Thyroid as a target of adjuvant autoimmunity/inflammatory syndrome due to mRNA-based SARS-CoV2 vaccination: from Graves' disease to silent thyroiditis.

BACKGROUND: As COVID-19 became a pandemic, the urgent need to find an effective treatment vaccine has been a major objective. Vaccines contain adjuvants which are not exempt from adverse effects and can trigger the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is very little information about autoimmune endocrine disease and the ASIA after the use of mRNA-based SARS-CoV2 vaccination. CASE SERIES: We report three cases and also review the literature showing that the thyroid gland can be involved in the ASIA induced by the mRNA-based SARS-CoV2 vaccination. We present the first case to date of silent thyroiditis described in the context of SARS-CoV2 vaccination with Pfizer/BioNTech. Also, we discuss the first subacute thyroiditis in the context of SARS-CoV2 vaccination with the Moderna's vaccine. Finally, we provide another case to be added to existing evidence on Graves' disease occurring post-vaccination with the Pfizer/BioNTech vaccine. DISCUSSION: Adjuvants play an important role in vaccines. Their ability to increase the immunogenicity of the active ingredient is necessary to achieve the desired immune response. Both the Moderna and the Pfizer/BioNTech vaccines use mRNA coding for the SARS-CoV2 S protein enhanced by adjuvants. In addition, the cross-reactivity between SARS-CoV2 and thyroid antigens has been reported. This would explain, at least, some of the autoimmune/inflammatory reactions produced during and after SARS-CoV2 infection and vaccination. CONCLUSION: The autoimmune/inflammatory syndrome induced by adjuvants involving the thyroid could be an adverse effect of SARS-CoV2 vaccination and could be underdiagnosed.

Nutritional Aspects of Dysphagia Management.

This chapter describes the nutritional aspects of dysphagia management by starting with the definition of these two conditions (dysphagia and malnutrition) that share three main clinical characteristics: (a) their prevalence is very high, (b) they can lead to severe complications, and (c) they are frequently underrecognized and neglected conditions. From an anatomical standpoint, dysphagia can result from oropharyngeal and/or esophageal causes; from a pathophysiological perspective, dysphagia can be caused by organic or structural diseases (either benign or malignant) or diseases causing impaired physiology (mainly motility and/or perception disorders). This chapter gathers up-to-date information on the screening and diagnosis of oropharyngeal dysphagia, the consequences of dysphagia (aspiration pneumonia, malnutrition, and dehydration), and on the nutritional management of dysphagic patients. Concerning this last topic, this chapter reviews the rheological aspects of swallowing and dysphagia (including shear and elongational flows) and its influence on the characteristics of the enteral nutrition for dysphagia management (solid/semisolid foods and thickened liquids; ready-to-use oral nutritional supplements and thickening powders), with special focus on the real characteristics of the bolus after mixing with human saliva.

How to improve the diagnosis of eosinophilic esophagitis: Experience from a case series in Mexico. / Cómo mejorar el diagnóstico de esofagitis eosinofílica: experiencia de una serie de casos en México.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, immune disorder mediated largely by food antigens. It shares nonspecific symptoms with gastroesophageal reflux disease (GERD). EoE is rarely reported in Mexico, perhaps due to the racial characteristics of the population or because of insufficient diagnostic suspicion. AIMS: Our aim was to describe a Mexican cohort with EoE and evaluate the usefulness of the clinical history and endoscopy in the EoE diagnosis, in comparison with GERD patients. MATERIALS AND METHODS: A retrospective study was carried out on the clinical characteristics and endoscopic and histopathologic findings in patients with EoE, along with a case-control study on patients with GERD. The endoscopic images obtained were interpreted in a blind and randomized manner by 4 gastroenterologists, before and after providing them with information on the characteristic alterations of EoE. The esophageal biopsies were also blinded to 2 pathologists that evaluated their diagnostic correlation. The Fisher's exact test and Mann-Whitney U test were used in the statistical analysis. RESULTS: Fourteen patients with EoE were included in the study. Ten (71%) of them were men and the mean age of the patients was 35 years. There were more subjects with a personal history of asthma (p=0.0023) and food impaction (p=0.04) in the EoE group. The initial evaluation of the endoscopic findings showed 53% correct EoE interpretations and rose to 96% in the second revision (sensitivity 100%, specificity 71%, PPV 65%, NPV 100%). CONCLUSIONS: Mexican patients with EoE have similar characteristics to those of patients in western case series. Clinical awareness of the disorder increases endoscopic diagnosis in up to 40% of cases.

