A Case Report of Idiopathic Acquired Hemophilia Type A.

Acquired hemophilia A (AHA) is a rare hemorrhagic coagulopathy caused by the presence of autoantibodies that inhibit the activity of factor VIII (FVIII). Its diagnosis requires a high index of suspicion. It should be suspected in the presence of extensive hematomas or intense mucosal bleeding in patients with no history of previous trauma or hemorrhagic symptoms. We present two clinical cases of AHA, with different presentations and therapeutic management based on immunosuppression and hemostatic control through bypass agents such as activated recombinant FVII (rFVIIa; Novoseven®) and activated prothrombin complex concentrate (aPCC; Feiba®). The first case was an idiopathic AHA that presented with extensive subcutaneous hematomas with inhibitor titer >40 Bethesda units/ml (BU/mL), prolonged activated partial thromboplastin time (aPTT), and FVIII of 0.8%. In contrast, the second case involved a patient with a history of autoimmune disease, who presented with epistaxis and inhibitor titer of 10.8 BU/ml and FVIII of 5.3%.

Molecular Actors of Inflammation and Their Signaling Pathways: Mechanistic Insights from Zebrafish.

Inflammation is a hallmark of the physiological response to aggressions. It is orchestrated by a plethora of molecules that detect the danger, signal intracellularly, and activate immune mechanisms to fight the threat. Understanding these processes at a level that allows to modulate their fate in a pathological context strongly relies on in vivo studies, as these can capture the complexity of the whole process and integrate the intricate interplay between the cellular and molecular actors of inflammation. Over the years, zebrafish has proven to be a well-recognized model to study immune responses linked to human physiopathology. We here provide a systematic review of the molecular effectors of inflammation known in this vertebrate and recapitulate their modes of action, as inferred from sterile or infection-based inflammatory models. We present a comprehensive analysis of their sequence, expression, and tissue distribution and summarize the tools that have been developed to study their function. We further highlight how these tools helped gain insights into the mechanisms of immune cell activation, induction, or resolution of inflammation, by uncovering downstream receptors and signaling pathways. These progresses pave the way for more refined models of inflammation, mimicking human diseases and enabling drug development using zebrafish models.

Growth hormone secretagogue peptide A233 upregulates Mx expression in teleost fish in vitro and in vivo.

Aquaculture constitutes an alternative source for food production and contributes to a reduction in the indiscriminate catching of aquatic organisms in their natural environment. However, high mortality during the larval state remains a challenge in this sector, mainly because of factors such as diet and diseases caused by pathogens. Therefore, growth and health management is a key strategy for sustainable aquaculture. Synthetic growth hormone secretagogues (GHSs) are a family of ligands that can stimulate pituitary growth hormone release as well as the function of ghrelin, contributing to the immune responses in a variety of vertebrates, including fish. The A233 decapeptide is a GHS with a demonstrated impact on growth, immune system function, and antioxidant defense in tilapia fish, but no antiviral activity has been described for this peptide. Here, using an in vitro model (TRG-2 cells) and two in vivo models (sea bream [Sparus aurata]) and zebrafish [Danio rerio]), we demonstrate for the first time the potential antiviral effect of A233 in teleost fish.

Growth hormone secretagogue peptide-6 enhances oreochromicins transcription and antimicrobial activity in tilapia (Oreochromis sp.).

Growth Hormone-Releasing Peptide 6 (GHRP-6) (His-(D-Trp)-Ala-Trp-(D-Phe)-Lys-NH2) is an agonist of the growth hormone secretagogue receptor. GHRP-6 mimics the effect of ghrelin. The present study focuses on the immunomodulatory effects of GHRP-6 in tilapia with and without the presence of Pseudomonas aeruginosa infection. GHRP-6 up-regulated the transcription levels of three piscidin-like antimicrobial peptides (Oreochromicins I, II, and III) and granzyme in a tissue-dependent manner. Antimicrobial activity stimulation in serum (lysozyme and anti-protease activity) was also confirmed. Besides, GHRP-6 enhanced the in vitro antimicrobial activity against P. aeruginosa in tilapia gills mucus and serum samples and decreased the bacterial load in vivo after infection with this Gram-negative bacterium. Our results evidenced, for the first time, a direct link between a growth hormone secretagogue ghrelin mimetic in fish and the enhancement of antimicrobial peptides transcription, which suggests that this secretagogue is capable to lead the activation of microbicidal activity in tilapia. Thus, these results open new possibilities for GHRP-6 application in aquaculture to stimulate the teleost immune system as an alternative treatment against opportunistic bacteria.

Impact of a candidate vaccine on the dynamics of salmon lice (Lepeophtheirus salmonis) infestation and immune response in Atlantic salmon (Salmo salar L.).

