[Evaluation of Implementation of the HEARTS Initiative in a Rural Community in Venezuela, 2023Avaliação da implementação da iniciativa HEARTS em uma comunidade rural da Venezuela, 2023]. / Evaluación de la implementación de la iniciativa HEARTS en una comunidad rural de Venezuela, 2023.

Objective: To evaluate the implementation of HEARTS strategies in a community in the Bolivarian Republic of Venezuela. Methods: Quasi-experimental study evaluating the cascade of care, driving factors, and maturity and performance indicators four months after implementation of the HEARTS initiative in 52 patients with high blood pressure (BP) in the community of La Marroquina. The data were processed using SPSS® Statistics, version 25.0. Student's t-distribution and chi-square tests were applied to determine statistical significance. Results: Fifty patients, 63.5% of them with a low educational level and low or very low socioeconomic status, completed the four-month monitoring period. At baseline, 11.5% had controlled BP and 40.4% initiated monotherapy. By the fourth month, 100% of patients with high BP had been diagnosed, 92% had received treatment, and 52% had achieved control of their BP. Seventy-two percent were receiving combined therapy. Seventy percent of the hypertensive individuals maintained blood pressure levels <140/90 mmHg. The maturity index score was 4 of 5, and the performance index was classified as incipient. Conclusion: This work shows that, in a short time, a good maturity index was achieved through the implementation, by medical and supervised non-medical personnel, of a standardized protocol for diagnosis, treatment, and monitoring of high blood pressure in a rural population. Rates of diagnosis, treatment, and BP control improved, with incipient performance results. Sustaining this initiative will have a major impact on the health of this population. Its implementation as a national public health policy is recommended.

Objetivo: Avaliar a implementação das estratégias da iniciativa HEARTS em uma comunidade da República Bolivariana da Venezuela. Métodos: Estudo quase-experimental que avaliou a cascata de cuidados, fatores determinantes e índices de maturidade e desempenho quatro meses após a implementação da iniciativa HEARTS na comunidade de La Marroquina, Venezuela. Foram avaliados 52 pacientes com hipertensão arterial. A análise estatística foi realizada no software SPSS®, versão 25.0. O teste t de Student e o teste qui-quadrado foram usados para determinar a significância estatística. Resultados: Cinquenta pacientes completaram o acompanhamento de quatro meses. Desses, 63,5% tinham baixa escolaridade e nível socioeconômico baixo ou muito baixo. No início do estudo, 11,5% apresentavam doença controlada e 40,4% estavam em monoterapia. No quarto mês, 100% dos pacientes com hipertensão arterial haviam sido diagnosticados, 92% haviam recebido tratamento, 52% haviam atingido a meta de controle da hipertensão e 72% estavam recebendo terapia combinada. Dos pacientes com hipertensão, 70% mantinham níveis pressóricos <140 × 90 mmHg. O índice de maturidade foi avaliado como nível 4 (de 5), e o desempenho foi classificado como incipiente. Conclusão: Este estudo demonstra, após pouco tempo, um bom índice de maturidade na implementação de um protocolo padronizado de diagnóstico, tratamento e acompanhamento da hipertensão arterial em uma população rural atendida por pessoal médico e não médico supervisionado. Observa-se melhoria das taxas de diagnóstico, tratamento e controle dos pacientes com hipertensão, demonstrando de forma incipiente seu desempenho. Dar continuidade a essa iniciativa terá uma repercussão importante na saúde dessa população. Recomendando-se que a iniciativa seja implementada como política nacional de saúde pública.

Parthenolide inhibits proliferation and invasion, promotes apoptosis, and reverts the cell-cell adhesion loss through downregulation of NF-κB pathway TNF-α-activated in colorectal cancer cells.

