Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

BACKGROUND: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls. RESULTS: This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components. CONCLUSIONS: Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Biological behavior of familial papillary thyroid microcarcinoma: Spanish multicenter study.

PURPOSE: Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain. METHODS: Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence). RESULTS: Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210-5.473; p = 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638-1000; p < 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405-333.333; p < 0.001). CONCLUSION: FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA.

In vitro nematicidal activity of two ferrocenyl chalcones against larvae of Haemonchus contortus (L3) and Nacobbus aberrans (J2).

The main goal of this work was to evaluate the in vitro biological activity of two ferrocenyl chalcones (FcC-1 and FcC-2) against Haemonchus contortus (third-stage larvae (L3)) and Nacobbus aberrans (second-stage juveniles (J2)). Both compounds were synthesized and characterized by usual spectroscopic methods and their molecular structures were confirmed by single-crystal X-ray diffractometry. Nematode strains were examined in terms of percentage mortality of H. contortus (L3) by the action of FcC-1, which showed an effectivity of 100% at a concentration of 342 µM in 24 h, with EC50 = 20.33 µM and EC90 = 162.76 µM, whereas FcC-2 had an effectivity of 72% at a concentration of 342 µM in 24 h, with EC50 = 167.39 µM and EC90 = 316.21 µM. The effect of FcC-1 against nematode phytoparasite N. aberrans showed a better percentage of 95% at a concentration of 342 µM, with EC50 = 7.18 µM and EC90 = 79.25 µM, whereas the effect of FcC-2 was 87% at 342 µM, with EC50 = 168 µM and EC90 = 319.56 µM at 36 h. After treatment, the scanning electron micrographs revealed deformities in the dorsal flank and posterior part close to the tail of H. contortus L3. They showed moderate in vitro nematicidal activity against H. contortus L3 and N. aberrans J2.

Fleas of the genus Neotyphloceras associated with rodents from Bolivia: new host and distributional records, description of a new species and remarks on the morphology of Neotyphloceras rosenbergi.

The flea genus Neotyphloceras Rothschild (Siphonaptera: Ctenophthalmidae) includes five species and two subspecies distributed from Venezuela to southern Chile and Argentina. Only Neotyphloceras crassispina hemisus Jordan has been registered in Bolivia. The present study examines species of Neotyphloceras collected in Bolivian localities in the Departments of La Paz, Cochabamba and Tarija, and describes the morphology of the modified abdominal segments in males and females of Neotyphloceras rosenbergi Rothschild on the basis of type material and specimens collected from Tarija. A new species, Neotyphloceras boliviensis n. sp., is described and new host associations are reported for N. rosenbergi, Neotyphloceras crassispina crassispina and N. crassispina hemisus. Neotyphloceras c. crassispina and N. rosenbergi are reported for the first time in Bolivia. The distribution of N. rosenbergi is extended 1600 km to the south. Given the potential medical and veterinary significance of fleas as disease vectors, and considering that in the Departments of La Paz and Tarija several human cases of plague have been reported, and species of flea have been identified as main vectors of these diseases, the new records of fleas in Bolivia reported herein may be useful for epidemiological studies on flea-borne diseases.

[Update on management of cow's milk protein allergy: Available milk formulas and other juices]. / Actualización en manejo de Alergia a la proteína de leche de vaca: fórmulas lácteas disponibles y otros brebajes.

Cow's milk protein allergy (CMPA) is a common disease with a prevalence of 2-7%, increasingly so. It is characterized by an allergic reaction to one or more cow's milk proteins. There are not pathog nomonic clinical symptoms, and these will depend on the type of immune reaction involved. A good diagnostic approach avoids under and over diagnosis and, therefore, under and over treatment. The CMPA treatment is the elimination of cow's milk protein from the diet. A restricted diet in a child does not require it or who has developed tolerance can alter growth, quality of life, including unne cessary costs. The objective of this review is to present the different milk formulas available in Chile to treat CMPA in those cases where breastfeeding with exclusion diet is not possible. For this purpose, nutritional composition, ingredients and other relevant characteristics of all the milk formulas and juices marketed in Chile as CMPA treatment were reviewed. The information was obtained from the official distributors or sellers or failing that, from the official websites. There are multiple milk formulas and beverages used for the treatment of CMPA, and not all of them are nutritionally or immunologically secure. Knowing them in detail will help the pediatrician to indicate them in a more informed way according to their benefits and their deficiencies for the proper management of this pathology.

