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The attempt of this paper is to find an empirical relationship between Foreign Direct Investment and New Firms (Paid up Capital) and Gross Capital Formation (proxy for business growth) and Credit to Commercial Sector and Gross Capital Formation using the test of stationarity (ADF, PP, and KPSS methods), Johansen Cointegration and Granger’s Causality. The results show that FDI crowds out creation of new firms and capital formation and it is the Credit flow to the commercial sector that causes Gross Capital Formation at current price. It shows domestic flow of credit is more influential in capital formation rather than foreign capital inflow.

Thiago Domingues Stocco,1 Tianyi Zhang,2 Edgar Dimitrov,2 Anupama Ghosh,3 Alessandro Marcio Hakme da Silva,1 Wanessa CMA Melo,4 Willian Gonçalves Tsumura,1 André Diniz Rosa Silva,5,6 Gustavo F Sousa,6 Bartolomeu C Viana,6 Mauricio Terrones,2 Anderson Oliveira Lobo6 1Bioengineering Program, Scientific and Technological Institute, Brazil University, São Paulo, SP, Brazil; 2Pennsylvania State University, University Park, PA, USA; 3Department of Chemical and Materials Engineering (DEQM), Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil; 4FTMC, State Research institute Center for Physical Sciences and Technology, Department of Functional Materials and Electronics, Vilnius, Lithuanian; 5FATEC, Ribeirão Preto, SP, Brazil; 6Interdisciplinary Laboratory for Advanced Materials (LIMAV), BioMatLab Group, Materials Science and Engineering Graduate Program, Federal University of Piauí (UFPI), Teresina, PI, BrazilCorrespondence: Anderson Oliveira Lobo, Tel +55 86 981115013, Email lobo.aol@gmail.com; lobo@ufpi.edu.brAbstract: Carbon-based nanomaterials (CBNs) are a category of nanomaterials with various systems based on combinations of sp2 and sp3 hybridized carbon bonds, morphologies, and functional groups. CBNs can exhibit distinguished properties such as high mechanical strength, chemical stability, high electrical conductivity, and biocompatibility. These desirable physicochemical properties have triggered their uses in many fields, including biomedical applications. In this review, we specifically focus on applying CBNs as scaffolds in tissue engineering, a therapeutic approach whereby CBNs can act for the regeneration or replacement of damaged tissue. Here, an overview of the structures and properties of different CBNs will first be provided. We will then discuss state-of-the-art advancements of CBNs and hydrogels as scaffolds for regenerating various types of human tissues. Finally, a perspective of future potentials and challenges in this field will be presented. Since this is a very rapidly growing field, we expect that this review will promote interdisciplinary efforts in developing effective tissue regeneration scaffolds for clinical applications.Keywords: carbon, biomaterial, nanotechnology, tissue engineering, scaffold

