Pooled Rate of Pseudoprogression, Patterns of Response, and Tumor Burden Analysis in Patients Undergoing Immunotherapy Oncologic Trials for Different Malignancies.

AIMS: Assess rates of true pseudoprogression in unconfirmed progressive disease (iUPD) in a pool of immunotherapy clinical trials for different cancers, analyze tumor characteristics that drive iUPD classification, and investigate potentials predictors of pseudoprogression. MATERIALS AND METHODS: Retrospective interpretation of prospectively acquired data. Patients from 18 immunotherapy clinical trials with two arms (RECIST 1.1, iRECIST), of 10 cancer types were selected. Pooled rate of true pseudoprogression among iUPD was estimated using a common effect meta-analysis. Target, Non-target, and new lesions as the trigger of confirmed-vs pseudo-progression were compared using Chi-Square and Fisher exact tests. Conditional logistic regression was used to investigate the association between age, sex, tumor burden at baseline, and number of follow ups and pseudoprogression. RESULTS: 60/287 (21%) patients (17 women) were classified as iUPD with at least one subsequent confirmatory timepoint. The overall pooled estimate of pseudoprogression was 15% (95%CI: 8%--26%). Nontarget lesions were significantly more frequent the cause of iUPD than change in Target lesions size (p< 0.001). Most observations of true pseudoprogression occurred in the first follow-up (77%), whereas confirmed progression occurred in later time points during the trial. Pseudoprogression was not significantly associated with age, sex, tumor burden at baseline, or number of timepoints. CONCLUSION: In a pool of immunotherapy trials, the rate of true pseudoprogression was 15%, most often in the first timepoint after baseline than later in treatment. iUPD categorization was mostly driven by changes in NT lesions rather than objective changes in measurements of target lesions.

Malnutrition risk and oropharyngeal dysphagia in the chronic post-stroke phase.

Background: Oropharyngeal dysphagia (OD) and malnutrition are associated with poor clinical outcomes after stroke. The present study evaluated (1) malnutrition risk and OD-related characteristics in patients with chronic post-stroke OD, and (2) the relationship between on the one hand OD severity and on the other hand functional oral intake and dysphagia-specific quality of life. Methods: A cross-sectional study was conducted in a Dutch interdisciplinary outpatient clinic for OD. The standardized examination protocol comprised: clinical ear, nose, and throat examination, body mass index, the short nutritional assessment questionnaire (SNAQ), a standardized fiberoptic endoscopic evaluation of swallowing (FEES), the functional oral intake scale (FOIS), and the MD Anderson dysphagia inventory (MDADI). Results: Forty-two consecutive patients with chronic post-stroke OD were included. Mean (±SD) age and BMI of the population were 69.1 (±8.7) years and 26.8 (±4.1) kg/m2 respectively. Seventeen (40.4%) patients presented a moderate to high risk of malnutrition (SNAQ score≥2). The FEES examination showed moderate to severe OD in 28 (66.7%) patients. The severity of OD was significantly related to the FOIS score but not to the MDADI scores. Conclusion: In this specific sample of referred stroke patients, moderate to severe OD and moderate to high risk of malnutrition were common. Despite the use of clinical practice guidelines on stroke and a normal nutritional status at first sight, repeated screening for malnutrition and monitoring the severity and management of OD remain important elements in the care of patients with chronic post-stroke OD.

Introduction of the method of intravaginal culture (IVC), through the device INVOCell routine laboratory RHA in Brazil.

INTRODUCTION: The conventional in vitro fertilization and the intracytoplasmic sperm microinjection are currently the established techniques for the treatment of infertility. In the last decade, however, the process of in vitro fertilization has suffered several changes in ovulation induction and oocyte retrieval (Ranoux 1990, ; ).The INVO procedure has been used to treat patients with different causes of infertility in many countries. This is a procedure which was developed over 20 years ago and is simpler and less costly to the infertility treatment when compared to conventional techniques. Interesting finding of this intravaginal culture technique are the physiological benefits and the reduction of the number of handling steps, reducing the risk of contamination. OBJECTIVE: This study aimed to evaluate the possibility of including the method INVO through the use of the deviceINVOCell™ in routine laboratory treatments of couple infertility. That, in turn, tends to provide the simplification of laboratory work and thereby reduce the costs of infertility treatment. MATERIAL AND METHODS: 40 women were included in this study, who were treated at the Service of Human Reproduction School Hospital Álvaro Alvim, in the period from August 2011 to January 2012. On all of them it was used the protocol of modified mild ovarian stimulation. The number of pre-embryos transferred into the uterine cavity followed the CFM Resolution nº. 1.957/10. RESULTS AND CONCLUSION: There was no significant difference in the results presented by the device INVOCell™. Therefore showing that it can be included in routine laboratory assisted human reproduction.

