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Purpose: The aim of this study was to evaluate the effect of an oral rehabilitation program on masticatory performance and ability as a function of the number of masticatory cycles. Subjects with a mandibular fixed implant-supported prosthesis (ISP), complete dentures (CDs), or a natural dentition (ND) were evaluated. Materials and Methods: Masticatory performance was tested with an artificial test food (Optocal). Optocal was provided to subjects in two portions of 17 cubes and collected after both 20 and 40 masticatory cycles. The particles were collected on stacks of eight sieves. The geometric mean diameter of the chewed particles was calculated using the sieves. Questionnaires were used to assess masticatory ability before and after the fixed mandibular rehabilitation program. The geometric mean diameter of the chewed particles was compared by two-way analysis of variance followed by the Tukey test (P < .05). Results: The geometric mean diameter for all groups was lower after 40 cycles versus 20 cycles. When compared to the ND group, masticatory performance for the CD and ISP groups was 12% and 28% after 20 cycles and 31% and 61% after 40 cycles, respectively. The data for the masticatory ability of the ISP group before and after fixed mandibular rehabilitation were compared by the McNemar test (P < .05), and showed that 100% of these subjects were satisfied with their chewing capacity after fixed mandibular rehabilitation. Conclusions: These results quantify the differences in masticatory function among different types of dentition. Greater masticatory function for fixed mandibular rehabilitation versus CDs was demonstrated. Int J Prosthodont 2009;22:399-404. [ABSTRACT FROM AUTHOR]

This in vitro research assessed the influence of the instrument kinematics (rotary and reciprocating) and the apical preparation limit on the root canal disinfection and apical bacterial extrusion. After 21 days of Enterococcus faecalis biofilm formation in 72 mesial root canals of mandibular molars, the root canals were distributed into 2 groups (n = 36) according to the systems used for preparation: ProDesign S and Reciproc. The groups were redistributed according to the limit of apical preparation (n = 11): (a) 1 mm up to the apical foramen (TL-1); (b) at the apical foramen (TL = 0); (c) 1 mm beyond the apical foramen (TL + 1). After preparation, the remaining biofilm adhered to the dentin walls at the apical third was removed by sonication. The aliquots of bacterial suspension released, and the irrigating solution leaked through the apical foramen during preparation were plated for colony-forming units (CFUs) counting. Data were statistically assessed by the Kruskal-Wallis and Dunn tests (α = 5%). Both systems promoted decontamination of the apical third, regardless the limit of apical preparation (p > 0.05). A larger quantity of bacteria was extruded from the root canals prepared 1 mm beyond the apical foramen, regardless the instrumentation kinematics (p < 0.05). The apical third of the root canal was efficiently decontaminated after preparation, regardless the instrumentation kinematics and the apical limit. However, a larger quantity of bacterial extrusion was observed when preparation was performed beyond the anatomical root canal limits., Competing Interests: Declarations. Conflict of interest: The authors deny any conflicts of interest related to this study. Ethical approval: This quantitative experimental laboratory study was approved by the Human Research Ethics Committee (No. 3.463.333) and was conducted in full compliance with the ethical standards outlined in the 2008 Declaration of Helsinki., (© 2025. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Background: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease., Methods: Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma)., Results: Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC., Conclusions: This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence., (© 2024. The Author(s).)

The electronic prescription refill rate (EPRR) of 183 consecutive patients was determined over a 19-month retrospective study period, divided into 7 months PRE (Sep-19 to Mar-20) and 12 months POST pandemic (Apr-20 to Mar-21), in order to compare adherence to inhaled corticosteroids (ICS) in patients with asthma prior to and during the COVID-19 pandemic. Before the pandemic (PRE), an average of 0.58 inhalers/month were refill from the pharmacy; [SD 0.33], very similar to the 0.59 inhalers/month; [SD 0.34] retrieved during the 12 subsequent months since the pandemic (POST) (p = 0.768). EPRR showed no differences (p = 0.784). When EPRR was dichotomous or ordinal categorised no differences were found either (p = 0.851 and 0.928), even when McNemar's test was used (p = 0.949), with prevalences of nonadherence (EPRR < 80%) of 57 and 58% respectively. Our results do not support increased adherence to inhaler treatment in terms of EPRR, comparing before and since COVID-19 pandemic. Compliance with prescription remains suboptimal., (© 2023. Springer Nature Limited.)

The current literature on guided bone regeneration (GBR) and guided tissue regeneration (GTR) membrane contamination reports that the physicochemical characteristics of these biomaterials might influence affinity to bacteria, which appears to be a major drawback for the clinical outcome of the regenerative procedures. Thus, this study aimed to evaluate, in vitro, a multispecies biofilm adherence and passage of bacteria through different types of commercially available membranes for GTR/GBR. Four types of membranes were tested (n=12): LC) Lumina Coat®; JS) Jason®; BG) Biogide®; and LP) Lumina PTFE®. Aluminum foil (AL) simulated an impermeable barrier and was used as the control. The membranes were adapted to specific apparatus and challenged with a mixed bacterial culture composed of A. actinomycetemcomitans b, S. mutans, S. mitis, and A. israelii. After 2 h or 7 days, bacterial adhesion and passage of bacteria were evaluated through CFU counting, which was analyzed by two-way ANOVA e post hoc Tukey, at a 5% significance level. Representative areas of two membranes of each group were analyzed through scanning electron microscopy (SEM) to assess the morphology and organization of the biofilm over the membrane fibers. LC and LP presented similar values of adhered bacterial cells (p > 0.05), significantly inferior when compared to the other groups, in both time points (p < 0.05). All the tested groups were permeable to bacterial cells, with no significant difference between the trial period of 2 h and 7 days (p > 0.05). SEM analyses demonstrated that adhered bacteria number increased throughout the time points (2 h < 7 days). Commercially available biological membranes demonstrated intense bacterial adherence and passage of bacteria, which increased throughout the trial period.

