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Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in stress-induced sensitization (SIS) of behavioral responses, in which a particular stressor triggers a state of hyper-responsiveness to other stressors after an incubation period, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents SIS; blocking NOS-2 90 min after stress also prevents stress-induced sensitization, as does blocking calcium-activated potassium channels in this latter time window. Stress-induced sensitization is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce stress-induced sensitization.

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Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae preferentially infects skin macrophages and Schwann cells-glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host-pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signaling molecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor A2AR involved in neuroimmune response, lipid metabolism, and neuron-glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during M. leprae-Schwann cell interaction. Methods: M. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae in the presence or absence of specific agonists or antagonists of AdoS. Enzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR analysis were performed. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzyme-linked immunosorbent assay. Results: We demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular M. leprae viability; 4) increased levels of p-CREB. Conclusion: These findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.

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Genome-wide association studies (GWASs) allow for inferences about the relationships between genomic variants and phenotypic traits in natural or breeding populations. However, few have used this methodology in Coffea arabica. We aimed to identify chromosomal regions with significant associations between SNP markers and agronomic traits in C. arabica. We used a coffee panel consisting of 195 plants derived from 13 families in F2 generations and backcrosses of crosses between leaf rust-susceptible and -resistant genotypes. The plants were phenotyped for 18 agronomic markers and genotyped for 21,211 SNP markers. A GWAS enabled the identification of 110 SNPs with significant associations (p < 0.05) for several agronomic traits in C. arabica: plant height, plagiotropic branch length, number of vegetative nodes, canopy diameter, fruit size, cercosporiosis incidence, and rust incidence. The effects of each SNP marker associated with the traits were analyzed, such that they can be used for molecular marker-assisted selection. For the first time, a GWAS was used for these important agronomic traits in C. arabica, enabling applications in accelerated coffee breeding through marker-assisted selection and ensuring greater efficiency and time reduction. Furthermore, our findings provide preliminary knowledge to further confirm the genomic loci and potential candidate genes contributing to various structural and disease-related traits of C. arabica.

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Parkinson's disease (PD) is a debilitating condition that can cause locomotor problems in affected patients, such as tremors and body rigidity. PD therapy often includes the use of monoamine oxidase B (MAOB) inhibitors, particularly phenylhalogen compounds and coumarin-based semi-synthetic compounds. The objective of this study was to analyze the structural, pharmacokinetic, and pharmacodynamic profile of a series of Triazolo Thiadiazepine-fused Coumarin Derivatives (TDCDs) against MAOB, in comparison with the inhibitor safinamide. To achieve this goal, we utilized structure-based virtual screening techniques, including target prediction and absorption, distribution, metabolism, and excretion (ADME) prediction based on multi-parameter optimization (MPO) topological analysis, as well as ligand-based virtual screening techniques, such as docking and molecular dynamics. The findings indicate that the TDCDs exhibit structural similarity to other bioactive compounds containing coumarin and MAOB-binding azoles, which are present in the ChEMBL database. The topological analyses suggest that TDCD3 has the best ADME profile, particularly due to the alignment between low lipophilicity and high polarity. The coumarin and triazole portions make a strong contribution to this profile, resulting in a permeability with Papp estimated at 2.15 × 10-5 cm/s, indicating high cell viability. The substance is predicted to be metabolically stable. It is important to note that this is an objective evaluation based on the available data. Molecular docking simulations showed that the ligand has an affinity energy of - 8.075 kcal/mol with MAOB and interacts with biological substrate residues such as Pro102 and Phe103. The results suggest that the compound has a safe profile in relation to the MAOB model, making it a promising active ingredient for the treatment of PD.

