Non Invasive Preimplantation Testing for Aneuploidies in Assisted Reproduction: A SWOT Analysis.

The implementation of non-invasive PGT-A offers a new strategy to genetically assess the preimplantation embryo and to enhance IVF results. The extraction of DNA from the embryo culture medium has been sufficiently demonstrated, and the ability to obtain chromosomal information as a result is particularly interesting. As morphological criteria have proven to have a weak correlation with embryo ploidy status, this technique emerges as a promising alternative for embryo selection. It also appears reasonable that avoiding biopsy may enhance further embryo development. However, there are growing concerns regarding several aspects of this technique, such as the origin of this cell free DNA, the degree of representativeness of the whole embryo, the need for extended culture or the absence of standardized protocols. Despite the published data on good prognosis couples are promising, niPGT-A is yet to be considered a substitute for trophectoderm biopsy. The current SWOT analysis aims to summarize both resolved and unresolved issues, as well as limiting aspects of niPGT-A.

Plasmonic Biosensing for Label-Free Detection of Two Hallmarks of Cancer Cells: Cell-Matrix Interaction and Cell Division.

Two key features of cancer cells are sustained proliferation and invasion, which is preceded by a modification of the adhesion properties to the extracellular matrix. Currently, fluorescence-based techniques are mainly used to detect these processes, including flow cytometry and fluorescence resonance energy transfer (FRET) microscopy. We have previously described a simple, fast and label-free method based on a gold nanohole array biosensor to detect the spectral response of single cells, which is highly dependent on the actin cortex. Here we used this biosensor to study two cellular processes where configuration of the actin cortex plays an essential role: cell cycle and cell-matrix adhesion. Colorectal cancer cells were maintained in culture under different conditions to obtain cells stopped either in G0/G1 (resting cells/cells at the initial steps of cell growth) or G2 (cells undergoing division) phases of the cell cycle. Data from the nanohole array biosensor showed an ability to discriminate between both cell populations. Additionally, cancer cells were monitored with the biosensor during the first 60 min after cells were deposited onto a biosensor coated with fibronectin, an extracellular matrix protein. Spectral changes were detected in the first 20 min and increased over time as the cell-biosensor contact surface increased. Our data show that the nanohole array biosensor provides a label-free and real-time procedure to detect cells undergoing division or changes in cell-matrix interaction in both clinical and research settings.

Signaling Pathways Regulating the Expression of the Glioblastoma Invasion Factor TENM1.

Glioblastoma (GBM) is one of the most aggressive cancers, with dismal prognosis despite continuous efforts to improve treatment. Poor prognosis is mostly due to the invasive nature of GBM. Thus, most research has focused on studying the molecular players involved in GBM cell migration and invasion of the surrounding parenchyma, trying to identify effective therapeutic targets against this lethal cancer. Our laboratory discovered the implication of TENM1, also known as ODZ1, in GBM cell migration in vitro and in tumor invasion using different in vivo models. Moreover, we investigated the microenvironmental stimuli that promote the expression of TENM1 in GBM cells and found that macrophage-secreted IL-6 and the extracellular matrix component fibronectin upregulated TENM1 through activation of Stat3. We also described that hypoxia, a common feature of GBM tumors, was able to induce TENM1 by both an epigenetic mechanism and a HIF2α-mediated transcriptional pathway. The fact that TENM1 is a convergence point for various cancer-related signaling pathways might give us a new therapeutic opportunity for GBM treatment. Here, we briefly review the findings described so far about the mechanisms that control the expression of the GBM invasion factor TENM1.

HIF2α Upregulates the Migration Factor ODZ1 under Hypoxia in Glioblastoma Stem Cells.

