SOX9 immunosuppression in primary colorectal cancer tumors with lymph node metastasis.

INTRODUCTION AND AIMS: Colorectal cancer is the most frequent malignant tumor of the digestive system. Its pathogeny is complex and involves the APC/ß-catenin sequence. Lymph node metastases are a significant indicator for determining treatment and are a prognostic factor. SOX9 overexpression is related to oncogenic qualities and the capacity for metastasis. Our aim was to analyze SOX9 immunoexpression in primary colorectal cancer and lymph node metastasis status. MATERIAL AND METHODS: Seventy-nine available cases were divided into the group with lymph node metastasis (n=38) and the group without lymph node metastasis (n=41), evaluating their SOX9 expression. The IBM SPSS version 27 program in Spanish was utilized to carry out the statistical analysis, obtaining measures of central tendency, the kappa index, standard deviation, Wilcoxon Mann-Whitney nonparametric measurements, Spearman's correlation coefficient, and chi-square test and Student's t test values. SOX9 immunoexpression was evaluated through the mean-based H-score, with high immunoexpression as a score ≥145 and low immunoexpression as a score ≤144. RESULTS: A p=0.73 was obtained that was not statistically significant, regarding the relation of SOX9 expression in primary colorectal cancer to lymph node metastasis. CONCLUSIONS: The absence or presence of lymph node metastasis was independent from SOX9 immunoexpression in primary colorectal cancer. However, due to the limited size of the population analyzed, further research is needed.

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.

Genome-wide association analysis of body conformation traits in Mexican Holstein cattle using a mix of sampled and imputed SNP genotypes.

In arid and semi-arid zones, animal health and production are closely correlated with body conformation traits. These selected traits, in turn, allow livestock to adapt unfavorable soil and environmental conditions. The primary objective of this study was to perform a genome-wide association analysis for a set of sampled and imputed SNPs with 16 conformation traits in a population of Holstein cows from a desert area of Northwestern Mexico. Imputation from 6K to 50K SNPs was performed as a low-cost optimization strategy. Results show eight SNPs associated with two conformation traits. The Udder Depth trait resulted in seven associated SNPs from chromosome 10, that related to Marbling Score, Milk Yield, Fat Yield, Protein Yield, and Protein Percentage Quantitative Trait Loci (QTLs). The Body Depth trait resulted in one associated SNP from chromosome 2, although no QTL relation was found. The discovery of genes associated with conformation traits may be indicative of the adaptive selection pressures the Holstein breed has undergone in response to the extreme weather conditions found in the northwestern areas of Mexico. Results of this study indicate that traits such as stature and body depth may be used as indicators of cows' potential genetic merits for milk, fat, and protein production.

[Cemented total knee replacement: comparative study between the use or not of tourniquet on the inmediate results]. / Artroplastía total cementada de rodilla: comparación entre el uso o no de isquemia en el resultado postoperatorio inmediato.

Comparison of immediate postoperative results of patients undergoing cemented total knee arthroplasty with and without ischemia. Observational, cross-sectional, retrospective, analytical, single-center study that included 180 patients who underwent total knee arthroplasty from 2011 to 2014: 120 without ischemia, 60 with ischemia. Mean age was 70 years with SD ± 7. Criteria to assess the immediate postoperative results include intraoperative bleeding, hemoglobin differential and pain. Exclusion criteria comprised patients being treated at a pain clinic, those on anticoagulants, with a history of bleeding disorders, psychiatric conditions, kidney failure or those intolerant to NSAIDs. In total knee arthroplasty without ischemia there is better pain control (p = 0.026). The hemoglobin differential and intraoperative bleeding were less with ischemia (p = 0.008). 32.8% of patients required blood transfusion, but no statistically significant relationship was established with the use or non-use of ischemia (p = 0.301). The most commonly reported pain was within a VAS of 0-3; 62.2% of cases reported mild pain. Mean hemoglobin differential was 3.7 with SD ± 1.3 with a range from 0 to 7.4. Patients in whom no ischemia was used during the surgical procedure experienced less pain. There was less bleeding and hemoglobin differential with the use of ischemia. However, this did not result in a statistically significant difference in the need for blood transfusion. The use of ischemia with caution and according to the surgeons preference is recommended.

