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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.)

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.)

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.)

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.)

Proinflammatory microenvironmental is crucial for the Human Immunodeficiency Virus Type 1 (HIV-1) pathogenesis. The viral glycoprotein 120 (gp120) must interact with the CD4+ T cell chemokine receptor (CCR5) and a co-receptor C-X-C chemokine receptor type 4 (CXCR4) to let the virus entry into the host cells. However, the interaction of the viral particle with other cell surface receptors is mandatory for its attachment and subsequently entry. Tumor Necrosis Factor receptor type I (TNFR1), type II (TNFR2) and Fas are a superfamily of transmembrane proteins involved in canonical inflammatory pathway and cell death by apoptosis as responses against viral pathogens. In our study, we performed an in silico evaluation of the molecular interactions between viral protein gp120 and TNF receptors (TNFR1, TNFR2 and Fas). Protein structures were retrieved from Protein Databank (PDB), and Molecular Docking and dynamics were performed using ClusPro 2.0 server and GROMACS software, respectively. We observed that gp120 is able to bind TNFR1, TNFR2 and Fas receptors, although only the TNFR2-gp120 complex demonstrated to produce a stable and durable binding. Our findings suggest that gp120 may act as an agonist to TNF-α and also function as an attachment factor in HIV-1 entry process. These molecular interaction by gp120 may be the key to HIV-1 immunopathogenesis. In conclusion, gp120 may stimulate pro-inflammatory and apoptotic signaling transduction pathways mediated by TNFR2 and may act as an attachment factor retaining HIV-1 viral particles on the host cell surface., (Copyright © 2021 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.)

Zika virus (ZIKV) is an enveloped, mosquito-borne Flavivirus, which infects cells through clathrin-mediated endocytosis and fusion employing acidic endosomes. Cell entry is mostly mediated by the viral glycoprotein E, although incomplete particle maturation enables viral protein prM and anionic lipids present in the viral membrane to mediate this process. Incomplete proteolytic maturation results in a set of highly heterogeneous particles. These heterogeneous and dynamic infectious particles offer a variety of possible receptor interaction sites on their surfaces, thus contributing to the wide range of cells susceptible to ZIKV as well as to variation in tissue tropism. This review addresses recent advances in the understanding of ZIKV entry process into cells and put together fundamental questions about viral replication, maturation and host-cell interactions., (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.)

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.

Background: Host restriction factors are cellular proteins able to diminish or block viral replication in a cell-specific way., Objective and Method: We evaluated the distribution of single nucleotide polymorphisms (SNPs) in APOBEC3G (rs3736685, rs2294367) and CUL5 (rs7117111, rs7103534, rs11212495) genes, among 264 HIV-1 infected (HIV-1+) and 259 unexposed- uninfected individuals from Northeast Brazil, looking for a possible association with susceptibility to HIV-1 infection, viral load during treatment, CD4+ T cell count and therapeutic success of the antiretroviral treatment., Results: The rs11212495 CUL5 G allele and the CUL5 rs7103534-rs7117111 CG haplotype were more frequent among unexposed-uninfected than in HIV-1+ individuals, suggesting an association with a lower HIV-1 infection susceptibility. The APOBEC3G rs2294367 G/C genotype correlated with delayed viral load suppression. Our results showed a great heterogeneity in relation to the literature findings, possibly due to ethnic differences among the studied populations, sample size used in the studies and, also, to the type of controls, i.e. in our study used unexposed-uninfected rather than exposed-uninfected individuals (rare and considered gold standard for susceptibility studies)., Conclusion: Our findings report genetic variants possibly associated with susceptibility to HIV-1 infection (CUL5 rs11212495, rs7103534, rs7117111) and partial viral load control (APOBEC3G rs2294367). Replica studies performed on higher number of subjects are envisaged to confirm our results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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 CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03-0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02-0.04) and 4% (95%-CI, 0.03-0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta-analysis study that provides a descriptive study of the distribution of CCR5-delta32 allele in Brazilian population., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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.

This study aims to comprehensively analyze human leucocyte antigen (HLA)-G polymorphisms association with susceptibility to systemic lupus erythematosus (SLE) development and clinical manifestations. The HLA-G 5' upstream regulatory region (URR), 3' untranslated region (UTR) and a cytosine deletion at exon 3 (ΔC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c extended HLA-G allele were significantly more frequent in SLE patients than healthy controls (+3003C allele frequency: 12% in SLE patients vs 6% in controls; odds ratio (OR), 2.10, 95% confidence interval (CI), 1.06-4.28, P = 0.026; HG010101c frequency: 11.8% in SLE patients and 6.3% in controls; OR, 2.14, 95% CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease development. Other polymorphisms were associated with different clinical manifestations. Although HLA-G role in SLE disease is far from being elucidated yet, our association study results along with a systematic review and meta-analysis suggest that HLA-G might be able to slightly modulate the complex SLE phenotype (pooled OR, 1.14, 95% CI, 1.02-1.27, P = 0.021)., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Here we review the prevalence of HIV-1 primary drug resistance in Latin America and Caribbean using meta-analysis as well as time-series modeling. We also discuss whether there could be a drawback to HIV/AIDS programs due to drug resistance in Latin America and Caribbean in the next years. We observed that, although some studies report low or moderate primary drug resistance prevalence in Caribbean countries, this evidence needs to be updated. In other countries, such as Brazil and Argentina, the prevalence of drug resistance appears to be rising. Mutations conferring resistance against reverse transcriptase inhibitors were the most frequent in the analyzed populations (70% of all mutational events). HIV-1 subtype B was the most prevalent in Latin America and the Caribbean, although subtype C and B/F recombinants have significant contributions in Argentina and Brazil. Thus, we suggest that primary drug resistance in Latin America and the Caribbean could have been underestimated. Clinical monitoring should be improved to offer better therapy, reducing the risk for HIV-1 resistance emergence and spread, principally in vulnerable populations, such as men who have sex with men transmission group, sex workers and intravenous drug users.

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.

Coumarin is a compound known to be present in a wide variety of plants, microorganisms and animal species. Most of its effects were studied in organs and systems other than the central nervous system. The present work evaluated the effect of coumarin administration on the levels of gamma-aminobutyric acid (GABA), glutamate (GLU), glycine (GLY) and taurine (TAU) in the prefrontal cortex and hippocampus of mice. Male Swiss mice were treated with distilled water (controls), coumarin (20 or 40 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Results showed that in the prefrontal cortex, coumarin at the lowest dose increased the levels of GLU and TAU, while GABA increased with both doses studied and GLY had its levels increased only at the dose of 40 mg/kg. Diazepam (DZP) increased the levels of GABA and TAU and decreased the levels of GLU and GLY in this area. In the hippocampus, only glutamate had its levels decreased after coumarin treatment, while diazepam increased the levels of GABA and TAU and decreased the levels of GLU in this brain region. We concluded that coumarin stimulates the release of endogenous amino acids, increasing the levels of inhibitory and excitatory amino acids in the prefrontal cortex, and decreasing glutamate levels in the hippocampus. Together, these results are of interest, considering that some neurodegenerative diseases and seizures are related to the imbalance of the amino acid levels in the CNS suggesting a perspective of a therapeutic use of coumarins in these disorders.