Human plasmacytoid dendritic cells express the functional purinergic halo (CD39/CD73).

Plasmacytoid dendritic cells (pDCs) are a specialized DC subset mainly associated with sensing viral pathogens and high-type I interferon (IFN-I) release in response to toll-like receptor (TLR)-7 and TLR-9 signaling. Currently, pDC contribution to inflammatory responses is extensively described; nevertheless, their regulatory mechanisms require further investigation. CD39 and CD73 are ectoenzymes driving a shift from an ATP-proinflammatory milieu to an anti-inflammatory environment by converting ATP to adenosine. Although the regulatory function of the purinergic halo CD39/CD73 has been reported in some immune cells like regulatory T cells and conventional DCs, its presence in pDCs has not been examined. In this study, we uncover for the first time the expression and functionality of the purinergic halo in human blood pDCs. In healthy donors, CD39 was expressed in the cell surface of 14.0 ± 12.5% pDCs under steady-state conditions, while CD73 showed an intracellular location and was only expressed in 8.0 ± 2.2% of pDCs. Nevertheless, pDCs stimulation with a TLR-7 agonist (R848) induced increased surface expression of both molecules (43.3 ± 23.7% and 18.6 ± 9.3%, respectively), as well as high IFN-α secretion. Furthermore, exogenous ATP addition to R848-activated pDCs significantly increased adenosine generation. This effect was attributable to the superior CD73 expression and activity because blocking CD73 reduced adenosine production and improved pDC allostimulatory capabilities on CD4 + T cells. The functional expression of the purinergic halo in human pDCs described in this work opens new areas to investigate its participation in the regulatory pDC mechanisms in health and disease.

Novel requirements for HAP2-mediated gamete fusion in Tetrahymena.

The ancestral gamete fusion protein, HAP2, catalyzes sperm-egg fusion in a broad range of taxa dating to the last eukaryotic common ancestor. Remarkably, HAP2 orthologs are structurally related to the class II fusogens of modern-day viruses, and recent studies make clear that these proteins utilize similar mechanisms to achieve membrane merger. To identify factors that may regulate HAP2 activity, we screened mutants of the ciliate Tetrahymena thermophila for behaviors that mimic Δhap2 knockout phenotypes in this species. Using this approach, we identified two new genes, GFU1 and GFU2, whose products are necessary for the formation of membrane pores during fertilization and show that the product of a third gene, namely ZFR1, may be involved in pore maintenance and/or expansion. Finally, we propose a model that explains cooperativity between the fusion machinery on apposed membranes of mating cells and accounts for successful fertilization in T. thermophila's multiple mating type system.

Abdominal wall reconstruction for extensive necrosis following abdominoplasty in a patient with subcostal scars - case report.

Abdominal wall defects encompass a broad spectrum of musculo-fasciocutaneous anomalies. We present case of a 42-year-old woman with a history of multimorbidity and bilateral subcostal scars. The patient underwent incisional ventral hernia repair and abdominoplasty performed by a general surgeon at another institution. However, she developed extensive necrosis of the cutaneous-fatty panniculus between the bilateral subcostal incisions and the abdominoplasty incision. The patient presented with a medial area of 50 × 60 cm with loss of soft tissue vitality and necrotic plaques. Tangential escharotomies were performed to remove devitalized tissue, and management of the open wound included hydrocolloid and alginate dressings. Finally, a defect of 45 × 40 cm was achieved. Three tissue expanders were used to reconstruct the abdominal wall, allowing sufficient adjacent autologous tissue to be harvested for definitive correction of the abdominal defect. An acceptable aesthetic result was observed 5 years after surgery. This report highlights the importance of adequate evaluation of the previously scarred abdominal wall prior to abdominoplasty.

Scaling Analysis of an Image Encryption Scheme Based on Chaotic Dynamical Systems.

