Effect of three training programs on surgical performance in single-port laparoscopic surgery.

OBJECTIVE: The aim of this study was to evaluate the effect of three training methodologies on the acquisition of psychomotor skills for laparoendoscopic single-site surgery (LESS), using straight and articulating instruments. METHODS: A prospective study was conducted with subjects randomly divided into three groups, who performed a specific training for 12 days using three laparoscopic tasks in a laparoscopic simulator. Group-A trained in conventional laparoscopy setting using straight instruments and in LESS setting using both straight and articulating instruments. Group-B trained in LESS setting using straight and articulating instruments, whereas Group-C trained in LESS setting using articulating instruments. Participants' performance was recorded with a video-tracking system and evaluated with 12 motion analysis parameters (MAPs). RESULTS: All groups obtained significant differences in their performance in most of the MAPs. Group-C showed an improvement in nine MAPs, with a high level of technical competence. Group-A presented a marked improvement in bimanual dexterity skills. CONCLUSIONS: Training in LESS surgery using articulating laparoscopic instruments improves the quality of skills and allows smoother learning curves.

OBJETIVO: Evaluar el efecto de tres métodos de entrenamiento en la adquisición de habilidades psicomotrices para la cirugía laparoendoscópica por puerto único (LESS, laparoendoscopic single-site surgery) utilizando instrumental recto y articulado. MÉTODO: Se realizó un estudio prospectivo con sujetos divididos aleatoriamente en tres grupos, quienes realizaron un entrenamiento específico durante 12 días utilizando tres tareas laparoscópicas en un simulador laparoscópico. El grupo A entrenó en el entorno laparoscópico convencional con instrumentos rectos, y en el entorno LESS con instrumentos rectos y articulados. El grupo B entrenó en el entorno LESS con instrumentos rectos y articulados. El Grupo C entrenó en el entorno LESS con instrumentos articulados. El desempeño de los participantes se registró con un sistema de seguimiento en video y fue evaluado con 12 parámetros de análisis de movimiento (MAP, motion analysis parameters). RESULTADOS: Todos los grupos obtuvieron diferencias significativas en su desempeño para la mayoría de los MAP. El grupo C mostró una mejora en nueve MAP, con un alto nivel de competencia técnica. El grupo A mostró una marcada mejora en la habilidad de destreza bimanual. CONCLUSIONES: El entrenamiento en cirugía LESS con instrumentos articulados mejora la calidad de las habilidades adquiridas y permite curvas de aprendizaje más suaves.

Long Noncoding RNA TALAM1 Is a Transcriptional Target of the RUNX2 Transcription Factor in Lung Adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development contribute to this pathology. Runt-related transcription factor (RUNX) proteins belong to a family of master regulators of embryonic developmental programs. Specifically, RUNX2 is the master transcription factor (TF) of osteoblastic differentiation, and it can be involved in pathological conditions such as prostate, thyroid, and lung cancer by regulating apoptosis and mesenchymal-epithelial transition processes. In this paper, we identified TALAM1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) as a genetic target of the RUNX2 TF in lung cancer and then performed functional validation of the main findings. METHODS: We performed ChIP-seq analysis of tumor samples from a patient diagnosed with lung adenocarcinoma to evaluate the target genes of the RUNX2 TF. In addition, we performed shRNA-mediated knockdown of RUNX2 in this lung adenocarcinoma cell line to confirm the regulatory role of RUNX2 in TALAM1 expression. RESULTS: We observed RUNX2 overexpression in cell lines and primary cultured lung cancer cells. Interestingly, we found that lncRNA TALAM1 was a target of RUNX2 and that RUNX2 exerted a negative regulatory effect on TALAM1 transcription.

Selective Concurrence of the Long Non-Coding RNA MALAT1 and the Polycomb Repressive Complex 2 to Promoter Regions of Active Genes in MCF7 Breast Cancer Cells.