The development of oral biofilm models has been extremely important to study the specific role of most microbial species at the early stages of periodontitis. The current knowledge on monospecies or multispecies biofilms originates mainly from the observation of in vitro dynamic or static biofilm model systems, which were engineered to mimic clinical oral conditions. In the last few decades, mounting evidence has confirmed that biofilms are the major form of bacterial lifestyle, and more importantly, that microorganisms dwelling in sessile mixed-species aggregates display completely different phenotypes and physiological characteristics than when living in planktonic pure cultures. Interspecies interactions within these communities, mediated by chemical communication systems, have been shown to affect biofilm physiology and increase antimicrobial resistance by up to 1000 fold. These aspects reinforce the importance of developing multispecies biofilm models to better understand and control biofilms. Literature reports demonstrate that while monospecies models are still most commonly used in caries research, authors have used different multispecies models to study periodontal diseases. Periodontitis is a polymicrobial biofilm-dependent disease mainly associated with Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Interestingly, these species hardly adhere to substrates commonly used for biofilm formation, which makes multispecies models essential for an accurate analysis of periodontitis-related biofilms. The multispecies models currently available are generally composed of 6-10 species, but a more recent 34-species model was developed to better examine the dynamics within oral biofilms. The complexity of such polymicrobial biofilm models mimics more consistently the oral microbiome and different aspects of the oral environment. Collectively, the evidence on multispecies biofilm models described herein may support future studies on the use of antimicrobials for biofilm control as well as provide research opportunities to expand the current knowledge on interspecies interactions. The present manuscript reviews the most recent updates on in vitro biofilm model systems for periodontitis., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objectives: The aim of this study was to evaluate bacterial nanocellulose (BNC) membranes incorporated with antimicrobial agents regarding cytotoxicity in fibroblasts of the periodontal ligament (PDLF), antimicrobial activity, and inhibition of multispecies biofilm formation., Materials and Methods: The tested BNC membranes were BNC + 1% clindamycin (BNC/CLI); BNC + 0.12% chlorhexidine (BNC/CHX); BNC + nitric oxide (BNC/NO); and conventional BNC (BNC; control). After PDLF culture, the BNC membranes were positioned in the wells and maintained for 24 hours. Cell viability was then evaluated using the MTS calorimetric test. Antimicrobial activity against Enterococcus faecalis , Actinomyces naeslundii , and Streptococcus sanguinis ( S. sanguinis ) was evaluated using the agar diffusion test. To assess the antibiofilm activity, BNC membranes were exposed for 24 hours to the mixed culture. After sonicating the BNC membranes to remove the remaining biofilm and plating the suspension on agar, the number of colony-forming units (CFU)/mL was determined. Data were analyzed by 1-way analysis of variance and the Tukey, Kruskal-Wallis, and Dunn tests (α = 5%)., Results: PDLF metabolic activity after contact with BNC/CHX, BNC/CLI, and BNC/NO was 35%, 61% and 97%, respectively, compared to BNC. BNC/NO showed biocompatibility similar to that of BNC ( p = 0.78). BNC/CLI showed the largest inhibition halos, and was superior to the other BNC membranes against S. sanguinis ( p < 0.05). The experimental BNC membranes inhibited biofilm formation, with about a 3-fold log CFU reduction compared to BNC ( p < 0.05)., Conclusions: BNC/NO showed excellent biocompatibility and inhibited multispecies biofilm formation, similarly to BNC/CLI and BNC/CHX., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. The Korean Academy of Conservative Dentistry.)

The objective of this work was to develop a subgingival biofilm model using a stirred bioreactor. Discs of bovine teeth were adapted to a stirred bioreactor filled with a culture medium containing bacterial species associated with periodontal health or disease. After anaerobic incubation, the biofilms growing on the substratum surfaces were collected and analyzed. The mean number of Colony-forming Units (CFUs) varied, but with no difference between 3 and 7 days of biofilm formation ( p  > 0.05). Scanning Electron Microscopy (SEM) analysis showed a uniform biofilm layer covering the cement layer of the root surface containing bacteria with diverse morphology. In checkerboard DNA-DNA hybridization, bacterial species were identified in both biofilms. In conclusion, a subgingival biofilm model was developed using a stirred bioreactor, allowing the in vitro reproduction of complex microbial communities. This is an advanced model that may be useful to mimic complex clinical periodontal biofilms.