The activation of the nuclear factor-κB (NF-κB) pathway has been associated with the development and progression of colorectal cancer (CRC). Parthenolide (PTL), a well-known inhibitor of the NF-κB pathway, has emerged as an alternative treatment. However, whether PTL activity is tumor cell-specific and dependent on the mutational background has not been defined. This study investigated the antitumor role of PTL after tumor necrosis factor-α (TNF-α) stimulation in various CRC cell lines with different mutational statuses of TP53. We observed that CRC cells displayed different patterns of basal p-IκBα levels; PTL reduced cell viability according to p-IκBα levels and p-IκBα levels varied among the cell lines according to the time of TNF-α stimulation. High concentrations of PTL reduced more effectively p-IκBα levels than low doses of PTL. However, PTL increased total IκBα levels in Caco-2 and HT-29 cells. In addition, PTL treatment downregulated p-p65 levels in HT-29 and HCT-116 cells stimulated by TNF-α in a dose-dependent manner. Moreover, PTL induced cell death via apoptosis and reduced the proliferation rate of TNF-α-treated HT-29 cells. Finally, PTL downregulated the messenger RNA levels of interleukin-1ß, a downstream cytokine of NF-κB, reverted the E-cadherin-mediated disorganization of cell-cell contacts, and decreased the invasion of HT-29 cells. Together, these results suggest a differential antitumoral activity of PTL on CRC cells with different mutational statuses of TP53, modulating cell death, survival, and proliferation underlying the NF-κB pathway TNF-α-induced. Therefore, PTL has emerged as a potential treatment for CRC in an inflammatory NF-κB-dependent manner.

AC-PLT: An algorithm for computer-assisted coding of semantic property listing data.

In this paper, we present a novel algorithm that uses machine learning and natural language processing techniques to facilitate the coding of feature listing data. Feature listing is a method in which participants are asked to provide a list of features that are typically true of a given concept or word. This method is commonly used in research studies to gain insights into people's understanding of various concepts. The standard procedure for extracting meaning from feature listings is to manually code the data, which can be time-consuming and prone to errors, leading to reliability concerns. Our algorithm aims at addressing these challenges by automatically assigning human-created codes to feature listing data that achieve a quantitatively good agreement with human coders. Our preliminary results suggest that our algorithm has the potential to improve the efficiency and accuracy of content analysis of feature listing data. Additionally, this tool is an important step toward developing a fully automated coding algorithm, which we are currently preliminarily devising.

Optimization of the Production Factors of Boards Obtained from Arundo donax L. Fibers Without Added Adhesives.

The main objective of this work was to further analyze the optimization of the production factors of Arundo donax L. fiberboards obtained without adhesives. The production of boards derived from Arundo donax L. without added adhesives and with high mechanical performance has already been demonstrated. This present study explored a modification in the production process through a final curing thermal treatment (final heat treatment, FHT). Since pressing time is an influential factor in the production cost, it is expected that curing allows a reduction of this time. This study compared the results obtained by three panel-production alternatives: long pressing time (tp) without curing and long and short tp with FHT. Of the two factors analyzed, pressing pressure (Pp) was the most important production factor in both the modulus of elasticity (MOE) and modulus of rupture (MOR), while curing was the most important factor for the internal bond (IB). The study shows that a FHT facilitates the distribution of lignin and a possible improvement in the quantity and quality of bonds between lignin and cellulosic fibers. As a consequence, it improves the IB, produces boards with more homogeneous physical and mechanical properties and thereby makes them more hydrophobic. The curing thermal treatment allows high performance panels to be obtained in a manner which is more ecological, quicker, and cheaper.

Quantitative Assessment of Individual Populations Present in Nanoparticle-Antibody Conjugate Mixtures Using AF4-ICP-MS/MS.

