Combined Supplementation of Two Selenium Forms (Organic and Inorganic) and Iodine in Dairy Cows' Diet to Obtain Enriched Milk, Cheese, and Yogurt.

This study evaluated the effects of dietary supplementation in dairy cows with two Se forms (organic and inorganic) and I at the maximum levels permitted in the European Union, with the aim to obtain naturally enriched milk and derived products. A total of 20 Holstein Friesian cows in lactation were fed 2 diets for 64 days: a control diet with a supply of 0.57 mg of inorganic Se and 0.57 mg of I per kg of ration in dry matter (DM), and an experimental diet (SeI) with a supply of 0.34 mg of inorganic Se, 0.23 mg of organic Se, and 5.68 mg of I per kg of ration in DM. The SeI diet did not modify the performance or, in general, the metabolic profile of cows. Se and I levels in milk were affected by diet type and time of measurement (p < 0.01). Thus, a marked increase of both microminerals was evident between the beginning and the end of the test, when the SeI diet was administered. For Se, this increase ranged from 1.95 to 3.29 µg/100 g of milk; and for I, from 19.69 to 110.06 µg/100 g of milk. The SeI diet increased (p < 0.01) the Se and I content in the cheese, reaching levels of 16.4 µg/100 g for Se and 269.7 µg/100 g for I. An increase in I was observed in yogurt from the SeI diet (p < 0.001). The supplementation of two forms of Se and I in the cows' ration, at the levels evaluated, produced milk and dairy products enriched in these microelements without altering their quality parameters. However, a responsible intake of these products is necessary to avoid risks of deficiencies or excesses that could negatively affect the health of consumers.

The host Rab9a/Rab32 axis is actively recruited to the Trypanosoma cruzi parasitophorous vacuole and benefits the infection cycle.

Trypanosoma cruzi, the etiological agent of Chagas disease is a protozoan parasite that infects phagocytic and non-phagocytic mammalian cells. At early stages of infection, trypomastigotes, the infective forms of this parasite, localize in a vesicular compartment called the T. cruzi parasitophorous vacuole until the exit of parasites to the host cell cytoplasm where continue their infective cycle. Rab proteins participate in the membrane traffic's molecular machinery, functioning as central regulators of vesicle recognition and transport. In previous work, we demonstrated that endocytic Rabs are key factors of the T. cruzi infection process in non-phagocytic cells, regulating the formation and the maturation of the vacuole. In this work, we identified and characterized other molecular components of the vesicular transport pathways and their participation in the T. cruzi infection. We found that Rab9a and Rab32, two regulators of the endocytic and autophagic pathways, were actively recruited to the T. cruzi vacuoles and favored the late stages of the infective process. The recruitment was specific and dependent on T. cruzi protein synthesis. Interestingly, Rab32 association depends on the presence of Rab9a in the vacuolar membrane, while the inhibition of the cysteine-protease cruzipain, a T. cruzi virulence factor, significantly decreases both Rab9a and Rab32 association with the vacuole. In summary, this work showed for the first time that specific molecules produced and secreted by the parasite can subvert intracellular components of host cells to benefit the infection. These new data shed light on the complex map of interactions between T. cruzi and the host cell and introduce concepts that can be useful in finding new forms of intervention against this parasite in the future.

Clinical-epidemiological analysis of patients with elevated lipoprotein A in a third level hospital. / Análisis clínico-epidemiológico de pacientes con lipoproteína(a) elevada en un hospital de tercer nivel.