Corticosterone affects the differentiation of a neuronal cerebral cortex-derived cell line through modulation of the nicotinic acetylcholine receptor.

Chronic exposure to stress hormones has an impact on brain structures relevant to cognition. Nicotinic acetylcholine receptors (AChRs) are involved in numerous cognitive processes including learning and memory formation. In order to better understand the molecular mechanisms of chronic stress-triggered mental disease, the effect of corticosterone (CORT) on the biology of AChRs was studied in the neuronal cell line CNh. We found that chronic treatment with CORT reduced the expression levels of the α7-type neuronal AChR and, to a lesser extent, of α4-AChR. CORT also delayed the acquisition of the mature cell phenotype in CNh cells. Chronic nicotine treatment affected the differentiation of CNh cells and exerted a synergistic effect with CORT, suggesting that AChR could participate in signaling pathways that control the cell cycle. Overexpression of α7-AChR-GFP abolished the CORT effects on the cell cycle and the specific α7-AChR inhibitor, methyllycaconitine, mimicked the proliferative action exerted by CORT. Whole-cell voltage-clamp recordings showed a significant decrease in nicotine-evoked currents in CORT-treated cells. Taken together, these observations indicate that AChRs, and the α7-AChR in particular, could act as modulators of the differentiation of CNh cells and that CORT could impair the acquisition of a mature phenotype by affecting the function of this AChR subtype.

Dependence of eelgrass (Zostera marina) light requirements on sediment organic matter in Massachusetts coastal bays: implications for remediation and restoration.

Using a calibrated bio-optical model we determined that the optical water quality conditions in several nitrogen-impaired embayments and in one unimpaired system were within the range of values known to support eelgrass growth. We also used the model to identify a range of light requirements for eelgrass (Zostera marina). Higher eelgrass light requirements, expressed as a percentage of surface-incident irradiance, corresponded with higher sediment organic matter content. These results corroborated findings by previous studies which indicate a generalized relationship: seagrasses growing in turbid conditions with poorer water and sediment quality have higher light requirements than those growing in less degraded conditions. The mechanistic reason for the variation in light requirements is still not completely explained and cannot be attributed to a single independent variable. Varying light requirement have important implications for eelgrass protection and should be considered when setting restoration targets for eelgrass in water quality and nitrogen remediation programs.

Linear viscoelastic behaviour of oil-in-water food emulsions stabilised by tuna-protein isolates.

This work deals with the manufacture of oil-in-water food emulsions stabilised by tuna proteins. The influence of protein and oil concentrations on the linear viscoelastic properties and microstructure of these emulsions was analysed. Stable emulsions with suitable linear viscoelastic response and microstructural characteristics were formulated with 70 wt.% oil and, at least, 0.25 wt.% tuna protein. Similarly, emulsions with oil concentrations between 45 and 70 wt.% were prepared using 0.50 wt.% protein. All these emulsions showed a predominantly elastic response in the linear viscoelastic region and a well-developed plateau region in its mechanical spectrum. Rheological and droplet size distribution results pointed out an extensive droplet flocculation, due to interactions among emulsifier molecules located at the oil-water interface of adjacent droplets. As a result, the linear viscoelastic behaviour was controlled by protein-protein interactions, allowing the use of the plateau modulus to successfully normalise both the storage and loss moduli as a function of frequency onto a master curve, irrespective of the selected emulsion formulation.

Dialysis Efficiency of AN69, a Semisynthetic Membrane Not Well Suited for Diffusion.