Performance of polymyxin B agar-based tests among carbapenem-resistant Enterobacterales.

Therapeutic options for infections caused by Carbapenem-resistant Enterobacterales (CRE) are restricted and include polymyxins-centred schemes. Evaluation of in vitro susceptibility is difficult and time consuming. Agar-based methodologies are an alternative to broth microdilution (BMD) and we aimed to evaluate the accuracy of those methods among Enterobacterales. A total of 137 non-duplicated CRE were subjected to polymyxin B BMD, agar screening test (Mueller Hinton plates containing 3 µg ml-1 of polymyxin B) and agar dilution (antibiotic serially diluted 0·25-64 µg ml-1 ). CRE of 42·3% were resistant to polymyxin B (MICs range: 0·25->64 µg ml-1 ) and 16·8% presented borderline MICs. Sensitivity, specificity, PPV and NPV were 86·2, 98·7, 98 and 90·7% for screening test and 86·2, 97·5, 96·1 and 90·6% for agar dilution. ME was 0·73 and 1·5% for screening and agar dilution respectively; VME was 5·8% for both techniques. In general, agar-based methods had a good performance. As far as we know, this is the first study to propose an agar screening test using polymyxin B instead of colistin.

A randomised clinical pilot trial to test the effectiveness of parent training with video modelling to improve functioning and symptoms in children with autism spectrum disorders and intellectual disability.

BACKGROUND: Poor eye contact and joint attention are early signs of autism spectrum disorder (ASD) and important prerequisites for developing other socio-communicative skills. Teaching parents evidence-based techniques to improve these skills can impact the overall functioning of children with ASD. We aimed to analyse the impact of conducting a group parent-training intervention with video modelling to improve the intelligent quotient (IQ), social and communication functioning and to minimise symptoms in children with ASD and intellectual disability (ID). METHODS: Study design: A multicentre, single-blinded, randomised clinical pilot trial of parent training using video modelling was conducted. SAMPLE: Sixty-seven parents of children with ASD, aged between 3 and 6 years and with IQs between 50 and 70, were randomised: 34 to the intervention group and 33 to the control group. Intervention program: The intervention group received parent training over 22 sessions, and the control group received the standard community treatment. INSTRUMENTS: Pre-evaluation and post-evaluation (week 28), the following were used: Autism Diagnostic Interview, Vineland Adaptive Behaviour Scale I, Snijders-Oomen Nonverbal Intelligence Test, Autism Behaviour Checklist and Hamilton Depression Rating Scale. DATA ANALYSIS: Intention to treat and complier-average causal effect (CACE) were used to estimate the effects of the intervention. RESULTS: There was a statistically significant improvement in the Vineland standardized communication scores in CACE (Cohen's d = 0.260). There was a non-statistically significant decrease in autism symptomatology (Autism Behaviour Checklist total scores) and a significant increase in the non-verbal IQ in the intervention group. After the false discovery rate correction was applied, IQ remained statistically significant under both paradigms. The effect size for this adjusted outcome under the intention-to-treat paradigm was close to 0.4, and when considering adherence (CACE), the effect sizes were more robust (IQ's Cohen's d = 0.433). CONCLUSIONS: Parent training delivered by video modelling can be a useful technique for improving the care given to children with ASD and ID, particularly in countries that lack specialists.

MRI estimated changes in visceral adipose tissue and liver fat fraction in patients with obesity during a very low-calorie-ketogenic diet compared to a standard low-calorie diet.

