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The United Nations (UN) Decade of Ocean Science highlights a need to improve the way in which scientific results effectively inform action and policies regarding the ocean. Our research contributes to achieving this goal by identifying practical actions, barriers, stakeholder contributions and resources required to increase the sustainability of activities carried out in the context of artisanal fisheries to meet UN Sustainable Development Goals (SDG) and International Year of Artisanal Fisheries and Aquaculture (IYAFA) Global Action Plan (GAP) Pillar targets. We conducted a novel ‘social value chain analysis’ via a participatory workshop to elicit perspectives of value chain actors and fisheries stakeholders associated with two Spanish artisanal common octopus (Octopus vulgaris) fisheries (western Asturias—Marine Stewardship Council [MSC] certified, and Galicia—non-MSC certified) about their priorities regarding sustainable octopus production and commercialization. Our adapted Rapfish sustainability framework emphasised the importance of economic, environmental, ethical, institutional, social, and technological indicators to different actors across the value chain. We mapped participants’ shared sustainability priorities (e.g. integrated fisheries management, knowledge-based management, product traceability) to six Rapfish indicators, seven IYAFA Pillars and twelve SDGs to reveal how our results can inform ocean policy and actions. This identified how certification incentives and other cooperative approaches can facilitate environmental, economic and social sustainability (e.g. value-added products, price premiums for producers, gender inclusive organisations); support IYAFA priority outcomes (raised awareness, strengthened science-policy interface, empowered stakeholders, partnerships); and help to achieve UN SDG targets (e.g. SDG 14.b, SDG 17.17). The results can inform actors, stakeholders and policymakers about how different actors contribute to efforts to achieve the SDGs and how to manage priorities for sustainable actions within artisanal fisheries and their value chains. We recommend inclusive and equitable participatory knowledge transfer and governance platforms as part of the UN Decade of Ocean Science and beyond where participants can create theories of change towards sustainability involving the development of multi-sectoral ocean policies framed at the level of the value chain and supported by appropriate governance structures. Graphical Abstract

Spondylocarpotarsal synostosis syndrome (SCT) is a very rare skeletal dysplasia characterized by vertebral, carpal, and tarsal fusion; growth retardation; and mild dysmorphic facial features. Variants in FLNB, MYH3, and RFLNA have been implicated in this dysplasia. We report the clinical and radiological follow-up of seven SCT pediatric cases associated with biallelic FLNB variants, from four Argentinian families. The seven cases share previously described facial characteristics: round facies, large eyes, and wide based nose; all of them had variable height deficit, in one case noted early in life. Other findings included clinodactyly, joint limitation without bone fusion, neurosensorial hearing loss, and ophthalmological compromise. All cases presented with spinal fusion with variable severity and location, carpal bones coalition, and also delay in carpal ossification. The heterozygous carrier parents had normal height values to −2.5 score standard deviation, without skeletal defects detected. Three different FLNB variants, one nonsense and two frameshift, were detected, all of which were predicted to result in a truncated protein or are degraded by nonsense mediated decay. All cases had at least one copy of the nonsense variant, c.1128C> G; p. (Tyr376*), suggesting the presence of a common ancestor.

We developed a new type of generalized depletion model adapted to the rapid life cycle of Octopus vulgaris and the data collection framework put in place in its co-managed small-scale fishery (SSF) in Asturias, northwest Spain. The model uses weekly data from 19 seasons to estimate annual recruitment and female spawners emigration out of the vulnerable stock to attend to their broods. The matched annual spawners-recruitment (SR) magnitudes are then used as observations in a non-Bayesian hierarchical inference framework. The Shepherd SR model was selected among three alternatives. The stock has a high degree of density-dependence, leading to overcompensation. The estimated SR model has an unstable equilibrium point, driving the stock to deterministic cyclic fluctuations under small disturbances. Under those conditions the maximum sustainable yield (MSY) is not applicable, lending further credence to Sidney Holt’s opposition to the MSY as a basis for the elaboration of fishery management objectives, with potentially wide relevance to the management of SSF and cephalopod fisheries. We argue that harvest rates based on mean latent productivity, a concept that includes the MSY as a special case, are more adequate and sustainable for fluctuating stocks.

Describe growth at different periods of life to understand the effects of genetic impairment in FGFR3-related conditions. We hope this data will be used to compare different populations and the effects of future treatments towards growth improvement. The FGFR3 plays a critical role in early mammalian skeletal development, especially in postembryonic linear bone growth; however, little is known about its role during all of the growth process stages. In the achondroplasia growth curve, infancy, childhood, and puberty periods can be well recognized, coexisting with fast changes in body proportions. FGFR3 gain-of-function mutations are responsible for autosomal dominant chondrodysplasias characterized by a severe disproportionate short stature, as thanatophoric dysplasia, severe achondroplasia with developmental delay and acanthosis nigricans, achondroplasia, and hypochondroplasia. While achondroplasia is homogeneous with low variability, hypochondroplasia findings are less constant due to genotypic heterogeneity. In both conditions, birth size is slightly reduced, followed by a period of fast growth deceleration during infancy and a low magnitude pubertal growth spurt, most evident in sitting height. Some phenomena as shifting centile lines during infancy and parent-child height correlation are well described. A slight variability is shown between achondroplasia and hypochondroplasia populations within different ethnic backgrounds.