Comparar el resultado postoperatorio inmediato en el paciente sometido a artroplastía total cementada de rodilla con y sin el uso de isquemia. Estudio observacional, transversal, retrospectivo, analítico y unicéntrico. 180 pacientes operados de artroplastía total cementada de rodilla: 120 sin isquemia, 60 con isquemia, de 2011 a 2014, edad promedio 70 años con DE ± 7 años, se comparará el sangrado operatorio, diferencial de hemoglobina y dolor como criterios de resultado postoperatorio inmediato. Se excluyeron pacientes de clínica de dolor, manejo con anticoagulantes, coagulopatía previa, patología siquiátrica, insuficientes renales o con intolerancia a AINEs. En artroplastía total cementada de rodilla sin isquemia se presenta mejor control del dolor (p = 0.026). El diferencial de hemoglobina y sangrado operatorio es menor cuando está asociado al uso de isquemia (p = .008). Se requirió transfusión sanguínea en 32.8%, sin establecer una relación entre el uso o exclusión de isquemia con relevancia estadística (p = 0.301). El dolor referido más común se encuentra entre 0 y 3 de EVA correspondiente a dolor leve en 62.2% de los casos. El diferencial de hemoglobina promedio se reporta en 3.7 con desviación estándar de ± 1.3 en un rango de 0 a 7.4. Existe menor dolor postoperatorio en el paciente al que no se aplica isquemia durante el procedimiento quirúrgico; hay menor sangrado y diferencial de hemoglobina con el uso de isquemia; sin embargo, esto no representa estadísticamente una diferencia en la necesidad de transfusión sanguínea. Se recomienda utilizar con cautela la isquemia y su uso queda a elección del cirujano.

A functional BH3 domain in an aquaporin from Leishmania infantum.

Despite the absence of sequences showing significant similarity to any of the members of the Bcl-2 family of proteins in protozoa, experiments carried out in yeast or trypanosomatids have demonstrated that ectopic expression of some of these members alters their response to different death stimuli. Because the BH3 domain is the smallest common signature in all the proteins of this family of apoptosis regulators and also because they are essential for molecular interactions between antagonistic members, we looked for sequences with significant similarity to the BH3 motif in the Leishmania infantum genome. Among the top scoring ones, we found the MYLALQNLGDEV amino-acid stretch at the C terminus of a previously described aquaporin, now renamed as Li-BH3AQP. This motif is highly conserved in homologous proteins from other species of the Leishmania genus. The association of Li-BH3AQP with human Bcl-XL was demonstrated by both co-immunoprecipitation and yeast two-hybrid experiments. Ectopic expression of Li-BH3AQP reduced viability of HeLa cells and this deleterious effect was abrogated by the simultaneous overexpression of Bcl-XL. Although we were not able to demonstrate a reduction in parasite viability when the protein was overexpressed in Leishmania promastigotes, a prodeath effect could be observed when the parasites overexpressing Li-BH3AQP were treated with staurosporine or antimycin A. Surprisingly, these parasites were more resistant, compared with wild-type parasites, to hypotonic stress or nutrient deprivation. The prodeath activity was abolished upon replacement of two highly conserved amino acids in this BH3 domain. Taken together, these results point to Li-BH3AQP as the first non-enzymatic protein ever described in trypanosomatids that is involved in cell death.

Influence of Wheat Straw Pelletizing and Inclusion Rate in Dry Rolled or Steam-flaked Corn-based Finishing Diets on Characteristics of Digestion for Feedlot Cattle.

