Association between gait speed and balance disorders in older adults from 12 high Andean Peruvian communities, 2013-2019.

Background: Gait speed is associated with a higher prevalence of balance disorders in older adults residing at high altitudes. This study investigated this association in older adults from 12 high-altitude Andean Peruvian communities. Methods: We performed a secondary data analysis from an analytical cross-sectional study of adults >60 years of age, residing in 12 high-altitude Andean Peruvian communities, enrolled between 2013 and 2019. The exposure and outcome variables were gait speed (categorized in tertiles), and balance disorders (defined as a functional reach value of ≤20.32 cm), respectively. We built generalized linear models of the Poisson family with a logarithmic link function and robust variances, and estimated crude prevalence ratios (cPR) and adjusted prevalence ratios (aPR) with 95% confidence intervals (CIs). Results: We analyzed 418 older adults; 38.8% (n=162) were male, and the mean age was 73.2 ± 6.9 years. The mean gait speed and functional reach were 0.66 ± 0.24 m/s and 19.9 ± 6.48 cm, respectively. In the adjusted regression model, the intermediate (aPR=1.88; 95% CI: 1.39-2.55; p<0.001) and low (aPR=2.04; 95% CI: 1.51-2.76; p<0.001) tertiles of gait speed were associated with a higher prevalence of balance disorders. Conclusions: The intermediate and low tertiles of gait speed were associated with a higher prevalence of balance disorders among older adult residents of 12 high-altitude Andean communities. We recommend further research on the behavior of this association to propose interventions for these vulnerable groups and reduce the impact of geriatric conditions.

A time-resolved single-cell roadmap of the logic driving anterior neural crest diversification from neural border to migration stages.

Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of early molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification toward definitive neural crest. Here, we combine ultradense single-cell transcriptomes with machine-learning and large-scale transcriptomic and epigenomic experimental validation of selected trajectories, to provide the general principles and highlight specific features of the GRN underlying neural crest fate diversification from induction to early migration stages using Xenopus frog embryos as a model. During gastrulation, a transient neural border zone state precedes the choice between neural crest and placodes which includes multiple converging gene programs. During neurulation, transcription factor connectome, and bifurcation analyses demonstrate the early emergence of neural crest fates at the neural plate stage, alongside an unbiased multipotent-like lineage persisting until epithelial-mesenchymal transition stage. We also decipher circuits driving cranial and vagal neural crest formation and provide a broadly applicable high-throughput validation strategy for investigating single-cell transcriptomes in vertebrate GRNs in development, evolution, and disease.

Conserved chromatin and repetitive patterns reveal slow genome evolution in frogs.

Frogs are an ecologically diverse and phylogenetically ancient group of anuran amphibians that include important vertebrate cell and developmental model systems, notably the genus Xenopus. Here we report a high-quality reference genome sequence for the western clawed frog, Xenopus tropicalis, along with draft chromosome-scale sequences of three distantly related emerging model frog species, Eleutherodactylus coqui, Engystomops pustulosus, and Hymenochirus boettgeri. Frog chromosomes have remained remarkably stable since the Mesozoic Era, with limited Robertsonian (i.e., arm-preserving) translocations and end-to-end fusions found among the smaller chromosomes. Conservation of synteny includes conservation of centromere locations, marked by centromeric tandem repeats associated with Cenp-a binding surrounded by pericentromeric LINE/L1 elements. This work explores the structure of chromosomes across frogs, using a dense meiotic linkage map for X. tropicalis and chromatin conformation capture (Hi-C) data for all species. Abundant satellite repeats occupy the unusually long (~20 megabase) terminal regions of each chromosome that coincide with high rates of recombination. Both embryonic and differentiated cells show reproducible associations of centromeric chromatin and of telomeres, reflecting a Rabl-like configuration. Our comparative analyses reveal 13 conserved ancestral anuran chromosomes from which contemporary frog genomes were constructed.