AN69 membrane is not suited for diffusion, with an suggested limit at 25 mL/min dialysate flow rate. When prescribing continuous hemodialysis this threshold must be surpassed to achieve. We designed a study aimed to check if a higher dose of dialysis could be delivered efficiently with this membrane. Ten ICU patients under continuous hemodiafiltration with 1.4 m(2) AN69 membrane were included and once a day we set the monitor to exclusively 50 mL/min dialysate flow rate and 250 mL/min blood flow rate and after 15 minutes measured dialysate saturation for urea, creatinine, and ß 2-microglobulin. We detected that urea saturation of dialysate was nearly complete (1.1 ± 0.09) for at least 40 hours, while creatinine saturation showed a large dispersion (0.86 ± 0.22) and did not detect any relation for these variables with time, blood flow, or anticoagulation regime. Saturation of ß 2-microglobulin was low (0.34 ± 0.1) and decreased discretely with time (r (2) = 0.15, P < 0.05) and significantly with TMP increases (r (2) = 0.31, P < 0.01). In our experience AN69 membrane shows a better diffusive capability than previously acknowledged, covering efficiently the range of standard dosage for continuous therapies. Creatinine is not a good marker of the membrane diffusive capability.

Does the difference in donor and recipient weight influence renal graft survival?

INTRODUCTION: Grafts from older donors or those in recipients with a greater body mass index (BMI) as compared with the donor may develop hyperfiltration syndrome that shortens renal graft survival. OBJECTIVES: To assess whether the differences in weight and BMI between donor and recipient correlated with renal function, proteinuria, or graft survival among recipients of grafts from expanded criteria donors. MATERIALS AND METHODS: We undertook a prospective, observational study in 180 recipients of grafts from expanded criteria donors performed between 1999 and 2006. All grafts had been biopsied previously for viability. The recipients underwent immunosuppression with basiliximab, late introduction of tacrolimus, mycophenolate mofetil and steroids. The study population was divided into three groups, depending on the tertile of the donor-to-recipient weight ratio (<1, n=64; 1-1.2, n=56; >1.2, n=60), and the donor-to-recipient BMI ratio (<0.97, n=59; 0.97-1.13, n=60; >1.13, n=60). The glomerular filtration rate was estimated from the modified diet in renal disease (MDRD) equation. RESULTS: The mean age of the donors was 63.54 years and of the recipients, 58.38 years. The proportion of male-to-female donors was 52:48 and recipients 57.8:42.2 (P=NS). No significant differences in overall graft survival were observed between the tertiles. There was a negative correlation between the donor-to-recipient weight ratio and serum creatinine value at 1 (P<.001), 3 (P=.013), and 12 months (P=.005) after transplantation, and a positive correlation with the MDRD at 1 month (P<.001). No relation was noted between weight and proteinuria at 1 (P=.25), 3 (P=.51), or 12 months (P=.90). The results were similar after analyzing the ratio of the BMI to creatinine, MDRD or proteinuria, as well as in cases of a female donor to a male recipient. CONCLUSIONS: Differences in weights between the donor and the recipient did not appear to affect graft survival or proteinuria among patients receiving grafts from expanded criteria donors, though it may be related to renal function during the early posttransplant stages.

Creatinine clearance and proteinuria as early markers of kidney graft survival.

INTRODUCTION: In patients who receive a kidney transplant from expanded criteria donors (ECDs), few studies are available concerning the relation between the clinical characteristics, pretransplant biopsies, and graft outcomes. AIM: To identify early clinical markers predicting worse graft survival in recipients of kidneys from ECDs. MATERIALS AND METHODS: Between 1999 and 2006, we performed a prospective, observational study in 180 recipients of kidney grafts from ECDs that had undergone a preoperative biopsy to evaluate viability. The patients received immunosuppression with basiliximab, late introduction of tacrolimus, mycophenolate mofetil, and steroids. Data were gathered on demographic and posttransplantation clinical characteristics at 1, 3, 6, and 9 months, including estimates of proteinuria and of the glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: The mean age of the donors was 63.54 years and of the recipients, 58.38 years. A creatinine clearance below the median (40 mL/min, interquartile range 32-50 mL/min) in the first posttransplant year was significantly associated with worse death-censored graft survival (log-rank 14.22, P<.0001). A proteinuria value above the median (100 mg/24 h, interquartile range 40-275 mg/24 h) at 1 year posttransplant significantly reduced the death-censored graft survival (log-rank 14.3, P<.0001). Multivariate Cox analysis showed that a creatinine clearance<40 mL/min in the first year (hazards ratio [HR] 5.7, 95% Confidence Interval [CI] 1.62-20.37; P=.007) and proteinuria at 1 year greater tan 100 mg/24 h (HR 8.3, 95% CI 2.15-32.06; P=.002) were independent risk factors for death-censored graft loss after adjusting for donor age and acute rejection episodes. CONCLUSIONS: Limited renal function and/or low proteinuria at 1 year posttransplant were associated with worse kidney graft survival among recipients of kidneys from ECDS.

