Tumor de Buschke-Löwenstein en el embarazo adolescente / Buschke-Löwenstein Tumor in Adolescent Pregnancy

Resumen El tumor de Buschke-Löwenstein, también denominado condiloma acuminado gigante, es una entidad rara causada por el virus del papiloma humano (VPH), con una incidencia de 0.01% en la población en general y solo 6 casos reportados en embarazadas. No existe un consenso con respecto al tratamiento; sin embargo, la cirugía es la técnica más descrita. Caso clínico: Paciente primigesta de 14 años, con un embarazo de 21 semanas de gestación, quien ingresó a urgencias por una masa dolorosa en región perineal de 5 meses de evolución. A la exploración física se encontraron en región perineal 2 lesiones exofíticas, coliformes, irregulares, ulceradas de aproximadamente 20 × 10 cm con presencia de secreción amarillenta fétida. Se realizó escisión del tumor con amplios márgenes quirúrgicos y cierre por segunda intención. Por parte de patología se reportó un condiloma acuminado gigante sin lesión en borde quirúrgico. La prueba por PCR detectó el genotipo 53 del virus de papiloma humano. Después de 12 semanas se presentó epitelización completa, sin complicaciones. Conclusión: El tumor de Buschke-Löwenstein es considerado como benigno, no obstante, representa cierto grado de malignidad y tiende a recurrir después del tratamiento, por lo que es importante reforzar las medidas de tamizaje y prevención del Virus del Papiloma Humano.

Abstract Buschke-Löwenstein tumor also called giant condyloma acuminatum is a rare condition due to the human papillomavirus with an incidence of 0.01% and just 6 cases reported in pregnancy. There is no consensus on the treatment, although surgery has been the most reported. Clinical case: A 14 year-old primigravid patient with a 21- week pregnancy who was admitted to the Emergency Department due to a perineal painful tumor which appeared 5 months before. On physical examination two irregular exophytic, cauliflower-like and ulcerated lesions of 20 × 10 cm of size each one with malodorous discharge were found on her perineal region suggestive of giant condyloma acuminatum. We decided to resect the tumor with tumor-free margin control and healing per secundam. The pathology report showed a giant condyloma acuminatum with tumor-free margin. The PCR analysis revealed human papillomavirus genotype 53. Complete epithelialization was noted at 12 weeks with no complications noted. Conclusion: Buschke-Löwenstein tumor is considered as a benign tumor, but it carries a risk of malignant transformation and it can appear after treatment, which makes important to strengthen the prevention and screening of human papillomavirus.

Engineered Gold and Silica Nanoparticle-Incorporated Hydrogel Scaffolds for Human Stem Cell-Derived Cardiac Tissue Engineering.

Electrically conductive biomaterials and nanomaterials have demonstrated great potential in the development of functional and mature cardiac tissues. In particular, gold nanomaterials have emerged as promising candidates due to their biocompatibility and ease of fabrication for cardiac tissue engineering utilizing rat- or stem cell-derived cardiomyocytes (CMs). However, despite significant advancements, it is still not clear whether the enhancement in cardiac tissue function is primarily due to the electroconductivity features of gold nanoparticles or the structural changes of the scaffold resulting from the addition of these nanoparticles. To address this question, we developed nanoengineered hydrogel scaffolds comprising gelatin methacrylate (GelMA) embedded with either electrically conductive gold nanorods (GNRs) or nonconductive silica nanoparticles (SNPs). This enabled us to simultaneously assess the roles of electrically conductive and nonconductive nanomaterials in the functionality and fate of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Our studies revealed that both GNR- and SNP-incorporated hydrogel scaffolds exhibited excellent biocompatibility and similar cardiac cell attachment. Although the expression of sarcomere alpha-actinin did not significantly differ among the conditions, a more organized sarcomere structure was observed within the GNR-embedded hydrogels compared to the nonconductive nanoengineered scaffolds. Furthermore, electrical coupling was notably improved in GNR-embedded scaffolds, as evidenced by the synchronous calcium flux and enhanced calcium transient intensity. While we did not observe a significant difference in the gene expression profile of human cardiac tissues formed on the conductive GNR- and nonconductive SNP-incorporated hydrogels, we noticed marginal improvements in the expression of some calcium and structural genes in the nanomaterial-embedded hydrogel groups as compared to the control condition. Given that the cardiac tissues formed atop the nonconductive SNP-based scaffolds (used as the control for conductivity) also displayed similar levels of gene expression as compared to the conductive hydrogels, it suggests that the electrical conductivity of nanomaterials (i.e., GNRs) may not be the sole factor influencing the function and fate of hiPSC-derived cardiac tissues when cells are cultured atop the scaffolds. Overall, our findings provide additional insights into the role of electrically conductive gold nanoparticles in regulating the functionalities of hiPSC-CMs.

