Shigella IpaA mediates actin bundling through diffusible vinculin oligomers with activation imprint.

Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion.

Efficacy of astigmatic correction after femtosecond laser-guided cataract surgery using intraoperative aberrometry in eyes with low-to-moderate levels of corneal astigmatism.

PURPOSE: To evaluate the efficacy of astigmatic correction with two types of toric intraocular lenses (IOLs) after femtosecond laser-assisted cataract surgery (FLACS) in eyes with low-to-moderate corneal astigmatism using intraoperative aberrometry for optimizing the position of the toric IOL. METHODS: Retrospective study includes a total of 99 eyes of 73 patients with anterior keratomeric astigmatism ≤ 3 D and undergoing FLACS (Catalys, Johnson & Johnson Vision) with implantation of a monofocal (Ankoris, PhysIOL) or a multifocal toric IOL with the same platform (Pod FT, PhysIOL). In all cases, intraoperative aberrometry was used (Optiwave refractive analysis, ORA, system, Alcon). Visual and refractive outcomes were evaluated preoperatively and at 4 months after surgery with vector analysis of astigmatic changes. RESULTS: A total of 89.9%, 93.9% and 97.0% showed a postoperative sphere, cylinder and spherical equivalent within ± 0.50 D, respectively. Mean difference vector (DV) was 0.22 ± 0.27 D, mean magnitude of error (ME) was 0.13 ± 0.29 D, and mean angle of error (AE) was 1.52 ± 11.64°. Poor correlations of preoperative corneal astigmatism with DV (r = - 0.032, p = 0.833), ME (r = - 0.344, p = 0.001) and AE (r = - 0.094, p = 0.377) were found. Likewise, no statistically significant differences were found between monofocal and multifocal toric IOL subgroups in DV (p = 0.580), ME (p = 0.702) and AE (p = 0.499). CONCLUSIONS: The combination of FLACS and intraoperative aberrometry to optimize the position of a toric IOL allows a very efficacious correction of preexisting low-to-moderate corneal astigmatism.

Towards a gamete matching platform: using immunogenetics and artificial intelligence to predict recurrent miscarriage.

The degree of Allele sharing of the Human Leukocyte Antigen (HLA) genes has been linked with recurrent miscarriage (RM). However, no clear genetic markers of RM have yet been identified, possibly because of the complexity of interactions between paternal and maternal genes during embryo development. We propose a methodology to analyse HLA haplotypes from couples either with histories of successful pregnancies or RM. This article describes a method of RM genetic-risk calculation. The proposed HLA representation techniques allowed us to create an algorithm (IMMATCH) to retrospectively predict RM with an AUC = 0.71 (p = 0.0035) thanks to high-resolution typing and the use of linear algebra on peptide binding affinity data. The algorithm features an adjustable threshold to increase either sensitivity or specificity, allowing a sensitivity of 86%. Combining immunogenetics with artificial intelligence could create personalised tools to better understand the genetic causes of unexplained infertility and a gamete matching platform that could increase pregnancy success rates.

Shigella IpaA Binding to Talin Stimulates Filopodial Capture and Cell Adhesion.

The Shigella type III effector IpaA contains three binding sites for the focal adhesion protein vinculin (VBSs), which are involved in bacterial invasion of host cells. Here, we report that IpaA VBS3 unexpectedly binds to talin. The 2.5 Å resolution crystal structure of IpaA VBS3 in complex with the talin H1-H4 helices shows a tightly folded α-helical bundle, which is in contrast to the bundle unraveling upon vinculin interaction. High-affinity binding to talin H1-H4 requires a core of hydrophobic residues and electrostatic interactions conserved in talin VBS H46. Remarkably, IpaA VBS3 localizes to filopodial distal adhesions enriched in talin, but not vinculin. In addition, IpaA VBS3 binding to talin was required for filopodial adhesions and efficient capture of Shigella. These results point to the functional diversity of VBSs and support a specific role for talin binding by a subset of VBSs in the formation of filopodial adhesions.

Unhealthy Sugars in Bacterial Cytotoxicity.

