Clinical reasoning pattern used in oral health problem solving - A case study in Indonesian undergraduate dental students.

BACKGROUND: Health professionals are known to use various combinations of knowledge and skills, such as critical thinking, clinical reasoning, clinical judgment, problem-solving, and decision-making, in conducting clinical practice. Clinical reasoning development is influenced by knowledge and experience, the more knowledge and experience, the more sophisticated clinical reasoning will be. However, clinical reasoning research in dentistry shows varying results . AIMS: This study aims to observe the clinical reasoning pattern of undergraduate dental students when solving oral health problems, and their accordance with their knowledge acquisition. MATERIAL AND METHODS: This qualitative study employed the think-aloud method and the result was assessed through verbal protocol analyses. Five respondents from final year dental undergraduate students were agreed to participate. A unique hypothetical clinical scenario was used as a trigger. The audio data were transcribed, interpreted, and categorized as a clinical reasoning pattern; and the concept maps created were assessed by a Structure of Learning Outcomes (SOLO) taxonomy as knowledge acquisition. RESULTS: Observations on clinical reasoning patterns and the level of knowledge acquisition in five undergraduate dental students showed varying results. They applied clinical reasoning patterns according to their knowledge acquisition during didactical phase. Learners with inadequate knowledge relied on guessing, meanwhile learners with adequate knowledge applied more sophisticated reasoning pattern when solving problems. CONCLUSIONS: Various problem-solving strategies were encountered in this study, which corresponded to the level of knowledge acquisition. Dental institutions must set minimum standards regarding the acquisition of conceptual knowledge accompanied by improvement of clinical reasoning skills, as well as refinement of knowledge and procedural skills.

Structure of the EphB6 receptor ectodomain.

Eph receptors are the largest group amongst the receptor tyrosine kinases and are divided into two subgroups, A and B, based on ligand binding specificities and sequence conservation. Through ligand-induced and ligand-independent activities, Ephs play central roles in diverse biological processes, including embryo development, regulation of neuronal signaling, immune responses, vasculogenesis, as well as tumor initiation, progression, and metastasis. The Eph extracellular regions (ECDs) are constituted of multiple domains, and previous structural studies of the A class receptors revealed how they interact with ephrin ligands and simultaneously mediate Eph-Eph clustering necessary for biological activity. Specifically, EphA structures highlighted a model, where clustering of ligand-bound receptors relies on two distinct receptor/receptor interfaces. Interestingly, most unliganded A class receptors also form an additional, third interface, between the ligand binding domain (LBD) and the fibronectin III domain (FN3) of neighboring molecules. Structures of B-class Eph ECDs, on the other hand, have never been reported. To further our understanding of Eph receptor function, we crystallized the EphB6-ECD and determined its three-dimensional structure using X-ray crystallography. EphB6 has important functions in both normal physiology and human malignancies and is especially interesting because this atypical receptor innately lacks kinase activity and our understanding of the mechanism of action is still incomplete. Our structural data reveals the overall EphB6-ECD architecture and shows EphB6-LBD/FN3 interactions similar to those observed for the unliganded A class receptors, suggesting that these unusual interactions are of general importance to the Eph group. We also observe unique structural features, which likely reflect the atypical signaling properties of EphB6, namely the need of co-receptor(s) for this kinase-inactive Eph. These findings provide new valuable information on the structural organization and mechanism of action of the B-class Ephs, and specifically EphB6, which in the future will assist in identifying clinically relevant targets for cancer therapy.

Therapeutic potential of targeting the Eph/ephrin signaling complex.

The Eph-ephrin signaling pathway mediates developmental processes and the proper functioning of the adult human body. This distinctive bidirectional signaling pathway includes a canonical downstream signal cascade inside the Eph-bearing cells, as well as a reverse signaling in the ephrin-bearing cells. The signaling is terminated by ADAM metalloproteinase cleavage, internalization, and degradation of the Eph/ephrin complexes. Consequently, the Eph-ephrin-ADAM signaling cascade has emerged as a key target with immense therapeutic potential particularly in the context of cancer. An interesting twist was brought forth by the emergence of ephrins as the entry receptors for the pathological Henipaviruses, which has spurred new studies to target the viral entry. The availability of high-resolution structures of the multi-modular Eph receptors in complexes with ephrins and other binding partners, such as peptides, small molecule inhibitors and antibodies, offers a wealth of information for the structure-guided development of therapeutic intervention. Furthermore, genomic data mining of Eph mutants involved in cancer provides information for targeted drug development. In this review we summarize the distinct avenues for targeting the Eph-ephrin signaling pathway, including its termination by ADAM proteinases. We highlight the latest developments in Eph-related pharmacology in the context of Eph-ephrin-ADAM-based antibodies and small molecules. Finally, the future prospects of genomics- and proteomics-based medicine are discussed.