AIM: To compare the changes in visceral adipose tissue (VAT), liver fat fraction, and liver stiffness using quantitative magnetic resonance imaging (MRI) during a very-low-calorie ketogenic (VLCK) diet and a standard low-calorie diet (LC). MATERIALS AND METHODS: The study involved secondary analysis of prospective collected clinical data. Patients undergoing weight loss interventions were randomised to either a LC or a VLCK diet. VAT, liver fat fraction, and stiffness were measured at baseline and after 2 months. RESULTS: Forty-six patients were included; 39 patients were evaluated at baseline and at 2 months follow-up. Mean weight loss was -9.7±3.8 kg (interquartile range [IQR]: -12.3; -7 kg) in the VLCK group and -1.67±2.2 kg (IQR: -3.3, -0.1 kg) in the LC group (p<0.0001). Mean VAT reductions were -39.3±40 cm2 (IQR: -52, -10 cm2) and -12.5±38.3 cm2 (IQR: -29, 5 cm2; p=0.0398), and mean liver proton density fat fraction (PDFF) reductions were -4.77±4.2% (IQR: -7.3, -1.7%) and -0.79±1.7%, (IQR: -1.8, -0.4%; p<0.005) in the VLCK group and in the LC group, respectively. No significant changes in liver stiffness occurred from baseline to follow-up. CONCLUSION: A VLCK diet resulted in greater weight loss than a standard low-calorie diet and in significantly greater reduction in liver PDFF. As anthropometric measurements may not correlate with liver fat changes, it may be advantageous to include quantitative MRI to the monitoring strategies of patients undergoing weight-loss programmes.

Early use of alcohol associated with sociodemographic, nutritional and lifestyle factors: survival analysis with Brazilian students.

BACKGROUND: To evaluate the early age of onset (AOO) of alcohol consumption and its association with sociodemographic, nutritional and lifestyle characteristics. METHODS: A national cross-sectional multi-centered study assessed 12-17-year old adolescents from 1247 public and private schools in 124 Brazilian municipalities with more than 100 000 habitants. Our variable of interest was the AOO of alcohol consumption. Covariates comprised sociodemographic status, lifestyle habits and nutritional parameters. We used adapted survival models to investigate the association between covariates and the AOO of alcohol consumption. RESULTS: From a sample of 67 672 adolescents, 50% were females. The mean AOO of alcohol consumption was 12.9 years. Male adolescents had a lower mean age of alcohol experimentation when compared to females in Northeast and South regions. The difference between private and public school for AOO was observed only for the Northeast Region (12.6 versus 13.1, respectively). Adolescents who reported smoking or mental health problems or from the Southern Region presented earlier alcohol use. Physical activity and overweight were positively associated with earlier use of alcohol. CONCLUSIONS: There is no homogeneity in the AOO of alcohol consumption among adolescents, which should be considered when formulating public policies and government campaigns directed toward reducing alcohol consumption.

How does bone thickness affect the split pattern of sagittal ramus osteotomy?

This study examined the influence of bone thickness on the split pattern of sagittal ramus osteotomy at 62 sites using Dolphin 3D software. Four measurements of thickness were obtained from the preoperative computed tomography scans: measurement A was made 1.5mm above the lingula, using the coronal and sagittal planes; measurement B was made at the same height as measurement A and 1mm from the anterior border of the ramus; measurement C was obtained 5mm distal to the last molar and 5mm below the upper border of the mandible; measurement D was made in the area between the first and second molars, 6mm above the mandibular border. Three-dimensional postoperative images were used to classify the split pattern into types, based on the classification of Plooij et al. The data were analyzed using the Kruskal-Wallis test, followed by Dunn post-hoc test. Thirty-five sagittal splits were type I, one was type II, 19 were type III, and seven were type IV. Type I presented the greatest thickness, whereas type IV presented the lowest. There was a statistically significant difference in thickness only for measurement A, when types I and IV were compared. The results indicate that thinner mandibular rami are more prone to bad splits.

Emergence of serotype 19A Streptococcus pneumoniae after PCV10 associated with a ST320 in adult population, in Porto Alegre, Brazil.

