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Lygia Paccini Lustosa,1 Patrícia Parreira Batista,1 Daniele Sirineu Pereira,2 Leani Souza Máximo Pereira,1 Aline Scianni,1 Giane Amorim Ribeiro-Samora1 1Physical Therapy Department, Universidade Federal de Minas Gerais, Belo Horizonte, 2Physical Therapy Department, Universidade Federal de Alfenas, Alfenas, Brazil Background: Sarcopenia is a multifactorial geriatric syndrome with complex interrelationships. Increased plasma levels of inflammatory mediators increase the catabolic stimuli of the musculature, thereby causing a decrease in mass and muscular function. Objective: The objective of this study was to compare the performance of the knee extensors test (by isokinetic dynamometer) and plasma levels of interleukin-6 (IL-6) and soluble receptors of tumor necrosis factor alpha (sTNFR1) between sarcopenics and non-sarcopenics community-dwelling elderly women residents of Brazil. Material and methods: The diagnosis of sarcopenia included measurements of body composition (by densitometry with dual energy source of X-ray), handgrip strength (by Jamar® dynamometer), and the usual gait velocity according to the recommendations of the European Working Group on Sarcopenia in Older People. In both sarcopenics and non-sarcopenics elderly women, we evaluated the muscle function by knee extensors test (using an isokinetic dynamometer Byodex System 4 Pro®) at angular speeds of 60°/s and 180°/s) and also we evaluated the plasma concentrations of IL-6 and sTNFR1. Comparisons of muscle performance between groups were carried out using mixed factorial ANOVA with post hoc Bonferroni test; sTNFR1 and IL-6 variables were analyzed by applying Mann–Whitney U test. Results: Statistical differences were observed between groups regarding muscle power (P=0.01), total work adjusted to body weight (P=0.01) at a rate of 180°/s, and plasma levels of sTNFR1 (P=0.01). Conclusion: Sarcopenic elder women showed lower performance of the lower limbs, especially at a higher speed, predisposing these older women to greater vulnerability in functional activities that require agility and postural stability. Plasma levels of sTNFR1 were higher for non-sarcopenics elderlies. However, due to the observational nature of the study, it was impossible to infer causality among the variables surveyed. Keywords: sarcopenia, muscle performance, inflammatory mediators, aging

Leani Souza Máximo Pereira,1,2 Catherine Sherrington,2,3 Manuela L Ferreira,2 Anne Tiedemann,2,3 Paulo H Ferreira,4 Fiona M Blyth,5 Jacqueline CT Close,3,6 Morag Taylor,3,6 Stephen R Lord3 1Department of Physiotherapy, School of Physical Education, Physiotherapy, and Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; 2Musculoskeletal Division, The George Institute for Global Health, The University of Sydney, Sydney, Australia; 3Neuroscience Research Australia, University of New South Wales, Sydney, Australia; 4Discipline of Physiotherapy, Faculty of Health Sciences, The University of Sydney, Sydney, Australia; 5Pain Management and Research Institute, Royal North Shore Hospital, The University of Sydney, Sydney, Australia; 6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia Background/objectives: The impact of pain on the physical performance of patients in aged care rehabilitation is not known. The study sought to assess 1) the prevalence of pain in older people being discharged from inpatient rehabilitation; 2) the association between self-reported pain and physical performance in people being discharged from inpatient rehabilitation; and 3) the association between self-reported pain and physical performance in this population, after adjusting for potential confounding factors. Methods: This was an observational cross-sectional study of 420 older people at two inpatient aged care rehabilitation units. Physical performance was assessed using the Lower Limb Summary Performance Score. Pain was assessed with questions about the extent to which participants were troubled by pain, the duration of symptoms, and the impact of chronic pain on everyday activity. Depression and the number of comorbidities were assessed by questionnaire and medical file audit. Cognition was assessed with the Mini-Mental State Examination. Results: Thirty percent of participants reported chronic pain (pain lasting more than 3 months), and 17% reported that this pain interfered with daily activities to a moderate or greater extent. Chronic pain (P=0.013) and chronic pain affecting daily activities (P

