Time for What? Dissociating Explicit Timing Tasks through Electrophysiological Signatures.

Estimating durations between hundreds of milliseconds and seconds is essential for several daily tasks. Explicit timing tasks, which require participants to estimate durations to make a comparison (time for perception) or to reproduce them (time for action), are often used to investigate psychological and neural timing mechanisms. Recent studies have proposed that mechanisms may depend on specific task requirements. In this study, we conducted electroencephalogram (EEG) recordings on human participants as they estimated intervals in different task contexts to investigate the extent to which timing mechanisms depend on the nature of the task. We compared the neural processing of identical visual reference stimuli in two different tasks, in which stimulus durations were either perceptually compared or motorically reproduced in separate experimental blocks. Using multivariate pattern analyses, we could successfully decode the duration and the task of reference stimuli. We found evidence for both overlapping timing mechanisms across tasks as well as recruitment of task-dependent processes for comparing intervals for different purposes. Our findings suggest both core and specialized timing functions are recruited to support explicit timing tasks.

Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience.

PURPOSE: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina. PATIENTS Y METHODS: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92). CONCLUSION: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.

Elaboration of guideline for monitoring in relative bioavailability / pharmaceutical bioequivalence study by the sponsor / Elaboração de diretriz para monitoramento em biodisponibilidade relativa / estudo de bioequivalência farmacêutica pelo patrocinador / Elaboración de la directriz para el seguimiento en la biodisponibilidad relativa / estudio de bioequivalencia farmacéutica por parte del promotor

For registration of generic and similar drugs, it is necessary to carry out pharmaceutical equivalence (PE) tests and pharmaceutical bioequivalence (PB). To carry out these tests, duly qualified research centers are contracted, which need to be monitored by the sponsor who is legally responsible for the activities. To this end, it is the recommendation of the Document of the Americas, periodic monitoring to verify compliance with quality requirements, Standard Operating Procedures, Good Clinical Practices (GCP), Good Laboratory Practices (GLP), of the applicable regulatory framework, as well as of compliance with the study protocol. Thus, monitoring is a methodical and documented process to evaluate the degree of adhesion of the center to the planned design for the evaluation of the formulations. To this end, the implementation of a standardized and easily completed guideline is a very important tool to guarantee a consistent evaluation and maintain the organizational memory of the evaluated items by monitors designated by the sponsor, contributing to the constant improvement of the contracted centers and supporting traceability of the studies. This work provided a systemic view of the evidence process related mainly to pharmaceutical bioequivalence, with the monitoring guideline summarizing the items of greatest relevance to be verified.

Para registro de medicamentos genéricos e similares, é necessária a realização de testes de equivalência farmacêutica (EF) e bioequivalência farmacêutica (BF). Para a realização desses testes, são contratados centros de pesquisa devidamente habilitados, que precisam ser monitorados pelo patrocinador legalmente responsável pelas atividades. Há também a recomendação do Documento das Américas de realizar monitoramentos periódicos para verificar o cumprimento dos requisitos de qualidade, Procedimentos Operacionais Padrão, Boas Práticas Clínicas (BPC), Boas Práticas de Laboratório (BPL), de marco regulatório aplicável, bem como de cumprimento do protocolo do estudo. Assim, o monitoramento é um processo metódico e documentado para avaliar o grau de adesão do centro ao desenho planejado para a avaliação das formulações. Para tanto, a implantação de uma diretriz padronizada e de fácil preenchimento é uma ferramenta muito importante para garantir uma avaliação consistente e manter a memória organizacional dos itens avaliados por monitores designados pelo patrocinador, contribuindo para a melhoria constante dos centros contratados e apoiando rastreabilidade dos estudos. Este artigo forneceu uma visão sistêmica do processo de evidência relacionado principalmente à bioequivalência farmacêutica, com a diretriz de monitoramento resumindo os itens de maior relevância a serem verificados.