Despite that many image encryption systems based on chaotic or hyperchaotic systems have been proposed to protect different kinds of information, it has been crucial to achieve as much security as possible in such systems. In this sense, we numerically implement a known image encryption system with some variants, making special emphasis when two operations are considered in the scrambling stage. The variants of such an encryption system are based on some hyperchaotic systems, which generated some substitution boxes and the keys of the system. With the aim to have a more complete evaluation, some internal stages of the image encryption scheme have been evaluated by using common statistical tests, and also the scaling behavior of the encrypted images has been calculated by means of a two-dimensional detrended fluctuation analysis (2D-DFA). Our results show that the image encryption systems that include two operations or transformations in the scrambling stage present a better performance than those encryption systems that consider just one operation. In fact, the 2D-DFA approach was more sensitive than some common statistical tests to determine more clearly the impact of multiple operations in the scrambling process, confirming that this scaling method can be used as a perceptual security metric, and it may contribute to having better image encryption systems.

Assessment of physical functioning in patients with chronic obstructive pulmonary disease (COPD) requiring long-acting dual bronchodilation in routine clinical practice.

OBJECTIVE: We aim to determine the effect of a fixed-dose combination (FDC) of tiotropium/olodaterol on Physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) in a real world setting. METHODS: COPD patients were prospectively enrolled to evaluate the effect of a FDC of tiotropium/olodaterol inhaler therapy via the Respimat® Soft Mist™ inhaler (SMI) on the physical functioning scale (PF-10), and the general condition of the patient as assessed by the physician (Physician's Global Evaluation, PGE), and the patient's satisfaction after 6 weeks of treatment. The primary end-point was the percentage of patients with therapeutic success at 6th week follow-up, defined as a ≥10-points increase in the standardised PF-10 score from baseline. RESULTS: A total of 257 patients from 57 sites were enrolled, and 234 completed the follow up. After 6 weeks of treatment, 155 out of 234 patients (66.2%) showed therapeutic success in the physical functioning score, coupled with significant improvement in PGE score: 78 (33.3%) patients with good/excellent PGE score at baseline, increasing to 172 (73.5%) at 6th week (p<0.0001). The patient's satisfaction was excellent: 77.2% reporting to be satisfied/very satisfied with the treatment, 79.9% with inhaling and 79.0% with the handling of SMI device. 1.6% of patients reported an investigator-defined drug-related adverse event. CONCLUSION: Treatment of COPD patients with a FDC of tiotropium/olodaterol SMI for 6 weeks resulted in significant improvements in the patients' condition as assessed by patients and physicians, with no new safety findings.

Conversion of Adjustable Gastric Banding to Roux-en-Y Gastric Bypass in One or Two Steps: What Is the Best Approach? Analysis of a Multicenter Database Concerning 832 Patients.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is often the preferred conversion procedure for laparoscopic adjustable gastric banding (LAGB) poor responders. However, there is controversy whether it is better to convert in one or two stages. This study aims to compare the outcomes of one and two-stage conversions of LAGB to RYGB. METHODS: Retrospective review of a multicenter prospectively collected database. Data on conversion in one and two stages was compared. RESULTS: Eight hundred thirty-two patients underwent LAGB conversion to RYGB in seven specialized bariatric centers. Six hundred seventy-three (81%) were converted in one-stage. Patients in the two-stage group were more likely to have experienced technical complications, such as slippage or erosions (86% vs. 37%, p = 0.0001) and to have had a higher body mass index (BMI) (41.6 vs. 39.9 Kg/m2, p = 0.005). There were no differences in postoperative complications and mortality rates between the one-stage and two-stage groups (13.5% vs. 10.8%, and 0.7% vs. 0.0% respectively, p = ns). Mean final BMI and %total weight loss (%TWL) for the one-stage and the two-stage groups were 31.6 vs. 32.4 Kg/m2 (p = ns) and 30.4 vs. 26.8 (p = 0.017) after a mean follow-up of 33 months. Follow-up at 1, 3, and 5 years was 98%, 75%, and 54%, respectively. CONCLUSIONS: One-stage conversion of LAGB to RYGB is safe and effective. Two-stage conversion carries low morbidity and mortality in the case of band slippage, erosion, or higher BMI patients. These findings suggest the importance of patient selection when choosing the appropriate conversion approach.