Alexandra Miranda Assumpção Picorelli, Daniele Sirineu Pereira, Diogo Carvalho Felício, Daniela Maria Dos Anjos, Danielle Aparecida Gomes Pereira, Rosângela Corrêa Dias, Marcella Guimarães Assis, Leani Souza Máximo Pereira Graduate Program in Rehabilitation Sciences, Department of Physical Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Background: Participation of older people in a program of regular exercise is an effective strategy to minimize the physical decline associated with age. The purpose of this study was to assess adherence rates in older women enrolled in two different exercise programs (one aerobic exercise and one strength training) and identify any associated clinical or functional factors. Methods: This was an exploratory observational study in a sample of 231 elderly women of mean age 70.5 years. We used a structured questionnaire with standardized tests to evaluate the relevant clinical and functional measures. A specific adherence questionnaire was developed by the researchers to determine motivators and barriers to exercise adherence. Results: The adherence rate was 49.70% in the aerobic exercise group and 56.20% in the strength training group. Multiple logistic regression models for motivation were significant (P=0.003) for the muscle strengthening group (R2=0.310) and also significant (P=0.008) for the aerobic exercise group (R2=0.154). A third regression model for barriers to exercise was significant (P=0.003) only for the muscle strengthening group (R2=0.236). The present study shows no direct relationship between worsening health status and poor adherence. Conclusion: Factors related to adherence with exercise in the elderly are multifactorial. Keywords: older women, adherence, therapeutic exercises

Background: With the increase in the elderly population, a growing number of chronic degenerative diseases and a greater dependency on caregivers have been observed. Elderly persons in states of frailty remain more susceptible to significant health complications. There is evidence of an inverse relationship between plasma levels of inflammatory mediators and levels of functionality and muscle strength, suggesting that muscle-strengthening measures can aid in inflammatory conditions. The purpose of this study will be verified the effect of a muscle-strengthening program with load during a ten-week period in pre-frail elderly women with attention to the following outcomes: (1) plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), (2) functional capacity and (3) knee extensor muscle strength.Methods/design: The study design is a randomized crossover clinical trial evaluating 26 elderly women (regardless of their race and/or social condition) who are community residents, older than 65, and classified as pre-frail according to the criteria previously described by Fried et al. (2004). All subjects will be assessed using the Timed up and go and 10-Meter Walk Test functional tests. The plasma levels of IL-6 and TNF-alpha will be assessed by ELISA (enzyme-linked immunosorbent assay) with high sensitivity kits (QuantikineHS, R&D Systems Minneapolis, MN, U.S.). Knee extensor muscle strength will be assessed using the Byodex System 3 Pro(R) isokinetic dynamometer at angular speeds of 60 and 180 degrees/s. The intervention will consist of strengthening exercises of the lower extremities at 50 to 70% of 1RM (maximal resistance) three times per week for ten weeks. The volunteers will be randomized into two groups: group E, the intervention group, and group C, the control group that did not initiate any new activities during the initial study period (ten weeks). After the initial period, group C will begin the intervention and group E will maintain everyday activities without exercising. At the end of the total study period, all volunteers will be reassessed.Discussion: To demonstrate and discuss possible influences of load-bearing exercises on the modification of plasma levels of IL-6 and TNF-alpha and in the functional performance of pre-frail elderly women.Trial Registration: ISRCTN62824599. [ABSTRACT FROM AUTHOR]

We followed the COVID-19 pandemic in Manaus, one of the epicenters of COVID-19 in Brazil, using an epidemiological mathematical model and made five main conclusions. First, in early 2022, the actual cases exceed officially reported data by up to 8 times. Second, despite vaccination campaigns, the collective immunity threshold necessary was insufficient to contain severe cases of COVID-19. Next, the low observed mortality demonstrated the effectiveness of vaccination. Next, the drop in the vaccination rate combined with immune escape by the Omicron sub-variants (BA.2.12.1, BA.4, and BA.5) resulted in new wave after November 2022. Finally, to minimize severe cases of COVID-19, we need to raise vaccination thresholds above 90-95% of the entire population including children aged 6 months and older and require booster doses at least in four-month intervals. This approach would help to prevent severe cases of COVID-19 that cause hospitalizations and deaths., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post-symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post-symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Between 2016 and 2018, Brazil experienced major sylvatic yellow fever (YF) outbreaks that caused hundreds of casualties, with Minas Gerais (MG) being the most affected state. These outbreaks provided a unique opportunity to assess the immune response triggered by the wild-type (WT) yellow fever virus (YFV) in humans. The plaque reduction neutralization test (PRNT) is currently the standard method to assess the humoral immune response to YFV by measuring neutralizing antibodies (nAbs). The present study aimed to evaluate the humoral immune response of patients from the 2017-2018 sylvatic YF outbreak in MG with different disease outcomes by using PRNTs with a WT YFV strain, isolated from the 2017-2018 outbreak, and a vaccine YFV strain. Samples from naturally infected YF patients were tested, in comparison with healthy vaccinees. Results showed that both groups presented different levels of nAb against the WT and vaccine strains, and the levels of neutralization against the strains varied homotypically and heterotypically. Results based on the geometric mean titers (GMTs) suggest that the humoral immune response after a natural infection of YFV can reach higher levels than that induced by vaccination (GMT of patients against WT YFV compared to GMT of vaccinees, P < 0.0001). These findings suggest that the humoral immune responses triggered by the vaccine and WT strains of YFV are different, possibly due to genetic and antigenic differences between these viruses. Therefore, current means of assessing the immune response in naturally infected YF individuals and immunological surveillance methods in areas with intense viral circulation may need to be updated.IMPORTANCEYellow fever is a deadly febrile disease caused by the YFV. Despite the existence of effective vaccines, this disease still represents a public health concern worldwide. Much is known about the immune response against the vaccine strains of the YFV, but recent studies have shown that it differs from that induced by WT strains. The extent of this difference and the mechanisms behind it are still unclear. Thus, studies aimed to better understand the immune response against this virus are relevant and necessary. The present study evaluated levels of neutralizing antibodies of yellow fever patients from recent outbreaks in Brazil, in comparison with healthy vaccinees, using plaque reduction neutralization tests with WT and vaccine YFV strains. Results showed that the humoral immune response in naturally infected patients was higher than that induced by vaccination, thus providing new insights into the immune response triggered against these viruses., Competing Interests: The authors declare no conflict of interest.

