Study of the Influence of Boundary Conditions on Corneal Deformation Based on the Finite Element Method of a Corneal Biomechanics Model.

Implementing in silico corneal biomechanical models for surgery applications can be boosted by developing patient-specific finite element models adapted to clinical requirements and optimized to reduce computational times. This research proposes a novel corneal multizone-based finite element model with octants and circumferential zones of clinical interest for material definition. The proposed model was applied to four patient-specific physiological geometries of keratoconus-affected corneas. Free-stress geometries were calculated by two iterative methods, the displacements and prestress methods, and the influence of two boundary conditions: embedded and pivoting. The results showed that the displacements, stress and strain fields differed for the stress-free geometry but were similar and strongly depended on the boundary conditions for the estimated physiological geometry when considering both iterative methods. The comparison between the embedded and pivoting boundary conditions showed bigger differences in the posterior limbus zone, which remained closer in the central zone. The computational calculation times for the stress-free geometries were evaluated. The results revealed that the computational time was prolonged with disease severity, and the displacements method was faster in all the analyzed cases. Computational times can be reduced with multicore parallel calculation, which offers the possibility of applying patient-specific finite element models in clinical applications.

Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a serious public health problem due to its high incidence and metastatic potential. It may progress from actinic keratosis (AK), a precancerous lesion, or the in situ carcinoma, Bowen's disease (BD). During this progression, malignant keratinocytes activate dermal fibroblasts into tumor promoting cancer-associated fibroblasts (CAFs), whose origin and emergence remain largely unknown. Here, we generate and analyze >115,000 single-cell transcriptomes from healthy skin, BD and cSCC of male donors. Our results reveal immunoregulatory and matrix-remodeling CAF subtypes that may derive from pro-inflammatory and mesenchymal fibroblasts, respectively. These CAF subtypes are largely absent in AK and interact with different cell types to establish a pro-tumorigenic microenvironment. These findings are cSCC-specific and could not be recapitulated in basal cell carcinomas. Our study provides important insights into the potential origin and functionalities of dermal CAFs that will be highly beneficial for the specific targeting of the cSCC microenvironment.

Reinvestigating the clinical relevance of the m6A writer METTL3 in urothelial carcinoma of the bladder.

METTL3 is the major writer of N6-Methyladenosine (m6A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the role of METTL3 in UCB. METTL3 knockout reduced the oncogenic phenotype and m6A levels of UCB cell lines. However, complete depletion of METTL3/m6A was not achieved due to selection of cells expressing alternative METTL3 isoforms. Systematic vulnerability and inhibitor response analyses suggested that uroepithelial cells depend on METTL3 for viability. Furthermore, expression and survival analyses of clinical data revealed a complex role for METTL3 in UCB, with decreased m6A mRNA levels in UCB tumors. Our results suggest that METTL3 expression may be a suitable diagnostic UCB biomarker, as the enzyme promotes UCB formation. However, the suitability of the enzyme as a therapeutic target should be evaluated carefully.

Riesgo biológico en el personal de enfermería de la Unidad de Cuidados Intensivos del Hospital Alberto Sabogal Sologuren / Biological risk in the nursing staff of the Intensive Care Unit of the Alberto Sabogal Sologuren Hospital