Nanoblades allow high-level genome editing in murine and human organoids.

Genome engineering has become more accessible thanks to the CRISPR-Cas9 gene-editing system. However, using this technology in synthetic organs called "organoids" is still very inefficient. This is due to the delivery methods for the CRISPR-Cas9 machinery, which include electroporation of CRISPR-Cas9 DNA, mRNA, or ribonucleoproteins containing the Cas9-gRNA complex. However, these procedures are quite toxic for the organoids. Here, we describe the use of the "nanoblade (NB)" technology, which outperformed by far gene-editing levels achieved to date for murine- and human tissue-derived organoids. We reached up to 75% of reporter gene knockout in organoids after treatment with NBs. Indeed, high-level NB-mediated knockout for the androgen receptor encoding gene and the cystic fibrosis transmembrane conductance regulator gene was achieved with single gRNA or dual gRNA containing NBs in murine prostate and colon organoids. Likewise, NBs achieved 20%-50% gene editing in human organoids. Most importantly, in contrast to other gene-editing methods, this was obtained without toxicity for the organoids. Only 4 weeks are required to obtain stable gene knockout in organoids and NBs simplify and allow rapid genome editing in organoids with little to no side effects including unwanted insertion/deletions in off-target sites thanks to transient Cas9/RNP expression.

Nanoengineering of gold nanoribbon-embedded isogenic stem cell-derived cardiac organoids.

Cardiac tissue engineering is an emerging field providing tools to treat and study cardiovascular diseases (CVDs). In the past years, the integration of stem cell technologies with micro- and nanoengineering techniques has enabled the creation of novel engineered cardiac tissues (ECTs) with potential applications in disease modeling, drug screening, and regenerative medicine. However, a major unaddressed limitation of stem cell-derived ECTs is their immature state, resembling a neonatal phenotype and genotype. The modulation of the cellular microenvironment within the ECTs has been proposed as an efficient mechanism to promote cellular maturation and improve features such as cellular coupling and synchronization. The integration of biological and nanoscale cues in the ECTs could serve as a tool for the modification and control of the engineered tissue microenvironment. Here we present a proof-of-concept study for the integration of biofunctionalized gold nanoribbons (AuNRs) with hiPSC-derived isogenic cardiac organoids to enhance tissue function and maturation. We first present extensive characterization of the synthesized AuNRs, their PEGylation and cytotoxicity evaluation. We then evaluated the functional contractility and transcriptomic profile of cardiac organoids fabricated with hiPSC-derived cardiomyocytes (mono-culture) as well as with hiPSC-derived cardiomyocytes and cardiac fibroblasts (co-culture). We demonstrated that PEGylated AuNRs are biocompatible and do not induce cell death in hiPSC-derived cardiac cells and organoids. We also found an improved transcriptomic profile of the co-cultured organoids indicating maturation of the hiPSC-derived cardiomyocytes in the presence of cardiac fibroblasts. Overall, we present for the first time the integration of AuNRs into cardiac organoids, showing promising results for improved tissue function.

Development and Characterization of Isogenic Cardiac Organoids from Human-Induced Pluripotent Stem Cells Under Supplement Starvation Regimen.