Background: Severe yellow fever infection (YFI) may be complicated by a hemorrhagic diathesis. However, the hemostasis profile of YFI has rarely been reported., Objectives: The aim of this study was to characterize the hemostatic features of YFI by using a rotational thromboelastometry (ROTEM)., Methods: We evaluated clinical, laboratory, and ROTEM parameters in adults with severe YFI and their correlation with hemostatic variables according to bleeding and death., Results: A total of 35 patients were included (median age, 49 years). ROTEM was performed in 22 patients, of whom 21 (96%) presented bleeding and 4 (18%) died. All patients who died had major bleeding. Patients who died presented prolonged clotting time (CT; median, 2326 seconds; IQR, 1898-2986 seconds) and reduced alpha angle (median, 12°; IQR, 12°-15°) in comparison with patients who had minor (median CT, 644 seconds; IQR, 552-845 seconds and alpha angle, 47°; IQR, 28°-65°) and major (median CT, 719 seconds; IQR, 368-1114 seconds and alpha angle, 43°; IQR, 32°-64°) bleeding who survived. In patients who had bleeding, CT showed a strong negative correlation with factor (F)V ( r  = -.68), FIX ( r  = -.84), and FX ( r  = -.63) as well as alpha angle showed a strong negative correlation with FIX ( r  = -.92). In patients who died, the correlations were even stronger. A total of 19/21 (90%) patients presented hypocoagulability assessed by ROTEM., Conclusion: Hypocoagulabitity is the hallmark of the bleeding diathesis of severe YFI. Abnormal CT and alpha angle associated with death and could be used as potential predictors of adverse outcome in severe YFI., (© 2024 The Authors.)

Growth and carcass traits are essential selection criteria for beef cattle breeding programs. However, it is necessary to combine these measurements with body composition traits to meet the demand of the consumer market. This study aimed to estimate the genetic parameters for visual scores, growth (pre and post-weaning weights), and carcass (rib eye area (REA), back and rump fat thickness) traits in Nellore cattle using Bayesian inference. Data from 12,060 animals belonging to the HoRa Hofig Ramos herd were used. Morphological traits were evaluated by the MERCOS methodology. The heritability estimates obtained ranged from low to high magnitude, from 0.15 to 0.28 for visual scores, 0.13 to 0.44 for growth, and from 0.42 to 0.46 for carcass traits. Genetic correlations between visual scores and growth traits were generally of moderate to high magnitudes, however, visual scores showed low correlations with carcass traits, except between sacral bone and structure and REA. Selection for visual score traits can lead to favorable responses in body weight and vice versa, but the same is not true for carcass traits. Morphological categorical traits can be used as complementary tools that add value to selection.

Food labeling serves as a crucial medium for industries to communicate product qualities to consumers. Sanitary inspection and artisanal seals are significant markers for traditional cheeses, yet current information on this topic is limited. Therefore, this study aims to evaluate the impact of sanitary inspection and the ARTE seal on the acceptance of artisanal cheese. To achieve this objective, four hypothetical cheese labels featuring all combinations of sanitary inspection and ARTE seals were presented to 404 consumers. These consumers rated their acceptance of each label, a conjoint analysis was conducted, and the relative importance of each seal was calculated. Subsequently, consumers were segmented using hierarchical cluster analysis. Their socio-demographic profiles were statistically correlated to the clusters through a chi-squared method. The results revealed the existence of three distinct consumer groups: those who strongly prefer cheeses with a sanitary seal (assigning a relative importance of 80.2% to the seal), those who favor cheeses with an artisanal seal (assigning a relative importance of 52.5% to the seal), and those for whom the presence of either seal did not significantly affect acceptance. Consumers residing in metropolitan areas generally placed less value on both seals, whereas frequent purchasers of artisanal foods and residents of rural areas showed a preference for the artisanal seal. Other socio-demographic variables did not statistically correlate with cluster membership. In conclusion, consumer segmentation based on preferences for sanitary inspection and artisanal seals in food labeling is vital for developing effective marketing strategies and food safety education policies.