Para el registro de medicamentos genéricos y similares, es necesario realizar pruebas de equivalencia farmacéutica (EP) y de bioequivalencia farmacéutica (PB). Para llevar a cabo estas pruebas se contratan centros de investigación debidamente cualificados, que deben ser supervisados por el promotor, que es el responsable legal de las actividades. Para ello, es la recomendación del Documento de las Américas, el monitoreo periódico para verificar el cumplimiento de los requisitos de calidad, los Procedimientos Operativos Estándar, las Buenas Prácticas Clínicas (BPC), las Buenas Prácticas de Laboratorio (BPL), del marco regulatorio aplicable, así como del cumplimiento del protocolo del estudio. Así, la monitorización es un proceso metódico y documentado para evaluar el grado de adhesión del centro al diseño previsto para la evaluación de las formulaciones. Para ello, la implantación de una pauta estandarizada y de fácil cumplimentación es una herramienta muy importante para garantizar una evaluación consistente y mantener la memoria organizativa de los elementos evaluados por parte de los monitores designados por el promotor, contribuyendo a la mejora constante de los centros contratados y apoyando la trazabilidad de los estudios. Este trabajo proporcionó una visión sistémica del proceso de evidencia relacionado principalmente con la bioequivalencia farmacéutica, con la pauta de monitoreo que resume los ítems de mayor relevancia a ser verificados.

Active Surveillance of Small Metastatic Lymph Nodes as an Alternative to Surgery in Selected Patients with Low-Risk Papillary Thyroid Cancer: A Retrospective Cohort Study.

Background: It has been suggested that small metastatic lymph nodes (LNs) detected after initial surgery in patients with differentiated thyroid cancer (DTC) can be managed with active surveillance (AS). However, there is still concern regarding the clinical outcomes of these patients. The main aims of our study were as follows: (1) to assess the frequency of growth and the need of additional treatment in a group of patients with LN recurrences selected for AS, and (2) to determine predictive factors of LN progression. Methods: We retrospectively reviewed 856 clinical records from our DTC patient's database (May 2010 to January 2022). Eighty patients had suspicious cervical LNs on consecutive ultrasound (US) after initial surgery, but we included 50 patients with cytological confirmation of metastatic disease and at least 12 months follow-up. Exclusion criteria were as follows: any LN ≥2 cm or multiple LNs ≥1.5 cm in size, proximity to vital structures, PET-positive disease (standard uptake value ≥5), aggressive histology, and distant metastasis. Patients were followed with thyroglobulin (Tg) and thyroglobulin antibodies measurements on suppressive therapy and neck US every 6-12 months. LN growth was defined as an increase of ≥3 mm in any of its diameters. Results: A total of 50 patients had a median age of 41 years (range, 18-75). Most patients were women (80%) and had classical papillary thyroid cancer (86%). The mean size of the LNs was 10.1 ± 4.4 mm. After a median follow-up of 29 months (range, 12-144), 12 patients (24%) had an increase in size of the metastatic LN, 7 (58%) of whom were surgically removed. None of these seven patients had a structural incomplete response at the end of follow-up. The only variable that predicted an increase in LN size was a rise in Tg levels ≥0.5 ng/mL (p = 0.016). Based on a multivariate analysis, patients with increase in Tg levels ≥0.5 ng/mL had a significantly higher chance of developing LN growth (odds ratio [OR] 16.2 [confidence interval, CI 1.5-120.2], p = 0.020). The median progression-free survival rate was 6.6 years [CI 5.6-9.5]. Conclusion: AS of small LNs could be a feasible alternative to immediate surgery in properly selected patients.

Time experience during social distancing: A longitudinal study during the first months of COVID-19 pandemic in Brazil.

Social distancing in response to the COVID-19 pandemic brought several modifications in our daily lives. With these changes, some people have reported alterations in their feelings of how fast time was passing. In this study, we assessed whether and how social distancing and the evolution of the COVID-19 pandemic influenced participants' time awareness and production of time intervals. Participants (n = 3855) filled in the first questionnaire approximately 60 days after the start of social distancing in Brazil and weekly questionnaires for 15 weeks during social distancing. Our results indicate that time was perceived as expanded at the beginning, but this feeling decreased across the weeks. Time awareness was strongly associated with psychological factors such as loneliness, stress, and positive emotions, but not with time production. This relation was shown between participants and within their longitudinal reports. Together, our findings show how emotions are a crucial aspect of how time is felt.

Dynamic risk allows us to adequately select patients with differentiated thyroid cancer who do not require radioiodine treatment.

OBJECTIVE: The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. METHODS: We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). RESULTS: LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). CONCLUSION: This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.

Post-interval EEG activity is related to task-goals in temporal discrimination.