A current remaining challenge in nanotechnology is the fast and reliable determination of the ratios between engineered nanoparticles and the species attached to their surface after chemical functionalization. The approach proposed herein based on the online coupling of asymmetric flow field-flow fractionation (AF4) with inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS) allows for the first time the direct determination of such ratios in CdSe/ZnS core-shell quantum dot:rat monoclonal IgG2a antibody (QD:Ab) conjugate mixtures in a single run without any previous sample preparation (i.e., derivatization). AF4 provides full recovery and adequate resolution of the resulting bioconjugate from the excess of nanoparticles and proteins used in the different bioconjugation mixtures (1:1, 2:1, and 3:1 QD:Ab molar ratios were assessed). The point-by-point determination by ICP-MS/MS of the metal to sulfur ratios along the bioconjugate fractographic peak allowed disclosing the mixture of the different species in the bioconjugated sample, providing not only the limits of the range of QD:Ab ratios in the different bioconjugate species resulting after functionalization but also a good estimation of their individual relative abundance in the mixture. Interestingly, a wide variety of compositions were observed for the different bioconjugate mixtures studied (QD:Ab molar ratios ranging from 0.27 to 4.6). The resulting weighted QD:Ab ratio computed in this way for each bioconjugate peak matches well with both the global (average) QD:Ab ratio experimentally obtained by the simpler peak area ratio computation and the theoretical QD:Ab molar ratios assayed, which internally validates the procedure developed.

Apert syndrome without craniosynostosis.

BACKGROUND: Apert syndrome is a rare form of syndromic craniosynostosis, also known as acrocephalosyndactyly, which is a disorder characterized by a unique set of craniofacial, hand, and foot abnormalities. Diagnosis is made through a genetic analysis, where the mutation of FGFR2, Ser252Trp, and Pro253Arg confirms the diagnosis. CASE PRESENTATION: Although craniosynostosis is the most common characteristic in clinical presentation, we present an atypical case of a one-and-a-half-year-old girl with Apert syndrome confirmed by genetic testing but without craniosynostosis.

Controlling Ligand Surface Density on Streptavidin-Magnetic Particles by a Simple, Rapid, and Reliable Chemiluminescent Test.

The use of functionalized magnetic particles is increasing because they simplify the analytical process and yield promising results in a wide range of applications. Particularly, streptavidin-coated magnetic beads offer the possibility of rapid and very efficient grafting of biomolecules. Unfortunately, current methods to monitor and compute this grafting process are cumbersome and scarce. We describe herein a simple, rapid, and reliable chemiluminescent assay we have developed to check the grafting rate of functionalized magnetic beads. The power of the assay also relies on its ability to predict the amount of ligands required to obtain a precise grafting rate. In addition, results were correlated with a more general parameter in material functionalization characterization like surface ligand density. Finally, the assay was validated for a wide variety of biotinylated biomolecule sizes, ranging from small molecules (around 200 Da) to antibodies (around 150 kDa). This approach will allow a precise quantification and prediction of the functionalization of magnetic particles that is of enormous importance for quality control in many applications.

All-lignocellulosic Fiberboard from Steam Exploded Arundo Donax L.

This paper explores the possibility of producing all-lignocellulosic fiberboards from Arundo donax L. as a source of lignocellulosic fibers with no synthetic binders. This raw material was steam exploded with a thermomechanical aqueous vapor process in a batch reactor. The Arundo donax raw material and its obtained pulp were characterized in terms of chemical composition and the results were compared to other lignocellulosic materials. The chemical composition of steam exploded Arundo fibers showed high cellulose and a moderate lignin content suggesting it was a good raw material for fiberboard production. The all-lignocellulosic fiberboards were produced on laboratory scale; using the steam exploded Arundo donax by means of a wet process. The effects of pressing pressure on physical and mechanical properties were evaluated and the conditions that optimize the responses were found. The analyzed properties were density (d); water absorption (WA); thickness swelling (TS); modulus of elasticity (MOE); modulus of rupture (MOR); and internal bond strength (IB). The tested levels of the pressing pressure range from 0.35 to 15 MPa. The optimum IB; MOE; MOR; WA and TS were 1.28 MPa, 7439 MPa, 40.4 MPa, 17.6% and 13.3%, respectively. The obtained fiberboards were of very good quality and more than satisfy the requirements of the relevant standard specifications.

Deproteinization assessment using isotopically enriched compounds to trace the coprecipitation of low-molecular-weight selenium species with proteins.