Liver damage in bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis is an emerging disease with a poor prognosis and high mortality rate that is even surpassing some types of cancer. This disease has been linked to the concomitant appearance of liver cirrhosis. Bleomycin-induced pulmonary fibrosis is a widely used mouse model that mimics the histopathological and biochemical features of human systemic sclerosis, an autoimmune disease that is associated with inflammation and expressed in several corporal systems as fibrosis or other alterations. To determine the effects on proliferation, redox and inflammation protein expression markers were analyzed by immunohistochemistry. Analyses showed a significant increase in protein oxidation levels by lipoperoxidation bio-products and in proliferation and inflammation processes. These phenomena were associated with the induction of the redox status in mice subjected to 100 U/kg bleomycin. These findings clearly show that the bleomycin model induces histopathological alterations in the liver and partially reproduces the complexity of systemic sclerosis. Our results using the bleomycin-induced pulmonary fibrosis model provide a protocol to investigate the mechanism underlying the molecular alteration found in the liver linked to systemic sclerosis.

Exploring the ancestry and admixture of Mexican Oaxaca Mestizos from Southeast Mexico using next-generation sequencing of 11 HLA loci.

The Mestizos of Oaxaca resulted from the admixture of Zapotecan Natives with Spaniards and Africans. We selected 112 donors from Oaxaca and applied next-generation sequencing to characterize exon and intron variants in complete or extended HLA genes. Some alleles found, are unique to Mexican Natives and most likely will be absent in most major ethnicities, namely: Caucasians, Africans or Asians. Among these are HLA-A*68:03:01, HLA-A*68:05:01, HLA-C*03:04:01:02, HLA-C*15:09, HLA-C*3:05, HLA-C*03:06:01, HLA-B*39:05:01, HLA-B*35:14:01, HLA-B*35:12:01, HLA-B*35:43:01, HLA-B*40:05, HLA-B:40:08, HLA-B*51:02:01, HLA-B*35:24:01 and HLA-B*39:08. HLA-DQA1*05:05:01:05 and some HLA-DRB1 alleles were only present in Amerindians/Mestizos. Three haplotypes are unique to Mexican Natives, five to Middle-Eastern and Sephardi-Jews. We detected a novel HLA-DQA1*04:01:01 exon 4 variant. Any novel allele may have been positively selected to enlarge the peptide-binding repertoire, and some, like HLA-B*39:02:02 and HLA-B*39:05:01 were found with unique haplotype associations, suggesting convergent evolution events and/or allele lineage diversification. The allele frequencies were fairly evenly distributed in most HLA loci with the exception of HLA-DPB1. The application of NGS in Oaxaca is novel and will lead to better use in the clinical setting. It offers deep knowledge on the population structure, origins, migration, and discovery of new alleles and haplotypes that other techniques did not achieve.

Allele diversity of the killer cell immunoglobulin-like receptors KIR3DL1/S1 and the combination with their HLA ligands in Mexican Mestizos from Mexico City.