Zhongxing Zhang,1 Yves Dauvilliers,2– 4 Giuseppe Plazzi,5,6 Geert Mayer,7 Gert Jan Lammers,8,9 Joan Santamaria,10 Markku Partinen,11 Sebastiaan Overeem,12,13 Rafael del Rio Villegas,14 Karel Sonka,15 Rosa Peraita-Adrados,16 Raphaël Heinzer,17 Aleksandra Wierzbicka,18 Birgit Högl,19 Mauro Manconi,20 Eva Feketeova,21 Antonio Martins da Silva,22 Jitka Bušková,23 Claudio LA Bassetti,24,25 Lucie Barateau,2– 4 Fabio Pizza,5,26 Elena Antelmi,5,6 Jari K Gool,8,9 Rolf Fronczek,8,9 Carles Gaig,10 Ramin Khatami1,24 1Center for Sleep Medicine, Sleep Research and Epileptology, Klinik Barmelweid AG, Barmelweid, Aargau, Switzerland; 2Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, Montpellier, France; 3National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia, and Kleine-Levin Syndrome, Montpellier, France; 4Institute for Neurosciences of Montpellier INM, Univ Montpellier, INSERM, Montpellier, France; 5Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 6IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 7Neurology Department, Hephata Klinik, Schwalmstadt, Germany; 8Sleep Wake Center SEIN Heemstede, Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands; 9Department of Neurology and Clinical Neurophysiology, Leiden University Medical Center, Leiden, the Netherlands; 10Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; 11Helsinki Sleep Clinic, Vitalmed Research Center, Helsinki, Finland; 12Sleep Medicine Center Kempenhaeghe, Heeze, the Netherlands; 13Eindhoven University of Technology, Eindhoven, the Netherlands; 14Neurophysiology and Sleep Disorders Unit, Hospital Vithas Nuestra Señora de América, Madrid, Spain; 15Neurology Department and Centre of Clinical Neurosciences, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 16Sleep and Epilepsy Unit – Clinical Neurophysiology Service, University General Hospital Gregorio Marañón, Research Institute Gregorio Marañón, University Complutense of Madrid, Madrid, Spain; 17Center for Investigation and Research in Sleep, Lausanne University Hospital, Lausanne, Vaud, Switzerland; 18Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland; 19Neurology Department, Sleep Disorders Clinic, Innsbruck Medical University, Innsbruck, Austria; 20Neurology Department, EOC, Ospedale Regionale di Lugano, Lugano, Ticino, Switzerland; 21Neurology Department, Medical Faculty of P. J. Safarik University, University Hospital of L. Pasteur Kosice, Kosice, Slovak Republic; 22Serviço de Neurofisiologia, Hospital Santo António/Centro Hospitalar Universitário do Porto and UMIB-Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; 23Department of Sleep Medicine, National Institute of Mental Health, Klecany, Czech Republic; 24Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 25Department of Neurology, Sechenov First Moscow State University, Moscow, Russia; 26Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyCorrespondence: Yves Dauvilliers, National Reference Network for Narcolepsy, Sleep-Disorders Center, Department of Neurology, Hopital Gui de Chauliac, INSERM U1061, Montpellier, UM1, France, Email ydauvilliers@yahoo.fr Ramin Khatami, Center for Sleep Medicine, Sleep Research and Epileptology, Klinik Barmelweid AG, Barmelweid, CH-5017, Switzerland, Email ramin.khatami@barmelweid.chPurpose: Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990– 2018) and the factors associated with the delay in Europe.Patients and Methods: We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay.Results: The mean age at EDS onset and diagnosis of our patients was 20.9± 11.8 (mean ± standard deviation) and 30.5± 14.9 years old, respectively. Their mean and median diagnostic delay was 9.7± 11.5 and 5.3 (interquartile range: 1.7− 13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤ 2-year) and long (≥ 13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay.Conclusion: Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.Keywords: cataplexy, diagnostic delay, misdiagnosis, symptom onset, machine learning

Gabrielle Messias De Souza, Estevan Rodrigues Dos Santos Neto, Alaor Martins da Silva, Maria Vitoria Minzoni de Souza Iacia, Marcus Vinícius Pimenta Rodrigues, Valéria Cataneli Pereira, Lizziane Kretli Winkelstroter Health Sciences Faculty, University of Western Sao Paulo, Sao Paulo, BrazilCorrespondence: Lizziane Kretli WinkelstroterHealth Sciences Faculty, University of Western Sao Paulo, 700, Jose Bongiovani St, Presidente Prudente, Sao Paulo 19050-920, BrazilTel +55 18 3229-1289Email lizzianekretli@gmail.comIntroduction: Escherichia coli is a Gram-negative opportunistic human pathogen, which has aroused considerable medical interest for being involved in cases of urinary tract infection.Aim: Characterize the E. coli isolated both in the hospital and in the community.Methodology: A total of 200 E. coli isolated in urine samples from hospital and community were evaluated in biofilm formation assay and hydrophobicity MATS method. Antimicrobial susceptibility was performed through agar-diffusion technique. Virulence and ESBL production genes were observed through the polymerase chain reaction amplification of papC, fimH, fliC, kpsMTII, blaTEM, blaCTX-M, blaSHV, and blaOXA.The phylogenetic classification was based on the pattern chuA and yjaA and the region TspE4.C2 by PCR Multiplex.Results: A higher frequency of non-adherent or poorly adherent isolates was observed in the community group. Approximately 85% of the community isolates were distributed in the highest hydrophilicity group (p0.05). About 14% of the hospital isolates were positive in the ESBL phenotypic detection test (p>0.05). Among the samples, 95% presented ESBL-encoding genes. The predominant phylogenetic group was B2 (78%). Community isolates showed a higher prevalence of virulence genes fimH, papC, and kpsMTII when compared to hospital samples.Conclusion: These data confirm the worldwide trend that isolates in the community present sometimes higher levels of virulence and antimicrobial resistance.Keywords: adhesion, control, ESBL, UTI

The present paper reports the assessment of the vegetation occupancy rate of the roadside, through analysis of aerial photographs. Using such value the potential of these areas to be employed as carbon (C) sinks was also assessed. Moreover, for the areas suitable for afforestation, the potential for carbon sequestration was estimated considering different species of vegetation, both native (scenario 1) and exotic (formed by Pinus sp. and Eucalyptus sp. - scenario 2). The study was carried out through GIS techniques and two regions were considered. A set of equations was used to estimate the rate of occupancy over the study areas, as well as amounts of fixed C under the above scenarios. The average occupancy rate was 0.06%. The simulation showed a higher potential for C sequestration in scenario 2, being the estimated amounts of CO2 sequestered from the atmosphere per km of roadside: 131 tons of CO2 km-1 of highway to native species and 655 tons of CO2 km-1 of highway for exotic species (over period of 10 years for both estimates). If we consider the whole road network of the São Paulo State (approximately 190 000 km) and that a considerable part of this road work is suitable to receive this kind of service, it is possible to predict the very high potential for C sequestration if managers and planners consider roadside as area for afforestation.