This article provides a brief account of the career of Eugenia M. del Pino. Casual events and serendipity played important roles in modeling her career as a developmental biologist. In collaboration with colleagues and students, she analyzed the biology and development of the marsupial frog Gastrotheca riobambae (family: Hemiphractidae) in comparison with Xenopus laevis and tropical frogs. The emphasis was placed on oogenesis and the early stages of development. Topics include the mono- and multi-nucleated modes of oogenesis. She described two modes of gastrulation in frogs, gastrulation modes one and two, according to the timing of notochord elongation. She was able to establish a pioneer laboratory for the comparative analysis of frog development in Ibero America at the Pontifical Catholic University of Ecuador, in Quito. Her contributions to society include her influence in the establishment of the National Academy of Sciences of Ecuador, and efforts toward the conservation of the Galápagos Archipelago. She is part of a pioneer group of professors that placed Biology as an academic discipline in Ecuador. The experiences of her career reveal that we all face difficulties in our jobs. However, nothing is impossible when we follow a passion. Her work reveals that the key to success is to turn obstacles into opportunities.

Introduction/Background* Molecular landscape and carcinogenesis of vulvar squamous cell carcinoma (VSCC) have been poorly explored and lack a biomarker-driven targeted therapy. In this non-systematic review we aimed to summarize findings of studies exploring molecular landscape of VSCC. Methodology Key word search was conducted (PubMed, Scopus) in January 2021, using the terms (“vulvar” and “cancer” or “carcinoma”) and (“molecular” or “genomic” or “mutation”). Observational studies evaluating molecular alterations in VSCC were deemed eligible. Pre-specified data were extracted from the selected articles, including the number of samples analyzed, DNA sequencing technique, number and frequency of identified mutations, HPV prevalence and prognostic data. Result(s)* Fourteen studies published between 2005 and 2020 were identified, including a total of 747 VSCC samples. Selected studies were highly heterogeneous in terms of DNA sequencing and HPV testing strategies and included small samples. Twelve studies performed next generation sequencing (NGS), nine of whom used targeted approach, two used whole exome sequencing and one used whole genome sequencing. The two remaining studies used multiplex ligation-dependent probe amplification assay and Sanger sequencing. The most frequently studies and mutated genes were TP53 and CDKN2A, followed by PIK3CA, HRAS and PTEN (table 1). Evidence on genomic differences between HPV-associated and -independent VSCC is particularly scarce and variable between studies. Only a single, targeted NGS study showed notorious differences in molecular profiles based on HPV status. Accumulated evidence indicates that in HPV-associated VSCC more frequently involves PI3K/AKT/mTOR pathway, involving HRAS, KRAS, PIK3CA, KMT2D, PTEN and FBXW7 mutations. On the other hand, HPV-independent VSCC involve alterations in TP53, CDKN2A, CCND1. The prognostic role of molecular alterations in VSCC was assessed in seven articles, with discordant results. Some articles suggest that TP53 alterations are associated to worse prognosis in patients with VSCC, particularly when combined with PIK3CA, HRAS or CDKN2A. Conclusion* Limitations and heterogeneity of available molecular series contribute to a limited view of the molecular landscape of VSCC. Prognostic or therapeutic roles of identified mutations and pathways in VSCC remain to be elucidated. Large-scale, genome or exome-wide studies with robust HPV testing are necessary to expand the knowledge on molecular landscape in VSCC.

Introduction/Background* The aim of this study was to correlate the serum concentrations of tumor markers HE4 and CA125 with the tumor burden evaluated through the volumetric parameters of FDG-PET/CT FDG in patients with advanced epithelial ovarian cancer (EOC) before primary treatment. Methodology Sixty-six patients with advanced stage high grade serous ovarian carcinoma (HGSOC) or undifferentiated carcinoma (UOC) were included. Serum HE4, serum CA125 and FDG PET/CT were performed before primary treatment. Volumes of interest (VOIs) were delimited on every pathological uptake in PET images. Whole-body metabolic tumor volume (wbMTV) and total lesion glycolysis (wbTLG) were calculated as the sum of every single VOI value. SUVmax thresholds were set at 40% and 50%. Four VOIs subgroups were defined for analysis: carcinomatosis, retroperitoneal, supradiaphragmatic and metastases. MTV and TLG values were calculated for each of them. The associations between these parameters and serum tumor markers were assessed through Pearson and Spearman tests. Result(s)* When correlating wbMTV and wbTLG with both CA125 and HE4, significant associations were found. The strongest correlation was observed between HE4 and wbMTV40% (r=0.61, p Conclusion* Peritoneal tumor burden measured by FDG PET/CT volumetric parameters correlates better with HE4 than with CA125 in patients with advanced epithelial ovarian cancer. These results support the increasing utility of HE4 to improve the stratification of these patients in clinical practice

Introduction/Background* Systematic pelvic and paraortic lymphadenectomy is part of the initial epithelial ovarian cancer (EOC) staging surgery but this procedure is associated with potential severe morbidity. Moreover, there is no evidence suggesting a possible therapeutic value. The detection of the sentinel lymph node (SLN) in the early stage of EOC is in the experimental phase and there is little literature about it. This study evaluates the lymphatic mapping with radiotracer and indocyanine green (ICG)) and the detection of ovarian SLN. Methodology Prospective cohort study in ovarian masses suspected of malignancy or re-staging surgery after confirmed malignancy. Albumin [99mTc] Tc-nanocolloid was injected into the utero-ovarian and infundibulo-pelvic ligaments. After 15 minutes, intraoperative images were acquired with a portable gammacamera. Subsequently, the adnexectomy and intraoperative pathological analysis were performed. In the cases in which malignancy was confirmed, ICG was injected proximally to the sectioned area of the ligaments and the lymphatic chains were traced with the fluorescence camera prior to the pelvic and paraortic lymphadenectomy. Ultrastaging of the SLN was done. The follow-up for possible adverse events lasted 30 days after surgery. Result(s)* 20 patients were included between September-2020 and May-2021. Ovarian carcinoma was confirmed in 8 (40%) cases. In all cases gamma probe was used, in 60% the gamma camera and 40% the fluorescence camera. Some SLN was detected in 18/20 cases (90%) with exclusive paraortic drainage in 5/18 (28%), pelvic in 1/18 (6%) and in both territories in 12/18 (66%). Overall para-aortic drainage was observed in 17/18 (94%) patients (35% supramesenteric, 30% at the level of the inferior mesenteric artery, and 35% inframesenteric). 100% of aortic SLNs were detected with a gamma probe after being visualized with the gamma camera. In the 8 patients who underwent lymphadenectomy, 1 case had positive nodes diagnosed by ultrastaging and the rest of the lymph nodes were negative. No complications related to the technique were observed. Conclusion* The SLN technique is feasible and safe. The intraoperative gamma camera shows the lymphatic map and is especially useful in the paraortic region.