Según la Organización Internacional del Trabajo (OIT) se estima que 2,34 millones de personas mueren cada año a causa de accidentes y enfermedades relacionados con el trabajo. Entre las áreas hospitalarias, la unidad de cuidados intensivos (UCI) es considerada como la más tensa, traumática y agresiva, que ha pesar de la pesada rutina de trabajo, los peligros a la que el personal de enfermería (enfermeros, técnicos y asistentes) está continuamente expuesto. No sólo el medio ambiente es insalubre, sino que dada la ocurrencia frecuente de situaciones de emergencia y la alta concentración de pacientes en estado crítico que se someten a cambios en su estado de salud. El personal de enfermería la UCI tienen un mayor riesgo relacionado con los peligros biológicos, ya que están expuestos a organismos infecciosos durante los procedimientos invasivos y no invasivos. En ese sentido, este trabajo busca indagar sobre percepción acerca de la exposición a los riesgos biológicos para las enfermeras que laboran en la UCI en el Hospital Alberto Sabogal Sologuren, Perú. Los resultados llevados con las trabajadoras de la salud de Unidad de Cuidados Intensivos en el Hospital Alberto Sabogal indicaron que en general, las enfermeras de ese centro asistencial hacen uso de buenas prácticas de riesgo, siendo el de mayor prevalecencia (71%) el relacionado con los principios de bioseguridad, y siendo el de menor cuidado (37%), el referente al lavado de las manos antes y después de tener contacto con los pacientes. Es preocupante, que un porcentaje bajo de enfermeras, entre un 5 y 22% respondieron algunas veces a las prácticas de riesgo, siendo un factor importante de contaminación o peligro con su salud(AU)

According to the International Labor Organization (ILO), an estimated 2.34 million people die each year from work-related accidents and diseases. Among the hospital areas, the intensive care unit (ICU) is considered the most tense, traumatic and aggressive, which has despite the heavy work routine, the dangers to which the nursing staff (nurses, technicians and assistants) They are continually exposed. Not only is the environment unhealthy, but given the frequent occurrence of emergency situations and the high concentration of critically ill patients undergoing changes in their health status. ICU nursing staff are at increased risk related to biohazards, as they are exposed to infectious organisms during invasive and non-invasive procedures. In this sense, this work seeks to investigate the perception of exposure to biological risks for nurses who work in the ICU at the Alberto Sabogal Sologuren Hospital, Peru. The results carried out with the health workers of the Intensive Care Unit at the Alberto Sabogal Hospital indicated that in general, the nurses of this care center make use of good risk practices, with the highest prevalence (71%) being related to the principles of biosafety, and being the least careful (37%), the reference to washing hands before and after having contact with patients. It is worrisome that a low percentage of nurses, between 5 and 22% sometimes responded to risk practices, being an important factor of contamination or danger to their health(AU)

Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses.

Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell multi-omics, transcriptomics, and methylomics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~3,800 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell-type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the phenotypic traits of the subclasses and the study of additional unstratified KC entities uncovered distinct clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis.

The high mobility group protein HMG20A cooperates with the histone reader PHF14 to modulate TGFß and Hippo pathways.

High mobility group (HMG) proteins are chromatin regulators with essential functions in development, cell differentiation and cell proliferation. The protein HMG20A is predicted by the AlphaFold2 software to contain three distinct structural elements, which we have functionally characterized: i) an amino-terminal, intrinsically disordered domain with transactivation activity; ii) an HMG box with higher binding affinity for double-stranded, four-way-junction DNA than for linear DNA; and iii) a long coiled-coil domain. Our proteomic study followed by a deletion analysis and structural modeling demonstrates that HMG20A forms a complex with the histone reader PHF14, via the establishment of a two-stranded alpha-helical coiled-coil structure. siRNA-mediated knockdown of either PHF14 or HMG20A in MDA-MB-231 cells causes similar defects in cell migration, invasion and homotypic cell-cell adhesion ability, but neither affects proliferation. Transcriptomic analyses demonstrate that PHF14 and HMG20A share a large subset of targets. We show that the PHF14-HMG20A complex modulates the Hippo pathway through a direct interaction with the TEAD1 transcription factor. PHF14 or HMG20A deficiency increases epithelial markers, including E-cadherin and the epithelial master regulator TP63 and impaired normal TGFß-trigged epithelial-to-mesenchymal transition. Taken together, these data indicate that PHF14 and HMG20A cooperate in regulating several pathways involved in epithelial-mesenchymal plasticity.

