Samara Alves Stocki, Mísia Beatriz Bueno Alvarenga, Davi de Souza Pinheiro
et al.
Introduction: Severe Acute Respiratory Syndrome (SARI) became one of the main causes of hospitalization and death among older adults during the coronavirus pandemic (COVID-19), especially due to the greater severity of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this group. With the start of COVID-19 vaccination in Brazil in January 2021, prioritizing older adults, a reduction in severe outcomes was expected. This study aimed to assess the trend in hospital lethality from SARI caused by COVID-19 among Brazilian older adults between 2020 and 2023, and its relationship with vaccination coverage against SARS-CoV-2. Methods: This is a retrospective ecological study that analyzed public data from 2020 to 2023 on hospitalizations for SARI caused by SARS-CoV-2 among older adults (≥60 years). Lethality by age group was calculated and related to vaccination coverage (complete primary series and booster doses) obtained from OpenDataSUS. A descriptive analysis of the annual evolution of lethality and vaccination was performed. Results: In 2020, before vaccination, lethality from COVID-19–related SARI among older adults was 47.2%. In the following year, with the start of immunization, the rate dropped to 35.6%. In 2022 and 2023, with expansion of vaccine schedules and boosters, stabilization was observed between 24% and 26%. Vaccination coverage with complete primary series reached 87% of older adults in 2021, increasing to more than 95% in 2022. The introduction of booster doses coincided with the maintenance of lower levels of lethality, even with circulation of the Delta and Omicron variants. The data suggest an inverse association between vaccination coverage and hospital lethality from SARI among older adults over the years analyzed. Conclusion: COVID-19 vaccination significantly reduced lethality from SARI among older adults in Brazil between 2020 and 2023. The findings confirm its effectiveness against severe forms, even in the face of new variants, especially with the administration of booster doses. High vaccination coverage, together with surveillance and hospital strengthening, contributed to the decline in mortality. Despite the limitations of aggregated data, standardization of SIVEP-Gripe strengthens the analysis. Continued vaccination and surveillance are essential to prevent new outbreaks.
Visceral leishmaniasis (VL), caused by Leishmania infantum, is endemic in Brazil. In people living with HIV (PLHIV), coinfection may present with atypical manifestations, severe course, and higher risk of relapse. Among the rare presentations is post- or para-kala-azar dermal leishmaniasis (PKDL), characterized by a maculopapular or nodular rash predominantly on the face, upper limbs, and trunk that occurs during or shortly after the visceral disease. Most cases described in the literature come from areas with higher prevalence of L. donovani; presentation with L. infantum is rare. We report the case of a 50-year-old Black woman from Chapada Diamantina (Bahia), diagnosed with VL in 2000 and treated with meglumine antimoniate. In 2013, she was diagnosed with HIV, with CD4 count 102 cells/mm³ and viral load 470,717 copies/mL. Initially with poor ART adherence, she had virologic failure and was later rescued with a new regimen. In 2019, with undetectable viral load and CD4 134 cells/mm³, she presented bicytopenia and gastrointestinal symptoms. Amastigotes were identified on duodenal biopsy, confirming the first VL relapse, treated with liposomal amphotericin B. She then started biweekly secondary prophylaxis with amphotericin. In 2020, during the COVID-19 pandemic, prophylaxis became irregular. In 2021, a new relapse occurred with pancytopenia and hepatosplenomegaly, confirmed by bone-marrow examination. In 2023, even on regular secondary prophylaxis, she developed epistaxis and bicytopenia associated with multiple cutaneous nodules on the face, limbs, and back. Workup for VL relapse was undertaken. Bone-marrow examination showed Leishmania spp. amastigotes. Histopathology of skin lesions revealed a nodular hypodermal lesion with epithelioid macrophages containing Leishmania spp. amastigotes, compatible with PKDL. She received liposomal amphotericin B (40 mg/kg) plus miltefosine, with clinical resolution of lesions within three months. She currently remains on biweekly prophylaxis, without further relapses. HIV/VL coinfection is a clinical challenge, particularly in patients with CD4 < 200 cells/mm³. PKDL is rare in areas with L. infantum and is more prevalent in PLHIV. This case underscores the importance of continuous prophylaxis, ART adherence, and recognition of PKDL as a manifestation of VL relapse.