Antifungal activity of the essential oil obtained from Cryptocarya alba against infection in honey bees by Nosema ceranae.

The honeybee disease nosemosis type C is a serious problem since its causative agent, microsporidium Nosema ceranae, is widespread among adult honey bees. Some of the feasible alternative treatments that are used to control this disease are plant extracts. The aim of the present work was to evaluate the effects of essential oils of Chilean plant species, such as Cryptocarya alba, which is used against N. ceranae, and to identify and quantify the majority active compounds in the EO as well as their potential use for the control of nosemosis. Essential oils were obtained using the stripping steam technique with Clevenger equipment and were subsequently analyzed by Gas chromatography-mass spectrometry. Mortality was recorded daily over at least 8days as worker honeybees were exposed to a range of doses of EO dispersed in a sucrose solution. C. alba oil appears to be nontoxic to A. mellifera adults at the tested concentration (the same concentration inhibits the growth of N. ceranae), showing that this oil can be used for the treatment of nosemosis. EO effectiveness was demonstrated against N. ceranae by calculating the percentage of decrease in infected bees from untreated infected groups vs infected groups treated with EO or the reference drug fumagillin. It was determined that a dose of 4µg EO/bee was most effective in controlling N. ceranae development. We determined innocuous doses of C. alba essential oil for honeybees. We demonstrated the antifungal activity of C. alba EO at 4µg/bee against N. ceranae and compared it to its major monoterpenes, such as ß-phellandrene (20µg/bee), eucalyptol (20µg/bee) and α-terpineol (20µg/bee). The major compounds of C. alba EO, α-terpineol, eucalyptol and ß-phellandrene, had significant effects against Apis mellifera infection by N. ceranae, but the antifungal effect of the complete essential oil on N. ceranae was larger than the effect of α-terpineol, eucalyptol or ß- phellandrene separately, showing that C. alba oil may be a candidate for the treatment or prevention of nosemosis.

Differential innate immune response of European seabass (Dicentrarchus labrax) against Streptococcus iniae.

Streptococcus iniae is a Gram-positive bacteria that causes invasive infections with severe septicemia and meningitis, producing high economic losses in marine and continental aquaculture. Head kidney leukocytes of European sea bass (Dicentrarchus labrax) were used to measure the differential innate immune response upon infection with S. iniae. The complete inhibition in the production of intracellular superoxide radicals and total peroxidase content was observed in infected cells. This study also elucidates changes in the relative expression of some immune-related genes. Interleukin 1ß, tumor necrosis factor-α and interleukin-6 reached a peak of expression at 4-8 h post-infection, subsequently decreasing significantly up to 48 h post-infection. However, interleukin-10 and Mx protein increased over time, reaching the pick of expression at 48 h post-infection, whereas caspase-3 showed down regulation until 48 h post-infection. The in vivo study of immune related genes show the same kinetics of mRNAs expression as in vitro experience. The proinflammatory cytokines mRNA transcription levels peaked at an earlier time in vivo than in vitro system. Our findings indicate that there is a direct relationship between the dissemination of bacteria and the resulting infection-associated inhibition of respiratory burst, apoptosis, and the pro- and anti-inflammatory gene expression profiles.

Immunization of sea bream (Sparus aurata) juveniles against Photobacterium damselae subsp. piscicida by short bath: Effect on some pro-inflammatory molecules and the Mx gene expression.