Bacterial type three secretion systems (T3SSs) are central to virulence, but the processes stimulating their activation are unclear. In this issue of Cell Host & Microbe, Blondel et al. (2016) perform a genome-wide screen using CRISPR/Cas technology to identify a role for cell surface sulfation and fucosylation in cytotoxicity mediated by Vibrio parahaemolyticus T3SSs.

Propiedades psicométricas de la Escala Hospitalaria de Ansiedad y Depresión (HADS) en una población de pacientes oncológicos mexicanos / Psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in a Mexican population of cancer patients

ANTECEDENTES: La sintomatología ansiosa y depresiva es parte de los principales problemas de salud mental en pacientes oncológicos, lo cual afecta la calidad de vida y la adhesión al tratamiento, además de que se asocia con mayor número de síntomas y estancia hospitalaria. Mediante instrumentos de tamizaje válidos y confiables, como la Escala hospitalaria de ansiedad y depresión (HADS), ha sido posible detectar posibles casos en pacientes hospitalarios. Sin embargo, hasta ahora no se habían caracterizado las propiedades psicométricas en pacientes oncológicos en población mexicana.OBJETIVO: Determinar las propiedades psicométricas de la HADS en una muestra de pacientes oncológicos.MÉTODO: Participaron 400 pacientes del Instituto Nacional de Cancerología, de los cuales 226 eran mujeres (56.5%) y 174 eran hombres (43.6%); la edad promedio fue de 47.4 ± 14.1 años. Los participantes contestaron, además de la HADS, los siguientes inventarios: depresión de Beck, ansiedad de Beck, termómetro de distrés.RESULTADOS: Un análisis factorial ajustado a dos factores presentó un instrumento con 12 reactivos, similar a la versión original. La consistencia interna de la escala global mostró un índice satisfactorio (a=0.86). Los alfas de Cronbach de cada subescala tuvieron un valor de .79 y .80 que explicaron el 48.04% de la varianza. La validez, por medio de correlación con las medidas concurrentes, mostró resultados significativos (r de Pearson de .51 a .71, p<0.05).DISCUSIÓN Y CONCLUSIÓN: La HADS en pacientes con cáncer en población mexicana presentó adecuadas características psicométricas. La relevancia de los resultados obtenidos radica en que se trata de una población que puede llegar a requerir atención oportuna en salud mental en etapas tempranas de su tratamiento. La detección de sintomatología ansiosa y depresiva por medio de la HADS deriva en beneficios para la población oncológica y en estrategias funcionales de atención adecuada y costo-efectivas.

BACKGROUND: Symptoms of anxiety and depression are among the major mental health problems in cancer patients. These symptoms affect the quality of life and treatment adherence, and are associated with other symptoms and longer hospital stays. Valid and reliable screening instruments such as the Hospital Anxiety and Depression Scale (HADS), have made possible the detection of possible cases of depression and anxiety in medically ill patients. However, the psychometric properties of this instrument have not been documented in different types of cancer diagnoses in the Mexican population.OBJECTIVE: To determine the psychometric properties of the HADS in a sample of patients with cancer from the Mexican population.METHOD: Four hundred patients from the National Cancer Institute participated, of which 226 were women (56.5%) and 174 men (43.6%), with a mean age of 47.4 ±14.1 years. Participants completed concurrently the HADS as well as the following inventories: 1. Beck Depression, 2. Beck Anxiety and 3. Distress Thermometer.RESULTS: A factor analysis adjusted to two factors explained 48.04% of the variance, with 12 items loading on these two factors in a way similar to the original version. The internal consistency of the overall scale was satisfactory (α=0.86). Cronbach's alphas for each subscale were .79 and .80. The concurrent validity assessed by way of correlations with concurrent measures showed significant associations (Pearson r=51-71, p<0.05).DISCUSSION AND CONCLUSION: The HADS has adequate construct validity, internal consistency and concurrent validity for its use in cancer patients from the Mexican population. The relevance of these results is a cost effective tool to provide timely mental health care early in oncological treatment for those in need. Detecting anxiety and depression symptoms through the HADS may benefit cancer patients by ensuring appropriate care that may increase their quality of life and treatment adherence, and reduce their hospital stays.