What Is Known and Objective: CYP2C19 genotypes presumably allow the prediction of the metabolizer phenotypes: poor (PMs), extensive (EMs) and ultra-rapid (UMs). However, evidence from previous studies regarding this predictive power is unclear, which is important because the benefits expected by healthcare institutions and patients are based on this premise. Therefore, we aimed to complete a formal evaluation of the diagnostic value of CYP2C19 and CYP3A4 genes for predicting metabolizer phenotypes established by omeprazole (OME) administration in 118 healthy children from Jalisco (western Mexico)., Methods: The genotypes for CYP3A4*1B and CYP2C19*2, *3, *4, *5 and *17 alleles were determined. CYP2C19 and CYP3A4 phenotypes were obtained after 20 mg OME administration and HPLC quantification in plasma to estimate the Hydroxylation Index (HI = OME/HOME) and Sulfonation Index (SI = OME/SOME), respectively., Results and Discussion: The distribution of genotypes and phenotypes for CYP2C19 and CYP3A4 was similar to previous studies in Mexico and Latin America. We estimated the CYP2C19 UM, EM and PM phenotype frequency in 0.84%, 96.61% and 2.54%, respectively. Although differences in the HI distribution were observed between CYP2C19 genotypes, they showed a poor diagnostic ability to predict the CYP2C19 metabolizer phenotype. Similarly, the number of CYP2C19 and CYP3A4 functional alleles was correlated with the HI distribution, but also their diagnostic ability to predict the CYP2C19 phenotype was poor., What Is New and Conclusion: The CYP2C19 phenotype is not predicted by the number of functional alleles of CYP2C19 and CYP3A4 genes. Phenotyping is still the most valuable alternative to dose individualization for CYP2C19 substrate drugs., (© 2018 John Wiley & Sons Ltd.)

Background: Glypican-1 (GPC1) is expressed in pancreatic ductal adenocarcinoma (PDAC) cells and adjacent stromal fibroblasts. Recently, GPC1 circulating exosomes (crExos) have been shown to be able to detect early stages of PDAC. In this study, we investigated the usefulness of crExos GPC1 as a biomarker for PDAC., Methods: Plasma was obtained from patients with benign pancreatic disease ( n = 16) and PDAC ( n = 27) prior to pancreatectomy, and crExos were isolated by ultra-centrifugation. Protein was extracted from surgical specimens (adjacent normal pancreas, n = 13; and PDAC, n = 17). GPC1 levels were measured using enzyme-linked immunosorbent assay (ELISA)., Results: There was no significant difference in GPC1 levels between normal pancreas and PDAC tissues. This was also true when comparing matched pairs. However, GPC1 levels were enriched in PDAC crExos ( n = 11), compared to the source tumors ( n = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; P < 0.001). In addition, PDACs with high GPC1 expression tended to have crExos with higher GPC1 levels. Despite these findings, we were unable to distinguish PDAC from benign pancreatic disease using crExos GPC1 levels. Interestingly, we found that in matched pre and post-operative plasma samples there was a significant drop in crExos GPC1 levels after surgical resection for PDAC ( n = 11 vs. 11; 97 ± 54 vs. 77.8 ± 32.4 pg/mL; P = 0.0428). Furthermore, we found that patients with high crExos GPC1 levels have significantly larger PDACs (>4 cm; P = 0.012)., Conclusions: High GPC1 crExos may be able to determine PDAC tumor size and disease burden. However, further efforts are needed to elucidate its role as a diagnostic and/or prognostic biomarker using larger cohorts of PDAC patients., Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

Cholangiocarcinoma (CCA) is a lethal malignancy originating from the biliary tract epithelium. Most patients are diagnosed at an advanced stage. Even after resection with curative intent, prognosis remains poor. Previous studies have reported the evolving role of miRNAs as novel biomarkers in cancer diagnosis, prognostication and chemotherapy response. Various miRNAs, such as miR-21, miR-26, miR-122 and miR-150, have been identified as possible blood-based biomarkers for noninvasive diagnosis of CCA. Moreover, epithelial-mesenchymal transition (EMT)- and angiogenesis-associated miRNAs have been implicated in tumor cell dissemination and are able to determine clinical outcome. In fact, miRNAs involved in cell survival might even determine chemotherapy response. This review provides an overview of known miRNAs as CCA-specific biomarkers.

Aim: To analyze possible factors associated with the quality of life (QoL) of mothers of preterm infants with very low birth weight (VLBW) during the first 3 years after delivery., Methods: The World Health Organization Quality of Life (WHOQOL)-bref scores were compared and correlated with maternal and infant-related sociodemographic and clinical variables at maternal discharge (T0) and at 6 (T1), 12 (T2), 24 (T3), and 36 (T4) months after delivery. Multiple linear regression models were fitted to investigate the effect of these variables on the mothers' QoL., Results: The WHOQOL-BREF physical domain scores were higher at T1 and T2 compared to T0 (p = 0.013). Maternal variables that contributed to maternal QoL scores (p < 0.05) were stable marital union (b = 13.60; T0), family income (b = -12.75; T3), Evangelical religion (b = 8.11; T4), and beck depression inventory (BDI) score (-1.42 ≤ b ≤ -0.36; T0, T1, T2, T3, and T4). Infants' variables that most affected maternal QoL (p < 0.05) were posthemorrhagic hydrocephalus (PHH) (-18.84 ≤ b ≤ -10.05; T1, T2, and T4), bronchopulmonary dysplasia (BPD) (b = -7.41; T2), female gender (b = 8.09; T2), and SNAPPE severity score (b = -0.23; T3)., Conclusion: Mothers of preterm infants with VLBW exhibited transient improvements in physical well-being during the first year after delivery. The presence of depressive symptoms in mothers and the diagnosis of PHH or BPD were negatively associated with QoL. Social, religious, and economic aspects were also important factors for the QoL of mothers of preterm infants with VLBW.