Background: Glioblastoma (GBM) remains a major clinical challenge due to its invasive capacity, resistance to treatment, and recurrence. We have previously shown that ODZ1 contributes to glioblastoma invasion and that ODZ1 mRNA levels can be upregulated by epigenetic mechanisms in response to hypoxia. Herein, we have further studied the transcriptional regulation of ODZ1 in GBM stem cells (GSCs) under hypoxic conditions and analyzed whether HIF2α has any role in this regulation. Methods: We performed the experiments in three primary GSC cell lines established from tumor specimens. GSCs were cultured under hypoxia, treated with HIF regulators (DMOG, chetomin), or transfected with specific siRNAs, and the expression levels of ODZ1 and HIF2α were analyzed. In addition, the response of the ODZ1 promoter cloned into a luciferase reporter plasmid to the activation of HIF was also studied. Results: The upregulation of both mRNA and protein levels of HIF2α under hypoxia conditions correlated with the expression of ODZ1 mRNA. Moreover, the knockdown of HIF2α by siRNAs downregulated the expression of ODZ1. We found, in the ODZ1 promoter, a HIF consensus binding site (GCGTG) 1358 bp from the transcription start site (TSS) and a HIF-like site (CCGTG) 826 bp from the TSS. Luciferase assays revealed that the stabilization of HIF by DMOG resulted in the increased activity of the ODZ1 promoter. Conclusions: Our data indicate that the HIF2α-mediated upregulation of ODZ1 helps strengthen the transcriptional control of this migration factor under hypoxia in glioblastoma stem cells. The discovery of this novel transcriptional pathway identifies new targets to develop strategies that may avoid GBM tumor invasion and recurrence.

Correlation between systemic iron parameters and substantia nigra iron stores in restless legs syndrome.

OBJECTIVE: To evaluate the relation between systemic iron parameters (SIP) and substantia nigra (SN) iron deposits, as assessed by transcranial sonography (TCS) in restless legs syndrome (RLS). METHODS: We conducted a cross-sectional study in RLS patients, from whom blood samples with SIP were obtained, consisting of total iron-binding capacity (TIBC), serum ferritin, hemoglobin, transferrin saturation (TSAT), serum iron, and serum transferrin. TCS was performed over the SN, and the substantia nigra echogenicity index (SNEI) was determined according to established methods. Symptom severity was evaluated using the international restless legs scale (IRLS). A Spearman correlation was performed. RESULTS: A total of 167 patients were studied. Correlations between SNEI and SIP were as follows: serum ferritin (R = 0.0422; n.s.), TSAT (R = 0.0883; n.s.), TIBC (R = -0.1091; n.s.), serum transferrin (R = -0.0420; n.s.), hemoglobin (R = 0.0185; n.s.), serum iron (R = 0.0389; n.s.). No correlation was found with age and IRLS (R = 0.1375; n.s. and R = 0.0880, n.s., respectively). CONCLUSIONS: SIP are not correlated with SN iron content in RLS, quantified by means of TCS. TCS of the SN might be a more valid estimate and could be useful in the evaluation of RLS patients.

Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway.

We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade the surrounding tissue through activation of RhoA/ROCK pathway. However, the transcriptional machinery used by GBM cells to regulate the expression of ODZ1 is unknown. Here we show that interaction with tumor microenvironment elements, mainly activated monocytes through IL-6 secretion, and the extracellular matrix protein fibronectin, induces the Stat3 transcriptional pathway and upregulates ODZ1 which results in GBM cell migration. This signaling route is abrogated by blocking the IL-6 receptor, inhibiting Jak kinases or knocking down Stat3. Furthermore, we have identified a Stat3 responsive element in the ODZ1 gene promoter, about 1 kb from the transcription start site. Luciferase-reporter assays confirmed that the promoter responds to the presence of monocytic cells and this activation is greatly reduced when the Stat3 site is mutated or following treatment with a neutralizing anti-IL-6 receptor antibody or transfecting GBM cells with a dominant negative variant of Stat3. Overall, we show that monocyte-secreted IL-6 and the extracellular matrix protein fibronectin activate the axis Stat3-ODZ1 and promote migration of GBM cells. This is the first described transcriptional mechanism used by tumor cells to promote the expression of the invasion factor ODZ1.

Renal function dynamics following co-administration of sacubitril/valsartan and empagliflozin in patients with heart failure and type 2 diabetes.