[National consensus of diagnosis and treatment of non-small cell lung cancer]. / Consenso nacional de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.

Habilidades del cuidador primario de mujeres mastectomizadas / Habilidades do cuidador primário de mulheres mastectomizadas / Mastectomized women primary caregiver's abilities

Objetivo. Describir las habilidades del cuidador primario (CP) en términos de conocimiento, valor y paciencia del de mujeres mastectomizadas. Metodología. En 2010 se llevó a cabo un estudio descriptivo de tipo transversal en una muestra de 100 cuidadores primarios del Instituto Nacional de Cancerología de la Ciudad de México. Para la medición de la habilidad se utilizó el instrumento “Inventario de habilidad de cuidado”, que tiene tres subescalas: conocimiento, valor y paciencia. Se estimaron las correlaciones entre la sumatoria de los términos, comparándolas con las variables sociodemográficas. Resultados. El 41% de los CP fueron hombres, casados en un 77%; predominantemente fueron hijos (41%) o esposos (32%) del paciente. La edad mediana del CP, fue 43 años. En las habilidades del cuidador se encontró: alta puntuación para las dimensiones de conocimiento y paciencia, y baja para la de valor. Se identificó una correlación significativa entre las dimensiones de conocimiento y paciencia, mientras que la correlación de valor y paciencia fue menor. Conclusión. Las habilidades más importantes con que debe contar el CP son el conocimiento y la paciencia; el valor no mostró tal relevancia.

Objective. To describe the abilities in care, mastectomized women primary caregivers (PC) have, in terms of knowledge, value and patience. Methodology. Cross sectional descriptive study carried out in 2010 in the National Institute of cancerology in Mexico City. A sample of 100 primary caregivers was used. For the abilities measurement the instrument “caring abilities inventory”, which has 3 subscales, Knowledge, value and patience, was used. Correlations were estimated among the sum of the terms comparing them with the sociodemographic variables. Results.41% of the PC were men, 77% were married, 41% were the patient’s children and 32% their couple, most of them had a paid job. Caregivers mean age was 43 years. Regarding caregiver abilities a high score for the dimensions knowledge and patience, and a low score for value was found. The correlation between value and patience was low. Conclusion. The most important abilities caregivers must have are knowledge and patience. Value didn’t show such relevance.

Objetivo. Descrever as habilidades no cuidado em termos de conhecimento, valor e paciência do cuidador primário (CEP) de mulheres mastectomizadas. Metodologia. Em 2010 se levou a cabo um estudo descritivo de tipo transversal numa mostra de 100 cuidadores primários do Instituto Nacional de Cancerologia da Cidade do México. Para a medição da habilidade se utilizou o instrumento “Inventário de habilidade de cuidado”, que tem três sub-escalas: conhecimento, valor e paciência. Estimaram-se as correlações entre a sumatória dos termos, comparando-as com as variáveis sócio-demográficas. Resultados. O 41% dos CEP foram homens, casados num 77%; predominantemente foram filhos (41%) ou esposos (32%) do paciente, e a maioria tinham um trabalho remunerado. A média de idade do CEP foi de 43 anos. Nas habilidades do cuidador se encontrou: alta pontuação para as dimensões de conhecimento e paciência, e baixa para a de valor. Identificou-se uma correlação significativa entre as dimensões de conhecimento e paciência, enquanto a correlação de valor e paciência foi menor. Conclusão. As habilidades mais importantes com do que deve contar o CEP são o conhecimento e a paciência; o valor não mostrou tal relevância.

[Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"]. / Tercer Consenso Nacional de Cáncer de Ovario 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM".

INTRODUCTION: Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically. CONCLUSIONS: In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.

[Psychosocial adjustment in colorectal cancer patients undergoing chemotherapy or chemoradiotherapy].