In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies focus on single genes that are usually repressed. Due to the genomic binding properties of both macromolecules, we wondered whether there are binding sites shared by PRC2 and MALAT1. Using public genome-binding datasets for PRC2 and MALAT1 derived from independent ChIP- and CHART-seq experiments performed with the breast cancer cell line MCF7, we searched for regions containing PRC2 and MALAT1 overlapping peaks. Peak calls for each molecule were performed using MACS2 and then overlapping peaks were identified by bedtools intersect. Using this approach, we identified 1293 genomic sites where PRC2 and MALAT1 concur. Interestingly, 54.75% of those sites are within gene promoter regions (<3000 bases from the TSS). These analyses were also linked with the transcription profiles of MCF7 cells, obtained from public RNA-seq data. Hence, it is suggested that MALAT1 and PRC2 can concomitantly bind to promoters of actively-transcribed genes in MCF7 cells. Gene ontology analyses revealed an enrichment of genes related to categories including cancer malignancy and epigenetic regulation. Thus, by re-visiting occupancy and transcriptomic data, we identified a key gene subset controlled by the collaboration of MALAT1 and PRC2.

Discordant results for ALK based on immunohistochemistry versus fluorescence in situ hybridization in a cohort of patients diagnosed with lung adenocarcinoma.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangement located on the short arm of chromosome 2, region 2 and band 3 is frequent in lung cancer patients who respond to targeted therapies with ALK inhibitors Therefore, their identification has become a standard diagnostic test in patients with advanced NSCLS, as such chromosomal alterations may lead to the activation of important signalling pathways involved in cell survival and proliferation. METHODS: To investigate the ALK gene status, we performed FISH and IHC assays in 18 lung adenocarcinoma patients, 12 women and 6 men, aged between 29 and 85 years. Paraffin-embedded samples were analyzed in the Pathology Department of the Hospital Universitario San Ignacio. RESULTS: Results between the two techniques in 5 patients showed discordant patterns, being positive for FISH and negative for IHC. The borderline to define ALK positivity was set at 15%, These results present experimental evidence that the techniques differ in specific situations. CONCLUSIONS: Our findings show that it is advisable to investigate the ALK gene status in patients with suspected lung cancer using both FISH and IHC in combination.

Lung Cancer Gene Regulatory Network of Transcription Factors Related to the Hallmarks of Cancer.

The transcriptomic analysis of microarray and RNA-Seq datasets followed our own bioinformatic pipeline to identify a transcriptional regulatory network of lung cancer. Twenty-six transcription factors are dysregulated and co-expressed in most of the lung cancer and pulmonary arterial hypertension datasets, which makes them the most frequently dysregulated transcription factors. Co-expression, gene regulatory, coregulatory, and transcriptional regulatory networks, along with fibration symmetries, were constructed to identify common connection patterns, alignments, main regulators, and target genes in order to analyze transcription factor complex formation, as well as its synchronized co-expression patterns in every type of lung cancer. The regulatory function of the most frequently dysregulated transcription factors over lung cancer deregulated genes was validated with ChEA3 enrichment analysis. A Kaplan-Meier plotter analysis linked the dysregulation of the top transcription factors with lung cancer patients' survival. Our results indicate that lung cancer has unique and common deregulated genes and transcription factors with pulmonary arterial hypertension, co-expressed and regulated in a coordinated and cooperative manner by the transcriptional regulatory network that might be associated with critical biological processes and signaling pathways related to the acquisition of the hallmarks of cancer, making them potentially relevant tumor biomarkers for lung cancer early diagnosis and targets for the development of personalized therapies against lung cancer.

Identification of the Transcriptional Regulatory Role of RUNX2 by Network Analysis in Lung Cancer Cells.

The use of a new bioinformatics pipeline allowed the identification of deregulated transcription factors (TFs) coexpressed in lung cancer that could become biomarkers of tumor establishment and progression. A gene regulatory network (GRN) of lung cancer was created with the normalized gene expression levels of differentially expressed genes (DEGs) from the microarray dataset GSE19804. Moreover, coregulatory and transcriptional regulatory network (TRN) analyses were performed for the main regulators identified in the GRN analysis. The gene targets and binding motifs of all potentially implicated regulators were identified in the TRN and with multiple alignments of the TFs' target gene sequences. Six transcription factors (E2F3, FHL2, ETS1, KAT6B, TWIST1, and RUNX2) were identified in the GRN as essential regulators of gene expression in non-small-cell lung cancer (NSCLC) and related to the lung tumoral process. Our findings indicate that RUNX2 could be an important regulator of the lung cancer GRN through the formation of coregulatory complexes with other TFs related to the establishment and progression of lung cancer. Therefore, RUNX2 could become an essential biomarker for developing diagnostic tools and specific treatments against tumoral diseases in the lung after the experimental validation of its regulatory function.