The prevalence of cardiovascular risk factors is expected to increase the occurrence of cardiovascular diseases (CVDs) worldwide. Cardiac organoids are promising candidates for bridging the gap between in vitro experimentation and translational applications in drug development and cardiac repair due to their attractive features. Here we present the fabrication and characterization of isogenic scaffold-free cardiac organoids derived from human induced pluripotent stem cells (hiPSCs) formed under a supplement-deprivation regimen that allows for metabolic synchronization and maturation of hiPSC-derived cardiac cells. We propose the formation of coculture cardiac organoids that include hiPSC-derived cardiomyocytes and hiPSC-derived cardiac fibroblasts (hiPSC-CMs and hiPSC-CFs, respectively). The cardiac organoids were characterized through extensive morphological assessment, evaluation of cellular ultrastructures, and analysis of transcriptomic and electrophysiological profiles. The morphology and transcriptomic profile of the organoids were improved by coculture of hiPSC-CMs with hiPSC-CFs. Specifically, upregulation of Ca2+ handling-related genes, such as RYR2 and SERCA, and structure-related genes, such as TNNT2 and MYH6, was observed. Additionally, the electrophysiological characterization of the organoids under supplement deprivation shows a trend for reduced conduction velocity for coculture organoids. These studies help us gain a better understanding of the role of other isogenic cells such as hiPSC-CFs in the formation of mature cardiac organoids, along with the introduction of exogenous chemical cues, such as supplement starvation.

Tumor de Buschke-Löwenstein en el embarazo. Reporte de un caso / Buschke-Löwenstein tumor in pregnancy: A case report

Resumen ANTECEDENTES: El tumor de Buschke-Löwenstein, también denominado condiloma acuminado gigante, es una alteración excepcional causada por el virus del papiloma humano, con una incidencia de 0.01% en la población general y solo 6 casos reportados en pacientes embarazadas. No existe un consenso respecto al tratamiento; sin embargo, la cirugía es la técnica más descrita. CASO CLÍNICO: Paciente primigesta de 14 años, con embarazo de 21 semanas, que ingresó al servicio de Urgencias por una masa dolorosa en la región perineal, de cinco meses de evolución. A la exploración física se encontraron, en la región perineal, dos lesiones exofíticas, coliformes, irregulares, ulceradas, de aproximadamente 20 x 10 cm, acompañadas de secreción amarillenta fétida. El tumor se extirpó y se dejaron márgenes quirúrgicos amplios y cierre por segunda intención. El estudio de patología reportó un condiloma acuminado gigante, sin lesión en el borde quirúrgico. La prueba de PCR detectó el genotipo 53 del virus del papiloma humano. Después de 12 semanas hubo epitelización completa, sin complicaciones adicionales para la paciente. CONCLUSIÓN: El tumor de Buschke-Löwenstein es benigno pero representa cierto grado de malignidad y tiende a recurrir después del tratamiento, por lo que es importante reforzar las medidas de tamizaje y prevención del virus del papiloma humano.

Abstract BACKGROUND: Buschke-Löwenstein tumor, also called giant condyloma acuminatum, is a rare condition due to the human papillomavirus with an incidence of 0.01% and just 6 cases reported in pregnancy. There is no consensus on the treatment, although surgery has been the most reported. CLINICAL CASE: A 14-year-old primigravid patient with a 21 weeks pregnancy who was admitted to the Emergency Department due to a perineal painful tumor which appeared 5 months before. On physical examination two irregular exophytic, cauliflower-like and ulcerated lesions of 20x10 cm of size each one with malodorous discharge were found on her perineal region suggestive of giant condyloma acuminatum. We decided to respect the tumor with tumor-free margin control and healing per second time. The pathology reports a giant condyloma acuminatum with tumor-free margin. The PCR analysis revealed human papillomavirus genotype 53. Complete epithelialization was noted at 12 weeks without complications noted. CONCLUSION: Buschke-Löwenstein tumor is considered as a benign tumor, but it carries a risk of malignant transformation, and it can appear after treatment which makes important to strengthen the prevention and screening of human papillomavirus.

Passive and Flexible Wireless Electronics Fabricated on Parylene/PDMS Substrate for Stimulation of Human Stem Cell-Derived Cardiomyocytes.

