RESUMO

The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.

Assuntos

Hematologia , Neoplasias , Criança , Consenso , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/terapia , Medicina de Precisão/métodos , Espanha

RESUMO

BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.

Assuntos

Doenças Fetais/genética , Neoplasias/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos

RESUMO

In recent years, the demographic transition has resulted in an aging population, which has increased the number of illnesses such as depression. Often, the family physician is the first contact with these patients, therefore, comprehensive patient management is essential, emphasizing the primary and secondary prevention of depression in the elderly population. From primary health care, all risk and protective factors related to depression should be comprehensively evaluated. Among the former, widowhood, disability, and chronic diseases stand out. Likewise, the diagnostic criteria must be known to provide timely treatment. And, on the other hand, knowing the appropriate treatment will reduce the symptoms of depression, suicidal behavior, relapse, or recurrence of symptoms. Treatment usually consists of psychotherapy, psychosocial interventions, antidepressants, and electroconvulsive therapy. Therefore, the objective of this review is to offer family physicians a guide on the primary prevention, secondary prevention, and treatment of depression in the elderly.

Assuntos

Depressão , Médicos de Família , Idoso , Antidepressivos , Humanos , Psicoterapia , Prevenção Secundária

RESUMO

INTRODUCTION: Adenosine A2A and A2B receptor intracellular pathway is associated with either increasing endothelial nitric oxide (NO) synthase (eNOS) expression or eNOS activation (i.e., tyrosine 1177 phosphorylation); a mechanism linked to pro or anti-proliferative effects depending of the cell type. However, there are no reports in pre-eclampsia. OBJECTIVES: Investigate whether NO signaling pathway is involved in fetal endothelium proliferation induced by adenosine receptor activation in early and late-onset pre-eclampsia. METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated from normal (n=25), late-onset pre-eclampsia (n=11) and early-onset pre-eclampsia (n=22). Adenosine A2A and A2B expression was evaluated by immunocytochemistry and Western blot. Cell proliferation was analyzed using MTS-assay in absence or presence of non-selective adenosine receptor agonist (NECA 10µM), adenosine A2A receptor selective agonist (CGS-21680, 100nM), and/or the antagonists ZM-241385 (0-100µM) or MRS-1754 (0-1µM) for A2A and A2B receptors during 24h. In parallel experiments NOS inhibitor (L-NAME, 100µM) was used in co-incubation by either adenosine receptor agonist or antagonists. Nitrite concentration in the culture medium and protein nitration assessed by Western blot were measured in cells exposed to CGS-21680 (30min). RESULTS: Early-onset pre-eclampsia was associated to low A2A (∼70%), but high (∼2-fold) A2B adenosine receptor protein abundance compared with normal or late-onset pre-eclampsia. Basally, HUVEC from early-onset showed a low (∼42%), whereas late-onset exhibited high proliferation (∼1.5-fold) compared with normal pregnancy. Cell proliferation was increased by CGS-21680 (∼2-fold) in late-onset or normal pregnancy and ∼5-fold in early-onset pre-eclampsia compared with respective control. NECA increased cell proliferation only in normal cells. Stimulatory effect of CGS-21680, was inhibited by ZM-241385 in normal pregnancies (Ki, 25nM) and late-onset (Ki 50nM) but not in early-onset (Ki ambiguous). Interestingly, MRS-1754 showed an increase in cell proliferation in a dose-response manner only in early-onset group. L-NAME partially blocked (∼25%) the stimulatory effect of CGS-21680 in late-onset and normal pregnancy. Interestingly, L-NAME revert the maximal stimulatory effect of MRS-1754 observed in early-onset. Total and phosphorylated eNOS protein was reduced (∼50%) in early-onset pre-eclampsia compared to late-onset or normal pregnancy. In turn, cells from late-onset pre-eclampsia exhibited high (∼2-fold) eNOS phosphorylation compared with normal pregnancy. In normal pregnancy, CGS-21680 (30min) increased (∼2-fold) the eNOS phosphorylation and nitrotyrosine formation, without changes in nitrite levels, but non-significant changes were observed in early or late-onset pre-eclamptic cells. CONCLUSION: Fetal endothelium from early-onset exhibits a predominant anti-proliferative effect mediated by adenosine A2B receptors activation, whereas the stimulatory effect of adenosine A2A receptors prevails in cells from late-onset pre-eclampsia. Both pro and anti-proliferative effects seem mediated by a nitric oxide-depended intracellular pathway. Supported by FONDECYT 1100684, Conicyt Anillo ACT73.