Regulatory Role of the RUNX2 Transcription Factor in Lung Cancer Apoptosis.

Lung cancer is the leading cause of cancer death globally. Numerous factors intervene in the onset and progression of lung tumors, among which the participation of lineage-specific transcription factors stands out. Several transcription factors important in embryonic development are abnormally expressed in adult tissues and thus participate in the activation of signaling pathways related to the acquisition of the tumor phenotype. RUNX2 is the transcription factor responsible for osteogenic differentiation in mammals. Current studies have confirmed that RUNX2 is closely related to the proliferation, invasion, and bone metastasis of multiple cancer types, such as osteosarcoma, breast cancer (BC), prostate cancer, gastric cancer, colorectal cancer, and lung cancer. Thus, the present study is aimed at evaluating the role of the RUNX2 transcription factor in inhibiting the apoptosis process. Loss-of-function assays using sh-RNA from lentiviral particles and coupled with Annexin/propidium iodide (PI) assays (flow cytometry), immunofluorescence, and quantitative PCR analysis of genes related to cell apoptosis (BAD, BAX, BCL2, BCL-XL, and MCL1) were performed. Silencing assays and Annexin/PI assays demonstrated that when RUNX2 was absent, the percentage of dead cells increased, and the expression levels of the BCL2, BCL-XL, and MCL1 genes were downregulated. Furthermore, to confirm whether the regulatory role of RUNX2 in the expression of these genes is related to its binding to the promoter region, we performed chromatin immunoprecipitation (ChIP) assays. Here, we report that overexpression of the RUNX2 gene in lung cancer may be related to the inhibition of the intrinsic apoptosis pathway, specifically, through direct transcriptional regulation of the antiapoptotic gene BCL2 and indirect regulation of BCL-XL and MCL1.

Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis.

The bioinformatic pipeline previously developed in our research laboratory is used to identify potential general and specific deregulated tumor genes and transcription factors related to the establishment and progression of tumoral diseases, now comparing lung cancer with other two types of cancer. Twenty microarray datasets were selected and analyzed separately to identify hub differentiated expressed genes and compared to identify all the deregulated genes and transcription factors in common between the three types of cancer and those unique to lung cancer. The winning DEGs analysis allowed to identify an important number of TFs deregulated in the majority of microarray datasets, which can become key biomarkers of general tumors and specific to lung cancer. A coexpression network was constructed for every dataset with all deregulated genes associated with lung cancer, according to DAVID's tool enrichment analysis, and transcription factors capable of regulating them, according to oPOSSUM´s tool. Several genes and transcription factors are coexpressed in the networks, suggesting that they could be related to the establishment or progression of the tumoral pathology in any tissue and specifically in the lung. The comparison of the coexpression networks of lung cancer and other types of cancer allowed the identification of common connectivity patterns with deregulated genes and transcription factors correlated to important tumoral processes and signaling pathways that have not been studied yet to experimentally validate their role in lung cancer. The Kaplan-Meier estimator determined the association of thirteen deregulated top winning transcription factors with the survival of lung cancer patients. The coregulatory analysis identified two top winning transcription factors networks related to the regulatory control of gene expression in lung and breast cancer. Our transcriptomic analysis suggests that cancer has an important coregulatory network of transcription factors related to the acquisition of the hallmarks of cancer. Moreover, lung cancer has a group of genes and transcription factors unique to pulmonary tissue that are coexpressed during tumorigenesis and must be studied experimentally to fully understand their role in the pathogenesis within its very complex transcriptomic scenario. Therefore, the downstream bioinformatic analysis developed was able to identify a coregulatory metafirm of cancer in general and specific to lung cancer taking into account the great heterogeneity of the tumoral process at cellular and population levels.

Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence.

Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16INK4A protein is a key regulator of this process via its cyclin­dependent kinase inhibitor (CDKI) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD+)­dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non­senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl­transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene.

