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Pyoderma gangrenosum (PG) is a rare inflammatory skin disease classified within the spectrum of neutrophilic dermatoses. The pathophysiology of PG is yet incompletely understood but a prominent role of genetics facilitating immune dysregulation has been proposed. This study investigated the potential contribution of disrupted molecular pathways in determining the susceptibility and clinical severity of PG. Variant Enrichment Analysis, a bioinformatic pipeline applicable for Whole Exome Sequencing data was performed in unrelated PG patients. Eleven patients were enrolled, including 5 with unilesional and 6 with multilesional PG. Fourteen pathways were exclusively enriched in the "multilesional" group, mainly related to immune system (i.e., type I interferon signaling pathway), cell metabolism and structural functions. In the "unilesional" group, nine pathways were found to be exclusively enriched, mostly related to cell signaling and cell metabolism. Genetically altered pathways involved in immune system biology and wound repair appear to be nodal pathogenic drivers in PG pathogenesis., (© 2023. The Author(s).)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin's physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tricarico, Gratton, Santos-Silva, Moura, Ura, Sommella, Campiglia, Del Vecchio, Moltrasio, Berti, D’Adamo, Elsherbini, Staudenmaier, Chersi, Boniotto, Krismer, Schittek and Crovella.)

Titanium is usually used in the manufacturing of metal implants due to its biocompatibility and high resistance to corrosion. A structural and functional connection between the living bone and the surface of the implant, a process called osseointegration, is mandatory for avoiding prolonged healing, infections, and tissue loss. Therefore, osseointegration is crucial for the success of the implantation procedure. Osseointegration is a process mediated by bone-matrix progenitor cells' proteins, named integrins. In this study, we used an in silico approach to assemble and test peptides that can be strategically used in sensitizing TiO 2 implants in order to improve osseointegration. To do so, we downloaded PDB structures of integrins α5β1, αvβ3, and αIIbβ3; their biological ligands; and low-cost proteins from the Protein Data Bank, and then we performed a primary (integrin-protein) docking analysis. Furthermore, we modeled complex peptides with the potential to bind to the TiO 2 surface on the implant, as well as integrins in the bone-matrix progenitor cells. Then we performed a secondary (integrin-peptide) docking analysis. The ten most promising integrin-peptide docking results were further verified by molecular dynamics (MD) simulations. We recognized 82 peptides with great potential to bind the integrins, and therefore to be used in coating TiO 2 implants. Among them, peptides 1 (GHTHYHAVRTQTTGR), 3 (RKLPDATGR), and 8 (GHTHYHAVRTQTLKA) showed the highest binding stability during the MD simulations. This bioinformatics approach saves time and more effectively directs in vitro studies., Competing Interests: The authors declare no conflict of interest.

The variant enrichment analysis (VEA), a recently developed bioinformatic workflow, has been shown to be a valuable tool for whole-exome sequencing data analysis, allowing finding differences between the number of genetic variants in a given pathway compared to a reference dataset. In a previous study, using VEA, we identified different pathway signatures associated with the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic radiation therapy. Here, we used VEA to discover novel pathways altered in individuals exposed to asbestos who developed or not asbestos-related diseases (lung cancer or mesothelioma). A population-based autopsy study was designed in which asbestos exposure was evaluated and quantitated by investigating objective signs of exposure. We selected patients with similar exposure to asbestos. Formalin-fixed paraffin-embedded (FFPE) tissues were used as a source of DNA and whole-exome sequencing analysis was performed, running VEA to identify potentially disrupted pathways in individuals who developed thoracic cancers induced by asbestos exposure. By using VEA analysis, we confirmed the involvement of pathways considered as the main culprits for asbestos-induced carcinogenesis: oxidative stress and chromosome instability. Furthermore, we identified protective genetic assets preserving genome stability and susceptibility assets predisposing to a worst outcome.