Aims: To assess the cumulative rate of HIV Pre-Exposure Prophylaxis (PrEP) users in Brazil since its 2018 implementation and to analyze the association between PrEP usage and state-level structural factors. Methods: A nationwide ecological study from 2018 to 2022 was conducted, examining the 5-year cumulative rate of PrEP users in relation to demographic, socioeconomic, and healthcare infrastructure variables. Multiple linear regression analysis identified significant predictors of PrEP utilization. Results: Between 2018 and 2022, 124,796 individuals used PrEP, with a cumulative rate of 61.5 per 100,000 population. The highest usage was in Minas Gerais, São Paulo, and Santa Catarina, while the lowest was in Distrito Federal, Maranhão, and Alagoas. Regression analysis showed that higher PrEP usage was associated with lower population density, a younger median age, a lower male to female ratio, and reduced social vulnerability. Additionally, PrEP usage was positively associated with the density of medical doctors and the number of dispensing units. Conclusions: The study reveals significant regional disparities in PrEP usage across Brazil, influenced by socioeconomic and healthcare factors. It highlights the need for targeted public health strategies to enhance PrEP access and uptake, especially in socially vulnerable regions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study focuses on developing accurate immunoassays for diagnosing Chagas disease (CD), a challenging task due to antigenic similarities between Trypanosoma cruzi and other parasites, leading to cross-reactivity. To address this challenge, chimeric recombinant T. cruzi antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) were synthesized to enhance specificity and reduce cross-reactivity in tests. While these antigens showed minimal cross-reactivity with leishmaniasis, their performance with other trypanosomatid infections was unclear. This study aimed to assess the diagnostic potential of these IBMP antigens for detecting CD in patients with Crithidia sp. LVH-60A, a parasite linked to visceral leishmaniasis-like symptoms in Brazil. This study involved seven Crithidia sp. LVH-60A patients and three Leishmania infantum patients. The results indicated that these IBMP antigens displayed 100% sensitivity, with specificity ranging from 87.5% to 100%, and accuracy values between 90% and 100%. No cross-reactivity was observed with Crithidia sp. LVH-60A, and only one L. infantum -positive sample showed limited cross-reactivity with IBMP-8.1. This study suggests that IBMP antigens offer promising diagnostic performance, with minimal cross-reactivity in regions where T. cruzi and other trypanosomatids are prevalent. However, further research with a larger number of Crithidia sp. LVH-60A-positive samples is needed to comprehensively evaluate antigen cross-reactivity., Competing Interests: The authors declare no conflicts of interest.

This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental in vitro studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the in vitro experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble Leishmania antigen (SLA) or infected with stationary promastigotes of Leishmania infantum in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL., 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. The reviewer VA declared a shared affiliation with the author MR to the handling editor at the time of review., (Copyright © 2022 Magalhães, Melo, Damascena, Albuquerque, Santos, Rebouças, Bezerra, Louzada da Silva, de Oliveira, Santos, da Silva, Lipscomb, da Silva, de Jesus and de Almeida.)

This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP-10 μg/ml) or egg (SEA-10 μg/ml) antigens or purified protein derivative of turberculin (PPD-10 μg/ml) or phytohemagglutinin (PHA-1 μg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17 , IL10 , and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis., 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 Franco, de Amorim, Santos, Rollemberg, de Oliveira, França, Santos, Magalhães, Cazzaniga, de Lima, Benevides, Carregaro, Silva, Brito, Fernandes, da Silva, de Almeida, Bezerra-Santos and de Jesus.)