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Candida spp. can be found in the human microbiome. However, immunocompromised patients are likely to develop invasive Candida infections, with mortality rates higher than 50%. The discovery of C. auris, a species that rapidly acquire antifungal resistance, increased the concern about Candida infections. The limited number of antifungal agents and the high incidence of resistance to them make imperative the development of new antifungal drugs. ß-lapachone is a biological active naphthoquinone that displays antifungal activity against C. albicans and C. glabrata. The aim of this study was to evaluate if this substance affects C. auris growth and elucidate its mechanism of action. A fluconazole-resistant C. auris isolate was used in this study. The antifungal activity of ß-lapachone was determined through microbroth dilution assays, and its mechanism of action was evaluated using fluorescent probes. Interaction with fluconazole and amphotericin B was assessed by disk diffusion assay and checkerboard. ß-lapachone inhibited planktonic C. auris cell growth by 92.7%, biofilm formation by 84.9%, and decrease the metabolism of preformed biofilms by 87.1% at 100 µg/ml. At 100 µg/ml, reductions of 30% and 59% of Calcofluor White and Nile red fluorescences were observed, indicating that ß-lapachone affects cell wall chitin and neutral lipids content, respectively. Also, the ratio 590 nm/529 nm of JC-1 decreased 52%, showing that the compound affects mitochondria. No synergism was observed between ß-lapachone and fluconazole or amphotericin B. Data show that ß-lapachone may be a promising candidate to be used as monotherapy to treat C. auris resistant infections.

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This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

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Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

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The persistent symptoms of post-COVID-19 syndrome negatively impact health, quality of life, and productivity. This study aimed to describe the persistent symptoms of post-COVID-19 syndrome (especially neurological ones) and their 12-month post-infection cognitive, emotional, motor, quality of life, and indirect cost repercussions. Patients showing the first symptoms of COVID-19 from January to June 2021 who developed post-COVID-19 syndrome and sought care at the Fortaleza Unit (Ceará, Brazil) of the SARAH Network of Rehabilitation Hospitals were included in this study. Information was obtained at the baseline follow-up and by telephone interview 12 months post-infection. In total, 58 people participated in this study with an average age of 52.8±10.5 years, of which 60% required an ICU. The most frequent symptoms on admission included fatigue (64%), arthralgia (51%), and dyspnea (47%), whereas, after 12 months, fatigue (46%) and memory impairment (39%). The following scales/functional tests showed alterations: PCFS, MoCA, HAD, FSS, SF-36, TLS5x, timed up and go, 6-minute walk, and handgrip. Indirect costs totaled USD 227,821.00, with 11,653 days of absenteeism. Moreover, 32% of patients were unable to return to work. Better TLS5x and higher SF-36 scores in the functional capacity, physical functioning, vitality, and pain dimensions were associated with return to work (p ≤ 0.05). The most frequent persistent symptoms referred to fatigue, arthralgia, dyspnea, anxiety, and depression, which negatively affected cognitive, emotional, and motor function and quality of life. These symptoms lasted for over a year, especially fatigue and memory alteration, the latter of which being the most reported after COVID-19 infections. Results also show a significant difficulty returning to work and indirect costs of USD 4,847.25 per person/year.

