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Purpose: To analyze the adverse events reported in the pharmacovigilance of the health service provider institutions of the municipality of Monteria in the period 2018– 2021.Patients and Methods: Descriptive, cross-sectional, retrospective, and quantitative approach study, the information was analyzed by statistical analysis by multiple correspondence using Orange Data Mining software; the analysis consisted of visual programming to perform interactive data exploration, to identify and differentiate associations or oppositions between different categories in space.Results: The most frequently reported adverse events were allergic reactions, with 28.5%. Female sex and adult age are the groups most prone to present these events; antibiotics were the pharmacological group that produced the most adverse events with 18.3%; the main errors that produce these events are related to prescription.Conclusion: Age and sex increase the risk of adverse drug events; most of these events are the product of erroneous prescriptions. The findings presented in this article are useful for pharmacovigilance programs in health institutions. [ABSTRACT FROM AUTHOR]

Citizen science and related engagement programmes have proliferated in recent years throughout the sciences but have been reasonably limited in the cryospheric sciences. In the semiarid Andes we at the Centro de Estudios Avanzados en Zonas Áridas have developed a range of initiatives together with the wider community and stakeholder institutions to improve our understanding of the role snow and ice play in headwater catchments. In this paper we reflect on ongoing engagement with communities living and working in and near study sites of cryospheric science in northern Chile as a strategy that can both strengthen the research being done and empower local communities. [ABSTRACT FROM AUTHOR]

Background: The Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome (HIV/AIDS) constitute one of the main public health problems worldwide. With the appearance of antiretroviral treatments (ART), the history of the disease has changed, going from being highly fatal to being considered a chronic disease, since these drugs contribute to improving the quality of life of these patients by preventing replication viral. Objective: To identify adherence to antiretroviral treatment in children under 13 years of age living with HIV/AIDS. Methods: Descriptive, retrospective study with a quantitative approach. The population was made up of 21 children under 13 years of age living with HIV/AIDS and their family caregivers. The "Morisky Medication Adherence Scale-8 items (MMAS-8)" was used, and the SPSS statistical program was used for data processing. Version 21. Results: The majority of minors are unaware of the diagnosis (86%), are female (57.1%), live with their biological parents (81%), whose parents or caregivers earn less than the current minimum monthly wage (90.5 %), level of education of the primary caregiver complete (61.9%), non-adherent to antiretroviral treatment (71.4%) the factors associated with non-adherence identified are socioeconomic (Significance 0.004), and those associated with side effects of medications, which were estimated using the Chi square test for categorical variables and the T Student test for quantitative variables, selecting an α=0.05 and a confidence level of 95%. Conclusions: Poverty is a conditioning factor for practices that lead to non-adherence to antiretroviral treatment. [ABSTRACT FROM AUTHOR]

Early events during axolotl limb regeneration include an immune response and the formation of a wound epithelium. These events are linked to a clearance of damaged tissue prior to blastema formation and regeneration of the missing structures. Here, we report the resorption of calcified skeletal tissue as an active, cell-driven, and highly regulated event. This process, carried out by osteoclasts, is essential for a successful integration of the newly formed skeleton. Indeed, the extent of resorption is directly correlated with the integration efficiency, and treatment with zoledronic acid resulted in osteoclast function inhibition and failed tissue integration. Moreover, we identified the wound epithelium as a regulator of skeletal resorption, likely releasing signals involved in recruitment/differentiation of osteoclasts. Finally, we reported a correlation between resorption and blastema formation, particularly, a coordination of resorption with cartilage condensation. In sum, our results identify resorption as a major event upon amputation, playing a critical role in the overall process of skeletal regeneration. [ABSTRACT FROM AUTHOR]

Citizen science and related engagement programmes have proliferated in recent years throughout the sciences but have been reasonably limited in the cryospheric sciences. In the semiarid Andes we at the Centro de Estudios Avanzados en Zonas Áridas have developed a range of initiatives together with the wider community and stakeholder institutions to improve our understanding of the role snow and ice play in headwater catchments. In this paper we reflect on ongoing engagement with communities living and working in and near study sites of cryospheric science in northern Chile as a strategy that can both strengthen the research being done and empower local communities. [ABSTRACT FROM AUTHOR]