Descripción anatómica de los segmentos óseos que componen el esqueleto apendicular torácico de la especie Puma concolor / Anatomical description of the bony segments that make up the thoracic appendicular skeleton of the species Puma concolor

RESUMEN: El Puma concolor es uno de los carnívoros más grandes presentes en Chile, aunque su tamaño varía según la zona geográfica en la que se encuentra. Cada vez es más común encontrarlos fuera de su hábitat y más en nuestro entorno. Se conocen sus aspectos ecológicos, reproductivos y nutricionales, pero muy poco de su anatomía, lo que genera un desafío en el área morfológica veterinaria que necesita fortalecimiento. El presente estudio consistió en una descripción anatómica del esqueleto apendicular de tres ejemplares adultos de Puma concolor (3 machos) en el laboratorio de anatomía veterinaria de la Universidad San Sebastián, sede de la Patagonia Puerto Montt, lo que permitió un estudio detallado de la conformación del esqueleto de cada estructura presente en el esqueleto apendicular torácico de estos ejemplares. Esto nos permitió lograr resultados de interés morfológico y profundizar en la anatomía de esta especie.

SUMMARY: The Puma concolor is one of the largest carnivores present in Chile, although its size varies according to the geographical area in which it is found. It is increasingly common to find them outside their habitat and more in our environment. Its ecological, reproductive and nutritional aspects are known, but very little is known about its anatomy, which creates a challenge in the veterinary morphological area that needs strengthening. The present study consisted of an anatomical description of the appendicular skeleton of three adult specimens of Puma concolor (3 males) in the veterinary anatomy laboratory of the Universidad San Sebastián, headquarters of Patagonia Puerto Montt, which allowed a detailed study of the conformation of the skeleton of each structure present in the thoracic appendicular skeleton of these specimens. This allowed us to achieve results of morphological interest and delve into the anatomy of this species.

Base editing repairs an SGCA mutation in human primary muscle stem cells.

Skeletal muscle can regenerate from muscle stem cells and their myogenic precursor cell progeny, myoblasts. However, precise gene editing in human muscle stem cells for autologous cell replacement therapies of untreatable genetic muscle diseases has not yet been reported. Loss-of-function mutations in SGCA, encoding α-sarcoglycan, cause limb-girdle muscular dystrophy 2D/R3, an early-onset, severe, and rapidly progressive form of muscular dystrophy affecting both male and female patients. Patients suffer from muscle degeneration and atrophy affecting the limbs, respiratory muscles, and heart. We isolated human muscle stem cells from 2 donors, with the common SGCA c.157G>A mutation affecting the last coding nucleotide of exon 2. We found that c.157G>A is an exonic splicing mutation that induces skipping of 2 coregulated exons. Using adenine base editing, we corrected the mutation in the cells from both donors with > 90% efficiency, thereby rescuing the splicing defect and α-sarcoglycan expression. Base-edited patient cells regenerated muscle and contributed to the Pax7+ satellite cell compartment in vivo in mouse xenografts. Here, we provide the first evidence to our knowledge that autologous gene-repaired human muscle stem cells can be harnessed for cell replacement therapies of muscular dystrophies.

Aggressive PDACs Show Hypomethylation of Repetitive Elements and the Execution of an Intrinsic IFN Program Linked to a Ductal Cell of Origin.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral transcripts and double-stranded RNA sensors, which lead to a cell-intrinsic activation of an interferon signature (IFNsign). This results in a protumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived Kras G12D/Trp53 -/- mouse PDACs show higher expression of IFNsign compared with acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN signaling. SIGNIFICANCE: The mutational landscapes of PDAC alone cannot explain the observed interpatient heterogeneity. We identified two PDAC subtypes characterized by differential DNA methylation, preserving traits from normal ductal/acinar cells associated with IFN signaling. Our work suggests that epigenetic traits and the cell of origin contribute to PDAC heterogeneity.This article is highlighted in the In This Issue feature, p. 521.

