Application of natural language processing to predict final recommendation of Brazilian health technology assessment reports.

INTRODUCTION: Health technology assessment (HTA) plays a vital role in healthcare decision-making globally, necessitating the identification of key factors impacting evaluation outcomes due to the significant workload faced by HTA agencies. OBJECTIVES: The aim of this study was to predict the approval status of evaluations conducted by the Brazilian Committee for Health Technology Incorporation (CONITEC) using natural language processing (NLP). METHODS: Data encompassing CONITEC's official report summaries from 2012 to 2022. Textual data was tokenized for NLP analysis. Least Absolute Shrinkage and Selection Operator, logistic regression, support vector machine, random forest, neural network, and extreme gradient boosting (XGBoost), were evaluated for accuracy, area under the receiver operating characteristic curve (ROC AUC) score, precision, and recall. Cluster analysis using the k-modes algorithm categorized entries into two clusters (approved, rejected). RESULTS: The neural network model exhibited the highest accuracy metrics (precision at 0.815, accuracy at 0.769, ROC AUC at 0.871, and recall at 0.746), followed by XGBoost model. The lexical analysis uncovered linguistic markers, like references to international HTA agencies' experiences and government as demandant, potentially influencing CONITEC's decisions. Cluster and XGBoost analyses emphasized that approved evaluations mainly concerned drug assessments, often government-initiated, while non-approved ones frequently evaluated drugs, with the industry as the requester. CONCLUSIONS: NLP model can predict health technology incorporation outcomes, opening avenues for future research using HTA reports from other agencies. This model has the potential to enhance HTA system efficiency by offering initial insights and decision-making criteria, thereby benefiting healthcare experts.

The potential of metabolomics in assessing global compositional changes resulting from the application of CRISPR/Cas9 technologies.

Exhaustive analysis of genetically modified crops over multiple decades has increased societal confidence in the technology. New Plant Breeding Techniques are now emerging with improved precision and the ability to generate products containing no foreign DNA and mimic/replicate conventionally bred varieties. In the present study, metabolomic analysis was used to compare (i) tobacco genotypes with and without the CRISPR associated protein 9 (Cas9), (ii) tobacco lines with the edited and non-edited DE-ETIOLATED-1 gene without phenotype and (iii) leaf and fruit tissue from stable non-edited tomato progeny with and without the Cas9. In all cases, multivariate analysis based on the difference test using LC-HRMS/MS and GC-MS data indicated no significant difference in their metabolomes. The variations in metabolome composition that were evident could be associated with the processes of tissue culture regeneration and/or transformation (e.g. interaction with Agrobacterium). Metabolites responsible for the variance included quantitative changes of abundant, well characterised metabolites such as phenolics (e.g. chlorogenic acid) and several common sugars such as fructose. This study provides fundamental data on the characterisation of gene edited crops, that are important for the evaluation of the technology and its assessment. The approach also suggests that metabolomics could contribute to routine product-based analysis of crops/foods generated from New Plant Breeding approaches.

A comprehensive model for assessing and classifying patients with thrombotic microangiopathy: the TMA-INSIGHT score.

BACKGROUND: Thrombotic Microangiopathy (TMA) is a syndrome characterized by the presence of anemia, thrombocytopenia and organ damage and has multiple etiologies. The primary aim is to develop an algorithm to classify TMA (TMA-INSIGHT score). METHODS: This was a single-center retrospective cohort study including hospitalized patients with TMA at a single center. We included all consecutive patients diagnosed with TMA between 2012 and 2021. TMA was defined based on the presence of anemia (hemoglobin level < 10 g/dL) and thrombocytopenia (platelet count < 150,000/µL), signs of hemolysis, and organ damage. We classified patients in eight categories: infections; Malignant Hypertension; Transplant; Malignancy; Pregnancy; Thrombotic Thrombocytopenic Purpura (TTP); Shiga toxin-mediated hemolytic uremic syndrome (STEC-SHU) and Complement Mediated TMA (aHUS). We fitted a model to classify patients using clinical characteristics, biochemical exams, and mean arterial pressure at presentation. RESULTS: We retrospectively retrieved TMA phenotypes using automatic strategies in electronic health records in almost 10 years (n = 2407). Secondary TMA was found in 97.5% of the patients. Primary TMA was found in 2.47% of the patients (TTP and aHUS). The best model was LightGBM with accuracy of 0.979, and multiclass ROC-AUC of 0.966. The predictions had higher accuracy in most TMA classes, although the confidence was lower in aHUS and STEC-HUS cases. CONCLUSION: Secondary conditions were the most common etiologies of TMA. We retrieved comorbidities, associated conditions, and mean arterial pressure to fit a model to predict TMA and define TMA phenotypic characteristics. This is the first multiclass model to predict TMA including primary and secondary conditions.