OBJECTIVE: The objective of the study is to describe the clinical and epidemiological characteristics of our patients with elevated Lp(a). MATERIALS AND METHODS: A descriptive cross-sectional study was conducted on 316 patients with elevated Lp(a) (>125 nmol/L) in a random sample between January and August 2022. We measured epidemiological, anthropometric, clinical and laboratory variables (lipid metabolism parameters, carbohydrates and hormones). RESULTS: Mean age of our sample subject's was 59 ± 15 years with 56% males. The average BMI was 27.6 kg/m2 (71% with elevated BMI). Elevated waist circumference was observed in 54.1% of men and 77.8% of women. 48% had hypertension, 30.7% had diabetes mellitus and 91.5% dyslipidemia. Only 39.7% of the patients had never smoked. The mean values of total cholesterol were 158 ± 45 mg/dl, LDL was 81 ± 39 mg/dl, HDL was 53 ± 17 mg/dl, Triglycerides were 127 ± 61 mg/dl, and Lp(a) was 260 ± 129 nmol/L. Regarding lipid lowering treatment, 89% were on statins, 68.6% on ezetimibe, and 13.7% on PCSK9 inhibitors. 177 patients (57,7%) had established cardiovascular disease (CVD), 16.3% had polyvascular disease, 11.7% had subclinical CVD, and 30.6% had no known CVD. Among patients with established CVD, 174 (98.3%) were on lipid-lowering treatment (97.2% on statins) and 86.4% were on antiplatelet therapy. The mean age of cardiovascular events was 55 ± 12 years in males and 60 ± 11 years in females. 65,1% of female and 56,2% of male patients suffered an early cardiovascular event. CONCLUSIONS: Patients with elevated Lp(a) are at very high cardiovascular risk, particularly for early cardiovascular disease.

Influence of Dietary Lipid Source Supplementation on Milk and Fresh Cheese from Murciano-Granadina Goats.

This study analyzes the influence of the incorporation of flaked linseed and fish oil in the diet on the resulting milk and cheese. Three dietary treatments were assayed in 350 milking Murciano-Granadina multiparous goats in full-lactation: a control diet and two experimental diets, one including flaked linseed (FL) at 3.88% of dry matter, and the other containing salmon oil (SO) at 2.64% of dry matter for three periods of 21 d. None of the dietary treatments affected the daily milk yield, cheese yield, or the physicochemical parameters of the milk and cheese. Regarding the fatty acid profile (FA), the milk and cheese from animals whose diets were supplemented with SO had a higher percentage of fatty acids than those obtained with the FL-supplemented diet, except for C18:0, C18:1, C18:2 n-6, trans-9, trans-12 C18:2, cis-9, trans-11 C18:2, C18:3, and C19:0, which reached their highest levels in milk obtained with the diet supplemented with FL. The decrease in the percentage of C16:0 was greater in the milk derived from the FL diet than from the SO diet. The FL-supplemented diet improved the nutritional value of milk due to a reduction in saturated fatty acids (SFAs) and increases in polyunsaturated fatty acids (PUFAs) and conjugated linoleic acid (CLA). The decrease in n-6/n-3 in the observed milk was more pronounced with the FL diet. No differences in the sensory profile were found for the milk and cheese derived from the different dietary treatments. Dietary n-3 treatments modified the fatty acid profile without making any sensory difference to milk and fresh cheese, accompanied by marginal modifications to the physicochemical profile. We conclude that dietary supplementation with flaked linseed or fish oil produces milk and cheese from Murciano-Granadina goats with a higher nutritional quality without modifying the sensory profile of the corresponding products obtained from animals that were fed a routine diet.

An 11-year epidemiological analysis of schistosomiasis in Ecuador: Investigating a non-endemic, neglected, and challenging-to-identify parasitic disease.

Schistosomiasis is a neglected disease caused by parasites of the genus Schistosoma and transmitted by snails of the genus Biomphalaria. At least five species have the potential to infect humans living in or visiting tropical areas worldwide. In Latin America, Schistosoma mansoni is particularly common; however, it has not been reported in Ecuador. In this study, we assess the available official data on schistosomiasis in Ecuador to describe the prevalence of this neglected disease. We conducted a nationwide study to determine the demographic and spatial distribution patterns of schistosomiasis infection in Ecuador, using hospital discharge official data as a proxy for infection incidence from 2011 to 2021. We calculated crude and age-sex-adjusted morbidity and hospital admission rates by region, province, canton, and elevation. In the last decade of available data, schistosomiasis accounted for at least 551 hospital admissions in Ecuador. Women represented 53.7% (n = 296) of cases, equivalent to 3.2 cases per 1,000,000 inhabits. The highest number of cases (61.2%, n = 337) was found in the Coastal region. However, the highest incidence rates were observed in the Amazon region's provinces of Pastaza (173.44 cases/1,000,000).