Background: Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46-60 days after YF symptom onset., Methods: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post-symptom onset., Results: From 46 to 60 days post-symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF., Conclusions: These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF., Competing Interests: Potential conflicts of interest. A. R. C. C. reports consulting fees from the International Horizon Scanning Initiative’s Horizon Scanning System tracked by ECRI, a global, independent authority on healthcare technology and safety. B. P. D. reports unpaid roles as financial council and vice-president of the Brazilian Society for Virology and as virology chair for the Brazilian Society for Microbiology. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Yellow fever (YF) is an acute tropical infectious disease caused by an arbovirus and can manifest as a classic hemorrhagic fever. The mechanism of the bleeding diathesis in YF is not well understood. We assessed clinical and laboratory data (including a panel of coagulation tests) from 46 patients with moderate (M) and severe (S) YF admitted to a local hospital between January 2018 and April 2018. Among 46 patients, 34 had SYF of whom 12 (35%) patients died. A total of 21 (45%) patients developed some type of bleeding manifestation and 15 (32%) presented severe bleeding. Patients with SYF had more severe thrombocytopenia (p = 0.001); prolonged activated partial thromboplastin time (aPTT) and thrombin time (TT) (p = 0.03 and p = 0.005, respectively); reduced plasma levels of coagulation factor (F) II (p < 0.01), FIX (p = 0.01), and FX (p = 0.04); and D-dimer levels almost 10 times higher (p < 0.01) when compared with patients with MYF. Patients who died had more bleeding (p = 0.03), more major bleeding (p = 0.03), prolonged international normalized ratio (INR) and aPTT (p = 0.003 and p = 0.002, respectively), as well as lower activity of FII (p = 0.02), FV (p = 0.001), FVII (p = 0.005), FIX (p = 0.01), and protein C (p = 0.01) than the ones who survived. FVIII levels were either normal or increased in all patients studied. Our results suggest that the bleeding diathesis of SYF is associated with the deficiency of coagulation factors produced by the liver. Prolonged INR and aPTT and reduced FII, FV, FVII, FIX, and protein C were associated with death., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study described a soluble mediator storm in acute Yellow Fever/YF infection along the kinetics timeline towards convalescent disease. The analyses of the YF Viral RNAnemia, chemokines, cytokines, and growth factors were performed in YF patients at acute/(D1-15) and convalescent/(D16-315) phases. Patients with acute YF infection displayed a trimodal viremia profile spreading along D3, D6, and D8-14. A massive storm of mediators was observed in acute YF. Higher levels of mediators were observed in YF with higher morbidity scores, patients under intensive care, and those progressing to death than in YF patients who progress to late-relapsing hepatitis/L-Hep. A unimodal peak of biomarkers around D4-6 with a progressive decrease towards D181-315 was observed in non-L-Hep patients, while a bimodal pattern with a second peak around D61-90 was associated with L-Hep. This study provided a comprehensive landscape of evidence that distinct immune responses drive pathogenesis, disease progression, and L-Hep in YF patients., Competing Interests: Conflict of interest The authors have declared that no conflict of interest exists., (Copyright © 2023. Published by Elsevier Inc.)