Os sintomas persistentes da síndrome pós-COVID-19 acarretam impactos negativos na saúde, qualidade de vida e produtividade. O objetivo deste trabalho foi descrever os sintomas persistentes da síndrome pós-COVID-19, principalmente neurológicos, e as repercussões cognitivas, emocionais, motoras, de qualidade de vida e de custos indiretos, 12 meses após a infecção. Pacientes com primeiros sintomas entre janeiro e junho de 2021 evoluíram com síndrome pós-COVID-19 e procuraram atendimento na unidade da Rede SARAH de Hospitais de Reabilitação em Fortaleza, Ceará, Brasil. As informações foram obtidas no início do acompanhamento e por entrevista telefônica após 12 meses da infecção. Participaram do estudo 58 pessoas, com idade média de 52,8 anos (±10,5) e 60% permaneceram em UTI. Os sintomas mais frequentes na admissão foram: fadiga (64%), artralgia (51%) e dispneia (47%); e após 12 meses: fadiga (46%) e alteração de memória (39%). Foram identificadas alterações nas escalas/testes funcionais: PCFS, MoCA, HAD, FSS, SF-36, TLS5x, Timed up and go, caminhada de 6 minutos e preensão manual. Os custos indiretos totais foram de USD 227.821,00, com 11.653 dias de absenteísmo; 32% dos pacientes não voltaram a trabalhar. Melhores resultados de TLS5x e SF-36, nas dimensões capacidade funcional, aspecto físico, vitalidade e dor, demonstraram associação com retorno laboral (p ≤ 0,05). Os sintomas persistentes mais frequentes foram: fadiga, artralgia, dispneia, ansiedade e depressão, com repercussões negativas na funcionalidade cognitiva, emocional, motora e qualidade de vida. Esses sintomas perduraram por mais de um ano, principalmente fadiga e alteração de memória, sendo esta última mais relatada tardiamente. Houve dificuldade importante de retorno laboral e custos indiretos de USD 4.847,25 por pessoa/ano.

Síntomas persistentes del síndrome post-COVID-19 provocan impactos negativos en la salud, calidad de vida y productividad. El objetivo fue describir los síntomas persistentes del síndrome post-COVID-19, sobre todo neurológicos, y las repercusiones cognitivas, emocionales, motoras, de calidad de vida y los costos indirectos, 12 meses tras la infección. Pacientes que tuvieron los primeros síntomas entre enero y junio de 2021, desarrollaron síndrome post-COVID-19 y buscaron atención en la unidad de la Red SARAH de Hospitales de Rehabilitación en Fortaleza, Ceará, Brasil. Las informaciones se obtuvieron al inicio del seguimiento y por entrevista telefónica 12 meses tras la infección. Participaron 58 personas, con edad de 52,8±10,5 años y el 60% permaneció en la UTI. Los síntomas más frecuentes al ingreso fueron: fatiga (64%), artralgia (51%) y disnea (47%); tras 12 meses fueron: fatiga (46%) y alteración de memoria (39%). Se identificaron alteraciones en las escalas/testes funcionales: PCFS, MoCA, HAD, FSS, SF-36, TLS5x, timed up and go, caminar por 6 minutos y prensión manual. Los costos indirectos totales fueron USD 227.821,00, con 11.653 días de absentismo. El 32% de los pacientes no volvió a trabajar. Mejor TLS5x y SF-36 en las dimensiones capacidad funcional, aspecto físico, vitalidad y dolor demostraron una asociación con el retorno al trabajo (p ≤ 0,05). Los síntomas persistentes más frecuentes fueron fatiga, artralgia, disnea, ansiedad y depresión, con repercusiones negativas en la funcionalidad cognitiva, emocional, motora y calidad de vida. Estos síntomas continuaron por más de un año, sobre todo la fatiga y la alteración de la memoria, siendo esta última reportada con más frecuencia tardíamente. Hubo una dificultad importante en el retorno al trabajo y costos indirectos de USD 4.847,25 persona/año.

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23 livers of South American fur seal (Arctocephalus australis) found stranded in southern Brazilian beaches were evaluated for Persistent Organic Pollutants (POPs) and Polycyclic Aromatic Hydrocarbons (PAHs). POPs (DDTs, mirex, eldrin, dieldrin, aldrin, isodrin, HCHs, chlordanes and PCBs) and PAHs in livers were Soxhlet extracted, analyzed and quantified using Gas Chromatography Tandem Mass Spectrometry (GC-TQMS). The main POPs found were PCBs and DDTs, totaling 81 %. Among pesticides, mirex followed DDTs, possibly due to usage in Uruguay, followed by Σdrins, ΣCHLs and ΣHCHs. Naphthalene was the major PAH found, while heavier compounds did not significantly bioaccumulate. Concentrations of POPs resembled previous findings for A. australis. Considering only juveniles, no POPs showed significant differences between sexes. Lipidic content, weight and length did not show any correlation with POP concentration. This was the first record of PAHs and PBDEs in South American fur seals, and the levels of these pollutants were relatively low.

