Consensus for Operating Room Multimodal Data Management: Identifying Research Priorities for Data-Driven Surgery.

Introduction: This study aimed to identify research areas that demand attention in multimodal data-driven surgery for improving data management in minimally invasive surgery. Background: New surgical procedures, high-tech equipment, and digital tools are increasingly being introduced, potentially benefiting patients and surgical teams. These innovations have resulted in operating rooms evolving into data-rich environments, which, in turn, requires a thorough understanding of the data pipeline for improved and more intelligent real-time data usage. As this new domain is vast, it is necessary to identify where efforts should be focused on developing seamless and practical data usage. Methods: A modified electronic Delphi approach was used; 53 investigators were divided into the following groups: a research group (n=9) for problem identification and a narrative literature review, a medical and technical expert group (n=14) for validation, and an invited panel (n=30) for two electronic survey rounds. Round 1 focused on a consensus regarding bottlenecks in surgical data science areas and research gaps, while round 2 prioritized the statements from round 1, and a roadmap was created based on the identified essential and very important research gaps. Results: Consensus panelists have identified key research areas, including digitizing operating room (OR) activities, improving data streaming through advanced technologies, uniform protocols for handling multimodal data, and integrating AI for efficiency and safety. The roadmap prioritizes standardizing OR data formats, integrating OR data with patient information, ensuring regulatory compliance, standardizing surgical AI models, and securing data transfers in the next generation of wireless networks. Conclusions: This work is an international expert consensus regarding the current issues and key research targets in the promising field of data-driven surgery, highlighting the research needs of many operating room stakeholders with the aim of facilitating the implementation of novel patient care strategies in minimally invasive surgery.

Gastrointestinal Kaposi: A Rare Case Unveiling the Presentation and Management Challenges of an Uncommon Neoplasm in the Digestive Tract.

Gastrointestinal Kaposi's sarcoma (GI-KS), which is frequently observed in individuals with HIV/AIDS, tends to manifest with vague symptoms or may not show any symptoms at all. These symptoms can include abdominal discomfort, nausea, vomiting, and low levels of iron in the blood, and they may worsen as the tumor enlarges, leading to more severe issues such as blockage or perforation of the bowel. Diagnosis usually requires an endoscopy to confirm the presence of GI-SK in individuals showing symptoms. In this case report, we describe a 29-year-old Hispanic male with vague symptomatology, anemia, and a probable unknown bleeding site.

Profiling of the genetic features of patients with breast, ovarian, colorectal and extracolonic cancers: Association to CHEK2 and PALB2 germline mutations.

BACKGROUND AND AIMS: Cancer predisposition goes beyond BRCA and DNA Mismatch Repair (MMR) genes since multi-gene panel testing has become the routine diagnostic tool for hereditary cancer suspicion (HCS) cases. CHEK2 and PALB2 are some of the foremost-mutated non-BRCA/MMR actionable genes in families with a significant familial aggregation. Therefore, the purpose of this work is to unravel which tumours other than breast, ovary or colorectal display the patients. MATERIALS AND METHODS: We have analysed 528 probands that meet the inclusion criteria for Hereditary Breast and Ovarian Cancer and Lynch Syndrome established by our Hereditary Cancer Regional Program with a customized 35 genes-panel by using Ion Torrent™ Technology. RESULTS: We have identified pathogenic variants (PVs) in 61 families (1.55%), of which more than half (31 probands) harboured PVs in CHEK2 and PALB2 genes. Ours results reveal that not only were PVs CHEK2 and PALB2 carriers more likely to have family history of cancer not limited to breast, ovarian or colorectal cancers, but also they are prone to other extracolonic cancers, noteworthy endometrial and gastric cancers. CONCLUSIONS: Multigene panel testing improves the chance of finding PVs in actionable genes in families with HCS. In addition, the coexistence of variants should be recorded to implement a polygenic risk algorithm that might explain the missing heritability in the aforementioned families.