The objective of this study was to estimate the genetic parameters for feed efficiency-related traits and their genetic correlations with growth, male fertility, and carcass traits using multi-trait analysis in Guzerat cattle. Further, it aimed to predict the direct and correlated responses for feed efficiency traits when selection was applied for growth, male fertility, and carcass traits. The evaluated traits were adjusted weight at 120 (W120), 210 (W210), 365 (W365), and 450 days of age (W450), adjusted scrotal circumference at 365 days of age (SC365) and at 450 days of age (SC450), scrotal circumference, ribeye area (REA), backfat thickness (BFT), rump fat thickness (RFT), residual feed intake (RFI), and dry matter intake (DMI). The genetic parameters were obtained by the restricted maximum likelihood method (REML), using an animal model in multi-trait analyses. The heritability estimates for W120, W210, W365, W450, SC365, and SC450 varied from low to high (0.17 to 0.39). The carcass traits, REA, BFT, and RFT, displayed low to moderate heritability estimates, 0.27, 0.10, and 0.31, respectively. The heritability estimates for RFI (0.15) and DMI (0.23) were low and moderate, respectively. The RFI showed low genetic correlations with growth traits, ranging from - 0.07 to 0.22, from 0.03 to 0.05 for scrotal circumference, and from - 0.35 to 0.16 for carcass, except for DMI, which ranged from 0.42 to 0.46. The RFI and DMI presented enough additive genetic variability to be used as selection criteria in Guzerat breed genetic improvement program. Additionally, the response to selection for RFI would be higher when selection is performed directly for this trait. The selection for residual feed intake would not promote unfavorable correlated responses for scrotal circumference, carcass (yield and finish), and growth traits. Therefore, the selection for more efficient animals would not compromise the productive, reproductive, and carcass performance, contributing to reduce the production costs, increasing the profitability and sustainability of beef cattle production in tropical areas., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Noncoding microRNAs are involved in lipid and carbohydrate metabolism pathways and are powerful regulators of gene expression. The goals of this study were to evaluate the temporal expression profiles of miRNAs in rat adipose tissue and predict mRNA−microRNA interactions. Newly weaned Wistar rats were divided into groups fed a standard diet and high-sucrose diet (HSD). The HSD contains 66.86% carbohydrates (40.45% standard diet, 40.45% condensed milk, and 8.58% crystal sugar), and the HSD was provided for 4, 8 and 15-week periods to investigate the expression levels of miRNAs in visceral adipose tissue using RT−qPCR. Target selection, enriched pathways and networks were analyzed in silico. The factor consumption time significantly was associated to decreases (p < 0.05) in the expression levels of the following miRNAs: 124-5p, 125-5p, 126-5p, 200c-3p, and 212-3p in all experimental groups. The factor diet significantly influenced rno-miR-124-5p, 200c-3p, and 212-3p expression (p < 0.05). A significant reduction (p < 0.05) in rno-miR-27a-3p expression was observed. The biological processes involved key pathways regulating fat deposition. Our findings provide important insights into downregulated miRNA expression patterns in visceral adipose tissue, adiposity level, hyperinsulinemia and increased VLDL-c and triglyceride levels.

Prior studies have demonstrated prolonged presence of yellow fever virus (YFV) RNA in saliva and urine as an alternative to serum. To investigate the presence of YFV RNA in urine, we used RT-PCR for YFV screening in 60 urine samples collected from a large cohort of naturally infected yellow fever (YF) patients during acute and convalescent phases of YF infection from recent YF outbreaks in Brazil (2017 to 2018). Fifteen urine samples from acute phase infection (up to 15 days post-symptom onset) and four urine samples from convalescent phase infection (up to 69 days post-symptom onset), were YFV PCR-positive. We genotyped YFV detected in seven urine samples (five collected during the acute phase and two collected during the YF convalescent phase). Genotyping indicated the presence of YFV South American I genotype in these samples. To our knowledge, this is the first report of wild-type YFV RNA detection in the urine this far out from symptom onset (up to 69 DPS), including YFV RNA detection during the convalescent phase of YF infection. The detection of YFV RNA in urine is an indicative of YFV infection; however, the results of RT-PCR using urine as sample should be interpreted with care, since a negative result does not exclude the possibility of YFV infection. With a possible prolonged period of detection beyond the viremic phase, the use of urine samples coupled with serological tests, epidemiologic inquiry, and clinical assessment could provide a longer diagnostic window for laboratory YF diagnosis.