Studies investigating the neural mechanisms of time perception often measure brain activity while participants perform a temporal task. However, several of these studies are based exclusively on tasks in which time is relevant, making it hard to dissociate activity related to decisions about time from other task-related patterns. In the present study, human participants performed a temporal or color discrimination task of visual stimuli. Participants were informed which magnitude they would have to judge before or after presenting the two stimuli (S1 and S2) in different blocks. Our behavioral results showed, as expected, that performance was better when participants knew beforehand which magnitude they would judge. Electrophysiological data (EEG) was analysed using Linear Discriminant Contrasts (LDC) and a Representational Similarity Analysis (RSA) approach to investigate whether and when information about time and color was encoded. During the presentation of S1, we did not find consistent differences in EEG activity as a function of the task. On the other hand, during S2, we found that temporal and color information was encoded in a task-relevant manner. Taken together, our results suggest that task goals strongly modulate decision-related information in EEG activity.

Site-specific framework of sustainable practices for a Brazilian contaminated site case study.

Management of contaminated sites requires application of remediation technologies to reduce environmental and human health risks, but these actions can also produce negative effects, such as energy and natural resources consumption, greenhouse gas emissions, and impacts on local communities. The tenets of sustainability can be used to select sustainable alternatives in the environmental cleanup of these areas to reduce negative consequences and seek new solutions for site reuse. The present study evaluates seven case studies of contaminated sites to identify how sustainable practices were adopted at each site and how environmental, economic and social benefits were achieved. Based on this survey, an in-depth analysis of 48 sustainable management practices was conducted to assess interim actions and institutional controls at a contaminated site located on the campus of University of Sao Paulo (USP) in the city of Sao Paulo, Brazil. The analysis involved a discussion about how future potential improvements to sustainable practices at the site could generate benefits and sustainable gains, such as improvement of quality of life of university students and surrounding communities; reduction of natural resource use, reduction of costs represented by the consumption of water and reduction of demand of potable water for society. The result of this analysis is a site-specific framework of 36 sustainable practices represented by a graphical approach with several examples that can be adopted during assessment and remediation on a case study basis, taking into account the needs and guidelines of the administration of the contaminated site. This approach can easily be adopted by the public and stakeholders who want to apply sustainable practices in other sites. The site-specific framework demonstrates how sustainable principles can be included in the process of contaminated sites management in an integrated process, meeting the needs and expectations of all affected stakeholders.

Dynamic risk allows us to adequately select patients with differentiated thyroid cancer who do not require radioiodine treatment

ABSTRACT Objective: The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. Materials and methods: We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). Results: LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). Conclusions: This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.

Dynamic risk allows us to adequately select patients with differentiated thyroid cancer who do not require radioiodine treatment.

OBJECTIVE: The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. METHODS: We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). RESULTS: LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). CONCLUSION: This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.

Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic

SUMMARY Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic.

Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

Role of 18F-FDG-PET/CT in patients with differentiated thyroid cancer with biochemical incomplete or indeterminate response to treatment / Utilidad de la tomografía por emisión de positrones con 18F-FDG (18F-FDG PET/TC) en pacientes con carcinoma diferenciado de tiroides con respuesta bioquímica incompleta o indeterminada

OBJECTIVES: To assess the value of 18F-FDG-PET/CT for detecting recurrent/persistent disease in patients with biochemical incomplete (BIR) or indeterminate response (IR) and to assess the impact of 18F-FDG-PET/CT on the therapeutic management of these patients. METHODS: The study included patients with BIR, in whom 18F-FDG PET/CT was used within the diagnostic algorithm from our database. Patients with IR referred to our hospital with the 18F-FDG PET/CT already performed were also enrolled. All patients had neck ultrasonography with no structural changes. A change in therapeutic approach was defined as repeat surgery; administration of external beam radiotherapy; and/or the start of systemic therapy. RESULTS: Sixty patients (85% women) aged 18-86 years were enrolled in this retrospective study. Of these, 75% had BIR and 25% IR. Increased FDG uptake suggesting locoregional lesions was seen in 40% of patients. Sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT to detect local disease were 95%, 87.5% and 90% respectively. The therapeutic approach was modified in 50% of patients with locoregional lesions. CONCLUSIONS: Our study confirmed that 18F-FDG-PET/CT is a useful tool for detecting locoregional recurrence in thyroid cancer patients with BIR or IR with conflicting findings in standard diagnostic procedures. In 50% of patients with locoregional lesions, there was an immediate change in the treatment approach