Empatía, agresividad y perdón en contextos de vulnerabilidad, hostilidad y seguridad en niños y adolescentes

Introducción: El objetivo de este artículo fue identificar las variables que mejor predicen las medidas de agresión, empatía y perdón, como también las principales diferencias en contextos vulnerables, hostiles y seguros, en una muestra de niños, niñas y adolescentes pertenecientes a una población vulnerable. Método: se realizó un estudio cuantitativo transversal con una muestra no probabilística incidental de 85 participantes, se emplearon medidas psicométricas para la empatía, agresión y perdón. Los participantes fueron convocados en una fundación de atención a víctimas para realizar una entrevista y aplicar el test. Resultados: Se encontraron efectos estadísticamente significativos entre las variables del modelo verificado, donde la empatía predice la agresión en el contexto hostil, pero no en el vulnerable y seguro. A su vez, la empatía predice el perdón en los contextos vulnerables y seguros, y la agresión predice el perdón en el modelo hostil, pero no es significativo su efecto en el contexto vulnerable y seguro. Además, la empatía tiene un papel clave en la comprensión del perdón, dado que se asocia a conductas agresivas en los contextos de hostilidad, mientras que un modelo de perdón debería ser diferencial en estos contextos. Conclusiones: Los hallazgos de este estudio brindan evidencia empírica que sustenta la importancia de la implementación de estrategias para mejorar las habilidades relacionadas con la empatía en niños y adolescentes, desde la perspectiva de la educación para la paz y el perdón. Además, se demostró que los aspectos como el clima familiar, las vulnerabilidades de los contextos de riesgo y la misma cultura, pueden determinar el desarrollo de habilidades socioemocionales que favorecen el perdón, empatía y otras capacidades interpersonales.

Introduction: The aim of this study was to identify the variables that best predict measures of aggression, empathy, and forgiveness, as well as the main differences in vulnerable, hostile and safe contexts, in a sample of children and adolescents belonging to a vulnerable population. Method: A cross-sectional quantitative study was conducted with a non-probabilistic incidental sample of 85 participants. Psychometric measures of empathy, aggression, and forgiveness were used. The participants were invited to a victim assistance foundation for an interview and test application. Results: Statistically significant effects were found among the variables in the verified model, where empathy predicts aggression in the hostile context, but not in the vulnerable and safe context. In turn, empathy predicts forgiveness in the vulnerable and safe contexts, and aggression predicts forgiveness in the hostile model, but its effect in the vulnerable and safe context is not significant. Furthermore, empathy plays a key role in understanding forgiveness, given that it is associated with aggressive behaviors in the hostile contexts, whereas a forgiveness model should be differential in these contexts. Conclusions: The findings of this study provide empirical evidence that supports the importance of implementing strategies to improve empathy-related skills in children and adolescents, from the perspective of peace education and forgiveness. In addition, it was shown that aspects such as family climate, vulnerabilities of risk contexts and culture itself, can determine the development of socioemotional skills that favor forgiveness, empathy, and other interpersonal skills.

Hypersensitivity Reactions to Taxanes: A Comprehensive and Systematic Review of the Efficacy and Safety of Desensitization.

Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first line therapy. Drug desensitization induces transient immunological tolerance and has allowed the reintroduction of taxanes in highly allergic patients. Increase the knowledge of hypersensitivity reactions (HSR) during the administration of taxanes. A systematic review regarding the safety and efficacy of rapid drug desensitization (RDD) for taxanes HSR. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in PROSPERO(CRD42021242324) and a comprehensive search was conducted in Medline, Embase, Web of Science and Scopus databases. 25 studies encompassing 10 countries were identified and 976 patients with initial HSR to paclitaxel (n = 707) and docetaxel (n = 284), that underwent a total of 2,396 desensitizations. The most common symptoms were cutaneous (74.6%) with paclitaxel and respiratory (72.6%) with docetaxel. Severe initial hypersensitivity reactions including anaphylaxis occurred in 39.6% and 13% of paclitaxel and docetaxel cases respectively and during the first (87.4%) or second exposure (81.5%). Patients tolerated well RDD and breakthrough reactions (BTR) occurred in 32.2% of paclitaxel-treated patients and in 20.6% of docetaxel treated patients. Premedications included corticosteroids, antihistamines and leukotriene receptor antagonists. The most commonly used protocol was the BWH 3 bags 12 steps, all protocols showed a success rate between 95-100%, with no reported deaths. RDD is a safe and effective procedure in patients with HSR to taxanes and protocols should be standardized for wide range implementation.