Effects of inspiratory muscle training on the severity of obstructive sleep apnea in individuals after stroke: a protocol for a randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing in cerebrovascular diseases, requiring a multidisciplinary approach. There are few studies evaluating the effects of inspiratory muscle training (IMT) in individuals with OSA and the findings regarding the possible effect on apnea hypopnea index (AHI) reduction are controversial. OBJECTIVE: This protocol for a randomized clinical trial will assess the effects of IMT on the severity of obstructive sleep apnea, sleep quality, and daytime sleepiness in individuals after stroke participating in a rehabilitation program. METHODS: This study will be a randomized controlled trial with blinded assessors. Forty individuals after stroke will randomized to two groups. For 5 weeks, both groups will participate in the rehabilitation program activities, including aerobic exercise, resistance training, and educational class when they will receive guidance on the behavioral management of OSA. The experimental group will also perform high-intensity IMT 5 times a week, for 5 weeks, consisting initially of five sets of five repetitions achieving 75% of the maximal inspiratory pressure, increasing one set each week, totaling nine sets at the end of training. The primary outcome will be the severity of OSA measured as AHI at 5 weeks. Secondary outcomes will include sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness measured by Epworth Sleepiness Scale (ESS). Outcomes will be collected by a researcher blinded to group allocation at baseline (week 0), after intervention (week 5), and 1 month beyond intervention (week 9). TRIAL REGISTRATION: Clinical Trials Register: NCT05135494.

Effects of photobiomodulation therapy (PBMT) on the management of pain intensity and disability in plantar fasciitis: systematic review and meta-analysis.

To review the effects of photobiomodulation therapy (PBMT) on pain intensity and disability in people with plantar fasciitis (PF) when compared with control conditions, other interventions, and adjunct therapies. Systematic searches were conducted in five database randomized controlled trials (RCT). We only included randomized controlled trials (RCTs) in adults with PF that compared PBMT to placebo, as well as RCTs that compared PBMT to other interventions; and as an adjunct to other therapies. The methodological quality and certainty were assessed through PEDro Scale and GRADE approach, respectively. The data of comparison were pooled and a meta-analysis was conducted when possible. Nineteen RCTs involving 1089 participants were included in this review. PBMT alone (MD = - 22.02 [- 35.21 to - 8.83]) or with exercise (MD = - 21.84 [- 26.14 to - 17.54]) improved pain intensity in short-term treatment. PBMT was superior to (extracorporeal shock wave therapy) EWST for relief of pain (MD = - 20.94 [- 32.74 to - 9.13]). In the follow-up, PBMT plus exercise had a superior to exercise therapy alone (MD = - 18.42 [- 26.48 to - 10.36]). PBMT may be superior to (ultrasound therapeutic) UST in medium- and long-term follow-ups for disability, but can be not clinically relevant. There is uncertainty that PBMT is capable of promoting improvement in disability. PBMT when used with adjuvant therapy does not enhance outcomes of interest. PBMT improves pain intensity with or without exercise. PBMT has been shown to be superior to ESWT for pain relief, but not superior to other interventions for pain intensity and disability. The evidence does not support PBMT as an adjunct to other electrotherapeutic modalities.

Photo-Fenton process applied for the treatment of industrial wastewaters containing diclofenac: optimization with low iron ions concentrations and without pH control.

Diclofenac (DCF) can cause several adverse effects in the environment and it should be removed from industrial pharmaceutical wastewaters. Advanced oxidation processes (AOPs) are promising methods for the DCF degradation. But, in many cases, AOPs require acidic pH. However, at this condition, DCF precipitates, which may hinder its oxidation. Thus, in this work, some AOP were studied for the DCF degradation, especially the photo-Fenton process, applying the experimental design technique (Doehlert matrix), operating without and with pH control (between 6.5 and 7.0). As independent variables, the initial ferrous ion concentration ([Fe2+]) and the molar addition rate of H2O2 (FH2O2) were evaluated. Empirical models were proposed and optimized conditions were determined without ([Fe2+] = 0.27 mmol L-1 and FH2O2 = 1.64 mmol min-1) and with pH control ([Fe2+] = 1.0 mmol L-1 and FH2O2 = 1.64 mmol L-1), with the following predicted mineralization percentages: 93% and 68%, respectively. So, photo-Fenton process without pH control presented the best performances. Furthermore, at this condition, iron concentration respects the limit value established by the Brazilian environmental legislation. That is, in this condition, additional processes, in order to remove iron ions, would not be necessary, that is very interesting for applications on an industrial scale.