Background: To what extent high sensitivity C-reactive protein (hsCRP) is associated with known cardiovascular risk factors in children with type 1 diabetes (T1D) has not been fully explored., Methods: Forty-two T1D children (age: 12+/-1 years) without hypertension, retinopathy, hypothyroidism, albuminuria or other endocrine diseases and 20 controls were studied. Out of the 42 T1D patients studied 57% were prepubertal or early pubertal (Tanner I/II), 38% were pubertal (Tanner III/IV) and 5% post-pubertal (Tanner V)., Results: Children with T1D showed higher hsCRP than controls [0.51 (0.31-1.71 vs. 0.20 (0.20-0.90) mg/L, p<0.05]. However, hsCRP levels were not different in subgroup analysis [hemoglobin A1c (HbA1c)>7.5% or disease duration>3 years] within the group of children with T1D. Conversely, non-high density lipoprotein (HDL)-cholesterol was different in the subgroup analysis. Moreover non-HDL-cholesterol was correlated with age (r=0.37, p<0.01), disease duration (r=0.36, p<0.01) and fasting glucose (r=0.55, p<0.0001)., Conclusions: Non-HDL-cholesterol might be more useful than hsCRP to evaluate future cardiovascular risk in children with T1D.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel biomarkers are required to aid treatment decisions and improve patient outcomes. MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable molecules, and tumour and tissue specific., Results: Logistic regression analysis revealed an endoscopic-ultrasound fine-needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable of distinguishing benign from malignant pancreatic lesions with a sensitivity of 81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed both miRNAs were overexpressed in malignant disease, while circulating miRNAs performed poorly., Methods: Fifty-five patients with a suspicious pancreatic lesion on cross-sectional imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was sent for cytological assessment and the second part was used for total RNA extraction. Candidate miRNAs were selected after careful review of the literature and expression was quantified by qRT-PCR. Validation was performed on an independent cohort of EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples., Conclusions: We provide further evidence for using miRNAs as diagnostic biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant transformation and the potential to enhance risk stratification and selection for surgery., Competing Interests: Conflicts of Interest: None declared.

Epidemiological studies have suggested that the daily intake of flavonoids is associated with a decreased risk of developing cardiovascular disease. Our purpose was to evaluate the effect of the addition of dietary flavonoids (DF) to antihypertensive treatment (AHT), based on telmisartan (Tms) or captopril (Cpr), on blood pressure (BP), body mass index (BMI), waist/hip ratio, leptin, lipid profile and inflammation in hypertensive young patients. An open-label, randomized, controlled trial was performed among 79 patients aged 20-55 years with grade I or grade II systemic arterial hypertension. The subjects were assigned to one of four groups for AHT plus DF during 6 months: Cpr (n = 14), Cpr + DF (n = 19), Tms (n = 25) and Tms + DF (n = 21). DF consisted of dark chocolate, dehydrated red apple and green tea in an infusion to obtain a daily dose of 425.8 ± 13.9 mg epicatechin equivalents. The BP and anthropometric parameters were measured every 2 weeks. Lipid profile, leptin and hsCRP were determined by standard methods. The combination AHT-DF produced an additional and significant reduction in (i) SBP/DBP of -5/-4 mmHg, being -7/-5 for Cpr + DF and -4/-3 for Tms + DF; (ii) triglyceride levels (-30.6%) versus AHT alone (-9.6%); and (iii) leptin: Cpr + DF versus Tms + DF (p < 0.005). Finally, C-reactive protein plasma levels were reduced significantly in all groups independently of the applied treatment. We conclude that the addition of flavonoids to pharmacological antihypertensive therapy shows additional benefits on BP, lipid profile, leptin, obesity and inflammation., (© 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

There is an urgent need for novel and reliable biomarkers for the diagnosis and prognostication of pancreatic ductal adenocarcinoma (PDAC). Circulating microRNAs (miRNAs) have been extensively profiled in PDAC blood samples, but few studies have performed adequate validation of candidate markers. The evaluated study by Xu et al. investigated pre-operative plasma miRNAs from PDAC patients over three phases and three surgical centers. They revealed miR-486-5p and miR-938 were able to discriminate PDAC patients from healthy controls and those with chronic pancreatitis. The diagnostic ability of miR-486-5p for identifying PDAC from healthy controls was comparable to that of CA 19-9. This study provides further evidence for the use of blood-based miRNAs as diagnostic biomarkers in PDAC. However, as these have not been identified in previous studies these require further validation and methodology needs to be standardized if these are ever to be used in the clinic.

