Description of the new HIV-1 intersubtype B/C circulating recombinant form (CRF146_BC) detected in Brazil.

BACKGROUND: The human immunodeficiency virus 1 (HIV-1) infections in Brazil are predominantly caused by two subtypes, B and C. OBJECTIVES: Here we present the characterisation of a novel HIV-1 recombinant form, indicating a new Brazilian CRF_BC, named CRF146_BC. METHODS: RDP, JphMM and Simplot recombination tools were used to evaluate the mosaic pattern. FINDINGS: In this work, we identified three HIV-1 nucleotide sequences previously classified as unique recombinant forms (URFs), plus one new partial genome sharing the same BC recombination pattern. The mosaic genome is almost entirely represented by the subtype C sequence, with a small subtype B recombination region in the pol gene, at the Integrase level. The phylogenetic analyses strongly indicate a common origin between the strains, which were isolated in Rio Grande do Sul, Rio de Janeiro and Bahia states. MAIN CONCLUSIONS: Thus, the new HIV-1 CRF146_BC is circulating in three different Brazilian regions: South, Southeast and Northeast.

Helping WWTP managers to address the volatile methylsiloxanes issue-Behaviour and complete mass balance in a conventional plant.

Volatile methylsiloxanes (VMSs) are a group of additives employed in different consumer products that can affect the quality of the biogas produced in wastewater treatment plants (WWTPs). The main objective of this study is to understand the fate of different VMSs along the treatment process of a WWTP located in Aveiro (Portugal). Thus, wastewater, sludge, biogas, and air were sampled in different units for two weeks. Subsequently, these samples were extracted and analyzed by different environment-friendly protocols to obtain their VMS (L3-L5, D3-D6) concentrations and profiles. Finally, considering the different matrix flows at every sampling moment, the mass distribution of VMSs within the plant was estimated. The levels of ∑VMSs were similar to those showed in the literature (0.1-50 µg/L in entry wastewater and 1-100 µg/g dw in primary sludge). However, the entry wastewater profile showed higher variability in D3 concentrations (from non detected to 49 µg/L) than found in previous studies (0.10-1.00 µg/L), likely caused by isolated releases of this compound that could be related to industrial sources. Outdoor air samples showed a prevalence of D5, while indoor air locations were characterized by a predominance of D3 and D4. Differences in sources and the presence of an indoor air filtration system may explain this divergence. Biogas was characterized by ∑VMSs concentrations (8.00 ± 0.22 mg/m3) above the limits recommended by some engine manufacturers and mainly composed of D5 (89%). Overall, 81% of the total incoming mass of VMSs is reduced along the WWTP, being the primary decanter and the secondary treatment responsible for the highest decrease (30.6% and 29.4% of the initial mass, respectively). This reduction, however, is congener dependant. The present study demonstrates the importance of extending sampling periods and matrices (i.e., sludge and air) to improve sample representativity, time-sensitivity, and the accuracy of mass balance exercises.

Tracing the relationship among HIV-1 sub-subtype F1 strains: a phylodynamic perspective.

BACKGROUND: The human immunodeficiency virus type 1, F1 sub-subtype (HIV-1 F1) circulates in three continents: Africa, Europe, and South America. In Brazil, this sub-subtype co-circulates with subtypes B and C and several recombinant forms, mainly BF1 variants. OBJECTIVES: This study aimed to reconstruct the dynamic history of HIV-1 F1 in Brazil. METHODS: HIV-1 near full-length genome and pol gene nucleotide sequences available in public databases were assembled in two datasets (POL671 and NFLG53) to cover the largest number of F1 sub-subtype sequences. Phylodynamic and temporal analyses were performed. FINDINGS: Two main strains of the F1 sub-subtype are circulating worldwide. The first (F1.I) was found among Brazilian samples (75%) and the second (F1.II) among Romanian (62%) and other European and African isolates. The F1 subtype epidemic in Brazil originated from a single entry into the country around 1970. This ancestral sample is related to samples isolated in European countries (France, Finland, and Belgium), which are possibly of African origin. Moreover, further migration (1998 CI: 1994-2003) of strains from Brazil to Europe (Spain and the UK) was observed. Interestingly, all different recombinant BF patterns found, even those from outside Brazil, present the same F1 lineage (F1.I) as an ancestor, which could be related to the acquisition of adaptive advantages for the recombinant progenies. MAIN CONCLUSIONS: These findings are important for the understanding of the origin and dynamics of the F1 sub-subtype and a consequent better and greater understanding of the HIV-1 F1 and BF epidemic that still spreads from Brazil to other countries.