Killer cell immunoglobulin-like receptors (KIRs), expressed on Natural Killer (NK) cells, activate/inhibit NK cell function through interactions with their HLA-A, B and C ligands. KIR3DL1 is one of the most polymorphic genes and its effect varies depending on the interaction of the specific allotype with its Bw4 ligand. We investigated the allelic diversity of KIR3DL1/S1 using sequence based typing and we typed as well, their Bw4 ligands in Mexican Mestizos of Mexico City. The results showed that this population has a great KIR3DL1 allelic diversity with ∗01502 (19.9%), ∗00101 (13.2%) and ∗00501 (12.8%) being the most common alleles, while KIR3DS1 showed predominance of ∗01301 (86%); these data agree with the diversity found in most populations studied. At least one KIR3DL1-HIGH surface expression allele was present in 67.5% of the subjects. Phylogenetic comparisons between Mestizos and 28 different populations showed that allelic diversity of KIR3DL1/S1 was similar in Mexican Mestizos from Mexico and in Hispanics from USA. Knowledge of KIR and MHC diversity worldwide is fundamental for understanding the impact of KIR and KIR-ligand polymorphism on NK cell effector functions and is relevant in genetic anthropology, disease association and transplantation.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma

No disponible

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

La redacción de acrónimos en artículos científicos / The wording of acronyms in scientific papers

No disponible

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Autocuidados de la estenosis uretral en atención Primaria / No disponible

Existe multitud de enfermedades que pueden afectar a la uretra, como es el caso de la estenosis uretral. Sus causas son diversas: recidivas de uretritis, infecciones de transmisión sexual, traumatismos pélvicos, incluso sondajes, exploraciones y resección transuretral de la próstata. Excepcionalmente se dan casos de estenosis congénita y estenosis femenina. El 80,6% de las estenosis son producidas por la instrumentación de la vía urinaria, sobre todo en el sexo masculino por las características anatómicas de la uretra. La incidencia es muy variable, pudiendo afectar hasta al 0,6% de la población. Se estima que el gasto sanitario en EEUU es de 200 millones de dólares anuales, 5.000 hospitalizaciones y 1,5 millones de consultas ambulatorias anuales. Los síntomas más comunes son intermitencia del flujo durante la micción, disuria, incontinencia y retención de orina. Las principales complicaciones son infecciones recurrentes como consecuencia de la disminución del flujo urinario, pudiendo llegar al bloqueo completo. Uno de los métodos más utilizados para prevenir el estrechamiento recurrente es el uso de dilatadores uretrales. Para un buen manejo de los dilatadores, el profesional de enfermería de atención primaria debe proporcionar unos cuidados adecuados a la situación del paciente en su domicilio o en consulta, proporcionándole autonomía, promoviendo su participación activa y mejorando así su calidad de vida

There are lots of illnesses that can affect the urethra as it is the case of urethral stenosis. Its causes are several: relapses of urethritis, sexual transmission infections, pelvic traumatisms, even cathetering, prostate explorations and transurethral resection. Exceptionally cases of congenital stenosis and female stenosis occur. 80.6% of stenoses are caused by the instrumentation of the urinary tract especially among male due to anatomical characteristics of the urethra. The incidence rate is very variable, and can affect up to 0.6% of the population. It is estimated that health expense in the US is 200 million dollars per year, 5,000 hospitalizations and 1.5 million ambulatory practices. The most common symptoms are intermittence of the flow during the urination, dysuria, incontinence and urine retention. The main complications are recurrent infections as consequence of the decrease of the urinary flow, it can cause the complete blocking. One of the most used methods to prevent recurrent narrowing is the use of urethral dilator. For a good handling of the expanders, professional nurses of primary care must provide some cares adapted to the situation of the patient in their residence or in practice, providing them autonomy, promoting their active participation and in this way improving their quality of life

Correlación entre la fiebre y la frecuencia respiratoria en menores de 5 años / Correlation between fever and respiratory rate in children under 5 years of age