RESUMO

INTRODUCTION: Elevated uric acid levels during the first or third trimester of gestation have been associated with poor perinatal outcomes in women with hypertensive pregnancies. OBJECTIVES: Investigate whether uric acid levels are related to adverse perinatal outcomes in Chilean hypertensive women. METHODS: It is a post-hoc analysis from a retrospective study including clinical records (n=416) of women with diagnosis of hypertension in pregnancy treated in the Hospital Clínico Herminda Martin, Chillán, Chile. From these records, 86 showed quantification of uric acid plasma levels at the moment of hypertension diagnosis ((3) 140/90mmHg; at 34±5weeks). Women were divided into three groups, considering uric acid levels below 25th percentile (Low group, n=27, <3.7mg/dl), from 25th to 75th percentile (Middle group, n=38, 3.8 to 5.7mg/dl) and above 75th percentile (High group, n=21, >5.8mg/dl) for the studied population. RESULTS: In the entire group of hypertensive women, the uric acid/creatinine ratio was positively related to hospitalization days (p=0.04), and negatively associated with newborn weight (p=0.02) and size (p=0.01). ANOVA analysis did not show statistical differences in age, parity, systolic, diastolic or media blood pressure, body mass index, proteinuria, hepatic enzymes or hypoxia perinatal in women with low, middle or high uric acid levels. However, women with high uric acid levels showed a longer-hospitalization period (∼1.2days more), less platelet count (∼40×10(3)/ml) and high creatinine plasma levels (∼0.2mg/dl) and their babies showed less birth weight (∼800g) and were smaller (∼3cm) compared with women with low uric acid levels. Relative risk of intrauterine growth restriction in women with high levels of uric acid was 1.3 (CI, 0.96 to 1.73) compared with women with low levels. CONCLUSION: These data reinforce the general agreement about the utility of hyperuricemia in the prognosis of adverse perinatal outcomes in hypertensive pregnancies.

RESUMO

Recently, attempts have been made to construct actuators with similar behaviour to natural muscles. However the results have been inadequate for application to practical prostheses. For example, muscle wire, which has too low an efficiency to be powered by batteries and McKibben muscles which require two power supplies, one electric and one pneumatic. Electrochemical muscles are still in the development stage and cannot yet be used for prostheses. In this paper, a new electromechanical actuator is presented, which provides rectilinear movement and linear characteristics. This electromechanical actuator is based on a ball screw and rare earth magnet coreless motors. The system has been characterised and some of the most important results are that it produces a force of 167N while developing a velocity of 7x10(-3)m/s. The force developed is proportional to the current drained. Its efficiency is about 32%, its total mass 0.19kg and it is light and compact enough to be used in practical clinical prosthesis.

Assuntos

Membros Artificiais , Tecnologia Biomédica , Humanos , Desenho de Prótese

Assuntos

Produtos Agrícolas , Economia , Internacionalidade , Indústria do Tabaco , Colonialismo/história , Comércio/economia , Comércio/educação , Comércio/história , Comércio/legislação & jurisprudência , Produtos Agrícolas/economia , Produtos Agrícolas/história , Países em Desenvolvimento/economia , Países em Desenvolvimento/história , República Dominicana/etnologia , Economia/história , Economia/legislação & jurisprudência , História do Século XVIII , Internacionalidade/história , Internacionalidade/legislação & jurisprudência , Governo Local , Espanha/etnologia , Nicotiana/fisiologia , Indústria do Tabaco/economia , Indústria do Tabaco/educação , Indústria do Tabaco/história , Indústria do Tabaco/legislação & jurisprudência