The present study assessed the identification of animal and object hoarding disorder cases by contact and mapping and the presence of animal protection programs in association with seven social-economic indicators of the metropolitan area of the ninth-biggest metropolitan area of Brazil. City Secretaries of Health and Environment provided demographic information and responded to a questionnaire. Overall, a very high level of hoarding case identification per municipality was associated with a higher Human Development Index, population, density, and income and related to distance from Curitiba, the capital of Parana State. Low and very low levels of hoarding case identification were related to greater area, higher Social Vulnerability Index (SVI), inequality, illiteracy, and rural areas. Very high identification level of animal protection programs was also associated with higher HDI, density and population, urban area, and high income, and geographical area. Similarly, low and very low levels of animal protection programs identification were major explained by low income, illiteracy, and distance related to higher population, urbanization, and higher HDI. In summary, better identification of hoarding cases and animal protection programs have shown an association with better socioeconomic indicators and higher population, density, and urban area. Whether municipalities with better human socioeconomic indicators may stimulate society's demands for identification of cases of individuals with hoarding disorder and animal programs should be further established. Regardless, animal health and welfare have been associated with improving human quality of life in a major Brazilian metropolitan area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Moura, de Castro, Farinhas, da Cunha, Pegoraro, Kmetiuk, dos Santos and Biondo.)

Animals can eavesdrop on other competitors during territorial defense disputes to better choose rivals weaker than themselves and increase the chances of monopolizing resources. In dragonflies, males often compete for access to water bodies, which attract sexually receptive females to mate and lay eggs. During the breeding season, satellite males can observe fights between territory owners and intruders and, therefore, obtain information about potential rivals through visual cues. Consequently, weaker competitors may face more intense competition than stronger ones when defending a territory. In this study, we conducted field experiments with the dragonfly Erythrodiplax fusca to investigate whether eavesdropping on territorial disputes, using visual cues, affects the intensity of competition that territory owners face. We recorded the number of intruders that engage in disputes against males that recently occupied territories in two groups: the "eavesdropping" group (i.e., individuals with access to rivals' prior information) and the control group (i.e., competitors with no access to prior information). The number of intruders was greater in the eavesdropping group compared to the control group. This effect depended on the interaction between the size of the territory owners and the presence of eavesdropping. The number of intruders decreased with increase in the size of the owners in the presence of eavesdropping, but this relationship did not occur in the control group. We discuss the implications of our findings for the male decision-making process to initiate agonistic disputes and how investigating eavesdropping behavior can improve current models of conflict resolution in animals., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Zika virus (ZIKV) is an enveloped, single-stranded RNA arbovirus belonging to the genus Flavivirus. It was first isolated from a sentinel monkey in Uganda in 1947. More recently, ZIKV has undergone rapid geographic expansion and has been responsible for outbreaks in Southeast Asia, the Pacific Islands, and America. In this review, we have highlighted the influence of viral genetic variants on ZIKV pathogenesis. Two major ZIKV genotypes (African and Asian) have been identified. The Asian genotype is subdivided into Southwest Asia, Pacific Island, and American strains, and is responsible for most outbreaks. Non-synonymous mutations in ZIKV proteins C, prM, E, NS1, NS2A, NS2B, NS3, and NS4B were found to have a higher prevalence and association with virulent strains of the Asian genotype. Consequently, the Asian genotype appears to have acquired higher cellular permissiveness, tissue persistence, and viral tropism in human neural cells. Therefore, mutations in specific coding regions of the Asian genotype may enhance ZIKV infectivity. Considering that mutations in the genomes of emerging viruses may lead to new virulent variants in humans, there is a potential for the re-emergence of new ZIKV cases in the future.

The challenge of unravelling the molecular basis of multifactorial disorders nowadays cannot rely just on association studies searching for potential causative variants shared by groups of patients and not present in healthy individuals; indeed, association studies have as a main limitation the lack of information on the interactions between the disease-causing variants. Thus, new genomic analysis tools focusing on disrupted pathways rather than associated gene variants are required to better understand the complexity of a disease. Therefore, we developed the Variant Enrichment Analysis (VEA) workflow, a tool applicable for whole exome sequencing data, able to find differences between the numbers of genetic variants in a given pathway in comparison with a reference dataset. In this study, we applied VEA to discover novel pathways altered in patients with complex autoinflammatory skin disorders, namely PASH ( n = 9), 3 of whom are overlapping with SAPHO) and PAPASH ( n = 3). With this approach we have been able to identify pathways related to neutrophil and endothelial cells homeostasis/activations, as disrupted in our patients. We hypothesized that unregulated neutrophil transendothelial migration could elicit increased neutrophil infiltration and tissue damage. Based on our findings, VEA, in our experimental dataset, allowed us to predict novel pathways impaired in subjects with autoinflammatory skin disorders.