Cognitive Frailty as a Predictor of Mortality in Older Adults: A Longitudinal Study in Peru.

Objective: To evaluate the role of cognitive frailty and its components as risk factors of mortality in older adults of the Centro Médico Naval (CEMENA) in Callao, Peru during 2010-2015. Methods: We performed a secondary analysis of data from a prospective cohort that included older adults (60 years and older) treated at the CEMENA Geriatrics service between 2010-2015. Frailty was defined as the presence of three or more criteria of the modified Fried Phenotype. Cognitive impairment was assessed using the Peruvian version of the Mini Mental State Examination (MMSE), considering a score <21 as cognitive impairment. Cognitive frailty was defined as the coexistence of both. In addition, we included sociodemographic characteristics, medical and personal history, as well as the functional evaluation of each participant. Results: We included 1,390 older adults (mean follow-up: 2.2 years), with a mean age of 78.5 ± 8.6 years and 59.6% (n = 828) were male. Cognitive frailty was identified in 11.3% (n = 157) and 9.9% (n = 138) died during follow-up. We found that cognitive frailty in older adults (aHR = 3.57; 95%CI: 2.33-5.49), as well as its components, such as sedentary behavior and cognitive impairment (aHR = 7.05; 95%CI: 4.46-11.13), weakness and cognitive impairment (aHR = 6.99; 95%CI: 4.41-11.06), and exhaustion and cognitive impairment (aHR = 4.51; 95%CI: 3.11-6.54) were associated with a higher risk of mortality. Conclusion: Cognitive frailty and its components were associated with a higher risk of mortality in older adults. It is necessary to develop longitudinal studies with a longer follow-up and that allow evaluating the effect of interventions in this vulnerable group of patients to limit adverse health outcomes, including increased mortality.

Multifocal contact lens vision simulated with a clinical binocular simulator.

PURPOSE: The purpose of this study is to compare the binocular visual perception of participants wearing multifocal contact lenses and these same lens designs viewed through a temporal multiplexing visual simulator. METHODS: Visual performance and perceived visual quality at various distances were obtained in 37 participants wearing soft M-CLs and through the SimVis Gekko programmed with the same lenses. In a pilot study (n = 10) visual performance was measured in terms of LogMAR visual acuity (VA) at far (4 m), intermediate (64 cm) and near (40 cm) distances and through-focus VA (TFVA) curves with the simulated M-CLs. In the follow-up study (n = 27), LogMAR VA at far, intermediate and near distances were measured both with the actual and simulated M-CLs. Perceived visual quality was measured in both studies using the Multifocal Acceptance Score (MAS-2EV), and a Participants Reported Outcomes Vision questionnaire. Differences between the metrics obtained with simulated and actual lenses were obtained. RESULTS: Both actual and simulated M-CLs increased depth-of-focus by a similar amount. Mean LogMAR VA differences with actual and simulated M-CLs ranged between 4 and 6 letters (0.08 ± 0.01, 0.12 ± 0.01 and 0.10 ± 0.01, for far, intermediate and near distances, respectively). MAS-2EV average score differences with actual and simulated M-CLs ranged between -1.00 and + 4.25. Average MAS-2EV scores were not correlated significantly with VA. However, MAS-2EV (average and individual scores) were highly correlated to visual quality questionnaire responses (p < 0.005). CONCLUSIONS: A simultaneous vision simulator accurately represented vision with M-CLs both VA at various distances and perceived visual quality, as measured in a clinical setting. The MAS-2EV metric accurately captured participant reported outcomes of standard vision questionnaires. The combination of SimVis Gekko and MAS-2EV has the potential to largely reduce chair time in M-CLs fitting.

