Pharmacogenomics, CYP2D6, and tamoxifen: A survey of the reasons sustaining european clinical practice paradigms

Tamoxifen is a drug that is often used in the clinical management of breast cancer. CYP2D6 is a key metabolizing enzyme that is involved in the conversion of tamoxifen to its active drug metabolites. CYP2D6 has several alleles that metabolize tamoxifen and other drugs at different rates that can alter therapeutic impact, a characteristic that renders it one of the most studied enzymes in the field of pharmacogenetics. Background and objectives: Portugal has no implemented measures based on pharmacogenomics analysis prior to therapy that might function as a cultural sample control when analyzing the individual and economic factors present in clinical practice paradigms. Therefore, we aim to investigate the impact of CYP2D6 genotyping of the tamoxifen metabolizing enzymes in the clinical management of breast cancer patients. Materials and Methods: Qualitative/quantitative studies regarding the impact of pharmacogenomics in breast cancer; personal interviews in different Portuguese laboratories within hospital setting using a survey. Analysis of data through interviews to management board and/or decision makers from major oncological centers. Results: Reasons for common adoption of pharmacogenomics practice are contradictory and based both in economic factors and cultural/clinical bias. Conclusions: This research study identifies specific cultural and/or clinical bias that act as obstacles to pharmacogenomic implementation and proposes viable courses of action that might bring about change in cultural/medical habits.This research was partially support by UID/BIM/04293/2013 and UID/EQU/0470/2019

STEREOTACTIC BRAIN BIOPSY: A REVIEW OF 15 CASES WITH OUTCOMES

Objectives: Despite improvements in the imaging techniques which aid pre-operative diagnosis, starting specific treatment requires confirmation by histopathological examination (HPE). However dilemma arises in deep seated lesions, lesions in eloquent areas, and lesion in a patient with a poor performance score for palliation/adjuvant therapy. The aim of this study is to determine the diagnostic accuracy and benefits of stereotactic biopsy (STB) in cases of clinical dilemma plus its effect on post-operative stay, morbidity and mortality, and overall management of patients. Methods: In this study, a prospective analysis of 15 patients who underwent STB in our hospital from September 2019 to July 2020 was made. The histopathological data derived from the STB, its clinical benefits, and post-operative hospital stay were analyzed. Results: In terms of histopathology, glial tumor (66.7%) was the most common lesion. The success of obtaining positive STB samples in our study was 100%. Average post-operative stay was 3 days. The clinical benefits were immense as seen in the varied presentations and clinical dilemma with which the patients presented and a how a safely sourced tissue for histopathological diagnosis by STB greatly altered the treatment of the patient. Conclusion: STB is a multifaceted tool in clinical practice. It can be used in diagnostic and therapeutic situations. Furthermore, in recurrent high-grade cases, it aids in providing HPE diagnosis for a more logical adjuvant treatment than one that follows an assumed diagnosis based on image findings/undergo a high-risk interventional procedure to get a specimen. It is a relatively safe procedure