Multi-feedstock biorefinery concept: Valorization of winery wastes by engineered yeast.

The wine industry produces significant amounts of by-products and residues that are not properly managed, posing an environmental problem. Grape must surplus, vine shoots, and wine lees have the potential to be used as renewable resources for the production of energy and chemicals. Metabolic engineering efforts have established Saccharomyces cerevisiae as an efficient microbial cell factory for biorefineries. Current biorefineries designed for producing multiple products often rely on just one feedstock, but the bioeconomy would clearly benefit if these biorefineries could efficiently convert multiple feedstocks. Moreover, to reduce the environmental impact of fossil fuel consumption and maximize production economics, a biorefinery should be capable to supplement the manufacture of biofuel with the production of high-value products. This study proposes an integrated approach for the valorization of diverse wastes resulting from winemaking processes through the biosynthesis of xylitol and ethanol. Using genetically modified S. cerevisiae strains, the xylose-rich hemicellulosic fraction of hydrothermally pretreated vine shoots was converted into xylitol, and the cellulosic fraction was used to produce bioethanol. In addition, grape must, enriched in sugars, was efficiently used as a low-cost source for yeast propagation. The production of xylitol was optimized, in a Simultaneous Saccharification and Fermentation process configuration, by adjusting the inoculum size and enzyme loading. Furthermore, a yeast strain displaying cellulases in the cell surface was applied for the production of bioethanol from the glucan-rich cellulosic. With the addition of grape must and/or wine lees, high ethanol concentrations were reached, which are crucial for the economic feasibility of distillation. This integrated multi-feedstock valorization provides a synergistic alternative for converting a range of winery wastes and by-products into biofuel and an added-value chemical while decreasing waste released to the environment.

The Interference of Age and Gender on Smile Characterization Analyzed on Six Parameters: A Clinical-Photographic Pilot Study.

Background and Objective: This study aimed to evaluate six smile-esthetic parameters (deviation of the upper dental midline from the facial midline, upper lip curvature, smile line, smile arch, smile width, and shape of the maxillary central incisors), correlating them with age and gender. Materials and methods: Caucasian individuals (N = 114) were grouped by gender (male and female) and age (group I-18 to 30 years old; group II-31 to 50 years old; and group III-over 50 years old). Using a digital camera, extra and intraoral pictures were taken to analyze the variables above-mentioned. The data were statistically evaluated, considering a significance level of p < 0.05. Results: Most participants found deviations of the upper dental midline, straight upper lip curvature, and the medium smile line coincided with the facial midline. The parallel smile arch exposing 9 to 11 upper teeth, the absence of exposure of lower teeth when smiling, and oval upper incisors were prevalent parameters. Regarding gender, significant results were found for the curvature of the upper lip (p = 0.049), the smile arch (p = 0.001), and the shape of the upper central incisors (p = 0.004). For age, the association with the curvature of the upper lip (p = 0.032), the smile line (p = 0.001), the smile arch (p = 0.007), the width of the smile exposing lower teeth (p = 0.002), and the shape of the upper central incisors (0.012) were significant. Conclusions: Within this study's limitations, gender and age affect the anterior teeth shape and upper lip curves; gender and age did not influence the coincidence between dental and facial midlines.

A patent review of the antimicrobial applications of lectins: Perspectives on therapy of infectious diseases.