In this paper, we report the development of a wireless, passive, biocompatible, and flexible system for stimulation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMS). Fabricated on a transparent parylene/PDMS substrate, the proposed stimulator enables real-time excitation and characterization of hiPSC-CMs cultured on-board. The device comprises a rectenna operating at 2.35 GHz which receives radio frequency (RF) energy from an external transmitter and converts it into DC voltage to deliver monophasic stimulation. The operation of the stimulator was primarily verified by delivering monophasic voltage pulses through gold electrodes to hiPSC-CMs cultured on the Matrigel-coated substrates. Stimulated hiPSC-CMs beat in accordance with the monophasic pulses when delivered at 0.5, 1, and 2 Hz pulsing frequency, while no significant cell death was observed. The wireless stimulator could generate monophasic pulses with an amplitude of 8 V at a distance of 15 mm. These results demonstrated the proposed wireless stimulator's efficacy for providing electrical stimulation to engineered cardiac tissues. The proposed stimulator will have a wide application in tissue engineering where a fully wireless stimulation of electroconductive cells is needed. The device also has potential to be employed as a cardiac stimulator by delivering external stimulation and regulating the contractions of cardiac tissue.

Dietary intakes among people with vs without food addiction: A systematic review and meta-analysis.

BACKGROUND & AIMS: Individuals with food addiction (FA) may experience addictive behaviours like those observed in other substances of abuse, which may affect their dietary intake habits. In fact, previous studies have reported associations between FA and dietary patterns, but this evidence has not been quantitatively summarised before. Therefore, this study aimed to explore differences in dietary intakes among adults with vs without food addiction. METHODS: A systematic-review and meta-analysis was conducted. Interventional or observational studies evaluating dietary intakes associated with FA that used the Yale Food Addiction Scale (YFAS) were explored. PubMed, WoS and SCOPUS databases were searched up to September 2021, and selected articles were confirmed manually. Potentially eligible studies were checked independently by two researchers. YFAS and dietary habits were obtained from the studies selected by the search protocol. Standardized mean differences were retrieved and random effects meta-analyses were used for those studies reporting quantitative data. RESULTS: From 162 potentially appropriate studies, 16 studies were finally included, all of which used cross-sectional designs. FA was generally related to higher intakes of total fat, proteins, sugar, and processed/energy-dense foods. The meta-analysis revealed that this association was only statistically significant in overweighted/obese individuals (P < 0.001 in all cases), while in those studies that included the general population (all weight categories), this association was not evident (p = 0.18). CONCLUSIONS: Being addicted to food was not associated with a higher energy intake in the general population. However, among those with overweight or obesity, FA was associated with higher energy and nutrient consumption. This provides evidence on the influence of addictive behaviours on dietary intake patterns of people with excess body weight and reinforces the concept of food addiction and its influence in the development of obesity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020212866.

Severe congenital diarrhea secondary to tufting enteropathy. case report

ABSTRACT Introduction: Tufting enteropathy is a rare cause of congenital diarrhea in neonates. It is characterized by the abnormal distribution of epithelial adhesion molecules, which causes enterocytes to shed into the lumen, forming the characteristic tufts. Case summary: A 15-day-old female neonate was taken by her parents to the emergency department of a tertiary care hospital due to diarrheal stools she had been experiencing since birth. The patient presented with dehydration, abnormal weight loss, metabolic acidosis, and acute kidney failure. She received treatment with alizapride, loperamide, zinc sulfate, and probiotics, but after 75 days of treatment she was still symptomatic. An upper tract endoscopy and colonoscopy were performed, finding flattening of the villi and lymphoid cells in the lamina propria. However, the symptoms persisted, and she died at the age of ten months. A post-mortem exome sequencing reported tufting enteropathy. Conclusions. When congenital diarrhea is present, tufting enteropathy should be considered. An early molecular study would allow to evaluate the possibility of performing an intestinal transplant or modifying the treatment to meet the patient's palliative care needs.