Infection with parasitic copepod salmon louse Lepeophtheirus salmonis, represents one of the most important limitations to sustainable Atlantic salmon (Salmo salar L.) farming today in the North Atlantic region. The parasite exerts negative impact on health, growth and welfare of farmed fish as well as impact on wild salmonid populations. It is therefore central to ensure continuous low level of salmon lice with the least possible handling of the salmon and drug use. To address this, vaccination is a cost-effective and environmentally friendly control approach. In this study, efficacy of a vaccine candidate, containing a peptide derived from ribosomal protein P0, was validated post infestation with L. salmonis, at the lab-scale. The sampling results showed good potential of the vaccine candidate when administered intraperitoneally in the host, in reducing the ectoparasite load, through reduction of adult female lice counts and fecundity and with greater presumptive effect in F1 lice generation. The sampling results correlated well with the differential modulation of pro-inflammatory, Th1, Th2 and T regulatory mediators at the transcript level at different lice stages. Overall, the results supports approximately 56% efficacy when administered by intraperitoneal injection. However, additional validation is necessary under large-scale laboratory trial for further application under field conditions.

Promiscuous T cell epitopes boosts specific IgM immune response against a P0 peptide antigen from sea lice in different teleost species.

The development of vaccines employing conserved protein antigens, for instance ribosomal protein P0, has as disadvantage the high degree of identity between pathogen and host proteins due to possible induction of tolerance or auto antibodies in the host organism. To overcome this drawback, peptide-based vaccines have been designed with a proved high efficacy. The use of defined peptides as antigens has the problem that they are generally poor immunogenic unless coupled to a carrier protein. Several studies have established the potential for promiscuous T cell epitopes incorporated into chimeric peptides to enhance the immunogenicity in mammals. On the contrary, studies about the role of these epitopes on teleost immune system are scarce. Therefore, the main objective of our present study was to evaluate the potential of promiscuous T cell epitopes to boost specific IgM immune response in teleost fish against a peptide antigen. With this aim, we used a peptide of 35 amino acids from the ribosomal P0 protein of Lepeophtheirus salmonis, an important parasite in salmon aquaculture. We fused this peptide to the C-terminal of T cell epitopes from tetanus toxin and measles virus and produced the chimeric protein in Escherichia coli. Following vaccination, IgM antibody production was monitored in different immunization schemes in Tilapia, African catfish and Atlantic salmon. The results demonstrated for first time that the addition of T cell epitopes at the N-terminal of a target peptide increased IgM specific response in different teleost species, revealing the potential of this approach to develop peptide-based vaccines for aquaculture. The results are also of great importance in the context of vaccine development against sea lice using ribosomal protein P0 as antigen taking into account the key role of P0 in protein synthesis and other essential physiological processes.

Growth hormone releasing peptide-6 enhanced antibody titers against subunit antigens in mice (BALB/c), tilapia (Oreochromis niloticus) and African catfish (Clarias gariepinus).

Modern subunit vaccines have excellent safety profiles and improved tolerability, but do not elicit strong immune responses without the addition of adjuvants. Developing a safe and affective adjuvant remains a challenge for peptide-based vaccine design. Growth Hormone Releasing Peptide-6 (GHRP-6) is one of the earliest-developed, synthetic, peptidyl growth hormone secretagogue receptor agonists. These compounds mimic the effect of the endogenous ligand, ghrelin. In the present study, we evaluated the ability of GHRP-6 to enhance the humoral immune response against co-injected antigens in mice, tilapia and African catfish. This peptide was able to increase the antigen-specific antibody response using heterologous proteins and peptides as antigens, which were also formulated in "water in oil" emulsions (Freund and Montanide). As long as we know there is no previous report describing any ghrelin analogous as molecular immunomodulator stimulating a humoral immune response. Further studies will be conducted to evaluate the functionality of this humoral immune response in challenge trials.

Current treatment of early breast cancer: adjuvant and neoadjuvant therapy.

Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer.

Isquemia miocárdica silente en diabéticos tipo 2 / Silent myocardial ischemia in type 2 diabetes patients