Introduction/Background* In patients with early-stage, grade 1-2, endometrioid endometrial cancer, preoperative assessment of myometrial invasion is essential to define the need of pelvic and paraaortic lymph node dissection. Our aim was to evaluate the role of three-dimensional transvaginal ultrasound (3D-TVUS) and diffusion-weighted magnetic resonance imaging (DW-RMI) for the assessment of myometrial infiltration in patients with well-differentiated (G1) or moderately differentiated (G2) endometrioid endometrial carcinoma (EC). Methodology We performed a retrospective observational study. Myometrial infiltration was assessed by 3D-TVUS and DW-MRI in 152 women with G1 or G2 endometroid EC who underwent surgical treatment in a tertiary referral center between 2012 and 2019. Sensitivity, specificity, predictive values and accuracy for the two techniques and for a combination of both were computed. Definitive histopathological data in the surgical specimen regarding myometrial infiltration was used as ‘Gold Standard’. Result(s)* One hundred and fifty-two patients were included, 120 (79%) patients presented myometrial infiltration 50%). 3D-TVUS and DW-MRI showed an agreement of 78.9% with a kappa index of 0.44 for the detection of deep myometrial infiltration. Sensitivity, specificity and accuracy of 3D-TVUS for the detection of deep myometrial infiltration were 71.0%, 80.5% and 78.5% respectively. Evaluation of myometrial infiltration with DW-MRI had a sensitivity, specificity and accuracy of 76.2%, 84.4% and 82.9% respectively. Association of both techniques increased sensitivity and specificity up to 84.6% and 93.2% and provided a low false negative rate (2.3%). Conclusion* The combination of 3D-TVUS and DW-RMI offers a high sensitivity and specificity to identify deep myometrial infiltration in patients with endometrioid G1 or G2 EC, thus these patients might benefit from performance of both techniques in preoperative evaluation.

To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4–6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5–6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. Statistics: the chi-square test. The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.

Patients with hereditary hypophosphatemic rickets are short and disproportionate and very little information is available on segmental growth, but the body disproportion at adulthood leads us to think that the growth velocity of legs is slower.A total of 96 children were included and molecular testing was carried out in 42. Children who reached adult height were classified into two groups according to their compliance to conventional treatment (phosphate supplement and calcitriol). Individual growth records of height and sitting height/height were plotted using Argentine reference data in 96 children and growth curves were estimated by fitting Preece-Baines Model 1 in 19 of the children.Molecular testing revealed sequence deleterious alterations or large deletions in 36/42 patients. During childhood, 76% of children grew below - 1.88 standard deviation score (SDS) and 97% had body disproportion. During adolescence, the mean peak height velocity for the good and poor compliance to treatment groups was 7.8 (0.6) and 5.4 (0.4) cm/year in boys and 7.0 (0.7) and 5.2 (0.8) cm/year in girls, respectively. At adulthood, the median sitting height/height ratio was 2.32 and 6.21 SDS for the good and poor compliance to treatment groups, respectively. The mean pubertal growth spurt of the trunk was -0.8 (1.4) SDS, with a short pubertal growth spurt of - 1.8 (0.4) SDS for limbs in the good compliance group. Median adult height in 13/29 males and 30/67 females was -4.56 and -3.16 SDS, respectively.For all patients the growth spurt was slower, secondary to a short growth spurt of limbs, reaching a short adult height with body disproportion that was more prominent in the poor compliance group.

Marsupial frogs (Hemiphractidae) evolved exceptional mechanisms for the conquest of terrestrial life. These adaptations include very large eggs. In some species eggs reach 10 mm in diameter, and are considered to be the largest in frogs. Females have reproductive modifications for the incubation of embryos in their bodies. Modifications of embryos include adaptations for development inside the body of the mother, and changes in the developmental pattern. Moreover, in some species, oocytes are multinucleated instead of having a single germinal vesicle as in most vertebrates. This chapter provides an overview of the adaptations of marsupial frogs associated with terrestrial life, with a discussion of gastrulation and multinucleated oogenesis.

This issue of the International Journal of Developmental Biology is dedicated to Ibero America, and includes research articles from Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Panama, Puerto Rico, and Uruguay. It also describes the history of developmental biology in several Ibero American countries. Moreover, the volume contains interviews with scientists living in the region and abroad. Other articles highlight The Latin American Society for Developmental Biology (LASDB), and the International Courses. The main purpose of this volume is to stimulate interest and reseach in developmental biology in Ibero America.