RESUMEN Introducción. La enteropatía en penacho es una causa rara de diarrea congénita en neonatos; esta se caracteriza por una alteración de la adhesión epitelial que ocasiona desprendimiento de enterocitos hacia el lumen y, en consecuencia, forma los característicos penachos. Se describe el caso de una paciente con esta patología. Presentación del caso. Neonata de 15 días de vida, quien fue llevada por sus padres al servicio de urgencias de un hospital de tercer nivel debido a que desde su nacimiento tuvo deposiciones diarreicas y a causa de esto presentó deshidratación, pérdida de peso, acidosis metabólica e insuficiencia renal aguda. La paciente recibió manejo con alizaprida, loperamida, sulfato de zinc y probióticos, pero a los 75 días de tratamiento continuaba sintomática. Se le practicó una endoscopia de vías digestivas y una colonoscopia que mostraron aplanamiento de las vellosidades e infiltrado de células linfoides en la lámina propia. Los síntomas continuaron y la menor falleció a los 10 meses de nacida. El resultado del exoma post mortem reportó enteropatía en penacho. Conclusiones. Ante la presencia de diarrea congénita, se debe sospechar de una enteropatía en penacho y considerar el estudio molecular temprano, pues este permite evaluar la posibilidad de realizar un trasplante intestinal o modificar el tratamiento según las necesidades de cuidado paliativo del paciente.

Immune regulation by fungal strain diversity in inflammatory bowel disease.

The fungal microbiota (mycobiota) is an integral part of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation1-6. Although aberrant changes in the mycobiota have been linked to several diseases, including inflammatory bowel disease3-9, it is currently unknown whether fungal species captured by deep sequencing represent living organisms and whether specific fungi have functional consequences for disease development in affected individuals. Here we developed a translational platform for the functional analysis of the mycobiome at the fungal-strain- and patient-specific level. Combining high-resolution mycobiota sequencing, fungal culturomics and genomics, a CRISPR-Cas9-based fungal strain editing system, in vitro functional immunoreactivity assays and in vivo models, this platform enables the examination of host-fungal crosstalk in the human gut. We discovered a rich genetic diversity of opportunistic Candida albicans strains that dominate the colonic mucosa of patients with inflammatory bowel disease. Among these human-gut-derived isolates, strains with high immune-cell-damaging capacity (HD strains) reflect the disease features of individual patients with ulcerative colitis and aggravated intestinal inflammation in vivo through IL-1ß-dependent mechanisms. Niche-specific inflammatory immunity and interleukin-17A-producing T helper cell (TH17 cell) antifungal responses by HD strains in the gut were dependent on the C. albicans-secreted peptide toxin candidalysin during the transition from a benign commensal to a pathobiont state. These findings reveal the strain-specific nature of host-fungal interactions in the human gut and highlight new diagnostic and therapeutic targets for diseases of inflammatory origin.

Electroconductive biomaterials for cardiac tissue engineering.

Myocardial infarction (MI) is still the leading cause of mortality worldwide. The success of cell-based therapies and tissue engineering strategies for treatment of injured myocardium have been notably hindered due to the limitations associated with the selection of a proper cell source, lack of engraftment of engineered tissues and biomaterials with the host myocardium, limited vascularity, as well as immaturity of the injected cells. The first-generation approaches in cardiac tissue engineering (cTE) have mainly relied on the use of desired cells (e.g., stem cells) along with non-conductive natural or synthetic biomaterials for in vitro construction and maturation of functional cardiac tissues, followed by testing the efficacy of the engineered tissues in vivo. However, to better recapitulate the native characteristics and conductivity of the cardiac muscle, recent approaches have utilized electroconductive biomaterials or nanomaterial components within engineered cardiac tissues. This review article will cover the recent advancements in the use of electrically conductive biomaterials in cTE. The specific emphasis will be placed on the use of different types of nanomaterials such as gold nanoparticles (GNPs), silicon-derived nanomaterials, carbon-based nanomaterials (CBNs), as well as electroconductive polymers (ECPs) for engineering of functional and electrically conductive cardiac tissues. We will also cover the recent progress in the use of engineered electroconductive tissues for in vivo cardiac regeneration applications. We will discuss the opportunities and challenges of each approach and provide our perspectives on potential avenues for enhanced cTE. STATEMENT OF SIGNIFICANCE: Myocardial infarction (MI) is still the primary cause of death worldwide. Over the past decade, electroconductive biomaterials have increasingly been applied in the field of cardiac tissue engineering. This review article provides the readers with the leading advances in the in vitro applications of electroconductive biomaterials for cTE along with an in-depth discussion of injectable/transplantable electroconductive biomaterials and their delivery methods for in vivo MI treatment. The article also discusses the knowledge gaps in the field and offers possible novel avenues for improved cardiac tissue engineering.