Structural Analysis of the Black-Legged Tick Saliva Protein Salp15.

Salp15 is one of the proteins in the saliva of the tick Ixodes scapularis. Together with other biomolecules injected into the mammalian host at the biting site, it helps the tick to sustain its blood meal for days. Salp15 interferes with the cellular immune response of the mammalian host by inhibiting the activation of CD4+ T-lymphocytes. This function is co-opted by pathogens that use the tick as a vector and invade the host when the tick bites, such as Borrelia burgdorferi, the causative agent of Lyme borreliosis. Because of the immunity-suppressing role of Salp15, it has been proposed as a candidate for therapeutic applications in disorders of the immune system. The protein is produced as a 135-residue long polypeptide and secreted without its N-terminal signal 1-21 sequence. Detailed structural studies on Salp15 are lacking because of the difficulty in producing large amounts of the folded protein. We report the production of Salp15 and its structural analysis by NMR. The protein is monomeric and contains a flexible N-terminal region followed by a folded domain with mixed α + ß secondary structures. Our results are consistent with a three-dimensional structural model derived from AlphaFold, which predicts the formation of three disulfide bridges and a free C-terminal cysteine.

Preescolar con divertículo de Zenker y hallazgo intraoperatorio de cuerpo extraño esofágico / Preschool-age child with Zenker's diverticulum and intraoperative finding of an esophageal foreign body

Introducción. El divertículo de Zenker es una evaginación sacular ciega que puede presentarse a nivel faringoesofágico. No se conoce exactamente su incidencia en la edad pediátrica, constituyendo una patología muy infrecuente. La sintomatología es inespecífica, lo que dificulta el diagnóstico precoz y determina un mayor riesgo de complicaciones asociadas. Caso clínico. Paciente preescolar femenina con cuadro recurrente de emesis con deshidratación, posteriormente asociado a disfagia, a quien se le diagnosticó un divertículo de Zenker. Se realizó tratamiento quirúrgico con hallazgo intraoperatorio de dilatación esofágica, un área de estenosis secundaria al hallazgo incidental de un cuerpo extraño y divertículo de Zenker en la región lateral del esófago dilatado. Discusión. Esta patología es extremadamente rara, pero se debe tener en cuenta dentro de los diagnósticos diferenciales en pacientes con sintomatología faringo-esofágica. Conclusión. Se presenta una preescolar sin antecedente de procedimientos esofágicos o malformaciones congénitas asociadas con diagnóstico de un divertículo de Zenker y dilatación esofágica por un cuerpo extraño, tratada quirúrgicamente de forma exitosa.

Introduction. Zenker's diverticulum is a blind saccular evagination that can present at the pharyngoesophageal level. Its incidence in pediatric age is not exactly known, constituting a very infrequent pathology. The symptoms are nonspecific, which makes early diagnosis difficult and determines a higher risk of associated complications.Clinical case. Female preschool patient with recurrent dehydration due to emesis, later associated with dysphagia, who was diagnosed with Zenker's diverticulum. Surgical treatment was performed with intraoperative finding of esophageal dilation, an area of stenosis secondary to the incidental finding of a foreign body, and a Zenker's diverticulum in the lateral region of the dilated esophagus. Discussion. This pathology is extremely rare, but it should be taken into account within the differential diagnoses in patients with pharyngo-esophageal symptoms. Conclusion: We present a preschool female patient with no history of esophageal procedures or congenital malformations associated with a diagnosis of Zenker's diverticulum and esophageal dilation due to a foreign body, successfully treated surgically.

An update on Fanconi anemia: Clinical, cytogenetic and molecular approaches (Review).

Fanconi anemia is a genetic syndrome clinically characterized by congenital malformations that affect several human systems, leads to progressive bone marrow failure and predisposes an individual to cancer, particularly in the urogenital area as well as the head and neck. It is commonly caused by the biallelic compromise of one of 22 genes involved in the FA/BRCA repair pathway in most cases. The diagnosis is based on clinical suspicion and confirmation using genetic analysis, where the chromosomal breakage test is considered the gold standard. Other diagnostic methods used include western blotting, multiplex ligation-dependent probe amplification and next-generation sequencing. This genetic condition has variable expressiveness, which makes early diagnosis difficult in certain cases. Although early diagnosis does not currently allow for improved cure rates for this condition, it does enable healthcare professionals to perform a specific systematic follow-up and, if indicated, a bone marrow transplantation that improves the mobility and mortality of affected individuals. The present review article is a theoretical revision of the pathophysiology, clinical manifestations and diagnosis methods intended for different specialists and general practitioners to improve the diagnosis of this condition.