Lactobacillus group and arterial hypertension: A broad review on effects and proposed mechanisms.

Hypertension is the leading risk factor for cardiovascular diseases and is associated with intestinal dysbiosis with a decrease in beneficial microbiota. Probiotics can positively modulate the impaired microbiota and impart benefits to the cardiovascular system. Among them, the emended Lactobacillus has stood out as a microorganism capable of reducing blood pressure, being the target of several studies focused on managing hypertension. This review aimed to present the potential of Lactobacillus as an antihypertensive non-pharmacological strategy. We will address preclinical and clinical studies that support this proposal and the mechanisms of action by which these microorganisms reduce blood pressure or prevent its elevation.

Genomic and Biological Characterization of Ralstonia solanacearum Inovirus Brazil 1, an Inovirus that Alters the Pathogenicity of the Phytopathogen Ralstonia pseudosolanacearum.

Filamentous bacteriophages contain a single-stranded DNA genome and have a peculiar lifestyle, since they do not cause host cell lysis, but establish a persistent association with the host, often causing behavioral changes, with effects on bacterial ecology. Over the years, a gradual reduction in the incidence of bacterial wilt has been observed in some fields from Brazil. This event, which has been associated with the loss of pathogenicity of Rasltonia spp. isolates due to infection by filamentous viruses of the inovirus group, is widely reported for Ralstonia spp. Asian isolates infected by inoviruses. In an attempt to elucidate which factors are associated with the phenomenon reported in Brazil, we investigated one isolate of R. solanacearum (UB-2014), with unusual characteristics for R. solanacearum, obtained from eggplant with mild wilt symptoms. To verify if the presence of filamentous bacteriophage was related to this phenotype, we performed viral purification and nucleic acid extraction. The phage genome was sequenced, and phylogenetic analyses demonstrated that the virus belongs to the family Inoviridae and was named as Ralstonia solanacerarum inovirus Brazil 1 (RSIBR1). RSIBR1 was transmitted to R. pseudosolanacearum GMI1000, and the virus-infected GMI1000 (GMI1000 VI) isolate showed alterations in phenotypic characteristics, as well as loss of pathogenicity, similarly to that observed in R. solanacearum isolate UB-2014. The presence of virus-infected UB-2014 and GMI1000 VI plants without symptoms, after 3 months, confirms that the infected isolates can colonize the plant without causing disease, which demonstrates that the phage infection changed the behavior of these pathogens.

Local understandings of PTSD and complex PTSD among health professionals working with adolescents in violent neighbourhoods of São Paulo city, Brazil.

BACKGROUND: Adolescents in low-resource urban settings in Brazil are often exposed to high levels of trauma that can result in post-traumatic stress disorder (PTSD). However, preliminary evidence indicates that PTSD tends to be under-reported in Brazilian health services, despite the high prevalence of trauma. Additionally, little is known about the perceived applicability among clinicians of the new ICD-11 diagnosis of complex PTSD (CPTSD), despite its potential relevance for contexts of chronic trauma. The current study investigated local understandings of PTSD and CPTSD among health professionals working with adolescents in violent neighbourhoods of São Paulo city. METHODS: Semi-structured interviews were conducted with 58 health professionals working at both the primary care and specialized mental health levels in two areas of São Paulo city with high levels of community violence. RESULTS: Most participants knew about PTSD, but most did not know about CPTSD. There were mixed views concerning the commonality of PTSD among adolescents exposed to community violence. Many participants reported having no experience working with patients with the PTSD diagnosis. According to some, community violence was normalized by adolescents and health professionals, and did not result in PTSD. Others highlighted how they did not use psychiatric diagnoses in their practice, had critical perspectives towards psychiatric diagnoses and/or PTSD, or simply knew little about PTSD. Furthermore, many highlighted how the chronic nature of multiple traumas experienced by adolescents often resulted in complex clinical presentations characterised by many symptoms beyond PTSD. The diagnosis of CPTSD was considered appropriate to the context by many participants as it captured the complex traumatic histories and symptom presentations of adolescents exposed to community violence in Brazil. CONCLUSIONS: These findings have important implications for the assessment and treatment of mental health among adolescents exposed to community violence in Brazil.