Cytokines are a family of proteins derived from macrophages, lymphocytes, granulocytes, mast cells and epithelial cells and can be divided into interferons (IFNs), Interleukins (ILs) and Tumor Necrosis factors (TNFs) among others. The presence of cytokines in a wide number of fish species has been proved and several molecules types have been already cloned and sequenced. In this work some proinflamatory molecules and Mx gene were detected in the liver of vaccinated sea bream juveniles with an average body weight of 5 g. The method of immunization was by short bath and three different bacterins against the marine pathogen Photobacterium damselae subsp. piscicida were designed and used to immunize fish. Five genes encoding for five different molecules were analyzed by real time PCR: IL-1ß, IL Ir-2, Cox-2, Mx and TNFα. Gene expression was quantified along four days after fish immunization and results were compared among groups. Results show that the heat-inactivated vaccine stimulates the up-regulation of IL-1ß, IL Ir-2, Cox-2 and TNFα genes whereas the UV-light inactivated vaccine was the unique vaccine which stimulates the expression of Mx gene. The present is a novel study that shows by the first time the effect of the inactivation process of vaccines on the expression levels of genes involved in the defense against Photobacterium damselae subsp piscicida.

The in vitro immunomodulatory effect of extracellular products (ECPs) of Vagococcus fluvialis L21 on European sea bass (Dicentrarchus labrax) leucocytes.

The immune associated genes, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), ciclo-oxigenase-2 (COX-2), and Mx gene were studied by real-time PCR in head-kidney leucocytes of sea bass after incubation with the extracellular products (ECPs) of the probiotic strain Vagococcus fluvialis L21 and polyinosinic:polycytidylic acid (POLY I:C), at different times (T1.5, T6, T12, T24, T48 and T72). In general, we can observe how pro-inflammatory cytokines IL-1ß, TNF-α, IL-6 and COX-2 studied displayed a strong peak after stimulation with 1.5 h of ECPs of V. fluvialis L21, significant differences (P < 0.05) exist with other periods and with the POLY I: C at the same time. Similarly to the case of IL-10 also produced a statistically significant (P < 0.05) peak of expression on leukocytes that were stimulated with the ECPs of V. fluvialis L21. In the case of Mx gene expression, we note that in almost all sampling times there is an up-regulation of the Mx gene in leucocytes incubated with ECPs and POLY I:C compared to the control and Mx expression was higher in leucocytes that were stimulated with the ECPs of V. fluvialis for all times, except in T24. With these results we can consider that the ECPs of V. fluvialis L21 have a great power of stimulating the in vitro expression of immune-related genes and may even be useful as adjuvants for vaccine in aquaculture.

Periodic nanostructures on unpolished substrates and their integration in solar cells.

We present a novel fabrication process based on laser interference lithography, lift-off and reactive ion etching, which allows us to fabricate periodic nanostructures on photovoltaic substrates with an average root mean square (RMS) roughness of 750 nm. We fabricate nanostructures on unpolished crystalline silicon substrates, which reduces their reflectance 30% as fabricated. When an additional passivation layer is deposited, the light trapping grows, achieving a reflectance reduction of 60%. In addition, we have successfully integrated the nanostructured substrates in silicon wafer-based solar cells following standard processes, achieving a final efficiency of 15.56%.

NFC as a Childhood Obesity Treatment Tool.

Childhood Obesity is associated with a wide range of serious health complications and constitutes an increased risk of premature syndromes, including diabetes or heart diseases. Its treatment seems to be complicated. So, in order to help parents we have developed a system that will try to make easier the process of choosing foodstuff for overweight and obese children at the supermarket. To interact with the system, Near Field Communication mobile phones and tags are used. Those tags would have nutritional information such as energy or fat contain of each product. When the interaction takes place, the system will generate an alert determining if the product is adequate for the user diet or not. Decision will be influenced by specific prescript diets, which would have been previously generated by the system based on user profile parameters. At the same time the diet is established, the shopping list would be generated automatically. Therefore, the user could download and print both things at home easily by the PC application. The system also takes into account physical activity of the user. Children mobile phone includes an accelerometer that will detect and collect user activities in order to modify calorical requirements and, if necessary, to change physical activity too. In the future, it would be possible to extend this project system for adults, managing diets not just for obese and overweight, but also to diabetic or celiac people.

Influence of the shear stress and salinity on Anammox biofilms formation: modelling results.