AIMS: The aim of this study was to evaluate the safety profile in terms of changes in renal function after co-treatment with sacubitril/valsartan and empagliflozin in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: This multicentre observational analysis included 108 patients with T2D and HFrEF treated with both agents: baseline sacubitril/valsartan (Group A; n = 43), baseline empagliflozin (Group B; n = 42), or both agents initiated simultaneously (Group C; n = 23). The primary endpoint was estimated glomerular filtration rate (eGFR) dynamics across treatment groups. A binary characterization of worsening renal function (WRF)/improved renal function (IRF) was included in the primary endpoint. WRF and IRF were defined as an increase/decrease in serum creatinine ≥ 0.3 mg/dL or GFR ≥ 20%. Changes in quantitative variables were evaluated using joint modelling of survival and longitudinal data (JM). Rates and their treatment differences were determined by Poisson regression. The mean left ventricle ejection fraction and eGFR were 32 ± 6% and 70 ± 28 mL/min/1.73 m2 , respectively. At a median follow-up of 1.01 years (inter-quartile range 0.71-1.50), 377 outpatient visits were recorded. Although there were differences in GFR trajectories over time within each treatment, they did not achieve statistical significance (omnibus P = 0.154). However, when these differences were contrasted among groups, there was a significant decrease in GFR in Group A as compared with Group B (P = 0.002). The contrast between Groups C and B was not significant (P = 0.430). These differences were also reflected when the rates for WRF and IRF were contrasted among treatments. CONCLUSIONS: The co-administration of sacubitril/valsartan and empagliflozin in patients with HFrEF and concomitant T2D appears to be safe in terms of renal function.

Low risk of iron overload or anaphylaxis during treatment of restless legs syndrome with intravenous iron: a consecutive case series in a regular clinical setting.

OBJECTIVE: To evaluate the incidence of iron overload and anaphylaxis following intravenous (IV) iron treatment of restless legs syndrome (RLS). METHODS: A total of 58 consecutive RLS patients, meeting clinical requirements for IV iron treatment according to current IRLSSG guidelines were recruited. IV iron treatment consisted of two 500 mg infusions of ferric carboxymaltose (FCM) administered five days apart. During each of the three follow-up visits we obtained blood samples, substantia nigra echogenity index (SNEI) by means of transcranial sonography (TCS), and assessed the severity of RLS symptoms (IRLS scale). "Iron overload risk" was defined as transferrin saturation (TSAT) > 45% on two consecutive follow-up visits. In patients who had a reduction in systemic iron levels following treatment, an additional 500 mg of FCM was administered when feasible. In such cases an additional two follow-up visits were performed. RESULTS: Among the total sample, only 2/58 participants met criteria for iron overload risk. They had no evidence of liver damage and did not require additional treatment. Among the 21 patients receiving an additional 500 mg infusion after, only one patient was diagnosed with iron overload risk. Among these three patients, only one was a hemochromatosis gene carrier. No anaphylaxis or other side-effects were reported. CONCLUSIONS: In real-life clinical conditions, the risk of iron overload is low when IV FCM is administered according to the safety limits defined in the current RLS treatment guidelines. However, a close clinical follow-up with periodic blood sampling for iron status, is needed.

Prevalencia y factores de riesgo de sobrepeso y obesidad en niños de 5° y 6° año de una escuela pública de Montevideo, Uruguay / Prevalence and risk factors for overweight and obesity in 5th and 6th school year children in a public school in Montevideo, Uruguay

Resumen:

Introducción: el aumento del sobrepeso y obesidad en niños es preocupante en el ámbito nacional e internacional y se ha convertido en una epidemia.Objetivos: este estudio tuvo como objetivo general identificar la prevalencia y los factores de riesgo de sobrepeso y obesidad en niños de 5º y 6º año que concurren en una escuela pública de Montevideo (Uruguay) durante el periodo de julio-agosto de 2015. Los objetivos específicos son: conocer el perfil sociodemográfico de la población estudiada, identificar sus hábitos alimentarios, detectar los factores de riesgo y los casos de sobrepeso y obesidad.Metodología: estudio cuantitativo, descriptivo de corte transversal (julio-agosto de 2015), en una escuela pública de Montevideo. Muestra por conveniencia de 54 niños de 5º y 6º año.Resultados: por índice cintura/talla (ICT) un 16% presenta sobrepeso y obesidad, por índice de masa corporal un 48%. El 9% tiene cifras elevadas de presión arterial; el 77% considera que las frutas y verduras forman parte de la dieta saludable; el 45% que la comida casera, pescado y agua son importantes; el 30% da importancia al desayuno, el 38% no lo realiza. Colación a media mañana con predominancia de snacks. Las comidas rápidas son las más frecuentes. El 26% nunca come pescado y el 20% nunca come frutas. La mayoría de las actividades extracurriculares son sedentarias.Conclusiones: se identificó prevalencia y factores de riesgo de sobrepeso y obesidad, encontrándose un porcentaje preocupante. Desbalance nutricional, comidas a deshoras y ausencia de desayuno son las características predominantes.