Boundary lipids in the nicotinic acetylcholine receptor microenvironment.

The structural and functional properties of the nicotinic acetylcholine receptor (AChR), the archetype molecule in the superfamily of Cys-looped ligand-gated ion channels, are strongly dependent on the lipids in the vicinal microenvironment. The influence on receptor properties is mainly exerted by the AChR-vicinal ("shell" or "annular") lipids, which occur in the liquid-ordered phase as opposed to the more disordered and "fluid" bulk membrane lipids. Fluorescence studies from our laboratory have identified discrete sites for fatty acids, phospholipids, and cholesterol on the AChR protein, and electron-spin resonance spectroscopy has enabled the establishment of the stoichiometry and selectivity of the shell lipid for the AChR and the disclosure of lipid sites in the AChR transmembrane region. Experimental evidence supports the notion that the interface between the protein moiety and the adjacent lipid shell is the locus of a variety of pharmacologically relevant processes, including the action of steroids and other lipids. I surmise that the outermost ring of M4 helices constitutes the boundary interface, most suitable to convey the signals from the lipid microenvironment to the rest of the transmembrane region, and to the channel inner ring in particular.

Development of highly-transparent protein/starch-based bioplastics.

Striving to achieve cost-competitive biomass-derived materials for the plastics industry, the incorporation of starch (corn and potato) to a base formulation of albumen and glycerol was considered. To study the effects of formulation and processing, albumen/starch-based bioplastics containing 0-30 wt.% starch were prepared by thermo-plastic and thermo-mechanical processing. Transmittance measurements, DSC, DMTA and tensile tests were performed on the resulting bioplastics. Optical and tensile properties were strongly affected by starch concentration. However, DMTA at low deformation proved to be insensitive to starch addition. Thermo-mechanical processing led to transparent albumen/starch materials with values of strength at low deformation comparable to commodity plastics. Consequently, albumen biopolymers may become a biodegradable alternative to oil-derived plastics for manufacturing transparent packaging and other plastic stuffs.

Viscosity modification of high-oleic sunflower oil with polymeric additives for the design of new biolubricant formulations.

Although most common lubricants contain mineral or synthetic oils as basestocks, new environmental regulations are demanding environmentally friendly lubricants. In this sense, vegetable oils represent promising alternatives to mineral-based lubricants because of their high biodegradability, good lubricity, and low volatility. However, their poor thermooxidative stability and the small range of viscosity represent a clear disadvantage to be used as suitable biolubricants. The main objective of this work was to develop new environmentally friendly lubricant formulations with improved kinematic viscosity values and viscosity thermal susceptibility. With this aim, a high-oleic sunflower oil (HOSO) was blended with polymeric additives, such as ethylene vinyl acetate (EVA) and styrene-butadiene-styrene (SBS) copolymers, at different concentrations (0.5-5% w/w). Dynamic viscosity and density measurements were performed in a rotational rheometer and capillary densimeter, respectively, in a temperature range between 25 and 120 degrees C. An Arrhenius-like equation fits the evolution of viscosity with temperature fairly well. Both EVA and SBS copolymers may be satisfactorily used as additives to increase the viscosity of HOSO, thus improving the low viscosity values of this oil. HOSO viscosity increases with polymer concentration. Specifically, EVA/HOSO blends exhibit higher viscosity values, which are needed for applications such as lubrication of bearings and four-stroke engines. On the other hand, viscositythermal susceptibility of HOSO samples increases with EVA or SBS concentration.

Rheological behaviour and physical properties of controlled-release gluten-based bioplastics.