Studies have shown that information related to the presence of low-molecular-weight metabolites is frequently lost after deproteinization of complex matrices, such as blood and plasma, during sample preparation. Therefore, the effect of several deproteinization reagents on low-molecular-weight selenium species has been compared by species-specific isotope labeling. Two isotopically enriched selenium tracers were used to mimic models of small inorganic anionic (77Se-selenite) and organic zwitterionic (76Se-selenomethionine) species. The results presented here show that the use of a methanol-acetonitrile-acetone (1:1:1 v/v/v) mixture provided approximately two times less tracer loss from plasma samples in comparison with the classic procedure using acetonitrile, which may not be optimal as it leads to important losses of low-molecular-weight selenium species. In addition, the possible interactions between selenium tracers and proteins were investigated, revealing that both coprecipitation phenomena and association with proteins were potentially responsible for selenite tracer losses during protein precipitation in blood samples. However, coprecipitation phenomena were found to be fully responsible for losses of both tracers observed in plasma samples and of the selenomethionine tracer in blood samples. This successfully applied strategy is anticipated to be useful for more extensive future studies in selenometabolomics.

Comparative study between open and minimally invasive approach in the surgical management of esophageal leiomyoma.

INTRODUCTION: Leiomyomas are the most common benign tumors of the esophagus. Although classically surgical enucleation through thoracotomy or laparotomy has been widely accepted as treatment of choice, development of endoscopic and minimally invasive procedures has completely changed the surgical management of these tumors. MATERIAL AND METHODS: We performed a retrospective review of all esophageal leiomyoma operated at Hospital Universitario Ramón y Cajal (Madrid, Spain) between January 1986 and December 2014, analyzing patients' demographic data, symptomatology, tumor size and location, diagnostic tests, surgical data, complications and postoperative stay. RESULTS: Thirteen patients were found within that period, 8 men and 5 women, with a mean age of 53.62 years (range 35-70 years). Surgical enucleation was achieved in all patients. In 8 cases (61.54%) a thoracic approach was performed (4 thoracotomies and 4 thoracoscopies), and in 5 cases (38.56%) an abdominal approach was performed (3 laparotomies and 2 laparoscopies); enucleation was carried out through a minimally invasive approach in 6 patients (46.15%). There were no cases of endoscopic resection alone. Surgery mean length was 174.38 minutes (range 70-270 minutes) and median postoperative stay was 6.5 days (range 2-27 days). There was neither mortality nor cases of intraoperative complications were described. No postoperative major complications were reported; however one patient presented important pain in his right hemithorax that required management and long term follow-up by the Pain Management Unit. With a mean follow-up of 165.57 months (median 170; range 29-336 months) no recurrences were reported. CONCLUSION: Enucleation is the treatment of choice for the majority of esophageal leiomyomas. In our experience, duration of the surgical procedure through minimally invasive approach was longer than surgery through open approach; however, postoperative stay was shorter in the first group. Paradoxically, incision pain after surgery (thoracic neuralgia) was found to be higher in the minimally invasive approach group. Nevertheless, none of the results obtained in the study reached statistical significance, probably due to the small simple size.

Duodenal fistula after gastrectomy: Retrospective study of 13 new cases.

INTRODUCTION: Duodenal stump fistula (DSF) after gastrectomy has a low incidence but a high morbidity and mortality, and is therefore one of the most aggressive and feared complications of this procedure. MATERIAL AND METHODS: We retrospectively evaluated all DSF occurred at our hospital after carrying out a gastrectomy for gastric cancer, between January 1997 and December 2014. We analyzed demographic, oncologic, and surgical variables, and the evolution in terms of morbidity, mortality and hospital stay. RESULTS: In the period covered in this study, we performed 666 gastrectomies and observed DSF in 13 patients (1.95%). In 8 of the 13 patients (61.5%) surgery was the treatment of choice and in 5 cases (38.5%) conservative treatment was carried out. Postoperative mortality associated with DSF was 46.2% (6 cases). In the surgical group, 3 patients developed severe sepsis with multiple organ failure, 2 patients presented a major hematemesis which required endoscopic haemostasis, 1 patient had an evisceration and another presented a subphrenic abscess requiring percutaneous drainage. Six patients (75%) died despite surgery, with 3 deaths in the first 24 hours of postoperative care. The 2 patients who survived after the second surgical procedure had a hospital stay of 45 and 84 days respectively. In the conservative treatment group the cure rate was 100% with no significant complications and an average postoperative hospital stay of 39.5 days (range, 26-65 days). CONCLUSION: FMD is an unusual complication but it is associated with a high morbidity and mortality. In our experience, conservative management has shown better results compared with surgical treatment.

