that used the 3 + 3 design, identified an MTD, published toxicity data, and had more than two dose levels. We compared the published MTD with the estimated MTD using the continual reassessment method and BOIN using target toxicity rates of 25% and 30% and toxicity data from the trial. Moreover, we compared patient allocation and sample size assuming that these novel designs had been implemented. RESULTS: Model-based designs chose dose levels higher than the published MTD in about 40% of the trials, with estimated and observed toxicity rates closer to the target toxicity rates of 25% and 30%. They also assigned less patients to suboptimal doses and permitted faster dose escalation. CONCLUSION: This study using published dose-finding trials shows that novel designs would recommend different MTDs and confirms the advantages of these designs compared with the 3 + 3 design, which were demonstrated by simulation studies.

Desafios da pandemia para a mentoria: o papel dos mentores juniores e das redes sociais / Challenges of the pandemic for mentoring: the role of junior mentors and social networks

Resumo: Introdução: A aprovação no curso de Medicina traz consigo a euforia e, por vezes, associa-se a grandes mudanças no dia a dia dos alunos. Essas mudanças estão relacionadas a momentos de medo, sofrimento e adaptação. Os programas de mentoria surgem como espaços importantes de cuidado que oferecem acolhimento e suporte às vivências dos alunos, de modo a contribuir para o desenvolvimento pessoal e acadêmico deles. Relato de experiência: Diante da necessidade de adaptar o ensino presencial ao modelo remoto, em detrimento da pandemia de Covid-19, o programa de mentoria da Universidade Federal do Rio Grande do Norte investiu na realização de atividades on-line, protagonizadas por monitores denominados mentores juniores. Essas atividades se valeram do potencial das mídias sociais, por meio das plataformas de videoconferência, além de interações nas redes sociais, para realizar os encontros e promover a manutenção do vínculo, bem como proporcionar um espaço de acolhimento e integração entre estudantes e mentores. Discussão: A partir da realização de atividades remotas, alunos e mentores mostraram-se muito participativos e satisfeitos. A atuação dos mentores juniores na elaboração dessas atividades virtuais foi um importante diferencial, possibilitando o engajamento dos mais tímidos e daqueles que tinham dificuldade em cumprir os horários presenciais. Conclusão: Mediante a observação no desenvolvimento das atividades do programa e com base na avaliação dos alunos e mentores sobre o desempenho da mentoria no semestre remoto, considera-se que é de grande valia investir no potencial das mídias sociais para impulsionar as reuniões dos grupos de mentoria, garantir a manutenção do acolhimento e suporte aos alunos, bem como para estreitar os vínculos entre os participantes. Sob esse prisma, é necessário considerar a possibilidade de adotar um modelo misto no aperfeiçoamento do programa de mentoria.

Abstract: Introduction: Being accepted for medical school brings euphoria, and is sometimes associated to major changes in the student's daily life. These changes pertain to moments of fear, suffering and adaptation. The mentoring programs, therefore, appear as essential care spaces, offering welcoming and support to students, in order to contribute to their personal and academic development. Experience Report: Faced with the need to adapt from face-to-face teaching to the remote model, to help control the Covid-19 pandemic, the Mentoring program of the Federal University of Rio Grande do Norte invested in conducting online activities led by junior mentors. These activities took advantage of the potential of social media, through video conferencing platforms, in addition to interactions on social networks, to hold the meetings and maintain the link, as well as providing a space for welcoming and integrating students and mentors. Discussion: In relation to the remote activities, students and mentors were found to be very participative and satisfied. The role of junior mentors in developing these virtual activities was an important differential, enabling the engagement of the most timid and those who had difficulty in meeting the face-to-face schedules. Conclusion: Through observation during the development of the program activities, and based on the evaluation of students and mentors on the performance of mentoring in the remote semester, the conclusion is drawn that it is important to invest in the potential of social media to boost mentoring group meetings, ensure that the students are offered reception and support, and to strengthen the bonds with the participants. In light of this, it is necessary to consider the possibility of adopting a mixed teaching model to improve the mentoring program.

Collagen I and collagen III polymorphisms in women with pelvic organ prolapse.