Can Moderate Levels of Organic Selenium in Dairy Cow Feed Naturally Enrich Dairy Products?

This work studied the effect of dairy cow ration supplementation with inorganic plus organic Se on metabolic status, milk yield, and the quality of milk and dairy products, especially its Se content. Twenty multiparous Holstein Friesian lactating cows were assigned to two feeding treatments. The cows were fed with 22.5 kg dry matter (DM) of total mixed ration (11.75 kg DM of forage plus 10.75 kg DM of concentrate) by head. There were two different concentrates with the same Se content (0.240 mg/kg of ration DM) but with different Se sources: The control (CON) was supplemented with inorganic Se (sodium selenite); and the other (IOSe) was supplemented with sodium selenite plus organic Se (Sel-Plex®), at 0.144 and 0.096 mg Se/kg of ration DM, respectively. The results indicated that, in general, the IOSe treatment did not modify the metabolic profile, and even decreased the total oxidant status (p < 0.05) and did not lead to a deterioration of quality and yield of milk. However, milk and cheese from IOSe had higher Se content (an increase of 29.7% and 38.2%, respectively) than CON (p < 0.01), but this effect was not observed in yogurt. In general, physical or sensorial parameters of cheeses did not show differences between treatments. Moderate inorganic plus organic Se supplementation may be more effective than inorganic Se, increasing the Se content in milk and cheese, without causing a deterioration in quality or productive parameters.

The chromatin nuclear protein NUPR1L is intrinsically disordered and binds to the same proteins as its paralogue.

NUPR1 is a protumoral multifunctional intrinsically disordered protein (IDP), which is activated during the acute phases of pancreatitis. It interacts with other IDPs such as prothymosin α, as well as with folded proteins such as the C-terminal region of RING1-B (C-RING1B) of the Polycomb complex; in all those interactions, residues around Ala33 and Thr68 (the 'hot-spot' region) of NUPR1 intervene. Its paralogue, NUPR1L, is also expressed in response to DNA damage, it is p53-regulated, and its expression down-regulates that of the NUPR1 gene. In this work, we characterized the conformational preferences of isolated NUPR1L and its possible interactions with the same molecular partners of NUPR1. Our results show that NUPR1L was an oligomeric IDP from pH 2.0 to 12.0, as judged by steady-state fluorescence, circular dichroism (CD), dynamic light scattering, 1D 1H-NMR (nuclear magnetic resonance), and as indicated by structural modelling. However, in contrast with NUPR1, there was evidence of local helical- or turn-like structures; these structures were not rigid, as judged by the lack of sigmoidal behaviour in the chemical and thermal denaturation curves obtained by CD and fluorescence. Interestingly enough, NUPR1L interacted with prothymosin α and C-RING1B, and with a similar affinity to that of NUPR1 (in the low micromolar range). Moreover, NUPR1L hetero-associated with NUPR1 with an affinity of 0.4 µM and interacted with the 'hot-spot' region of NUPR1. Thus, we suggest that the regulation of NUPR1 gene by NUPR1L does not only happen at the DNA level, but it could also involve direct interactions with NUPR1 natural partners.

Reduction of androstenone perception in pan-fried boar meat by different masking strategies.

BACKGROUND: Consumers highly sensitive to androstenone María (AND) will probably reject meat from entire male pigs, which tends to have high levels of this hormone. To avoid this, the effect of different masking strategies (sprinkling with mixed spices or fennel, marinating and breading with garlic-parsley or curry) on the sensory parameters of pork loin chops obtained from entire animals with high levels of AND (1.0-2.9 mg kg-1 AND in fat) and castrated animals (<0.4 mg kg-1 AND in fat), both with low levels of skatole (<0.1 mg kg-1 skatole in fat) was investigated. RESULTS: The garlic-parsley breadcrumbs led to the highest reduction in the perception of AND compared with the other masking strategies used, and preserved the juiciness of the product. There was a negative correlation between AND and fat content. CONCLUSION: AND odor and flavor can be reduced in meat from entire male pigs by using suitable strategies, the best strategy being the garlic-parsley breadcrumbs. © 2017 Society of Chemical Industry.