RUNX1 gene expression changes in the placentas of women smokers.

The placenta can be affected by environmental factors, such as exposure to cigarette smoke. This exposure in the fetal context is considered a risk factor for the development of short-term postnatal diseases, such as asthma. Asthma is an inflammatory disease characterized by predominant acquisition of CD4 T lymphocytes (TLs) of the Th2 type. Transcription factors such as GATA binding protein 3 (GATA3) and STAT6 actively participate in the differentiation of virgin TLs towards the Th2 profile, while transcription factors such as STAT1, T-Box transcription factor 21 (T-BET), RUNX1 and RUNX3 participate in their differentiation towards the Th1 profile. The objective of the current study was to evaluate the impact of exposure to cigarette smoke on the gene expression of STAT1, T-BET, GATA3, IL-4, RUNX1 and RUNX3 during the gestation period, and to determine whether the expression levels of these genes are associated with changes in global methylation. STAT1, GATA3, RUNX1 and RUNX3 protein and mRNA expression levels in the placental tissue of women smokers and non-smoking women were determined via immunohistochemistry and quantitative PCR (qPCR) respectively. Additionally, T-BET and IL-4 mRNA expression levels were determined by qPCR. On the other hand, global methylation was determined via ELISA. In the present study, significant increases were observed in RUNX1 transcription factor expression in placentas from women smokers when compared with placentas of non-smoking women. Similarly, significant increases in the expression of GATA3, IL-4 and RUNX3 mRNA were observed. The changes in gene expression were not associated with changes in the global methylation levels. Finally, a higher frequency of low-birth-weight infants were identified in cases of exposure to cigarette smoke during pregnancy when compared with infants not exposed to cigarette smoke during pregnancy. Thus, the data of the present study contributed to the understanding of the genetic and clinical impacts of exposure to cigarette smoke during pregnancy and its importance in maternal and fetal health.

Perspectiva global y acción local para un programa doctoral en ciencias de la salud / Global perspective and local actions for a doctoral program in health sciences

Con el objeto de ponderar las condiciones actuales requeridas para un programa doctoral en Ciencias de la Salud en Colombia, se elaboró un documento base y de posición para explorar su viabilidad y factibilidad de desarrollo. Mediante una estrategia de revisión teórica, discusión de expertos y definición de categorías, se establecieron temas centrales para el estudio y comprensión de la situación. A través de un proceso heurístico, se definieron cinco categorías clave; "historia de los doctorados", "perspectiva global", "situación nacional", "elementos en la FUCS" y "prospectiva", que muestran un panorama mundial de sobreoferta y precariedad laboral versus la necesidad y la posibilidad de generar localmente desarrollos e innovaciones en salud, a condición que un doctorado respete condiciones de excelencia, integralidad y protección del estudiante y del talento humano formado. La conclusión fundamental es que un programa PhD en Ciencias de la Salud es viable en la medida de la factibilidad y la fortaleza de factores tales como unos proyectos bien planteados y ejecutados, un equipo de supervisores y codirectores expertos y competentes, y un conjunto de capacidades administrativa, financiera y estructural, todo lo cual implica, al final, voluntades políticas y directivas.

A base and position document was designed with the objective of considering the current conditions required to conceptualize a doctorate program in health sciences in Colombia, and explore its viability and feasibility. Some central topics were established by means of a theoretical review, expert discussion and defining categories in order to gain a better understanding of the situation. Five key categories were defined by an heuristic process, that is, "history of doctorates"; "global perspective"; "situation at the national level"; "elements available in the FUCS"; and "prospective", which show a global panorama of excess offer and job insecurity versus the need and the possibility to generate local health care developments and innovations to conduct a doctorate program respecting excellence, integrity and students and trained human talent. The fundamental conclusion was that a PhD program in health sciences depends on how feasible and strong some factors such as well formulated and implemented projects, a team of expert and competent supervisors and co-directors and a set of administrative, financial and structural capabilities are, all ultimately implying political and directive will

Structural insight into the membrane targeting domain of the Legionella deAMPylase SidD.

