Nonviral Expression of LL-37 in a Human Skin Equivalent to Prevent Infection in Skin Wounds

Inefficient autologous tissue recovery in skin wounds increases the susceptibility of patients to infections caused by multidrug resistant microorganisms, resulting in a high mortality rate. Genetic modification of skin cells has become an important field of study because it could lead to the construction of more functional skin grafts, through the overexpression of antimicrobial peptides that would prevent early contamination and infection with bacteria. In this study, we produce and evaluate human skin equivalents (HSEs) containing transfected human primary fibroblasts and keratinocytes by polyplexes to express the antimicrobial peptide LL-37. The effect of LL-37 on the metabolic activity of normal HSEs was evaluated before the construction of the transfected HSEs, and the antimicrobial efficacy against Pseudomonas aeruginosa and Staphylococcus aureus was evaluated. Subsequently, the levels of LL-37 in the culture supernatants of transfected HSEs, as well as the local expression, were determined. It was found that LL-37 treatment significantly promoted the cellular proliferation of HSEs. Furthermore, HSEs that express elevated levels of LL-37 were shown to possess histological characteristics close to the normal skin and display enhanced antimicrobial activity against S. aureus in vitro. These findings demonstrate that HSEs expressing LL-37 through nonviral modification of skin cells are a promising approach for the prevention of bacterial colonization in wounds

On cytoadhesion of Plasmodium vivax: raison d'être?

It is generally accepted that Plasmodium vivax, the most widely distributed human malaria parasite, causes mild disease and that this species does not sequester in the deep capillaries of internal organs. Recent evidence, however, has demonstrated that there is severe disease, sometimes resulting in death, exclusively associated with P. vivax and that P. vivax-infected reticulocytes are able to cytoadhere in vitro to different endothelial cells and placental cryosections. Here, we review the scarce and preliminary data on cytoadherence in P. vivax, reinforcing the importance of this phenomenon in this species and highlighting the avenues that it opens for our understanding of the pathology of this neglected human malaria parasite.798

Modeling Gamma-ray burst Afterglow observations with an Off-axis Jet emission

Gamma-ray bursts (GRBs) are fascinating extragalactic objects. They represent a fantastic opportunity to investigate unique properties not exhibited in other sources. Multi-wavelength afterglow observations from some short- and long-duration GRBs reveal an atypical long-lasting emission that evolves differently from the canonical afterglow light curves favoring the off-axis emission. We present an analytical synchrotron afterglow scenario, and the hydrodynamical evolution of an off-axis top-hat jet decelerated in a stratified surrounding environment. The analytical synchrotron afterglow model is shown during the coasting, deceleration (off- and on-axis emission), and the post-jet-break decay phases, and the hydrodynamical evolution is computed by numerical simulations showing the time evolution of the Doppler factor, the half-opening angle, the bulk Lorentz factor, and the deceleration radius. We show that numerical simulations are in good agreement with those derived with our analytical approach. We apply the current synchrotron model and describe successfully the delayed non-thermal emission observed in a sample of long and short GRBs with evidence of off-axis emission. Furthermore, we provide constraints on the possible afterglow emission by requiring the multi-wavelength upper limits derived for the closest Swift-detected GRBs and promising gravitational-wave events.Comment: 36 pages, 16 figures, accepted for publication in Ap

Occurrence of Goniozus legneri (Hymenoptera: Bethylidae) and its association to lepidopteran pests in Northern cultivated oasis of Mendoza province, Argentina

Goniozus legneri Gordh (Hymenoptera: Bethylidae) es un ectoparasitoide larvario de lepidópteros, con trayectoria mundial como agente de biocontrol de diversas plagas agrícolas. Mediante amplios monitoreos, esta avispa fue encontrada en cuatro distritos distantes de la provincia de Mendoza parasitando tres plagas de lepidópteros: Lobesia botrana (Den. et Shiff.) en vid, Ectomyelois ceratoniae (Zeller) en nogal y “espinillo” ( Vachellia caven (Molina) . ) Seigler et Ebinger) y Cydia pomonella (L.) en nogal. Para corroborar la identificación de especies de parasitoides y analizar su viabilidad poblacional en esta región, se realizaron estudios de genitales masculinos y cruces sexuales entre avispas silvestres y criadas en laboratorio. Además, informamos por primera vez la interacción natural huésped-parasitoide de L. botrana con este parasitoide en viñedos de Argentina.Goniozus legneri Gordh (Hymenoptera: Bethylidae) is a larval ectoparasitoid of lepidopterans, with a worldwide history as a biocontrol agent of various agricultural pests. By means of extensive monitoring, this wasp was found in four distant districts of Mendoza province parasitizing three lepidopteran pests: Lobesia botrana (Den. et Shiff.) in grapevine, Ectomyelois ceratoniae (Zeller) in walnut and “espinillo” (Vachellia caven (Molina) Seigler et Ebinger) and Cydia pomonella (L.) in walnut. To corroborate the parasitoid species identification and to analyze its population viability in this region, studies of male genitalia and sexual crossings between wild and laboratory-reared wasps were conducted. Further, we report for the first time the natural host-parasitoid interaction of L. botrana with this parasitoid in vineyards from Argentina.EEA MendozaFil: Marcucci, Bruno. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza. Laboratorio de Fitofarmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mazzitelli, María E. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza. Laboratorio de Fitofarmacia; Argentina.Fil: Garrido, Silvina A. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle. Sanidad Vegetal; Argentina.Fil: Cichón, Liliana I. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle. Sanidad Vegetal; Argentina.Fil: Becerra, Violeta C. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza. Laboratorio de Fitofarmacia; Argentina.Fil: Luna, María G. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios de Parasitológicos y Vectores; Argentina. Universidad Nacional de La Plata. Centro de Estudios de Parasitológicos y Vectores; ArgentinaFil: Luna, María G. Universidad Nacional de San Antonio de Areco; Argentina