Use of pneumococcal conjugate vaccines has caused emergence of non-vaccine serotypes. No Brazilian data specifically about serotype 19A are available. We aimed to evaluate the frequency of occurrence, susceptibility profile and molecular epidemiology of serotype 19A before and after vaccine introduction in Brazil. Pneumococcal identification was performed by the conventional method. Strain serotype was determined by multiplex polymerase chain reaction (PCR) and/or Quellung reaction. Resistance was determined by Etest® and PCR was performed to determine the presence of macrolide resistance genes, ermB and/or mefA. Pneumococci were typed by Multilocus Sequence Typing. Thirty-eight serotype 19A Streptococcus pneumoniae were recovered, mostly from invasive diseases. Prevalence of serotype 19A increased following vaccination (from 3.5% before vaccination to 8.1% after, p = 0.04196). Non-susceptibility increased to most antimicrobials after vaccine introduction and was associated with clonal complex (CC)320. MLST showed nine different STs, which were grouped in one main CC: CC320 (63.9%). During the post-vaccination era, the frequency of this serotype increased significantly from 1.2% in 2011 to 18.5% in 2014 (p = 0.00001), with a concomitant decrease in the genetic variability: ST320 consistently predominated after vaccine-introduction (61.1%). Overall, our results showed a post-PCV10 increase in the frequency of serotype 19A. This was accompanied by a selection of CC320 and antimicrobial resistance.

Presence of parasite DNA in clinically unaffected nasal mucosa during cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.

OBJECTIVES: We aimed to detect Leishmania DNA carriage in nasal mucosa of individuals with cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis. METHODS: A cross-sectional study was performed in all individuals with CL without nasal lesions (n = 153) attended within 2 years in an endemic area of L. (Viannia) braziliensis in Bahia (Brazil). An otorhinolaryngologist assessed the clinical status of the nasal mucosa by anterior rhinoscopy and endoscopic examinations. Swab samples were collected for parasite DNA detection by PCR from all individuals before standard treatment for leishmaniasis. A second evaluation 3 months after treatment was performed to assess clinical outcomes. RESULTS: Parasite DNA was detected in 7.8% (12/153) of clinically healthy nasal mucosa of individuals with CL. Interestingly, DNA was more frequently identified in individuals with more skin lesions (median 1.5, interquartile range (IQR) 1-3.5 versus 1.0, IQR 1-1.5; p 0.044), or larger injuries (median 2.7, IQR 2-3.8 versus 1.6, IQR 1-2.5; p 0.013). Additionally, the disease of those individuals with positive PCR evolved more frequently to unusual forms of leishmaniasis (recidiva cutis and disseminated) (45.5% (5/11) versus 11.5% (14/122); p 0.009), and required more cycles of treatment to reach clinical cure (median 2, IQR 1-4 versus 1, IQR 1-2; p 0.05). CONCLUSION: These findings suggest an early parasite tropism to nasal mucosa in L. (Viannia) braziliensis infection and a clinical phenotype of CL cases associated with parasite DNA in nasal mucosa. Future studies should evaluate whether PCR of nasal swab samples could serve as a prognostic tool for individuals at risk of mucocutaneous leishmaniasis.

Cardiorespiratory Adaptations in Elderly Men Following Different Concurrent Training Regimes.

BACKGROUND: This study aimed to investigate the effects of different intra-session exercise orders during concurrent training (CT) on endurance performance in elderly men, as well as to verify its influence on individual responses in endurance performance. DESIGN: Twenty-five healthy elderly men (64.7 ± 4.1 years) were placed into two groups: strength training prior to endurance training (SE, n=13), and one in the reverse order (ES, n=12). CT was performed three times a week during 12 weeks. Before and after training, peak oxygen uptake (VO2peak), maximal workload (Wmax), absolute and relative cycling economy at 25, 50, 75 and 100 W (i.e., average VO2 at different stages) were assessed. RESULTS: Similar increases in VO2peak were observed in the SE and ES groups (SE: 8.1 ± 9.9%; ES: 9.3 ± 9.8%; P<0.001), as well as in Wmax (SE: 19.9 ± 19.3%; ES: 24.1 ± 24.0%; P<0.001). Moreover, significant reductions were observed in the absolute VO2 at 100 W (P<0.05) in the SE and ES groups. No difference between groups was observed. In the ES group, one subject did not respond positively in terms of both VO2max and Wmax, whereas 4 subjects did not respond positively in terms of both VO2max and Wmax in SE group. CONCLUSIONS: CT improved maximal and submaximal endurance performance in elderly men, independent of intra-session exercise order. However, it seems that the ES order elicited more individual responsiveness in terms of maximal endurance performance than SE order.