Eight Holstein steers (216±48 kg body weight) fitted with ruminal and duodenal cannulas were used to evaluate effects of wheat straw processing (ground vs pelleted) at two straw inclusion rates (7% and 14%; dry matter basis) in dry rolled or steam-flaked corn-based finishing diets on characteristics of digestion. The experimental design was a split plot consisting of two simultaneous 4×4 Latin squares. Increasing straw level reduced ruminal (p<0.01) and total tract (p = 0.03) organic matter (OM) digestion. As expected, increasing wheat straw level from 7% to 14% decreased (p<0.05) ruminal and total tract digestion of OM. Digestion of neutral detergent fiber (NDF) and starch, per se, were not affected (p>0.10) by wheat straw level. Likewise, straw level did not influence ruminal acetate and propionate molar proportions or estimated methane production (p>0.10). Pelleting straw did not affect (p≥0.48) ruminal digestion of OM, NDF, and starch, or microbial efficiency. Ruminal feed N digestion was greater (7.4%; p = 0.02) for ground than for pelleted wheat straw diets. Although ruminal starch digestion was not affected by straw processing, post-ruminal (p<0.01), and total-tract starch (p = 0.05) digestion were greater for ground than for pelleted wheat straw diets, resulting in a tendency for increased post-ruminal (p = 0.06) and total tract (p = 0.07) OM digestion. Pelleting wheat straw decreased (p<0.01) ruminal pH, although ruminal volatile fatty acids (VFA) concentration and estimated methane were not affected (p≥0.27). Ruminal digestion of OM and starch, and post-ruminal and total tract digestion of OM, starch and N were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal NDF digestion was greater (p = 0.02) for dry rolled than for steam-flaked corn, although total tract NDF digestion was unaffected (p = 0.94). Ruminal microbial efficiency and ruminal degradation of feed N were not affected (p>0.14) by corn processing. However, microbial N flow to the small intestine and ruminal N efficiency (non-ammonia N flow to the small intestine/N intake) were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal pH and total VFA concentration were not affected (p≥ 0.16) by corn processing method. Compared with dry rolled corn, steam-flaked corn-based diets resulted in decreased acetate:propionate molar ratio (p = 0.02). It is concluded that at 7% or 14% straw inclusion rate, changes in physical characteristics of wheat straw brought about by pelleting negatively impact OM digestion of both steam-flaked and dry-rolled corn-based finishing diets. This effect is due to decreased post-ruminal starch digestion. Replacement of ground straw with pelleted straw also may decrease ruminal pH.

A new reference collection of documented human skeletons from Mérida, Yucatan, Mexico.

This report documents the history and composition of a new reference collection currently composed of 84 identified human skeletons from the modern cemetery of Xoclán in Mérida, Yucatan, Mexico. The skeletal sample is the first of its kind in the Yucatan peninsula, a region with a population short of two million mostly local and non-local Mexican residents and descendants of the ancient Maya. The growing collection is curated at the Facultad de Ciencias Antropológicas (School of Anthropological Sciences) of the Autonomous University of Yucatan. Here we describe recovery procedures, preservation, background information and validation measures of the individuals who make up the collection. Detailed information on the generational pattern, sex, and age distribution, along with socioeconomic context and provenance of the skeletons are provided. The majority of the skeletal series is represented by males and by older individuals of both sexes. Almost all of these individuals come from Mérida's middle and lower socioeconomic sectors and died within the urban city boundaries. Biographic information was collected on each individual at the municipal civil registry and confronted with information of national and municipal censuses (2000 and 2005), to be validated and to be discussed here in terms of the representativeness of the reference series and its potential uses in forensic, anthropological and medical research.

Effects of Replacing Dry-rolled Corn with Increasing Levels of Corn Dried Distillers Grains with Solubles on Characteristics of Digestion, Microbial Protein Synthesis and Digestible Energy of Diet in Hair Lambs Fed High-concentrate Diets.

