Discussões sobre corredores ecológicos no Brasil 2006-2016

Objetivou-se nesse estudo analisar as produções sobre o contexto de corredores ecológicos publicados em periódicos nacionais de Geografia no recorte temporal de 2006 a 2016, atentando para as discussões realizadas para conservação dos ecossistemas e de seus remanescentes. Para isso, a pesquisa foi desenvolvida mediante 4 fases de organização de dados: 1) Levantamento de Periódicos de Geografia de qualis A1, A2 e B1 na plataforma oficial de periódicos da CAPES (plataforma sucupira); 2) Levantamento nas edições das revistas, por artigos científicos que abordassem corredores ecológicos, 3) organização de quadro síntese quanto as variáveis título, área do conhecimento, nome da revista, objetivos, métodos e discussões dos trabalhos e 4) Exposição dos dados das produções de maneira quantitativa e qualitativa. Diante dessa fase de trabalho, objetiva-se futuramente propor um corredor ecológico no entorno do Parque Estadual do Desengano ao Parque estadual da Lagoa do Açu, visando conexão de ambientes e preservação

Voriconazole Use in Children: Therapeutic Drug Monitoring and Control of Inflammation as Key Points for Optimal Treatment

Infeccions fúngiques pediàtriques; Monitorització terapèutica de fàrmacs; VoriconazolInfecciones fúngicas pediátricas; Monitorización terapéutica de fármacos; VoriconazolPaediatric fungal infections; Therapeutic drug monitoring; VoriconazoleVoriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged.This research was funded by an Investigator Sponsored Research Grant from Pfizer (Grant Number WI182544

A Novel Generation of Tailored Antimicrobial Drugs Based on Recombinant Multidomain Proteins

Antibiotic resistance has exponentially increased during the last years. It is necessary to develop new antimicrobial drugs to prevent and treat infectious diseases caused by multidrug- or extensively-drug resistant (MDR/XDR)-bacteria. Host Defense Peptides (HDPs) have a versatile role, acting as antimicrobial peptides and regulators of several innate immunity functions. The results shown by previous studies using synthetic HDPs are only the tip of the iceberg, since the synergistic potential of HDPs and their production as recombinant proteins are fields practically unexplored. The present study aims to move a step forward through the development of a new generation of tailored antimicrobials, using a rational design of recombinant multidomain proteins based on HDPs. This strategy is based on a two-phase process, starting with the construction of the first generation molecules using single HDPs and further selecting those HDPs with higher bactericidal efficiencies to be combined in the second generation of broad-spectrum antimicrobials. As a proof of concept, we have designed three new antimicrobials, named D5L37βD3, D5L37D5L37 and D5LAL37βD3. After an in-depth exploration, we found D5L37D5L37 to be the most promising one, since it was equally effective against four relevant pathogens in healthcare-associated infections, such as methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis (MRSE) and MDR Pseudomonas aeruginosa, being MRSA, MRSE and P. aeruginosa MDR strains. The low MIC values and versatile activity against planktonic and biofilm forms reinforce the use of this platform to isolate and produce unlimited HDP combinations as new antimicrobial drugs by effective means.info:eu-repo/semantics/publishedVersio

Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses

Longitudinal studies in HIV-1 infected individuals have indicated that 2-3 years of infection are required to develop broadly neutralizing antibodies. However, we have previously identified individuals with broadly neutralizing activity (bNA) in early HIV-1 infection, indicating that a vaccine may be capable of bNA induction after short periods of antigen exposure. Here, we describe 5 HIV-1 envelope sequences from individuals who have developed bNA within the first 100 days of infection (early neutralizers) and selected two of them to design immunogens based on HIV-1-Gag virus like particles (VLPs). These VLPs were homogeneous and incorporated the corresponding envelopes (7 to 9μg of gp120 in 1010 VLPs). Both envelopes bound to well-characterized bNAbs, including trimer-specific antibodies (PGT145, VRC01 and 35022). For immunogenicity testing, we immunized rabbits with the Env-VLPs or with the corresponding stabilized soluble Envelope trimers. A short immunization protocol (105 days) was used to recapitulate the early nAb induction observed after HIV-1 infection in these two individuals. All VLP and trimeric Envelope immunogens induced a comparably strong anti-gp120 response, despite having immunized rabbits with 30 times less gp120 in the case of the Env-VLPs. In addition, animals immunized with VLP-formulated Envs induced antibodies that cross-recognized the corresponding soluble stabilized trimer and vice versa, even though no neutralizing activity was observed. Nevertheless, our data may provide a new platform of immunogens, based on HIV-1 envelopes from patients with early broadly neutralizing responses, with the potential to generate protective immune responses using vaccination protocols similar to those used in classical preventive vaccines. Importance: It is generally accepted that an effective HIV-1 vaccine should be able to induce broad-spectrum neutralizing antibodies. Since most of these antibodies require long periods of somatic maturation in vivo, several groups are developing immunogens, based on the HIV envelope protein, that require complex and lengthy immunization protocols that would be difficult to implement to the general population. Here, we show that rabbits immunized with new envelopes (VLP-formulated) from two individuals who demonstrated broadly neutralizing activity very early after infection, induced specific HIV-1 antibodies after a short immunization protocol. This evidence provides the basis for generating protective immune responses with classic vaccination protocols with vaccine prototypes based on HIV envelope sequences from individuals who have developed early broadly neutralizing responses.This project received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no. 681137 to I.B., N.G., A.O., C.B., J.A., R.W.S., and E.Y. It was also partially supported by the Spanish AIDS Research Network (RIS), funded by the Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF) “A way to build Europe” (projects RD16CIII/0002/0001, RD16CIII/0002/0005, and RD16CIII/0025/0041), Plan Estatal de I1D1I 2013-2016 to N.G., A.M.M., J.A., V.S.M., E.Y., M.P., A.O., and C.B.; by IDIBAPS to J.M.M. (80:20 Research grant); by the Fondation Dormeur, Vaduz to C.B.; by the Ministerio de Economía, Industria y Competitividad to N.G., V.S.M., and E.Y. (PI17CIII/00049); by the Ministerio de Ciencia e Innovación to N.G., V.S.M., and E.Y. (PI20CIII/00039); by the Consejo Nacional de Innovación, Ciencia y Tecnología to C.B.P.; and by the HHS/ National Institutes of Health (NIH) to C.B. (P01-AI131568).S