Patents of lectins with antiviral, antibacterial and antifungal applications were searched and reviewed. Lectins are proteins that reversibly bind to specific carbohydrates and have the potential for therapy of infectious diseases as biopharmaceuticals, biomedical tools or in drug design. Given the rising concerns over drug resistance and epidemics, our patent review aims to add information, open horizons and indicate our view of the future perspectives about the antimicrobial applications of lectins. Patents with publications until December 2020 were retrieved from Espacenet using defined search terms and Boolean operators. The documents were used to identify the geographical and temporal distribution of the patents, characterize their lectins, and classify and summarize their antiviral, antibiotic and antifungal applications. Lectins are promising antiviral agents against viruses with epidemics and drug resistance concerns. Mannose-binding lectins were the most suggested antiviral agents since glycans with mannose residues are commonly involved in viral entry mechanisms. They were also immobilized onto surfaces to trap viral particles and inhibit their spread and replication. Many patents described the extraction, isolation, amino acid and nucleotide sequences, and expression vectors of lectins with antibiotic and/or antifungal activities in terms of MIC and IC50 for in vitro assays. The inventions also included lectins as biological tools in nanosensors for antibiotics susceptibility tests, drug-delivery systems for the treatment of resistant bacteria, diagnostics of viral diseases and as a vaccine adjuvant. Although research and development of new medicines is highly expensive, antimicrobial lectins may be worth investments given the emergence of epidemics and drug resistance. For this purpose, less invasive routes should be developed as alternatives to the parenteral administration of biologics. While anti-glycan neutralizing antibodies are difficult to develop due to the low immunogenicity of carbohydrates, lectins can be produced more easily and have a broad-spectrum activity. Protein engineering technologies may make the antimicrobial applications of lectins more successful.

Molecular and physiological basis of Saccharomyces cerevisiae tolerance to adverse lignocellulose-based process conditions.

Lignocellulose-based biorefineries have been gaining increasing attention to substitute current petroleum-based refineries. Biomass processing requires a pretreatment step to break lignocellulosic biomass recalcitrant structure, which results in the release of a broad range of microbial inhibitors, mainly weak acids, furans, and phenolic compounds. Saccharomyces cerevisiae is the most commonly used organism for ethanol production; however, it can be severely distressed by these lignocellulose-derived inhibitors, in addition to other challenging conditions, such as pentose sugar utilization and the high temperatures required for an efficient simultaneous saccharification and fermentation step. Therefore, a better understanding of the yeast response and adaptation towards the presence of these multiple stresses is of crucial importance to design strategies to improve yeast robustness and bioconversion capacity from lignocellulosic biomass. This review includes an overview of the main inhibitors derived from diverse raw material resultants from different biomass pretreatments, and describes the main mechanisms of yeast response to their presence, as well as to the presence of stresses imposed by xylose utilization and high-temperature conditions, with a special emphasis on the synergistic effect of multiple inhibitors/stressors. Furthermore, successful cases of tolerance improvement of S. cerevisiae are highlighted, in particular those associated with other process-related physiologically relevant conditions. Decoding the overall yeast response mechanisms will pave the way for the integrated development of sustainable yeast cell-based biorefineries.

Abnormal Eye and Cranial Movements Triggered by Examination in People with Functional Neurological Disorder.

The diagnosis of functional neurological disorder (FND) relies on the demonstration of positive symptoms and signs, as supported by recent changes in DSM5. We recorded the findings of routine clinical eye movement assessment in 101 consecutive new patients with FND. Clinical examination triggered facial and eye movement disorders in 46% of patients, all with positive characteristics of functional movement disorder. These are useful as supporting features in making a positive diagnosis of FND.

HAA1 and PRS3 overexpression boosts yeast tolerance towards acetic acid improving xylose or glucose consumption: unravelling the underlying mechanisms.