Eficacia comparada de tres fármacos acaricidas utilizados en el tratamiento de otocariasis por Otodectes cynotis en gatos domésticos de Puerto Montt, región de Los Lagos, Chile / Compared Efficacy of Three Anti-Mite Drugs Used to Treat Otoacariasis Caused by Otodectes cynotis in Domestic Cats in Puerto Montt, Los Lagos Region, Chile

Resumen Otodectes cynotis es uno de los ácaros responsables de causar dermatosis parasitaria en el pabellón auricular en animales de compañía, lo que les produce prurito intenso e incluso complicaciones óticas por falta del tratamiento adecuado. Su prevalencia en felinos domésticos puede llegar al 37 y el 85 % de los casos de otitis externa. Son variados los productos que pueden utilizarse para el tratamiento de este ácaro, aunque algunos no declaran en su etiquetado su uso en determinadas especies. Por otra parte, los datos disponibles sobre la eficacia comparada de los diversos fármacos utilizados son escasos. Los fármacos más utilizados son selamectina, fipronil, tiabendazol, ivermectina, entre otros. El objetivo de este estudio fue comparar la eficacia acaricida de tres fármacos utilizados en el tratamiento de otoacariasis por Otodectes cynotis, empleando ivermectina 1 %, fipronil 10 % y selamectina 6 % en gatos domésticos de Puerto Montt. Se revisaron 117 gatos domésticos, de los cuales 60 presentaron otocariasis positiva a Otodectes cynotis. Estos 60 pacientes fueron distribuidos en cuatro grupos de 15 individuos cada uno: grupo A, tratados con ivermectina al 1 %, vía ótica; grupo B, tratados con fipronil al 10 %, vía ótica; grupo C, tratados con selamectina al 6 %, vía tópica (spot-on), y grupo D o grupo control, al que se le aplicó un placebo de glicerina, vía ótica. Se realizaron controles a los 7, 14, 21 y 28 días posteriores a la administración del fármaco. El análisis estadístico demostró leves diferencias significativas entre los grupos A, B y C, con el grupo D. Estos resultados sugieren que los tratamientos para la otocariasis provocada por Otodectes cynotis, con ivermectina, fipronil y selamectina en las concentraciones, dosis y vías de administración anteriormente mencionadas, presentan la misma eficacia, pero con diferencias en el valor por tratamiento.

Abstract Otodectes cynotis is one the mite causing parasitic dermatosis in the ear pinna of pets. It produces an intense itching and even some ear complications in the absence of an adequate treatment. The prevalence in domestic cats may reach to 37% and accounts for 85 % of the external otitis cases. Products for treating this mite problem are assorted, even though some of them do not state in the labels whether they are intended to any specific species. On the other hand, there is scarce data available on the compared efficacy of the different drugs used for treatment. Mostly used drugs include selamectin, fipronil, thiabendazole, ivermectin, among others. This study aims to compare the anti-mite efficacy of three drugs in the treatment of otoacariasis caused by Otodectes cynotis, administering ivermectin 1%, fipronil 10%, and selamectin 6% to domestic cats in Puerto Montt. One hundred and seventeen domestic cats were examined and 60 were positive to otoacariasis caused by Otodectes cynotis. These 60 patients were divided into four groups with 15 subjects each: group A, ivermectin 1%, ear drops; group B, fipronil 10%, ear drops; group C, selamectin 6%, topical (spot-on); and group D or control group that received a glycerin placebo as ear drops. Checkups were carried out on days 7, 14, 21 and 28 after applying the drugs. The statistical analysis showed significant mild differences between A, B and C groups and the D group. These results suggest that the treatments with ivermectin, fipronil and selamectin in the concentrations, dosages and administration routes indicated above to solve the otoacariasis caused by Otodectes cynotis are equally efficacious, but show some differences in the specific value of each treatment.

The first GHEP-ISFG collaborative exercise on forensic applications of massively parallel sequencing.