Evaluation of waste biomasses and their biochars for removal of polycyclic aromatic hydrocarbons.

This work evaluates the use of biomasses and their biochars as adsorbents to remove polycyclic aromatic hydrocarbons from water. Coconut waste (CW) and orange waste (OW) were pyrolyzed at 350 °C to produce the corresponding biochars (BCW and BOW). Adsorption tests using a mixed solution of benzo(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, and dibenzo(a,h)anthracene showed removal percentages of 30.33-83.43% (CW), 47.09-83.02% (BCW), 24.20-74.25% (OW), and 23.84-84.02% (BOW). The adsorption mechanisms appeared to involve π-π interactions of similar groups of the adsorbate and adsorbent, together with hydrophobic effects. There was no indication of competition between the PAHs for the adsorption sites, and there was evidence of cooperative adsorption. The PAHs could be desorbed from the adsorbents with efficiencies in the range 34.88-72.32%, and the reuse of the adsorbents in two further cycles demonstrated their potential for use in the removal of PAHs from water.

Metabolizabilidade da energia de farinhas mistas contendo silagem de peixes para frangos de corte / Energy metabolizability of mixed flour containing fish silage for broiler chicken

Objetivou-se com este trabalho determinar o valor nutricional e os valores de energia metabolizável aparente (EMA) e EMA corrigida para o balanço de nitrogênio (EMAn) de quatro farinhas mistas contendo silagem de resíduo de filetagem de tilápia para frangos de corte do tipo crescimento lento com 28 a 38 dias de idade. Analisou-se a composição físico-química das silagens e, em seguida, realizou-se um ensaio de metabolismo pelo método de coleta total de excretas com 180 pintos machos da linhagem Vermelho Pesadão Francês, distribuídos em um delineamento inteiramente ao acaso, com cinco tratamentos, seis repetições e seis aves por unidade experimental. Os tratamentos consistiram de uma ração referência (RR) e quatro dietas teste compostas de 70% da (RR), com a inclusão de 30% de farinha mista contendo silagem de peixes produzida com o farelo de algaroba (SFA), com a farinha de varredura de mandioca (SFVM), com o farelo de milho (SFM) e com a casca da mandioca (SCM). Os valores para composição físico-química das SFA, SFVM, SFM, SCM foram de 20,63, 20,76, 21,99 e 14,54% de proteína bruta; 17,04, 23,22, 21,97 e 20,27% de extrato etéreo; 7,53, 7,79, 8,65 e 8,83% de matéria mineral; 23,07, 10,55, 16,81 e 12,34% de fibra bruta; 1,79, 2,30, 1,57 e 2,72% de cálcio; 1,12, 1,72, 1,45 e 1,94% de fósforo; 532, 528, 598 e 508 densidade, g/L; 4,5, 4,0, 4,4 e 4,4 de pH. Quanto aos valores de EMA e EMAn das farinhas mistas contendo silagem de peixes em base de matéria seca, foram, respectivamente, 3560kcal/kg e 3402kcal/kg para a SFA, 3574kcal/kg e 3415kcal/kg para a SFVM, 3570kcal/kg e 3412kcal/kg para a SFVM e 3571kcal/kg e 3413kcal/kg para a SCM, com a SFA apresentando menor valor (P=0,01). Com base nos resultados, as silagens contendo restos de peixe podem ser utilizadas em dietas para frangos de corte.(AU)