AIMS: Verify the presence of the single nucleotide polymorphisms rs1800012 of the collagen I (COL1A1) and rs1800255 of the collagen III (COL3A1) genes and their association with pelvic organ prolapse (POP) in Brazilian women and to determine risk factors for POP. METHODS: We assessed 826 postmenopausal women divided into POP (stages III and IV) and control groups (stages 0 and I) by examination and peripheral blood sample collection. DNA sequences of interest were analyzed by real-time reverse-transcriptase polymerase chain reaction. We used logistic regression analyses, recessive and codominance models of inheritance, and P < .05 for significance. RESULTS: Six-hundred and thirty-four postmenopausal women were included: 348 (54.8%) POP cases and 286 (45.1%) controls. The frequencies of GG, GA, and AA genotypes for COL1A1 were 69.12%, 20.24%, and 10.59% in POP group and 71.79%, 20%, and 8.21% in controls; GG, GT, and TT for COL3A1 were 37.54%, 59.53%, and 2.93% in POP group and 36.24%, 60.14%, and 3.62% in controls. There were no genotypic or allelic association with POP phenotype that link both SNPs rs1800012 and rs1800255 to increased risk of POP. Vaginal delivery (odds ratio [OR] = 13; 95% confidence interval [CI] [4.00-47.08]), POP family history (OR = 3.1; 95% CI [1.49-6.50]), diabetes mellitus (OR = 2.3; 95% CI [1.08-5.21]), number of pregnancies (OR = 1.2; 95% CI [1.05-1.36]), and age (OR = 1.1; 95% CI [1.09-1.19]), were variables of increased risk for POP (P < .05 for all). CONCLUSION: Our study suggests lack of association between DNA polymorphisms rs1800012 of COL1A1 and rs1800255 of COL3A1 with advanced POP. Vaginal delivery, POP family history, diabetes mellitus, number of pregnancies, and age are risk factors for POP.

Sensitive and Label-Free SERS Detection of Single-Stranded DNA Assisted by Silver Nanoparticles and Gold-Coated Magnetic Nanoparticles.

An efficient surface-enhanced Raman scattering (SERS) method combined with DNA ligation is demonstrated in this proof-of-concept study for the detection of the single-strand DNA associated with BRAF V600E mutation. Gold-coated magnetic nanoparticles with 6-mercaptopyridine-3-carboxylic acid (MPCA) as internal reference attached on the surface (MNP@SiO2@Au-MPCA) and silver nanoparticles with Raman reporter 4-mercaptobenzonic acid (4-MBA) on the surface (Ag@4-MBA) are used as the SERS substrates. Rationally designed DNA probes are conjugated to these two types of nanoparticles, respectively. The single-stranded DNA containing the BRAF V600E mutation is the target analyte, which would act as the substrate for MNP@SiO2@Au-MPCA and Ag@4-MBA to be linked together through ligation. After multiple cycles of DNA ligation, more Ag@4-MBA are brought to the surface of MNP@SiO2@Au-MPCA. The resulting nanoparticles are easily isolated by a magnet rapidly from the mixture and redispersed in aqueous solution for homogeneous SERS measurement. The detection sensitivity is improved by the enhancement of the SERS peaks of 4-MBA between the plasmonic nanoparticles, and the detection quantification is improved by the use of internal reference, MPCA, for signal normalization. The intensity ratio of 4-MBA/MPCA increases linearly in the 1-100 fmol range of the matched DNA (BRAF mutation). Different ratios of matched DNA in the background of a large number of the single-base mismatched DNA (BRAF normal) are used to mimic real samples, and the intensity ratios of 4-MBA/MPCA are linear in the 0.02-1% range of matched DNA/mismatched DNA. The high sensitivity and specificity of the method demonstrate its potential for clinical use.

Accuracy of real-time multi-model ensemble forecasts for seasonal influenza in the U.S.

Seasonal influenza results in substantial annual morbidity and mortality in the United States and worldwide. Accurate forecasts of key features of influenza epidemics, such as the timing and severity of the peak incidence in a given season, can inform public health response to outbreaks. As part of ongoing efforts to incorporate data and advanced analytical methods into public health decision-making, the United States Centers for Disease Control and Prevention (CDC) has organized seasonal influenza forecasting challenges since the 2013/2014 season. In the 2017/2018 season, 22 teams participated. A subset of four teams created a research consortium called the FluSight Network in early 2017. During the 2017/2018 season they worked together to produce a collaborative multi-model ensemble that combined 21 separate component models into a single model using a machine learning technique called stacking. This approach creates a weighted average of predictive densities where the weight for each component is determined by maximizing overall ensemble accuracy over past seasons. In the 2017/2018 influenza season, one of the largest seasonal outbreaks in the last 15 years, this multi-model ensemble performed better on average than all individual component models and placed second overall in the CDC challenge. It also outperformed the baseline multi-model ensemble created by the CDC that took a simple average of all models submitted to the forecasting challenge. This project shows that collaborative efforts between research teams to develop ensemble forecasting approaches can bring measurable improvements in forecast accuracy and important reductions in the variability of performance from year to year. Efforts such as this, that emphasize real-time testing and evaluation of forecasting models and facilitate the close collaboration between public health officials and modeling researchers, are essential to improving our understanding of how best to use forecasts to improve public health response to seasonal and emerging epidemic threats.