AMPylation, the post-translational modification with adenosine monophosphate (AMP), is catalyzed by effector proteins from a variety of pathogens. Legionella pneumophila is thus far the only known pathogen that, in addition to encoding an AMPylase (SidM/DrrA), also encodes a deAMPylase, called SidD, that reverses SidM-mediated AMPylation of the vesicle transport GTPase Rab1. DeAMPylation is catalyzed by the N-terminal phosphatase-like domain of SidD. Here, we determined the crystal structure of full length SidD including the uncharacterized C-terminal domain (CTD). A flexible loop rich in aromatic residues within the CTD was required to target SidD to model membranes in vitro and to the Golgi apparatus within mammalian cells. Deletion of the loop (Δloop) or substitution of its aromatic phenylalanine residues rendered SidD cytosolic, showing that the hydrophobic loop is the primary membrane-targeting determinant of SidD. Notably, deletion of the two terminal alpha helices resulted in a CTD variant incapable of discriminating between membranes of different composition. Moreover, a L. pneumophila strain producing SidDΔloop phenocopied a L. pneumophila ΔsidD strain during growth in mouse macrophages and displayed prolonged co-localization of AMPylated Rab1 with LCVs, thus revealing that membrane targeting of SidD via its CTD is a critical prerequisite for its ability to catalyze Rab1 deAMPylation during L. pneumophila infection.

Breast cancer detection in Mexico City during 2017. / Detección del cáncer de mama en la Ciudad de México durante 2017.

BACKGROUND: Breast cancer is the leading cause of death of women in Mexico; its detection is among the priorities of Mexico City's (CDMX) Southern Local Office from the Instituto Mexicano del Seguro Social (IMSS: Mexican Institute for Social Security). OBJECTIVE: To describe the incidence and mortality related to breast cancer detection in the CDMX's Southern Local Office units from IMSS in 2017. MATERIAL AND METHODS: Databases from the Coordination of Prevention and Health Care (CPAS), Information and Strategic Analysis (CIAE) and the Breast Clinic (UDDC Mama) were analyzed. Among data, it was included age, study (mastography, ultrasound and biopsy), and histological type, incidence and mortality. For statistical analysis it was used Student's t, and Spearman correlation (p < 0.05). RESULTS: In a population of 589,683 women (40-69 years), 97,779 mastographs were performed. Out of these, there were 94,883 normal (BI-RADS 1) and 1933 suspicious (BIRADS 3-5). In 436 biopsies, infiltrating ductal carcinoma was the most frequent. The incidence rate was 39.3/100,000 and the mortality rate was 3.54/100,000 inhabitants (in 2015 and 2016 it was 6.84 and 7.02/100,000, respectively). CONCLUSIONS: An increase in the incidence and a decrease in breast cancer mortality has been observed, which is related to improvements in screening programs in 2017. It is important to maintain and optimize screening programs.

INTRODUCCIÓN: El cáncer de mama es la principal causa de muerte de mujeres en México; su detección se ubica entre las prioridades de la Delegación Sur de la Ciudad de México del Instituto Mexicano del Seguro Social (IMSS). OBJETIVO: Describir la incidencia y la mortalidad relacionadas con la detección del cáncer de mama en las unidades de la Delegación Sur de la Ciudad de México del IMSS en 2017. MATERIAL Y MÉTODOS: Se analizaron las bases de datos de las Coordinaciones de Prevención y Atención a la Salud (CPAS), de Información y Análisis Estratégico (CIAE) y de la Clínica de Mama (UDDC Mama). Entre los datos se incluyó edad, estudio (mastografía, ultrasonido y biopsia) y tipo histológico, incidencia y mortalidad. Para el análisis estadístico se empleó t de Student y correlación de Spearman (p ≤ 0.05). RESULTADOS: En una población de 589 683 mujeres (40-69 años), se realizaron 97 779 mastografías. De estas hubo 94 883 normales (BIRADS 1) y 1933 sospechosas (BIRADS 3-5). En 436 biopsias, el carcinoma ductal infiltrante fue el más frecuente. La tasa de incidencia fue 39.3/100 000 y de mortalidad de 3.54/100 000 habitantes (en 2015 y 2016 fue de 6.84 y 7.02/100 000, respectivamente). CONCLUSIONES: Se ha observado un incremento en la incidencia y disminución de mortalidad por cáncer de mama, el cual está relacionado con mejoras en programas de detección en 2017. Es importante mantener y optimizar los programas de detección.