A transcriptomic, metabolomic and cellular approach to the physiological adaptation of tomato fruit to high temperature.

High temperatures can negatively influence plant growth and development. Besides yield, the effects of heat stress on fruit quality traits remain poorly characterised. In tomato, insights into how fruits regulate cellular metabolism in response to heat stress could contribute to the development of heat-tolerant varieties, without detrimental effects on quality. In the present study, the changes occurring in wild type tomato fruits after exposure to transient heat stress have been elucidated at the transcriptome, cellular and metabolite level. An impact on fruit quality was evident as nutritional attributes changed in response to heat stress. Fruit carotenogenesis was affected, predominantly at the stage of phytoene formation, although altered desaturation/isomerisation arose during the transient exposure to high temperatures. Plastidial isoprenoid compounds showed subtle alterations in their distribution within chromoplast sub-compartments. Metabolite profiling suggests limited effects on primary/intermediary metabolism but lipid remodelling was evident. The heat-induced molecular signatures included the accumulation of sucrose and triacylglycerols, and a decrease in the degree of membrane lipid unsaturation, which influenced the volatile profile. Collectively, these data provide valuable insights into the underlying biochemical and molecular adaptation of fruit to heat stress and will impact on our ability to develop future climate resilient tomato varieties.

Neutrophil extracellular traps in inflammatory bowel diseases: Implications in pathogenesis and therapeutic targets.

Crohn's disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD). Among the various immune cells involved in IBD, neutrophils are the first to infiltrate and appear to contribute to the impairment of the epithelial barrier, destruction of tissues by oxidative and proteolytic damage, as well as to the perpetuation of inflammation by the release of cytokines and chemokines associated with pro-inflammatory effects. In addition to basic effector mechanisms, such as phagocytosis and chemotaxis, neutrophils can also form extracellular traps (NETs), which is made up of a mesh-like structure - which contains its chromatin (DNA + histones) together with granules and enzymes, such as myeloperoxidase (MPO) and neutrophilic elastase (NE) - and that acts as a trap that can result in the death of extracellular pathogens and/or can promote tissue damage. Recent evidence indicates that NETs also play an important and significant role in the pathogenesis of IBD. Previous studies have reported increased levels of NETs in tissue and serum samples from patients with IBD, as well as in experimental colitis. In this review, we discuss current knowledge about the formation of NETs and their role in the pathophysiology of IBD, pointing out potential mechanisms by which NETs promote tissue damage, as well as their involvement in complications associated with IBD. In addition, we propose potential targets for therapy to regulate the production of NETs, making it possible to expand the current spectrum of therapies for IBD.

Effects of inspiratory muscle training on walking capacity of individuals after stroke: A double-blind randomized trial.

OBJECTIVES: Identify the effects of inspiratory muscle training (IMT) on walking capacity, strength and inspiratory muscle endurance, activities of daily living, and quality of life poststroke. DESIGN: Double-blind randomized trial. SETTING: The Sarah Network of Rehabilitation Hospitals. SUBJECTS: Adult poststroke inpatients with inspiratory muscle weakness. INTERVENTIONS: The Experimental Group (EG) (n = 23) underwent IMT for 30 minutes/day, five times/week over six weeks. The Control Group (CG) (n = 27) performed sham IMT. Both groups underwent standard rehabilitation. MAIN MEASURES: Primary outcome was post-intervention six-minute walking test (6MWT) distance. We also measured maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), inspiratory muscle endurance, activities of daily living (functional independence measure - FIM), and quality of life at baseline and post-intervention. Three months after intervention, we measured MIP, walking capacity and quality of life. RESULTS: Baseline characteristics were similar, with mean age 53 ± 11 years and FIM 74 ± 10p. Both groups similarly increased the walking capacity at six weeks (63 vs 67 m, P = 0.803). Compared to the CG, the EG increased the inspiratory endurance (22 vs 7 cmH2O, P = 0.034) but there was no variation in MEP (14 vs 5 cmH2O, P = 0.102), MIP (27 vs 19 cmH2O, P = 0.164), FIM (6 vs 6, P = 0.966) or quality of life (0 vs 0.19, P = 0.493). Gains in both groups were sustained at three months. CONCLUSION: Adding IMT to a rehabilitation program improves inspiratory muscle endurance, but does not further improve MIP, 6-MWT distance, activities of daily living or quality of life of individuals after stroke beyond rehabilitation alone.Registered in Clinical Trials, NCT03171272.

