Panicolytic-like effects of environment enrichment on male mice threatened by Bothrops jararaca lancehead pit vipers.

Environment enrichment (EE) is a well-known eustress model showing beneficial effects in different psychiatric diseases, but its positive properties in panic disorders are not yet established. The confrontation between prey and predator in complex arenas has been validated as a putative panic attack model. The principal aim of this work was to investigate the role of the EE on panic-like defensive responses elicited by mice threatened by venomous snakes. After 6 weeks of exposure either to an enriched or standard environments, 36 male mice were habituated in a complex polygonal arena for snakes containing an artificial burrow and elevated platforms for escape. The animals were confronted by Bothrops jararaca for 5 min, and the following antipredatory responses were recorded: defensive attention, stretched attend posture, flat back approach, prey versus predator interaction, oriented escape behavior, time spent in a safe place, and number of crossings. Mice threatened by snakes displayed several antipredatory reactions as compared to the exploratory behavior of those animals submitted to a nonthreatening situation (toy snake) in the same environment. Notably, EE causes anxiolytic- and panicolytic-like effects significantly decreasing the defensive attention and time spent in safe places and significantly increasing both prey versus predator interaction and exploratory behavior. In conclusion, our data demonstrate that EE can alter the processing of fear modulation regarding both anxiety- and panic-like responses in a dangerous condition, significantly modifying the decision-making defensive strategy.

The Impact of Interdisciplinary, Gender and Geographic Distributions on the Citation Patterns of the Journal of Chemical Information and Modeling.

There has been a growing recognition of the need for diversity and inclusion in scientific fields. This trend is reflected in the Journal of Chemical Information and Modeling (JCIM), where there has been a gradual increase in the number of papers that embrace this diversity. In this viewpoint, we analyze the evolution of the profile of papers published in JCIM from 1996 to 2022 addressing three diversity criteria, namely interdisciplinarity, geographic and gender distributions, and their impact on citation patterns. We used natural language processing tools for the classification of main areas and gender, as well as metadata, to analyze a total of 7384 articles published in the categories of research articles, reviews, and brief reports. Our analyses reveal that the relative number of articles and citation patterns are similar across the main areas within the scope of JCIM, and international collaboration and publications encompassing two to three research areas attract more citations. The percentage of female authors has increased from 1996 (less than 20%) to 2022 (more than 32%), indicating a positive trend toward gender diversity in almost all geographic regions, although the percentage of publications by single female authors remains lower than 20%. Most JCIM citations come from Europe and the Americas, with a tendency for JCIM papers to cite articles from the same continent. Furthermore, there is a correlation between the gender of the authors, as JCIM manuscripts authored by females are more likely to be cited by other JCIM manuscripts authored by females.

Risk Factors, Incidence, and Outcomes Associated With Clinically Significant Airway Ischemia.

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for CSAI. Eighty-two patients (37.8%) met criteria for CSAI. Of these, twenty-six (32%) developed stenosis and/or dehiscence, and 17 (21%) required interventions. Patients with CSAI had lower one-year (80.5% vs. 91.9%, p = 0.05) and three-year (67.1% vs. 77.8%, p = 0.08) survival than patients without CSAI. Factors associated with CSAI included younger recipient age, recipient diabetes, single running suture technique, performance of the left anastomosis first, lower venous oxygen saturation within 48-h, and takeback for major bleeding. Our single-center analysis suggests that airway ischemia remains a major obstacle in contemporary lung transplantation. Improving the local healing milieu of the airway anastomosis could potentially mitigate this risk.

Molecular and morphometric study of Brazilian populations of Psychodopygus davisi.