One Health has been defined as a comprehensive approach to human, animal, and environmental health, but unsuccessful in providing a specific index for city, state, or country assessment. Accordingly, the present study aimed to calculate the One Health Index (OHI) in 29 cities of the Curitiba metropolitan area, the ninth largest in Brazil. Animal and Environmental health indicators were obtained from the city secretary of environment. The social vulnerability index (SVI) was used as the overall human health indicator. The indicators were parameterized following a binary logic Principal component analysis (PCA) was applied in association with city population, per capita income, and distance from the capital Curitiba. Permutational multivariate analysis of variance (PERMANOVA) was applied using the three first coefficients of the principal components obtained from Principal Component Analysis Plot (PCA) and exploring a pairwise comparison between the scenario ranges. A value of p less than 0.05 was considered significant. Overall, a higher OHI was associated with a higher city population and income, and shorter distance from the capital, and tendency of low-income cities to present lower OHI compared to higher-income cities. In conclusion, the OHI proposed herein portrays a holistic representation of a city's overall health. Moreover, animal issues should be considered part of local to global sustainability, considering OHI to calculate sustainability indexes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Crovella, Revelant, Muraro, Moura, Brandão, Trovò, Steffan, Zacchi, Zabucchi, Minatel and Borelli.)

Orb-webs show diversity in several traits, including silk types, architecture, physical properties, locale, and period of exposition. The investigation of how they determine the identity of intercepted prey is important to functional ecology and to the evaluation of trophic niche partitioning within communities. However, the influence of several of these variables on the composition of intercepted insects remains to be determined. In this study, we evaluated the effects of web architectural traits, height, and daily periods of exposition on the interception of different insects in terms of sizes, masses, and taxa. We conducted observations of prey intercepted by the orb webs of 16 sympatric spider species and artificial webs. We found that all orb webs mainly intercepted small and light insects, sharing the most abundant insect families found in the study area. However, spiders that show nocturnal activity, more radii in their webs, large and high webs captured heavier insects. Other orb-web traits, such as the density of capture threads did not influence the kind of intercepted insects. We discuss why some variables affected prey interceptions in terms of mass. Finally, we discuss the implications of these influential variables to functional ecology, niche differentiation, and how behavioral assessments can complete this investigation in future studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co-activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (-168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations., (© 2021 John Wiley & Sons Ltd.)

Kleptoparasitism is assumed to be the main foraging strategy in some animal groups, such as the spiders of the subfamily Argyrodinae (Theridiidae). However, some species may also feed on silk threads, egg sacs, or even their hosts. The conditions determining these alternative foraging tactics remain unknown for most species. We performed field observations, stable isotope analysis and laboratory experiments to investigate kleptoparasitism and araneophagy of Argyrodes elevatus and Faiditus caudatus in webs of Manogea porracea (Araneidae). We evaluated the following hypotheses: (1) both species exhibit higher trophic positions than their hosts and closest to an araneophagic sympatric species; (2) host web selection is influenced by the presence of alternative resources (adult male and female, and egg sacs); and (3) they preferentially consume egg sacs instead of stored prey items. Both argyrodines showed higher trophic positions than their female hosts and closest to an araneophagic spider species. The invaders were found mainly on host webs with one adult and egg sacs and with egg sacs only. Finally, A. elevatus preferred to feed on prey captured by the host spider instead of egg sacs. We discussed the factors that can potentially determine the choices between foraging exclusively as kleptoparasites and consuming the hosts., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Trophobiotic interactions occur when phytophagous insects provide a sugary liquid, the honeydew, for ants and obtain defence against predators or parasitoids. The plants may indirectly benefit from an increased ant foraging activity by reducing the herbivorous abundance. These three trophic interactions have been previously studied for several species, but mainly involving plants with extrafloral nectaries, which is a plant structure that also produce attractive substances for ants. Previous studies have reported an ant preference for honeydew over extrafloral nectary content. Therefore, trophobiosis can be an important mediator of ant-plant interactions. In this study, we describe a trophobiotic interaction between Edessa contermina stink bugs and Camponotus blandus ants on the Byrsonima verbascifolia plants occurring in a conservation area of Brazilian savanna. Stink bugs excreted a sugary liquid which was consumed by the ants, and C. blandus ants were observed consuming potential parasitoids. Stink bugs were more abundant in plants containing high food supply and shelter availability. The occurrence of ants depended of the number of inflorescences and trunk circumference of B. verbascifolia. Ant abundance, however, was positively correlated with stink bug abundance and the number of inflorescences. Herbivory was not explained by neither plant architecture nor ant abundance. This high ant activity may benefit plants from a protection against herbivory, but we did not detect this effect during the study period. Hence, the interaction among ants and plants was apparently commensal. We concluded that plant traits were important in ant attraction, but stink bugs foraging also increased ant activity on the plant, but mainly on inflorescences. Therefore, the plant may benefit from an increased defence of inflorescences rather than leaves., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The human immunodeficiency virus (HIV-1) causes a progressive depletion of CD4+ T cells, hampering immune function. Current experimental strategies to fight the virus focus on the reactivation of latent HIV-1 in the viral reservoir to make the virus detectable by the immune system, by searching for latency reversal agents (LRAs). We hypothesize that if common molecular pathways elicited by the presence of LRAs are known, perhaps new, more efficient, "shock-and-kill" strategies can be found. Thus, the objective of the present study is to re-evaluate RNA-Seq assays to find differentially expressed genes (DEGs) during latency reversal via transcriptome analysis. We selected six studies (45 samples altogether: 16 negative controls and 29 LRA-treated CD4+ T cells) and 11 LRA strategies through a systematic search in Gene Expression Omnibus (GEO) and PubMed databases. The raw reads were trimmed, counted, and normalized. Next, we detected consistent DEGs in these independent experiments. AZD5582, romidepsin, and suberanilohydroxamic acid (SAHA) were the LRAs that modulated most genes. We detected 948 DEGs shared by those three LRAs. Gene ontology analysis and cross-referencing with other sources of the literature showed enrichment of cell activation, differentiation and signaling, especially mitogen-activated protein kinase ( MAPK ) and Rho-GTPases pathways.