Four male lambs (Katahdin; average live weight 25.9±2.9 kg) with "T" type cannulas in the rumen and proximal duodenum were used in a 4×4 Latin square experiment to evaluate the influence of supplemental dry distillers grain with solubles (DDGS) levels (0, 10, 20 and 30%, dry matter basis) in substitution for dry-rolled (DR) corn on characteristics of digestive function and digestible energy (DE) of diet. Treatments did not influence ruminal pH. Substitution of DR corn with DDGS increased ruminal neutral detergent fiber (NDF) digestion (quadratic effect, p<0.01), but decreased ruminal organic matter (OM) digestion (linear effect, p<0.01). Replacing corn with DDGS increased (linear, p≤0.02) duodenal flow of lipids, NDF and feed N. But there were no treatment effects on flow to the small intestine of microbial nitrogen (MN) or microbial N efficiency. The estimated UIP value of DDGS was 44%. Postruminal digestion of OM, starch, lipids and nitrogen (N) were not affected by treatments. Total tract digestion of N increased (linear, p = 0.04) as the DDGS level increased, but DDGS substitution tended to decrease total tract digestion of OM (p = 0.06) and digestion of gross energy (p = 0.08). However, it did not affect the dietary digestible energy (DE, MJ/kg), reflecting the greater gross energy content of DDGS versus DR corn in the replacements. The comparative DE value of DDGS may be considered similar to the DE value of the DR corn it replaced up to 30% in the finishing diets fed to lambs.

Advances on aptamers targeting Plasmodium and trypanosomatids.

Aptamers are single-stranded oligonucleotides (ssDNA or RNA) selected from combinatorial libraries by an in vitro process and possess a specific three-dimensional structure depending on its sequence. These molecules are able to recognize and, eventually, alter the activity of their targets by binding directly in a similar way to antibodies. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against Plasmodium and trypanosomatid proteins associated with parasitic diseases which affect hundreds of millions people. One approach tries to block the interaction between the parasite and the host using aptamers targeting host-cell matrix receptors. A second strategy consists in attack the parasite intracellularly targeting heme group or interfering in the intracellular RNA transport. In another strategy, aptamers targeting invariant polypeptides could be used as a specific drug delivery system into the parasite. Finally, aptamers addressed to re-direct the immune response of the infected host are being studied. Other potential use of the aptamers is as biorecognition element in diagnostic systems for parasitic diseases. In this paper, we briefly review how aptamers against Plasmodium and trypanosomatids are discovered, with a focus on recent advances that improve the aptamers properties as a real tool for parasite fighting.

Aptasensor based on the selective electrodeposition of protein-linked gold nanoparticles on screen-printed electrodes.

The electrodeposition of DNA-gold nanoparticles previously developed in our group has been used as starting point for the electrodeposition of proteins attached to gold nanoparticles. We have performed a proof of principle by developing a methodology based on the electrodeposition of proteins bound to gold nanoparticles on screen-printed gold microelectrodes using, in a first approach, horseradish peroxide-conjugated gold nanoparticles (gold-HRP). The electrodeposition was achieved at a current positive potential of 800 mV vs. Ag/AgCl and the functionality of the electrodeposited HRP-particles was tested by electrochemical reduction of H(2)O(2). Furthermore, we used this proof of concept in an aptasensor application to detect Leishmania infantum KMP-11. Hence, we have demonstrated not only the functionality of the electrodeposition of proteins bound to gold nanoparticles, but also the utility of the method with the aim of developing a real biosensor containing multiple enzymes or proteins in a multimodular device.

Tumor lipoesclerosante mixofibroso de cadera. A propósito de un caso / Lipoesclerosante mixofibroso hip tumor. A case

Introducción: El objetivo de esta investigación es estudiar el tumor lipoesclerosante mixofibroso (TLEMF), una tumoración benigna y rara con predilección de asiento en el extremo proximal femoral. Caso clínico: Se presenta un caso clínico atendido en este centro con realización de raspado y relleno de la cavidad, con injerto de cresta ilíaca de una lesión que inicialmente fue etiquetada de quiste óseo o encondroma en cadera. La anatomía patológica informó de TLEMF; aunque no se sospechaba el diagnóstico, se realizó un tratamiento correcto y el sujeto evolucionó de manera adecuada. Conclusiones: El TLEMF es infrecuente y se sospecha ante una lesión radiológica lítica, geográfica, con márgenes de esclerosis variable y asiento en la epífisis y metáfisis proximal femoral. No hay una aceptación unánime de esta entidad en la literatura médica, pero hay autores que argumentan que es una variante de la displasia fibrosa (AU)