C-reactive protein (CRP) is a homopentameric oligoprotein composed of monomeric subunits that are about 21 kD each. The form of detectable native CRP in validated assays was developed in 2007 and from that time has been considered as an excellent biomarker for peripheral artery disease and/or atherosclerosis, as well as a cardiovascular disease marker for risk prediction. The improvements in the detection of CRP levels could predict significantly the population that have increased risk of stroke being the modulation of CRP levels as a therapeutical outcome for prevention of cardiovascular diseases. Nowadays antibodies that specifically bind CRP, as monoclonal anti-CRP antibodies, are available from commercial sources. Aptamers are biomolecules conformed principally by RNA or DNA, able to adopt secondary structures that can bind to epitopes from oligopeptides or complete proteins. The sensitivity and accuracy of aptamers has let to consider them as more efficient to identify proteins than just antibodies. These properties have become the base for testing these molecules for different uses. A battery of patented aptamers has been developed for detecting and/or measuring CRP. In this sense, aptamers against CRP (CRP-apt) would help to modulate CRP physiological actions at systemic, tissue, cellular and molecular levels by using appropriate experimental designs. This kind of studies would lead to fully understand which systems are regulated by the protein, what disturbances are produced if the CRP is missing or overexpressed. Finally, we hallmark other applications of CRP in terms of patents for both basic and applied research.

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrP(C)). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20-50, 100-200, and 300-400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrP(C). STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrP(C)-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1-PrP(C) signaling.

Recent studies of the Brazilian case suggest that successful litigation can have regressive effects and negatively impact the health care system. While the data to support this claim is not conclusive, this paper assumes that such immediate regressive effects are indeed taking place, but asks if these are the only consequences that should be analyzed in assessing the impact of right to health litigation in Brazil. The answer is no. The current perspective adopted to assess right to health litigation in Brazil is too narrow. Other consequences can and should be considered in analyzing the overall impact of litigation. To go beyond the set of questions asked by the existing experts on the topic, this paper analyzes whether the right to health litigation in Brazil has the potential, and could be generating: (i) policy changes within the health care system; (ii) institutional changes within the health care system; and (iii) institutional changes outside the health care system. After presenting anecdotal evidence that suggests these three types of changes may be happening in Brazil, I conclude the paper by discussing what would be required to assess them, and how these changes may affect our overall assessment of the more immediate and supposedly negative impact that litigation has had on the system., (© 2013 American Society of Law, Medicine & Ethics, Inc.)

The child overweight is associated with overweight/obesity at the adult age. The obese adipose tissue produces an increase of proinflammatory cytokines as the tumor necrosis factor alpha (TNF-α), causing a deleterious effect on vascular functions. The aim of this work was to evaluate TNF-α levels in a children's population with overweight and its relationship with clinical and laboratory variables. Thirty overweight children were studied, with ages between 8-13 years old, and twenty control children. In both groups waist circumference was measured and body mass index (BMI) calculated. The inclusion criterium was a >85th < 95 th BMI percentile for age and sex. In both groups were determined: fasting blood glucose (glucose-oxidase method); plasma insulin (ECLIA); plasma fibrinogen (Fg, Clauss method); high sensitivity C reactive protein (hsCRP, immunoturbidimetric method); plasma myeloperoxidase (ELISA); TNF-α (ELISA); lipid profile (enzymatic methods); erythrosedimentation rate (ESR) and homeostasis model assessment index (HOMA). Data were expressed as the median and interquartile range. Correlations between variables were investigated with the Spearman's coefficient. A p < 0.05 was considered significant. The TNF-α levels were higher in overweight children [15.4 (13.2-24.0) vs. 12.7 (11.2-14.8) pg/ml; p = 0.028]. Levels of Fg, plasma insulin, HOMA index, uCRP and triglycerides were also statistically significant higher than the control group. The TNF-α was positively correlated with the waist circumference (r = 0.654; p = 0.021). The high TNF-α levels found, with the CRP and Fg levels, confirm a low grade proinflammatory state associated to abdominal obesity in the studied population.

The use of scales that have been validated and standardized for different cultures is very useful for identifying demands in the field of Palliative Care and implementing the most appropriate care. This integrative literature review focuses on instruments assessing the Quality of Life of patients under Palliative Care through a journal search in electronic databases. The study consisted of 49 papers identified in Medline/PubMed, of which 18 met the inclusion criteria previously defined. Information concerning the selected studies is presented and later categorized, with a greater emphasis on the analysis of the psychometric properties of validations of the Palliative Outcome Scale, conducted in three countries. This review enabled the identification of instruments already developed and validated for different cultures, increasing the possibility of knowledge in the field.

The study of human growth hormone isoforms has conduced to the elaboration of patents related to very important items: codifying and regulatory sequences, production of the protein at large-scale, modifications to prolong half-life as monomer, dimer and fusion protein for treatments directed to growth-associated diseases. The designs to identification and quantification of hGH are besides the formers establishing very important basis of patented sources that can be used for a specific and opportune diagnosis and treatment of biological abnormalities or undesirable effects when these growth hormones are involved.

This study evaluated the health-related quality of life (HRQL) of caregivers of overweight and obese children and adolescents. Three-hundred and sixty caregives of children and adolescents (ages ranging from 9 to 12 years) diagnosed with overweight (n=96; average age 11.1 years), obesity (n=62; average age 10.9 years) and eutrophy (n=202; average age 10.7 years), regular students of public and private schools in Uberlândia (Minas Gerais), were invited to answer The 36 item Short Form Questionnaire (SF-36). The scores obtained were compared according to the body mass index (BMI) of the children and adolescents, and no significant differences were found between caregivers of overweight, obese and etrophic children and adolescents. Hence, there is no harm to the HRQL of caregivers of overweight and obese children and adolescents.