Genome and transcriptome mechanisms driving cephalopod evolution.

Cephalopods are known for their large nervous systems, complex behaviors and morphological innovations. To investigate the genomic underpinnings of these features, we assembled the chromosomes of the Boston market squid, Doryteuthis (Loligo) pealeii, and the California two-spot octopus, Octopus bimaculoides, and compared them with those of the Hawaiian bobtail squid, Euprymna scolopes. The genomes of the soft-bodied (coleoid) cephalopods are highly rearranged relative to other extant molluscs, indicating an intense, early burst of genome restructuring. The coleoid genomes feature multi-megabase, tandem arrays of genes associated with brain development and cephalopod-specific innovations. We find that a known coleoid hallmark, extensive A-to-I mRNA editing, displays two fundamentally distinct patterns: one exclusive to the nervous system and concentrated in genic sequences, the other widespread and directed toward repetitive elements. We conclude that coleoid novelty is mediated in part by substantial genome reorganization, gene family expansion, and tissue-dependent mRNA editing.

A cell-free approach with a supporting biomaterial in the form of dispersed microspheres induces hyaline cartilage formation in a rabbit knee model.

The objective of this study was to test a regenerative medicine strategy for the regeneration of articular cartilage. This approach combines microfracture of the subchondral bone with the implant at the site of the cartilage defect of a supporting biomaterial in the form of microspheres aimed at creating an adequate biomechanical environment for the differentiation of the mesenchymal stem cells that migrate from the bone marrow. The possible inflammatory response to these biomaterials was previously studied by means of the culture of RAW264.7 macrophages. The microspheres were implanted in a 3 mm-diameter defect in the trochlea of the femoral condyle of New Zealand rabbits, covering them with a poly(l-lactic acid) (PLLA) membrane manufactured by electrospinning. Experimental groups included a group where exclusively PLLA microspheres were implanted, another group where a mixture of 50/50 microspheres of PLLA (hydrophobic and rigid) and others of chitosan (a hydrogel) were used, and a third group used as a control where no material was used and only the membrane was covering the defect. The histological characteristics of the regenerated tissue have been evaluated 3 months after the operation. We found that during the regeneration process the microspheres, and the membrane covering them, are displaced by the neoformed tissue in the regeneration space toward the subchondral bone region, leaving room for the formation of a tissue with the characteristics of hyaline cartilage.

Targeted treatment approaches in refractory germ cell tumors.

Germ cell tumors (GCTs) are the most common type of solid tumor amongst patients between 15 and 35 years of age. They are also one of the types of tumor with the highest cure rate, due to their high sensitivity to cisplatin based chemotherapy. Nonetheless, around 15-20% of metastatic patients will not have curative options after a relapse on the first and second line. This proves that new therapeutic options for these refractory GCTs patients need to be developed. This article offers a bibliographic review of all studies using targeted treatment or immunotherapy for refractory GCTs patients.

A High-Demanding Strategy to Ensure the Highest Quality Standards of Oral Liquid Individualized Medicines for Pediatric Use.

Individualized medicines for pediatrics are a useful alternative if there is no correct dosage marketed for this segment (easy to swallow, adequate volume and content, correct composition for pediatrics, good organoleptic properties, etc.). Its validation process must ensure quality testing: its content uniformity, physical (homogeneity after shaking), chemical, and microbiological stability. Some of these attributes are checked by the recommendations of European Pharmacopoeia (Ph. Eur.), International Conference of Harmonization (ICH), and National Formularies but others are not. The aim of this study is to develop a general high-demanding strategy to ensure the final quality of liquid dosage forms testing and developing standard operating processes (SOPs) for the elaboration of individualized oral liquid medicines for pediatric use. Furosemide was used as an example of the validation of an individualized liquid solution for pediatric use. Three SOPs were selected according to their composition and the recommendations of liquid dosage forms for pediatric use. Quality attributes according to National Formularies, Ph. Eur., and ICH were tested: pH, organoleptic properties, uniformity of mass of delivered dose from multidose containers, and chemical stability. In this study, a general high-demanding strategy was elaborated to validate oral liquid dosage forms, including validation of the analytical method used to test their quality. A second part focuses on the elaboration of liquid formulations for pediatrics with the highest standards of quality taking into account CQAs that were not contemplated by official compendial such as content uniformity and physical stability.

ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis.

Developing and mature chondrocytes constantly interact with and remodel the surrounding extracellular matrix (ECM). Recent research indicates that integrin-ECM interaction is differentially regulated during cartilage formation (chondrogenesis). Integrin signaling is also a key source of the catabolic reactions responsible for joint destruction in both rheumatoid arthritis and osteoarthritis. However, we do not understand how chondrocytes dynamically regulate integrin signaling in such an ECM-rich environment. Here, we found that developing chondrocytes express integrin-ß-like 1 (Itgbl1) at specific stages, inhibiting integrin signaling and promoting chondrogenesis. Unlike cytosolic integrin inhibitors, ITGBL1 is secreted and physically interacts with integrins to down-regulate activity. We observed that Itgbl1 expression was strongly reduced in the damaged articular cartilage of patients with osteoarthritis (OA). Ectopic expression of Itgbl1 protected joint cartilage against OA development in the destabilization of the medial meniscus-induced OA mouse model. Our results reveal ITGBL1 signaling as an underlying mechanism of protection against destructive cartilage disorders and suggest the potential therapeutic utility of targeting ITGBL1 to modulate integrin signaling in human disease.

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates.

During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal component analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes directly from its transcriptome. In parallel, we use nonnegative matrix factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g., Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research.

Transanal endoscopic microsurgery for the treatment of uncommon rectal lesions. / Microcirugía endoscópica transanal en el tratamiento de lesiones rectales atípicas.

INTRODUCTION: Transanal endoscopic microsurgery (TEM) was developed as a less aggressive alternative treatment for rectal lesions (mainly adenomas and adenocarcinomas). However, its use for other rectal lesions has become more frequent, trying to reduce the morbidity associated with more invasive techniques. The aim of this study is to describe our experience in the use of TEM in other rectal lesions. METHODS: Retrospective and descriptive study including patients operated with TEM (from June 2008 to December 2016) for the treatment of rectal lesions different from adenomas or adenocarcinomas. RESULTS: Among the 138 patients treated by TEM in our department, 10 patients were operated on for rectal lesions other than adenomas or adenocarcinomas. Rectal lesions were 3neuroendocrine tumours, a neuroendocrine tumour metastasis, a rectal stenosis, a cloacogenic polyp, an endometrioma, a retrorrectal tumour, a presacral abscess and a lesion in the rectovaginal septum. Mean operative time was 72min and postoperative stay was 4.2 days. Only one patient needed a reoperation, due to rectal bleeding. CONCLUSIONS: TEM could be a useful tool for the treatment of rectal lesions different from adenomas or adenocarcinomas, potentially decreasing the morbidity associated with more aggressive surgical techniques.

Microcirugía endoscópica transanal en el tratamiento de lesiones rectales atípicas / Transanal endoscopic microsurgery for the treatment of uncommon rectal lesions