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The Enterobacteriaceae family is recognized as a primary group of Gram-negative pathogens responsible for foodborne illnesses and is frequently associated with antibiotic resistance. The present study explores the natural-based compound trans-cinnamaldehyde (TC) against drug-resistant Enterobacteriaceae and its synergism with gentamicin (GEN) to address this issue. The research employs three strains of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, previously isolated from shrimp. The antibacterial activity was evaluated by the disk diffusion method, microdilution test, kinetics of growth, and time-kill curve. In addition, the synergistic effect between TC/GEN was investigated by checkerboard assay. All strains showed sensitivity to TC with an inhibition zone diameter > 35 mm. The TC showed inhibitory and bactericidal action in the most tested bacteria around 625 µg/mL. Sub-inhibitory amounts (1/2 and 1/4 MIC) of TC interfered with the growth kinetics by lag phase extension and decreased the log phase. Time-kill curves show a reduction of viable cells after the first hour of TC treatment at bactericidal concentrations. The synergistic effect between TC/GEN was observed for E. coli and E. cloacae strains with FICi ranging from 0.15 to 0.50. These findings, therefore, suggest TC as a promising alternative in the fight against drug-resistant Enterobacteriaceae that can cause foodborne illnesses.

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Introduction: The COVID-19 pandemic may lead to reduced physical activity (PA) in health care workers (HCWs). Objective: To evaluate leisure and transport-related PA in HCW of a COVID-19-dedicated hospital during the first wave of the COVID-19 pandemic. Methods: This is a cross-sectional study with a sample of 1,527 HCWs. Socioeconomic aspects, occupational characteristics, and engagement in leisure and transport-related PA were investigated through an online survey administered in August of 2020. Results: More than 80 % HCWs performed < 150 min/week of leisure-related PA, and 85 % performed ≤ 30 min/day transport-related PA. Being male was associated with more PA (OR: 1.93; 95 % CI:1.40-2.66) and transport-related PA; working in nursing, physical therapy, and cleaning/housekeeping services was associated with low PA (OR: 0.70; 95 % CI:0.51-0.95). Physicians and administrative staff were less active in transport-related PA. Conclusions: HCWs working in a COVID-19 hospital had low levels of PA in the domains of leisure and transportation.

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BACKGROUND: the integration of dentistry services in the Unified Health System in Brazil (SUS) is essential in primary care assistance. OBJECTIVE: we aimed to develop a tool for improving demand flowby evaluating the impact of oral health on the daily activities of users of the Family Health Unitusing the Oral Impacts of Daily Performance (OIDP)tool. METHODS: In Barretos, Brazil, a cross-sectional study was conducted at a Family Health Unit (FHU)including patients over 12 years old. Oral health impact was assessed using the Oral Impacts of Daily Performance (OIDP) tool, and family risk was measured with the Coelho-Savassi scale. RESULTS: 430 participants, including 411 adults and 19 young people, were recruited. Of the adults, 31% had an average OIDP score of 16.61. For young people, 53% reported an impact (average OIDP score: 28.61). Family risk (R1) was prevalent in 57.9% of young people and 53.3% of adults. Among adults, different activities were affected by risk: smiling without embarrassment (risk level 2), enjoying contact with people (risk level 3), and performing one's job or social role (risk level 1). Emotional state (R3) had the lowest OIDP score (p = 0.029). CONCLUSION: implementation of the OIDP scale in clinical practice enhances healthcare planning and ensures better-quality and equitable services, thus emphasizing comprehensive oral healthcare within the SUS.