Análise da postura cranio-cervical em pacientes com disfunção temporomandibular

OBJECTIVE: To compare head positioning and cervical spine alignment between individuals with and without temporomandibular disorders (TMDs), by means of positional evaluation using photographs, radiographs and visual observation, and to investigate whether the type of TMD influences head posture and cervical spine positioning. METHODS: Ninety randomly chosen women were diagnosed using the research diagnostic criteria for TMDs (RDC/TMD) by a trained examiner and were divided into three groups: Group 1, with a diagnosis of myofascial dysfunction (group I of RDC axis I); Group 2, with mixed TMD (groups I, II and III of RDC axis I); and Control, without TMD. Following this, the participants were photographed in frontal and lateral views by a single examiner. To produce these photos, the following anatomical points were marked out on the skin: occipital protuberance, C4, C7, acromioclavicular joint and sternoclavicular joint. From these points, different angles were analyzed by means of the ALCimagem-2000 application. These same photos were then evaluated qualitatively (visual evaluation). Next, lateral teleradiography and radiography of the cervical spine was requested. The examiner was blind when analyzing the images. To compare the results, the chi-squared test and analysis of variance were used, with significance levels of 5%. RESULTS: Regardless of the method used, the results revealed that head and cervical spine posture did not differ between the groups with and without TMD, independent of the diagnostic group. CONCLUSION: The posture of individuals with myogenic or arthrogenous TMD does not differ from the posture of individuals without TMD. The presence of TMD does not influence the head and cervical spine posture.OBJETIVO: Comparar o posicionamento da cabeça e o alinhamento da coluna cervical em indivíduos com e sem DTM, por meio da avaliação postural por fotografias, radiografias e por observação visual e verificar se o tipo de DTM influencia na postura da cabeça e no posicionamento da coluna cervical. MÉTODOS: Noventa mulheres escolhidas aleatoriamente foram diagnosticadas por meio dos Critérios para Diagnóstico em Pesquisa para Disfunções Temporomandibulares (RDC/TMD) por um examinador treinado e divididas em três grupos: grupo 1, diagnóstico de disfunção miofascial (grupo I do eixo I do RDC); grupo 2, com DTM mista (grupo I, II e III do eixo I do RDC) e controle, sem DTM . Em seguida, foram fotografadas em vista anterior e em perfil por um único examinador. Para a realização dessas fotografias, foram demarcados sobre a pele os seguintes pontos anatômicos: protuberância occiptal, C4, C7, articulação acromioclavicular e esternoclavicular. A partir desses pontos, foram analisados diferentes ângulos por meio do aplicativo ALCimagem-2000. Essas mesmas fotos foram posteriormente avaliadas qualitativamente (avaliação visual). Em seguida, foi solicitada uma radiografia e uma telerradiografia em perfil. O examinador foi cego ao analisar as imagens. Para comparação dos resultados, foi utilizado o teste qui-quadrado e a análise de variância com nível de significância de 5%. RESULTADOS: Independentemente do método utilizado, os resultados revelaram que a postura da cabeça e da coluna cervical não diferem entre o grupo com DTM e sem DTM, independentemente do grupo diagnosticado. CONCLUSÃO: A postura do indivíduo com DTM miogênica ou artrogênica não é diferente do indivíduo sem DTM. A presença da DTM não influencia na postura da cabeça e da coluna cervical

The chick chorioallantoic membrane model: A new in vivo tool to evaluate breast cancer stem cell activity

The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immuneincompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities— in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44+/CD24-/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints.This work was funded by FEDER—Fundo Europeu de Desenvolvimento Regional— funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior under the projects PestC/SAU/LA0003/2013, NORTE-01-0145-FEDER-000029, SAICTPAC/0022/2015 and FCT/02/SAICT/2017/030625. FCT funded the research grant of RC (SFRH/BD/135831/2018). IPATIMUP integrated the i3S Research Unit, which was partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145FEDER-007274)

Effects of genotype and environment on B-glucan and dietary fibre contents in whole grain of barley grown in Brazil

The aim of this study was to determine general quality characteristics of whole grain of advanced lines of barley grown in Brazil and to determine the effects of genotype and growing location on β-glucan and dietary fibre contents. Barley cultivars, designated BRS 225, BRS 195 and MN 743, crop year 2008 and 2009, with three replications in field trial coordinated by the EMBRAPA Trigo/Passo Fundo were used in this research. The barley samples were analyzed in relation to their Total Dietary Fibre (TDF) contents and fractions for moisture and protein (N × 6.25) by using AACC Methods (American Association of Cereal Chemists, 1990). The β-Glucan content was assessed using the McCleary Enzymic Method for barley (McCleary and Codd, 1991). The data was statistically evaluated by System for Analysis and Separation Averages in Agricultural Experiment (SASM-Agri - version 4) and differences between means were located using Scott-Knott’s test (p<0,05). There were significant differences among the barley genotypes and different locations and crop years in terms of β-glucan, total dietary fibre (TDF), soluble dietary fibre (SDF) and insoluble dietary fibre (IDF) content (p<0.05). Climatic factors can affect positively or negatively the content of total dietary fibre and β-glucan, impacting on the final quality of the barley grain. Substantial variation in the content of fibre components was observed for barley cultivars grown in different years on the same location. These results indicate that environmental and genetic factors are involved in the total β-glucan content and dietary fibre of barley