Acetic acid tolerance and xylose consumption are desirable traits for yeast strains used in industrial biotechnological processes. In this work, overexpression of a weak acid stress transcriptional activator encoded by the gene HAA1 and a phosphoribosyl pyrophosphate synthetase encoded by PRS3 in a recombinant industrial Saccharomyces cerevisiae strain containing a xylose metabolic pathway was evaluated in the presence of acetic acid in xylose- or glucose-containing media. HAA1 or PRS3 overexpression resulted in superior yeast growth and higher sugar consumption capacities in the presence of 4 g/L acetic acid, and a positive synergistic effect resulted from the simultaneous overexpression of both genes. Overexpressing these genes also improved yeast adaptation to a non-detoxified hardwood hydrolysate with a high acetic acid content. Furthermore, the overexpression of HAA1 and/or PRS3 was found to increase the robustness of yeast cell wall when challenged with acetic acid stress, suggesting the involvement of the modulation of the cell wall integrity pathway. This study clearly shows HAA1 and/or, for the first time, PRS3 overexpression to play an important role in the improvement of industrial yeast tolerance towards acetic acid. The results expand the molecular toolbox and add to the current understanding of the mechanisms involved in higher acetic acid tolerance, paving the way for the further development of more efficient industrial processes.

Detection of human neutrophil elastase (HNE) on wound dressings as marker of inflammation.

Chronic wound fluids have elevated concentration of human neutrophil elastase (HNE) which can be used as inflammation/infection marker. Our goal is to develop functional materials for fast diagnosis of wound inflammation/infection by using HNE as a specific marker. For that, fluorogenic peptides with a HNE-specific cleavage sequence were incorporated into traditional textile dressings, to allow real-time detection of the wound status. Two different fluorogenic approaches were studied in terms of intensity of the signal generated upon HNE addition: a fluorophore 7-amino-4-trifluormethylcoumarin (AFC) conjugated to a HNE-specific peptide and two fluorophore/quencher pairs (FAM/Dabcyl and EDANS/Dabcyl) coupled to a similar peptide as a Förster resonance energy transfer (FRET) strategy. Also, two immobilization methods were tested: sonochemistry immobilization onto a cotton bandage and glutaraldehyde (GTA)-assisted chemical crosslinking onto a polyamide dressing. The immobilized fluorogenic AFC peptide showed an intense fluorescence emission in the presence of HNE. HNE also induced an enhanced fluorescent signal with the EDANS/Dabcyl FRET peptide which showed to be a more sensitive and effective strategy than the AFC peptide. However, its chemical immobilization onto the polyamide dressing greatly decreased its detection, mainly due to the more difficult access of the enzyme to the cleavage sequence of the immobilized peptide. After optimization of the in situ immobilization, it will be possible to use these fluorescence-functionalized dressings for an effective and specific monitoring of chronic wounds by simply using a portable ultraviolet (UV) light source. We envision that the development of this point-of-care medical device for wound control will have a great impact on patient's life quality and reduction of costs on health care system.

An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil.

BACKGROUND: The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. OBJECTIVE: The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. METHODS: DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed. FINDINGS: Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals. MAIN CONCLUSIONS: This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.

Leishmania-infected MHC class IIhigh dendritic cells polarize CD4+ T cells toward a nonprotective T-bet+ IFN-γ+ IL-10+ phenotype.

A differential behavior among infected and bystander dendritic cells (DCs) has been explored in different infection models. We have analyzed both populations sorted on contact with visceral Leishmania infantum on a susceptible mice model evaluating the subsequent repercussions on adaptive immune response. Our results demonstrate a clear dichotomy between the immunomodulatory abilities of bystander and infected DCs. The bystander population presents increased levels of IL-12p40 and costimulatory molecules being capable to induce CD4(+) T cell activation with immune protective capabilities. In contrast, infected DCs, which express lower costimulatory molecules and higher levels of IL-10, promote the development of Leishmania Ag-specific, nonprotective T-bet(+)IFN-γ(+)IL-10(+) CD4(+) T cells with an effector phenotype. This specific polarization was found to be dependent on IL-12p70. Splenic infected DCs recovered from chronic infected animals are similarly capable to polarize ex vivo syngeneic naive CD4(+) T cells toward a T-bet(+)IFN-γ(+)IL-10(+) phenotype. Further analysis revealed that only MHC class II(high)-infected DCs were responsible for this polarization. The adoptive transfer of such polarized CD4(+) T cells facilitates visceral leishmaniasis in BALB/c mice in a clear contrast with their counterpart generated with bystander DCs that significantly potentiate protection. Further, we demonstrated that CD4(+) T cells primed by infected DCs in an IL-10 free system, thus deprived of T-bet(+)IFN-γ(+)IL-10(+) population, restore the immune response and reduce parasite load, supporting a deleterious role of IFN-γ(+)IL-10(+) T cells in the maintenance of infection. Overall, our results highlight novel subversion mechanisms by which nonprotective T-bet(+)IFN-γ(+)IL-10(+) T cells are associated with chronicity and prolonged parasite persistence.