Bioplastics based on glycerol, water and wheat gluten have been manufactured in order to determine the effect that mechanical processing and further thermal treatments exert on different thermo-mechanical properties of the biomaterials obtained. An "active agent", KCl was incorporated in these matrices to develop controlled-release formulations. Oscillatory shear, dynamic mechanical thermal analysis (DMTA), diffusion and water absorption tests were carried out in order to study the influence of the above-mentioned treatments on the physico-chemical characteristics and rheological behaviour of these bioplastic samples. Wheat gluten protein-based bioplastics studied in this work present a high ability for thermosetting modification, due to protein denaturation, which may favour the development of a wide variety of biomaterials. Bioplastic hygroscopic properties depend on plasticizer nature and processing procedure, and may be a key factor for industrial applications where water absorption is required. On the other hand, high water absorption and slow KCl release from bioplastic samples (both of them suitable properties in agricultural applications) may be obtained by adding citric acid to a given formulation, at selected processing conditions.

Ceramides modulate cell-surface acetylcholine receptor levels.

The effects of ceramides (Cer) on the trafficking of the nicotinic acetylcholine receptor (AChR) to the plasma membrane were studied in CHO-K1/A5 cells, a clonal cell line that heterologously expresses the adult murine form of the receptor. When cells were incubated with short- (C6-Cer) or long- (brain-Cer) chain Cer at low concentrations, an increase in the number of cell-surface AChRs was observed concomitant with a decrease in intracellular receptor levels. The alteration in AChR distribution by low Cer treatment does not appear to be a general mechanism since the surface expression of the green fluorescent protein derivative of the vesicular stomatitis virus protein (VSVG-GFP) was not affected. High Cer concentrations caused the opposite effects, decreasing the number of cell-surface AChRs, which exhibited higher affinity for [125I]-alpha-bungarotoxin, and increasing the intracellular pool, which colocalized with trans-Golgi/TGN specific markers. The generation of endogenous Cer by sphingomyelinase treatment also decreased cell-surface AChR levels. These effects do not involve protein kinase C zeta or protein phosphatase 2A activation. Taken together, the results indicate that Cer modulate trafficking of AChRs to and stability at the cell surface.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Majorcan hospitals: high prevalence of the epidemic clone EMRSA-15.

Clinical isolates (n = 389) of methicillin-resistant Staphylococcus aureus (MRSA) recovered from 371 patients between January 2003 and June 2004 at the three major public hospitals on the island of Majorca, Spain were studied. The clonal relatedness of MRSA isolates was determined by pulsed-field gel electrophoresis (PFGE) after digestion with SmaI. During the study period, MRSA was found in 31% of patients with S. aureus-positive cultures. PFGE analysis identified three predominant clones, affecting 94% of the patients. The three clones had been detected since 1999 in one hospital, and were designated as clones A, B and C. Whereas clones A and B (multidrug-resistant) were related to the two most prevalent clones in Spain at this time, clone C was identical to EMRSA-15, currently one of the most common MRSA clones in UK hospitals and also detected in other countries, but rarely in Spanish hospitals. This imported epidemic clone was detected in c. 10% of patients admitted to one of the three hospitals in 2002, but its prevalence has increased significantly (32% of the patients investigated in the three hospitals in the present study), and this clone also accounted for 44% of the isolates from non-hospitalised patients. Even though EMRSA-15 showed the least multidrug resistance of the three major clones, it was apparently more virulent, since it was associated significantly (p 0.001) with bacteraemia, and positive blood cultures were documented for 21% of the patients infected by this clone, compared with only 10% and 7% of patients infected with clones A and B, respectively.

Rheological characterization of polysaccharide-surfactant matrices for cosmetic O/W emulsions.

Rheometrical techniques can be profitably used for polysaccharide matrices in order to evaluate their suitability for the preparation of stable cosmetic O/W emulsions. In particular, the rheological properties of aqueous scleroglucan systems were investigated under continuous and oscillatory shear conditions in a polymer concentration range (0.2-1.2% w/w) embracing the sol/gel transition. The effects due to the addition of two different surfactants (up to 10% w/w) were examined at constant polymer concentration (0.4% w/w). The selected additives are a nonionic polymeric siliconic surfactant (dimethicone copolyol) and a cationic surfactant (tetradecyltrimethylammonium bromide), respectively. Polysaccharide-surfactant interactions leading to complex formation were detected also through rheology. The combined action of both nonionic and cationic surfactants in the polymer solution was examined at two different surfactant concentration levels (5 and 10% w/w), demonstrating the beneficial effects produced on the mechanical properties of the polymer matrix by the coexistence of both surfactants. Such beneficial effects are confirmed by the stability and rheology shown by the emulsions prepared. In this way, the results point out the good agreement between the rheology of the continuous phase and the final characteristics of the emulsion obtained.