Manifestaciones dermatológicas en una lactante con síndrome de kwashiorkor Claves para el diagnóstico y tratamiento oportuno / Dermatological Manifestations in an Infant with Kwashiorkor Syndrome: Keys for Diagnosis and Timely Treatment

Resumen El síndrome de kwashiorkor se caracteriza por malnutrición proteica y edema generalizado; algunos de los factores de riesgo que se asocian a su aparición son: vivir en pobreza, el destete reciente, las infecciones y las dietas basadas en maíz y arroz. Este síndrome puede generar manifestaciones cutáneas como piel delgada y seca, hiperpigmentación, áreas confluentes de descamación, cabello seco, hipopigmentado y desprendible, así como una dermatitis erosiva con predominio en pliegues cutáneos. El diagnóstico se basa principalmente en una evaluación nutricional integral, exploración física y estudios de laboratorio, y el éxito del tratamiento se basa en la rehabilitación nutricional temprana. Caso clínico: lactante del sexo femenino de 8 meses de edad, que acudió al Instituto Nacional de Pediatría (INP), por presentar una dermatosis generalizada de tipo descamativa de 1 mes de evolución, que fue tratada con ketoconazol tópico. Al interrogatorio la madre refiere alimentación exclusiva con atole de maíz por un diagnóstico de "alergia a la leche" y falta de recursos económicos para comprar la fórmula hidrolizada. La paciente presentaba una dermatosis diseminada que afectaba todos los segmentos corporales, caracterizada por placas hiperpigmentadas, bien definidas, de forma irregular, con descamación en láminas gruesas en región perioral y extremidades, así como áreas erosionadas, pálidas y edema generalizado en extremidades. Se realizaron exámenes de laboratorio que mostraron que la paciente tenía anemia (Hb 11.2 g/dL) e hipoalbuminemia (3.3 g/dL) que, en conjunto con las manifestaciones clínicas, integraron el diagnóstico de síndrome de Kwashiorkor. Se informaron los hallazgos clínicos y de laboratorio al servicio de Gastroenterología y Nutrición, quienes realizaron una valoración nutricional integral y decidieron iniciar tratamiento nutricional; por parte del servicio de Dermatología, se indicó el uso de emolientes y cuidados generales de la piel. Veinte días después la dermatosis y el edema habían remitido.

Abstract Kwashiorkor syndrome is characterized by protein malnutrition and edema, risk factors are recent weaning, infections, and diets based on corn and rice. This malnutrition can lead to skin manifestations such as thin, dry skin, hyperpigmentation, confluent areas of scaling, dry, hypopigmented, and detachable hair, as well as erosive dermatitis, predominantly in skin folds. The diagnosis is based on a nutritional evaluation exam, physical examination and laboratory finding, the treatment is based on early nutritional rehabilitation. Clinical case: 8-month-old female infant who attended the Instituto Nacional de Pediatría, presenting a scaling dermatosis of 1 month's evolution that was treated with topical ketoconazole. The mother reported exclusive feeding with corn gruel due to the diagnosis of "lactose allergy" and commented not enough resources to buy hydrolyzed formula. The patient presented a disseminated dermatosis to all body segments, characterized by well-defined, irregularly shaped, hyperpigmented plaques with scaling in thick sheets in the perioral region and extremities, as well as areas of eroded skin and paleness and edema of extremities. Laboratory tests were taken, where anemia (Hb 11.2 g/dl) and hipoalbuminemia (3.3 g/dl) were documented, the diagnosis of kwashiorkor syndrome was integrated. The clinical and laboratory findings were reported to the Gastroenterology and Nutrition service, who performed a nutritional assessment, and began nutritional treatment, emollients and general skin care were documented; twenty days later, the dermatosis and edema had subsided.

Crosstalk between diacylglycerol kinase and protein kinase A in the regulation of airway smooth muscle cell proliferation.

BACKGROUND: Diacylglycerol kinase (DGK) regulates intracellular signaling and functions by converting diacylglycerol (DAG) into phosphatidic acid. We previously demonstrated that DGK inhibition attenuates airway smooth muscle (ASM) cell proliferation, however, the mechanisms mediating this effect are not well established. Given the capacity of protein kinase A (PKA) to effect inhibition of ASM cells growth in response to mitogens, we employed multiple molecular and pharmacological approaches to examine the putative role of PKA in the inhibition of mitogen-induced ASM cell proliferation by the small molecular DGK inhibitor I (DGK I). METHODS: We assayed cell proliferation using CyQUANT™ NF assay, protein expression and phosphorylation using immunoblotting, and prostaglandin E2 (PGE2) secretion by ELISA. ASM cells stably expressing GFP or PKI-GFP (PKA inhibitory peptide-GFP chimera) were stimulated with platelet-derived growth factor (PDGF), or PDGF + DGK I, and cell proliferation was assessed. RESULTS: DGK inhibition reduced ASM cell proliferation in cells expressing GFP, but not in cells expressing PKI-GFP. DGK inhibition increased cyclooxygenase II (COXII) expression and PGE2 secretion over time to promote PKA activation as demonstrated by increased phosphorylation of (PKA substrates) VASP and CREB. COXII expression and PKA activation were significantly decreased in cells pre-treated with pan-PKC (Bis I), MEK (U0126), or ERK2 (Vx11e) inhibitors suggesting a role for PKC and ERK in the COXII-PGE2-mediated activation of PKA signaling by DGK inhibition. CONCLUSIONS: Our study provides insight into the molecular pathway (DAG-PKC/ERK-COXII-PGE2-PKA) regulated by DGK in ASM cells and identifies DGK as a potential therapeutic target for mitigating ASM cell proliferation that contributes to airway remodeling in asthma.

Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?

The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH) for both BRCA1/BRCA2, one ovarian cancer case DH for BRCA1/RAD51C, and another breast and colorectal cancer who is DH for BRCA2/PMS2 were identified in our cohort. Ages at diagnosis and severity of disease in BRCA1/BRCA2 DH resembled BRCA1 single-carrier features. Similarly, the co-existence of the BRCA2 and PMS2 mutations prompted the development of breast and colorectal cancer in the same patient. The first BRCA1/BRCA2 DH was identified by HA-based and Sanger sequencing (1 of 623 families with BRCA PVs). However, this ratio has increased up to 2.9% (1 DH carrier vs. 103 single PV carriers) since using a custom 35-cancer gene on-demand panel. The type of cancer developed in each DH patient was consistent with the independently inherited condition, and the clinical outcome was no worse than in patients with single BRCA1 mutations. Therefore, the clinical impact, especially in patients with two hereditary syndromes, lies in genetic counseling tailor-made for each family based on the clinical guidelines for each syndrome. The number of DH is expected to be increased in the future as a result of next generation sequencing routines.

Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: Relevance to Airway Remodeling in Asthma.

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We assessed the effect of pharmacological inhibition of DGK on pro-mitogenic signaling and proliferation in primary human ASM cells. Pretreatment with DGK inhibitor I (DGKI) significantly inhibited platelet-derived growth factor-stimulated ASM cell proliferation. Anti-mitogenic effect of DGKI was associated with decreased mTOR signaling and expression of cyclin D1. Exogenous PA promoted pro-mitogenic signaling and rescued DGKI-induced attenuation of ASM cell proliferation. Finally, house dust mite (HDM) challenge in wild type mice promoted airway remodeling features, which were attenuated in DGKζ-/- mice. We propose that DGK serves as a potential drug target for mitigating airway remodeling in asthma.

Colorectal Cancer and Polyp Detection Using a New Preparation-Free, Colon-Scan Capsule: A Pilot Study of Safety and Patient Satisfaction.

BACKGROUND: Current strategies to prevent colorectal cancer (CRC) vary considerably regarding safety, invasiveness, and patient satisfaction. A known deterrent for patients is the required bowel cleansing for colonoscopy. A new colon-scan capsule system is a unique preparation-free approach that provides structural information on colonic mucosa intended for detection of colorectal polyps and masses. AIMS: The aim of this study was to determine safety and patient satisfaction with the colon-scan capsule. METHODS: Prospective single-arm pilot study conducted at two tertiary care centers. Patients with a pre-scheduled colonoscopy for CRC screening or surveillance were included. Patients participating in this study underwent the colon-scan capsule and colonoscopy. Safety was defined by the occurrence of procedure or device-related adverse events. Satisfaction was based on survey questionnaires using a scoring system 1 (strongly disagree) to 5 (strongly agree). Patient satisfaction with the colon-scan capsule was compared to colonoscopy. RESULTS: Forty patients were included (52.9 [5.7] years; 64.1% females). There were no serious adverse events and no occurrences of capsule retention. The most common (12.5%) complaint was self-limiting abdominal cramping. Satisfaction questionnaires were completed by more than 87% of patients, with patients likely to recommend the capsule (score 4.1 [1.03]) compared to colonoscopy (score 2.8 [1.2]), p = 0.001. CONCLUSIONS: The new prepless colon-scan capsule system is an innovative, minimally invasive technology with demonstrated safety and high patient satisfaction. A multicenter pivotal study is planned to validate the performance, safety, and accuracy of polyp detection using the capsule system in comparison with colonoscopy.