Disruption of HIV-1 co-receptors CCR5 and CXCR4 in primary human T cells and hematopoietic stem and progenitor cells using base editing.

Disruption of CCR5 or CXCR4, the main human immunodeficiency virus type 1 (HIV-1) co-receptors, has been shown to protect primary human CD4+ T cells from HIV-1 infection. Base editing can install targeted point mutations in cellular genomes, and can thus efficiently inactivate genes by introducing stop codons or eliminating start codons without double-stranded DNA break formation. Here, we applied base editors for individual and simultaneous disruption of both co-receptors in primary human CD4+ T cells. Using cytosine base editors we observed premature stop codon introduction in up to 89% of sequenced CCR5 or CXCR4 alleles. Using adenine base editors we eliminated the start codon in CCR5 in up to 95% of primary human CD4+ T cell and up to 88% of CD34+ hematopoietic stem and progenitor cell target alleles. Genome-wide specificity analysis revealed low numbers of off-target mutations that were introduced by base editing, located predominantly in intergenic or intronic regions. We show that our editing strategies prevent transduction with CCR5-tropic and CXCR4-tropic viral vectors in up to 79% and 88% of human CD4+ T cells, respectively. The engineered T cells maintained functionality and overall our results demonstrate the effectiveness of base-editing strategies for efficient and specific ablation of HIV co-receptors in clinically relevant cell types.

Baboon Envelope Pseudotyped "Nanoblades" Carrying Cas9/gRNA Complexes Allow Efficient Genome Editing in Human T, B, and CD34+ Cells and Knock-in of AAV6-Encoded Donor DNA in CD34+ Cells.

Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into human blood cells can be challenging. Here, we have utilized "nanoblades," a new technology that delivers a genomic cleaving agent into cells. These are modified murine leukemia virus (MLV) or HIV-derived virus-like particle (VLP), in which the viral structural protein Gag has been fused to Cas9. These VLPs are thus loaded with Cas9 protein complexed with the guide RNAs. Highly efficient gene editing was obtained in cell lines, IPS and primary mouse and human cells. Here, we showed that nanoblades were remarkably efficient for entry into human T, B, and hematopoietic stem and progenitor cells (HSPCs) thanks to their surface co-pseudotyping with baboon retroviral and VSV-G envelope glycoproteins. A brief incubation of human T and B cells with nanoblades incorporating two gRNAs resulted in 40 and 15% edited deletion in the Wiskott-Aldrich syndrome (WAS) gene locus, respectively. CD34+ cells (HSPCs) treated with the same nanoblades allowed 30-40% exon 1 drop-out in the WAS gene locus. Importantly, no toxicity was detected upon nanoblade-mediated gene editing of these blood cells. Finally, we also treated HSPCs with nanoblades in combination with a donor-encoding rAAV6 vector resulting in up to 40% of stable expression cassette knock-in into the WAS gene locus. Summarizing, this new technology is simple to implement, shows high flexibility for different targets including primary immune cells of human and murine origin, is relatively inexpensive and therefore gives important prospects for basic and clinical translation in the area of gene therapy.

Recent Progress in Genome Editing for Gene Therapy Applications: The French Perspective.