Before using estimators, it is essential to consider their efficiency in order to avoid bias in results. Due to the architectural and structural complexity of spider webs, some important variables involved in prey capture are usually estimated based on a few measurements obtained from photographs. One of these variables is the capture thread length (CTL), which can provide valuable information on foraging behaviours and the energetic investment in prey capture. However, many of the webs found in the field are damaged, and there is no automatic method to measure the CTL. Therefore, the determination of a simple and accurate estimator of this variable is important to several studies involving spider foraging strategies. In this study, we assessed the accuracy of traditional and new CTL estimators and their vulnerability to web shape and asymmetry. Our results validated the accuracy of the previous estimators. However, we also presented a simple new estimator that can be even more accurate, irrespective of whether the webs exhibit circular shapes or asymmetry in thread investment between superior and inferior web parts. Moreover, we presented an accurate CTL estimator for non-circular orb webs, for which the traditional ones are not applicable., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Zika virus (ZIKV) has spread globally and has been linked to the onset of microcephaly and other brain abnormalities. The ZIKV genome consists of an ~10.7 kb positive-stranded RNA molecule that encodes three structural (C, prM and E) and seven nonstructural (5'-NS1-NS2A-NS2B-NS3- NS4A/2K-NS4B-NS5-3') proteins. In this work, we looked for genetic variants in 485 ZIKV complete genomes from GenBank (NCBI) and performed a computational systematic approach using MAESTROweb server to assess the impact of nonsynonymous mutations in ZIKV proteins (C, M, E, NS1, NS2A, NS2B-NS3 protease, NS3 helicase and NS5). Then, we merged the data and correlated it with the phenotypic reports of ZIKV circulating strains. The sensitivity profile of the proteins showed 96 mutational hotspots. We found 22 relevant mutations in proteins C (I80T), NS2A (I34M/T/V, I45V, I80T/V, L113F, A117V, I118V, L128P, V143A, T151A, M199I/V, R207K and L208I) and NS3 helicase (D436G, Y498H, R525K, Q528R and R583K) of the circulating strains. Our analysis exploited the impact of nonsynonymous mutations on ZIKV proteins, their structural and functional insights. The results presented here could advance our current understanding on ZIKV proteins functions and pathogenesis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Dihydropyridines (DHPs) obtained from Hantzsch multicomponent reactions are an important pharmaceutical class of compounds marketed as antihypertensive (e.g., nifedipine, nitrendipine, and amlodipine) drugs. This study synthesized new symmetrical and unsymmetrical long-chain fatty DHPs using multicomponent reactions under metal-free conditions with sulfamic acid as a catalyst. The DHPs were tested for antioxidant activity using three different methods. The insertion of a long chain into the DHP core contributed to antioxidant potential, and compounds derived from nitro aldehydes have better antioxidant potential than the antihypertensive drug nifedipine. In addition, fatty analogs to nifedipine derived from palmitic and oleic chains showed similar antioxidant activity to the common standards butylated hydroxytoluene and vitamin E. These results showed that our new synthesized products may find novel applications as antioxidant additives or for tools for use in drug discovery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated., Objective: To identify predictive genetic markers of immune response to ART., Methods: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure., Results: Male patients were overrepresented in non-responder group (p=0.01). Non-responders also started with lower absolute CD4+ T cell counts (p<0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p=0.04), rs1128503 (ABCB1) A allele (p=0.03) and rs707265 (CYP2B6) A allele (p=0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p=0.004) and rs4646437 (CYP3A4) A allele (p=0.04)., Conclusion: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response., (Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Non-compressible torso hemorrhage (NCTH) remains a significant cause of morbidity and mortality in the field of trauma and emergency medicine. In recent times, there has been a resurgence in the adoption of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for patients who present with NCTH. Like all medical procedures, there are benefits and risks associated with the REBOA technique. However, in the case of REBOA, these complications are not unanimously agreed upon with varying viewpoints and studies. This article aims to review the current knowledge surrounding the complications of the REBOA technique at each step of its application., Competing Interests: Ethics approval was not required for this review.Dr. Megan Brenner is a Clinical Advisory Board Member––Prytime Medical Inc. All other authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