SARS-CoV-2 Vaccination Coverage and Factors Associated with Low Uptake in a Cohort of People Living with HIV

People living with HIV (PLWH) are prioritised for SARS-CoV-2 vaccination due to their vulnerability to severe COVID-19. Therefore, the epidemiological surveillance of vaccination coverage and the timely identification of suboptimally vaccinated PLWH is vital. We assessed SARS-CoV-2 vaccination coverage and factors associated with under-vaccination among PLWH in Catalonia, Spain. As of 11.12.2021, 9945/14942 PLWH (66.6%) had received >= 1 dose of a SARS-CoV-2 vaccine. Non-Spanish origin (adjusted odds ratio (aOR) 0.64, 95% CI 0.59-0.70), CD4 count of 200-349 cells/mu L (aOR 0.74, 95% CI 0.64-0.86) or 350-499 cells/mu L (aOR 0.79, 95% CI 0.70-0.88), detectable plasma HIV-RNA (aOR 0.61 95% CI 0.53-0.70), and previous SARS-CoV-2 diagnosis (aOR 0.58 95% CI 0.51-0.65) were associated with under-vaccination. SARS-CoV-2 diagnosis (437 [9.5%] vs. 323 [3.5%], p 200 cells/mu L, detectable plasma HIV-RNA, previous SARS-CoV-2 diagnosis, and migrants. SARS-CoV-2 diagnosis, associated hospitalisations, and deaths among PLWH were lower among the vaccinated compared with the unvaccinated. SARS-CoV-2 vaccination prioritisation has not completely reached vulnerable PLWH with poorer prognosis. This information can be used to inform public health strategies

Effect of Maraviroc Intensification on HIV-1-Specific T Cell Immunity in Recently HIV-1-Infected Individuals

The effect of maraviroc on the maintenance and the function of HIV-1-specific T cell responses remains unknown. Subjects recently infected with HIV-1 were randomized to receive anti-retroviral treatment with or without maraviroc intensification for 48 weeks, and were monitored up to week 60. PBMC and in vitro -expanded T cells were tested for responses to the entire HIV proteome by ELISpot analyses. Intracellular cytokine staining assays were conducted to monitor the (poly)-functionality of HIV-1-specific T cells. Analyses were performed at baseline and week 24 after treatment start, and at week 60 (3 months after maraviroc discontinuation). Maraviroc intensification was associated with a slower decay of virus-specific T cell responses over time compared to the non-intensified regimen in both direct ex-vivo as well as in in-vitro expanded cells. The effector function profiles of virus-specific CD8 + T cells were indistinguishable between the two arms and did not change over time between the groups. Maraviroc did not negatively impact any of the measured parameters, but was rather associated with a prolonged maintenance of HIV-1-specific T cell responses. Maraviroc, in addition to its original effect as viral entry inhibitor, may provide an additional benefit on the maintenance of virus-specific T cells which may be especially important for future viral eradication strategies

Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection

Introduction: Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (7%) [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI. Methods: Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (]1) adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiatedsix months after SC: deferred). We also considered time to CD4 count normalization (]900 cells/mm3 ). Results: In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.755.01, pB0.001). The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.960.99 for each 30-day increase). CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.0011.002, pB0.001). There was an association between normal CD4/CD8 ratio and being virally suppressed (B400 copies HIV RNA/ml) pB0.001. CD4 count normalization was also significantly more likely for those initiating early (HR 5.00, 95% CI 1.5216.41, p0.008). Conclusions: The likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of PHI. Higher CD4/CD8 ratio may reflect a more ‘‘normal’’ immune phenotype conferring enhanced prognosis and predict posttreatment control. Refe

Epidemiological and clinical characteristics of Streptococcus tigurinus endocarditis

Background: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. Methods: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. Results: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. Conclusions: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.JMM received a personal 80:20 research grant from the Institut d’InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain during 2017–19. Nofunding entity played any role in the design of the study and data collection,analysis, and interpretation of data and in writing the manuscript

The Incidence of AIDS-Defining Illnesses at a Current CD4 Count ≥200 Cells/µL in the Post-Combination Antiretroviral Therapy Era

The incidence of AIDS was higher in patients with a current CD4 count of 500-749 cells/µL compared to 750-999 cells/µL, but did not decrease further at higher CD4 levels. Results were similar in those virologically suppressed on combination antiretroviral therapy, suggesting immune reconstitution is incomplete until CD4 >750/µ

Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily). METHODS: This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as "definite," "probable," or "possible" using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40. DISCUSSION: The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT04145258. Registered on October 30, 2019