In this study, we analysed the molecular and morphometric differences of several populations of the putative sand fly vector Psychodopygus davisi (Root, 1934) (Diptera, Psychodidae, Phlebotominae) in Brazil. We amplified the 658 base pair fragments of the DNA barcoding region-cytochrome c oxidase subunit 1 (COI) gene-for 57 specimens of P. davisi and three specimens of Psychodopygus claustrei (Abonnenc, Léger & Fauran, 1979). We merged our data with public sequences of the same species available from GenBank. Then, the combined dataset-87 sequences and 20 localities-was analysed using population structure analysis and different species delimitation approaches. Geometric morphometry of wings was performed for 155 specimens of P. davisi populations from the North, Midwest and Southeast Brazilian regions, analysing the differences in centroid sizes and canonical variates. Molecular analysis indicated high intraspecific genetic distance values for P. davisi (maximum p distance = 5.52%). All algorithms identified P. davisi and P. claustrei as distinct molecular taxonomic units, despite the low interspecific distance (p distance to the nearest neighbour = 4.79%). P. davisi sequences were split into four genetic clusters by population structure analysis and at least five genetic lineages using intermediate scenarios of the species delimitation algorithms. The species validation analysis of BPP strongly supported the five-species model in our dataset. We found high genetic diversity in this taxon, which is in agreement with its wide geographic distribution in Brazil. Furthermore, the wing analysis showed that specimens from the Southeast Region of Brazil are different from those in the North and the Midwest. The evolutionary patterns of P. davisi populations in Brazil suggest the presence of candidate species, which need to be validated in future studies using a more comprehensive approach with both genomic data and morphological characters.

The Biological Role of Platelet Derivatives in Regenerative Aesthetics.

Bioproducts derived from platelets have been extensively used across various medical fields, with a recent notable surge in their application in dermatology and aesthetic procedures. These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles in inducing blood vessel proliferation through growth factors derived from peripheral blood. PRP and PRF, in particular, facilitate fibrin polymerization, creating a robust structure that serves as a reservoir for numerous growth factors. These factors contribute to tissue regeneration by promoting cell proliferation, differentiation, and migration and collagen/elastin production. Aesthetic medicine harnesses these effects for diverse purposes, including hair restoration, scar treatment, striae management, and wound healing. Furthermore, these biological products can act as adjuvants with other treatment modalities, such as laser therapy, radiofrequency, and microneedling. This review synthesizes the existing evidence, offering insights into the applications and benefits of biological products in aesthetic medicine.

[Renal carcinoma: what therapeutic options in 2024?] / Carcinome rénal : quelles attitudes thérapeutiques en 2024 ?

The most important modifiable risk factors of renal cell carcinoma are smoking, obesity and hypertension. A biopsy of the renal tumour is not always necessary. It is important in situations where it can change the therapeutic attitude and should be discussed in particular for tumors < 4 cm in size and in metastatic stage. Treatment of localized and locoregional disease consists mainly of surgical removal of the tumor. Local ablative therapy (radiofrequency, thermoablation) or active surveillance are options for small tumors < 4 cm and frail patients with high surgical risk. Systemic treatment of metastatic disease consists of antiangiogenic tyrosine kinase inhibitors and immunotherapy with checkpoint inhibitors.

Les facteurs de risque modifiables du carcinome à cellules rénales les plus importants sont le tabagisme, l'obésité et l'hypertension. Une biopsie de la néoplasie rénale n'est pas toujours nécessaire. Elle est importante dans les situations où elle peut conduire à un changement d'attitude thérapeutique et devrait être discutée notamment pour les néoplasies dont la taille est < 4 cm et lors de situation métastatique. Le traitement de la maladie localisée consiste surtout en une exérèse chirurgicale. Un traitement ablatif local (radiofréquence, thermoablation) ou une surveillance active sont des options pour les petites néoplasies < 4 cm et pour les patients ayant un risque chirurgical élevé. Le traitement systémique de la maladie métastatique comprend les immunothérapies et les inhibiteurs de tyrosine kinases antiangiogéniques.

Interfacial Bonding between a Crystalline Metal-Organic Framework and an Inorganic Glass.