Estado gingival de dientes temporales con y sin restauración de coronas de acero en niños de 3 a 9 años / Gingival Condition around the Temporary Teeth with and without Steel Crown Restorations in 3-to-9 Year-Old Children

Antecedentes: Con las coronas de acero es posible conservar los dientes temporales hasta su exfoliación fisiológica; sin embargo, en la literatura existe controversia con respecto al comportamiento del tejido gingival de los dientes restaurados con coronas de acero. Propósito: /Analizar el estado gingival de dientes temporales con restauración de coronas de acero y sin esta en niños de 3 a 9 años de edad atendidos en las clínicas odontológicas de la Pontificia Universidad Javeriana, en Bogotá, entre 2013 y 2014. Métodos: Se realizó un estudio descriptivo de corte transversal. Se observaron 110 dientes temporales restaurados con corona de acero y sus antagonistas sin corona de acero. Se analizaron los índices gingival y de biopelíeula, la adaptación clínica de las coronas de acero y la presencia o ausencia de exceso de cemento en todas las superficies de los dientes. Resultados: No hubo diferencias estadísticamente significativas entre la adaptación de las coronas de acero y el estado gingival. El único indicador relevante fixe la superficie vestibular (p = 0,018). Por otra parte, el estado gingival y la biopelíeula presentaron una baja correlación (¡9 %). Conclusiones: El índice gingival de dientes restaurados con coronas de acero y sin estas presentó una correlación positiva entre la inflamación gingival y la edad de la población pediátrica, aun cuando la retención de biopelíeula no fue significativa.

Bideground: Ihc use of steel crowns enables to preserve the temporary teeth until their physiological changeover; however, in the literature there is a controversy regarding the behavior of the gingival tissue around teeth restored with steel crowns. Purpose: To analyze the gingival condition around the temporary teeth that have been restored with and without steel crowns in children from 3 to 9 years old who attended to the dental clinic at the Pontificia Universidad de Colombia in Bogotá between 2013 and 2014. Methods: A cross-sectional descriptive study was carried out and 110 temporary teeth restored with steel crown were observed and compared to the teeth restored without it. Biofilm and gingival indexes were analyzed as well as the steel crown clinical adaptation and the presence of cement excess in any of the dental surfaces. Results: No significant statistical difference was found bccwccn the steel crown adaptation and the gingival condition. 'Ihc only relevant indicator was the vestibular surface (p = 0.018). On the other hand, both the biofilm and the gingival condition showed a poor correlation (19%). Conclusions: Ihc gingival index in teeth restored with and without steel crown showed a positive correlation between gingival inflammation and the children populación age, even chough the biofilm retention was not significant.

Pivotal Role of the Chromatin Protein Nupr1 in Kras-Induced Senescence and Transformation.

Nupr1 is a chromatin protein, which cooperates with Kras(G12D) to induce PanIN formation and pancreatic cancer development in mice, though the molecular mechanisms underlying this effect remain to be fully characterized. In the current study, we report that Nupr1 acts as a gene modifier of the effect of Kras(G12D)-induced senescence by regulating Dnmt1 expression and consequently genome-wide levels of DNA methylation. Congruently, 5-aza-2'-deoxycytydine, a general inhibitor of DNA methylation, reverses the Kras(G12D)-induced PanIN development by promoting senescence. This requirement of Nupr1 expression, however, is not restricted to the pancreas since in lung of Nupr1(-/-) mice the expression of Kras(G12D) induces senescence instead of transformation. Therefore, mechanistically this data reveals that epigenetic events, at least at the level of DNA methylation, modulate the functional outcome of common genetic mutations, such as Kras(G12D), during carcinogenesis. The biomedical relevance of these findings lies in that they support the rational for developing similar therapeutic interventions in human aimed at controlling either the initiation or progression of cancer.

Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1.