Outcomes of endoscopic ultrasound and endoscopic resection of gastrointestinal subepithelial lesions: a single-center retrospective cohort study.

BACKGROUND: Endoscopic resection (ER) is an emerging therapeutic alternative for subepithelial gastrointestinal lesions (SELs). We aimed to determine whether size, layer of origin, and histology based on endoscopic ultrasound (EUS) and EUS-guided sampling (EUS-GS) influenced the outcomes and selection of patients for ER. METHODS: We performed a retrospective review of patients who underwent EUS, EUS-GS and resection of SELs from 2012-2019. Two pathologists reviewed the histology and layer of origin of all resected specimens, serving as the criterion for EUS accuracy. RESULTS: Seventy-three patients were included, of whom 59 (81%) were gastric SELs. Per EUS, median lesion size was 21 mm (interquartile range 15-32), and 63 (86%) originated from the 4th layer. The overall accuracy of EUS and EUS-GS in predicting the layer of origin and histology was 88% (95% confidence interval [CI] 77-94%) and 96% (95%CI 87-98%), respectively. Based on EUS, 18 (25%) patients were referred for ER, 5 (7%) to laparoscopic-endoscopic cooperative surgery, and 50 (68%) to surgery. Size >20 mm was associated with the type of resection approach (P=0.005), while layer of origin and histology were not (P=0.06 and P=0.09, respectively). When SELs were inaccurately classified (n=4) there were no adverse events or revision of the resection approach. CONCLUSIONS: EUS plays an important role in the outcome of resection approach for SELs, with size significantly influencing the selection for ER. In patients undergoing ER, no revised resections were needed when EUS was inaccurate.

A comprehensive custom panel evaluation for routine hereditary cancer testing: improving the yield of germline mutation detection.

BACKGROUND: In the context of our Regional Program of Hereditary Cancer, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our standard diagnostic approach focuses on sequencing a few classic high-risk genes, a method that frequently renders uninformative genetic results. This study aims to examine the improved yield offered by an On-Demand panel. METHODS: We designed an On-Demand panel for the analysis of 35-genes associated with inherited cancer susceptibility in a total of 128 cases of Hereditary Breast and Ovarian Cancer (HBOC) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC). RESULTS: Eighteen deleterious mutations were detected, in both routinely (BRCA2, MLH1, MSH2, PMS2) and non-routinely (ATM, BLM, BRIP1, CHEK2, MUTYH) tested genes. The screening extended to 35 genes rendered by patients carrying several- up to 6-Variants of Unknown Significance (VUS). Moreover, we confirmed the splicing disruption at RNA level for a not previously reported BRIP1 splicing mutation. Using an On-Demand panel, we identified 18 pathogenic mutation carriers, seven of which would have gone unnoticed with traditional analysis. CONCLUSIONS: Our results reinforce the utility of NGS gene panels in the diagnostic routine to increase the performance of genetic testing, especially in individuals from families with overlapping cancer phenotypes.

Predictors of self-expanding metallic stent dysfunction in malignant gastric outlet obstruction. / Predictores de disfunción del stent metálico autoexplandible en la obstrucción de salida gástrica maligna.

INTRODUCTION AND OBJECTIVES: Self-expanding metallic stents (SEMS) are the ideal treatment for malignant gastric outlet obstruction (MGOO) in patients with a short life expectancy, but stent dysfunction is frequent. The primary aim of our study was to identify the predictive factors of SEMS dysfunction in MGOO and the secondary aim was to determine the technical success, clinical success, and nutritional impact after SEMS placement. MATERIAL AND METHODS: A retrospective, longitudinal study was conducted at the gastrointestinal endoscopy department of the Instituto Nacional de Cancerología in Mexico City. Patients diagnosed with MGOO that underwent SEMS placement within the time frame of January 2015 to May 2018 were included. We utilized the gastric outlet obstruction scoring system (GOOSS) to determine clinical success and SEMS dysfunction. RESULTS: The study included 43 patients, technical success was 97.7% (n=42), and clinical success was 88.3% (n=38). SEMS dysfunction presented in 30.2% (n=13) of the patients, occurring in<6 months after placement in 53.8% (n=7) of them. In the univariate analysis, the histologic subtype, diffuse gastric adenocarcinoma (p=0.02) and the use of uncovered SEMS (p=0.02) were the variables associated with dysfunction. Albumin levels and body mass index did not increase after SEMS placement. Medical follow-up was a mean 5.8 months (1-24 months). CONCLUSIONS: SEMS demonstrated adequate technical and clinical efficacy in the treatment of MGOO. SEMS dysfunction was frequent and diffuse type gastric cancer and uncovered SEMS appeared to be dysfunction predictors.