The interface within a composite is critically important for the chemical and physical properties of these materials. However, experimental structural studies of the interfacial regions within metal-organic framework (MOF) composites are extremely challenging. Here, we provide the first example of a new MOF composite family, i.e., using an inorganic glass matrix host in place of the commonly used organic polymers. Crucially, we also decipher atom-atom interactions at the interface. In particular, we dispersed a zeolitic imidazolate framework (ZIF-8) within a phosphate glass matrix and identified interactions at the interface using several different analysis methods of pair distribution function and multinuclear multidimensional magic angle spinning nuclear magnetic resonance spectroscopy. These demonstrated glass-ZIF atom-atom correlations. Additionally, carbon dioxide uptake and stability tests were also performed to check the increment of the surface area and the stability and durability of the material in different media. This opens up possibilities for creating new composites that include the intrinsic chemical properties of the constituent MOFs and inorganic glasses.

Promoting physical activity through supervised vs motivational behavior change interventions in breast cancer survivors on aromatase inhibitors (PAC-WOMAN): protocol for a 3-arm pragmatic randomized controlled trial.

BACKGROUND: Aromatase inhibitors (AI) are frequently used to treat hormone-receptor-positive breast cancer, but they have multiple adverse effects (e.g., osteoporosis, arthralgia), resulting in premature therapy discontinuation/switch. Physical activity (PA) can attenuate these negative effects and improve quality of life (QoL). However, most cancer survivors fail to perform/sustain adequate PA levels, especially in the long-term. Theory-based interventions, using evidence-based behavior change techniques, aimed at promoting long-term behavior change in breast cancer survivors are effective, but remain scarce and fail to promote self-regulatory skills and better-quality motivations associated with sustained PA adoption. This paper describes the design of the PAC-WOMAN trial, which will test the long-term effectiveness and cost-effectiveness of two state of the art, group-based interventions encouraging sustained changes in PA, sedentary behavior, and QoL. Additional aims include examining the impact of both interventions on secondary outcomes (e.g., body composition, physical function), and key moderators/mediators of short and long-term changes in primary outcomes. METHODS: A 3-arm pragmatic randomized controlled trial, involving a 4-month intervention and a 12-month follow-up, will be implemented, in a real exercise setting, to compare: 1) brief PA counseling/motivational intervention; 2) structured exercise program vs. waiting-list control group. Study recruitment goal is 122 hormone-receptor-positive breast cancer survivors (stage I-III), on AI therapy (post-primary treatment completion) ≥ 1 month, ECOG 0-1. Outcome measures will be obtained at baseline, 4 months (i.e., post-intervention), 10 and 16 months. Process evaluation, analyzing implementation determinants, will also be conducted. DISCUSSION: PAC-WOMAN is expected to have a relevant impact on participants PA and QoL and provide insights for the improvement of interventions designed to promote sustained adherence to active lifestyle behaviors, facilitating its translation to community settings. TRIAL REGISTRATION: April 20, 2023 - NCT05860621. April 21, 2023 - https://doi.org/10.17605/OSF.IO/ZAQ9N April 27, 2023 - UMIN000050945.

Implementation determinants of physical activity interventions in primary health care settings using the TICD framework: a systematic review.

BACKGROUND: Translation into practice of effective physical activity interventions in primary care is difficult, due to a complex interaction of implementation determinants. We aimed to identify implementation barriers and facilitators of four primary care interventions: physical activity assessment, counselling, prescription, and referral. METHODS: A systematic review of qualitative, quantitative and mixed-methods studies published since 2016 was conducted. The "Tailored Implementation for Chronic Diseases" (TICD) framework was adapted to extract and synthesize barriers and facilitators. RESULTS: Sixty-two studies met the inclusion criteria. Barriers (n = 56) and facilitators (n = 55) were identified across seven domains, related to characteristics of the intervention, individual factors of the implementers and receivers, organizational factors, and political and social determinants. The five most frequently reported determinants were: professionals' knowledge and skills; intervention feasibility/compatibility with primary health care routine; interventions' cost and financial incentives; tools and materials; and professionals' cognitions and attitudes. "Social, political and legal factors" domain was the least reported. Physical activity counselling, prescription, and referral were influenced by determinants belonging to all the seven domains. CONCLUSION: The implementation of physical activity interventions in primary care is influenced by a broader range of determinants. Barriers and facilitators related with health professionals, intervention characteristics, and available resources were the most frequently reported. A deep understanding of the local context, with particularly emphasis on these determinants, should be considered when preparing an intervention implementation, in order to contribute for designing tailored implementation strategies and optimize the interventions' effectiveness.