The predictive model of hydrobiological diversity in the Asana-Tumilaca basin, Peru based on water physicochemical parameters and sediment metal content.

The hydrobiological diversity in the basin depends on biotic and abiotic factors. A predictive model of hydrobiological diversity for periphyton and macrobenthos was developed through multiple linear regression analysis (MLRA) based on the physicochemical parameters of water (PPW) and metal content in sediments (MCS) from eight monitoring stations in the Asana-Tumilaca Basin during the dry and wet seasons. The electrical conductivity presented values between 47.9 and 3617 µS/cm, showing the highest value in the Capillune River due to the influence of geothermal waters. According to Piper's diagram, the water in the basin had a composition of calcium sulfate and calcium bicarbonate-sulfate. According to the Wilcox diagram, the water was found to be between good and very good quality, except for in the Capillune River. The Shannon-Wiener diversity indices (H') were 2.62 and 2.88 for periphyton, and 2.10 and 2.44 for macrobenthos, indicating moderate diversity; for the Pielou's evenness index (J'), they were 0.68 and 0.70 for periphyton, and 0.68 and 0.59 for macrobenthos, indicating similar equity, in the dry and wet seasons, respectively, for both indices. In the model there were three cases, where the first two cases only worked with PPW or MCS, and case 3 worked with PPW and MCS. For case 3, the predicted values for H' and J' of periphyton and macrobenthos concerning those observed presented correlation coefficients of 0.7437 and 0.6523 for periphyton and 0.9321 and 0.8570 for macrobenthos, respectively, which were better than those of cases 1 and 2. In addition, principal component analysis revealed that the As, Pb, and Zn contents in the sediments negatively influenced the diversity, uniformity, and richness of the macrobenthos. In contrast, Cu and Cr had positive impacts because of the adaptation processes.

Application of the galactomannan gel from Cassia grandis seeds for biomedical purposes: Study of the incorporation of collagenases and their release profile.

The galactomannan-based gel from Cassia grandis seeds was used to incorporate Penicillium sp. UCP 1286 and commercial collagenases. Experiments were carried out according to a 23-full factorial design to identify the most significant parameters for the incorporation process. The pH of the incorporation solution (pHi), stirring time (t), and initial protein concentration in the crude extract (PCi) were selected as the three independent variables, and the efficiency of collagenase incorporation (E) and collagenolytic activity (CA) after 360 min as the responses. pHi and PCi showed positive statistically significant effects on E, while CA was positively influenced by pHi and t, but negatively by PCi. The fungi collagenase was released from the gel following a pseudo-Fickian behavior. Additionally, no <76 % of collagenase was efficiently incorporated into the gel retaining a high CA (32.5-69.8 U/mL). The obtained results for the commercial collagenase (E = 93.88 %, CA = 65.8 U/mL, and n = 0.10) demonstrated a pseudo-Fickian behavior similar to the fungi-collagenase. The results confirm the biotechnological potential of the gel as an efficient matrix for the incorporation of catalytic compounds; additionally, the incorporation of collagenases was achieved by retaining the proteases CA and releasing them in a controlled manner.

Approaching Self-Bonded Medium Density Fiberboards Made by Mixing Steam Exploded Arundo donax L. and Wood Fibers: A Comparison with pMDI-Bonded Fiberboards on the Primary Properties of the Boards.

This study presents an unexplored method to produce formaldehyde-free MDF. Steam exploded Arundo donax L. (STEX-AD) and untreated wood fibers (WF) were mixed at different mixing rates (0/100, 50/50, and 100/0, respectively) and two series of boards were manufactured, with 4 wt% of pMDI, based on dry fibers, and self-bonded. The mechanical and physical performance of the boards was analyzed as a function of the adhesive content and the density. The mechanical performance and dimensional stability were determined by following European standards. The material formulation and the density of the boards had a significant effect on both mechanical and physical properties. The boards made solely of STEX-AD were comparable to those made with pMDI, while the panels made of WF without adhesive were those that performed the worst. The STEX-AD showed the ability to reduce the TS for both pMDI-bonded and self-bonded boards, although leading to a high WA and a higher short-term absorption for the latter. The results presented show the feasibility of using STEX-AD in the manufacturing of self-bonded MDF and the improvement of dimensional stability. Nonetheless, further studies are needed especially to address the enhancement of the internal bond (IB).