L9 is a potent human monoclonal antibody (mAb) that preferentially binds two adjacent NVDP minor repeats and cross-reacts with NANP major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) on malaria-infective sporozoites. Understanding this mAb's ontogeny and mechanisms of binding PfCSP will facilitate vaccine development. Here, we isolate mAbs clonally related to L9 and show that this B cell lineage has baseline NVDP affinity and evolves to acquire NANP reactivity. Pairing the L9 kappa light chain (L9κ) with clonally related heavy chains results in chimeric mAbs that cross-link two NVDPs, cross-react with NANP, and more potently neutralize sporozoites in vivo compared with their original light chain. Structural analyses reveal that the chimeric mAbs bound minor repeats in a type-1 β-turn seen in other repeat-specific antibodies. These data highlight the importance of L9κ in binding NVDP on PfCSP to neutralize sporozoites and suggest that PfCSP-based immunogens might be improved by presenting ≥2 NVDPs., Competing Interests: Declaration of interests R.A.S., J.R.F., and L.T.W. have submitted US Provisional Patent Application No. 62/842590, filed May 3, 2019, describing mAb L9. All other authors declare no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Yellow fever virus (YFV) is the causative agent of yellow fever (YF), a hemorrhagic and viscerotropic acute disease. Severe YF has been described in approximately 15-25% of YF patients, with 20-50% of severe YF cases being fatal. Here we analyzed cerebrospinal fluid (CSF) samples collected during the YF outbreak in Brazil in 2018, aiming to investigate CNS neuroinvasion in fatal YFV cases. YFV RNA was screened by RT-qPCR targeting the 3'UTR region of the YFV genome in CSF. CSF samples were tested for the presence of anti-YFV IgM and neutralizing antibodies, coupled with routine laboratory examinations. Among the 13 patients studied, we detected anti-YFV IgM in CSF from eight patients and YFV RNA in CSF from five patients. YFV RNA genomic load in CSF samples ranged from 1.75×103 to 5.42×103 RNA copies/mL. We genotyped YFV from three CSF samples that grouped with other YFV samples from the 2018 outbreak in Brazil within the South-American I genotype. Even though descriptions of neurologic manifestations due to wild type YFV (WT-YFV) infection are rare, since the last YF outbreak in Brazil in 2017-2018, a few studies have demonstrated WT-YFV RNA in CSF samples from YF fatal cases. Serological tests indicated the presence of IgM and neutralizing antibodies against YFV in CSF samples from two patients. Although the presence of viral RNA, IgM and neutralizing antibodies in CSF samples could indicate neuroinvasiveness, further studies are needed to better elucidate the role of YFV neuroinvasion and possible impacts in disease pathogenesis., Competing Interests: Conflict of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Combinations of monoclonal antibodies (mAbs) against different epitopes on the same antigen synergistically neutralize many viruses. However, there are limited studies assessing whether combining human mAbs against distinct regions of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) enhances in vivo protection against malaria compared to each mAb alone or whether passive transfer of PfCSP mAbs would improve protection following vaccination against PfCSP. Here, we isolated a panel of human mAbs against the subdominant C-terminal domain of PfCSP (C-CSP) from a volunteer immunized with radiation-attenuated Pf sporozoites. These C-CSP-specific mAbs had limited binding to sporozoites in vitro that was increased by combination with neutralizing human "repeat" mAbs against the NPDP/NVDP/NANP tetrapeptides in the central repeat region of PfCSP. Nevertheless, passive transfer of repeat- and C-CSP-specific mAb combinations did not provide enhanced protection against in vivo sporozoite challenge compared to repeat mAbs alone. Furthermore, combining potent repeat-specific mAbs (CIS43, L9, and 317) that respectively target the three tetrapeptides (NPDP/NVDP/NANP) did not provide additional protection against in vivo sporozoite challenge. However, administration of either CIS43, L9, or 317 (but not C-CSP-specific mAbs) to mice that had been immunized with R21, a PfCSP-based virus-like particle vaccine that induces polyclonal antibodies against the repeat region and C-CSP, provided enhanced protection against sporozoite challenge when compared to vaccine or mAbs alone. Collectively, this study shows that while combining mAbs against the repeat and C-terminal regions of PfCSP provide no additional protection in vivo, repeat mAbs do provide increased protection when combined with vaccine-induced polyclonal antibodies. These data should inform the implementation of PfCSP human mAbs alone or following vaccination to prevent malaria infection., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: R.A.S., J.F., L.T.W., and R.V. have submitted U.S. Provisional Patent Application No. 62/842,590, filed 3 May 2019, describing mAb L9. All other authors have declared that no competing interests exist.

Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: R.A.S., J.F., and L.T.W. have submitted U.S. Provisional Patent Application No. 62/842,590, filed 3 May 2019, describing L9. R.A.S, N.K.K. and A.H.I. hold a patent (International Application No. PCT/US2018/017826) describing CIS43 and related mAbs. Y. F-G., B.A., N.K.H, C.M and F.Z. have declared that no competing interests exist.