Trichophoromyia auraensis: evidence for cryptic species and first record in the state of Maranhão, Brazil.

Trichophoromyia auraensis (Mangabeira, 1942) (Diptera, Psychodidae, Phlebotominae) has a wide geographic distribution in the western region of the Amazon biome, where it is a putative Leishmania vector. Here, we reported for the first time a population of this species in the Brazilian state of Maranhão, in the eastern Amazon, from which we DNA-barcoded and compared with previously processed specimens from Acre State, in the western Amazon. For this, we analyzed the DNA barcoding fragment (658 bp) of the mitochondrial cytochrome c oxidase subunit I (COI) gene and the nuclear internal transcribed spacer 2 (ITS2) of Trichophoromyia species using phylogenetic gene trees, and species delimitation algorithms. The analyses of COI barcodes showed high values of genetic distance (mean K2P = 5.17) and well-supported clades/MOTUs for the eastern and western populations of T. auraensis, which may indicate a possible complex of cryptic species. The western population of this taxon merged with the close-related sand fly Trichophoromyia velezbernali Posada-López, Galvis and Galati, 2018 from Colombia, which may be associated with the recent speciation history and introgression between these populations. These evidences should be evaluated with a more comprehensive sampling in terms of analyzed populations and molecular markers.

Lignin-Supported Heterogeneous Photocatalyst for the Direct Generation of H2O2 from Seawater.

The development of smart and sustainable photocatalysts is in high priority for the synthesis of H2O2 because the global demand for H2O2 is sharply rising. Currently, the global market share for H2O2 is around 4 billion US$ and is expected to grow by about 5.2 billion US$ by 2026. Traditional synthesis of H2O2 via the anthraquinone method is associated with the generation of substantial chemical waste as well as the requirement of a high energy input. In this respect, the oxidative transformation of pure water is a sustainable solution to meet the global demand. In fact, several photocatalysts have been developed to achieve this chemistry. However, 97% of the water on our planet is seawater, and it contains 3.0-5.0% of salts. The presence of salts in water deactivates the existing photocatalysts, and therefore, the existing photocatalysts have rarely shown reactivity toward seawater. Considering this, a sustainable heterogeneous photocatalyst, derived from hydrolysis lignin, has been developed, showing an excellent reactivity toward generating H2O2 directly from seawater under air. In fact, in the presence of this catalyst, we have been able to achieve 4085 µM of H2O2. Expediently, the catalyst has shown longer durability and can be recycled more than five times to generate H2O2 from seawater. Finally, full characterizations of this smart photocatalyst and a detailed mechanism have been proposed on the basis of the experimental evidence and multiscale/level calculations.

Endoplasmic Reticulum Stress in Colonic Mucosa of Ulcerative Colitis Patients Is Mediated by PERK and IRE1 Pathway Activation.