In a current scenario where trauma injury and its consequences account for 9% of the worlds causes of death, the management of non-compressible torso hemorrhage can be problematic. With the improvement of medicine, the approach of these patients must be accurate and immediate so that the consequences may be minimal. Therefore, aiming the ideal method, studies have led to the development of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This procedure has been used at select trauma centers as a resuscitative adjunct for trauma patients with non-compressible torso hemorrhage. Although the use of this technique is increasing, its effectiveness is still not clear. This article aims, through a detailed review, to inform an updated view about this procedure, its technique, variations, benefits, limitations and future.

Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies., Competing Interests: The authors declare no conflict of interest.

The objective of this study was to evaluate the effects of diode laser and a desensitizing dentifrice on dentin permeability. Fifty-two root dentin fragments were obtained (5 × 5mm) and treated with 24% EDTA gel. The samples were divided into 4 groups (n = 13): G1, control (no treatment); G2, diode laser (λ = 908 nm, 1.5 W, continuous mode, 20s); G3, application of abrasive dentifrice for 1 minute (Elmex Sensitive Professional (International Gaba); and G4, application of abrasive dentifrice for 1 minute followed by irradiation with diode laser. Ten samples per group were immersed in 2% methylene blue solution for 4h. The specimens were washed, longitudinally sectioned, observed under optical microscopy, photographed and assessed based on the degree of dye leakage. The remaining samples were observed under scanning electron microscopy (SEM). The leakage data were subjected to ANOVA test, followed by Tukey's t-test (α = 5%). Groups 2, 3 and 4 showed less dye penetration than the control group (p < 0.05), but were similar among each other. SEM images showed that dentinal tubules were open in G1, and fused and occluded in G2. Group 3 showed dentinal tubules that were occluded by the metal ions from the toothpaste. G4 presented similar characteristics to G3, and the presence of fused dentin. The diode laser and the dentifrice were effective in reducing dentinal permeability, and the combination of the two treatments did not show better results than either one used alone.

Human leukocyte antigen (HLA)-G is a key tolerogenic molecule mainly expressed in the placenta and is crucial for implantation of the embryo and immunological tolerance of the fetus during pregnancy. However, under pathological conditions, such as cancer or viral infections, HLA-G can be expressed in other tissues. The gene coding for HLA-G (HLA-G, chromosome 6p21.3) presents numerous polymorphisms, some of them influencing its expression. One of the most studied, is the 14 bp ins/del (rs371194629) situated at the 3'-UTR of the gene. The insertion is thought to stabilize HLA-G mRNA. Different studies have analyzed the role of rs371194629 in hepatic injury, with either hepatotropic virus infection (i.e., HBV or HCV) or hepatocellular carcinoma (also induced by viral infection). Results from these studies are heterogeneous, differing with ethnicity and population age, and the role of rs371194629 is unclear. For these reasons, we decided to perform a meta-analysis of these results, concluding that the 14-bp ins/del polymorphism does not significantly contribute to hepatic injury., Competing Interests: The authors declare no conflict of interest.

Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals., Competing Interests: The authors declare no conflict of interest.