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Abstract Objective: To analyze the existing state legislation, including not only the ordinary laws, but also their infralegal regulation and the state legislation on Hospital Dentistry. Material and Methods: A survey was carried out in the databases of the Legislative Assemblies of the Brazilian States and the Federal District, as well as the Regional and Federal Councils of Dentistry in Brazil. Subsequently, a survey was carried out in the databases of the Ministry of Health, State Dental Councils and Federal Dental Council in Brazil. Results: Only 8 Brazilian states have legislation in force regarding hospital dentistry, which represents 29.63% of the federative units. Among the Brazilian regions, the Midwest presented the highest prevalence of the laws found (37.50%), followed by the North (25%) and the other regions with the same coverage (12.50%). Also, an orientation and an ordinance from the Ministry of Health, six resolutions from the Federal Council of Dentistry, and a technical note from the National Health Surveillance Agency were found. Conclusion: Several States do not have rules on the subject, making it imperative to create a federal rule that not only imposes the presence of the dentist, but also regulates the proportion of the team, workload, and availability.

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ABSTRACT This report presents the case of an adult patient with mental and intellectual limitations, whose main complaint was dental aesthetics. Dental treatment was performed at the Piracicaba Dental School and approved by the Ethics Committee (CAAE: 65752322.2.0000.5418). Clinically, the patient had inadequacies in the dental arrangement, with periodontal involvement that put the dental elements at risk. In intraoral clinical aspects, the deficiency was identified as maxillary atresia. The buccolingual inclination of the mandibular anterior teeth highlighted the severe crowding and anterior crossing of these teeth. Dental treatment was carried out aiming at the remission of periodontal and orthodontic problems in an integrated manner and with approaches that allowed greater interaction, participation, and patient compliance during treatment. Supra and subgingival scrapings and extraction of the upper left lateral incisor were performed. After three months of periodontal treatment, orthodontic treatment was started with fixed orthodontic appliances. The main objective was to level and align the teeth in both arches to achieve better aesthetic and functional conditions. Due to the COVID-19 pandemic, treatment has been discontinued. This resulted in the regression of the results obtained, including regarding self-care. People with disabilities require dental care with specific strategies for their needs, which must be carried out by a multidisciplinary team. Despite the access limitation imposed by the pandemic, the patient reestablished his motivation to restart treatment, which was facilitated by the bond of trust established between him and the team.

RESUMO Este relato apresenta o caso de um paciente adulto com limitações mentais e intelectuais, cuja queixa principal era a estética dental. O tratamento odontológico foi realizado na Faculdade de Odontologia de Piracicaba e aprovado pelo Comitê de Ética (CAAE: 65752322.2.0000.5418). Clinicamente, o paciente apresentava inadequações no arranjo dentário, com comprometimento periodontal, que colocava em risco os elementos dentais. Nos aspectos clínicos intrabucais, a deficiência foi identificada como atresia maxilar. A inclinação vestíbulo-lingual dos dentes anteriores inferiores destacou o apinhamento severo e o cruzamento anterior desses dentes. O tratamento odontológico foi realizado visando à remissão dos problemas periodontais e ortodônticos de forma integrada e com abordagens que permitissem maior interação, participação e adesão do paciente durante o tratamento. Foram realizadas raspagens supra e subgengivais e extração do incisivo lateral superior esquerdo. Após três meses de tratamento periodontal, iniciou-se o tratamento ortodôntico com aparelhos ortodônticos fixos. O objetivo principal foi nivelar e alinhar os dentes em ambas as arcadas para alcançar melhores condições estéticas e funcionais. Devido à pandemia de COVID-19, o tratamento foi interrompido. Isso resultou na regressão dos resultados obtidos, inclusive quanto ao autocuidado. As pessoas com deficiência requerem atendimento odontológico com estratégias específicas para suas necessidades, que devem ser realizadas por uma equipe multidisciplinar. Apesar da limitação de acesso imposta pela pandemia, o paciente restabeleceu sua motivação para reiniciar o tratamento, o que foi facilitado pelo vínculo de confiança estabelecido entre ele e a equipe.