Cáncer de Ovario: Tamizaje y diagnóstico imagenológico / Ovarian Cancer: Screening and imaging diagnosis

Resumen El cáncer de ovario se ha caracterizado por ser la neoplasia ginecológica de peor pronóstico. Lo anterior es consecuencia del curso silente de la enfermedad que ocasiona que la mayoría de las veces el diagnóstico se realice en etapas avanzadas. La información recolectada señala que los avances terapéuticos no han demostrado ser efectivos en mejorar la sobrevida de las pacientes con cáncer de ovario, lo cual orienta a la búsqueda constante de un método (o conjunto de éstos), que permita llevar a cabo el tamizaje y la detección temprana de dicha patología. Sin embargo, debido a que actualmente no se ha logrado identificar un método que sea costo-efectivo para el tamizaje, el mismo no se aplica a la población general y se reserva para casos específicos, como mujeres con antecedentes familiares de la enfermedad o que presentan síndromes hereditarios. Esta revisión incluye además información sobre las diferentes técnicas de imagen utilizadas tanto para el estudio y caracterización de masas anexiales, como para el estadiaje y pronóstico del cáncer de ovario. De las técnicas estudiadas, el ultrasonido (US) demostró ser la mejor opción para el abordaje inicial de masas anexiales; sin embargo, a la hora de realizar el estadiaje resultó ser inferior a la tomografía computarizada (TC) y la resonancia magnética (RM).

Abstract Ovarian cancer is the gynecological malignancy with the worst prognosis. Due to the silent course of the disease the diagnosis is made mainly in advanced stages. The literature reviewed showed that the therapeutic advances have not shown any major improvement in patient´s survival with ovarian cancer, therefore there is a constant research for a technique (or a set of them) that allows a proper screening and early detection of the disease. However, a cost effective method has not been found for screening, therefore it is not recommended for general population and it is reserved for specific cases, such as women with family history of ovarian cancer and with hereditary syndromes. This review also includes information about the different imaging techniques available not only for the study and characterization of neoplasms, but also for staging and prognosis of ovarian cancer. The ultrasound proved to be the best option for the initial approach of adnexal masses, however it has shown to be inferior for staging than CT-Scan and MRI.

Galactosialidosis: nueva mutación de novo en el gen CTSA en un paciente afecto de la forma infantil tardía / Galactosialidosis: a new "de novo" mutation in CTSA gene in a patient with late infantile galactosialidosis

La galactosialidosis (OMIM #256540) es una enfermedad metabólica lisosomal causada por mutaciones en el gen CTSA, que codifica la proteína protectora catepsina A. La pérdida de función de dicha proteína causa, secundariamente, un déficit combinado de dos enzimas, beta-galactosidasa y neuraminidasa. Se expone el caso de un paciente que presentó manifestaciones clínicas compatibles con el subtipo infantil tardío de galactosialidosis. El análisis bioquímico mostró déficits de las dos enzimas implicadas, mientras que el estudio molecular reveló dos mutaciones: una nueva mutación nunca antes descrita, p.His475Pro (c.1424 A>C), y una mutación previamente reportada, p.Arg441Cys (c.1321C>T), localizadas en los exones 15 y 14, respectivamente.

Galactosialidosis (OMIM #256540) is an autosomal recessive lysosomal storage disorder caused by mutations in the CTSAgene, which encodes the protective protein cathepsin A. The loss of function of this protein causes a secondarily deficiency of beta-galactosidase and N-acetyl-α-neuraminidase enzymes activities. We describe the clinical, biochemical and molecular analysis of a case report with a phenotype compatible with the late infantile form. The biochemical analysis reveled deficiencies of beta-galactosidase and neuraminidase activities in dried blood spot and fibroblasts and the molecular study showed two missense mutations in the CTSA gene: a previously reported mutation, p.Arg441Cys (c.1321C>T), and a novel mutation, p.His475Pro (c.1424 A>C), located in exons 14 and 15, respectively.