Particles' Organization in Direct Oil-in-Water and Reverse Water-in-Oil Pickering Emulsions.

This paper addresses the impact of the particle initial wetting and the viscosity of the oil phase on the structure and rheological properties of direct (Oil/Water) and reverse (Water/Oil) Pickering emulsions. The emulsion structure was investigated via confocal microscopy and static light scattering. The flow and viscoelastic properties were probed by a stress-controlled rheometer. Partially hydrophobic silica particles have been employed at 1 and 4 wt.% to stabilize dodecane or paraffin-based emulsions at 20 vol.% of the dispersed phase. W/O emulsions were obtained when the particles were dispersed in the oily phase while O/W emulsions were prepared when the silica was introduced in the aqueous phase. We demonstrated that, although the particles adsorbed at the droplets interfaces for all the emulsions, their organization, the emulsion structure and their rheological properties depend in which phase they were previously dispersed in. We discuss these features as a function of the particle concentration and the oil viscosity.

Yeast-amoeba interaction influences murine cryptococcosis.

The virulence of Cryptococcus spp. is modulated in the natural environment through interaction with abiotic and biotic factors, and this can occasionally have implications for the progression of cryptococcosis in mammals. Hence, we evaluated whether the prior interaction of highly virulent Cryptococcus gattii strain R265 with Acanthamoeba castellanii influenced the progression of cryptococcosis. The influence of the capsule on endocytosis was evaluated using amoeba and yeast morphometrics. Mice were intratracheally infected with yeast re-isolated from the amoeba (Interaction), yeast without prior contact with the amoeba (Non-Interaction), or sterile phosphate-buffered saline (SHAM). Morbidity signs and symptoms were monitored during the survival curve, while cytokine and fungal burden measurements and histopathological analysis were performed on the 10th day post infection. Morbidity and mortality parameters in experimental cryptococcosis were influenced by the prior interaction of yeast with amoeba, which led to phenotypic changes in the cryptococcal cells, polysaccharide secretion, and their tolerance to oxidative stress. Our results suggest that a prior yeast-amoeba interaction modulates yeast virulence, which is associated with a greater tolerance to oxidative stress related to the exo-polysaccharide content and influences the progression of cryptococcal infection.

Characterization of the myenteric neuronal population and subpopulation of the duodenum of adult wistar rat fed with hypoproteic chow.

The effects of severe protein malnutrition (4%) on myenteric neurons of Wistar rat duodenum, in relation to a standard 22%-protein diet for rodents, were assessed in this study. Segments of the duodenum from 10 rats from each nutritional group were submitted to the elaboration of whole mounts - 5 stained with Giemsa to determine the total population of myenteric neurons and the others stained by a histochemical method to detect nervous cells through the NADPH-diaphorase enzyme activity for studying the subpopulation of nitrergic neurons. The area of 100 neurons per animal, totalizing 2,000 neurons, were randomly measured by using the Image Pro-Plus(®)software. Malnourished rats presented 34.38% lower body weight and 10.60% duodenum length reduction when compared to the control group. Quantitative analysis demonstrated no significant differences between control and malnourished group by using Giemsa; however, as the organ reduction was not followed by an increase inversely proportional to the density of neurons, the condition imposed suggests the loss of neurons from the total population. Nevertheless, through NADPH-d histochemistry, there was a neuronal density increase for the malnourished group. There was no significant difference between the groups for both techniques with respect to the morphometric analysis of the body cell.

Pharmacist prescribing: a review of perceptions and attitudes of patients, pharmacists and other interested professionals. / Prescrição farmacêutica: uma revisão sobre percepções e atitudes de pacientes, farmacêuticos e outros interessados.