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Os sintomas persistentes da síndrome pós-COVID-19 acarretam impactos negativos na saúde, qualidade de vida e produtividade. O objetivo deste trabalho foi descrever os sintomas persistentes da síndrome pós-COVID-19, principalmente neurológicos, e as repercussões cognitivas, emocionais, motoras, de qualidade de vida e de custos indiretos, 12 meses após a infecção. Pacientes com primeiros sintomas entre janeiro e junho de 2021 evoluíram com síndrome pós-COVID-19 e procuraram atendimento na unidade da Rede SARAH de Hospitais de Reabilitação em Fortaleza, Ceará, Brasil. As informações foram obtidas no início do acompanhamento e por entrevista telefônica após 12 meses da infecção. Participaram do estudo 58 pessoas, com idade média de 52,8 anos (±10,5) e 60% permaneceram em UTI. Os sintomas mais frequentes na admissão foram: fadiga (64%), artralgia (51%) e dispneia (47%); e após 12 meses: fadiga (46%) e alteração de memória (39%). Foram identificadas alterações nas escalas/testes funcionais: PCFS, MoCA, HAD, FSS, SF-36, TLS5x, Timed up and go, caminhada de 6 minutos e preensão manual. Os custos indiretos totais foram de USD 227.821,00, com 11.653 dias de absenteísmo; 32% dos pacientes não voltaram a trabalhar. Melhores resultados de TLS5x e SF-36, nas dimensões capacidade funcional, aspecto físico, vitalidade e dor, demonstraram associação com retorno laboral (p ≤ 0,05). Os sintomas persistentes mais frequentes foram: fadiga, artralgia, dispneia, ansiedade e depressão, com repercussões negativas na funcionalidade cognitiva, emocional, motora e qualidade de vida. Esses sintomas perduraram por mais de um ano, principalmente fadiga e alteração de memória, sendo esta última mais relatada tardiamente. Houve dificuldade importante de retorno laboral e custos indiretos de USD 4.847,25 por pessoa/ano.

Síntomas persistentes del síndrome post-COVID-19 provocan impactos negativos en la salud, calidad de vida y productividad. El objetivo fue describir los síntomas persistentes del síndrome post-COVID-19, sobre todo neurológicos, y las repercusiones cognitivas, emocionales, motoras, de calidad de vida y los costos indirectos, 12 meses tras la infección. Pacientes que tuvieron los primeros síntomas entre enero y junio de 2021, desarrollaron síndrome post-COVID-19 y buscaron atención en la unidad de la Red SARAH de Hospitales de Rehabilitación en Fortaleza, Ceará, Brasil. Las informaciones se obtuvieron al inicio del seguimiento y por entrevista telefónica 12 meses tras la infección. Participaron 58 personas, con edad de 52,8±10,5 años y el 60% permaneció en la UTI. Los síntomas más frecuentes al ingreso fueron: fatiga (64%), artralgia (51%) y disnea (47%); tras 12 meses fueron: fatiga (46%) y alteración de memoria (39%). Se identificaron alteraciones en las escalas/testes funcionales: PCFS, MoCA, HAD, FSS, SF-36, TLS5x, timed up and go, caminar por 6 minutos y prensión manual. Los costos indirectos totales fueron USD 227.821,00, con 11.653 días de absentismo. El 32% de los pacientes no volvió a trabajar. Mejor TLS5x y SF-36 en las dimensiones capacidad funcional, aspecto físico, vitalidad y dolor demostraron una asociación con el retorno al trabajo (p ≤ 0,05). Los síntomas persistentes más frecuentes fueron fatiga, artralgia, disnea, ansiedad y depresión, con repercusiones negativas en la funcionalidad cognitiva, emocional, motora y calidad de vida. Estos síntomas continuaron por más de un año, sobre todo la fatiga y la alteración de la memoria, siendo esta última reportada con más frecuencia tardíamente. Hubo una dificultad importante en el retorno al trabajo y costos indirectos de USD 4.847,25 persona/año.