One of the main goals of the Spanish and Portuguese-Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the field of forensic genetics. The GHEP-ISFG supports several Working Commissions which develop different scientific activities. One of them, the Working Commission on "Massively Parallel Sequencing (MPS): Forensic Applications", organized its first collaborative exercise on forensic applications of MPS technology in 2019. The aim of this exercise was to assess the concordance between the MPS results and those obtained with conventional technologies (capillary electrophoresis and Sanger sequencing), as well as to compare the results obtained within the different MPS platforms and/or the different kits/panels and analysis software packages (commercial and open-access) available on the market. The seven participating laboratories analyzed some samples of the annual GHEP-ISFG proficiency test (EIADN No. 27 (2019)), using Ion Torrent™ or MiSeq FGx® platforms. Six of them sent autosomal STR sequence data, five laboratories performed MPS analysis of individual identification SNPs, four laboratories reported MPS data of Y-chromosomal STRs, and X-chromosomal STRs, three laboratories performed MPS analysis of ancestry informative SNPs and phenotype informative SNPs, two labs performed MPS analysis of the mitochondrial DNA control region, and only one lab produced MPS data of lineage informative SNPs. Autosomal STR sequencing results were highly concordant to the consensus obtained by capillary electrophoresis in the EIADN No. 27 (2019) exercise. Furthermore, in general, a high level of concordance was observed between the results of the participating laboratories, regardless of the platform used. The main discordances were due to errors during the analysis process or from sequence data obtained with low depth of coverage. In this paper we highlight some issues that still arise, such as standardization of the nomenclature for STRs analyzed by sequencing with MPS, the universal uptake of a nomenclature framework by the analysis software, and well established validation and accreditation of the new MPS platforms for use in routine forensic case-work.

Descripción anatómica del cráneo del gato / Anatomic Description of the Cat Skull

Resumen Este artículo tiene como propósito hacer un estudio descriptivo de las estructuras anatómicas del cráneo del gato doméstico (Felis catus). El cráneo, que deriva del griego kranos, "casco" o "yelmo", es una estructura de vital importancia en todo ser vivo vertebrado, debido a que en ella se aloja el encéfalo y los órganos de los sentidos, y es la entrada de órganos que conforman el aparato digestivo y respiratorio. El cráneo está conformado por una variedad de huesos que están fusionados o articulados entre sí y forman el esplacnocráneo y neurocráneo. No es mucha la literatura anatómica que existe en relación con el gato, a diferencia de lo que ocurre en caninos; por esta razón, una descripción en detalle de los segmentos óseos del esplacnocráneo y neurocráneo es un inicio a la profundización anatómica de esta especie.

Abstract This article aims to develop a descriptive study of the skull anatomic structures in home cats (Felis catus). The cranium -from the Greek kranos, "helmet" or "hood"- is a vital structure for every vertebrate living being because it provides the lodge to the encephalon and senses. It also provides the entrance organs to both the digestive and respiratory systems. The cranium is formed by an assortment of bones articulated or joined together thus forming the splanchnocranium and the neurocranium. There is not too much anatomic literature on the cat anatomy, unlike the canines. Therefore, a detailed description of the bone segments in the splanchnocranium and neurocranium is the starting point for an in-depth anatomic study of this species.

Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford progeria syndrome.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid disease characterized by the early onset of age-related phenotypes including arthritis, loss of body fat and hair, and atherosclerosis. Cells from affected individuals express a mutant version of the nuclear envelope protein lamin A (termed progerin) and have previously been shown to exhibit prominent histone modification changes. METHODS: Here, we analyze the possibility that epigenetic deregulation of lamina-associated domains (LADs) is involved in the molecular pathology of HGPS. To do so, we studied chromatin accessibility (Assay for Transposase-accessible Chromatin (ATAC)-see/-seq), DNA methylation profiles (Infinium MethylationEPIC BeadChips), and transcriptomes (RNA-seq) of nine primary HGPS fibroblast cell lines and six additional controls, two parental and four age-matched healthy fibroblast cell lines. RESULTS: Our ATAC-see/-seq data demonstrate that primary dermal fibroblasts from HGPS patients exhibit chromatin accessibility changes that are enriched in LADs. Infinium MethylationEPIC BeadChip profiling further reveals that DNA methylation alterations observed in HGPS fibroblasts are similarly enriched in LADs and different from those occurring during healthy aging and Werner syndrome (WS), another premature aging disease. Moreover, HGPS patients can be stratified into two different subgroups according to their DNA methylation profiles. Finally, we show that the epigenetic deregulation of LADs is associated with HGPS-specific gene expression changes. CONCLUSIONS: Taken together, our results strongly implicate epigenetic deregulation of LADs as an important and previously unrecognized feature of HGPS, which contributes to disease-specific gene expression. Therefore, they not only add a new layer to the study of epigenetic changes in the progeroid syndrome, but also advance our understanding of the disease's pathology at the cellular level.

Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming.

Fibroblasts are an essential cell population for human skin architecture and function. While fibroblast heterogeneity is well established, this phenomenon has not been analyzed systematically yet. We have used single-cell RNA sequencing to analyze the transcriptomes of more than 5,000 fibroblasts from a sun-protected area in healthy human donors. Our results define four main subpopulations that can be spatially localized and show differential secretory, mesenchymal and pro-inflammatory functional annotations. Importantly, we found that this fibroblast 'priming' becomes reduced with age. We also show that aging causes a substantial reduction in the predicted interactions between dermal fibroblasts and other skin cells, including undifferentiated keratinocytes at the dermal-epidermal junction. Our work thus provides evidence for a functional specialization of human dermal fibroblasts and identifies the partial loss of cellular identity as an important age-related change in the human dermis. These findings have important implications for understanding human skin aging and its associated phenotypes.

DNA Methylation in Epidermal Differentiation, Aging, and Cancer.

The formation and maintenance of the epidermis depend on epidermal stem cell differentiation and must be tightly regulated. Epigenetic mechanisms such as DNA methylation allow the precise gene expression cascade needed during cellular differentiation. However, these mechanisms become deregulated during aging and tumorigenesis, where cellular function and identity become compromised. Here we provide a review of this rapidly developing field. We discuss recent discoveries related to epidermal homeostasis, aging, and cancer, including the functional role of DNA methyltransferases, the methylation clock, and the determination of tumor cells-of-origin. Finally, we focus on future advances, greatly influenced by single-cell sequencing technologies.

Evaluación de la sensibilidad de la pared abdominal y ubre en vacas lecheras poscesárea por laparotomía en el flanco izquierdo / Assessment of Abdominal Wall and Udder Sensitivity in Dairy Cows after Cesarean Delivery by Laparotomy in the Left Flank / Avaliação da sensibilidade da parede abdominal e do úbere em vacas leiteiras pós-cesárea por laparotomia no flanco esquerdo

Resumen Este estudio tiene el objetivo de demostrar la pérdida de sensibilidad en la pared abdominal izquierda y primer cuarto craneal, en hembras bovinas productoras de leche sometidas a laparotomía por el flanco izquierdo con histerotomía, mediante pruebas de sensibilidad profunda en la pared abdominal y el pezón. Se incluyeron hembras bovinas sometidas al procedimiento quirúrgico de cesárea, con más de 90 días posintervención. El estudio se realizó en los sectores de la comuna de Ancud, Chiloé. Respecto a los predios, se recopiló información de los productores y médicos veterinarios de la zona para obtener datos vinculados con tipo de cirugía y consecuencias quirúrgicas. Para determinar la sensibilidad en el flanco y en la ubre, se dividieron estas zonas en seis cuadrantes, asignándoles letras (A, B, C, D, E, F); cada una de estas áreas forma parte del recorrido de los nervios espinales torácicos y lumbares evaluados en este estudio. Los resultados mostraron que el 54 % de las hembras sometidas al procedimiento de cesárea presentaron poca o nula sensibilidad en el flanco y en la ubre, condición que se manifiesta mayoritariamente en los cuadrantes C, D, E y F para ambas zonas anatómicas. Al evaluar la presencia de lesiones en la pared abdominal izquierda y en la ubre, las laceraciones fueron las más frecuentes en ambas zonas anatómicas. En el esfínter del pezón también se vio afectado, pues se observó un retado de esta estructura anatómica. Cerca del 50 % de las hembras sometidas a cesárea presentaron mastitis en los cuartos craneales en su mayoría.