Flavia Vitiello, Romain Lan, Giovanna Orsini
et al.
<b>Background:</b> The oral cavity is an entry site and a reservoir for viruses. Viral particles accumulate in saliva, which serves as a diagnostic fluid and vehicle for transmission (droplets and aerosols). Antiseptic mouthwashes were proposed as adjunctive measures to temporarily reduce oral viral load. <b>Objectives:</b> This scoping review aims to investigate the role of the oral cavity in viral infections, focusing on saliva and the use of antiseptic mouthwashes to reduce salivary viral load. <b>Methods:</b> Following the PRISMA-ScR guidelines, PubMed, EMBASE, and Web of Science were searched for human studies (2015–2025) investigating oral viral infections, saliva, or mouthwashes. Eligible studies were classified and analyzed for population, intervention, and outcomes. <b>Results:</b> Twenty-three studies met inclusion criteria (sixteen randomized controlled trials and seven systematic reviews). All included studies focused exclusively on SARS-CoV-2, as no clinical evidence on other oral viruses met the eligibility criteria. Saliva was consistently identified as a reliable, non-invasive specimen reflecting disease dynamics and transmission potential. Mouthwashes containing povidone-iodine, cetylpyridinium chloride, chlorhexidine, hydrogen peroxide or β-cyclodextrin–citrox produced measurable but short-lived reductions in salivary viral load. Heterogeneity and lack of standardized outcomes limited comparability. <b>Conclusions:</b> Antiseptic mouthwashes can provide a transient and complementary reduction in salivary viral load, particularly before aerosol-generating procedures; however, they should be regarded only as adjunctive measures and not as substitutes for standard infection-control protocols.
Michael Daniela Rodriguez-Afanado, Fabian Lopez-Vallejo, Cristian Ochoa-Puentes
et al.
Background:
The resistance of Mycobacterium tuberculosis (Mtb) on first- and second-line anti-tuberculosis (TB) drugs is an issue for TB control; therefore, developing new anti-TB drugs is a priority in TB research. In this sense, the Ca2+ P-type ATPase plasma membrane transporter CtpF is an interesting anti-TB drug target.
Methods:
In this work, the activity of 4C-substituted pyrrolo[1,2-a]quinoxalinic compounds on Mtb viability and Ca2+ ATPase activity mediated by the plasma membrane transporter, CtpF, was assessed. The pyrrolo[1,2-a]quinoxalines compounds were initially in silico and analyzed as potential inhibitors of the CtpF transporter. Molecular docking analyses showed that 4-(3,4-methylenedioxyphenyl) pyrrolo[1,2-a]quinoxaline (4b) and 4-(2-chlorophenyl) pyrrolo[1,2-a]quinoxaline (4c) compounds are potential CtpF inhibitors. These compounds were synthesized by green chemistry using deep eutectic solvent under environmentally friendly processes.
Results:
Even though both compounds, 4b and 4c, inhibit the plasma membrane Ca2+ ATPase activity mediated by the CtpF transporter (IC50 of 8.05 ± 0.04 µM and 9.15 ± 0.03 µM for 4b and 4c, respectively), only the 4b compound was active on Mtb cells (MIC = 25 µg/mL). Interestingly, compound 4b also showed low toxicity on VERO cells (19.65 ± 0.51%) and hemolytic activity (1.45 ± 0.20%) in human O Rh (+) erythrocytes.
Conclusions:
4-(3,4-methylenedioxyphenyl) pyrrolo[1,2-a]quinoxalinic core-derived compounds could be useful for developing alternative anti-TB compounds.
Abstract Due to envelope differences between Gram-positive and Gram-negative bacteria, engineering precision bactericidal contractile nanomachines requires atomic-level understanding of their structures; however, only those killing Gram-negative bacteria are currently known. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile. Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar linking the sheath with the membrane-penetrating tube. Compared to contractile machines targeting Gram-negative bacteria, major differences reside in the baseplate and contraction magnitude, consistent with target envelope differences. The multifunctional hub-hydrolase protein connects the tube and baseplate and is positioned to degrade peptidoglycan during penetration. The full-length tape measure protein forms a coiled-coil helix bundle homotrimer spanning the entire diffocin. Our study offers mechanical insights and principles for designing potent protein-based precision antibiotics.