Resultados de la aplicación de neurolépticos de depósito en pacientes psicóticos del Hospital "Víctor Larco Herrera" 2002-2003 / Results of the application of antipsychotics of deposit in psychotics patients of the Hospital

El Programa de Neurolépticos de Acción prolongada (NAP) es único en su género en el país. Nació con el propósito de evitar las recaídas y posteriores hospitalizaciones y evitar la larga permanencia de pacientes psicóticos en el Hospital "Víctor Larco Herrera". Si bien estos propósitos se mantuvieron, el programa necesitó de una reorganización que mejorase sus procesos. En la actualidad, el número de pacientes casi llega a los 500 y a pesar de que el sistema hospitalario aún acoge la idea de los programas organizados y sistematizados y no haberse desenvuelto al óptimo de su capacidad, el Programa NAP ha demostrado su eficiencia al conseguir con pocos recursos, una organización y un equipo cohesionado, disminuir los modos y frecuencias de aplicación, elevar el cumplimiento, disminuir las hospitalizaciones y contribuir a crear más conciencia de enfermedad en sus pacientes. Esperamos que en el futuro se creen en nuestro Hospital más programas que sistematicen y especialicen la atención en beneficio de los pacientes que acuden a él.

Metabolic cholesterol depletion hinders cell-surface trafficking of the nicotinic acetylcholine receptor.

The effects of metabolic inhibition of cholesterol biosynthesis on the trafficking of the nicotinic acetylcholine receptor (AChR) to the cell membrane were studied in living CHO-K1/A5, a Chinese hamster ovary clonal line that heterologously expresses adult alpha2betadeltaepsilon mouse AChR. To this end, we submitted CHO-K1/A5 cells to long-term cholesterol deprivation, elicited by Mevinolin, a potent inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase and applied a combination of biochemical, pharmacological and fluorescence microscopy techniques to follow the fate of the AChR. When CHO-K1/A5 cells were grown for 48 h in lipid-deficient medium supplemented with 0.5 microM Mevinolin, total cholesterol was significantly reduced (40%). Concomitantly, the maximum number of binding sites (Bmax) of the cell-surface AChR for the competitive antagonist alpha-bungarotoxin was reduced from 647+/-30 to 352+/-34 fmol/mg protein, i.e. by 46%. The apparent dissociation constant (Kdapp) for alpha-bungarotoxin of the AChRs remaining at the cell surface was not modified by cholesterol depletion. Similarly, the half-concentration inhibiting the specific binding of the radioligand (IC50) for another competitive antagonist, d-tubocurarine, did not differ from that in control cells. The decrease in cell-surface AChR was paralleled by an increase in intracellular AChR levels, which rose from 44+/-2.1% in control cells to 74+/-3.3% in Mevinolin-treated cells. When analyzed by wide-field fluorescence microscopy, the fluorescence signal arising from alpha-bungarotoxin labeled cell-surface AChRs was reduced by approximately 70% in Mevinolin-treated cells. The distribution of intracellular AChR also changed: Alexa594-alpha-bungarotoxin-labeled AChR exhibited a highly compartmentalized pattern, concentrating at the perinuclear and Golgi-like regions. Temperature-arrest of protein trafficking magnified this effect, emphasizing the Golgi localization of the AChR. Colocalization studies using the transiently expressed fluorescent trans-Golgi/trans-Golgi network marker pEYFP/human beta1,4-galactosyltransferase and the trans-Golgi network marker syntaxin 6 provided additional support for the Golgi localization of intracellular AChRs. The low AChR cell-surface expression and the increase in intracellular AChR pools in cholesterol-depleted cells raise the possibility that cholesterol participates in the trafficking of the receptor protein to the plasmalemma and its stability at this surface location.