The sediments inside the ballast tanks might compromise the effectiveness of the ballast water exchange procedure. In the present study, the sediment removal from double bottom ballast tanks due to flow-through ballast water exchange is investigated by simplified experimental and numerical models. Two flow rates and two sediment densities were considered to verify their influence on the process. Besides, the effectiveness of two tank configuration modifications to improve the sediments removal was investigated. The first is the introduction of a flow deflector inside the tank and the second is the water inflow from the bottom. A fully Lagrangian particle-based method is adopted to simulate the sediment removal process with complex tank geometry. A new boundary condition is proposed to model the mesh of the bottom inlet in the bottom inflow configuration. Despite the simplifications of the numerical model, the computational results are in good agreement with the experimental ones. The results show that the flow-through ballast water exchange method might not be effective to remove the sediments entrapped between the bottom stiffeners, and the proposed modifications, despite challenging implementation, improve the sediment removal., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Immunoglobulin (Ig)A antibodies play a critical role in protection against mucosal pathogens. However, the role of serum IgA in immunity to nonmucosal pathogens, such as Plasmodium falciparum , is poorly characterized, despite being the second most abundant isotype in blood after IgG. Here, we investigated the circulating IgA response in humans to P. falciparum sporozoites that are injected into the skin by mosquitoes and migrate to the liver via the bloodstream to initiate malaria infection. We found that circulating IgA was induced in three independent sporozoite-exposed cohorts: individuals living in an endemic region in Mali, malaria-naïve individuals immunized intravenously with three large doses of irradiated sporozoites, and malaria-naïve individuals exposed to a single controlled mosquito bite infection. Mechanistically, we found evidence in an animal model that IgA responses were induced by sporozoites at dermal inoculation sites. From malaria-resistant individuals, we isolated several IgA monoclonal antibodies that reduced liver parasite burden in mice. One antibody, MAD2-6, bound to a conserved epitope in the amino terminus of the P. falciparum circumsporozoite protein, the dominant protein on the sporozoite surface. Crystal structures of this antibody revealed a unique mode of binding whereby two Fabs simultaneously bound either side of the target peptide. This study reveals a role for circulating IgA in malaria and identifies the amino terminus of the circumsporozoite protein as a target of functional antibodies., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In Brazil, the first confirmed cases of hantavirus cardiopulmonary syndrome in Indigenous populations occurred in 2001. The purpose of this study was to determine the seroprevalence of orthohantavirus infections in the Utiariti Indigenous land located in the southeastern region of the Brazilian Amazon. In December 2014 and 2015, a survey was conducted using an enzyme-linked immunosorbent assay in nine villages belonging to the Haliti-Paresí Indigenous communities. A total of 301 participants were enrolled in the study. Of the two study cohorts, the one from 2014 showed a prevalence of 12.4%, whereas the one from 2015 had a serum prevalence of 13.4%. Analysis of the paired samples of 110 Indigenous people who participated in both stages of the study enabled identification of four individuals who had seroconverted during the study period. Identifying the circulation of orthohantaviruses in the Utiariti Indigenous land highlights a serious public health problem in viral expansion and highlights the need to implement preventive measures appropriate to the sociocultural reality of these communities.

Background: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4 + T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1β), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4-5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL., Methods: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4 + and CD8 + T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls., Results: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4 + T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4 + T counts in the R-VL group (r = - 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity., Conclusions: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.

Background: Cryptococcosis affects more than 220,000 patients/year, with high mortality even when the standard treatment [amphotericin B (AMB), 5-flucytosin (5-FC) and fluconazole] is used. AMB presents high toxicity and 5-FC is not currently available in Brazil. In a pre-clinical study, pioglitazone (PIO - an antidiabetic drug) decreased AMB toxicity and lead to an increased mice survival, reduced morbidity and fungal burden in brain and lungs. The aim of this trial is to evaluate the efficacy and safety of PIO combined with standard antifungal treatment for human cryptococcosis., Methods: A phase 1/2, randomized, double blind, placebo-controlled trial will be performed with patients from Belo Horizonte, Brazil. They will be divided into three groups (placebo, PIO 15 mg/day or PIO 45 mg/day) and will receive an additional pill during the induction phase of cryptococcosis' treatment. Our hypothesis is that treated patients will have increased survival, so the primary outcome will be the mortality rate. Patients will be monitored for survival, side effects, fungal burden and inflammatory mediators in blood and cerebrospinal fluid. The follow up will occur for up 60 days., Conclusions: We expect that PIO will be an adequate adjuvant to the standard cryptococcosis' treatment., Trial Registration: ICTRP/WHO (and International Clinical Trial Registry Plataform (ICTRP/WHO) (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR-9fv3f4), RBR-9fv3f4 (http://www.ensaiosclinicos.gov.br/rg/RBR-9fv3f4). UTN Number: U1111-1226-1535. Ethical approvement number: CAAE 17377019.0.0000.5149., (© 2021 Published by Elsevier Inc.)

Objective  The objective of the present study was to evaluate the relationship between patients with anterior cruciate ligament (ACL) injury by indirect trauma and increased posterior tibial inclination. Methods  Retrospective study, performed by analysis of medical records and digital radiographs of patients, present in a database of a tertiary orthopedic hospital. The sample consisted of two groups, the first group consisting of patients diagnosed with ACL injury by indirect trauma, and a control group matched by age. Results  Each group consisted of 275 patients, whose measurements of posterior tibial inclination were measured by three specialists. It was observed that the group of patients with ACL lesion presented a significantly higher tibial slope (in degrees) than the control group in the total sample and in the subsamples stratified by gender. The best cutoff point for the first group was identified as a posterior tibial inclination ≥ 8°, achieving a sensitivity of 63.3% and a specificity of 62.5%. The first group also had a tibial slope ratio ≥ 8° (63.3%), significantly higher than the control group (37.5%), with an odds ratio of 2.8. Conclusion  It was concluded that the increase of the posterior tibial inclination is associated with an increased risk for injury of the ACL by indirect trauma, mainly for values ≥ 8°., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Competing Interests: None