Effects of disorder on two-photon absorption in amorphous semiconductors.

Structural disorder inherent to amorphous materials affords them unique, tailorable properties desirable for diverse applications, but our ability to exploit these phenomena is limited by a lack of understanding of complex structure-property relationships. Here we focus on nonlinear optical absorption and derive a relationship between disorder and the two-photon absorption (2PA) coefficient. We employ an open-aperture Z-scan to measure the 2PA spectra of arsenic (III) sulfide (As2S3) chalcogenide glass films processed with two solvents that impart different levels of structural disorder. We find that the effect of solvent choice on 2PA depends on the energy of the exciting photons and explain this as a consequence of bonding disorder and electron state localization. Our results demonstrate how optical nonlinearities in As2S3 can be enhanced through informed processing and present a fundamental relationship between disorder and 2PA for a generalized amorphous solid.

Photoelectrocatalytic degradation of 17α-ethinylestradiol and estrone under UV and visible light using nanotubular oxide arrays grown on Ti-0.5wt%W.

Environmental concern with emerging contaminants has increased in recent years, especially with regard to endocrine-disrupting compounds (EDCs), among them hormones. Conventional water treatment processes have been shown to be ineffective in removing these compounds from water and sewage, while heterogeneous photocatalysis has been demonstrated to be a promising technique. However, the catalytic efficiency is strongly related to the choice of the photocatalyst material. In order to obtain a fast and efficient degradation of these endocrine disruptors, nanotubes grown on Ti-0.5wt%W alloy (NT/Ti-0.5W) were used in photocatalytic (PC) and photoelectrocatalytic (PEC) processes for the degradation of estrone (E1) and 17α-ethinylestradiol (EE2) under irradiation with ultraviolet (UV) and visible light. The NT/Ti-0.5W catalysts were synthesized by an anodization process, followed by thermal treatment at 450 °C. Raman, X-ray diffraction and diffuse reflectance spectroscopic analyses indicated that the tungsten doping process had modified the nanotubular TiO2. The doped samples exhibited superior photoactivity compared to un-doped samples and other semiconductors under UV and visible irradiation due to a reduction in the rate of recombination of photogenerated charges and the displacement of the flat-band potential to more negative values. Higher values of the degradation rate constant were found for both hormones in the PEC process using NT/Ti-0.5W under UV radiation; the percentage removals of EE2 and E1 were 66% and 53.4%, respectively, after only 2 min of treatment. With visible light, 1.8 min and 4.6 h were required for the removal of 50% of E1 and EE2, respectively. The degradation of E1 could be fit with a zero-order kinetic model, while a first-order kinetic model was required for EE2 degradation. Degradation routes were suggested for E1 and EE2. The results demonstrate that the combined use of NT/Ti-0.5W and the PEC process provides excellent performance for the degradation of emerging contaminants in wastewater when compared to a NT/TiO2 electrode.

Lactoferrin and lactoferricin B reduce adhesion and biofilm formation in the intestinal symbionts Bacteroides fragilis and Bacteroides thetaiotaomicron.

Several factors affect the composition of species that inhabit our intestinal tract, including mode of delivery, genetics and nutrition. Antimicrobial peptides and proteins secreted in the gastrointestinal tract are powerful tools against bacteria. Lactoferrin (LF) inhibits the growth of several bacterial species, such as Enterobacteriaceae, but may stimulate probiotic bacteria. Activity of LF against gut symbiotic species of the Bacteroides genus could give us insights on how these species colonize the gut. We investigated the effects of the antimicrobial protein lactoferrin and its derived peptide, lactoferricin B on two species of strict anaerobes, opportunistic pathogens that cause diseases in both adults and children, commonly found in the microbiota of the human gastrointestinal tract, Bacteroides fragilis and B. thetaiotaomicron., In vitro biofilm formation and binding to laminin were strongly inhibited by a low concentration of lactoferrin (12.5 µg/ml). Conversely, the growth of the strains in a micro-dilution assay in minimal media with different iron sources was not affected by physiological concentrations (2 mg/ml) of apo-lactoferrin or holo-lactoferrin. The combination of lactoferrin with antibiotics in synergism assays was also negative. The lactoferricin B fragment was also unable to inhibit growth in a similar test with concentrations of up to 32 µg/ml. Resistance to lactoferrin could confer an advantage to these species, even when high amount of this protein is present in the gastrointestinal tract. However, colonization is hampered by the binding and biofilm inhibitiory effect of lactoferrin, which may explain the low prevalence of Bacteroides in healthy babies. Resistance to this antimicrobial protein may help understand the success of these opportunistic pathogens during infection in the peritoneum.