RESUMO

Chronic antiarrhythmic therapy for the prevention of episodes of paroxysmal supraventricular tachycardia is limited by its elevated cost, the development of side effects and lack of patients' collaboration. In this study the efficacy and safety of a single oral dose of diltiazem (180 mg) and propranolol (80 mg) were assessed. Eighteen episodes of supraventricular tachycardia were treated in 17 patients, 9 female and 8 male, aged between 19 and 60 years old (mean 45.3 +/- 11.4). The episodes had begun 3 months to 40 years before. They were divided in 3 groups: group I (placebo), 6 episodes; group II (diltiazem-propranolol), 12 episodes; and group III (patients from the placebo group without spontaneous recovery of sinus rhythm who were given active drug), 6 episodes. There were no spontaneous conversions in group I (placebo) within 80 minutes. In group II, ten out of 12 episodes responded to the combination after 38.8 +/- 20.8 minutes (seven episodes were converted to sinus rhythm within the first 45 minutes). In group III (non-responders to placebo who were subsequently given active drugs), four out of 6 episodes were suppressed after 50.7 +/- 16.7 minutes. The cycle of the tachycardia lengthened before conversion to sinus rhythm both in groups II and III. Neither systolic nor diastolic blood pressure changed significantly in any group. Seven out of 14 patients who successfully converted to sinus rhythm in groups II and III, suffered mild to moderate sweat between 3 and 5 minutes before the end of the episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

Diltiazem/administração & dosagem , Propranolol/administração & dosagem , Taquicardia Supraventricular/tratamento farmacológico , Administração Oral , Adulto , Combinação de Medicamentos , Eletrofisiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade

RESUMO

El tratamiento crónico para prevenir la recurrencia de episodios de taquicardia supraventricular presenta el incoveniente del elevado costo, aparición de efectos adversos y escasa adherencia de los pacientes. En el presente estudio se evaluó la seguridad y eficacia de la combinación de ditiazem (180 mg) y propranolol (80 mg) en dosis única oral. Fueron incluidos 18 episodios de taquicardia supraventricular en 17 pacientes. La población fue dividida en 3 grupos I (placebo), 6 episodios; grupo II (droga activa), 12 episodios y grupo III (pacientes del grupo placebo en quienes, al no existir reversión a ritmo sinusal, se indicó diltiazem-propranolol), 6 episodios. No hubo ceses epontáneos de la arritmia en el grupo I (placebo) dentro de los 80 minutos. En el grupo II, 10 e 12 episodios fueron convertidos a ritmo sinusal a los 38,8 ñ 20,8 minutos post-droga. En el grupo III, 4 de 6 episodios fueron convertidos a ritmo sinusal a los 50,7 ñ 16,7 minutos post-droga activa. Dos pacientes tuvieron hipotensión arterial que no requirió tratamento específico. Es decir que 14 de 18 episodios revirtieron a ritmo sinusal con la combinación oral. Se concluye que el tratamiento episódico puede ser de utilidad en pacientes sin cardiopatía severa y con aceptable tolerancia hemodinámica durante las crisis

Assuntos

Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Diltiazem/administração & dosagem , Propranolol/administração & dosagem , Taquicardia Supraventricular/tratamento farmacológico , Administração Oral , Eletrofisiologia , Frequência Cardíaca

RESUMO

Chronic antiarrhythmic therapy for the prevention of episodes of paroxysmal supraventricular tachycardia is limited by its elevated cost, the development of side effects and lack of patients collaboration. In this study the efficacy and safety of a single oral dose of diltiazem (180 mg) and propranolol (80 mg) were assessed. Eighteen episodes of supraventricular tachycardia were treated in 17 patients, 9 female and 8 male, aged between 19 and 60 years old (mean 45.3 +/- 11.4). The episodes had begun 3 months to 40 years before. They were divided in 3 groups: group I (placebo), 6 episodes; group II (diltiazem-propranolol), 12 episodes; and group III (patients from the placebo group without spontaneous recovery of sinus rhythm who were given active drug), 6 episodes. There were no spontaneous conversions in group I (placebo) within 80 minutes. In group II, ten out of 12 episodes responded to the combination after 38.8 +/- 20.8 minutes (seven episodes were converted to sinus rhythm within the first 45 minutes). In group III (non-responders to placebo who were subsequently given active drugs), four out of 6 episodes were suppressed after 50.7 +/- 16.7 minutes. The cycle of the tachycardia lengthened before conversion to sinus rhythm both in groups II and III. Neither systolic nor diastolic blood pressure changed significantly in any group. Seven out of 14 patients who successfully converted to sinus rhythm in groups II and III, suffered mild to moderate sweat between 3 and 5 minutes before the end of the episodes.(ABSTRACT TRUNCATED AT 250 WORDS)