Objetivos: determinar la frecuencia de isquemia miocárdica silente en diabéticos tipo 2 y su relación con el control metabólico. Métodos: se realizó un estudio descriptivo transversal en 79 pacientes asintomáticos con diabetes mellitus tipo 2 sin antecedentes de cardiopatía isquémica, hipertensión arterial o de ser fumador, que acudieron a la Consulta de Endocrinología del Hospital Militar Central Dr Carlos J Finlay, entre febrero de 2009 y febrero de 2011. Se les realizó ecocardiografía con doppler tisular y se determinaron los niveles de glucemia en ayunas, posprandial, hemoglobina glucosilada, colesterol y triglicéridos. Las variables clínicas analizadas en relación con la isquemia miocárdica silente fueron: edad, sexo, tiempo de evolución de la diabetes e índice de masa corporal. Para las variables cualitativas se utilizaron distribuciones de frecuencia con el cálculo del porcentaje y para establecer relación entre variables la prueba de chi cuadrado. Resultados: la edad media del total de pacientes fue de 54 años, de ellos el 69,1 por ciento correspondió al sexo masculino y el 31,9 por ciento al femenino. En el 20,2 por ciento de los pacientes se observaron signos de isquemia miocárdica por doppler tisular, y de ellos, un 75 por ciento tuvo niveles patológicos de colesterol total, con relación estadísticamente significativa (p= 0,01), sujetos que tuvieron 4,4 veces más riesgo relativo de presentar isquemia miocárdica, que los pacientes con colesterol normal. Las cifras de glucemia en ayunas, posprandial y hemoglobina glucosilada fueron significativamente mayor en el grupo con isquemia. Los pacientes con niveles elevados de glucemia en ayunas tuvieron 10,5 veces más riesgo de isquemia miocárdica que los que tenían cifras adecuadas. Igualmente, los casos con cifras elevadas de glucemia posprandial presentaron 12 veces más riesgo de enfermar. Conclusiones: la isquemia miocárdica silente es frecuente en los diabéticos tipo 2 y se relaciona con los niveles patológicos de colesterol y el mal control glucémico(AU)

Objectives: to determine the frequency of silent myocardial infarction in type 2 diabetes patients and its relation with the metabolic control. Methods: a cross-sectional descriptive study of 79 asymptomatic patients suffering type 2 diabetes mellitus and without a history of ischemic cardiopathy, blood hypertension or smoking. These patients were seen at the endocrinology service of Dr Carlos J Finlay from February 2009 to February 2011. They underwent Doppler tissue imaging echocardiography and their levels of glycemia on fasting, pospandrial glycemia, glycated haemoglobin, cholesterol and triglycerides were determined. The analyzed clinical variables lfor the silent myocardial ischemia were age, sex, time of evolution of diabetes and body mass index. Frequency distributions and percentage estimations were used for the qualitative variables whereas the Chi square test served to establish relationships among variables. Results: the average age of the patients was 54 years, 69,1 percent were males and 31,9 percent females. The Doppler tissue imaging echocardiography showed signs of myocardial ischemia in 20 percent of these patients, and 75 percent had pathological levels of total cholesterol with statistically significant relation (p=0.01) and their relative risk of developing myocardial ischemia was 4.4 times higher than the rest of patients with normal cholesterol. The values of glycemia on fasting, pospandrial glycemia and glycated haemoglobin were significantly higher than in the ischemic group. The patients having significantly higher values of glycemia on fasting exhibited a risk of myocardial ischemia that was 10.5 times higher than that of the patients with adequate values for this variable. Likewise, the risk of getting sick was 12 times higher in those cases with high values of pospandrial glycemia. Conclusions: silent myocardial ischemia is frequent in type 2 diabetes mellitus patients and is associated with pathological levels of cholesterol and with poor glycemic control(AU)

Isquemia miocárdica silente en diabéticos tipo 2 / Silent myocardial ischemia in type 2 diabetes patients

Objetivos: determinar la frecuencia de isquemia miocárdica silente en diabéticos tipo 2 y su relación con el control metabólico. Métodos: se realizó un estudio descriptivo transversal en 79 pacientes asintomáticos con diabetes mellitus tipo 2 sin antecedentes de cardiopatía isquémica, hipertensión arterial o de ser fumador, que acudieron a la Consulta de Endocrinología del Hospital Militar Central Dr Carlos J Finlay, entre febrero de 2009 y febrero de 2011. Se les realizó ecocardiografía con doppler tisular y se determinaron los niveles de glucemia en ayunas, posprandial, hemoglobina glucosilada, colesterol y triglicéridos. Las variables clínicas analizadas en relación con la isquemia miocárdica silente fueron: edad, sexo, tiempo de evolución de la diabetes e índice de masa corporal. Para las variables cualitativas se utilizaron distribuciones de frecuencia con el cálculo del porcentaje y para establecer relación entre variables la prueba de chi cuadrado. Resultados: la edad media del total de pacientes fue de 54 años, de ellos el 69,1 por ciento correspondió al sexo masculino y el 31,9 por ciento al femenino. En el 20,2 por ciento de los pacientes se observaron signos de isquemia miocárdica por doppler tisular, y de ellos, un 75 por ciento tuvo niveles patológicos de colesterol total, con relación estadísticamente significativa (p= 0,01), sujetos que tuvieron 4,4 veces más riesgo relativo de presentar isquemia miocárdica, que los pacientes con colesterol normal. Las cifras de glucemia en ayunas, posprandial y hemoglobina glucosilada fueron significativamente mayor en el grupo con isquemia. Los pacientes con niveles elevados de glucemia en ayunas tuvieron 10,5 veces más riesgo de isquemia miocárdica que los que tenían cifras adecuadas. Igualmente, los casos con cifras elevadas de glucemia posprandial presentaron 12 veces más riesgo de enfermar...(AU)