We have previously demonstrated a crucial role of nuclear protein 1 (NUPR1) in tumor development and progression. In this work, we report the functional characterization of a novel Nupr1-like isoform (NUPR1L) and its functional interaction with the protumoral factor NUPR1. Through the use of primary sequence analysis, threading, and homology-based molecular modeling, as well as expression and immunolocalization, studies reveal that NUPR1L displays properties, which are similar to member of the HMG-like family of chromatin regulators, including its ability to translocate to the cell nucleus and bind to DNA. Analysis of the NUPR1L promoter showed the presence of two p53-response elements at positions -37 and -7, respectively. Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of NUPR1L expression by p53. Congruently, NUPR1L gene expression is activated in response to DNA damage induced by oxaliplatin treatment or cell cycle arrest induced by serum starvation, two well-validated methods to achieve p53 activation. Interestingly, expression of NUPR1L downregulates the expression of NUPR1, its closely related protumoral isoform, by a mechanism that involves the inhibition of its promoter activity. At the cellular level, overexpression of NUPR1L induces G1 cell cycle arrest and a decrease in their cell viability, an effect that is mediated, at least in part, by downregulating NUPR1 expression. Combined, these experiments constitute the first functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1.

A subgroup of pancreatic adenocarcinoma is sensitive to the 5-aza-dC DNA methyltransferase inhibitor.

Pancreatic Ductal Adenocarcinoma (PDAC) is a disease with a great heterogeneity in the response to treatments. To improve the responsiveness to treatments there are two different approaches, the first one consist to develop new and more efficient drugs that intent to cure all patients and the second one is to use already-approved drugs, alone or in combination, but selecting beforehand the most sensitive patients. In this work we explored the efficiency of the second possibility. We developed a collection of 17 PDAC samples collected by Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) or surgery and preserved as xenografts and as primary cultures. This collection was characterized at molecular level by a transcriptomic analysis using an Affymetrix approach. In this paper we present data demonstrating that a subgroup of PDAC responds to low doses of 5-aza-dC. These tumors show a specific RNA expression profile that could serve as a marker, but there is no correlation with Dnmt1, Dnmt3A or Dnmt3B expression. Responder tumors corresponded to well-differentiated samples and longer survival patients. In conclusion, we present data obtained with the well-known drug 5-aza-dC as a proof of concept that a drug that seems to be inefficient in solid tumors in general could be applicable to a particular subgroup of patients with PDAC.

Effect of feeding goats with distilled and non-distilled thyme leaves (Thymus zygis subp. gracilis) on milk and cheese properties.

The aim of this study was to evaluate the effect of feeding goats with distilled and non-distilled thyme leaves (Thymus zygis subsp. gracilis) on the physicochemical composition and technological properties of pasteurised goat milk, and on the physicochemical composition, phenolic content, oxidative stability, microbiology, sensory and texture profile of Murcia al Vino goat cheese. One group of goats was fed the basal diet (control), the second and third groups were fed with different levels of distilled (10 and 20%) or non-distilled (3·75 and 7·5%) thyme leaves. Goat milk physicochemical composition was significantly affected by the substitution of 7·5% of basal goat diet with non-distilled thyme leaves (increase in fat, protein, dry matter and PUFA content), while goat milk clotting time was increased significantly by the introduction of 20% distilled thyme leaves, which reduces its technological suitability. Microbiology, sensory and texture profiles were not affected by the introduction of distilled thyme leaves. The introduction of distilled and non-distilled thyme leaves as an alternative feed to diet can lead to an inhibition of lipids oxidation. The introduction of distilled and non-distilled thyme leaves into goat's diet can be successfully adopted as a strategy to reduce feeding costs and to take advantage of the waste from the production of essential oils, minimising waste removing costs and the environmental impact.

Expression profile of telomere-associated genes in multiple myeloma.