Objectives: Mental problems such as stress, anxiety and depression have been described among medical students and are associated with poor academic and professional performance. It has been speculated that these problems impair students' quality of life (QoL). The authors aimed to assess the health-related QoL (HRQL) of medical students throughout their 6 years of training at a school with a traditional curriculum., Methods: Of a total of 490 students attending our institution's medical school, 38 were surveyed in February 2006 (incoming Year 1 group, surveyed when students were in the second week of Year 1 classes) and 352 were surveyed in February 2007 (students in Years 1-6). Students self-reported their HRQL and depressive symptoms using the Short-Form Health Survey (SF-36) and the Beck Depression Inventory (BDI). Comparisons were performed according to year in training, presence of depressive symptoms, gender, living arrangements and correlations with family income., Results: The students' ages ranged from 18 to 31 years (median 22.3 years). Students in Years 2, 3, 4 and 6 had lower scores for mental and physical dimensions of HRQL compared with the incoming Year 1 group (P < 0.01), with the largest difference observed for Year 3 students. Students with depressive symptoms had lower scores in all domains of the SF-36 (P < 0.01). Female students had lower HRQL scores than males (P < 0.01). No differences were observed for students living with versus without family and no correlation with family income was found., Conclusions: Major impairments in HRQL were observed among Year 3 students, students with depressive symptoms and women. Medical schools should institute efforts to ensure that students' HRQL and emotional support are maintained, particularly during critical phases of medical training.

The metabolic conditions affecting placental development depend on nutritional state, genetic constitution and other external factors. The secretion of human placental growth hormone (hGH-V) had shown to be dependent of glucose, but the regulatory effects of this metabolite on hGH-V promoter activity and gene expression in presence of 5-azacytidine had not been studied. In this work we compared the hGH-V promoter activity and the endogenous mRNA expression in human placental choriocarcinoma cell line JAR in the presence of glucose and demethylating genome conditions. High glucose concentration in culture medium diminished hGH-V mRNA endogenous levels in JAR cells whereas the expression of hGH-V from transfected PACs was slightly higher; but in the presence of 5azaC a higher hGH-V gene expression from both the endogenous and the transfected ones was obtained. A drastic diminution of promoter analysis was shown when cells had no glucose (J0 cells) or in presence of 5azaC; the placental transcription factors that showed modified binding capacity were HES-2, PPAR-gamma, H4TF-1 and OCT-1. Our results suggest that in vitro suppressive glucose effect dictates a metabolic context to hGH-V gene expression and promoter regulation whereas a genomic methylation-dependent background is necessary to maintain placental transcription factors able to bind and regulate proximal promoter region of hGH-V in placental cells., (Crown Copyright 2009. Published by Elsevier B.V. All rights reserved.)

A subclinical inflammation state was detected in the early step of diabetes, which increases the serum levels of cytokines that induce acute-phase protein synthesis as C-reactive protein (PCR) and fibrinogen (Fg), stimulating the endothelial disfunction of adhesion molecules. Thirty patients (15 boys, 15 girls) with type 1 diabetes (DT1), without vascular complications, were studied. Their mean age and duration of diabetes were 11.8 +/- 2.1 and 3.9 +/- 3.2 years, respectively. The laboratory parameters evaluated were: blood leukocytes count, globular sedimentation velocity, fasting glycemia, glycosylated hemoglobin (HbA1c), high sensitivity PCR (uPCR), plasma soluble E-selectin (sE-S), sVCAM-1 and microalbuminuria. Increased levels of uPCR, sE-S and VCAM-1 were found, compared with the control group control [0.60 (0.30-1.25) vs. 0.20 (0.20-0.65) mg/l, p = 0.013], [108 (60-150) vs. 68 (56-82) ng/ml, p = 0.0031] y [750 (708-826) vs. 721 (674-751) ng/ml, p = 0.039] respectively. When diabetic patients were grouped according to duration of disease (3 and > de 3 years), uPCR values were higher in the second group. uPCR levels were better correlated with sE-S (r = 0.44, p = 0.03) and VCAM-1 (r = 0.49, p = 0.02). These results suggest the presence of pro-inflammatory and endothelial activation states, which are strongly associated with DT1.

The Brazilian Dentistry Code of Ethics (DCE), Resolution CFO-71 from May 2006, is an instrument created to guide dentists' behavior in relation to the ethical aspects of professional practice. The purpose of the study is to analyze the above mentioned code comparing the deontological and bioethical focuses. In order to do so, an interpretative analysis of the code and of twelve selected texts was made. Six of the texts were about bioethics and six on deontology, and the analysis was made through the methodological classification of the context units, textual paragraphs and items from the code in the following categories: the referentials of bioethical principlism--autonomy, beneficence, nonmaleficence and justice -, technical aspects and moral virtues related to the profession. Together the four principles represented 22.9%, 39.8% and 54.2% of the content of the DCE, of the deontological texts and of the bioethical texts respectively. In the DCE, 42% of the items referred to virtues, 40.2% were associated to technical aspects and just 22.9% referred to principles. The virtues related to the professionals and the technical aspects together amounted to 70.1% of the code. Instead of focusing on the patient as the subject of the process of oral health care, the DCE focuses on the professional, and it is predominantly turned to legalistic and corporate aspects.