Background: The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop postembryonically. In this work, we evaluated the postembryonic development of the appendicular skeleton and its changes with aging. Results: The juvenile limb skeleton is formed mostly by Sox9/Col1a2 cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte‐filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution of Col1a2‐descendants to bone and adipocytes. Moreover, ossification progresses with age toward the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to l‐thyroxine, increasing the rate of bone formation. Conclusions: In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth. Key Findings: The juvenile appendicular skeleton is formed mostly by Sox9/Col1a2 cartilage cells, transitioning to a slow and life‐long ossification that starts around sexual maturation.Axolotl growth is biphasic, defined by an explosive growth of axolotls in approximately the first 20 months of their life, after which growth velocity dramatically diminishes, however never reaching zero.A hybrid population of hypertrophic chondrocytes, expressing the chondrogenic marker SOX9 and the osteoblast marker OCN, resides next to the ossification center.Col1a2‐descendants contribute to bone and adipocytes during ossification. [ABSTRACT FROM AUTHOR]

Background Serological evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an alternative that allows us to determine the prevalence and dynamics of this infection in populations. The goal of this study was to determine the clinical and sociodemographic dynamics of SARS-CoV-2 infection in a region of the Colombian Caribbean. Methods Between July and November 2020, a cross-sectional observational study was carried out in Córdoba, located in northeast Colombia in the Caribbean area. Eight municipalities with the largest populations were chosen and 2564 blood samples were taken. A commercial enzyme-linked immunosorbent assay was used with the recombinant protein antigen N of SARS-CoV-2. The people included in the study were asked for sociodemographic and clinical data, which were analysed by statistical methods. Results A seroprevalence of 40.8% was obtained for SARS-CoV-2 in the Córdoba region. In the bivariate analysis, no differences were observed in seropositivity against SARS-CoV-2 for gender or age range (p>0.05). Higher seropositivity was found in low socio-economic status and symptomatic patients (p<0.0001). A total of 30.7% of the asymptomatic patients were seropositive for SARS-CoV-2, which could be linked to the spread of this infection. In the multivariate analysis, seroconversion was related to poverty and clinical manifestations such as anosmia and ageusia (p<0.05). Conclusions The high seropositivity in Córdoba is due to widespread SARS-CoV-2 in this population. The relationship between seropositivity and socio-economic status suggests a higher exposure risk to the virus caused by informal economic activities in low-income groups. Clinical manifestations such as anosmia and ageusia could be clinical predictors of infection by the new emergent coronavirus. [ABSTRACT FROM AUTHOR]

A serological survey was carried out in Monteria (500 000 population), a mid-size city in Colombia. An overall prevalence of 55.3% (95% confidence interval, 52.5%–57.8%) was found among a sample of 1.368 people randomly selected from the population. Test positivity was related to economic characteristics with the highest prevalence found in the most impoverished areas, representing 83.8% of the city's population. We found a prevalence that might be associated with some important level of population immunity. [ABSTRACT FROM AUTHOR]

Background and Aim: Venezuelan equine encephalitis virus (VEEV) is an alphavirus that causes encephalitis with a high impact on public health in Latin America. However, only in Guatemala, Trinidad and Tobago, and Mexico have found antibodies in VEEV in bats, using immunohistochemistry, the sensitivity and specificity are improved; thus, it is better for demonstrating natural infection in bats as potential hosts. This study aimed to determine the presence of VEEV in tissues of frugivorous bats. Materials and Methods: A prospective descriptive cross-sectional study with a non-probabilistic sampling was carried out in 12 localities of Córdoba and Sucre area of the Colombian Caribbean. Two hundred and eighty-six bats were captured using fog nets, and the specimens according to taxonomic keys were classified. According to the Ethics Committee of the University of Córdoba, the bats were treated with analgesics and anesthetics. Blood samples were taken and then euthanized to obtain tissues and organs which were preserved in liquid N2 at -196°C. A portion of each organ was fixed in 10% buffered formalin for the detection of antigens by immunohistochemistry. Several pathological anatomy analyses were performed to determine the histological characteristics of tissue lesions of frugivorous bats naturally infected with the VEEV. Results: Of the 286 bats captured, 23 species were identified. In samples of the brain, spleen, and lung of two frugivorous bats (2/286=0.70%) Artibeus planirostris and Sturnira lilium, the presence of VEEV was confirmed by immunohistochemistry. Conclusion: A fragment of the nsP4 non-structural protein gene corresponding to the alphavirus was amplified. Two samples were positive (2/286=0.70%) in frugivorous bats; A. planirostris (code GenBank: MG820274) and S. lilium (code GenBank: MG820275). The present study showed the first molecular evidence and cellular evidence (histopathology and immunohistochemistry) of natural VEEV infection in frugivorous bats in Colombia; these bats could be a host of this zoonosis. [ABSTRACT FROM AUTHOR]