Ulcerative colitis (UC) is characterized by a chronic overproduction of proinflammatory cytokines. During an acute phase, the endoplasmic reticulum (ER) is overloaded and the protein folding process is impaired, a condition named ER stress. This state induces a response (unfolded protein response (UPR)), initiated by the activation of IRE1/Xbp-1, PERK/eIF2α, and ATF6 pathways, which has previously been linked to intestinal inflammation in experimental models. ER stress and UPR activation trigger the activation of proinflammatory, autophagy, and apoptosis genes, in addition to promoting protein degradation. Therefore, the goal of this study was to evaluate the activation of ER stress and UPR in colonic mucosa of UC patients. Patient and Methods. Transcriptional analysis of ER stress- and UPR-related genes was performed by qPCR from intestinal mucosa of patients with UC. We also performed in situ hybridization (ISH) and immunohistochemistry (IHQ) of PERK/eIF2α and IRE1/Xbp-1 pathways and UPR-related chaperones. Results. We first evaluated inflammatory genes via qPCR, and we observed that all analyzed proinflammatory transcripts were upregulated in UC patients. ISH and IHQ images showed that ER stress is activated via PERK/eIF2α and IRE1/Xbp-1 pathways not only in intestinal epithelial cells but also in cells of the lamina propria of UC colonic mucosa. Transcriptional analysis confirmed that EIF2AK3 was upregulated in UC patients. UPR-related genes, such as ATF3, STC2, and DDIT3, along with the chaperones and cochaperones DNAJC3, CALR, HSP90B1, and HSPA5, were also upregulated in UC patients. In addition, we observed that proapoptotic and autophagy genes (Bax and ATG6L1, respectively) were also upregulated. Conclusion. Our results suggest that ER stress and UPR are indeed activated in UC patients and this may contribute to the chronic inflammatory process seen in UC. The increased apoptosis and autophagy markers further support the activation of these findings once they are activated to counterbalance tissue damage. These findings provide new insights into the molecular mechanisms that maintain UC activity and open new possibilities to attenuate intestinal inflammation.

Schools reopening and the COVID-19 pandemic: a case study from Macaé, Rio de Janeiro, Brazil.

Since the first reported case of COVID-19 in Brazil, the public and private educational system started to close. Up to November 2020, scientific discussions about the return of schooling activities have been rarely performed by the national scientific community and police-makers. The great delay of school returning in Brazil contrasts with successful international strategies of school reopening worldwide and seems counterintuitive with the reopening of non-essential activities. Here, important issues to be considered before and during school reopening are reviewed and discussed. COVID-19 testing is essential to avoid disease spreading, but high cost of individual RT-qPCRs impairs an extensive testing strategy for school returning. To reduce costs and increase the speed of diagnosis, we tested the efficiency of a pooled-sample PCR strategy in a cohort of the educational staff in the city of Macaé/RJ, finding five asymptomatic individuals (0,66%) among the 754 people tested. Thus, a polled-sample PCR testing strategy of the educational staff might prevent infection spreading in schools at a reasonable cost. We discuss how our test strategy could be coupled with internationally recognized safety rules to allow for a safe school return and how countries from different world regions are dealing with educational activities during COVID-19 pandemic.

The Mechanism of Action between Pulsed Radiofrequency and Orthobiologics: Is There a Synergistic Effect?

Radiofrequency energy is a common treatment modality for chronic pain. While there are different forms of radiofrequency-based therapeutics, the common concept is the generation of an electromagnetic field in the applied area, that can result in neuromodulation (pulsed radiofrequency-PRF) or ablation. Our specific focus relates to PRF due to the possibility of modulation that is in accordance with the mechanisms of action of orthobiologics. The proposed mechanism of action of PRF pertaining to pain relief relies on a decrease in pro-inflammatory cytokines, an increase in cytosolic calcium concentration, a general effect on the immune system, and a reduction in the formation of free radical molecules. The primary known properties of orthobiologics constitute the release of growth factors, a stimulus for endogenous repair, analgesia, and improvement of the function of the injured area. In this review, we described the mechanism of action of both treatments and pertinent scientific references to the use of the combination of PRF and orthobiologics. Our hypothesis is a synergic effect with the combination of both techniques which could benefit patients and improve the life quality.

Single-phase CT angiography predicts ASPECTS decay and may help determine when to repeat CT before thrombectomy.