Tobacco addiction is a chronic disorder that is characterized by a negative affective state upon smoking cessation and relapse after periods of abstinence. Previous research has shown that an increased central release of corticotropin-releasing factor (CRF) at least partly mediates the deficit in brain reward function associated with nicotine withdrawal in rats. The aim of these studies was to investigate the role of CRF in the central nucleus of the amygdala (CeA), the lateral bed nucleus of the stria terminalis (BNST), and the nucleus accumbens shell (Nacc shell) in the deficit in brain reward function associated with precipitated nicotine withdrawal. The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In all experiments, the nicotinic receptor antagonist mecamylamine (3 mg/kg) elevated the brain reward thresholds of the nicotine-dependent rats (9 mg/kg per day of nicotine salt) and did not affect the brain reward thresholds of the saline-treated control rats. The administration of the nonspecific CRF1/2 receptor antagonist D-Phe CRF((12-41)) into the CeA and the Nacc shell prevented the mecamylamine-induced elevations in brain reward thresholds in the nicotine-dependent rats. Blockade of CRF1/2 receptors in the lateral BNST did not prevent the mecamylamine-induced elevations in brain reward thresholds in the nicotine-dependent rats. These studies indicate that the negative emotional state associated with precipitated nicotine withdrawal is at least partly mediated by an increased release of CRF in the CeA and the Nacc shell.

Objective: Trauma is the third most important cause of death in Brazil. However, its impact on survivors' quality of life has been scarcely studied in this country. This study aimed to assess trauma victims' quality of life, cared for in an emergency hospital unit, six months after discharge., Methods: A total of 35 patients from the emergency unit of a university hospital in the city of Ribeirão Preto, Southeastern Brazil, were included in this study, between 2005 and 2006. Patients were interviewed in their homes, six months after hospital discharge. The short version of the World Health Organization Quality of Life (WHOQOL-BREF) instrument was applied to assess the physical, psychological, social relationships, and environmental domains. Associations between domain scores and hospital stay, age, sex and Injury Severity Score variables were analyzed with linear regression models., Results: Significant reduction in quality of life was found in the group studied, when compared to samples of normal people in national and international studies, especially as regards the physical, psychological, and environmental domains. The social relationships domain revealed the highest mean scores, with 69.7 points, whereas the environmental domain received the lowest score (52.4 points), both on the percentage scale. Variables associated with the physical domain were hospital stay (p=0.02), age (p<0.01) and sex (p=0.03). The analysis did not show association with the variables studied for the remaining domains., Conclusions: Trauma victims showed a reduction in quality of life scores. Even though the physical aspect was the most affected, there is evidence that the psychological and environmental domains remained far from the ideal conditions expected for the general population.

The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S) levels in children with type 1 diabetes (DT1) and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys), age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated hemoglobin (HbAlc), total cholesterol (TC), HDL-C, LDL-C, non-HDL-C and triglycerides (TG). sE-S values were 66% higher in diabetics than in control subjects (p = 0.001). Patients were grouped in: good glycemic control diabetics (GGCD, HbA1c < or = 8%) and poor glycemic control diabetics (PGCD, HbA1c > 8%). sE-S concentratios were in PGCD an GGCD respectively. 111.3 +/- 40.5 vs 68.0 +/- 11.3 ng/ml, p = 0.02. In the diabetic group, the incidence of non desirable values in the lipid profile parameters were: TC 50%; HDL-C 14%; LDL-C 52%, non-HDL-C 26.7% and TG 14%. sE-S values were better correlated with HbA1c (r = 0.53, p = 0.0001) than fasting glycemia (r = 0.36, p = 0.008), and CT (r = 0.36, p = 0.009). These results suggest that sE-S is an early marker of endothelial dysfunction and a probable risk marker of atherosclerosis in children with DT1.

The ascomycete Fusarium fujikuroi produces carotenoids by means of the enzymes encoded by three car genes. The enzymes encoded by carRA and carB are responsible of the synthesis of beta-carotene and torulene, respectively, while the product encoded by carT cleaves torulene to produce the acidic xanthophyll neurosporaxanthin. carRA and carB are found in a cluster with a third gene, carO, which codes for an opsin-like protein. However, no information is available on the sequence or chromosomal location of carT, which has been identified only by mutant analysis. Transcription of the three clustered genes is stimulated by light and by mutations in a regulatory gene, leading to overproduction of carotenoids. We have now identified a fourth gene in the car cluster, called carX, which codes for a protein similar to known carotenoid-cleaving oxygenases. carX is transcribed divergently from carRA, and exhibits the same transcriptional pattern as carRA, carB and carO. Targeted deletion of carX resulted in a phenotype characterized by a significant increase in the overall carotenoid content. In the dark, the carX mutants accumulate at least five times more carotenoids than the wild type, and exhibit partial derepression of carRA and carB transcription. The mutants also show more intense pigmentation in the light, but the increase in the carotenoid content relative to the wild type is less than twofold. Under these conditions, the mutants also show a relative increase in the amounts of phytoene and cyclic carotenoids formed, suggesting that CarRA activity is enhanced.