The objective of this study was to determine the nutritional value and the values of Apparent Metabolizable Energy (AME) and AME corrected for nitrogen balance (AMEn) of four mixed meals containing fish silage for slow growth type broiler chickens at 28-38 days of age. The physicochemical composition of the silage was analyzed and then a metabolism trial was performed using total excreta collection method with 180 male chicks of Red French Pesadão lineage distributed in a completely randomized design with five treatments and six replicates of six birds per experimental unit. Treatments consisted of a basal diet (RR) and four test diets containing 70% (RR), with the inclusion of 30% of mixed flour containing fish silage produced with mesquite meal (SFA) with flour of cassava meal (SFVM), with corn meal (SFM), and dehydrated cassava peel (SCM). The values for physico-chemical composition of the SFA, SFVM, SFM, SCM, were 20,63, 20.76, 21.99, and 14.54% of crude protein; 17.04, 23.22, 21.97 and 20.27% of ethereal extract; 7.53, 7.79, 8.65, and 8.83% of mineral matter; 23,07, 10,55, 16,81, and 12,34% of crude fiber; 1.79, 2.30, 1.57, and 2.72% of calcium; 1.12, 1.72, 1.45, and 1.94% of phosphorus; 532, 528, 598, and 508 of density, g / L; 4.5, 4.0, 4.4, and 4.4 of pH. As for AME and AMEn of the flours containing fish silage on dry matter basis, values were of, respectively, 3560 kcal/kg and 3402 kcal/kg for the SFA, 3574 kcal/kg and 3415 kcal/kg for SFVM, 3570 kcal/kg and 3412 kcal/kg for SFVM, and 3571 kcal/kg and 3413 kcal/kg for SCM, with the SFA showing lowest value. Based on the results, silage containing fish waste can be used in diets for broilers.(AU)

Cortical control of vertical and horizontal saccades in progressive supranuclear palsy: An exploratory fMRI study.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.

Serum n-3 polyunsaturated fatty acids are inversely associated with longitudinal changes in depressive symptoms during pregnancy.

BACKGROUNDS: N-3 polyunsaturated fatty acids (PUFAs) have been hypothesised to be protective for depression during pregnancy. However, there are few data and no consensus regarding this association. In this line, we aim to evaluate if the concentration of n-3 and n-6 PUFAs, and their ratio, are associated with depressive symptoms throughout pregnancy. METHOD: A prospective cohort of 172 Brazilian women was followed at 5-13th, 20-26th and 30-36th weeks of gestation. The presence of depressive symptoms was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at each pregnancy trimester. Depression was defined as an EPDS score ≥11. The concentrations of n-3 [α-linolenic acid; eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA)] and n-6 PUFAs [linoleic acid; γ linolenic acid; eicosadienoic acid; eicosatrienoic acid; arachidonic acid; docosatetraenoic acid and docosapentaenoic acid] were expressed as absolute (µg/ml) values. The total n-6/n-3 ratio was calculated. Statistical analyses were performed using univariate and adjusted random intercept logistic model for each fatty acid (FA) considering the longitudinal nature of data. Covariates were selected as potential confounders based on their biological plausibility of having an association with the concentration of FA and depressive symptoms during pregnancy. RESULTS: The prevalence of depressive symptoms was high in all pregnancy trimesters (1st = 33.7%; 2nd = 18.9%; 3rd = 17.4%). We did not find differences in means FA concentrations by depressive symptom classification, for each follow-up visit. The women presented a 5% decrease in the odds of having depressive symptoms for each one-week increase in the gestational age. As individual women progressed through pregnancy, higher concentrations of EPA (odds ratio (OR) = 0.92; 95% CI: 0.86-0.99), DHA (OR = 0.96; 95% CI: 0.93-0.99), DPA (OR = 0.87; 95% CI: 0.77-0.99) and total n-3 (OR = 0.98; 95% CI: 0.96-0.99) were associated with a lower odds of depressive symptoms, while higher total n-6/n-3 ratio were associated with greater odds of depressive symptoms (OR = 1.40; 95% CI: 1.09-1.79). We detected a decrease in the probability of depressive symptoms as concentrations of total n-3 FA, α-linolenic acid, DPA, and DHA increased. We also observed a sharper decline for women with initial greater chance of depressive symptoms compared with those with lower chance of having these symptoms. CONCLUSIONS: We found a high prevalence of depressive symptoms in low-income Brazilian pregnant women and no significant associations between n-6 FA and depressive symptoms. Lower serum concentrations of DHA, EPA and DPA and a higher n-6/n-3 ratio at each pregnancy trimester were associated with higher odds of depressive symptoms throughout pregnancy.