Disorders of sex development: Genetic characterization of a patient cohort.

Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as 'other' since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad­spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations.

Joint Transcriptomic Analysis of Lung Cancer and Other Lung Diseases.

Background: Epidemiological and clinical evidence points cancer comorbidity with pulmonary chronic disease. The acquisition of some hallmarks of cancer by cells affected with lung pathologies as a cell adaptive mechanism to a shear stress, suggests that could be associated with the establishment of tumoral processes. Objective: To propose a bioinformatic pipeline for the identification of all deregulated genes and the transcriptional regulators (TFs) that are coexpressed during lung cancer establishment, and therefore could be important for the acquisition of the hallmarks of cancer. Methods: Ten microarray datasets (six of lung cancer, four of lung diseases) comparing normal and diseases-related lung tissue were selected to identify hub differentiated expressed genes (DEGs) in common between lung pathologies and lung cancer, along with transcriptional regulators through the utilization of specialized libraries from R language. DAVID bioinformatics tool for gene enrichment analyses was used to identify genes with experimental evidence associated to tumoral processes and signaling pathways. Coexpression networks of DEGs and TFs in lung cancer establishment were created with Coexnet library, and a survival analysis of the main hub genes was made. Results: Two hundred ten DEGs were identified in common between lung cancer and other lung diseases related to the acquisition of tumoral characteristics, which are coexpressed in a lung cancer network with TFs, suggesting that could be related to the establishment of the tumoral pathology in lung. The comparison of the coexpression networks of lung cancer and other lung diseases allowed the identification of common connectivity patterns (CCPs) with DEGs and TFs correlated to important tumoral processes and signaling pathways, that haven´t been studied to experimentally validate their role in the early stages of lung cancer. Some of the TFs identified showed a correlation between its expression levels and the survival of lung cancer patients. Conclusion: Our findings indicate that lung diseases share genes with lung cancer which are coexpressed in lung cancer, and might be able to explain the epidemiological observations that point to direct and inverse comorbid associations between some chronic lung diseases and lung cancer and represent a complex transcriptomic scenario.

Novel homozygous mutation in a colombian patient with persistent müllerian duct syndrome: expanded phenotype

ABSTRACT The anti-Müllerian hormone triggers the regression of uterus and fallopian tubes in male embryos; if there are problems in the synthesis or action of this protein, Müllerian structures persist in an otherwise phenotypic male. The most frequent clinical presentation of Persistent Mullerian Duct syndrome is cryptorchidism and inguinal hernia. The few cases reported in adults are incidental findings or inguinal hernias. However, we present an adult male with history of bilateral cryptorchidism with unsuccessful orchidopexy, who presents with a large abdominal mass with the finding of a seminomatous tumor and persistence of Müllerian structures, in whom the variant c.916delC (p.Leu306Cysfs*29) in the AMHR2 gene not previously reported was documented.

Novel homozygous mutation in a colombian patient with persistent müllerian duct syndrome: expanded phenotype.

The anti-Müllerian hormone triggers the regression of uterus and fallopian tubes in male embryos; if there are problems in the synthesis or action of this protein, Müllerian structures persist in an otherwise phenotypic male. The most frequent clinical presentation of Persistent Mullerian Duct syndrome is cryptorchidism and inguinal hernia. The few cases reported in adults are incidental findings or inguinal hernias. However, we present an adult male with history of bilateral cryptorchidism with unsuccessful orchidopexy, who presents with a large abdominal mass with the finding of a seminomatous tumor and persistence of Müllerian structures, in whom the variant c.916delC (p.Leu306Cysfs*29) in the AMHR2 gene not previously reported was documented.