Fractionated stereotactic radiotherapy plus bevacizumab after response to bevacizumab plus irinotecan as a rescue treatment for high-grade gliomas.

AIM: To evaluate the possibility of implementing a new scheme of rescue treatment after relapse or progression of high-grade glioma (HGG) treated at the first-line with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT). MATERIALS AND METHODS: We retrospectively analysed data from 59 patients with relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp protocol that were treated with BVZ+CPT11 for progression between July 2007 and August 2012, after which the response was assessed according to the Revised Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of 10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three days a week. The median follow-up was 38 months. RESULTS: The treatment was well-tolerated by all patients. The response after nuclear magnetic resonance imaging (MRI) at 3-6 months was progression in two patients, stable disease in four, and three patients had a partial response. The median overall survival (OS) from diagnosis until death or the last control was 36.8 months. The median progression-free survival (PFS) was 10.8 months. The results from tumour sub-group analysis indicated that the PFS was not statistically significant although it seemed that it was higher in grade-III. The OS was higher in grade-III gliomas. CONCLUSIONS: The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well-tolerated and seems to offer promising results. We believe that multi-centre prospective studies are needed to determine the long-term efficacy and toxicity of this therapeutic approach.

Como o estudante de enfermagem percebe a comunicação com o paciente em saúde mental / How nursing students perceive communication with patients in mental health

Identificar como o estudante de Enfermagem percebe a comunicação do paciente na saúde mental e descrever como tal percepção influencia em sua própria comunicação para o cuidado. Métodos Qualitativo, com produção artística individual após relaxamento com música instrumental e desenho em cubo planificado. A análise de palavras e frases enunciadas no coletivo evidenciou a unidade temática sobre a percepção da comunicação através dos sentidos corporais compartilhada por 23 estudantes do sétimo período do curso de Enfermagem. Resultados A produção demonstra a comunicação percebida, verbalizada e indicativa de intervenção, aproximação, escuta ampliada e atenção. Os sentidos corporais percebem comportamento, linguagem, transtornos, mecanismos de defesa, aproximação e necessidades de melhorias no cuidado. Conclusão Os sentidos corporais do estudante registram e expressam a comunicação verbal e não verbal do paciente com transtorno mental por meio de sensações, do comportamento e das condições de higiene do corpo, que emanam necessidades de cuidado...

To identify how Nursing students perceive patient communication in mental health and describe how this perception influences their own communication for care. Method Qualitative, with individual artistic production after relaxation using instrumental music and drawing in a planned cube. The analysis of the words and phrases pronounced in the group evidenced the thematic unit about the perceived communication through the bodily senses, shared by 23 seventh-semester students from the Nursing program. Results The production demonstrates that the communication perceived and expressed indicates intervention, approximation, expanded listening and attention. The bodily senses perceive behavior, language, disorders, defense mechanisms, approximation and needs for improvements in care. Conclusion The student's bodily senses register and express the verbal and non-verbal communication of patients with mental disorders through feelings, behavior and body hygiene conditions, which give rise to care needs...

Oligometastases in prostate cancer: restaging stage IV cancers and new radiotherapy options.

There are various subgroups of patients with metastatic prostate cancer: polymetastatic, oligometastatic, or oligo-recurrent cancers whose progression follows different courses and for whom there are different treatment options. Knowledge of tumor dissemination pathways and different genetic and epigenetic tumor profiles, as well as their evolution during disease progression, along with new diagnostic and therapeutic advances has allowed us to address these situations with local ablative treatments such as stereotactic body radiation therapy or stereotactic radiosurgery. These treatments provide high rates of local control with low toxicity in metastatic spread for primary cancers including those of pulmonary, digestive, and renal origin, while these types of treatments are still emerging for cancers of prostatic origin. There are several retrospective studies showing the effectiveness of such treatments in prostate cancer metastases, which has led to the emergence of prospective studies on the issue and even some phase II studies intended to prevent or delay systemic treatments such as chemotherapy. Here we collect together and review these past experiences and the studies currently underway. These types of radiotherapy treatments redefine how we approach extracranial metastatic disease and open up new possibilities for combination therapy with new systemic treatment agents.