Diabetics have an increased risk of cardiovascular disease (CVD). The objective of this work was to evaluate the cardiovascular risk factors in infant-juvenile type 1 diabetics and their association with the degree of glycemic control. A total of 52 patients, aged 5-15 years, were studied and compared with 37 control subjects. The degree of glycemic control, lipid profile, plasma fibrinogen, microalbuminuria and blood pressure were investigated. The patients were grouped in diabetics with good glycemic control [DGGC, glycosilated hemoglobin (HbA1c) < 8%] and poor glycemic control [DPGC, HA1c > or = 8%]. Diabetic patients presented incremented values of total cholesterol (4.1 +/- 0.9 vs. 3.1 +/- 0.7 mmol/l, p = 0.0008), LDL-cholesterol (2.4 +/- 0.9 vs. 1.7 +/- 0.7 mmol/l, p = 0.0001), HDL-cholesterol (1.2 +/- 0.3 vs. 1.0 +/- 0.2 mmol/l, p = 0.0002), with respect to control group. Eighty three per cent of diabetics showed a poor glycemic control. There were not significant differences in lipid profile between DGGC and DPGC, excepting HDL-cholesterol which was higher in DPGC group (p = 0.007). Plasma fibrinogen levels were similar in diabetics and controls, but they were higher in DPGC than in DGGC (265 +/- 46 vs. 229 +/- 22 mg/dl, p = 0.02). Three patients with microalbuminuria and none with hypertension were detected. In these patients the most pronounced risk factors for CVD were dyslipidemia and hyperglycemia, which justify the need for the early detection of these factors as well as strict metabolic control.

Opsins are membrane photoreceptors closely related to the heat-shock proteins of the HSP30 family. Their functions include light-driven ion pumping in archaea and light detection in algae and animals, using the apocarotenoid retinal as a light-absorbing prosthetic group. We describe a gene of Fusarium fujikuroi, carO, coding for a polypeptide resembling opsins and HSP30-like proteins and contiguous to the genes of the carotenoid pathway, carRA and carB. Transcription of carO is induced by light and is deregulated in carotenoid-overproducing mutants. The same regulation pattern is exhibited by carRA and carB; and common conserved DNA elements are found in the three promoters. Heat shock resulted in a modest induction of carO transcription, similar to the one exhibited by carB, confirming a common regulation. Targeted mutagenesis of carO produced no apparent phenotypic modification, including no change in the photoinduction of carotenoid biosynthesis.

Phytoene synthase, phytoene dehydrogenase and carotene cyclase are three of the four enzyme activities needed to produce the acidic carotenoid neurosporaxanthin from the precursor geranylgeranyl pyrophosphate. In the filamentous fungus Fusarium fujikuroi, these three enzyme activities are encoded by two closely linked genes, carRA and carB, oriented in the same direction in the genome. The two genes are separated by 548 bp and code for two polypeptides of 612 and 541 amino acids, respectively, which are highly similar to the homologous proteins from other filamentous fungi. The ORF of carRA contains a 96-bp insertion that is absent in the other fungal homologues. The 32 additional residues are located in one of the two repeated domains responsible for the cyclase activity in the homologous fungal proteins. We have determined the function of carRA by gene disruption. The resulting mutants were albino and had lost the ability to produce phytoene, as expected from the simultaneous loss of phytoene synthase and carotene cyclase. In the same experiments, we also found transformants in which carB had been deleted. These mutants accumulate phytoene, confirming the function of the gene previously shown by gene-targeted mutagenesis. Expression of carRA and carB is strongly induced by light. Loss of carB or disruption of the carRA ORF led to enhanced expression of the carRA gene, suggesting the existence of a feedback regulatory mechanism.

This study is a critical reflection on attempts to alter the Declaration of Helsinki, a key document of the democratic theses achieved in the latter half of the 20th century and thus a legacy for humanity because of its ethical guidelines for research involving human beings. Therefore, there must be worldwide social control over such a document, and any change in it demands ample debate with international participation to avoid any reversal in its humanitarian thrust. The study analyzes current aspects of research with human subjects in so-called "outlying" or "developing" countries. It also brings a social and political focus to the matter, highlighting that the economic fundamentalism exercised by wealthy countries inevitably leads to an ethical imperialism, exposing communities of poor countries to even greater vulnerability, discrimination, and social exclusion.

Objective: The aim of this study was to know the incidence of serious bacterial infections (SBI) in children without sepsis or intracranial infection in which spinal puncture (LP) was performed in an Emergency Department., Patients and Methods: A retrospective study of all 471 previously healthy children between 1 month and 14 years of age in which a lumbar puncture was performed between July 1995 and March 1997 in the Emergency Department of our hospital was performed., Results: Two hundred and three children (43%) had sepsis, meningitis or encephalitis (aseptic meningitis 149, 31.6%; sepsis-bacterial meningitis 26, 5.5%; nonspecific meningitis 26, 5.5%; encephalitis 2, 0.4%) and 14 (5.2%) had pneumonia. Of the other 254 children, 36 (14.1%) had a SBI: 19 urinary tract infections (E. coli), 11 bacteremia (Streptococcus pneumoniae 8, Salmonella enteritidis 1, Proteus mirabilis 1, E. coli 1, the latter two also having a positive urine culture) and 6 bacterial gastroenteritis (salmonella 5, Campylobacter jejuni 1). The incidence of SBI was significantly higher in the group of children younger than 5 years old (32/175, 18.2%) than in the older group (4/79, 5.0%, p = 0.009). Two patients died (one with pneumococcal meningitis and one with meningococcal sepsis)., Conclusions: Children with fever and a normal result in the LP must be carefully examined and, especially in younger patients, urine, blood and stool (if stool abnormalities) cultures should be collected. These children must be closely observed in the hospital or at home and must be re-evaluated by their pediatrician in the following 24 hours.