Introducción: La microcirugía endoscópica transanal (TEM) se diseña como una alternativa menos agresiva en el tratamiento de lesiones rectales (principalmente adenomas y adenocarcinomas). Sin embargo, su uso se ha ampliado a otras lesiones rectales para intentar disminuir la morbilidad añadida a técnicas más invasivas. El objetivo de este estudio es mostrar nuestra experiencia en el uso de la TEM en el tratamiento de otras lesiones rectales, diferentes de adenomas y adenocarcinomas. Métodos: Estudio retrospectivo descriptivo en el que se incluyen pacientes intervenidos mediante TEM para el tratamiento de lesiones rectales (diferentes a adenomas o adenocarcinomas) desde junio de 2008 hasta diciembre de 2016. Resultados: Entre los 138 pacientes operados mediante TEM en nuestro servicio, 10 fueron tratados por lesiones diferentes a adenomas o adenocarcinomas. Las lesiones rectales fueron 3tumores neuroendocrinos primarios, una metástasis de tumor neuroendocrino, una estenosis rectal, un pólipo cloacogénico, un endometrioma, un tumor retrorrectal, un absceso presacro y una lesión sin filiar en tabique rectovaginal. El tiempo operatorio medio fue de 72 min y la estancia postoperatoria de 4,2 días. Solo un paciente necesitó reintervención por rectorragia. Conclusiones: La aplicación del TEM para el tratamiento de lesiones rectales diferentes a adenomas o adenocarcinomas puede ser una herramienta útil que potencialmente ayude a disminuir la morbilidad asociada a otros tipos de técnicas quirúrgicas más invasivas (AU)

Introduction: Transanal endoscopic microsurgery (TEM) was developed as a less aggressive alternative treatment for rectal lesions (mainly adenomas and adenocarcinomas). However, its use for other rectal lesions has become more frequent, trying to reduce the morbidity associated with more invasive techniques. The aim of this study is to describe our experience in the use of TEM in other rectal lesions. Methods: Retrospective and descriptive study including patients operated with TEM (from June 2008 to December 2016) for the treatment of rectal lesions different from adenomas or adenocarcinomas. Results: Among the 138 patients treated by TEM in our department, 10 patients were operated on for rectal lesions other than adenomas or adenocarcinomas. Rectal lesions were 3neuroendocrine tumours, a neuroendocrine tumour metastasis, a rectal stenosis, a cloacogenic polyp, an endometrioma, a retrorrectal tumour, a presacral abscess and a lesion in the rectovaginal septum. Mean operative time was 72min and postoperative stay was 4.2 days. Only one patient needed a reoperation, due to rectal bleeding. Conclusions: TEM could be a useful tool for the treatment of rectal lesions different from adenomas or adenocarcinomas, potentially decreasing the morbidity associated with more aggressive surgical techniques (AU)

Evolution of substrate specificity in a retained enzyme driven by gene loss.

The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.

Cell-fate determination by ubiquitin-dependent regulation of translation.

Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation requires changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell-fate determination is less well understood. Here we identify the ubiquitin ligase CUL3 in complex with its vertebrate-specific substrate adaptor KBTBD8 (CUL3(KBTBD8)) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. Ubiquitylation drives formation of a TCOF1-NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favour of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell-fate determination.

[Perioperative risk factors associated with allogeneic blood transfusion in patients with hip fracture surgery]. / Factores de riesgo asociados a hemotransfusión alogénica en pacientes con cirugía de cadera.

BACKGROUND: The aim of this article is to identify risk factors associated with allogeneic blood transfusion (ABT) in patients undergoing hip surgery during 2008-2009, at a General Hospital, in Yucatán, Mexico. METHODS: Data of patients who received at least one package of allogeneic blood either before, during, or after hip surgery, (cases, n = 118), was compared against that of patients having the same type of surgery, but not transfused with an ABT (controls, n =138). Logistic regression analysis was carried on in estimating associations. Odd Ratios (OR) and 95 % confidence intervals (95 % CI), were applied when appropriate. RESULTS: Bleeding grater than or equal to 400 ml during surgery (vs < 400 ml, OR 5.68, 95% CI 2.5-12.9, p = 0.007), and having pre surgical hemoglobin (Hb) concentration < 11 g/dL (vs = 11 g/dL, OR 2.86, 95% CI 1.5-5.6; p = 0.001) were both, associated with ABT. Duration of surgery, the femoral segment involved, the surgical procedure and the postsurgical Hb, were all excluded. CONCLUSION: Bleeding grater than or equal to 400 ml during surgery and having pre surgical Hb concentration < 11 g/dL were both, associated with increased risk of receiving an ABT.