Abstract This study aims to demonstrate loss of sensitivity in the left abdominal wall and the first cranial quarter in milk-producing cattle subjected to laparotomy in the left flank with hysterotomy, through deep sensitivity tests in the abdominal wall and the nipple. Dairy cows subjected to surgical cesarean section were included, at more than 90 days post-intervention. The study was carried out in the area of the Ancud colony, Chiloé. Regarding the properties, information was collected on producers and veterinarians from the area to obtain data related to type of surgery and surgical consequences. To determine sensitivity in the flank and the udder, these zones were divided into six quadrants, assigning to each of them a letter (A, B, C, D, E, F). Each of these areas is part of the thoracic and lumbar spinal nerve pathways evaluated in this study. The results showed that 54% of the females submitted to cesarean section had little or no sensitivity in the flank and the udder, a condition present mostly in quadrants C, D, E, and F for both anatomical areas. When assessing the presence of lesions in the left abdominal wall and the udder, lacerations were the most frequent in both anatomical areas. The nipple sphincter was also affected. Nearly 50% of females submitted to cesarean section presented with mastitis mostly in the cranial quarters.

Resumo Este estudo objetiva demostrar a perda de sensibilidade na parede abdominal esquerda e primeiro quarto cranial, em fêmeas bovinas produtoras de leite submetidas a laparotomia pelo flanco esquerdo com histerotomia, através de testes de sensibilidade profunda na parede abdominal e mamilo. Incluíram-se fêmeas bovinas submetidas a procedimento cirúrgico de cesárea, com mais de 90 dias pós-intervenção. O estudo foi realizado nos setores da comuna de Ancud, Chiloé. Respeito aos sítios, coletou-se informação dos produtores e médicos veterinários da área para obter dados relacionados ao tipo de cirurgia e consequências cirúrgicas. Para determinar a sensibilidade no flanco e no úbere, dividiram-se essas zonas em seis quadrantes, atribuindo-lhes letras (A, B, C, D, E, F); cada uma dessas áreas faz parte do trajeto dos nervos espinhais torácicos e lombares avaliados neste estudo. Os resultados mostraram que 54% das fêmeas submetidas ao procedimento de cesárea apresentaram pouca ou nenhuma sensibilidade no flanco e no úbere, condição que se manifesta principalmente nos quadrantes C, D, E e F para ambas as zonas anatómicas. Ao avaliar a presença de lesões na parede abdominal esquerda e no úbere, as lacerações foram as mais frequentes em ambas as zonas anatómicas. No esfíncter do mamilo também foi afetado, pois se observou um desafio dessa estrutura anatómica. Quase 50% das fêmeas submetidas à cesárea apresentaram mastite nos quartos craniais na maioria.

Descripción morfológica y biomecánica de la articulación de la rodilla del canino (Canis lupus familiaris) / Morphological and biomechanical description of the canine knee joint (Canis lupus familiaris) / Descrição morfológica e biomecânica da articulação do joelho canino (Canis lupus familiaris)

Resumen Las articulaciones sinoviales o también conocidas como diartroideas se caracterizan por presentar gran movilidad, estar constituidas por una cápsula articular de protección, la que a su vez internamente permite la formación de una cavidad, donde es posible observar el líquido sinovial, responsable de proveer elementos nutricios; producir la depuración de los desechos celulares; realizar una amortiguación entre las caras articulares y lubricar las superficies articulares. La rodilla es una de las articulaciones sinoviales más grandes del cuerpo y una de las más complejas en su morfología y biomecánica. Su conformación anatómica consta de la unión de estructuras óseas, cartilaginosas, ligamentosas, vasculares y musculares que permiten otorgar una funcionalidad específica en su capacidad extensora, flexora y leve rotación. Por lo que el objetivo del siguiente estudio fue realizar una descripción morfológica de las estructuras anatómicas macroscópicas, que participan en la conformación de la articulación de la rodilla y como ellas pueden permitir una funcionalidad biomecánica particular. Para ello se realizaron disecciones de 10 rodillas de perros machos conservados en el laboratorio de anatomía veterinaria de la Universidad Santo Tomás, sede Puerto Montt. Los resultados indican características detalladas de la morfología de la rodilla del canino y como cada uno de ellos permiten entender y explicar la capacidad biomecánica de esta articulación.