Purpose: To evaluate the effect of the aqueous extract of the Vigna angularis, popularly known as "Azuki beans", in rats subjected to an experimental model of moderate chronic kidney disease., Methods: Thirty rats underwent two surgeries - Ormrod and Miller (1980) - to obtain Moderate Chronic Kidney Disease (CKD-M). The animals were randomized into 3 groups. Group 1 (Control): distilled water. Group 2 (Azuki): Vigna angularis 5% aqueous extract. Group 3 (Treatment): 10mg/kg of enalapril maleate. The rats received their respective treatments for 14 days., Results: The treatment with azuki beans produced an increase in urine output from the second day until the end of the experiment compared to the Control groups (p<0.01) and Treatment (p<0.05). The treatment with azuki also produced significant reductions in the levels of glucose, triglycerides, VLDL, uric acid, Alanine aminotransferase (p<0.05), urea and serum creatinine (p<0.01), besides having produced a significant increase in the levels of HDL when compared to the Control group., Conclusion: Treatment with Azuki beans produced improvements in the parameters of renal function and significantly reduced glucose levels, triglycerides, VLDL, alanine aminostransferase, uric acid and creatinine, besides having produced a significant increase in the levels of HDL in rats submitted to a model of moderate chronic kidney disease.

NRLP1 (rs12150220, rs9889625, rs9900356, rs6502867, rs2670660) and NLRP3 (rs35829419, rs10754558) polymorphisms have been analyzed in 69 subjects with documented asbestos exposure and death for malignant pleural mesothelioma and 59 patients with documented asbestos exposure but death for other causes, all from a North East Italy. No association was found between NLRP1 and NLRP3 polymorphisms and susceptibility to develop mesothelioma using the general, dominant or recessive models. Also haplotype analysis did not reveal any significant association with mesothelioma. Our findings, being controversial with respect to another study on Italian patients, do suggest the need of further studies to unravel the contribution of NLRP1 and NLRP3 in susceptibility to mesothelioma.

Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the number of inhabitants. We examined the allele frequencies of 13 short tandem repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau of Investigation and commonly used in forensic genetics laboratories in Brazil, in a sample of 609 unrelated individuals from all geographic regions of Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant differences for any loci analyzed were observed compared with other publications in other various regions of Brazil. Most of the markers observed were in Hardy-Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles 35.1 and 39 (locus D21S11), also described in a single study of the Brazilian population, was observed. The other forensic parameters analyzed (matching probability, power of discrimination, polymorphic information content, paternity exclusion, complement factor I, observed heterozygosity, expected heterozygosity) indicated that the studied markers are very informative for human forensic identification purposes in the Pernambuco population.

Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time.

The human beta defensin 1 (hBD-1) antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV). In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5'UTR and c.*5G>A and c.*87A>G in the 3'UTR) in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs) and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed beta defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.

A significant number of deaths in trauma occurs days to weeks after the initial injury, being caused by infection and organ failure related to hypercatabolism and consequent acute protein malnutrition. Nutritional therapy should be planned and included with other routines of resuscitation for patients with multiple trauma and severe burns. The rapid acquisition of a route for nutritional support is important to start early nutritional therapy within 48 hours of care. The enteral route is the preferred option in traumatized postoperative patients but the parenteral route should be prescribed when enteral feeding is contraindicated or inadequate. After the initial measures dictated by ATLS, synthesized in the A (airway), B (breathing), C (circulation), D (disability) and E (exposure), we include the letter F (feed) to emphasize the importance of early nutritional care in trauma.

In order to produce transgenic goats with hG-CSF, a total of 24 adult Saanen and 48 adult undefined breed goats were used as donors and recipients, respectively. Donors were estrus-synchronized with vaginal sponges and superovulated by a treatment with 200 mg FSH given twice daily in decreasing doses over 3 days starting 48 h before sponge removal. Ovulation was induced by injecting 100 microg GnRH 36 h after sponge removal. The recipients also received an estrus synchronization treatment. Donors were mated with fertile Saanen bucks and, approximately 72 h after sponge removal, zygotes were recovered surgically by flushing oviducts. The recovered zygotes were briefly centrifuged to a reliable visualization of the pronuclei. The DNA construct containing hG-CSF gene flanked by goat and bovine alphas1-casein sequences was injected into pronuclei of 129 zygotes. The microinjected embryos (3-6 per female) were transferred to 27 recipients. Ten recipients became pregnant and 12 kids were born. One transgenic male founder was identified in the group of kids. This is the first report of a birth of a transgenic goat in Latin America.