VIH e Doença Coronária - Quando a Prevenção Secundária É Insuficiente

Highly active antiretroviral therapy (HAART) has created a new paradigm for human immunodeficiency virus (HIV)-infected patients, but their increased risk for coronary disease is well documented. We present the case of a 57-year-old man, co-infected with HIV-2 and hepatitis B virus, adequately controlled and with insulin-treated type 2 diabetes and dyslipidemia, who was admitted with non-ST elevation acute myocardial infarction. Coronary angiography performed on day four of hospital stay documented two-vessel disease (mid segment of the right coronary artery [RCA, 90% stenosis] and the first marginal). Two drug-eluting stents were successfully implanted. The patient was discharged under dual antiplatelet therapy (aspirin 100 mg/day and clopidogrel 75 mg/day) and standard coronary artery disease medication. He was admitted to the emergency room four hours after discharge with chest pain radiating to the left arm and inferior ST-segment elevation myocardial infarction was diagnosed. Coronary angiography was performed within one hour and documented thrombosis of both stents. Optical coherence tomography revealed good apposition of the stent in the RCA, with intrastent thrombus. Angioplasty was performed, with a good outcome. The acute stent thrombosis might be explained by the thrombotic potential of HIV infection and diabetes. There are no specific guidelines regarding HAART in secondary prevention of acute coronary syndromes. A multidisciplinary approach is essential for optimal management of these patients.info:eu-repo/semantics/publishedVersio

Endoscopic pilonidal sinus treatment versus total excision with primary closure for sacrococcygeal pilonidal sinus disease in the pediatric population

Purpose: To evaluate the effectiveness and safety of Endoscopic Pilonidal Sinus Treatment (EPSiT) in the pediatric population and compare it with excision followed by primary closure (EPC) regarding intra- and postoperative outcomes. Methods: A retrospective analysis of all patients with chronic sacrococcygeal pilonidal sinus submitted to EPSiT and EPC during a 12-month period in our institution was performed. Data concerning patients' demographics and surgical outcomes were collected and compared between the two groups. Results: We analyzed a total of 21 cases that underwent EPSiT and 63 cases of EPC, both groups with similar demographic characteristics. Operative time was similar for both groups (30 vs. 38 min; p > 0.05). No major intraoperative complications were reported. Wound infection rate was lower for EPSiT ((5.2% [n = 1] vs. 20.0% [n = 12]); p > 0.05). Healing time was similar for both groups (28 vs. 37.5 days). Recurrence occurred in 18,9% (n = 15), with 2 cases (10.5%) reported in the EPSiT group versus 13 (21.6%) in EPC. There were no differences between groups regarding postoperative complications, complete wound healing and recurrence rates or healing time (p > 0.05). Conclusions: Our results suggest that EPSiT is as viable as excision followed by primary closure in the management of sacrococcygeal pilonidal sinus in the pediatric population

Survival of Lactobacillus sakei during heating, drying and storage in the dried state when growth has occurred in the presence of sucrose or monosodium glutamate

Spray-dried cells of Lactobacillus sakei CTC 494 survived ca. 60% longer in the spray dried state when cells were grown in the presence of 20 g sucrose l)1 or 12.5 g monosodium glutamate l)1. No significant differences were observed in viability during storage in the freeze dried state with the addition of these compounds to the growth medium, nor in survival during a heat treatment (55ºC). Both sucrose and glutamate in the growth medium suppressed intracellular accumulation of total amino acids and changed the overall pattern of the individual amino acids. Glutamate in the growth medium enhanced intracellular glutamate by ca. 38

Squeezing generation and revivals in a cavity-ion system in contact with a reservoir

We consider a system consisting of a single two-level ion in a harmonic trap, which is localized inside a non-ideal optical cavity at zero temperature and subjected to the action of two external lasers. We are able to obtain an analytical solution for the total density operator of the system and show that squeezing in the motion of the ion and in the cavity field is generated. We also show that complete revivals of the states of the motion of the ion and of the cavity field occur periodically.Comment: 9 pages, 3 figure

Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways

Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize Vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells.This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação da Universidade Federal Fluminense (PROPPI/UFF). TGE, ID, and NAO were recipients of graduate student fellowships from CAPES. RPC is a research fellow from CNPq and FAPERJ. CCP and RS hold employment contracts financed by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., in the context of the program-contract described in paragraphs 4, 5 and 6 of art. 23 of Law no. 57/2016, of August 29, as amended by Law no. 57/2017 of July 19