Introducción: Entre los efectos de la fiebre está el incremento de la frecuencia respiratoria (FR) hasta alcanzar rangos de generar taquipnea. El diagnóstico de neumonía según la OMS basado en la presencia de taquipnea puede sobreestimarse durante la fiebre. El objetivo de este estudio fue determinar la correlación entre fiebre y FR en niños febriles menores de 5 años. Pacientes y Método: Estudio prospectivo de correlación en niños entre 2 y 60 meses. Se midió FR y temperatura corporal al ingreso a Servicio de Urgencia y luego de recibir acetaminofén. Se calculó la correlación entre el cambio de temperatura y el cambio en la FR. Se determinó la frecuencia de taquipnea al ingreso y al normalizar la temperatura. Resultados: 362 pacientes fueron incluidos, media 23,7 meses (DE 16,1). La FR en menores de un año disminuyó 12,9 respiraciones por minuto (DE 6,7) al normalizar temperatura; en mayores, disminuyó 10,7 respiraciones por minuto (DE 5,2). El coeficiente r² entre temperatura y FR fue 0,08 para menores de un año y 0,11 para mayores. De los niños que estaban taquipneicos, 57 por ciento no lo estaban al normalizar la temperatura. Conclusiones: Se recomienda reevaluar la FR de todo niño febril luego de normalizar su temperatura antes de definir taquipnea.

Introduction: Increased body temperature results in raised respiratory rate (RR) leading to tachypnea. According to World Health Organization (WHO), the diagnosis of pneumonia based on the presence of tachypnea can be overestimated during fever. The aim of this study is to determine the correlation between fever and RR in febrile children under five years of age. Patients and Method: A prospective study of correlation in children between 2 and 60 months was performed. RR and body temperature were measured on Emergency Room admission and after receiving acetaminophen. The correlation between the temperature change and the change in the RR was calculated. The frequency of tachypnea at admission and after normalizing the temperature was determined. Results: 362 patients were included, mean age 23.7 months old. RR in children under one year of age decreased 12.9 breaths per minute after normalizing the temperature, in older than one year of age, it decreased 10.7 breaths per minute. The r² coefficient between temperature and RR was 0.08 for children under one year and 0.11 for older. Among the children who were tachypneic, 57 percent did not present this condition after normalizing the temperature. Conclusions: It is recommended to reevaluate RR in all febrile children after normalizing the temperature and before diagnosing tachypnea.

The uterine myocyte as a target for prevention of preterm birth.

Preterm birth (PTB) remains the most common cause of neonatal morbidity and mortality as well as long-term disability. Current strategies to prevent or arrest spontaneous preterm labor (SPTL) have limited success. For almost three decades, there have been no novel pharmacological agents used clinically to address this important obstetrical complication. In this review, we focus on the uterine myocyte as a target for prevention of spontaneous PTB. After presenting an overview of intracellular signaling pathways that are important in regulation of smooth muscle contractility, we discuss previous and current pharmacological approaches to manage SPTL. We also present recent evidence from our own laboratories suggesting a potentially novel and uterine-specific approach to maintain or impose uterine relaxation. Finally, we briefly discuss extrinsic systems that might affect uterine activity and reinforce the concept that SPTL represents a syndrome that is the end result of a variety of pathophysiologic etiologies leading to PTB. We conclude by emphasizing the need for much more research to provide sufficient understanding of the mechanisms of SPTL and to make inroads towards reducing the incidence and adverse consequences of this common and serious syndrome.

Heat conduction in systems with Kolmogorov-Arnold-Moser phase space structure.

We study heat conduction in a billiard channel formed by two sinusoidal walls and the diffusion of particles in the corresponding channel of infinite length; the latter system has an infinite horizon, i.e., a particle can travel an arbitrary distance without colliding with the rippled walls. For small ripple amplitudes, the dynamics of the heat carriers is regular and analytical results for the temperature profile and heat flux are obtained using an effective potential. The study also proposes a formula for the temperature profile that is valid for any ripple amplitude. When the dynamics is regular, ballistic conductance and ballistic diffusion are present. The Poincaré plots of the associated dynamical system (the infinitely long channel) exhibit the generic transition to chaos as ripple amplitude is increased. When no Kolmogorov-Arnold-Moser (KAM) curves are present to forbid the connection of all chaotic regions, the mean square displacement grows asymptotically with time t as tln(t).