Distinct functional properties of the vertical and horizontal saccadic network in Health and Parkinson's disease: An eye-tracking and fMRI study.

Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements (e.g., antisaccade). Behavioural asymmetries between vertical and horizontal saccades have been described both in normal individuals (greater delay of vertical prosaccades) and in disease states such as Parkinson's disease (PD) (prosaccades are short and antisaccades are delayed, especially in the vertical plane, possibly due to a frontostriatal deficit). Importantly, the cortical mechanisms for the generation of vertical saccades are largely unknown, both in health and disease, when compared with their horizontal counterpart. Moreover, studies exploring saccadic neural correlates and putative compensatory mechanisms at a functional level in PD are scarce. We investigated horizontal and vertical prosaccades and antisaccades in an eye tracking paradigm in 19 PD patients off medication and 22 healthy controls, followed by a block-design functional Magnetic Resonance Imaging (fMRI) study, consisting of two runs (prosaccade, antisaccade) of 6 blocks each (3 vertical, 3 horizontal). While saccade metrics were not significantly different between groups, PD showed left frontal underactivation during horizontal prosaccades and right parietal overactivation during horizontal and vertical prosaccades and horizontal antisaccades. Moreover, controls showed greater deactivation of the default-mode network (DMN) during antisaccades. Vertical prosaccades were associated with greater right frontal and cerebellar activity in controls, and cuneus hypoactivity in PD. Vertical antisaccades were associated with greater DMN deactivation in both groups and left frontal hypoactivity in PD. Putative functional compensatory changes in the right parietal cortex in PD patients may help to keep saccadic behaviour at the same level as the healthy controls. We provide first time evidence showing that functional cortical asymmetries between vertical and horizontal saccades occur distinctively in PD patients and healthy controls.

Neonatal malnutrition programs the oxidant function of macrophages in response to Candida albicans.

Experimental maternal nutrition restriction models are used to investigate short or long-term consequences of nutritional deficiency on puppies' growth. By assuming that the immune function is directly related to host's nutritional status, the current study aims to investigate the effects of neonatal malnutrition on oxidative stress and on the cell death of the alveolar macrophage after in vitro infection by Candida albicans. Wistar rats were suckled by mothers fed on diets containing 17% protein (Nourished group) or 8% protein (Malnourished group) in the current assay. Both groups received the standard diet used in the vivarium until adulthood, after weaning. The results showed that the offspring from mothers fed on low-protein diet presented lower body weight from 5 days of life on. Their low weight remained until adulthood when it was compared to that of rats in the nourished group. Superoxide and nitric oxide production was lower in malnourished animals and it was accompanied by low inducible nitric oxide synthase gene expression levels in systems in which the alveolar macrophages were challenged by immunogenic stimulus. No significant differences were observed in comparisons performed between the nourished and malnourished groups in any of the analyzed cell viability (apoptosis/necrosis) parameters. The fungal inoculum-stimulated system induced higher oxidative stress and cell death by necrosis. The current study demonstrated that dietary restriction during lactation alters the oxidant function of alveolar macrophages in puppies; It happens from the gene transcription step to the release of mediators, thus compromising the host's defenses against Candida albicans. It raises the possibility that Candida albicans may cease to be a commensal fungus to become a pathogen in offspring that have suffered nutritional deficiency during critical developmental periods, due to impaired immune responses.

Androgen signaling is a confounding factor for ß-catenin-mediated prostate tumorigenesis.