Objective The aim of this study was to evaluate the oncological outcomes of vaginal fertility-sparing surgery plus laparoscopic sentinel lymph node biopsy in patients with early cervical cancer over a 15-years period. Patients and methods From March 2005 to April 2018, 38 patients diagnosed with early stage cervical cancer underwent vaginal fertility-sparing surgery at the Hospital Clinic, Barcelona, Spain. Patients with FIGO stage IA1 with lymphovascular space invasion and stage IA2 underwent simple trachelectomy and patients with stage IB1 underwent radical vaginal trachelectomy. All cases underwent laparoscopic sentinel lymph node biopsy. In the first 19 cases, laparoscopic bilateral pelvic lymphadenectomy was completed immediately after sentinel lymph node biopsy. Clinical and oncological follow-up data were collected. Results The median age at diagnosis was 33.5 years (range 22–44). Simple trachelectomy was performed in seven cases (18.4%) and vaginal radical trachelectomy in 31 (81.6%). Nineteen patients were exclusively treated with laparoscopic sentinel lymph node biopsy and 19 with sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy. There were no significant differences between the two lymph node assessment groups regarding histology and tumour size. The median follow-up was 73 months (range 1–160 months). There were 4 recurrences (3 patients with IB1 and 1 with IA2). Two occurred in the sentinel lymph node biopsy group and 2 in the sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy group. All the recurrences were diagnosed in patients with adenocarcinoma and in 3 patients without lymphovascular space invasion. Conclusion Vaginal fertility-sparing surgery combined with laparoscopic sentinel lymph node biopsy seems to be a safe oncological procedure in selected patients with early stage cervical cancer. Further studies are needed to clarify the role of sentinel lymph node biopsy in fertility- sparing surgery in cervical cancer. Adenocarcinoma histology seems to be an important risk factor for recurrence.

Se analizaron y compararon las características de la neurulación, morfología interna de los embriones desde la néurula hasta la eclosión del renacuajo y el modo de miogénesis de dos especies de ranas de la familia Dendrobatidae (Hyloxalus vertebralis y Dendrobates auratus) con otras especies de la misma familia y Xenopus laevis. Se realizó este análisis debido a que los huevos de H. vertebralis y D. auratus tienen el tamaño más grande detectado hasta ahora en la familia Dendrobatidae (2.6 y 3.5 mm de diámetro, respectivamente). La morfología interna de los embriones y la neurulación de H. vertebralis y D. auratus fueron similares a lo observado en X. laevis y otros Dendrobatidae. Se observó retraso en la diferenciación del cerebro en estas especies en comparación con X. laevis. La miogénesis de H. vertebralis y D. auratus ocurre por interdigitación celular como en Bombina variegata (Bombinatoridae), cuatro especies adicionales de Dendrobatidae, dos especies de Leiuperidae y una especie de Hemiphractidae. El estudio comparativo permite documentar la diversidad de programas del desarrollo entre los anuros y contribuir al conocimiento de la fauna ecuatoriana.

En la mayoría de los vertebrados usados como modelo del desarrollo, la determinación de la asimetría izquierda-derecha de la localización de órganos tales como el corazón se determina en la neurula y obedece a un flujo de fluido hacia el lado izquierdo. El flujo de fluido está guiado por el movimiento sincronizado de cilios en el techo del gastrocele, que corresponde a la cara interna del techo de la neurula de los anuros. Se estudió la morfología de la neurula y la placa del techo del gastrocele del anuro ecuatoriano, Epipedobates tricolor (Dendrobatidae). La placa del techo del gastrocele de la neurula de E. tricolor reviste dorsalmente a la cavidad del gastrocele y consiste de un epitelio monociliado, como en Xenopus laevis y otras ranas. La longitud de los cilios de E. tricolor fue de 8 μm en promedio. La placa del techo del gastrocele de E. tricolor comparte las características morfológicas observadas en la rana dendrobátida, Epipedobates machalilla y otras ranas con diversos modos reproductivos. La comparación sugiere que E. tricolor mantiene el mecanismo de flujo de fluido guiado por cilios para la determinación de la asimetría izquierda-derecha, como en otros anuros

Se describe la morfología externa e interna de la gástrula de la rana dendrobátida ecuatoriana, Epipedobates anthonyi. Los huevos tienen pigmento oscuro en el polo animal, su diámetro es de 2 mm en promedio y las posturas contienen entre 8 a 45 huevos. El tiempo requerido desde el inicio hasta culminar la gastrulación es de 1,5 días. La gástrula de E. anthonyi se caracterizó por la formación de un labio dorsal prominente en la región subecuatorial del embrión. El alargamiento del arquenterón estuvo retardado hasta después de terminar la gastrulación y las células que se acumularon en los labios del blastoporo formaron un prominente collar circumblastoporal. La gástrula de E. anthonyi comparte las características morfológicas observadas en otra rana dendrobátida, Colostethus (=Epipedobates) machalilla. Este estudio ha permitido una mejor comprensión de la gastrulación en ranas dendrobátidas y provee conocimientos adicionales sobre la biología de un miembro de la fauna ecuatoriana

This work studies the neural development of the dendrobatid frog Colostethus machalilla that is endemic to the Ecuadorian coast. It has a terrestrial way of life and it deposits its eggs directly on the ground. Immunostaining in whole embryos was done to study the pattern ofneural molecular markers. The neural development of C. machalilla is retarded in comparlson with the aquatic frog Xenopus laevis.

Se estudió la morfología de la gástrula y néurula en embriones de Ceratophrys stolzmanni (el sapo bocón de la costa). Los huevos, cuyo diámetro al comienzo de la gastrulación es de 2,2 mm, se desarrollan rápidamente. El proceso de gastrulación dura aproximadamente cinco horas. Los embriones fueron fijados y analizados en montaje entero, bisecciones y secciones de vibrátomo. Se encontró que los huevos tienen pigmento oscuro al igual que en Xenopus laevis, pero tienen un tamaño mayor. La morfología de la gástrula de C. stolzmanni es similar a la descrita para Ceratophrys ornata (el sapo cornudo argentino) por otros autores. Los estadios de gástrula tardía y néurula temprana, estudiados mediante secciones con tinción fluorescente para núcleos celulares, revelan ausencia de endodermo que recubra al notocordio y a los somitas en la parte dorsal posterior del embrión. Esta región se denomina GRP (Gastrocoel roof plate, por sus siglas en inglés) y tiene importancia en la determinación del eje izquierdo-derecho en anfibios. En este estudio se caracterizó el GRP de C. stolzmanni al nivel morfológico.