Adiposity, inflammation and fat-soluble vitamins in adolescents / Adiposidade, inflamação e vitaminas lipossolúveis em adolescentes

Abstract Objective: Evaluate the association between inflammatory process, adiposity, and vitamins A, D, and E in adolescents, according to gender. Methods: Cross-sectional study with adolescents aged 12-19 years old of both genders attending public schools in Recife. A questionnaire was used to collect data on socioeconomic level, lifestyle, and food intake of adolescents. Then, an anthropometric evaluation and a blood sampling were performed to analyze serum concentrations of α-1-acid glycoprotein, retinol, β-carotene, α-tocopherol, and 25-hydroxy-vitamin D. Results: The levels of α-1-acid glycoprotein were higher for abdominal obesity in both genders. Male adolescents with insufficient serum α-tocopherol levels had low levels of α-1-acid glycoprotein (p = 0.03) and an increased risk of 25-hydroxy-vitamin D and β-carotene deficiency in relation to total and abdominal fat; female adolescents had an increased risk of insufficient β-carotene with abdominal obesity (PR: 1.33; 95% CI: 1.2-1.5). Conclusion: Abdominal adiposity implies a higher risk of inflammation and causes different changes to the levels of fat-soluble vitamins according to gender.

Resumo: Objetivo: Avaliar a associação entre processo inflamatório, adiposidade e as vitaminas A, D e E em adolescentes, segundo o sexo. Métodos: Estudo transversal com adolescentes de 12 a 19 anos de ambos os sexos de escolas públicas de Recife. Foi utilizado um questionário para coleta de dados socioeconômicos, de estilo de vida e de consumo alimentar dos adolescentes. Em seguida, realizou-se a avalição antropométrica e coleta de sangue para análise das concentrações séricas de α-1-glicoproteína ácida, retinol, β-caroteno, α-tocoferol e 25-hidroxivitamina D. Resultados: Os níveis de α-1-glicoproteína ácida foram maiores na obesidade abdominal de ambos os sexos. Os meninos com níveis séricos insuficientes de α-tocoferol expressaram níveis reduzidos de α-1-glicoproteína ácida (p = 0,03) e apresentaram um maior risco de deficiência de 25-hidroxivitamina D e β-caroteno na adiposidade total e abdominal, enquanto as meninas mostraram maior risco de insuficiência de β-caroteno com a obesidade abdominal (RP 1,33; IC 95% 1,2-1,5). Conclusão: A adiposidade abdominal reflete maior risco de inflamação e causa alterações distintas nas concentrações das vitaminas lipossolúveis, de acordo com o sexo.

Nanoparticle assisted nuclear relaxation-based oligonucleotide detection.

We present a proof-of-concept "on-off" detection scheme, which uses gadolinium phthalocyanine (GdTcPc)-grafted silica nanoparticles as paramagnetic centers, capable of modifying the transverse relaxation time (T2) of water protons in solution. A DNA strand (as probe) was conjugated to the GdTcPc to act as a recognition element. In the presence of the target DNA, which was complementary to the probe, an increase in the T2 value was detected, with magnitude proportional to the target DNA concentration. The linear range was observed from 30 to 140 nM, with limit of detection of 15 nM. The developed nuclear relaxation-based detection scheme is shown to be a simple, fast and selective method to detect DNA and could be useful in point-of-care diagnostic applications.

Adiposity, inflammation and fat-soluble vitamins in adolescents.

OBJECTIVE: Evaluate the association between inflammatory process, adiposity, and vitamins A, D, and E in adolescents, according to gender. METHODS: Cross-sectional study with adolescents aged 12-19 years old of both genders attending public schools in Recife. A questionnaire was used to collect data on socioeconomic level, lifestyle, and food intake of adolescents. Then, an anthropometric evaluation and a blood sampling were performed to analyze serum concentrations of α-1-acid glycoprotein, retinol, ß-carotene, α-tocopherol, and 25-hydroxy-vitamin D. RESULTS: The levels of α-1-acid glycoprotein were higher for abdominal obesity in both genders. Male adolescents with insufficient serum α-tocopherol levels had low levels of α-1-acid glycoprotein (p=0.03) and an increased risk of 25-hydroxy-vitamin D and ß-carotene deficiency in relation to total and abdominal fat; female adolescents had an increased risk of insufficient ß-carotene with abdominal obesity (PR: 1.33; 95% CI: 1.2-1.5). CONCLUSION: Abdominal adiposity implies a higher risk of inflammation and causes different changes to the levels of fat-soluble vitamins according to gender.