[Prevalence and implicated risk factors associated with the exteriorization of cardiac pacemakers: 5 year follow-up]. / Factores asociados e implicados en la exteriorización de marcapasos definitivo, seguimiento a cinco años.

BACKGROUND: Infection is the most common complication related to permanent pacemaker implantation. The objetive of this study is to establish the prevalence and determine the frequency of risk factors associated with exteriorization of cardiac pacemakers at the Department of Cardiac Electrophysiology at the UMAE Hospital de Especialidades "Dr. Antonio Fraga Mouret" Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social. METHODS: A descriptive cross-sectional study from September 2005 to September 2010, where, for the analysis of the risk factors we selected cases and controls by age, sex and the diagnosis of Diabetes, or not. Was calculated measures of central tendency (mean, median and mode) and chi-squared, Fisher exact test and exact odds ratio. RESULTS: 3192 cardiac pacemakers were implanted, identifying 83 exteriorization cases, where 46 of them were selected for cases and controls, and the mean age was 71 years. CONCLUSIONS: Our prevalence of exteriorization of cardiac pacemakers is 2.6 %, these results are similar to previously published studies. None of the risk factors described are present as a cause in our population. The surgical technique used may be an important risk factor, so further studies analysing all techniques are needed.

Introducción: el objetivo de este estudio es establecer la prevalencia y determinar la frecuencia de factores de riesgo de exteriorización de marcapasos definitivos (MPD), en el departamento de Electrofisiología Cardiaca de la UMAE Hospital de Especialidades "Dr. Antonio Fraga Mouret" del Centro Médico Nacional La Raza del Instituto Mexicano del Seguro Social.Métodos: se llevó a cabo un estudio transversal, descriptivo del periodo: septiembre del 2005 a septiembre del 2010, para el análisis de los factores se manejó como casos y controles; se eligieron emparejándose por edad, sexo y presencia, o no, de factores de riesgo. Se realizó el cálculo de medidas de tendencia central (media, mediana y moda), así como pruebas de chi cuadrada, test de Fisher y razón de momios.Resultados: se implantaron 3192 MPD, identificando 83 casos de exteriorizaciones, seleccionando 43 casos para casos y controles, la edad promedio fue de 71 años. Ninguno de los factores de riesgo ni el tipo de técnica quirúrgica presentó significancia estadística.Conclusiones: nuestra prevalencia de exteriorizaciones es del 2.6 %, valores muy similares a los reportes publicados. Ninguno de los factores de riesgo descritos se encuentra presente como causa de exteriorización en nuestra población. El análisis de la técnica quirúrgica utilizada puede ser un factor importante, por lo que se necesitan estudios posteriores.

Uni-directional ciliary membrane protein trafficking by a cytoplasmic retrograde IFT motor and ciliary ectosome shedding.

The role of the primary cilium in key signaling pathways depends on dynamic regulation of ciliary membrane protein composition, yet we know little about the motors or membrane events that regulate ciliary membrane protein trafficking in existing organelles. Recently, we showed that cilium-generated signaling in Chlamydomonas induced rapid, anterograde IFT-independent, cytoplasmic microtubule-dependent redistribution of the membrane polypeptide, SAG1-C65, from the plasma membrane to the periciliary region and the ciliary membrane. Here, we report that the retrograde IFT motor, cytoplasmic dynein 1b, is required in the cytoplasm for this rapid redistribution. Furthermore, signaling-induced trafficking of SAG1-C65 into cilia is unidirectional and the entire complement of cellular SAG1-C65 is shed during signaling and can be recovered in the form of ciliary ectosomes that retain signal-inducing activity. Thus, during signaling, cells regulate ciliary membrane protein composition through cytoplasmic action of the retrograde IFT motor and shedding of ciliary ectosomes.

Regulated membrane protein entry into flagella is facilitated by cytoplasmic microtubules and does not require IFT.