The Impact of Spirituality and Religiosity on Mental Health and Quality of Life of Patients with Active Crohn's Disease.

We aim to investigate the association among religious/spiritual coping (RSC), quality of life (QOL), and mental health in patients with active Crohn's disease (CD). This cross-sectional study included 102 patients with active CD. Religious and spiritual beliefs were common among patients, being positive RSC higher than negative RSC. Negative coping was associated with mood disorders (depressive or anxiety symptoms) through the Hospital Anxiety and Depression Scale (ß = 0.260, p < 0.01) but not with QOL (Inflammatory Bowel Disease Questionnaire) (ß = - 0.105, p = NS) after adjustments. Positive coping and other religious/spiritual beliefs and behaviors were not associated with either QOL or mental health. This study suggests that a negative RSC is associated with worse mental health outcomes. This may detrimentally impact adaptations to deal with CD in the active phase, although patients generally tend to use more common positive strategies. These findings may increase the awareness of health professionals while dealing with spiritual beliefs in patients with CD.

Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice.

BACKGROUND: Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice. RESULTS: Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1ß, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis. CONCLUSION: These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders.

Marginal Fit of Metal-Ceramic Copings: Effect of Luting Cements and Tooth Preparation Design.

PURPOSE: To evaluate the effect of the triad finish line design, axial wall convergence angle, and luting cement on the marginal fit of metal copings used in metal-ceramic crowns. MATERIALS AND METHODS: Schematic dies and their respective copings were cast in NiCr alloy. The dies exhibited the following finish line/convergence angle combinations: sloping shoulder/6°, sloping shoulder/20°, shoulder/6°, shoulder/20°. Marginal fit was evaluated under a stereomicroscope, before and after cementation. Copings were air-abraded with 50 µm Al2 O3 particles and cemented with Cimento de Zinco, RelyX U100, or Panavia F cements (n = 10/group). Data were square-root transformed and analyzed by 3-way factorial random effect model and Tukey's post hoc test (α = 0.05). RESULTS: Statistical analysis showed significance for the interactions finish line and convergence angle (p < 0.05), convergence angle and time (p < 0.001), and luting cement and time (p < 0.001). Sloping shoulder/20° provided the highest marginal discrepancy when compared to the other finish line/convergence angle combinations, which were statistically similar among each other. For both convergence angles and for all luting cements, the marginal discrepancy was significantly higher after cementation. Before and after cementation, 6° provided better marginal fit than 20°. After cementation, Panavia F provided higher marginal discrepancy than Cimento de Zinco. CONCLUSION: Lower convergence angle combined with shoulder and a low-consistency luting cement is preferable to cement metal copings.

A Tomato Tocopherol-Binding Protein Sheds Light on Intracellular α-Tocopherol Metabolism in Plants.

Tocopherols are non-polar compounds synthesized in the plastids, which function as major antioxidants of the plant cells and are essential in the human diet. Both the intermediates and final products of the tocopherol biosynthetic pathway must cross plastid membranes to reach their sites of action. So far, no protein with tocopherol binding activity has been reported in plants. Here, we demonstrated that the tomato SlTBP protein is targeted to chloroplasts and able to bind α-tocopherol. SlTBP-knockdown tomato plants exhibited reduced levels of tocopherol in both leaves and fruits. Several tocopherol deficiency phenotypes were apparent in the transgenic lines, such as alterations in photosynthetic parameters, dramatic distortion of thylakoid membranes and significant variations in the lipid profile. These results, along with the altered expression of genes related to photosynthesis, and tetrapyrrole, lipid, isoprenoid, inositol/phosphoinositide and redox metabolism, suggest that SlTBP may act in conducting tocopherol (or its biosynthetic intermediates) between the plastid compartments and/or at the interface between chloroplast and endoplasmic reticulum membranes, affecting interorganellar lipid metabolism.