BACKGROUND: Psychosocial adaptation is a measurement that represents the patient's adjustment to those changes involved in their illness. We undertook this study to search for individual characteristics and clinical aspects associated with successful psychosocial adjustment in patients with colorectal cancer (CRC) undergoing (CT) chemotherapy or chemoradiotherapy (CRT). METHODS: Seventy-five patients with CRC treated with CT or CRT in a cancer center were included. Psychosocial Adjustment to Illness Scale Self-Reporting (PAIS-SR) questionnaire was used as a measurement of psychosocial adjustment. RESULTS: Psychosocial adaptation was successful in 18 patients (24%) and unsuccessful in 57 patients (76%). Young patients, married patients and males showed lower psychosocial adaptation to disease. This is associated with the decrease in sexual relations, economic resources and psychological symptoms. Patients complained that they were unsatisfied due to the lack of disease and treatment information offered by the heath care team. CONCLUSIONS: In the process of adaptation, clinical features such as tumor location and treatment scheme are considered basic, as well as age, education, marital status. Areas such as sexuality, interpersonal and family relationships, economic status and emotional state of patients affected by the disease and treatments provide a deep complexity in the study of the psychosocial adaptation process in patients with CRC.

Validation of the Mexican Spanish version of the EORTC C30 and STO22 questionnaires for the evaluation of health-related quality of life in patients with gastric cancer.

Health-related quality of life (HRQL) is a fundamental outcome in surgical oncology and culturally valid tools are essential for this purpose. Our aim was to validate the Mexican-Spanish versions of the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire QLQ-C30 and the QLQ-STO22 disease-specific questionnaire module in Mexican patients with gastric cancer (GC). The translation procedure followed EORTC guidelines. Both instruments were completed by patients with GC and analyses were performed within three clinically distinct groups: (1) patients undergoing palliative treatment, (2) patients undergoing treatment with curative intent, and (3) GC survivors. Tests for reliability and validity were performed. One hundred and fifty patients (mean age 54.2 years) completed both questionnaires. Sixty-seven, 55, and 28 patients were allocated to groups 1, 2, and 3, respectively. Compliance rates were high, and questionnaires were well-accepted. Survivors of treatment for GC reported better functional HRQL scores and lower symptom scores than patients in group 2 who were currently undergoing treatment. Patients selected for potentially curative treatment had better HRQL than group 1 (palliative treatments). Scales in the QLQ-C30 and QLQ-STO22 distinguished between other clinically distinct groups of patients. Cronbach's alpha coefficients of 14 scales of both questionnaires were >0.7. Multitrait scaling analysis demonstrated good convergent and discriminant validity. Test-retest scores were consistent. We conclude that the Mexican-Spanish versions of EORTC QLQ-C30 and QLQ-C22 questionnaires are reliable and valid for HRQL measurement in patients with GC and are therefore recommended for use in clinical trials of Mexican community.

Rebrote en alfalfa-ovillo bajo pastoreo mixto durante el invierno / Regrowth of alfalfa-orchard under mixed grazing in winter

El pastoreo mixto puede mejorar la eficiencia de cosecha del forraje al disminuir la competencia intraespecífica. El objetivo del estudio fue describir la respuesta de alfalfa (Medicago sativa-L)-ovillo (Dactylis glomerata L) al aplicar pastoreo mixto (vaca+borrega) con sobrecarga del 20 por ciento. Se compararon dos tratamientos: pastoreo monoespecífico (vacas solamente) y pastoreo mixto (vacas+borregas). El diseño fue completamente al azar con dos repeticiones. Se usaron como pastoreadores un total de 10 vacas Holstein y 24 borregas, el pastoreo fue en franjas con 30-32 días de descanso e intensidad de cosecha de 7 cm. El análisis de los datos fue por pruebas de "t de student". Cantidad y composición del forraje ofrecido, como cantidad y composición del forraje residual, fueron similares (alfa= 0,05) para ambos tratamientos. Los incrementos diarios de altura, número de tallos y hojas en alfalfa y ovillo fueron similares (alfa= 0,05) entre tratamientos, pero en ovillos fue menor (alfa= 0,05) la altura al inicio del período de rebrote, en el pastoreo mixto por una cosecha más severa por parte de las borregas, pero esto no afectó el rebrote del ovillo. Se concluyó que el pastoreo mixto vacas+borregas no ocasionó cambios en los atributos de la pradrera y que la mayor severidad de cosecha en ovillo no ocasionó daños en el rebrote del mismo