Dose-response study for the highly aggressive and metastatic primary F3II mammary carcinoma under direct current.

Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumor's long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. 39:460-475, 2018. © 2018 Wiley Periodicals, Inc.

Clickable prodrugs bearing potent and hydrolytically cleavable nicotinamide phosphoribosyltransferase inhibitors.

PURPOSE: Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl)-7-(4'-(trans-3″-(3'″-pyridyl)acrylamido)butyl)-1,7-dicarbadodecaborane (hm-MC4-PPEA), was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt). Nampt has been shown to be upregulated in most cancers and is a promising target for the treatment of many different types of cancers, including breast cancers. PATIENTS AND METHODS: To increase the selectivity of hm-MC4-PPEA toward cancer cells, three prodrugs were synthesized with different hydrolyzable linkers: ester, carbonate, and carbamate. Using click chemistry a fluorophore was attached to these prodrugs to act as a model for our conjugation strategy and to serve as an aid for prodrug stability studies. The stabilities of these drug conjugates were tested in phosphate-buffered saline (PBS) at normothermia (37°C) using three different pH levels, 5.5, 7.5, and 9.5, as well as in horse serum at physiological pH. The stability of each was monitored using reversed-phase HPLC equipped with both diode array and fluorescence detection. The inhibitory activity of hm-MC4-PPEA was also measured using a commercially available colorimetric assay. The biological activities of the drug conjugates as well as those of the free drug (hm-MC4-PPEA), were evaluated using the MTT assay against the human breast cancer cell lines T47D and MCF7, as well as the noncancerous, transformed, Nampt-dependent human breast epithelium cell line 184A1. RESULTS: hm-MC4-PPEA showed to be a potent inhibitor of recombinant Nampt activity, exhibiting an IC50 concentration of 6.8 nM. The prodrugs showed great stability towards hydrolytic degradation under neutral, mildly acidic and mildly basic conditions. The carbamate prodrug also showed to be stable in rat serum. However, the carbonate and the ester prodrug release at various rates in serum presumably owing to the presence of several different classes of esterase. The biological activities of the drug conjugates correlate with the stability of their cleavable linkers observed in serum. CONCLUSION: The targeted and selective delivery of potent Nampt inhibitors to cancer cells is a potentially new route for the treatment of many cancers. These prodrugs linked to small cancer-associated peptides may be optimum for their use as targetable Nampt inhibitors.

Improved synthesis of MC4-PPEA and the biological evaluation of its hydroxymethyl derivative.

Nicotinamide phosphoribosyltransferase (Nampt) is an intriguing target for the treatment of many diseases, including cancer. Previously, our group demonstrated that carborane clusters may be used to increase the potency of small molecule inhibitors of Nampt over other, similarly sized organic moieties. Herein, we report a greatly improved, gram-scale synthesis of our most potent agent: 1-(4'-(trans-3″-(3‴-pyridyl) acrylamide)butyl)-1,7-dicarba-closo-dodecaborane (MC4-PPEA). Additionally, the carborane moiety of the molecule has been modified with a hydroxymethyl functional group to allow for its covalent attachment to targeted prodrugs, the synthesis of which are underway. Using cell viability assays, we demonstrate that this new derivative exhibits low, to mid-nanomolar potencies against human breast cancer cell lines in vitro.

Glial cells modulate heparan sulfate proteoglycan (HSPG) expression by neuronal precursors during early postnatal cerebellar development.

Cerebellum controls motor coordination, balance, eye movement, and has been implicated in memory and addiction. As in other parts of the CNS, correct embryonic and postnatal development of the cerebellum is crucial for adequate performance in the adult. Cellular and molecular defects during cerebellar development can lead to severe phenotypes, such as ataxias and tumors. Knowing how the correct development occurs can shed light into the mechanisms of disease. Heparan sulfate proteoglycans are complex molecules present in every higher eukaryotic cells and changes in their level of expression as well as in their structure lead to drastic functional alterations. This work aimed to investigate changes in heparan sulfate proteoglycans expression during cerebellar development that could unveil control mechanisms. Using real time RT-PCR we evaluated the expression of syndecans, glypicans and modifying enzymes by isolated cerebellar granule cell precursors, and studied the influence of soluble glial factors on the expression of those genes. We evaluated the possible involvement of Runx transcription factors in the response of granule cell precursors to glial factors. Our data show for the first time that cerebellar granule cell precursors express members of the Runx family and that the expression of those genes can also be controlled by glial factors. Our results also show that the expression of all genes studied vary during postnatal development and treatment of precursors with glial factors indicate that the expression of heparan sulfate proteoglycan genes as well as genes encoding heparan sulfate modifying enzymes can be modulated by the microenvironment, reflecting the intricate relations between neuron and glia.