IQGAP1 is a scaffolding protein that serves a key role in cell dynamics by integrating internal and external stimuli to distinct signal outputs. Previous studies have identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of patients with colorectal adenocarcinoma (CRC), who underwent oxaliplatin-based chemotherapy (CT). In addition, screening studies have reported that IQ-motif containing GTPase activating protein 1 (IQGAP1) transcriptional expression levels varied from 'off' to 'on' following oxaliplatin CT. In order to determine if variations previously described in PWCs are able to be observed at the protein level in tumors and in metastases following CT, the present study performed an immunohistochemical analysis of IQGAP1 in CRC and primary metastases. IQGAP1 expression was observed in the nuclear envelope and in lateral cell membranes and cytoplasm in normal colon tissue. However, in tumor tissue, cells exhibited a diffuse pattern, with variable expression levels of staining in the nuclear membrane and cytoplasm, with the highest expression intensity observed at the invasive front. In healthy and metastasized liver tissue and in the metastases themselves, expression levels varied from cell to cell from no expression to a high level. In the majority of cells, IQGAP1 co-localized with microtubules at the cytoplasmic face of the nuclear envelope. Strong positive expression was observed in areas of the lesion where cells were detaching from the lesion into the lumen. Despite the homogeneous IQGAP1 staining pattern observed in healthy colon tissue sections, CRC demonstrated heterogeneity in staining, which was more marked in metastasized liver tissue resected following CT. However, the most notable findings were the observed effects on the cellular and subcellular distribution and its implications for cancer biology. These results suggest that IQGAP1 may be a putative biomarker, a candidate for clinical diagnostics and a potential novel target for anti-cancer therapeutics.

Recently, we demonstrated that in human intravascular papillary endothelial hyperplasia (IPEH), vein wall vascularization occurs in association with myriad papillae, a large part of which formed in the vascularized vein wall. Previously, using an animal model, we observed that PGE2 and glycerol administration around the femoral vein originates intense vascularization of the vein wall from its intimal endothelial cells (ECs). This vascularization is similar to that in IPEH. The aim of this study is to assess the mechanism of papillary formation, using this model after demonstrating papillary development in neo-vascularized femoral vein walls. In semithin and ultrathin sections, the sequential vascular and papillary development was as follows: (a) activation of vein intimal ECs, (b) sprouting of intimal ECs towards the vein media layer and microvessel development, (c) interconnection between neighboring microvessels originated elementary loops, which encircled vein wall components and formed papillae. The encircling ECs formed the papillary cover, and the encircled component formed the core. The papillae showed a similar structure to that of folds and pillars in intussusceptive angiogenesis, and (d) origin of secondary and complex loop systems by interconnection of neighboring elementary loops and by splitting of papillae by new loops, with abundant papillary development. In conclusion, the results support a piecemeal angiogenic mechanism in papillary formation, with association of sprouting and intussusceptive types of angiogenesis. Further studies are needed to assess whether the intravascular papillae described in several pathologic processes, including vessel tumors, such as Dabska's tumor, retiform hemangioendothelioma, and angiosarcoma, follow a similar mechanism. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1781-1792, 2017. © 2017 Wiley Periodicals, Inc.

Introduction/Background In early-stage cervical cancer, nodal involvement remains the most important prognostic factor. Imaging evaluation is not sensitive enough to replace histology. Achieving high detection rates is a prerequisite to introduce sentinel lymph node biopsy (SLNB). The aim of this study was to evaluate the evolution of SLNB detection techniques in women with early-stage cervical cancer treated in our institution. Methodology From 02/2001 until 01/2019, patients with FIGO 2009 stages IA1-IB1/IIA1 cervical carcinoma underwent SLNB. Those treated until 01/2010 endured SLNB followed by pelvic bilateral lymphadenectomy, thereafter only SLNB was performed. When SLNs were detected unilaterally or not detected, lymphadenectomy of the failed mapped side was performed. SLNB was achieved by laparoscopy after intracervical injection: first with blue dye (BD) plus radiocolloid (Tc) and, since 2014, with indocyanine green (ICG) also. SLN identification was performed with lymphoscintigraphy and SPECT/CT, facilitated by a laparoscopic gamma-probe and a fluorescence camera. Detection rate was calculated as the number of procedures in which at least one SLN was identified intraoperatively, divided by the total number of procedures undertaken. Results From 164 patients treated, 129 underwent SLNB with BD+Tc and 35 with BD+Tc+ICG. No differences regarding age at diagnosis, size of the tumor (≤2 cm vs >2 cm), FIGO stage, histologic subtype and surgical radicality were seen between both groups. In the first group, at least one SLN was identified in 123 cases, for an overall detection rate of 95.4%. The rate of bilateral detection was 61.2%. For the triple-technique group we detected SLNs in 35 cases, prompting a detection rate of 100%. SLNs were bilaterally detected in 34 patients (97.1%). Conclusion Both implemented techniques for SLNB in early-stage cervical cancer show a high detection rate. Nevertheless, triple technique with BD+Tc+ICG allows bilateral SLN detection in almost all patients. Disclosure Nothing to disclose.