Natural infection of dengue virus (DENV) in bats is an unexplored field in Colombia. To detect the presence of DENV in bats, a descriptive prospective study using a nonprobabilistic sampling was carried out; 286 bats in 12 sites were caught. Sample tissues of different animals were obtained; the RNA was obtained from tissues and a nested-RT-PCR was carried out and detected amplicons of 143 fragment of the NS5 gene were sequenced by the Sanger method. In nonhematophagous bats Carollia perspicillata and Phyllostomus discolor captured in Ayapel and San Carlos (Córdoba), respectively, an amplicon corresponding to NS5 was detected. The amplicons showed a high similarity with serotype-2 dengue virus (DENV-2). This is the first evidence of the DENV-2 genome in bats in from the Colombian Caribbean. [ABSTRACT FROM AUTHOR]

Highlights • A 195 nt fragment of the nsP4 non-structural protein gene of alphaviruses was amplified in several frugivorous bats. • Venezuelan equine encephalitis virus RNA was detected Artibeus planirostris and Sturnira lilium from Cordoba – Colombia. • Frugivorous bats from the Caribbean area of Colombian may be involved in the Venezuelan equine encephalitis virus enzootic cycle. Abstract Alphavirus infection associated encephalitis is an emerging infectious disease with a high impact on public health in Latin America. Objective To study the eco-epidemiology of alphaviruses in bats of departments of Córdoba and Sucre, Colombia. Methodology A prospective descriptive cross-sectional study with a non-probabilistic sampling, in 12 localities of Córdoba and Sucre was carried out. Using mist nets capture of the specimens was carried out. The size of the sample was 286 bats, each specimen captured was taxonomically classified. The bats were immobilized with anesthetic and analgesic treatment according to the ethics committee of the University of Córdoba, morphometric measurements and blood samples were taken, later they were necropsied in the field to obtain a collection of tissues which were preserved in liquid N 2 −190 °C. The averages of the climatic conditions of the sampling sites were extracted from the WorldClim database (http://www.worldclim.org/). The open source software QGIS (Quantum GIS Development Team.2015) was used to map and visualize bioclimatic regions of Córdoba. We used descriptive and retrospective information about the equine population and reports of foci of equine encephalitis. Results In Córdoba and Sucre, 286 bats were captured and 23 species were classified, Artibeus and Phyllostomus discolor were the most frequent captured genus. The geographic ranges of the captured species were variable, some had a wide distribution and others were restricted to some areas. Venezuelan equine encephalitis virus RNA was detected in Artibeus planirostris and Sturnira lilium (2/286 = 0.70%) from Cordoba – Colombia. The univariate descriptive analysis showed no significant association for any of the analyzed variables climatic. Conclusions Frugivorous bats from the Caribbean area of Colombia may be involved in the Venezuelan equine encephalitis virus enzootic cycle. [ABSTRACT FROM AUTHOR]

The digit tip is an exciting model for studying regeneration in mammals, but the precise mechanisms and the populations of cells involved in the formation and remodeling of the blastema remain unknown. In an exciting new work, Storer et al. take advantage of single-cell RNAseq combined with Pdgfra+ ​lineage-tracing to open the way into the enigmatic world of mammalian tissue regeneration. Image 1 • PDGFRa+ ​mesenchymal progenitors are required for mammalian digit tip regeneration. • Permissive regenerative blastema, but not non-regenerative fibroblasts, is what primed these cells to regenerate. • Comparisons between digit development and regeneration in mammals suggest that blastema progenitor cells do not recapitulate development. • Growing evidence indicates the essential contribution of mesenchymal progenitors to the regeneration and repair of most tissues. [ABSTRACT FROM AUTHOR]

