Dermatoscopia del carcinoma basocelular: revisión actualizada

La dermatoscopia es una técnica no invasiva que ha demostrado mejorar la precisión diagnóstica en el carcinoma basocelular (CBC). Desde la descripción inicial llevada a cabo por Menzies et al., basada fundamentalmente en hallazgos asociados a la presencia de pigmento, se ha generado una importante cantidad de bibliografía útil en la práctica clínica diaria. De una forma práctica, podemos clasificar las estructuras dermatoscópicas asociadas al diagnóstico de CBC en estructuras pigmentadas, vasculares y no pigmentadas/no vasculares. Una de las aplicaciones más recientes de la dermatoscopia en el CBC trata de pronosticar el subtipo histológico mediante el examen dermatoscópico y permite fundamentalmente diferenciar entre el CBC superficial y no superficial. Sin embargo, la dermatoscopia también nos permite sospechar variantes agresivas con mayor riesgo de recurrencia. La exploración dermatoscópica exhaustiva en el seguimiento de pacientes con daño actínico o historia de múltiples CBC posibilita la detección de lesiones muy incipientes, con repercusiones terapéuticas y pronósticas importantes. Dermoscopy is a noninvasive technique that has been demonstrated to improve diagnostic accuracy in basal cell carcinoma (BCC). The first dermoscopic model for the diagnosis of BCC, based mainly on the identification of pigmented structures, was described by Menzies et al., and since then dermoscopy has generated an abundance of literature useful to routine clinical practice. From a practical perspective, dermoscopic structures associated with BCC can be classified as pigmented, vascular, or nonpigmented/nonvascular. One of the most recent applications of dermoscopy in BCC is as an aid to predicting histologic subtype and essentially differentiating between superficial and nonsuperficial BCC. It can also, however, help raise suspicion of more aggressive variants with a higher risk of recurrence. A thorough dermoscopic examination during follow-up of patients with actinic damage or a history of multiple BCCs can facilitate the detection of very incipient lesions and significantly impact treatment and prognosis

Identification of β2 microglobulin, the product of B2M gene, as a Host Factor for Vaccinia Virus Infection by Genome-Wide CRISPR genetic screens

Genome-wide genetic screens are powerful tools to identify genes that act as host factors of viruses. We have applied this technique to analyze the infection of HeLa cells by Vaccinia virus, in an attempt to find genes necessary for infection. Infection of cell populations harboring single gene inactivations resulted in no surviving cells, suggesting that no single gene knock-out was able to provide complete resistance to Vaccinia virus and thus allow cells to survive infection. In the absence of an absolute infection blockage, we explored if some gene inactivations could provide partial protection leading to a reduced probability of infection. Multiple experiments using modified screening procedures involving replication restricted viruses led to the identification of multiple genes whose inactivation potentially increase resistance to infection and therefore cell survival. As expected, significant gene hits were related to proteins known to act in virus entry, such as ITGB1 and AXL as well as genes belonging to their downstream related pathways. Additionally, we consistently found β2-microglobulin, encoded by the B2M gene, among the screening top hits, a novel finding that was further explored. Inactivation of B2M resulted in 54% and 91% reduced VV infection efficiency in HeLa and HAP1 cell lines respectively. In the absence of B2M, while virus binding to the cells was unaffected, virus internalization and early gene expression were significantly diminished. These results point to β2-microglobulin as a relevant factor in the Vaccinia virus entry process.This work was supported by grants ERTA2014-00006, RTA2017-0066 and PID2021-128466OR-I00 funded by Ministerio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033 as part of the Plan Estatal de Investigación Científica, Desarrollo e Innovación (https://www.ciencia.gob.es) to R.B. A.M. was recipient of a predoctoral contract from Subprograma Estatal de Formación, Programa Estatal de Promoción del Talento y su Empleabilidad en I+D+I, Spain from the Ministerio de Ciencia e Innovación, grant number PRE2018-085415. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Video-assisted mitral surgery through a micro-access: A safe and reliable reality in the current era

Background and aim of the study: Minimally invasive mitral valve surgery was introduced into clinical practice during the mid 1990s. The clinical benefits of the technique, namely a reduction of surgical trauma, increased patient comfort and shorter hospital stay, are achieved by using a video-assisted, mini-thoracotomy approach rather than a standard median sternotomy. Herein is described the authors' experience with video-assisted mitral surgery through a micro-access. Methods: Between September 2003 and September 2006, 100 patients (mean age 65.7 years; range: 16-84 years; 29 aged >75 years) underwent video-assisted port-access mitral valve surgery through a 4- to 6-cm anterior mini-thoracotomy. Mitral valve repair was carried out in 36 patients (36%) and mitral valve replacement (MVR) in 64 (64%) for degenerative (n = 54), rheumatic (n = 44), functional (n = 1) or infective disease (n = 1). Redo procedures were performed in 14 patients. Results: Peripheral extra-thoracic cardiopulmonary bypass (CPB) was used in all cases, and Endoclamp occlusion of the ascending aorta in 94%. The median intensive care unit and hospital stays were 20.0 +/- 30.8 h and 7.0 +/- 5.9 days, respectively. Hospital mortality was 4% (n = 4). No patient required conversion to sternotomy. Five patients (5%) underwent minimally invasive surgical revision for bleeding, and one patient (1%) had an early reoperation for MVR during the immediate postoperative course due to failure of a mitral valve repair. There were no perioperative myocardial infarctions, permanent strokes, major vascular complications, or peripheral ischemic events. Among the patients, 63% had no complications at all during the postoperative course, and no wound infections were observed. Conclusion: Video-assisted mitral surgery through a micro-access may be performed safely, at low risk of morbidity and mortality, and with results and quality standards similar to those reported for a sternotomy approach. Of note, older patients may be successfully treated using this technique