The impact of distinct culture media in Leishmania infantum biology and infectivity.

An ideal culture medium for Leishmania promastigotes should retain the basic characteristics of promastigotes found in sandflies (morphology and infectivity). Furthermore, the media should not create a bias in experimental settings, thus enabling the proper extrapolation of results. To assess this we studied several established media for promastigote growth. We analysed morphology, viability, cell cycle progression, metacyclic profile, capacity to differentiate into axenic amastigotes and infectivity. Furthermore, using a rational approach from the evaluated media we developed a simple serum-free medium (cRPMI). We report that parasites growing in different media present different biological characteristics and distinct in vitro and in vivo infectivities. The developed medium, cRPMI, proved to be a less expensive substitute for traditional serum-supplemented media for the in vitro maintenance of promastigotes. In fact, cRPMI is ideal for the maintenance of parasites in the laboratory, diminishing the expected loss of virulence over time typical of the parasite cultivation. Ultimately this report is a clear warning that the normalization of culture media should be a real concern in the field as media-specific phenomena are sufficient to induce biological bias with consequences in infectivity and general parasite biology.

Crucial CD8(+) T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis.

This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was >90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8(+)- but not CD4(+)-T lymphocytes. Overall, we demonstrate a crucial role for CD8(+) cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. FROM THE CLINICAL EDITOR: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy.

Anterior Spinal Cord Infarction: A Rare Diagnosis With an Uncommon Presentation.

Spinal cord infarction (SCI) is a rare vascular event accounting for 1% of all strokes. Neurological syndromes may vary according to the arterial territory involved. This condition may differ in onset, severity, and recovery, making it a diagnostic challenge for clinicians. Diagnosis is made on a clinical basis, and neuroimaging (magnetic resonance imaging (MRI)) provides confirmatory evidence. A 72-year-old male, with a medical history of being overweight, hyperuricemia, dyslipidemia, and cigarette smoking presented to our emergency department (ED) with sudden-onset leg weakness. He reported chest pain with radiation to the back, followed by sudden arm and leg weakness, evolving to inferior limb plegia within four hours. He also noticed a loss of sensation below the breast region. On admission, vital signs were stable. Neurological examination demonstrated paraplegia of inferior limbs with absent deep tendon reflexes. Both pinprick, vibrational, and proprioceptive sensitivities were absent below T6. A diagnostic workup revealed lactescent serum suggesting severe hypertriglyceridemia. A clinical diagnosis of spinal cord infarction was made, which was later confirmed with MRI demonstrating an acute ischemic lesion in the anterior spinal artery (ASA) with the "owl's eye" sign, from T5 with extension to the cone. Neurological examination remained unaltered. He started aspirin and insulin perfusion. Since spinal cord injury is an uncommon cause of paraplegia, physicians should be extremely cautious. Despite the results of magnetic resonance imaging, the clinical picture was not consistent, which was finally explained by perilesional edema. To our knowledge, this is a rare case combining SCI with hypertriglyceridemia. Notwithstanding the lack of evidence linking reducing triglyceride levels to neurological recovery, insulin infusion was carried out given the hazards associated with sustaining such high levels of triglycerides. We aim to emphasize some characteristic MRI findings and the wealth of possible etiologies contributing to this clinical entity.

Alternative routes for parenteral nucleic acid delivery and related hurdles: highlights in RNA delivery.