Introduction: To look into the liposclerosing myxofibrous tumor, a rare benign tumor formation with a predilection for the proximal femur. Clinical case: We present a case treated in our hospital. We performed curettage and filling of the defect with an iliac crest graft; the lesion had initially been diagnosed as a one cyst/enchondroma in the hip. The pathological study revealed the presence of a liposclerosing myxofibrous tumor. Although this diagnosis was not suspected, the treatment administered was correct and the patient evolved satisfactorily. Conclusions: The liposclerosing myxofibrous tumor is a rare condition. Its presence may be suspected when the X-ray reveals a lytic lesion, with variable sclerotic margins, lodged in the femoral epiphysis or proximal shaft. There is no unanimous acceptance of this entity in the literature, with some authors claiming that it could be a variant of fibrous dysplasia (AU)

Selective immobilization of oligonucleotide-modified gold nanoparticles by electrodeposition on screen-printed electrodes.

Here, we describe a proof of concept procedure for the selective immobilization of oligonucleotides functionalized gold nanoparticle probes (affinity modules) on arrayed screen-printed gold electrodes. Current microarrays are using many different ways to address their DNA probes onto the transducer area. For that reason, we have mixed the electrodeposition of metals, which is a very well known process, in addition with the DNA-gold nanoparticles formation, which is an area of great interest in biosensing applications in the field of genomics, clinical and warfare applications. Combining these fields, we have developed a novel method for the immobilization of gold nanoparticles conjugated with oligonucleotides (affinity modules) onto screenprinting gold electrodes through electrodeposition at a current positive potential of 800mV vs. Ag/AgCl. The modules were selectively immobilized onto the electrode surface being, afterwards, ready for a successful hybridization. The gold colloids take the advantage of being a carrier that allows the immobilization of any kind of bioreceptor in the same conditions and the capability of quality control analysis before the electrodeposition procedure. With this system, we avoided non-specific interactions between the transduction layer and the bioreceptor and in the case of DNA oligonucleotides allowed us the immobilization of multiple sequences in a multimodular device for a further industrial process of cheaper biochip fabrication.

The primary care diagnosis of dementia in Europe: an analysis using multidisciplinary, multinational expert groups.

OBJECTIVES: To explore the extent of variation in the detection of dementia in primary care across Europe, and the potential for the development of European guidelines. METHOD: A mixture of focus group and adapted nominal group methods involving 23 experts of different disciplines and from eight European countries. RESULTS: The diagnosis of dementia should be 'timely' rather than 'early'. Timeliness has an impact on the patient, on the caregiver, on healthcare professionals, and on society. Ethical and moral issues may interfere with the aim of timely diagnosis. Guidelines may be important for facilitating a timely diagnosis of dementia, but were infrequently used and not even available in three of the eight countries. Referral pathways often depended on health care system characteristics, differing throughout the eight European countries, whilst diagnostic strategies differed due to varied cultural influences. There was consensus that national variations can be reduced and timely diagnosis enhanced by combining simple tests using a systematic stepwise case-finding strategy, in conjunction with a strong infrastructure of multidisciplinary collaboration. CONCLUSIONS: This study identified three key themes that should be considered in harmonizing European approaches to the diagnosis of dementia in primary care: (1) a focus on timely diagnosis, (2) the need for the development and implementation of guidelines, and (3) the identification of appropriate referral pathways and diagnostic strategies including multi-professional collaboration. The content of guidelines may be determined by the perspectives of the guideline developers.

[Recommendations guide for the treatment of migraine in the clinical practice]. / Guía de recomendaciones para el tratamiento de la migraña en la práctica clínica.