Introducción: el objetivo es identificar los factores de riesgo asociados a la hemotransfusión alogénica en pacientes con cirugía de cadera realizada en un hospital general citadino, durante 2008 y 2009. Métodos: fueron considerados como casos 118 pacientes que recibieron sangre alogénica en el pre, el trans o en el postquirúrgico inmediato, y como controles 138 pacientes que tuvieron el mismo tipo de cirugía, pero no fueron hemotransfundidos. La relación entre variables se investigó utilizando un modelo de regresión logística del que se obtuvieron la razón de momios (RM) y los intervalos de confianza (IC) de 95 %. Resultados: se identificaron como factores de riesgo: el sangrado transquirúrgico mayor o igual a 400 ml (frente a < 400 ml, RM 5.68, IC 95 % 2.5 a 12.9, p = 0.007) y la concentración prequirúrgica de hemoglobina < 11 g/dL (frente a = 11 g/dL, RM 2.86, IC 95 % 1.5 a 5.6; p = 0.001); pero no la duración de la cirugía, el segmento femoral intervenido, la técnica quirúrgica ni la Hb postquirúrgica. Conclusiones: el sangrado transquirúrgico mayor o igual a 400 ml y la Hb prequirúrgica < 11 g/dL incrementaron el riesgo de hemotransfusión alogénica.

A thioredoxin fold protein Sh3bgr regulates Enah and is necessary for proper sarcomere formation.

The sh3bgr (SH3 domain binding glutamate-rich) gene encodes a small protein containing a thioredoxin-like fold, SH3 binding domain, and glutamate-rich domain. Originally, it was suggested that increased expression of Sh3bgr may cause the cardiac phenotypes in Down's syndrome. However, it was recently reported that the overexpression of Sh3bgr did not cause any disease phenotypes in mice. In this study, we have discovered that Sh3bgr is critical for sarcomere formation in striated muscle tissues and also for heart development. Sh3bgr is strongly expressed in the developing somites and heart in Xenopus. Morpholino mediated-knockdown of sh3bgr caused severe malformation of heart tissue and disrupted segmentation of the somites. Further analysis revealed that Sh3bgr specifically localized to the Z-line in mature sarcomeres and that knockdown of Sh3bgr completely disrupted sarcomere formation in the somites. Moreover, overexpression of Sh3bgr resulted in abnormally discontinues thick firmaments in the somitic sarcomeres. We suggest that Sh3bgr does its function at least partly by regulating localization of Enah for the sarcomere formation. In addition, we provide the data supporting Sh3bgr is also necessary for proper heart development in part by affecting the Enah protein level.

Inclusiones glandulares benignas en ganglios centinelas de carcinoma de mama como causa de falsos positivos. Descripción de un caso y revisión de la literatura / Benign glandular inclusions in the sentinel nodes of breast cancer as a cause of false-positive diagnosis. A case report and literature review

Las inclusiones glandulares benignas de mama son entidades poco frecuentes y su presencia en el estudio intraoperatorio del ganglio centinela en la cirugía del cáncer de mama, puede dar lugar a diagnósticos erróneos que conllevan linfadenectomías innecesarias con su morbilidad asociada. Presentamos el caso clínico de una paciente con cáncer de mama, en cuya intervención se remitió un ganglio centinela que originó un diagnóstico falso positivo de metástasis y que ilustra la necesidad de conocer este proceso (AU)

Benign glandular inclusions are rare events. Their presence in the intraoperative evaluation of the sentinel lymph node in breast carcinoma surgery can result in diagnostic error and lead to an unnecessary axillary lymph node dissection with an increased risk of associated morbidity. We report the case of a woman with breast carcinoma. During surgery, evaluation of the sentinel node led to a false-positive diagnosis of metastasis. We discuss the diagnostic problem illustrated by this case, as well as the importance of avoiding overtreatment (AU)