Emerging evidence has demonstrated the critical roles for both androgen and Wnt pathways in prostate tumorigenesis. A recent integrative genomic analysis of human prostate cancers (PCas) has revealed a unique enrichment of androgen and Wnt signaling in early-onset PCas, implying their clinical significance in the disease. Additionally, interaction between the androgen receptor (AR) and ß-catenin has long been detected in PCa cells. However, the consequence of this interaction in prostate tumorigenesis is still unknown. Because mutations in adenomatous polyposis coli, ß-catenin and other components of the destruction complex are generally rare in PCas, other mechanisms of aberrant Wnt signaling activation have been speculated. To address these critical questions, we developed Ctnnb1(L(ex3)/+)/R26hAR(L/+):PB-Cre4 mice, in which transgenic AR and stabilized ß-catenin are co-expressed in prostatic epithelial cells. We observed accelerated tumor development, aggressive tumor invasion and a decreased survival rate in Ctnnb1(L(ex3)/+)/R26hAR(L/+):PB-Cre4 compound mice compared with age-matched Ctnnb1(L(ex3)/+):PB-Cre4 littermate controls, which only have stabilized ß-catenin expression in the prostate. Castration of the above transgenic mice resulted in significant tumor regression, implying an essential role of androgen signaling in tumor growth and maintenance. Implantation of the prostatic epithelial cells isolated from the transgenic mice regenerated prostate intraepithelial neoplasias and prostatic adenocarcinoma lesions. Microarray analyses of transcriptional profiles showed more robust enrichment of known tumor- and metastasis-promoting genes: Spp1, Egr1, c-Myc, Sp5, and Sp6 genes, in samples isolated from Ctnnb1(L(ex3)/+)/R26hAR(L/+):PB-Cre4 compound mice than those from Ctnnb1(L(ex3)/+):PB-Cre4 and R26hAR(L/+):PB-Cre4 littermate controls. Together, these data demonstrate a confounding role of androgen signaling in ß-catenin-initiated oncogenic transformation in prostate tumorigenesis.

Inflammation, neurotrophism and oxidative stress and childhood psychopathology in a large community sample.

OBJECTIVE: To investigate the association between peripheral biomarkers and child psychopathology in a large community sample. METHOD: A total of 625 aged 6- to 13-year old subjects were recruited from a community school-based study. Psychopathology was assessed using the Child Behaviour Checklist (CBCL). Psychiatric diagnosis was evaluated using the Development and Well-Being Assessment. The following biomarkers were examined in peripheral blood: brain-derived neurotrophic factor, cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-g, and TNF-α), chemokines (eotaxin/CCL11, IP-10, MCP-1), cytokine receptors (sTNFR1 and sTNFR2), and the oxidative stress marker TBARS. RESULTS: We found significant associations between sTNFR2, eotaxin/CCL11 and CBCL total score, as well as with specific dimensions of psychopathology. There were different patterns of association between these biomarkers and psychological and behavioural symptoms in children with and without a mental disorder. TBARS, IL-6 and MCP-1 were more specific to some clusters of symptoms in children with a psychiatric diagnosis. CONCLUSION: Our data support the potential use of biomarkers, especially those involved in immune-inflammatory pathways, in investigating neurodevelopmental psychopathology. Their association with different dimensions of symptoms might be of useful when analyzing illness severity and clusters of symptoms within specific disorders.

PLGA Implants containing vancomycin and dexamethasone: development, characterization and bactericidal effects.

Post-operative endophthalmitis is an infection and an inflammation of the eye following a surgical procedure. Its treatment is based on drug injections into the eye. However, this treatment can lead to ocular complications. Intraocular implants could substitute the conventional therapy. Poly(lactic-co-glycolic acid) (PLGA) implants comprising on vancomycin and dexamethasone were evaluated as drug delivery system to treat endophthalmitis after cataract surgery. Implants were characterized by drug content uniformity, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Wide Angle X-ray Scattering (WAXS), Scanning Electron Microscopy (SEM) and in vitro drug release. The bactericidal effect of vancomycin, eluted from the implants, was demonstrated against Staphylococcus aureus and Staphylococcus epidermidis. The drugs were uniformly distributed in the polymer. The analytical techniques revealed the chemical integrity of the drugs incorporated into the polymer and the modification of dexamethasone semi-crystalline nature. Drugs were controlled released from implants; and the eluted vancomycin showed bactericidal effects. In conclusion, PLGA implants containing vancomycin and dexamethasone may represent a therapeutic alternative to treat post-operative endophthalmitis.