Louafi Boutaina, Slimani Chaimae, Bessi Aymane
et al.
Silybum marianum L. Gaertn is a spontaneous plant whose medicinal properties have been used for over two thousand years. This study aims to clarify the understanding and utilisation of S. marianum by the rural and urban populations of Ouezzane region in Morocco, in order to assess the level of recognition and exploitation of this plant. An ethnobotanical survey in this region involved a sample of 140 individuals. Survey results are analyzed using SPSS. The survey results have revealed a significantly limited level of appreciation for S. marianum. Through the use of chi-square statistical tests, we identified significant relationships between our variables and the knowledge about S. marianum and its use. Based on the findings of our study, Silybum marianum L. remains one of Morocco's most neglected and underutilized plants. This may be due to a lack of knowledge or adequate information about its applications, a lack of general interest or even socio-economic factors that limit its exploitation.
Maria Luisa Beraldi Mestriner, Cacilda Tezelli Junqueira Padovani, Greizielle Barroso
et al.
Introdução/objetivo: O Papilomavírus humano (HPV) é causador de infecção sexualmente transmissível, a qual pode evoluir para o câncer, a depender do potencial de oncogenicidade viral. O início sexual cada vez mais precoce propicia alta vulnerabilidade das adolescentes às ISTs. O déficit do conhecimento entre os adolescentes acerca da infecção por HPV apresenta relevância e deve ser analisado. A vacinação é o método de prevenção mais eficaz e a cobertura vacinal ainda está abaixo da meta preconizada. A pesquisa teve como objetivo analisar o conhecimento sobre o HPV em estudantes da rede pública e promover ação educativa. Métodos: Trata-se de uma pesquisa descritiva, transversal, quantitativa, com coleta de dados primários, mediante entrevista estruturada com aplicação de questionário e atividades educativas (palestras, rodas de conversa, distribuição de cartilha e folders) a 194 estudantes do 6° ao 9° ano das escolas municipais Professor Luiz Cavallon e Domingos Gonçalves Gomes, no município de Campo Grande – MS (CEP/UFMS, Parecer n.: 5.596.389, 22/agosto/2022). Resultados: Os estudantes estavam na faixa etária de 10 a 15 anos, sendo a maioria do sexo feminino (63,4%). A maioria já ouviu falar sobre o HPV (70,1%; 136/194), no entanto, somente 38,1% (74/194) afirmaram que o HPV é um vírus que causa câncer e 11,3% (22/194) responderam que é um vírus que causa verrugas. Alguns deles (17,5%; 34/194) afirmaram que o HPV se referia diretamente ao termo câncer e 16,5% (32/194) apontaram que o HPV é a vacina. Cerca de um terço (61/194) demonstrou não ter conhecimento algum sobre o significado da sigla HPV e 10,8% (21/194) fizeram associação com o vírus herpes. Quando questionados sobre o que é o colo do útero, a maioria (73,2%; 142/194) respondeu que não sabia. A maioria 84,5% (164/194) sabem da existência da vacina contra o HPV e 57,7% (112/194) sabiam que a vacina está disponível de forma gratuita. Entre os participantes, 49% (95/194) afirmaram ter tomado a vacina, no entanto, quando consultados os dados referentes à vacinação no sistema e-SUS encontrou-se uma cobertura vacinal superior ao informado, onde 62,3% (121/194) dos alunos estavam vacinados e 40,7% (79/194) com esquema completo. Conclusão: Concluiu-se que há um déficit de conhecimento entre os participantes sobre a infecção por HPV, principalmente sobre a sua relação com o desenvolvimento do câncer e que há necessidade de intensificação de ações educativas e promoção da vacina
Marlene Jara, Jorge Arevalo, Alejandro Llanos-Cuentas
et al.