The persistent symptoms of post-COVID-19 syndrome negatively impact health, quality of life, and productivity. This study aimed to describe the persistent symptoms of post-COVID-19 syndrome (especially neurological ones) and their 12-month post-infection cognitive, emotional, motor, quality of life, and indirect cost repercussions. Patients showing the first symptoms of COVID-19 from January to June 2021 who developed post-COVID-19 syndrome and sought care at the Fortaleza Unit (Ceará, Brazil) of the SARAH Network of Rehabilitation Hospitals were included in this study. Information was obtained at the baseline follow-up and by telephone interview 12 months post-infection. In total, 58 people participated in this study with an average age of 52.8±10.5 years, of which 60% required an ICU. The most frequent symptoms on admission included fatigue (64%), arthralgia (51%), and dyspnea (47%), whereas, after 12 months, fatigue (46%) and memory impairment (39%). The following scales/functional tests showed alterations: PCFS, MoCA, HAD, FSS, SF-36, TLS5x, timed up and go, 6-minute walk, and handgrip. Indirect costs totaled USD 227,821.00, with 11,653 days of absenteeism. Moreover, 32% of patients were unable to return to work. Better TLS5x and higher SF-36 scores in the functional capacity, physical functioning, vitality, and pain dimensions were associated with return to work (p ≤ 0.05). The most frequent persistent symptoms referred to fatigue, arthralgia, dyspnea, anxiety, and depression, which negatively affected cognitive, emotional, and motor function and quality of life. These symptoms lasted for over a year, especially fatigue and memory alteration, the latter of which being the most reported after COVID-19 infections. Results also show a significant difficulty returning to work and indirect costs of USD 4,847.25 per person/year.

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Objective: The aim of this study was to present a new technique for hybrid marking of non-palpable breast lesions and in vivo evaluation of surgical margins, called Fluorescence and Seed for Hybrid Intraoperative Evaluation. Methods: Seven women with non-palpable breast lesions and suspected or confirmed malignancy underwent prior iodine-125 seed implantation and peripheral intravenous administration of indocyanine green 30 min before surgery. A hybrid gamma probe with an optonuclear probe was used to detect gamma radiation in the lesions and, sequentially, the fluorescence mode, in the same lesion and its margins, after its removal. Results: This method distinguished, in real time, one benign and six malignant lesions, guiding the removal, identifying the remaining neoplastic area in the surgical bed, and allowing its intraoperative enlargement. Conclusion: This pilot study evaluates the feasibility of this new technique in identifying the primary lesion and controlling surgical margins using hybrid technology. (AU)

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Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae preferentially infects skin macrophages and Schwann cells­glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host­pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signaling molecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor A2AR involved in neuroimmune response, lipid metabolism, and neuron­glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during M. leprae­Schwann cell interaction. Methods: M. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae in the presence or absence of specific agonists or antagonists of AdoS. nzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR nalysis were performed. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzymelinked immunosorbent assay. Results: We demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular M. leprae viability; 4) increased levels of p-CREB. Conclusion: These findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.

