Clinical progress in MSC-based therapies for the management of severe COVID-19.

Considering the high impact that severe Coronavirus disease 2019 (COVID-19) cases still pose on public health and their complex pharmacological management, the search for new therapeutic alternatives is essential. Mesenchymal stromal cells (MSCs) could be promising candidates as they present important immunomodulatory and anti-inflammatory properties that can combat the acute severe respiratory distress syndrome (ARDS) and the cytokine storm occurring in COVID-19, two processes that are mainly driven by an immunological misbalance. In this review, we provide a comprehensive overview of the intricate inflammatory process derived from the immune dysregulation that occurs in COVID-19, discussing the potential that the cytokines and growth factors that constitute the MSC-derived secretome present to treat the disease. Moreover, we revise the latest clinical progress made in the field, discussing the most important findings of the clinical trials conducted to date, which follow 2 different approaches: MSC-based cell therapy or the administration of the secretome by itself, as a cell-free therapy.

WNT-FRIZZLED-LRP5/6 Signaling Mediates Posterior Fate and Proliferation during Planarian Regeneration.

An organizer is defined as a group of cells that secrete extracellular proteins that specify the fate of surrounding cells according to their concentration. Their function during embryogenesis is key in patterning new growing tissues. Although organizers should also participate in adult development when new structures are regenerated, their presence in adults has only been identified in a few species with striking regenerative abilities, such as planarians. Planarians provide a unique model to understand the function of adult organizers, since the presence of adult pluripotent stem cells provides them with the ability to regenerate any body part. Previous studies have shown that the differential activation of the WNT/ß-catenin signal in each wound is fundamental to establish an anterior or a posterior organizer in the corresponding wound. Here, we identify the receptors that mediate the WNT/ß-catenin signal in posterior-facing wounds. We found that Wnt1-Fzd1-LRP5/6 signaling is evolutionarily conserved in executing a WNT/ß-catenin signal to specify cell fate and to trigger a proliferative response. Our data allow a better understanding of the mechanism through which organizers signal to a "competent" field of cells and integrate the patterning and growth required during de novo formation of organs and tissues.

A novel technique for transaxillary resection of fully formed cervical ribs with long-term clinical outcomes.

OBJECTIVE: Although the supraclavicular approach has been widely adopted for cervical rib resection, a transaxillary approach has been favored by many. We have reviewed more than two decades of experience with decompression of the thoracic outlet to treat thoracic outlet syndrome (TOS) in patients with complete cervical ribs using a novel transaxillary approach. METHODS: A prospectively maintained database of patients undergoing surgery for TOS was searched for patients with complete (class 3 and 4) cervical ribs from 1997 to 2019. All these patients had undergone transaxillary resection using a technique in which the cervical and first ribs were separated and then individually resected. The data abstracted included patient demographics, symptoms, surgical details, and complications. The outcomes were contemporaneously assessed clinically and using standardized functional tools: somatic pain scale (SPS) and Quick Disabilities of the Arm, Hand, and Shoulder questionnaire (QuickDASH). The cervical rib data were organized and reported in accordance with the Society for Vascular Surgery reporting standards. RESULTS: During the study period, 1506 patients had undergone surgery for TOS at our institution. Of these 1506 patients, 38 had undergone complete transaxillary resection of 40 fully formed cervical ribs (10 class 3 and 30 class 4). Of these 38 patients, 74% were women. The presentations had been neurogenic (65%), arterial (31%), and venous (5%). The average initial SPS and QuickDASH score was 6.4 and 50, respectively. The duration of surgery averaged 141 minutes, blood loss was 65 mL, and length of stay was 2.1 days. None of the patients had experienced brachial plexus, phrenic, or long thoracic nerve injury. The average follow-up period was 65 months. The final mean postoperative SPS and QuickDASH scores were lower than the scores at presentation (SPS score, 6.4 vs 1.2; P < .001; QuickDASH score, 50 vs 17; P < .001). CONCLUSIONS: To the best of our knowledge, the present study is the largest reported experience of resection of fully formed cervical ribs using a transaxillary approach that allowed for individual dissection and removal of cervical and first rib segments. This technique has proved to be successful, with low morbidity and reliable improvement in patient symptom and disability scores. Based on these reported outcomes, this novel approach to transaxillary resection of fully formed cervical ribs should be considered a safe and effective operation.

RGD Mutation of the Heparin Binding II Fragment of Fibronectin for Guiding Mesenchymal Stem Cell Behavior on Titanium Surfaces.