Introduction/Background It has been suggested that the evaluation of the expression of host-cell genes involved in cervical carcinogenesis induced by high-risk human papillomavirus (HR-HPV) may be useful to identify patients harbouring high-grade squamous intraepithelial lesions (HSIL). We aimed to evaluate the performance of mRNA detection of three biomarkers (CDKN2A, MKi67, TOP2A) in liquid-based cytology (LBC) to identify HSIL. Methodology Observational prospective study including 250 patients referred to colposcopy. Patients underwent Pap-test, HR-HPV testing, colposcopy, and at least one biopsy. CDKN2A, MKi67 and TOP2A mRNA was detected in LBC specimens by reverse transcription and quantitative polymerase chain reaction. Among HR-HPV positive patients, 49 showed negative pathological findings, 38 harboured low-grade squamous intraepithelial lesions (LSIL), 105 harboured HSIL, and 17 showed discordant results between cytology (HSIL) and biopsy (LSIL). Thirty-five patients were HR-HPV negative and presented negative biopsies (control group). mRNA expression was quantified using ΔCycle threshold and compared between groups. We performed ROC analysis and computed sensitivity and specificity of mRNA expression for HSIL detection. Results Two hundred and forty-three (97.2%) LBC samples yielded adequate material for mRNA determination. We found higher expression of the three biomarkers in HSIL group compared to control group (p Table 1 shows area under the curve (AUC), sensitivity and specificity of the biomarkers for HSIL detection, at the optimal cut-off point according to ROC curve. Conclusion Detection of mRNA of CKN2A, MKi67 and TOP2A in LBC samples showed higher sensitivity than Pap-test to identify women with HSIL. Further studies are needed to confirm that host-cell mRNA detection might have a role in secondary prevention of cervical cancer. Disclosure Nothing to disclose.

Introduction/Background In early FIGO stage patients (IA, IB1 and IIA1) nodal involvement is one of the most important prognostic factors. Pelvic lymphadenectomy (LDN) is performed in order to assess lymph node involvement. Sentinel lymph node (SLN) biopsy has been increasingly used with limited evidence of oncological safety. Methodology Patients with FIGO stage IA1-IB1/IIA1 cervical carcinoma treated with radical surgery after lymph node assessment in Hospital Clinic (Barcelona, Spain) from 2001 to 2018 were included. Between 02/2001 and 05/2011 patients underwent SLN biopsy followed by complete pelvic LDN and patients from 06/2011 and 08/2018 underwent SLN dissection alone. Patients in whom SLN were detected unilaterally or not detected underwent a complete LDN of the failed mapped side. Radical surgery after intraoperative negative nodes were laparoscopic assisted vaginal radical hysterectomy or vaginal radical trachelectomy if fertility preservation desire. SLN were postoperative evaluated by pathologic ultrastaging. Intraoperative and postoperative as well as follow up data were prospectively recorded. STATA 15.1 was used for statistical analysis. Results In 162 patients lymph node assessment was performed, 87 (53.7%) underwent SLN biopsy followed by pelvic bilateral LDN and 75 (46.3%) SLNB only. No differences regarding age at diagnosis, size of the tumor (≤2 cm vs >2 cm), FIGO stage or histology type were seen between both groups. 151 patients had negative nodes. From these patients, 7 patients (9.1%) recurred in the LDN group and 3 patients (4.3%) in the SLN group. Cox hazard ratios were not statistically significant for lymph node assessment group. Conclusion Sentinel lymph node detection in patients with early cervical cancer does not entail an increased risk of recurrence with respect to the patients in whom a complete pelvic lymphadenectomy is performed. Disclosure The authors have no relationships/conditions/circumstances that present a potential conflict of interest.

Introduction/Background The aim was to evaluate the impact on survival depending on paraaortic (PA) nodes involvement and size of metastasis in locally advanced cervical cancer (LACC) after staging surgery and its safety before applying chemoradiotherapy treatment. Methodology We conducted a retrospective study in patients with LACC (FIGO stages from IB2 to IVA) from 2000 to 2016. All patients underwent MRI imaging and a laparoscopic staging PA lymphadenectomy (LSPAL). We performed an accurate ultrastaging of positive PA nodes and classified them in two groups (node metastasis >5 mm vs ≤5 mm) in order to compare the overall survival (OS). Radiation fields were extended to the PA area only in patients with PA nodes involvement. We evaluated the morbidity and mortality of the surgery. Results One hundred eighty three patients were diagnosed as a LACC. One hundred fifty patients had squamous carcinoma and thirty three patients adenocarcinoma. We observed 34 (18.5%) patients with PA nodal involvement (8 patients with PA metastasis measuring ≤5 mm and 20 measuring >5 mm). Six patients with lymph node metastasis did not have an ultrastaging study and were excluded from the analysis. Hazar Ratio for OS at 15 years were 2.51 (CI 0.90–6.98) for ≤5 mm metastasis (p 0.08) and 2.34 (CI 1.27–4.32) for >5 mm metastasis (p 0.007). Regarding surgical complications, 4 intraoperative events were reported (2,19%) although no perioperative mortality occurred. Thirteen (7.14%) early complications during the first month and 7(3.91%) late complications were reported with no mortality events. Conclusion The size of the paraaortic lymph node metastasis in patients with LACC has prognostic implications. Overall survival in patients with negative nodes or with metastasis ≤5 mm is similar. Paraaortic lymph node staging and extended-field radiotherapy represent a survival benefit in cases with positive nodes ≤5 mm. In LACC patients LSPAL seems a safe procedure. Disclosure Nothing to disclose.