OBJETIVOS: Evaluar la utilidad de la tomografía por emisión de positrones con 18F-FDG (18F-FDG PET/TC) para detectar enfermedad recurrente o persistente en pacientes con respuesta bioquímica incompleta (RBI) o respuesta indeterminada (RI), y evaluar el impacto de los resultados del PET/TC en el manejo terapéutico de estos pacientes. MÉTODOS: Se incluyeron pacientes con RBI, en los cuales el PET/TC fue utilizado en el algoritmo diagnóstico durante el seguimiento, y además pacientes con RI referidos a nuestro hospital con el estudio realizado. Todos los pacientes presentaban ecografía de cuello sin evidencia de alteraciones estructurales. Se consideró como cambio en el enfoque terapéutico a: 1) realización de nuevas cirugías, 2) administración de radioterapia externa, y/o 3) inicio de terapia sistémica. RESULTADOS: Sesenta pacientes con edad entre 16 a 86 años fueron incluidos retrospectivamente (85% mujeres), el 75% con RBI y el 25% con RI. En el 40% de los pacientes el PET/TC evidenciaron lesiones locorregionales. La sensibilidad, la especificidad y la precisión diagnóstica del PET/TC para detectar enfermedad locorregional fue del 95, 87,5 y 90%, respectivamente. En el 50% de los pacientes con enfermedad locorregional los resultados del PET/TC determinaron un cambio en la conducta terapéutica. CONCLUSIONES: Nuestro estudio demostró que el PET/TC es una herramienta útil en la detección de enfermedad locorregional recurrente o persistente en pacientes con cáncer de tiroides con RBI o RI durante el seguimiento con hallazgos contradictorios en los métodos diagnósticos estándares. En el 50% de los casos con lesiones locorregionales hubo un cambio inmediato en el enfoque terapéutico

Correction to: Dynamics of serum antithyroglobulin antibodies in patients with differentiated thyroid cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Thyroid cancer in the Era of COVID-19.

The recent coronavirus infectious disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is placing health systems in serious challenges worldwide. Shocking statistics each day has prompted the World Health Organization to officially declare the COVID-19 outbreak as a pandemic in March 2020. Preliminary studies have shown increased mortality in patients with solid cancers and infection by SARS-CoV-2. Until now, the evidence on the behavior of COVID-19 in patients with a history of thyroid cancer remains scarce, and most of the recommendations given are based on common sense. Therefore, in this viewpoint, we present a brief review of several challenges we are frequently facing during this pandemic and a series of recommendations based on what we have implemented in our clinical practice at a university hospital currently mostly dedicated to COVID-19.

Role of 18F-FDG-PET/CT in patients with differentiated thyroid cancer with biochemical incomplete or indeterminate response to treatment.

OBJECTIVES: To assess the value of 18F-FDG-PET/CT for detecting recurrent/persistent disease in patients with biochemical incomplete (BIR) or indeterminate response (IR) and to assess the impact of 18F-FDG-PET/CT on the therapeutic management of these patients. METHODS: The study included patients with BIR, in whom 18F-FDG PET/CT was used within the diagnostic algorithm from our database. Patients with IR referred to our hospital with the 18F-FDG PET/CT already performed were also enrolled. All patients had neck ultrasonography with no structural changes. A change in therapeutic approach was defined as repeat surgery; administration of external beam radiotherapy; and/or the start of systemic therapy. RESULTS: Sixty patients (85% women) aged 18-86 years were enrolled in this retrospective study. Of these, 75% had BIR and 25% IR. Increased FDG uptake suggesting locoregional lesions was seen in 40% of patients. Sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT to detect local disease were 95%, 87.5% and 90% respectively. The therapeutic approach was modified in 50% of patients with locoregional lesions. CONCLUSIONS: Our study confirmed that 18F-FDG-PET/CT is a useful tool for detecting locoregional recurrence in thyroid cancer patients with BIR or IR with conflicting findings in standard diagnostic procedures. In 50% of patients with locoregional lesions, there was an immediate change in the treatment approach.

Real-life use of lenvatinib in patients with differentiated thyroid cancer: experience from Argentina.

PURPOSE: To describe the experience with radioiodine-resistant differentiated thyroid cancer (RR-DTC) patients treated with lenvatinib in two university hospitals from Argentina. METHODS: Adult patients with a diagnosis of RR-DTC treated with lenvatinib from April 2017 to February 2020 were registered into a retrospective database. Primary objectives were assessment of progression-free survival (PFS) and tumor response evaluated according to RECIST v 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v5.0. RESULTS: Twenty-two patients were treated with lenvatinib, 13 of whom had previously received one or more multikinase inhibitors. Median duration of treatment was 7.1 months (2.2-24). Best overall response was complete response in one patient (4.5%), partial response in seven (31.8%), stable disease in seven (31.8%), and progressive disease in six (27.3%). Median PFS was 13.7 months (95% CI 3.2-24.2). All patients experienced at least one AE. Grade ≥3 AEs were observed in eight (36.4%) patients. Hypertension was the most frequent AE (63.6%) and the most common grade ≥3 AE (22.7%). Definitive withdrawal was necessary in two patients due to recurrent proteinuria (9%). CONCLUSIONS: Tumor responses and PFS in our study were in line with other real-life clinical data and they seem to be inferior to the reported in the SELECT trial, probably related to the higher number of patients with prior MKI therapy, comorbidities, and poor performance status. Although virtually all patients experienced AEs, most of them were manageable and rarely a definitive withdrawal was necessary.