Viscoelastic properties of plasma-agarose hydrogels dictate favorable fibroblast responses for skin tissue engineering applications

Dermal wound healing relies on the properties of the extracellular matrix (ECM). Thus, hydrogels that replicate skin ECM have reached clinical application. After a dermal injury, a transient, biodegradable fibrin clot is instrumental in wound healing. Human plasma, and its main constituent, fibrin would make a suitable biomaterial for improving wound healing and processed as hydrogels albeit with limited mechanical strength. To overcome this, plasma-agarose (PA) composite hydrogels have been developed and used to prepare diverse bioengineered tissues. To date, little is known about the influence of variable agarose concentrations on the viscoelastic properties of PA hydrogels and their correlation to cell biology. This study reports the characterization of the viscoelastic properties of different concentrations of agarose in PA hydrogels: 0 %, 0.5 %, 1 %, 1.5 %, and 2 % (w/v), and their influence on the cell number and mitochondrial activity of human dermal fibroblasts. Results show that agarose addition increased the stiffness, relaxation time constants 1 (τ1) and 2 (τ2), and fiber diameter, whereas the porosity decreased. Changes in cell metabolism occurred at the early stages of culturing and correlated to the displacement of fast (τ1) and intermediate (τ2) Maxwell elements. Fibroblasts seeded in low PA concentrations spread faster during 14 d than cells cultured in higher agarose concentrations. Collectively, these results confirm that PA viscoelasticity and hydrogel architecture strongly influenced cell behavior. Therefore, viscoelasticity is a key parameter in the design of PA-based implants

Severe Plasmodium vivax Malaria, Brazilian Amazon

We describe a case series of 17 patients hospitalized in Manaus (western Brazilian Amazon) with PCR-confirmed Plasmodium vivax infection who were treated with chloroquine and primaquine. The major complications were jaundice and severe anemia. No in vivo chloroquine resistance was detected. These data help characterize the clinical profile of severe P. vivax malaria in Latin America

Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections.

--- - Label: BACKGROUND NlmCategory: BACKGROUND content: The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. - Label: METHODS NlmCategory: METHODS content: In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis. - Label: RESULTS NlmCategory: RESULTS content: We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Machine-Learning Enhanced Photometric Analysis of the Extremely Bright GRB 210822A

We present analytical and numerical models of the bright long GRB 210822A at $z=1.736$. The intrinsic extreme brightness exhibited in the optical, which is very similar to other bright GRBs (e.g., GRBs 080319B, 130427A, 160625A 190114C, and 221009A), makes GRB 210822A an ideal case for studying the evolution of this particular kind of GRB. We use optical data from the RATIR instrument starting at $T+315.9$ s, with publicly available optical data from other ground-based observatories, as well as X-ray data from the Swift/X-ray Telescope (XRT) and data from the Swift/Ultraviolet/Optical Telescope (UVOT). The temporal profiles and spectral properties during the late stages align consistently with the conventional forward shock model, complemented by a reverse shock element that dominates optical emissions during the initial phases ($T<300$ s). Furthermore, we observe a break at $T=80000$ s that we interpreted as evidence of a jet break, which constrains the opening angle to be about $\theta_\mathrm{j}=(3-5)$ degrees. Finally, we apply a machine-learning technique to model the multi-wavelength light curve of GRB 210822A using the AFTERGLOWPY library. We estimate the angle of sight $\theta_{obs}=(6.4 \pm 0.1) \times 10^{-1}$ degrees, the energy $E_0= (7.9 \pm 1.6)\times 10^{53}$ ergs, the electron index $p=2.54 \pm 0.10$, the thermal energy fraction in electrons $\epsilon_e=(4.63 \pm 0.91) \times 10^{-5}$ and in the magnetic field $\epsilon_B= (8.66 \pm 1.01) \times 10^{-6}$, the efficiency $\chi = 0.89 \pm 0.01$, and the density of the surrounding medium $n_\mathrm{0} = 0.85 \pm 0.01$.Comment: Submitted to MNRAS, 11 pages, 6 figures. Fixed typo

Plasmodium vivax gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile

Plasmodium vivax is the most widely distributed human malaria parasite and responsible for large amounts of disease and burden [1]. The presence of P. vivax in the bone marrow was first noticed in the late 19th century [2], and examinations of sternal bone marrow aspirates were performed as an accessory to examinations of peripheral blood in malaria, including P. vivax [3]. Since then, little progress has been made in studying P. vivax infections in this tissue. One report explored accumulation of dyserythropoietic cells in anaemic infected patients [4]. In addition, two case studies reported P. vivax infections after autologous bone marrow transplantation [5][6], and a third one documented an accidental P. vivax infection due to bone marrow transplantation between a malaria-infected donor and a malaria-free receptor [7]. In Brazil, one patient with persistent thrombocytopaenia and an enlarged spleen was diagnosed with chronic P. vivax malaria after the finding of schizonts in the bone marrow aspirate [8]. In all these reports and case studies, however, parasite loads and life stages found in the bone marrow were not investigated, and no molecular tools were available to rule out mixed infections or to characterize specific parasite stages