First Insight into the Genome Sequences of Two Linezolid-Resistant Nocardia farcinica Strains Isolated from Patients with Cystic Fibrosis

The draft genome sequences of two Nocardia farcinica strains isolated from two patients with cystic fibrosis (CF), resistant to trimethoprim/sulfamethoxazole and linezolid, are reported here. The estimated genome sizes were 5.8 Mb with a 70.63% G+C content. Transposases from Tn916 were detected, but not 23S rRNA mutation (G2576T) related to linezolid resistance.We are grateful to G. Carrasco, P. Jimenez, and J. A. Saéz-Nieto for their help in different stages of genome sequencing, and Adrian Burton for editing and language assistance (Physical Evidence Scientific Translations; http://www.physicalevidence.es). This work was funded by project MPY1278/15 of the Instituto de Salud Carlos III.S

Senescence in premalignant tumours

Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development1,2, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer

Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer

<p>Abstract</p> <p>Background</p> <p>Transcriptional profiling of prostate cancer (PC) has unveiled new markers of neoplasia and allowed insights into mechanisms underlying this disease. Genomewide analyses have also identified new chromosomal abnormalities associated with PC. The combination of both classes of data for the same sample cohort might provide better criteria for identifying relevant factors involved in neoplasia. Here we describe transcriptional signatures identifying distinct normal and tumoral prostate tissue compartments, and the inference and demonstration of a new, highly recurrent copy number gain on chromosome 17q25.3.</p> <p>Methods</p> <p>We have applied transcriptional profiling to tumoral and non-tumoral prostate samples with relatively homogeneous epithelial representations as well as pure stromal tissue from peripheral prostate and cultured cell lines, followed by quantitative RT-PCR validations and immunohistochemical analysis. In addition, we have performed <it>in silico </it>colocalization analysis of co-regulated genes and validation by fluorescent in situ hybridization (FISH).</p> <p>Results</p> <p>The transcriptomic analysis has allowed us to identify signatures corresponding to non-tumoral luminal and tumoral epithelium, basal epithelial cells, and prostate stromal tissue. In addition, <it>in silico </it>analysis of co-regulated expression of physically linked genes has allowed us to predict the occurrence of a copy number gain at chromosomal region 17q25.3. This computational inference was validated by fluorescent <it>in situ </it>hybridization, which showed gains in this region in over 65% of primary and metastatic tumoral samples.</p> <p>Conclusion</p> <p>Our approach permits to directly link gene copy number variations with transcript co-regulation in association with neoplastic states. Therefore, transcriptomic studies of carefully selected samples can unveil new diagnostic markers and transcriptional signatures highly specific of PC, and lead to the discovery of novel genomic abnormalities that may provide additional insights into the causes and mechanisms of prostate cancer.</p

Genomic Analysis of West Nile Virus Lineage 1 Detected in Mosquitoes during the 2020–2021 Outbreaks in Andalusia, Spain

Emerging infectious diseases are one of the most important global health challenges because of their impact on human and animal health. The vector-borne West Nile virus (WNV) is transmitted between birds by mosquitos, but it can also infect humans and horses causing disease. The local circulation of WNV in Spain has been known for decades, and since 2010, there have been regular outbreaks in horses, although only six cases were reported in humans until 2019. In 2020, Spain experienced a major outbreak with 77 human cases, which was followed by 6 additional cases in 2021, most of them in the Andalusian region (southern Spain). This study aimed to characterize the genomes of the WNV circulating in wild-trapped mosquitoes during 2020 and 2021 in Andalusia. We sequenced the WNV consensus genome from two mosquito pools and carried out the phylogenetic analyses. We also compared the obtained genomes with those sequenced from human samples obtained during the outbreak and the genomes obtained previously in Spain from birds (2007 and 2017), mosquitoes (2008) and horses (2010) to better understand the eco-epidemiology of WNV in Spain. As expected, the WNV genomes recovered from mosquito pools in 2020 were closely related to those recovered from humans of the same outbreak. In addition, the strain of WNV circulating in 2021 was highly related to the WNV strain that caused the 2020 outbreak, suggesting that WNV is overwintering in the area. Consequently, future outbreaks of the same strain may occur in in the future.This research was funded by the Research State Agency projects PGC2018-095704-B-I00 and PID2020-118921RJ-I00Instituto de Salud Carlos III Project PI19CIII_00014European Commission—NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global+)

Involvement of the TPR2 subdomain movement in the activities of ϕ29 DNA polymerase

The polymerization domain of ϕ29 DNA polymerase acquires a toroidal shape by means of an arch-like structure formed by the specific insertion TPR2 (Terminal Protein Region 2) and the thumb subdomain. TPR2 is connected to the fingers and palm subdomains through flexible regions, suggesting that it can undergo conformational changes. To examine whether such changes take place, we have constructed a ϕ29 DNA polymerase mutant able to form a disulfide bond between the apexes of TPR2 and thumb to limit the mobility of TPR2. Biochemical analysis of the mutant led us to conclude that TPR2 moves away from the thumb to allow the DNA polymerase to replicate circular ssDNA. Despite the fact that no TPR2 motion is needed to allow the polymerase to use the terminal protein (TP) as primer during the initiation of ϕ29 TP–DNA replication, the disulfide bond prevents the DNA polymerase from entering the elongation phase, suggesting that TPR2 movements are necessary to allow the TP priming domain to move out from the polymerase during transition from initiation to elongation. Furthermore, the TPR2-thumb bond does not affect the equilibrium between the polymerization and exonuclease activities, leading us to propose a primer-terminus transference model between both active sites