Recent advances in genome editing tools, especially novel developments in the clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases (CRISPR/Cas9)-derived editing machinery, have revolutionized not only basic science but, importantly, also the gene therapy field. Their flexibility and ability to introduce precise modifications in the genome to disrupt or correct genes or insert expression cassettes in safe harbors in the genome underline their potential applications as a medicine of the future to cure many genetic diseases. In this review, we give an overview of the recent progress made by French researchers in the field of therapeutic genome editing, while putting their work in the general context of advances made in the field. We focus on recent hematopoietic stem cell gene editing strategies for blood diseases affecting the red blood cells or blood coagulation as well as lysosomal storage diseases. We report on a genome editing-based therapy for muscular dystrophy and the potency of T cell gene editing to increase anticancer activity of chimeric antigen receptor T cells to combat cancer. We will also discuss technical obstacles and side effects such as unwanted editing activity that need to be surmounted on the way toward a clinical implementation of genome editing. We propose here improvements developed today, including by French researchers to overcome the editing-related genotoxicity and improve editing precision by the use of novel recombinant nuclease-based systems such as nickases, base editors, and prime editors. Finally, a solution is proposed to resolve the cellular toxicity induced by the systems employed for gene editing machinery delivery.

Lentiviral Vector Pseudotypes: Precious Tools to Improve Gene Modification of Hematopoietic Cells for Research and Gene Therapy.

Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived from the human immune deficiency virus allowing efficient gene transfer in mammalian cells. They represent one of the safest and most efficient treatments for monogenic diseases affecting the hematopoietic system. LVs are modified with different viral envelopes (pseudotyping) to alter and improve their tropism for different primary cell types. The vesicular stomatitis virus glycoprotein (VSV-G) is commonly used for pseudotyping as it enhances gene transfer into multiple hematopoietic cell types. However, VSV-G pseudotyped LVs are not able to confer efficient transduction in quiescent blood cells, such as hematopoietic stem cells (HSC), B and T cells. To solve this problem, VSV-G can be exchanged for other heterologous viral envelopes glycoproteins, such as those from the Measles virus, Baboon endogenous retrovirus, Cocal virus, Nipah virus or Sendai virus. Here, we provide an overview of how these LV pseudotypes improved transduction efficiency of HSC, B, T and natural killer (NK) cells, underlined by multiple in vitro and in vivo studies demonstrating how pseudotyped LVs deliver therapeutic genes or gene editing tools to treat different genetic diseases and efficiently generate CAR T cells for cancer treatment.

[Pulmonary mycosis in patients with diabetes mellitus. Clinical characteristics and risk factors]. / Micosis pulmonares en pacientes con diabetes mellitus. Características clínicas y factores de riesgo.

BACKGROUND: Diabetes mellitus is a public health problem in Mexico, and the trend of the disease is increasing. From 2000 to 2017, 7.32 million new cases were diagnosed, with pulmonary mycoses being one of the most serious complications. AIMS: To describe the frequency and the clinical characteristics of patients diagnosed with pulmonary mycoses, and to identify the risk factors associated with this entity. METHODS: Case-control study, paired by gender (1:1-3) and age (± 5 years), that analyzed patients with pulmonary mycosis (mucormycosis, histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, cryptococcosis, paracoccidioidomycosis) and studied the risk factors present in each patient. RESULTS: From the 162 patients studied, 56 suffered pulmonary mycosis and 106 were controls. The median of the age was 51 and 50 years for the cases and for the controls, respectively. Multiple logistic regression analysis showed that patients with diabetes mellitus had an odds ratio of 8,3 (p < 0.001), and patients with a history of tuberculosis had an odds ratio of 8,8 (p < 0.001). CONCLUSIONS: Our results show that 52% of the patients with pulmonary mycoses had a history of diabetes mellitus. Diabetes mellitus is a relevant risk factor for pulmonary mycoses, which are usually diagnosed in advanced stages and have a high mortality.

Three-dimensional scaffold-free microtissues engineered for cardiac repair.