INTRODUCTION: Nucleic acid-based therapies are promising advancements in medicine. They offer unparalleled efficacy in treating previously untreatable diseases through precise gene manipulation techniques. However, the challenge of achieving targeted delivery to specific cells remains a significant obstacle. AREAS COVERED: This review thoroughly examines the physicochemical properties of nucleic acids, focusing on their interaction with carriers and exploring various delivery routes, including oral, pulmonary, ocular, and dermal routes. It also examines the nonviral vector delivery efficiency of nucleic acids, focusing on RNA, and provides regulatory landscapes. EXPERT OPINION: The role of carriers in improving the effectiveness of nucleic acid-based therapies is emphasized. The discussion of published results covers regulatory frameworks, including insights into European Medicines Agency guidelines. It highlights cutting-edge biotechnological innovations and a quality-by-design approach that could facilitate clinical translation and smooth regulatory obstacles.

Peptide-Hitchhiking for the Development of Nanosystems in Glioblastoma.

Glioblastoma (GBM) remains the epitome of aggressiveness and lethality in the spectrum of brain tumors, primarily due to the blood-brain barrier (BBB) that hinders effective treatment delivery, tumor heterogeneity, and the presence of treatment-resistant stem cells that contribute to tumor recurrence. Nanoparticles (NPs) have been used to overcome these obstacles by attaching targeting ligands to enhance therapeutic efficacy. Among these ligands, peptides stand out due to their ease of synthesis and high selectivity. This article aims to review single and multiligand strategies critically. In addition, it highlights other strategies that integrate the effects of external stimuli, biomimetic approaches, and chemical approaches as nanocatalytic medicine, revealing their significant potential in treating GBM with peptide-functionalized NPs. Alternative routes of parenteral administration, specifically nose-to-brain delivery and local treatment within the resected tumor cavity, are also discussed. Finally, an overview of the significant obstacles and potential strategies to overcome them are discussed to provide a perspective on this promising field of GBM therapy.

Giant Tophaceous Gout: The Importance of Therapeutic Compliance.

Gout is a metabolic disease resulting from the deposition of monosodium urate crystals in joints, tissues, and organs. Nowadays, the treatment of hyperuricemia is easily accessible and widespread and mainly consists of xanthine oxidase inhibitors and uricosurics. In refractory and advanced cases of gout, amputation surgery may be required. The authors present the case of an 85-year-old man who is non-compliant with hypouricemic medication, has exuberant gout, and has refused amputation surgery several times. The patient went to the emergency department with a triad of acute kidney injuries, acute gout, and poorly controlled pain. Cases of tophaceus gout such as the one presented are very rare nowadays.

The potential of exosomes as a new therapeutic strategy for glioblastoma.

Glioblastoma (GBM) stands for the most common and aggressive type of brain tumour in adults. It is highly invasive, which explains its short rate of survival. Little is known about its risk factors, and current therapy is still ineffective. Hence, efforts are underway to develop novel and effective treatment approaches against this type of cancer. Exosomes are being explored as a promising strategy for conveying and delivering therapeutic cargo to GBM cells. They can fuse with the GBM cell membrane and, consequently, serve as delivery systems in this context. Due to their nanoscale size, exosomes can cross the blood-brain barrier (BBB), which constitutes a significant hurdle to most chemotherapeutic drugs used against GBM. They can subsequently inhibit oncogenes, activate tumour suppressor genes, induce immune responses, and control cell growth. However, despite representing a promising tool for the treatment of GBM, further research and clinical studies regarding exosome biology, engineering, and clinical applications still need to be completed. Here, we sought to review the application of exosomes in the treatment of GBM through an in-depth analysis of the scientific and clinical studies on the entire process, from the isolation and purification of exosomes to their design and transformation into anti-oncogenic drug delivery systems. Surface modification of exosomes to enhance BBB penetration and GBM-cell targeting is also a topic of discussion.

Molecular and Phylogenetic Analysis of HIV-1 Subtype C in Bahia State, Northeastern Brazil.

HIV-1 subtype C is associated with more than half of infections in southern Brazil and has been increasing in other regions of the country. In a previous study carried out in northeastern Brazil, we found a prevalence of 4.1% of subtype C. This work investigates the origin of subtype C in the state of Bahia based on five new viral sequences. The phylogenetic analysis showed that subtype C viruses found in Bahia descend from the main lineage that circulates in other Brazilian regions.