Migraine is the most frequent neurological reason for consultation. The differences regarding health care system, type of professional seeing these patients and therapeutic armamentarium available in the different countries are important, which makes it very recommendable to have an action guide that reflects the local clinical practice. Following the year 2005 WHO recommendations in its "Global Campaign" against migraine, the coordinators of the Headache Study Groups of the Spanish Society of Neurology, the Spanish Society of Family and Community Medicine, the Spanish Society of Rural and General Medicine, the Spanish Society of General Medicine and the Global Campaign decided to jointly make this guide. To do so, they made a search in MEDLINE, using the terms "migraine", "migraine treatment" and "headache guidelines" and "migraine guidelines". The most relevant articles were analyzed, including the references that we considered to be of interest. Furthermore, we reviewed the most important textbooks on headache and migraine. In this paper, we detail the recommendations agreed on, according to the evidence grade, on symptomatic and preventive treatment of migraine.

Heat-induced programmed cell death in Leishmania infantum is reverted by Bcl-X(L) expression.

An increasing number of reports indicate that single-celled organisms are able to die following what seems to be an ordered program of cell death with strong similarities to apoptosis from higher eukaryotes. DNA degradation and several other apoptotic-like processes have also been described in the parasitic protozoa Leishmania. However, the existence of an apoptotic death in this parasite is still a matter of controversy. Our results indicate that most of the processes of macromolecular degradation and organelle dysfunction observed in mammalian cells during apoptosis can also be reproduced in promastigotes of the genus Leishmania when incubated at temperatures above 38 degrees C. These processes can be partially reversed by the expression of the anti-apoptotic mammalian gene Bcl-X(L), which suggests that this family of apoptosis-regulating proteins was present very early in the evolution of eukaryotic cells.

A kinetic model for the B-Z transition of poly[d(G-C)].poly[d(G-C)] and poly[d(G-m5C)].poly[d(G-m5C)].

The analysis of the kinetic data of the B-Z conformational changes induced by salt in sized double-stranded poly[d(G-C)].poly[d(G-C)] and poly[d(G-m5C)].poly[d(G-m5C)] polymers indicated that there exists a salt threshold which reveals some largely, as yet, unrecognised characteristics of the transition. It was observed that there is a direct correlation between the length of the polymer and the rate of the B-Z transition when the salt concentration in the polymer solution is lower than the salt threshold. The correlation is inverse when the salt concentration is higher than the salt threshold. Thus, the molecular mechanism of the B- to Z-DNA transition varies depending on whether the salt concentration is higher or lower than the threshold. In this context, we have found that the contrasting results reported in the literature describing the rate of the B-Z transition are not contradictory but complementary. The finding of a salt threshold leads to the establishment of a relationship between the cooperativity index of the B-Z transition and the polymer chain length. That relationship is dependent on the chemical structure of the polymer but is temperature independent.

Chronic disease self-management program: 2-year health status and health care utilization outcomes.

OBJECTIVES: To assess the 1- and 2-year health status, health care utilization and self-efficacy outcomes for the Chronic Disease Self-Management Program (CDSMP). The major hypothesis is that during the 2-year period CDSMP participants will experience improvements or less deterioration than expected in health status and reductions in health care utilization. DESIGN: Longitudinal design as follow-up to a randomized trial. SETTING: Community. PARTICIPANTS: Eight hundred thirty-one participants 40 years and older with heart disease, lung disease, stroke, or arthritis participated in the CDSMP. At 1- and 2-year intervals respectively 82% and 76% of eligible participants completed data. MAIN OUTCOME MEASURES: Health status (self-rated health, disability, social/role activities limitations, energy/fatigue, and health distress), health care utilization (ER/outpatient visits, times hospitalized, and days in hospital), and perceived self-efficacy were measured. MAIN RESULTS: Compared with baseline for each of the 2 years, ER/outpatient visits and health distress were reduced (P <0.05). Self-efficacy improved (P <0.05). The rate of increase is that which is expected in 1 year. There were no other significant changes. CONCLUSIONS: A low-cost program for promoting health self-management can improve elements of health status while reducing health care costs in populations with diverse chronic diseases.