Cardiovascular diseases, including myocardial infarction (MI), persist as the leading cause of mortality and morbidity worldwide. The limited regenerative capacity of the myocardium presents significant challenges specifically for the treatment of MI and, subsequently, heart failure (HF). Traditional therapeutic approaches mainly rely on limiting the induced damage or the stress on the remaining viable myocardium through pharmacological regulation of remodeling mechanisms, rather than replacement or regeneration of the injured tissue. The emerging alternative regenerative medicine-based approaches have focused on restoring the damaged myocardial tissue with newly engineered functional and bioinspired tissue units. Cardiac regenerative medicine approaches can be broadly categorized into three groups: cell-based therapies, scaffold-based cardiac tissue engineering, and scaffold-free cardiac tissue engineering. Despite significant advancements, however, the clinical translation of these approaches has been critically hindered by two key obstacles for successful structural and functional replacement of the damaged myocardium, namely: poor engraftment of engineered tissue into the damaged cardiac muscle and weak electromechanical coupling of transplanted cells with the native tissue. To that end, the integration of micro- and nanoscale technologies along with recent advancements in stem cell technologies have opened new avenues for engineering of structurally mature and highly functional scaffold-based (SB-CMTs) and scaffold-free cardiac microtissues (SF-CMTs) with enhanced cellular organization and electromechanical coupling for the treatment of MI and HF. In this review article, we will present the state-of-the-art approaches and recent advancements in the engineering of SF-CMTs for myocardial repair.

Micosis pulmonares en pacientes con diabetes mellitus. Características clínicas y factores de riesgo / Pulmonary mycosis in patients with diabetes mellitus. Clinical characteristics and risk factors

ANTECEDENTES: La diabetes mellitus es un problema de salud pública en México. La tendencia de la enfermedad es creciente y del año 2000 al 2017 se confirmaron 7,32 millones de casos nuevos. Las micosis pulmonares son una de las posibles complicaciones de mayor gravedad. OBJETIVOS: Describir la frecuencia y las características clínicas de pacientes con diagnóstico de micosis pulmonar e identificar los factores de riesgo implicados en esta entidad. MÉTODOS: Estudio de casos-controles pareado 1:1-3 para género y edad (± 5 años). Se incluyeron pacientes con micosis pulmonares (mucormicosis, histoplasmosis, coccidioidomicosis, blastomicosis, aspergilosis, criptococosis, paracoccidioidomicosis) y se estudiaron los factores de riesgo presentes en cada uno de ellos. RESULTADOS: De los 162 pacientes, 56 presentaban una micosis pulmonar y 106 fueron controles; la mediana de la edad fue 51 y 50 años para los casos y controles, respectivamente. En el modelo de regresión logística múltiple los pacientes con diabetes mellitus presentaron una razón de momios (RM) de 8,3, p < 0,001, y el antecedente de tuberculosis una RM de 8,8, p <0,001. CONCLUSIONES: Los resultados muestran que el 52% de los casos con micosis pulmonares tuvieron la diabetes mellitus como factor de riesgo, siendo relevante para estas micosis, que se diagnostican en etapas avanzadas y tienen una alta mortalidad

BACKGROUND: Diabetes mellitus is a public health problem in Mexico, and the trend of the disease is increasing. From 2000 to 2017, 7.32 million new cases were diagnosed, with pulmonary mycoses being one of the most serious complications. AIMS: To describe the frequency and the clinical characteristics of patients diagnosed with pulmonary mycoses, and to identify the risk factors associated with this entity. METHODS: Case-control study, paired by gender (1:1-3) and age (± 5 years), that analyzed patients with pulmonary mycosis (mucormycosis, histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, cryptococcosis, paracoccidioidomycosis) and studied the risk factors present in each patient. RESULTS: From the 162 patients studied, 56 suffered pulmonary mycosis and 106 were controls. The median of the age was 51 and 50 years for the cases and for the controls, respectively. Multiple logistic regression analysis showed that patients with diabetes mellitus had an odds ratio of 8,3 (p < 0.001), and patients with a history of tuberculosis had an odds ratio of 8,8 (p < 0.001). CONCLUSIONS: Our results show that 52% of the patients with pulmonary mycoses had a history of diabetes mellitus. Diabetes mellitus is a relevant risk factor for pulmonary mycoses, which are usually diagnosed in advanced stages and have a high mortality