Pharmacist prescribing is a growing reality in some developed counties, with varied health systems. Understanding the contribution that this activity can offer in the healthcare process, and investigating its acceptance is of utmost importance for the countries that implement and regulate this type of system. This literature review aimed to design a state-of-the-art academic investigation on the perception, opinions, and attitudes in the context of pharmacist prescribing practices in countries that have adopted this system. To achieve this, the present study conducted an investigation of the Medline, Scopus, Embase, SciELO, and Lilacs databases, resulting in the selection of 17 studies. From the analysis of the articles, three categories of discussion arose: "understanding of the practice and perceived benefits", "acceptance and adherence to the practice, and "hindrances to the practice". The results showed varied acceptance and perceptions among the different publics, depending, among other questions, on the level of knowledge and experience of the patients and health professionals, on the profile of the pharmacists, or on the prescribing modality. This study highlights some challenges involved in the practice of pharmacist prescribing, and its findings can be useful in suggesting a means through which to strengthen the practice.

A prescrição farmacêutica é uma experiência em expansão em alguns países desenvolvidos, com diferentes sistemas de saúde. Conhecer a contribuição que essa atividade pode desempenhar no processo de assistência à saúde e investigar sua aceitação é de fundamental interesse para os países que a regularam. Este estudo de revisão de literatura, portanto, objetivou desenhar o estado da arte da investigação acadêmica sobre percepção, opiniões e atitudes no contexto da prática da prescrição farmacêutica em países que a adotaram. Para isso, realizou-se investigação nas bases de dados MEDLINE, Scopus, Embase, SciELO e LILACS, resultando na seleção de 17 estudos. Da análise dos artigos, emergiram três categorias de discussão: "compreensão da prática e benefícios percebidos"; "aceitação e adesão à prática"; "barreiras à prática". Os resultados mostraram aceitação e percepções variáveis nos diferentes públicos, dependendo, entre outras questões, do nível de conhecimento e experiência dos pacientes e dos profissionais de saúde, do perfil do farmacêutico ou da modalidade de prescrição. Este estudo aponta alguns desafios envolvidos na prática da prescrição farmacêutica e seus achados podem ser úteis para sugerir caminhos para o fortalecimento da prática.

Long-term resistance to 5-fluorouracil promotes epithelial-mesenchymal transition, apoptosis evasion, autophagy, and reduced proliferation rate in colon cancer cells.

The drug, 5-fluorouracil (5FU) is a standard first-line treatment for colorectal cancer (CRC) patients. However, drug resistance acquisition remains an important challenge for effective clinical outcomes. Here, we established a long-term drug-resistant CRC model and explored the cellular events underlying 5FU resistance. We showed that 5FU-treated cells (HCT-116 5FUR) using a prolonged treatment protocol were significantly more resistant than parental cells. Likewise, cell viability and IC50 values were also observed to increase in HCT-116 5FUR cells when treated with increasing doses of oxaliplatin, indicating a cross-resistance mechanism to other cytotoxic agents. Moreover, HCT-116 5FUR cells exhibited metabolic and molecular changes, as evidenced by increased thymidylate synthase levels and upregulated mRNA levels of ABCB1. HCT-116 5FUR cells were able to overcome S phase arrest and evade apoptosis, as well as activate autophagy, as indicated by increased LC3B levels. Cells treated with low and high doses displayed epithelial-mesenchymal transition (EMT) features, as observed by decreased E-cadherin and claudin-3 levels, increased vimentin protein levels, and increased SLUG, ZEB2 and TWIST1 mRNA levels. Furthermore, HCT-116 5FUR cells displayed enhanced migration and invasion capabilities. Interestingly, we found that the 5FU drug-resistance gene signature is positively associated with the mesenchymal signature in CRC samples, and that ABCB1 and ZEB2 co-expressed at high levels could predict poor outcomes in CRC patients. Overall, the 5FU long-term drug-resistance model established here induced various cellular events, and highlighted the importance of further efforts to identify promising targets involved in more than one cellular event to successfully overcome drug-resistance.