Introduction/Background The aim of this study was to analyze the oncological outcomes and risk factors for recurrence of vaginal fertility-sparing surgery (FSS) and laparoscopic sentinel lymph node biopsy (SLNB) in patients with early cervical cancer (CC). Methodology From March 2005 to April 2018, 38 patients diagnosed with early stage CC underwent vaginal FFS at the Hospital Clinic, Barcelona, Spain. Patients with FIGO stage IA1 with lymphovascular space invasion (LVSI) and stage IA2 underwent simple trachelectomy and patients with stage IB1 underwent vaginal radical trachelectomy (VRT). All cases underwent laparoscopic SLNB. In the first cases, laparoscopic bilateral pelvic lymphadenectomy (LBPL) was completed immediately after SLNB. Clinical and oncological follow-up data were prospective collected. Results The median age at diagnosis was 33.5 years old (range 22–44). Simple trachelectomy was performed in seven cases (18.4%) and VRT in 31 (81.6%). Nineteen patients were treated with laparoscopic SLNB exclusively and 19 with SLNB plus LBPL. There were no significant differences between the two groups regarding histology and tumor size. The median follow-up was 73 months (range 1–160 months). There were 4 recurrences (3 patients with IB1 and one in IA2). Two occurred in the SLNB group and 2 in the SLNB plus LBPL group. All recurrences were diagnosed in patients with adenocarcinoma tumors and three without LVSI. Conclusion Vaginal FFS with laparoscopic SLNB seems to be a safe oncological procedure in early stage CC patients. Further studies are needed to clarify the role of adenocarcinoma histology as a prognostic factor of recurrence. Disclosure Nothing to disclose.

The developmental adaptations of the marsupial frogs Gastrotheca riobambae and Flectonotus pygmaeus (Hemiphractidae) are described and compared with frogs belonging to seven additional families. Incubation of embryos by the mother in marsupial frogs is associated with changes in the anatomy and physiology of the female, modifications of oogenesis, and extraordinary changes in embryonic development. The comparison of early development reveals that gene expression is highly conserved. However, the timing of gene expression varies between frog species. There are two modes of gastrulation according to the onset of convergent extension. In gastrulation mode 1, convergent extension is an intrinsic mechanism of gastrulation. This gastrulation mode occurs in frogs with aquatic reproduction, such as Xenopus laevis. In gastrulation mode 2, convergent extension occurs after the completion of gastrulation movements. Gastrulation mode 2 occurs in frogs with terrestrial reproduction, such as the marsupial frog, G. riobambae. The two modes of frog gastrulation resemble the two transitions toward meroblastic cleavage of ray-finned fishes (Actinopterygii). The comparison indicates that a major event in the evolution of frog terrestrial development is the separation of convergent extension from gastrulation.

Objective To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. Design Cross-sectional single-centre study. Setting A colposcopy clinic in Spain. Population A cohort of 113 women referred for colposcopy after an abnormal Pap smear. Methods Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. Main outcome measures Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. Results Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10–14% discordance on hrHPV genotype. Conclusions CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. Tweetable abstract Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.

We investigated the relationship between egg and cell sizes in the early gastrula of ten species of frogs with eggs of 1,100-3,500 μm diameters. We asked whether differences in cell size of the vegetal region, blastocoel roof, and marginal zone of the early gastrula were associated with egg size. Alternatively, we proposed that cell size differences may associate with gastrulation characteristics. The analyzed species were as follows: Xenopus laevis, Engystomops randi, Engystomops coloradorum, Espadarana callistomma, Epipedobates machalilla, Epipedobates anthonyi, Epipedobates tricolor, Dendrobates auratus, Gastrotheca riobambae, and Eleutherodactylus coqui. A positive correlation between egg and cell size was detected in the three regions of the gastrula. The correlation was strong in the vegetal region and blastocoel roof, and weak in the marginal zone. Large eggs allowed the evolution of frog terrestrial reproductive modes by storing nourishment for the developing embryos. Large cells, laden with yolk, occur in the vegetal region. However, small cell size characterized the marginal zone and blastocoel roof. We proposed that small cells of the marginal zone are required for involution and blastopore formation. The evolution pressure toward small cells in the marginal zone contributed to maintain the blastopore as a universal feature of frog gastrulation in eggs of different sizes and gastrulation modes. Our comparative analysis revealed two fundamental and conserved properties of the frog early gastrula, the correlation of egg with cell sizes, and the general small size of cells in the marginal zone.

The intercultural education in the Mapuche context has been generating many criticisms in the Chilean context. One of the main criticisms is that intercultural education programs have been imposed by the State, but do not respond to the educational needs or requirements of indigenous communities. Moreover, these programs have not been built in collaboration with the indigenous communities themselves. In this sense, a mayor question remains: what is actually meant by “interculturality” by the Mapuche people themselves, as they state that they are already intercultural because they know both their language (mapuzungun) and the official language of Chile (Castilian) and have forcibly accepted the institutionality and western rationality in Chile. In this context, it is worth asking how “interculturality” can contribute to a sustainable development of education in the Mapuche context. Since “sustainable development”, as implemented in “interculturality programs”, has a western epistemic base, it tends to lead to a homogenization of the knowledge and its further development. Therefore, if we want to think of education for sustainable development in a hypothetical and ideal way, then we should establish a broader or expanded epistemology that covers both language and action of indigenous epistemologies such as “balance” and “harmony” with the land, the rivers, the lakes, the forests, the people, the peoples and the cosmos; we observe that parts of the western epistemologies are aligning to that “balance” with the aim to valorise and recognize the importance of life in “community”. Thus, from the above, there emerges the need to rescue territorial and sociocultural components, which show epistemic and epistemological categories, from both western and indigenous rationalities, in order to generate an education in the framework of “sustainable development”, which can establish a dialogue of educational knowledge between the indigenous and the Chilean western context.

The developmental adaptations of the marsupial frogs Gastrotheca riobambae and Flectonotus pygmaeus (Hemiphractidae) are described and compared with frogs belonging to seven additional families. Incubation of embryos by the mother in marsupial frogs is associated with changes in the anatomy and physiology of the female, modifications of oogenesis, and extraordinary changes in embryonic development. The comparison of early development reveals that gene expression is highly conserved. However, the timing of gene expression varies between frog species. There are two modes of gastrulation according to the onset of convergent extension. In gastrulation mode 1, convergent extension is an intrinsic mechanism of gastrulation. This gastrulation mode occurs in frogs with aquatic reproduction, such as Xenopus laevis. In gastrulation mode 2, convergent extension occurs after the completion of gastrulation movements. Gastrulation mode 2 occurs in frogs with terrestrial reproduction, such as the marsupial frog, G. riobambae. The two modes of frog gastrulation resemble the two transitions toward meroblastic cleavage of ray-finned fishes (Actinopterygii). The comparison indicates that a major event in the evolution of frog terrestrial development is the separation of convergent extension from gastrulation.