O cotidiano de crianças infectadas pelo HIV no adolescer: compromissos e possibilidades do cuidado de si / The daily life of infected dy HIV in the process of becoming adolescent: compromise and possibilities to the care for themselves

Introdução: as crianças com aids por transmissão vertical transitam da infância para a adolescência, e pouco se sabe sobre como cuidam de si. Objetivo: compreender as possibilidades de cuidado de si no cotidiano do adolescer com aids. Métodos: foram depoentes: 11 adolescentes não institucionalizados, de 12 a 14 anos, que conheciam seu diagnóstico, atendidos em três HU/RJ. O projeto obteve aprovação de todos os CEP. Utilizou-se a entrevista fenomenológica e a análise hermenêutica heideggeriana. Resultados: desde que acharam o "negócio no sangue" têm que tomar remédio todos os dias, várias vezes e sempre, e não sabem se um dia poderão parar. Com a descoberta de que possuem o "vírus", compreenderam que têm de cuidar da saúde para continuar vivendo, irem sozinhos às consultas hospitalares, fazerem exames e controlarem seu tratamento. Por conta da adolescência, precisam trocar de doutores quesão legais. Precisam tomar o remédio do modo certo para terem saúde, imunidade, e evitarem doenças ou coisas mais graves. Estão cansados do tamanho ruim dos comprimidos e da interferência no dia a dia. Alguns tomam os comprimidos sozinhos, mas fazer o tratamento é difícil, então precisam de ajuda de alguém. Alguns nunca pararam o tratamento, outros o fi zeram por orientação médica ou por conta própria. Justifi cam: não aceitam o "problema". Sabem que a alimentação e os exercícios ajudam no tratamento. Conclusão: a transmissão vertical do HIV determinou uma necessidade especial na sua saúde: a dependência da tecnologia medicamentosa. Essa facticidade envolve a criança em uma rede de cuidados profissional e familiar. Durante a infância, necessitam integralmente dos cuidados prestados pelos familiares e, na transição da infância para a adolescência, passam a compreender a necessidade decuidar de si, a partir de suas responsabilidades "com-sigo" e da ajuda familiar. Assim, as crianças revelam-se no movimento de ser-cuidado-por para sercuidado-com.

Introduction: children with vertical transmission HIV/aids pass from childhood to adolescence and little is known about how they care about themselves. Objective: understand the possibilities of the care for oneself in the daily life of adolescents with aids. Methods: phenomenological interview was developed with 11 non-institutionalized 12-14 year-old-boys and girls with disclosed diagnosis from Brazilian teaching hospitals. The project was approved by the Ethics Review Committees. Heiddeger"s hermeneutic analyzes was applied. Results: since that "thing in the blood" was found they have to take medication everyday, many times and ever. When they discovered about the "virus" , they understood that they had to take care of their health to continue alive, to go alone to consultation, to take medical exams and have control about their treatment. Due to adolescence they have to change doctors. They have to take medication in the right way to be healthy, to have biological immunity, and avoid diseases and "worst things". They get tired. The pills" size/fl avor isbad and interfere in their daily live. Some take medication alone, but following the treatment is hard, so they need help. Some never stopped the treatment, however, others did that due to medical orientation or because they did not accept the "problem". They know that nutrition and physical activities help the treatment. Conclusion: aids determined a special need in their health: the medication technology dependency. The facticity involved them in a web care by professionals and relatives. During childhood, they needed family care integrally; and, in the transition from childhood to adolescence, they have to take care of themselves acquiring responsibilities with-themselves and being helped by relatives. Thus, children were revealed in the movement from beingcared- for to being-cared-with.

Approaches to learning of students in an Indonesian medical school.

This paper reports on a study of approaches to learning of undergraduate medical students in the University of Gadjah Mada, Indonesia. The Lancaster Approaches to Studying Inventory was translated into Indonesian and the translated form pilot tested. The instrument was then completed by 90 students, 30 each in first, second and fifth year in the Faculty of Medicine. It was found that Indonesian students generally gave higher rates than previous studies have reported. Factor analysis of their responses showed strong resemblances to other groups in the factors of meaning and reproducing orientation. Differences found in Indonesian students' responses were in strategic and non-academic orientations. There were differences between the response patterns of first-, third- and fifth-year students. It is concluded that the instrument is valid for use in Indonesia.

Neoplasia primária do coto gástrico / Primary neoplasm of gastric stump

Os autores relatam oito pacientes com carcinoma primário do coto gástrico, vários anos após gastrectomia para úlcera péptica. Mostram que a literatura tem referido nos últimos anos essa doença com maior freqüência. Na experiência dos autores essa afecçäo representou 6,2% das neoplasias do estômago. Enfatizam a necessidade de um seguimento clínico e gastroscopias periódicas em pacientes que foram submetidos, no passado, a cirurgia gástrica por doenças benignas