To further contribute to the understanding of multiple myeloma, we have focused our research interests on the mechanisms by which tumour plasma cells have a higher survival rate than normal plasma cells. In this article, we study the expression profile of genes involved in the regulation and protection of telomere length, telomerase activity and apoptosis in samples from patients with monoclonal gammopathy of undetermined significance, smouldering multiple myeloma, multiple myeloma (MM) and plasma cell leukaemia (PCL), as well as several human myeloma cell lines (HMCLs). Using conventional cytogenetic and fluorescence in situ hybridization studies, we identified a high number of telomeric associations (TAs). Moreover, telomere length measurements by terminal restriction fragment (TRF) assay showed a shorter mean TRF peak value, with a consistent correlation with the number of TAs. Using gene expression arrays and quantitative PCR we identified the hTERT gene together with 16 other genes directly involved in telomere length maintenance: HSPA9, KRAS, RB1, members of the Small nucleolar ribonucleoproteins family, A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins, and 14-3-3 family. The expression levels of these genes were even higher than those in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), which have unlimited proliferation capacity. In conclusion, the gene signature suggests that MM tumour cells are able to maintain stable short telomere lengths without exceeding the short critical length, allowing cell divisions to continue. We propose that this could be a mechanism contributing to MM tumour cells expansion in the bone marrow (BM).

Modelling casein aggregation and curd firming in goats' milk from backscatter of infrared light.

A kinetic model was proposed for describing the curd assembly of skimmed goats' milk during enzymic coagulation. The enzymic coagulation of milk was monitored using an optical sensor that measured diffuse reflectance (light backscatter) at 880 nm. The appearance of a shoulder, at low temperatures and protein concentrations, in the diffuse reflectance ratio profile after the inflection point of the curve (Tmax) appeared to separate the aggregation and curd firming steps. The diffuse reflectance ratio profile after Tmax was attributed to the overlapping of casein micelles aggregation and curd firming reactions. The developed kinetic model combined a second order reaction model to describe aggregation reactions and a first order reaction model to describe firming processes reactions. A completely randomised block design with three replications was used to determine the effect of protein concentration and temperature on kinetic constants. Milk was adjusted to three levels of protein (30, 50 and 70 g/kg), and coagulated at five temperatures (20, 25, 30, 35 and 40 degrees C) to test a wide range of processing conditions. Data points from each profile after Tmax were fitted to the proposed model using non-linear regression. The average R2 and standard error of prediction (SEP) for 45 tests conducted were in the range of 0.9975 +/- 0.0027 and 0.0081 +/- 0.0037, respectively. A significant increase in characteristic times for aggregation (tau2) and curd firming processes (tau1) were found when temperature decreased or protein increased. Theoretical asymptotic value of reflectance ratio, R(infinity), increased with increasing level of protein and temperature (P < 0.05). The parameter beta1, which represented the fraction of diffuse reflectance ratio attributed to aggregation, decreased with increasing temperature and decreasing protein.

Effect of protein and temperature on cutting time prediction in goats' milk using an optical reflectance sensor.

An objective method for determining the coagulum cutting time is needed to improve consistency and processing efficiency of goats' cheese. A fibre optic sensor was used to measure the backscatter of near-infrared radiation at 880 nm during the coagulation of skimmed goats' milk for the purpose of predicting coagulum cutting time. A randomised block design, replicated three times, was used to test the effect of three protein concentrations (3, 5 and 7% (w/w)) on diffuse reflectance parameters for cutting time prediction of milk coagulated at five different temperatures (20, 25, 30, 35 and 40 degrees C) to assure a wide range of coagulation rates. The inclusion of a protein term in the existing algorithms was essential to reduce the standard error of prediction to under 6.2 min. An algorithm including a time-based parameter and a protein term, Tcut=beta0 T2min (1 + gamma% Protein) was found to predict cutting time with a SEP of 2.42 min and an R2 of 0.98. Gamma was considered constant (gamma=-0.0674, goats' milk) representing the protein effect on beta0. Algorithms using response-based parameters (such as change in reflectance ratio) and the composition parameter protein required additional regression parameters such as temperature and an intercept term to predict the cutting time with the same precision as algorithms using only time-based parameters. Time-based parameters were found to decrease proportionally with increasing temperature and decreasing protein concentration. Response-based and mixed-based parameters were found to decrease with decreasing temperature. Reflectance ratio at cutting time did not significantly change with protein concentration for skimmed goats' milk. The activation energy of kappa-casein hydrolysis was calculated based on changes in reflectance profile parameters and was found to be in the range 63-72 kJ mol(-1).