Installing bioactivity on metallic biomaterials by mimicking the extracellular matrix (ECM) is crucial for stimulating specific cellular responses to ultimately promote tissue regeneration. Fibronectin is an ECM protein commonly used for biomaterial functionalization. The use of fibronectin recombinant fragments is an attractive alternate to the use of full-length fibronectin because of the relatively low cost and facility of purification. However, it is necessary to combine more than one fragment, for example, the cell attachment site and the heparin binding II (HBII), either mixed or in one molecule, to obtain complete activity. In the present study, we proposed to install adhesion capacity to the HBII fragment by an RGD gain-of-function DNA mutation, retaining its cell differentiation capacity and thereby producing a small and very active protein fragment. The novel molecule, covalently immobilized onto titanium surfaces, maintained the growth factor-binding capacity and stimulated cell spreading, osteoblastic cell differentiation, and mineralization of human mesenchymal stem cells compared to the HBII native protein. These results highlight the potential capacity of gain-of-function DNA mutations in the design of novel molecules for the improvement of osseointegration properties of metallic implant surfaces.

A C-terminally truncated form of ß-catenin acts as a novel regulator of Wnt/ß-catenin signaling in planarians.

ß-Catenin, the core element of the Wnt/ß-catenin pathway, is a multifunctional and evolutionarily conserved protein which performs essential roles in a variety of developmental and homeostatic processes. Despite its crucial roles, the mechanisms that control its context-specific functions in time and space remain largely unknown. The Wnt/ß-catenin pathway has been extensively studied in planarians, flatworms with the ability to regenerate and remodel the whole body, providing a 'whole animal' developmental framework to approach this question. Here we identify a C-terminally truncated ß-catenin (ß-catenin4), generated by gene duplication, that is required for planarian photoreceptor cell specification. Our results indicate that the role of ß-catenin4 is to modulate the activity of ß-catenin1, the planarian ß-catenin involved in Wnt signal transduction in the nucleus, mediated by the transcription factor TCF-2. This inhibitory form of ß-catenin, expressed in specific cell types, would provide a novel mechanism to modulate nuclear ß-catenin signaling levels. Genomic searches and in vitro analysis suggest that the existence of a C-terminally truncated form of ß-catenin could be an evolutionarily conserved mechanism to achieve a fine-tuned regulation of Wnt/ß-catenin signaling in specific cellular contexts.

Liver biopsy-related infection in liver transplant recipients: A current matter of concern?

Data from published studies regarding risk factors for liver biopsy (LB)-related infectious complications in liver transplant recipients are inconsistent. We carried out a retrospective cohort study analyzing consecutive LBs for orthotopic liver transplant patients at a tertiary hospital (2001-2011): there were 667 LB procedures (575 percutaneous procedures and 92 transjugular procedures) in 286 liver transplant recipients. There were 20 complications in 19 patients (overall incidence = 3.0%): 10 were infectious complications (8 cases of bacteremia and 2 cases of peritonitis). The causal microorganisms were mainly Pseudomonas aeruginosa (4 patients) and Enterobacteriaceae (4 patients). All complications occurred with biopsies performed in patients hospitalized for more than 48 hours (381 biopsies for 201 patients); hence, only this group was included in the risk factor analysis. The variables associated with the development of infectious complications after LB were the presence of impaired biliary drainage at the time of biopsy (40% versus 15.1%, P = 0.03) and low albumin levels (2.4 versus 3.1 g/dL, P = 0.01). In conclusion, according to our experience, infectious complications secondary to LB in liver transplant recipients are related to hospitalization at the time of biopsy, particularly in the presence of impaired biliary drainage and low albumin levels.

Hydrothermal synthesis and extended structure of poly[aqua(µ5-ethylenediaminetetraacetato)dizinc(II)].

In the extended structure of the title compound, [Zn(2)(C(10)H(12)N(2)O(8))(H(2)O)], prepared under hydrothermal conditions, there are two distinct Zn(II) sites. The first, with octahedral geometry, bonds to two N and three O atoms from one ethylenediaminetetraacetate tetraanion (EDTA) and one water molecule. The second, with tetrahedral geometry, coordinates to O atoms from four different EDTA ligands. The EDTA ligand almost encapsulates the octahedral Zn(II) ion and binds to four symmetry-related tetrahedral Zn(II) ions, hence generating the extended structure. One noncoordinated O-atom site on the EDTA ligand connects to the water molecule by hydrogen bonding. Structural comparisons are made with other compounds containing zinc, EDTA and water.

Perfiles en hostilidad e impulsividad de una muestra de pacientes con trastorno límite de la personalidad en terapia dialectico-conductual / Hostility and Impulsivity profiles in a sample of patients with Borderline Personality Disorder receiving Dialectical Behavior Therapy

Descripción y seguimiento de niveles de hostilidad e impulsividad de una muestra de pacientes en terapia dialéctico-conductual grupal (AU)

Levels of hostility and impulsivity in a sample of patients with Borderline Personality Disorder treated with DBT in a group setting. Description and follow up (AU)