IntroductionResistance against anti-Leishmania drugs (DR) has been studied for years, giving important insights into long-term adaptations of these parasites to drugs, through genetic modifications. However, microorganisms can also survive lethal drug exposure by entering into temporary quiescence, a phenomenon called drug tolerance (DT), which is rather unexplored in Leishmania.MethodsWe studied a panel of nine Leishmania braziliensis strains highly susceptible to potassium antimonyl tartrate (PAT), exposed promastigotes to lethal PAT pressure, and compared several cellular and molecular parameters distinguishing DT from DR.Results and discussionWe demonstrated in vitro that a variable proportion of cells remained viable, showing all the criteria of DT and not of DR: i) signatures of quiescence, under drug pressure: reduced proliferation and significant decrease of rDNA transcription; ii) reversibility of the phenotype: return to low IC50 after removal of drug pressure; and iii) absence of significant genetic differences between exposed and unexposed lineages of each strain and absence of reported markers of DR. We found different levels of quiescence and DT among the different L. braziliensis strains. We provide here a new in-vitro model of drug-induced quiescence and DT in Leishmania. Research should be extended in vivo, but the current model could be further exploited to support R&D, for instance, to guide the screening of compounds to overcome the quiescence resilience of the parasite, thereby improving the therapy of leishmaniasis.
Veronika Heinz, Wenke Jäckel, Susann Kaltwasser
et al.
A cryo-electron microscopy reconstruction of a stressosome complex from a Gram-negative bacterium, Vibrio vulnificus, reveals variations in subunit composition and symmetry, which could serve to adjust the activation threshold in the response to low levels of oxygen and starvation.
Doppler ultrasonography is relatively a new method for evaluation of the renal diseases in dogs. This study was conducted to evaluate the efficacy of renal resistive index (RRI) in diagnosis and prognosis of acute kidney injury (AKI) in dogs and to ascertain its correlationwith other renal parameters. Twenty-seven dogs with AKI along with ten clinically healthy dogs were evaluated. The aetiology of AKI was multifactorial which included viper snake envenomation, pyometra, Babesiagibsoni infection, canine parvo viral infection, Ehrlichiacanis infection, leptospiral infection, bone meal poisoning and tetracycline-induced nephrotoxicity. Dogs with AKI were characterized
into five gradesas per the guidelines provided by International Renal Interest Society.Parameters such asblood urea nitrogen (BUN), creatinine, urine output, urine protein-creatinine (UPC) ratio and blood pressure were estimated. Both BUN and creatinine was significantly higher in affected dogs. Majority of the dogs with AKI were oliguric and had the presence of proteinuria, occult blood and leucocytes on urine dipstick examination. Urine Protein-Creatinine ratio was increased whereas no significant variation was noticed in blood pressure of dogs with AKI.B-mode ultrasonography of kidneys revealedrenomegaly, hyperechoic cortex, decreased cortico-medullary differentiation and loss of architecture in majority of the dogs with AKI. Renal resistive index was significantly
increased inAKI and a positive correlation was established between RRI and serumcreatinine but not with UPC ratio, blood pressure and size of kidneys. Re-evaluation of RRIseven days post treatment showed considerablereduction. It wasconcludedthat an increase in RRIwas associated with severity of renal parenchymal injuryin AKI and reduction of RRI post-treatment
indicated favorable prognosis.
Xiu Jia, Francisco Dini-Andreote, Joana Falcão Salles
Abstract Most ecological communities harbor many rare species (i.e., the rare biosphere), however, relatively little is known about how distinct ecological processes structure their existence. Here, we used spatiotemporal data on soil bacterial communities along a natural ecosystem gradient to model the relative influences of assembly processes structuring the rare and common biospheres. We found a greater influence of homogeneous selection (i.e., imposed by spatiotemporally constant variables) mediating the assembly of the rare biosphere, whereas the common biosphere was mostly governed by variable selection (i.e., imposed by spatial and/or temporal fluctuating variables). By partitioning the different types of rarity, we found homogeneous selection to explain the prevalence of permanently rare taxa, thus suggesting their persistence at low abundances to be restrained by physiological traits. Conversely, the dynamics of conditionally rare taxa were mostly structured by variable selection, which aligns with the ability of these taxa to switch between rarity and commonness as responses to environmental spatiotemporal variations. Taken together, our study contributes to the establishment of a link between conceptual and empirical developments in the ecology of the soil microbial rare biosphere. Besides, this study provides a framework to better understand, model, and predict the existence and dynamics of microbial rare biospheres across divergent systems and scales.