The membrane protein composition of the primary cilium, a key sensory organelle, is dynamically regulated during cilium-generated signaling [1, 2]. During ciliogenesis, ciliary membrane proteins, along with structural and signaling proteins, are carried through the multicomponent, intensely studied ciliary diffusion barrier at the base of the organelle [3-8] by intraflagellar transport (IFT) [9-18]. A favored model is that signaling-triggered accumulation of previously excluded membrane proteins in fully formed cilia [19-21] also requires IFT, but direct evidence is lacking. Here, in studies of regulated entry of a membrane protein into the flagellum of Chlamydomonas, we show that cells use an IFT-independent mechanism to breach the diffusion barrier at the flagellar base. In resting cells, a flagellar signaling component [22], the integral membrane polypeptide SAG1-C65, is uniformly distributed over the plasma membrane and excluded from the flagellar membrane. Flagellar adhesion-induced signaling triggers rapid, striking redistribution of the protein to the apical ends of the cells concomitantly with entry into the flagella. Protein polarization and flagellar enrichment are facilitated by cytoplasmic microtubules. Using a conditional anterograde IFT mutant, we demonstrate that the IFT machinery is not required for regulated SAG1-C65 entry into flagella. Thus, integral membrane proteins can negotiate passage through the ciliary diffusion barrier without the need for a motor.

Tongue granulomatous lesion caused by mandibular primary incisors eruption.

The aim of this report was to present a case of granulomatous lesion on the ventral surface of the tongue in a 9-month-old, healthy, infant girl, caused by the habit of scraping the tongue on mandibular central incisors. Clinical treatment consisted of manual smoothing of the sharp edges of both incisors and excision of the 2-cm pediculate ulcerative granulomatous mass localized on the ventral surface of the tongue. After 3 weeks, the child could be properly fed and a complete healing of the lesion was observed.

A new strategy to screen MMR genes in Lynch Syndrome: HA-CAE, MLPA and RT-PCR.

AIMS: Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant disorder that is genetically heterogeneous because of underlying mutations in mismatch repair (MMR) genes, primarily MLH1, MSH2 and MSH6. One challenge to correctly diagnose HNPCC is that the large size of the causative genes makes identification of mutations both labour intensive and expensive. METHODS: Our heteroduplex analysis by capillary array electrophoresis (HA-CAE) method, previously developed to increase the throughput and allow other multi-exon genes to be scanned, has been adapted for MMR genes. The altered peak patterns were then sequenced. Furthermore, the mutational scanning was completed using the Multiplex Ligation-Dependent Probe Amplification (MLPA) test in all negative HA-CAE cases, and these results were confirmed by RT-PCR. RESULTS: We studied 216 individuals belonging to 100 unrelated families that met the Amsterdam I/II criteria for HNPCC. We detected 40 different variants that are classified as follows: 8 (20%) deleterious mutation, 8 (20%) unknown pathogenic significance variants and 24 (60%) coding and intronic sequence variants. Pathogenic mutations were detected in 12% of the families and about 42% of these had a deletion variant. Unknown pathogenic significance variants (UVs) affected 13% of the families. We also found 12.5% of novel polymorphisms in the rest of the variants. CONCLUDING: In short, using a combined method that includes HA-CAE, MLPA and RT-PCR, it is possible to detect the entire mutational spectrum of MMR genes. Twenty percent of the mutations found in the three genes have not been reported before. Relatives at risk will be offered predictive molecular analysis with potential exclusion of non-carriers of mutations.

Retención de alimentos en la superficie oclusal de los segundos molares deciduos / Food retention at the occlusal surface of second deciduous molars

La literatura señala al segundo molar deciduo como el diente más afectado por caries. Objetivo: verificar la presencia y el área de retención alimenticia de la superficie oclusal de los segundos molares deciduos en niños de 36 a 48 meses. Material y métodos: Se examinaron 54 niños en dos tiempos (to: 0 y t1: 30 minutos), después de ingerir una galleta de chocolate. Se tomaron fotografías digitales para registrar la presencia y realizar el cálculo del área a través del programa Image Tool 3.0. Resultados: A pesar de que los dientes inferiores presentaron mayor presencia de retención en el tiempo final (90.74 por ciento) comparados a los superiores (85.18 por ciento) la diferencia no fue estadísticamente significativa (c2, p = 0.220). Mediante el examen de Mann-Whitney, fue observada una mayor área de retención en los dientes inferiores comparado a los superiores tanto en el tiempo inicial (Inferiores: 0.42 ± 0.02 y superiores: 0.27 ± 0.02) como en el tiempo final (Inferiores: 0.11 ±0.01 y superiores: 0.06 ± 0.01). Conclusiones: Los datos obtenidos están de acuerdo con las observaciones clínicas de ser los segundos molares deciduos inferiores, los molares de mayor complejidad oclusal y retención de alimentos, por tanto los más susceptibles.