Prevalence and factors associated with fat-soluble vitamin deficiency in adolescents.

BACKGROUND: fat-soluble vitamin deficiency may be a health problem not recognized in children and adolescents. OBJECTIVE: to estimate the prevalence and factors associated with the deficiency of vitamins A, D and E among adolescent students from Northeastern Brazil. METHODS: transversal study with adolescents aged 12 to 19 of both genders. A questionnaire to collect socioeconomic and lifestyle data and food intake was applied to adolescents. Then, an anthropometric evaluation and a blood sampling were performed to analyze serum concentrations of retinol, ß-carotene, α-tocopherol and 25-hydroxy vitamin D (25[OH]D). RESULTS: the intake of vitamins A (50.3%), E (94.0%) and D (99.8%), as well as α-tocopherol (88.1%), ß-carotene (74.1%), 25(OH)D (50.9%) and retinol (46.6%) serum levels were mostly deficient/insufficient. An increased risk of α-tocopherol deficiency was observed in girls (PR = 1.11) and an increased risk of 25(OH)D deficiency was observed in boys (PR = 1.41). An increased likelihood of ß-carotene (PR = 1.14) and 25(OH) D (PR = 1.38) insufficiency was observed in overweight individuals. CONCLUSIONS: the adolescents had a deficit in the intake and in serum levels of fat-soluble vitamins. The greatest risk of inadequacy was associated with gender and weight excess. However, the behavior of fat-soluble vitamins in adolescents needs further research.

Ultra-thin and strong formvar-based membranes with controlled porosity for micro- and nano-scale systems.

We present a methodology for developing ultra-thin and strong formvar-based membranes with controlled morphologies. Formvar is a thin hydrophilic and oleophilic polymer inert to most chemicals and resistant to radiation. The formvar-based membranes are viable materials as support structures in micro- and macro-scale systems depending on thinness and porosity control. Tunable sub-micron thick porous membranes with 20%-65% porosity were synthesized by controlling the ratios of formvar, glycerol, and chloroform. This synthesis process does not require complex separation or handling methods and allows for the production of strong, thin, and porous formvar-based membranes. An expansive array of these membrane characterizations including chemical compatibility, mechanical responses, wettability, as well as the mathematical simulations as a function of porosity has been presented. The wide range of chemical compatibility allows for membrane applications in various environments, where other polymers would not be suitable. Our formvar-based membranes were found to have an elastic modulus of 7.8 GPa, a surface free energy of 50 mN m-1 and an average thickness of 125 nm. Stochastic model simulations indicate that formvar with the porosity of ∼50% is the optimal membrane formulation, allowing the most material transfer across the membrane while also withstanding the highest simulated pressure loadings before tearing. Development of novel, resilient and versatile membranes with controlled porosity offers a wide range of exciting applications in the fields of nanoscience, microfluidics, and MEMS.

Molecular epidemiological survey of bacteremia by multidrug resistant Pseudomonas aeruginosa: the relevance of intrinsic resistance mechanisms.

The bacterial factors associated with bacteremia by multidrug-resistant and extensively drug-resistant P. aeruginosa, including overexpression of efflux pumps, AmpC overproduction, and loss/alteration of the OprD porin in isolates that are non-Metallo-ß-Lactamase producing were analyzed in a retrospective study. Molecular analyses included strain typing by Pulsed Field Gel Electrophoresis and identification of key genes via qualitative and quantitative PCR-based assays. Previous use of carbapenems and tracheostomy was independently associated with the development of bacteremia by extensively drug-resistant and multidrug-resistant strains of P. aeruginosa. A high consumption of antimicrobials was observed, and 75.0% of the isolates contained amplicons with the blaSPM-1 and blaVIM genes. Of the 47 non-Metallo-ß-Lactamase isolates, none had another type of carbapenemase. However, the isolates exhibited high rates of hyperproduction of AmpC, loss of the OprD porin (71.4%) and the presence of MexABOprM (57.1%) and MexXY (64.3%). This study suggests that in non-Metallo-ß-Lactamase isolates, the association of intrinsic resistance mechanisms could contributes to the expression of multidrug-resistant/extensively drug-resistant phenotypes.