Anammox biomass has a long duplication time and low yield, thus the process must be operated in reactors with good sludge retention, such as biofilm systems. Therefore, it would be important to research the ability of Anammox biomass to form biofilms under different conditions. The effects of shear stress and salinity (NaCl and CaCl2) on Anammox biofilm formation were studied. Anammox bacteria showed good attachment capacity, with an initial adhesion phase lasting for 5-7 days at the different flow rates tested (Reynolds numbers 54, 63, 188 and 400). A four-parameter model was developed and the experimental data fitted well into the model. The presence of 5 g/L of each of the two salts favoured the formation of Anammox biofilm. The effects of CaCl2 were stronger than those caused by NaCl. 15 g/L of NaCl was detrimental for the biofilm, probably due to an inhibitory effect.

[Hematological and neurological compromise due to vitamin B12 deficit in infant of a vegetarian mother: case report]. / Compromiso neurológico y hematológico por déficit de vitamina B12 en lactante hijo de madre vegetariana: caso clínico.

INTRODUCTION: Vitamin B12 deficiency is extremely common in strict vegetarians and their variants. Infants of vegetarian mothers have a higher risk of deficiency and are more prone to its effects. OBJECTIVE: To report a case in order to warn people about the importance of suspected vitamin B12 deficiency in children of vegetarian mothers. CASE REPORT: A 12-month old infant, daughter of a longtime vegetarian woman, who presented neurological and hematological compromise due to vitamin B12 deficiency, is discussed. After a short period of parenteral administration of cyanocobalamin and enteral nutrition, the patient evolved with clinical and laboratory improvement, although she still had residual development delay. CONCLUSIONS: Vitamin B12 deficiency is often not suspected by the pediatrician in healthy infants. Clinical manifestations can be nonspecific, such as apathy, food refusal and progressive impairment of psychomotor development. A nutritional anamnesis performed on the mother (with great emphasis on those strict vegetarians) to estimate her reserves in the period prior to, during and after delivery can be critical to detect the risk of this vitamin deficiency in young children.

[Update on acute management of inborn errors of metabolism]. / Actualización en el manejo agudo de errores congénitos del metabolismo.

Inborn metabolic disorders are genetic diseases which are uncommon each one, but together they are not. They are characterized by an enzimatic defect that blocks a metabolic pathway, producing specific signs and symptoms. The current article pretends be an updated guideline for their acute management which is based on: 1) Inmediate life support, hydroelectrolyte balance and sample procurement, 2) Avoiding the production of toxic endogenous metabolites and anabolism promotion, 3) The supplementation of substrates and 4) The removal of toxic substances. Their prompt suspicious, identification and treatment starting will be crucial for neurological prognosis and prevention of death.

Effect of lipopolysaccharides from Vibrio alginolyticus on the Mx gene expression and virus recovery from gilthead sea bream (Sparus aurata L.) experimentally infected with Nodavirus.

Infections with nodavirus affect a wild and farmed fish species throughout the world, mostly from the marine environment. The aim of this work was to determine the immune status of gilthead sea bream that comes as a result of a Nodavirus infection, induced by activation of the interferon response pathway by lipopolysaccharides from Vibrio alginolyticus and the expression of interferoninduced Mx protein in liver samples. The enhancement of Mx protein gene expression was detected in liver samples of experimentally nodavirus infected fish and, furthermore, the immunostimulant LPS of V. alginolyticus decreased almost three times the virus titration with respect to no-immunized or infected with nodavirus group of fish.

Assessment of frailty in the person with type 2 diabetes mellitus: Expert analysis.

INTRODUCTION: People with type 2 diabetes mellitus (DM2) have a higher prevalence of frailty compared to those without DM2. However, there is a lack of consensus on the diagnosis and clinical management of frail individuals with DM2. OBJECTIVES: This study aims to identify limitations and current needs in the use of the frailty concept in PCDM2 (people with DM2), as well as define and evaluate the dimensions that should be included in its routine clinical assessment. METHODS: A multidisciplinary team of eight health professionals from different hospitals in Spain participated in a process based on the nominal group technique. RESULTS: The study identified eight limitations in the assessment of frailty in PCDM2, categorized by importance, and 10 unmet needs related to the diagnosis and follow-up of the disease. Additionally, seven dimensions were identified that should be included in the definition of frail individuals with DM2, prioritized by importance and novelty. CONCLUSIONS: This article aims to increase knowledge and usage of the frailty concept in individuals with DM2 within the medical community. It also suggests the potential for future projects to develop a consensus definition of frailty tailored to this specific group.