Chemical analysis of the semipurified extract of Paullinia cupana and evaluation of in vitro inhibitory effects against Helicobacter pylori.

Paullinia cupana Kunth, commonly known as guarana, is a native Brazilian plant species from the Amazon area that presents various biological effects, including antimicrobial action. The aim of this study was to chemically analyse the semipurified aqueous extract (AqF) of the plant and to evaluate the activity of crude (CE), ethyl-acetate (EAF), and AqF extracts against Helicobacter pylori. The chemical profile of AqF was determined based on solid analysis 13C-NMR, direct infusion mass spectrometry (ESI-MS), and MALDI-TOF. The 13C-NMR spectrum showed characteristics of flavan-3-ol and oligomeric proanthocyanidins. ESI-MS revealed the presence of procyanidin, caffeic acid and its derivatives. MALDI-TOF analysis detected procyanidins of up to 6 units and profisetinidins of up to 5 units. Whereas CE and EAF showed inhibitory activity against H. pylori, CE, EAF, and AqF presented not high inhibitory activity against urease. The results demonstrate the potential of P. cupana to control and prevent H. pylori infection.

Dynamics of serum antithyroglobulin antibodies in patients with differentiated thyroid cancer.

PURPOSE: Serum antithyroglobulin antibodies (sTgAb) affect the reliability of Tg measurement in patients with thyroid cancer. We compared the outcome of patients with detectable and undetectable sTgAb, stratified according to the initial risk of recurrence (RR); also the response to treatment in patients with detectable sTgAb treated with total thyroidectomy (TT) with and without radioiodine remnant ablation (RA) and the sTgAb trend in the long-term follow-up according to the initial response. METHODS: We included 432 patients submitted to TT, with or without RA; 106 patients had detectable sTgAb levels. Median follow-up was 53 months. RESULTS: There were no statistically significant differences considering presentation between negative or positive sTgAb subjects. The frequency of structural incomplete response (SIR) in low, intermediate, and high RR was similar. Undetectable sTgAb in patients was achieved in a median of 16 months in ablated patients compared with 11 months in those without RA (p = 0.0232). Patients without RA had a higher rate of undetectable sTgAb during the first 12 months. A SIR was observed in 3% of patients with declining sTgAb, in 19% of those with stable levels, and in 43% with increasing sTgAb (p = 0.004). The status of no evidence of disease was achieved more frequently in patients with initial sTgAb levels < 200 mUI/l, independently of the initial RR. CONCLUSIONS: There was no impact of sTgAb on the initial clinical presentation and the response to therapy in low-risk patients treated with or without RA. sTgAb trend is more useful than an absolute value to predict a SIR.

Manufacturing Different Types of Solid Dispersions of BCS Class IV Polyphenol (Daidzein) by Spray Drying: Formulation and Bioavailability.

Daidzein (DZ) is a polyphenolic compound belonging to Biopharmaceutical Classification System class IV, which shows that it may have limited therapeutic effects due to its low solubility and poor bioavailability. This study aimed to obtain high-purity DZ and prepare and characterize different types of solid dispersions (SDs) in order to enhance aqueous solubility and bioavailability. Excipients were investigated in order to manufacture different types of solid dispersions (SDs). Second-generation solid dispersions (SG), third-generation solid dispersions (TG), and second- and third-generation pH-modulated solid dispersions (SD and TG pHM-SD) were produced via spray drying. The SDs were characterized and tested for in vitro DZ release and oral bioavailability. SDs have shown increased aqueous solubility and in vitro release rate. Solid-state characterization showed that DZ was in an amorphous state in most of the formulations. The enhanced aqueous solubility of TG-pHM SD was reflected by an increase in oral bioavailability, which significantly increased the maximum plasma concentration approximately 20-fold and decreased the time to reach the maximum plasma concentration. The production of pHM SDs that contain DZ via spray drying is a simple and effective approach for oral drug delivery, which has the potential to greatly reduce the dose and enhance therapeutics effects.