Abstract The synovial joints, or also known as diarthroids, are characterized by their high mobility, constituted by a protective joint capsule, which in turn internally allows the formation of a cavity, where it is possible to observe synovial fluid, responsible for providing Nutritional elements; Purifying cell debris; Make a damping between the articular faces and lubricate the articular surfaces. The knee is one of the largest synovial joints in the body and one of the most complex is its morphology and biomechanics. Its anatomical conformation consists of the union of bony, cartilaginous, ligamentous, vascular and muscular structures that allow to grant a specific functionality in its extensor, flexor and slight rotation capacity. Therefore, the objective of the following study was to perform a morphological description of the macroscopic anatomical structures, which participate in the conformation of the knee joint and how they can allow a particular biomechanical functionality. For this, dissections of 10 knees of male dogs were carried out in the veterinary anatomy laboratory of the Universidad Santo Tomas, Puerto Montt. The results indicate detailed characteristics of the canine knee morphology and how each of them allows to understand and explain the biomechanical capacity of this joint.

Resumo Articulações sinoviais ou também conhecido como diartroideas são caracterizados por uma elevada mobilidade, ser constituído por uma cápsula da articulação de protecção, o que por sua vez permite que internamente a formação de uma cavidade, onde se pode observar o fluido sinovial, responsável pelo fornecimento de elementos nutrientes; produzir a purificação do lixo celular; faça um amortecimento entre as faces das juntas e lubrifique as superfícies das juntas. O joelho é uma das maiores articulações sinoviais do corpo e uma das mais complexas em sua morfologia e biomecânica. conformação anatómica consiste na união de osso, cartilagem, ligamentos, estruturas vasculares e musculares que permitem dar uma funcionalidade específica na sua capacidade extensor, flexor e rotação ligeira. Assim, o objectivo do presente estudo foi realizar uma descrição morfológica das estruturas anatómicas macroscópicas, envolvidos na formação da articulação do joelho em que podem permitir que uma funcionalidade especial biomecânico. Para tanto, foram realizadas dissecações de 10 joelhos de cães machos preservados no laboratório de anatomia veterinária da Universidade Santo Tomás, sede de Puerto Montt. Os resultados indi cam características detalhadas da morfologia do joelho canino e como cada um de les permite entender e explicar a capacidade biomecânica desta articulação.

Cell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis.

Colorectal adenomas are precursor lesions of colorectal cancers and represent clonal amplifications of single cells from colonic crypts. DNA methylation patterns specify cell-type identity during cellular differentiation and, therefore, provide opportunities for the molecular analysis of tumors. We have now analyzed DNA methylation patterns in colorectal adenomas and identified three biologically defined subclasses that describe different intestinal crypt differentiation stages. Importantly, colorectal carcinomas could be classified into the same methylation subtypes, reflecting their shared cell types of origin with adenomas. Further data analysis also revealed significantly reduced overall survival for one of the subtypes. Our results provide a concept for understanding the methylation patterns observed in colorectal cancer and provide opportunities for tumor subclassification and patient stratification.

Transforming growth factor ß1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia.

Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia and found a specific molecular signature of genes commonly deregulated in these disorders. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines, thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level. Further analysis identified transforming growth factor ß1 as the most probable extrinsic trigger factor for this altered gene expression. Following exposure to transforming growth factor ß1, healthy mesenchymal stromal cells developed functional deficits and adopted a phenotype reminiscent of that observed in patient-derived stromal cells. These suppressive effects of transforming growth factor ß1 on stromal cell functionality were abrogated by SD-208, an established inhibitor of transforming growth factor ß receptor signaling. Blockade of transforming growth factor ß signaling by SD-208 also restored the osteogenic differentiation capacity of patient-derived stromal cells, thus confirming the role of transforming growth factor ß1 in the bone marrow microenvironment of patients with myelodysplastic syndromes and acute myeloid leukemia. Our findings establish transforming growth factor ß1 as a relevant trigger causing functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia and identify SD-208 as a candidate to revert these effects.