Assuntos

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The adaptive potential of plants is commonly used as an indicator of genotypes with higher breeding program potential. However, the complexity and interaction of plant metabolic parameters pose a challenge to selection strategies. In this context, this study aimed to explore phenotypic plasticity within the germplasm of Hybrid Timor coffee. Additionally, we assessed the utility of the multivariate phenotypic plasticity index (MVPi) as a promising tool to predict genotype performance across diverse climatic conditions. To achieve this, we evaluated the performance of seven accessions from the Hybrid Timor germplasm in comparison to the Rubi and IPR 100 cultivars, known for their susceptibility and resistance to drought, respectively. The experiment took place in a greenhouse under two conditions: one with normal soil moisture levels near maximum capacity, and the other with a water deficit scenario involving a period of no irrigation followed by rehydration. Data on physiological and biochemical factors were collected at three stages: before applying the water deficit, during its imposition, and after rehydration. Growth data were obtained by the difference between the beginning and end of the experimental period Furthermore, field evaluations of the productivity of the same genotypes were carried out over two consecutive seasons. Based on physiological and biochemical assessments, the MVPi was computed, employing Euclidean distance between principal component multivariate analysis scores. Subsequently, this index was correlated with growth and productivity data through linear regressions. Our findings reveal that the plastic genotypes that are capable of significantly altering physiological and biochemical parameters in response to environmental stimuli exhibited reduced biomass loss in both aerial and root parts. As a result, this positively influenced their productivity. Enhanced plasticity was particularly prominent in accessions from the MG Germplasm Collection: MG 311-Hybrid Timor UFV 428-02, MG 270-Hybrid Timor UFV 377-21, and MG 279-Hybrid Timor UFV 376-31, alongside the Rubi MG 1192 cultivar. The MVPi emerged as a valuable instrument to assess genotype adaptability and predict their performance under varying climatic scenarios.

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Candida species are one of the most concerning causative agents of fungal infections in humans. The treatment of invasive Candida infections is based on the use of fluconazole, but the emergence of resistant isolates has been an increasing concern which has led to the study of alternative drugs with antifungal activity. Sphingolipids have been considered a promising target due to their roles in fungal growth and virulence. Inhibitors of the sphingolipid biosynthetic pathway have been described to display antifungal properties, such as myriocin and aureobasidin A, which are active against resistant Candida isolates. In the present study, aureobasidin A did not display antibiofilm activity nor synergism with amphotericin B, but its combination with fluconazole was effective against Candida biofilms and protected the host in an in vivo infection model. Alterations in treated cells revealed increased oxidative stress, reduced mitochondrial membrane potential and chitin content, as well as altered morphology, enhanced DNA leakage and a greater susceptibility to sodium dodecyl sulphate (SDS). In addition, it seems to inhibit the efflux pump CaCdr2p. All these data contribute to elucidating the role of aureobasidin A on fungal cells, especially evidencing its promising use in clinical resistant isolates of Candida species.

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BACKGROUND: To evaluate the cost-effectiveness ratio and economic impact of the Rapid Antigen Test (TR-Ag) to replace RT-PCR for the detection of the new Coronavirus in the Unified Health System (SUS). METHODS: This is a cost-effectiveness analysis. Clinical protocols were used for the diagnosis of COVID-19 at the São José Municipal Hospital, located in the city of Itaberá-SP. The Incremental Cost-Effectiveness Ratio (ICER) was divided into two scenarios. In the first, the accuracy reported by the test manufacturers was included, and in the second, the cost resulting from a systematic review. Both were compared with the performance of the RT-PCR test. The increase in diagnoses was chosen as a health outcome and absenteeism was used as a criterion for assessing the economic impact. RESULTS: The analysis resulted in incremental cost-effectiveness ratios of R$ 42,136.67 and R$ 68,329.73 for every thousand tests, according to the accuracy of the manufacturers' TR-Ag tests and what is reported in the literature in relation to RT-PCR, respectively. The average value found for the RT-PCR test (R$ 202.87) represents an increase of 165.32% in cost in relation to the value found for the TR-Ag. 4,305 tests were performed between April 2020 and December 2021 at the referral hospital. Also, maintaining the use of RT-PCR as the first choice for diagnosing COVID-19 and regulating absenteeism in the economically active population could have an impact of up to R$ 1,022,779.68 on municipal management. CONCLUSION: It is concluded that the TR-Ag are configured as a cost-effective alternative for the SUS in the detection of the new Coronavirus. The strategy becomes economically favorable for the expansion of testing, combating the COVID-19 pandemic and reducing the impact on the local economy. However, studies are needed to validate the accuracy of the tests so that economic evaluations on the subject are more assertive.