Fibrosis is a common feature of several chronic diseases and is characterized by exacerbated accumulation of ECM. An understanding of the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong profibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA).The integrin/focal adhesion kinase (FAK) signaling pathway mediates this effect, since CTGF expression is abolished by the use of the Arg-Gly-Asp-Ser peptide and also by an inhibitor of FAK autophosphorylation at tyrosine 397. Cilengitide, a specific inhibitor of v integrins, inhibits the expression of CTGF mediated by LPA or transforming growth factor -1. We show that ECM obtained from decellularized myofibroblast cultures or derived from activated fibroblasts from muscles of the Duchenne muscular dystrophy mouse model (mdx) induces the expression of CTGF. This effect is dependent on FAK phosphorylation in response to its activation by integrin. We also found that the fibrotic ECM inhibits skeletal muscle differentiation. This novel regulatory mechanism of CTGF expression could be acting as a positive profibrotic feedback between the ECM and CTGF, revealing a novel concept in the control of fibrosis under chronic damage. [ABSTRACT FROM AUTHOR]

SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells ( Sharpin cpdm), and mice with a stromal ( S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty. In contrast, Sharpin cpdm mammary epithelial cells transplanted in vivo into wild-type stroma, fully repopulate the mammary gland fat pad, undergo unperturbed ductal outgrowth and terminal differentiation. Thus, SHARPIN is required in mammary gland stroma during development. Accordingly, stroma adjacent to invading mammary ducts of Sharpin cpdm mice displayed reduced collagen arrangement and extracellular matrix ( ECM) stiffness. Moreover, Sharpin cpdm mammary gland stromal fibroblasts demonstrated defects in collagen fibre assembly, collagen contraction and degradation in vitro. Together, these data imply that SHARPIN regulates the normal invasive mammary gland branching morphogenesis in an epithelial cell extrinsic manner by controlling the organisation of the stromal ECM. [ABSTRACT FROM AUTHOR]

Although more than half of the world's population is already vaccinated, the appearance of new variants of concern puts public health at risk due to the generation of new immunogens against the virus as a crucial and relevant strategy in the control of these new variants. A preclinical study used a potential vaccine candidate (RBD, SARS-CoV-2). Four groups of BALB/c mice were used, a control group, an adjuvant group, a group inoculated with one dose of RBD subunit protein, and the fourth group inoculated with two doses of RBD subunit protein. No inflammatory or cellular changes were shown in the mice's anatomopathological evaluation. Higher kinetics and 75% seroconversion were obtained in the mice inoculated with two doses of RBD (P < 0.0001). The application of two doses of the RBD vaccine candidate in BALB/c mice proved safe and immunogenic against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Rodent-borne hantaviruses (family Bunyaviridae, genus Hantavirus) cause hantavirus pulmonary syndrome in the Americas and hemorrhagic fever with renal syndrome in Europe and Asia. The viruses are transmitted to humans mainly by inhalation of virus-contaminated aerosols of rodent excreta and secreta. Classic clinical hemorrhagic fever with renal syndrome occurs in five phases: fever, hypotension, oliguria, polyuria, and convalescence. Hantavirus pulmonary syndrome is a severe acute disease that is associated with respiratory failure, pulmonary edema and cardiogenic shock. The diagnosis of hantavirus infections in humans is based on clinical and epidemiological information as well as laboratory tests. We review diagnosis for hantavirus infections based on serology, PCR, immunochemistry and virus culture. [ABSTRACT FROM AUTHOR]