Many frogs lay their eggs in water; the development of these frogs is well-known. However, many frogs reproduce on land; their eggs are large and have an altered early development. As examples, Gastrotheca riobambae broods its embryos in a pouch on the mother's back, and Eleutherodactylus coqui exhibits direct development with no tadpole stage. We provide practical information on obtaining eggs and embryos from these terrestrial-breeding species and on analyzing their development. Our aim is to make these species more accessible to researchers who are interested in the developmental and evolutionary consequences of terrestrial development.

The study of oogenesis and early development of frogs belonging to the family Hemiphractidae provide important comparison to the aquatic development of other frogs, such as Xenopus laevis, because reproduction on land characterizes the Hemiphractidae. In this review, the multinucleated oogenesis of the marsupial frog Flectonotus pygmaeus (Hemiphractidae) is analyzed and interpreted. In addition, the adaptations associated with the incubation of embryos in the pouch of the female marsupial frog Gastrotheca riobambae (Hemiphractidae) and the embryonic development of this frog are summarized. Moreover, G. riobambae gastrulation is compared with the gastrulation modes of Engystomops randi and Engystomops coloradorum (Leptodactylidae); Ceratophrys stolzmanni (Ceratophryidae); Hyalinobatrachium fleischmanni and Espadarana callistomma (Centrolenidae); Ameerega bilinguis, Dendrobates auratus, Epipedobates anthonyi, Epipedobates machalilla, Epipedobates tricolor, and Hyloxalus vertebralis (Dendrobatidae); Eleutherodactylus coqui (Terrarana: Eleutherodactylidae), and X. laevis (Pipidae). The comparison indicated two modes of frog gastrulation. In X. laevis and in frogs with aquatic reproduction, convergent extension begins during gastrulation. In contrast, convergent extension occurs in the post-gastrula of frogs with terrestrial reproduction. These two modes of gastrulation resemble the transitions toward meroblastic cleavage found in ray-finned fishes (Actinopterygii). In spite of this difference, the genes that guide early development seem to be highly conserved in frogs. I conclude that the shift of convergent extension to the post-gastrula accompanied the diversification of frog egg size and terrestrial reproductive modes.

CD34+ adipose stromal cells are scattered in the adipose tissue and found in the CD34+ population of the stromal vascular fraction (SVF). This fraction includes adipose-derived stromal/stem/progenitor cells (ASCs), which have attracted considerable attention and show great promise for the future of regenerative medicine. Studies in this field have been undertaken mainly in vitro. In this work, however, we assessed the characteristics of human adipose tissue-resident CD34+ stromal cells in normal conditions and when activated in vivo during inflammatory/repair processes at different stages of evolution. In normal adipose tissue, these cells showed a characteristic location (peri/paravascular and between adipocytes), a fusiform or stellate morphology, long and moniliform processes, and scarce organelles. During inflammatory/repair stages, native CD34+ stromal cells increased in size, proliferated, developed numerous organelles of synthesis, lost CD34 expression, and differentiated into myofibroblasts (αSMA expression and typical ultrastructure). In double-stained sections, cells expressing both CD34 and αSMA were observed. CD34 expression correlated positively with a high proliferative capacity (Ki-67 expression). Conversely, CD34 expression was lost with successive mitoses and with increased numbers of macrophages in the granulation tissue. CD34+ stromal cell behavior varied depending on proximity to (with myofibroblast differentiation) or remoteness from (with activated plump cells conserving CD34 expression) injury. In conclusion, our observations point to human adipose tissue-resident CD34+ stromal cells as an important source of myofibroblasts during inflammatory/repair processes. Moreover, stromal cell activation may occur with or without αSMA expression (with or without myofibroblast transformation) and with loss or persistence of CD34 expression, respectively.

Resumen Durante el periodo que denominamos perimenopausia en una mujer, con frecuencia se presentan alteraciones menstruales que consideramos dentro de la normalidad, no realizando estudios complementarios en la mayoria de las ocasiones y pautando tratamientos sintomaticos, si los precisa, hasta llegar el cese de la funcion ovarica. Presentamos un caso donde este tratamiento pautado tal vez intervino en el retraso diagnostico del problema principal, el cancer de mama lobulillar bilateral que, como primer sintoma, metastatizo en el endometrio provocando una metrorragia de dificil control.

Several epidemiological studies showed that gestational diabetes mellitus is the most frequent metabolic disorder of pregnancy, the pathogenesis of which has yet to be completely clarified. The aim of this study was to investigate the presence and processing of caspase 3 (Casp3) and poly(ADP-ribose) polymerase 1 (PARP1) in cord blood lymphocytes as markers of apoptosis in relation to glycaemic control during intrauterine life. Our results showed a specific positive correlation between the levels of active Casp3 (17-19 kDa) and the inactive form of PARP1 (89 kDa) in lymphocytes isolated from newborn babies of diabetic women with unbalanced glycaemic control, with a direct correlation between the activation of casp3 and the inactivation of PARP1, that makes lymphocytes unresponsive towards lipopolysaccharide stimulation, highlighting an altered functional response. Besides more studies are required to fully correlate the activation of the apoptotic process during the intrauterine life with the foetal health later in life, our study indicates that a cord blood lymphocyte, an easily accessible source, is informative about the activation of apoptotic stimuli in circulating cells of newborn babies in relation to the glycaemic control reached by the mother during pregnancy.