Is unicentric familial papillary thyroid microcarcinoma different from multicentric?

BACKGROUND: Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC. DESIGN AND METHODS: Type of study: National multicenter longitudinal analytical observational study. STUDY POPULATION: Patients with FPTMC. STUDY GROUPS: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). STUDY VARIABLES: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. STATISTICAL ANALYSIS: Cox regression analysis and survival analysis. RESULTS: Ninety-four patients were included, 44% (n = 41) with unicentric FPTMC and 56% (n = 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%; p = 0.003), lymph node dissection (41 vs. 15%; p = 0.005) and therapy with radioactive iodine (96 vs. 73%; p = 0.002). Tumor stage was similar in both groups (p = 0.237), with a higher number of T3 cases in the group B (24 vs. 5%; p = 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%; p = 0.337), disease recurrence rate (21 vs. 8%; p = 0.159) and disease-free survival (p = 0.075). CONCLUSIONS: Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.

The in vitro effect of probiotic Vagococcus fluvialis on the innate immune parameters of Sparus aurata and Dicentrarchus labrax.

In this study we evaluated the effect of the probiotic Vagococcus fluvialis on the cellular immune unspecific system of two different fish species of great interest in aquaculture such as gilthead sea bream (Sparus aurata) and European sea bass (Dicentrarchus labrax). Leucocytes from head kidney of the two fish species were extracted and concentration adjusted to 10(7) cells ml(-1). Phagocytic and respiratory burst activity and the peroxidase content of leucocytes were observed 30 min after incubation with the probiotic Vagococcus fluvialis alive or inactivated with heat shock or UV-light at different concentrations of 10(7), 10(8), 10(9) cfu ml(-1) (final concentration 10(6), 10(7), 10(8) cfu ml(-1)). V. fluvialis produced dose-dependent increments in respiratory burst in sea bream leucocytes. The respiratory burst activity of sea bream head kidney leucocytes incubated with 10(6) cfu ml(-1) of live and inactivated bacteria was not stimulated. The highest values of peroxidase content were observed in sea bass cells with stimulation indexes higher than 1 in HK leucocytes incubated with 10(8) cfu ml(-1) of live and inactivated bacteria. Statistical analysis revealed that differences being only significant in sea bass leucocytes where 10(8) cfu ml(-1) bacteria denote statistically significant differences (P < 0.05) respect to other concentrations. Highest values of phagocytic activity were obtained in sea bass macrophages incubated with UV-light inactivated bacteria (27.33% ± 1.45), where significantly differences with sea bass HK leucocytes were detected. Our results suggest that the in vitro assays are a useful tool to optimize the effective dose of probiotic bacteria. Although in vivo studies are necessary to confirm the immunomodulatory effect of this strain.

Toxoplasmosis in cord blood transplantation recipients.

Toxoplasmosis is a devastating opportunistic infection that can affect immunocompromised patients such as cord blood transplantation (CBT) recipients. The clinical characteristics of 4 toxoplasmosis CBT patients treated at our institution are reviewed, together with 5 cases collected from the literature. The rate of toxoplasmosis in our hospital was 6% in CBT recipients and 0.2% in other types of allogeneic hematopoietic stem cell transplantation (P < 0.001). Five patients (56%) presented disseminated toxoplasmosis and 4 patients (44%) had localized infection in the central nervous system. In 5 of the 9 patients considered (56%), cytomegalovirus viral replication had been detected before the clinical onset of toxoplasmosis. Seven patients (78%) had previously developed graft-versus-host disease. All patients who exhibited disseminated disease died due to Toxoplasma infection. Pre-transplant serology was positive in 1 patient, negative in 3 patients, and not performed in another. Only 1 of these 5 patients with disseminated disease had received Toxoplasma prophylaxis with cotrimoxazole. It could be concluded that mortality in CBT patients with disseminated toxoplasmosis is unacceptably high. The negative results of serology in the majority of these cases, and its unspecific clinical presentation, makes diagnosis exceedingly difficult. Better diagnostic tests and prophylaxis strategy are needed in CBT recipients.