Background: Chronic venous disease (CVD) and disability are worldwide problems and have significant socioeconomic implications. This study aims to analyze the time trends and social security burden of temporary work disability due to CVD in Brazil., Methods: An ecological time series study using the Brazilian Social Security System database was performed from 2005 to 2014. Data from all benefits granted to workers with temporary disability due to CVD were analyzed. The cases were identified using diagnosis codes I83-I83.9 of the International Classification of Diseases 10th Revision (ICD-10). The time trend analyses were performed by the Joinpoint Regression Model, with sex, age, regions, income, and category of affiliation as variables. Crude and age-standardized rates were calculated., Results: A total of 429,438 benefits were granted for temporary work disability due to CVD from 2005 to 2014, with a growing trend and an age-standardized annual percent change (APC) of 3.4 (95% CI: 2.6-4.2) (p < 0.05). Social security expense increased 3.5-fold, and the number of days in benefit doubled from 2005 to 2014. In total, 27,017,818 working days were lost. The average duration of benefits was 55.3 days. The majority of workers were women (68.2%) (p < 0.001), between 30 and 59 years old, employed, had a monthly income ≤2 minimum wages (MW) (83.2%), and lived in the regions southeast (53.6%) and south (29.3%). Significantly higher APCs were observed for women than for men (APC: 4.9, 95% CI: 4.0-5.7 versus APC: 1.2, 95% CI: 0.1-2.4). All regions in Brazil had a significant growing trend, except in the north. No significant growth was observed in the age group of 60-69 years. A decreasing trend was observed in workers with monthly incomes above 2 MW (p < 0.05)., Conclusions: Temporary work disability due to CVD and social security burden showed increasing trends with millions of working days lost, particularly among women and low-income workers. Preventing disability is challenging, and public policies are needed to reduce the social and economic impact of disability. Therefore, measures for promoting health at the workplace should be encouraged.

Congenital Zika syndrome (CZS) is a cluster of malformation, and the mechanisms that lead it are still unclear. Using hypothesis-driven candidate genes and their function in viral infections, single-nucleotide polymorphisms (SNPs) were genotyped by quantitative polymerase chain reaction in a sample population from Sergipe State, Brazil. This study shows that rs3775291 SNP at Toll-like receptor 3, which triggers type I interferon antiviral responses in mothers infected by Zika virus during pregnancy, is associated with CZS occurrence (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.158-4.148). Moreover, rs1799964 SNP at tumor necrosis factor-α gene in CZS babies is associated with severe microcephaly (OR, 2.63; 95% CI, 1.13-6.21)., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Visceral leishmaniasis is a life-threatening disease characterized by intense parasitism of the spleen, liver, and bone marrow. Antimonials have served as front-line antileishmanial therapeutics for decades, but the increasing failure rates under antimonial treatment have challenged the continued use of these drugs. Pentavalent antimonials are known to reinforce the killing mechanisms of macrophages, although the associated mechanism remains unclear. Here, for the first time, we determined whether Leishmania infantum strains isolated from patients refractory to antimony treatment (relapse cases) were cross-resistant to antimonials, liposomal amphotericin B, and/or nitric oxide, and also whether these strains modulate macrophage infection. We selected four clinical isolates from relapse cases and two clinical isolates from antimony-responsive patients (control group) for the present study. The L. infantum promastigotes from all four relapse cases were resistant to trivalent antimonial treatment and nitric oxide, while only one isolate was resistant to liposomal amphotericin B. We evaluated whether the resistant strains from relapse cases showed enhanced infectivity and amastigote survival in macrophages, or macrophage-killing mechanisms in macrophages activated by lipopolysaccharide plus interferon gamma. Infection indexes calculated using macrophages infected with isolates from relapse were higher than those observed with control strains that were stimulated independently. Macrophage infection was higher with L. infantum isolates from relapse cases and correlated with enhanced interleukin 1-β production but showed similar nitrite production. Our results demonstrate that L. infantum field isolates from relapse cases were resistant to antimonials and nitric oxide and that these parasites stimulated inflammatory cytokines and were resistant to macrophage-killing mechanisms, factors that may contribute to disease severity.

Background: While CD40L is typically a membrane glycoprotein expressed on activated T cells and platelets that binds and activates CD40 on the surface on antigen presenting cells, a soluble derivative (sCD40L) that appears to retain its biological activity after cleavage from cell membrane also exists. We recently reported that sCD40L is associated with clinical resolution of visceral leishmaniasis and protection against the disease. In the present study we investigated if this sCD40L is functional and exerts anti-parasitic effect in L. infantum-infected macrophages., Methodology/principal Findings: Macrophages from normal human donors were infected with L. infantum promastigotes and incubated with either sera from subjects exposed to L. infantum infection, monoclonal antibodies against human CD40L, or an isotype control antibody. We then evaluated infection by counting the number of infected cells and the number of parasites in each cell. We also measured a variety of immune modulatory cytokines in these macrophage culture supernatants by Luminex assay. The addition of sCD40L, either recombinant or from infected individuals' serum, decreased both the number of infected macrophages and number of intracellular parasites. Moreover, this treatment increased the production of IL-12, IL-23, IL-27, IL-15, and IL1β such that negative correlations between the levels of these cytokines with both the infection ratio and number of intracellular parasites were observed., Conclusions/significance: sCD40L from sera of subjects exposed to L. infantum is functional and improves both the control of parasite and production of inflamatory cytokines of infected macrophages. Although the mechanisms involved in parasite killing are still unclear and require further exploration, these findings indicate a protective role of sCD40L in visceral leishmaniasis.