Background: Ras nanoclusters contain 6-8 Ras proteins on the plasma membrane and serve as indispensable signaling platforms for Ras-MAPK signaling. Results: Ras membrane conformer mutants impart specific galectin-1-dependent nanoclustering responses. Conclusion: Mutations in Ras can affect its nanoclustering response and thus allosterically effector recruitment and downstream signaling. Significance: Disease-associated mutations that perturb Ras membrane conformers may alter signaling through nanoclustering. Solution structures and biochemical data have provided a wealth of mechanistic insight into Ras GTPases. However, information on how much the membrane organization of these lipid-modified proteins impacts on their signaling is still scarce. Ras proteins are organized into membrane nanoclusters, which are necessary for Ras-MAPK signaling. Using quantitative conventional and super-resolution fluorescence methods, as well as mathematical modeling, we investigated nanoclustering of H-ras helix α4 and hypervariable region mutants that have different bona fide conformations on the membrane. By following the emergence of conformer-specific nanoclusters in the plasma membrane of mammalian cells, we found that conformers impart distinct nanoclustering responses depending on the cytoplasmic levels of the nanocluster scaffold galectin-1. Computational modeling revealed that complexes containing H-ras conformers and galectin-1 affect both thenumberand lifetime of nanoclusters and thus determine the specific Raf effector recruitment. Our results show that mutations in Ras can affect its nanoclustering response and thus allosterically effector recruitment and downstream signaling. We postulate that cancer- and developmental disease-linked mutations that are associated with the Ras membrane conformation may exhibit so far unrecognized Ras nanoclustering and therefore signaling alterations. [ABSTRACT FROM AUTHOR]

The clonogenic or colony formation assay is a widely used method to study the number and size of cancer cell colonies that remain after irradiation or cytotoxic agent administration and serves as a measure for the anti-proliferative effect of these treatments. Alternatively, this assay is used to quantitate the transforming potential of cancer associated genes and chemical agents. Therefore, there is a need for a simplified and standardized analysis of colony formation assays for both routine laboratory use and for parallelized automated analysis. Here we describe the freely available ImageJ-plugin “ColonyArea”, which is optimized for rapid and quantitative analysis of focus formation assays conducted in 6- to 24-well dishes. ColonyArea processes image data of multi-well dishes, by separating, concentrically cropping and background correcting well images individually, before colony formation is quantitated. Instead of counting the number of colonies, ColonyArea determines the percentage of area covered by crystal violet stained cell colonies, also taking the intensity of the staining and therefore cell density into account. We demonstrate that these parameters alone or in combination allow for robust quantification of IC50 values of the cytotoxic effect of two staurosporines, UCN-01 and staurosporine (STS) on human glioblastoma cells (T98G). The relation between the potencies of the two compounds compared very well with that obtained from an absorbance based method to quantify colony growth and to published data. The ColonyArea ImageJ plugin provides a simple and efficient analysis routine to quantitate assay data of one of the most commonly used cellular assays. The bundle is freely available for download as supporting information. We expect that ColonyArea will be of broad utility for cancer biologists, as well as clinical radiation scientists. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a study which determined the prevalence of antibody to arenaviruses among wild rodents in Caribbean Colombia.

We demonstrate quantitative in situ viscosity measurements by tracking the thermal fluctuations of an optically trapped microsphere subjected to a small oscillatory flow. The measured power spectral density of the sphere’s positions displays a characteristic peak at the driving frequency of the flow, which is simply proportional to the viscosity, when measured in units of the thermal power spectral density at the same frequency. Measurements are validated on different water-glycerol mixtures, as well as in a glycerol gradient, where no a priori knowledge of the solution is used to determine the glycerol concentration. [ABSTRACT FROM AUTHOR]

Fibrillar adhesions are important structural and adhesive components in fibroblasts, and are required for fibronectin fibrillogenesis. While nascent and focal adhesions are known to respond to mechanical cues, the mechanoresponsive nature of fibrillar adhesions remains unclear. Here, we used ratiometric analysis of paired adhesion components to determine an appropriate fibrillar adhesion marker. We found that active α5β1-integrin exhibits the most definitive fibrillar adhesion localization compared to other proteins, such as tensin-1, reported to be in fibrillar adhesions. To elucidate the mechanoresponsiveness of fibrillar adhesions, we designed a cost-effective and reproducible technique to fabricate physiologically relevant stiffness gradients on thin polyacrylamide (PA) hydrogels, embedded with fluorescently labelled beads. We generated a correlation curve between bead density and hydrogel stiffness, thus enabling a readout of stiffness without the need for specialized knowhow, such as atomic force microscopy (AFM). We find that stiffness promotes growth of fibrillar adhesions in a tensin-1-dependent manner. Thus, the formation of these extracellular matrix-depositing structures is coupled to the mechanical parameters of the cell environment and may enable cells to fine-tune their matrix environment in response to changing physical conditions. [ABSTRACT FROM AUTHOR]