OBJETIVES: Time is relative in large-vessel occlusion acute ischemic stroke (LVO-AIS). We aimed to evaluate the rate of inter-hospital ASPECTS decay in patients transferred from a primary (PSC) to a comprehensive stroke center (CSC); and to identify patients that should repeat computed tomography (CT) before thrombectomy. MATERIALS AND METHODS: This was a retrospective cohort study of consecutive anterior circulation LVO-AIS transferred patients. The rate of ASPECTS decay was defined as (PSC-ASPECTS - CSC-ASPECTS)/hours elapsed between scans. Single-phase CT angiography (CTA) at the PSC was used to classify the collateral score. We compared patients with futile versus useful CT scan re-evaluation. RESULTS: We included 663 patients, of whom 245 (37.0%) repeated CT at a CSC. The median rate of ASPECTS decay was 0.4/h (0.0-0.9). Patients excluded from thrombectomy after a CT scan repeat (n=64) had a median ASPECTS decay rate of 1.18/h (0.83-1.61). Patients with absent collateral circulation had a median rate of 1.51(0.65-2.19). The collateral score was an independent predictor of the ASPECTS decay rate (aß = -0.35; 95%CI -0.45 - -0.19, p<0.001). Age (aOR: 1.04 95% CI 1.02-1.07, p<0.001), NIHSS (aOR: 1.11 95% CI 1.06-1.15, p<0.001), PSC ASPECTS (aOR: 0.74 95% CI 0.60-0.91, p=0.006) and the CTA collateral score (aOR: 0.14 95% CI 0.08-0.22, p<0.001) were independent predictors of the usefulness of a CT scan repeat. CONCLUSIONS: The rate of ASPECTS decay can be predicted by the CTA collateral score, helping in the selection of patients that would benefit from repeating a CT assessment on arrival at the CSC.

SARS-CoV-2 Spatiotemporal Genomic and Molecular Analysis of the First Wave of the COVID-19 Pandemic in Macaé, the Brazilian Capital of Oil.

The SARS-CoV-2 virus infection led to millions of deaths during the COVID-19 pandemic. Hundreds of workers from several other Brazilian cities, as well as from other countries, arrive daily in Macaé to work in the oil supply chain, making this city a putative hotspot for the introduction of new viral lineages. In this study, we performed a genomic survey of SARS-CoV-2 samples from Macaé during the first outbreak of COVID-19, combined with clinical data and a molecular integrative analysis. First, phylogenomic analyses showed a high occurrence of viral introduction events and the establishment of local transmissions in Macaé, including the ingression and spread of the B.1.1.28 lineage in the municipality from June to August 2020. Second, SARS-CoV-2 mutations were identified in patients with distinct levels of COVID-19 severity. Third, molecular interactions of the mutated spike protein from three B.1.1.33 local samples and human ACE2 showed higher interactions than that of the wild-type spike protein from the ancestral virus. Altogether, these results elucidate the SARS-CoV-2 genomic profile in a strategic Brazilian city and further explore the functional aspects of SARS-CoV-2 with a characterization of emerging viral mutations associated with clinical data and the potential targets for drug development against SARS-CoV-2.

[Non-steroidal anti-inflammatory drugs : clarification for the practitioner]. / Anti-inflammatoires non stéroïdiens : mise au point pour le praticien.

NSAID represent a widely used therapeutic class, but their side- effects profile can significantly limit their use. Introduction of selective cyclooxygenase-2 inhibitor has provided an alternative to non-selective NSAIDs, with a better digestive tolerance for similar efficiency. Nevertheless, introduction of these molecules has been associated with emergence of major cardiovascular events, motivating further studies on their safety profile. Numerous adverse effects, mainly gastrointestinal, renal and cardiovascular, have been more clearly characterized. This article intends to review some of the basic principles and main side effects of NSAIDs.

Les anti-inflammatoires non stéroïdiens représentent une classe thérapeutique largement utilisée, mais leurs profils d'effets secondaires peuvent limiter leur utilisation. Le développement des inhibiteurs sélectifs de la cyclo-oxygénase 2 a permis d'offrir une meilleure tolérance digestive pour une efficacité similaire. Néanmoins, ces substances sont associées à une recrudescence d'événements cardiovasculaires majeurs, motivant la réalisation de nouvelles études sur le profil sécuritaire. De nombreux effets indésirables, essentiellement gastro-intestinaux, rénaux et cardiovasculaires, ont dès lors été plus clairement caractérisés. Cet article propose une revue de quelques notions de base et des principaux effets secondaires liés à la prescription d'AINS.