Objectives: to determine the frequency of silent myocardial infarction in type 2 diabetes patients and its relation with the metabolic control. Methods: a cross-sectional descriptive study of 79 asymptomatic patients suffering type 2 diabetes mellitus and without a history of ischemic cardiopathy, blood hypertension or smoking. These patients were seen at the endocrinology service of Dr Carlos J Finlay from February 2009 to February 2011. They underwent Doppler tissue imaging echocardiography and their levels of glycemia on fasting, pospandrial glycemia, glycated haemoglobin, cholesterol and triglycerides were determined. The analyzed clinical variables lfor the silent myocardial ischemia were age, sex, time of evolution of diabetes and body mass index. Frequency distributions and percentage estimations were used for the qualitative variables whereas the Chi square test served to establish relationships among variables. Results: the average age of the patients was 54 years, 69,1 percent were males and 31,9 percent females. The Doppler tissue imaging echocardiography showed signs of myocardial ischemia in 20 percent of these patients, and 75 percent had pathological levels of total cholesterol with statistically significant relation (p=0.01) and their relative risk of developing myocardial ischemia was 4.4 times higher than the rest of patients with normal cholesterol. The values of glycemia on fasting, pospandrial glycemia and glycated haemoglobin were significantly higher than in the ischemic group. The patients having significantly higher values of glycemia on fasting exhibited a risk of myocardial ischemia that was 10.5 times higher than that of the patients with adequate values for this variable. Likewise, the risk of getting sick was 12 times higher in those cases with high values of pospandrial glycemia... (AU)

Understanding the attitudes of Latino parents toward confidential health services for teens.

OBJECTIVES: To explore the knowledge and attitudes that Latino parents have about confidential health services for their teens and to identify factors that may influence those attitudes. METHODS: Latino parents of teens (12-17 years) were randomly selected from a large health maintenance organization and a community-based hospital to participate in 1-hour focus groups. We conducted eight focus groups in the parent's preferred language. Spanish and English transcripts were translated and coded with intercoder reliability >80%. RESULTS: There were 52 participants (30 mothers, 22 fathers). There is a wide range of parental knowledge and attitudes about confidential health services for teens. Parents believed they had the right to know about their teens' health but were uncomfortable discussing sexual topics and thought confidential teen-clinician discussions would be helpful. Factors that influence parental acceptability of confidential health services include parental trust in the clinician; the clinician's interpersonal skills, clinical competencies, and ability to partner with parents and teens; and clinician-teen gender concordance. Most parents preferred teens' access to confidential services than having their teens forego needed care. CONCLUSIONS: This study identifies several underlying issues that may influence Latino youths' access to confidential health services. Implications for clinical application and future research are discussed.

Asociación entre prácticas en salud, somatización y algunos factores psicosociales en usuarios de clínicas de ASSBASALUD ESE: Manizales (Colombia), 2007 / Association between health practices, somatization and some psychosocial factors in clinics of ASSBASALUD ESE: Manizales (Colombia), 2007

Introducción: La evidencia investigativa sugiere que la población con una patología médica crónica presenta mayor riesgo de desarrollar un cuadro de somatización, definida como una serie de síntomas corporales sin causa orgánica demostrable, y asociada al estrés y cuadros depresivos, ansiosos, que generalmente pasan desapercibidos en la consulta. Este tipo de pacientes terminan convirtiéndose en consultantes crónicos o en abusadores de servicios de salud, lo que genera congestión en la prestación del servicio e incremento en los costos de salud. Metodología: Estudio de corte transversal, con 188 pacientes que asistieron a consultaexterna en los diferentes centros urbanos de Atención en Seguridad Social, Bienestar y Salud, Empresa Social del Estado (ASSBASALUD, ESE) del área urbana de Manizales (Colombia). Resultados: La edad promedio fue 51,3 años, 62,5 por ciento presentaban somatización, 61,9 por ciento ansiedad subclínica, 51,6 por ciento no presentaban depresión, estrés bajo 73,6 por ciento y buena función familiar 42,9 por ciento . Se encontró dependencia significativa entre somatización y ansiedad (p=0,000), depresión (p=0,005) estrés (p=0,000) funcionalidad familiar (p=0,007), entre otras. También se encontró dependencia significativa entre las variables prácticas en salud y somatización (p=0.002), Ansiedad (p=0,014), depresión (p=0.008) a nivel p<0,1 con funcionalidad familiar (p=0,093). Conclusiones: se encontró una alta comorbilidad de somatización en los pacientes con algún grado de depresión, ansiedad y estrés, al igual que deficientes prácticas de salud en este tipo de pacientes.