O familiar acompanhante como estimulo comportamental de pacientes internados em terapia intensiva / El acompanante familiar como dispositivo para la estimulacion de pacientes internados en cuidados intensivos / Family companionship as a behavioural stimulus for intensive care patients

O objetivos deste estudo foram levantar as expressões verbais e não verbais presentes no comportamento do paciente antes, durante a inserção e permanência do familiar acompanhante no centro de terapia intensiva, e analisar comparativamente as alterações comportamentais do paciente durante esses momentos da internação. MÉTODO: O cenário foi o centro de terapia intensiva de um hospital no Rio de Janeiro, conveniado com o Sistema Único de Saúde (SUS). A abordagem qualitativa resultou da observação livre sobre o comportamento de cinco pacientes e registros em diário de campo durante três dias consecutivos. Priorizou-se observação do paciente no primeiro dia de internação e após a inserção ininterrupta do familiar acompanhante por três dias consecutivos. RESULTADOS: As mudanças nas reações verbais e não verbais do paciente após os estímulos gerados pela presença do familiar variaram de ausência de fala e movimentos, passividade no agir, a reações de aceitação dos procedimentos, comunicação cinésica ampliada e maior participação no cuidado. .

OBJETIVOS: identificar las expresiones verbales y no verbales presentes en el comportamiento del paciente antes y durante la inserción y permanencia del familiar acompañante en el centro de terapia intensiva y analizar comparativamente las alteraciones comportamentales del paciente durante eses momentos de la hospitalización. MÉTODO: el escenario fue un centro de terapia intensiva de un hospital en Rio de Janeiro, convenio firmado con el Sistema Único de Salud (SUS). El enfoque cualitativo resultó de la observación libre sobre el comportamiento de cinco pacientes y de los registros en diario de campo durante tres días consecutivos. Se ha dado prioridad a la observación del paciente en el primer día de hospitalización y después de la inserción ininterrumpida del familiar acompañante por tres días consecutivos. RESULTADOS: los cambios en las reacciones verbales y no verbales del paciente después de los estímulos generados por la presencia del familiar cambiaron desde la ausencia de habla y movimientos y pasividad en el actuar, para reacciones de aceptación de los procedimientos; comunicación cinésica ampliada y mayor participación en el cuidado. .

OBJECTIVES: Record patients' verbal and nonverbal expressions and behavior when they were unaccompanied, and later when a family companion was present and comparatively analyze the alterations in patient behavior observed during these periods of hospitalization. METHOD: The study was conducted at the intensive care unit of a hospital in Rio de Janeiro, which accepts patients from the Brazilian unified health system (SUS). A qualitative approach was taken, involving free observation and daily record keeping in field diaries of five patients' behavior during three consecutive days. We prioritized the observation of patients on the first day of hospitalization and subsequently when they had continuous family companionship for three consecutive days. RESULTS: The family companion served as a stimulus for positive changes in the patients' verbal and nonverbal reactions, from of a lack of speech and movement and general passivity, to reactions that showed an acceptance of procedures, increased kinetic communication and greater participation in care. .

Comunicação e enfermagem: indicativos para inserção do familiar acompanhante no Centro de Terapia Intensiva / Comunication and nursing – indicative of the insertion in the ICU familiar companion

O estudo abordou a questão da comunicação não verbal expressada pelo paciente internado em CTI, antes e após a inserção do familiar acompanhante durante o período de internação. Teve como objetivos identificar as expressões não verbais do paciente internado antes e durante a inserção do familiar/acompanhante e analisar como a permanência do mesmo influencia na comunicação não verbal do paciente durante a internação. Metodologia: estudo descritivo com abordagem qualitativa, tendo como cenário o setor de terapia intensiva da Santa Casa de Misericórdia, localizada no município de Barra Mansa, no Estado do Rio de Janeiro. Os sujeitos foram sete pacientes graves, internados em CTI com ou sem comprometimento do nível de consciência. Os aspectos éticos da pesquisa foram rigorosamente observados, segundo a Resolução CNS-196/96. Resultados: A produção dos dados deu-se a partir da observação das manifestações não verbais dos pacientes, antes e após a inserção do familiar acompanhante no CTI....