Aerobic training prevents cardiometabolic changes triggered by myocardial infarction in ovariectomized rats.

This study aimed to evaluate the impact of aerobic training (AT) on autonomic, cardiometabolic, ubiquitin-proteasome activity, and inflammatory changes evoked by myocardial infarction (MI) in ovariectomized rats. Female Wistar rats were ovariectomized and divided into four groups: sedentary + sham (SS), sedentary + MI (SI), AT + sham surgery (TS), AT + MI (TI). AT was performed on a treadmill for 8 weeks before MI. Infarcted rats previously subjected to AT presented improved physical capacity, increased interleukin-10, and decreased pro-inflammatory cytokines. Metabolomic analysis identified and quantified 62 metabolites, 9 were considered significant by the Vip Score. SS, SI, and TS groups presented distinct metabolic profiles; however, TI could not be distinguished from the SS group. MI dramatically increased levels of dimethylamine, and AT prevented this response. Our findings suggest that AT may be useful in preventing the negative changes in functional, inflammatory, and metabolic parameters related to MI in ovariectomized rats.

Chikungunya virus produced by a persistently infected mosquito cell line comprises a shorter genome and is non-infectious to mammalian cells.

Although RNA viruses have high mutation rates, host cells and organisms work as selective environments, maintaining the viability of virus populations by eliminating deleterious genotypes. In serial passages of RNA viruses in a single cell line, most of these selective bottlenecks are absent, with no virus circulation and replication in different tissues or host alternation. In this work, Aedes aegypti Aag-2 cells were accidentally infected with Chikungunya virus (CHIKV) and Mayaro virus (MAYV). After numerous passages to achieve infection persistency, the infectivity of these viruses was evaluated in Ae. albopictus C6/36 cells, African green monkey Vero cells and primary-cultured human fibroblasts. While these CHIKV and MAYV isolates were still infectious to mosquito cells, they lost their ability to infect mammalian cells. After genome sequencing, it was observed that CHIKV accumulated many nonsynonymous mutations and a significant deletion in the coding sequence of the hypervariable domain in the nsP3 gene. Since MAYV showed very low titres, it was not sequenced successfully. Persistently infected Aag-2 cells also accumulated high loads of short and recombinant CHIKV RNAs, which seemed to have been originated from virus-derived DNAs. In conclusion, the genome of this CHIKV isolate could guide mutagenesis strategies for the production of attenuated or non-infectious (to mammals) CHIKV vaccine candidates. Our results also reinforce that a paradox is expected during passages of cells persistently infected by RNA viruses: more loosening for the development of more diverse virus genotypes and more pressure for virus specialization to this constant cellular environment.

The regenerative mechanisms of platelet-rich plasma: A review.

Orthobiologics continue to gain popularity in many areas of medical science, especially in the field of regenerative medicine. Platelet-rich plasma derivatives are orthobiologic tools of particular interest. These biologic products can be obtained via centrifugation of a patient's whole blood and the components can then be subsequently isolated, concentrated and ultimately administered into injured tissues, particularly in areas where standard healing is disrupted. The elevated concentration of platelets above the basal value enables accelerated growth of various tissues with minimal side effects. The application of autologous orthobiologics is a relatively new biotechnology undergoing expansion which continues to reveal optimistic results in the stimulation and enhanced healing of various sorts of tissue injuries. The local release of growth factors and cytokines contained in platelet alpha granules accelerates and ameliorates tissue repair processes, mimicking and supporting standard wound healing. This effect is greatly enhanced upon combination with the fibrinolytic system, which are essential for complete regeneration. Fibrinolytic reactions can dictate proper cellular recruitment of certain cell populations such as mesenchymal stem cells and other immunomodulatory agents. Additionally, these reactions also control proteolytic activity in areas of wound healing and regenerative processes of mesodermal tissues including bone, cartilage, and muscle, which makes it particularly valuable for musculoskeletal health, for instance. Although many investigations have demonstrated significant results with platelet-rich plasma derivatives, further studies are still warranted.