Discovering potent human monoclonal antibodies (mAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on sporozoites (SPZ) and elucidating their mechanisms of neutralization will facilitate translation for passive prophylaxis and aid next-generation vaccine development. Here, we isolated a neutralizing human mAb, L9 that preferentially bound NVDP minor repeats of PfCSP with high affinity while cross-reacting with NANP major repeats. L9 was more potent than six published neutralizing human PfCSP mAbs at mediating protection against mosquito bite challenge in mice. Isothermal titration calorimetry and multiphoton microscopy showed that L9 and the other most protective mAbs bound PfCSP with two binding events and mediated protection by killing SPZ in the liver and by preventing their egress from sinusoids and traversal of hepatocytes. This study defines the subdominant PfCSP minor repeats as neutralizing epitopes, identifies an in vitro biophysical correlate of SPZ neutralization, and demonstrates that the liver is an important site for antibodies to prevent malaria., Competing Interests: Declaration of Interests R.A.S., J.R.F., L.T.W., and R.V. have submitted US Provisional Patent Application 62/842,590, filed 3 May 2019, describing mAb L9. All other authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Older people's participation in structured exercise programs to improve balance and mobility is low. Senior Dance is an alternative option, as it may provide a safe and fun way of targeting balance., Objective: The aim was to investigate the effect of Senior Dance on balance, mobility, and cognitive function compared with a control intervention., Design: The study was a randomized controlled trial., Setting/patients: Eighty-two community-dwelling older people aged 60 years or over and cognitively intact were recruited in Brazil., Intervention: Participants were randomly allocated to 2 groups: Dance plus education (intervention group) and education alone (control group). The Senior Dance program consisted of 12 weeks of twice-weekly group-based dance classes. Participants in both groups attended a single 1-hour educational session on prevention of falls., Measurements: The primary outcome was single-leg stance with eyes closed. Secondary outcomes were timed sit-to-stand test, standing balance test, timed 4-m walk, and cognitive function tests, for example, Trail Making Test and Montreal Cognitive Assessment., Results: Of the 82 participants randomized, 71 (87%) completed the 12-week follow-up. Single-leg stance with eyes closed (primary outcome) improved in the Senior Dance group (mean difference [MD] = 2.3 seconds, 95% confidence interval [CI] = 1.1 to 3.6) compared with the control group at follow-up. Senior Dance group performed better in the standing balance tests (MD = 3.7 seconds, 95% CI = 0.6 to 6.8) and were faster in the sit-to-stand test (MD = - 3.1 seconds, 95% CI = -4.8 to -1.4) and 4-m walk test (MD = -0.6 seconds, 95% CI = -1.0 to -0.1). There were no significant between-group differences for cognitive function tests., Limitations: Participants and therapists were not blinded., Conclusion: Senior Dance was effective in improving balance and mobility but not cognitive function in community-dwelling older people., (© 2020 American Physical Therapy Association.)

One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and a rebound of alanine and aspartate transaminases, and total and direct bilirubin levels. Laboratory tests discarded autoimmune hepatitis, inflammatory or metabolic liver disease, and new infections caused by hepatotropic agents. Anti-YFV IgM, IgG and neutralizing antibodies were detected in different times, but no viremia. A liver biopsy was collected three months after YF onset and tested positive for YFV antigens and wild-type YFV-RNA (364 RNA-copies/gram/liver). Transaminases and bilirubin levels remained elevated for five months, and the arresting of symptoms persisted for six months after the acute YF onset. Several serum chemokines, cytokines, and growth factors were measured. A similar immune response profile was observed in the earlier phases of the disease, followed by more pronounced changes in the later stages, when transaminases levels returned to normal. The results indicated viral persistence in the liver and continual liver cell damage three months after YF onset and reinforced the need for extended follow-ups of YF patients. Further studies to investigate the role of possible viral persistence and the immune response causing relapsing hepatitis following YF are also necessary.

The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5'UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.

Extensive cow-calf beef cattle farms play a significant role in Portuguese livestock production, but records of important production variables, such as calf mortality, are scarce. To assess herd-level calf mortality and its potential economic impact, farmers from the Alentejo region were asked to fill a questionnaire regarding herd size, feeding and reproductive management practices, calf mortality (from birth to weaning), and detection of the main morbidity causes, as well as of sudden, unexplained deaths during the previous 12 months. Farmers were also requested to quantitatively assess the economic impact of calf mortality on their annual revenue. In the majority of farms, the herd size was larger than 100 animals. The median stocking rate was 0.41 adult animals/hectare, and 70% of farmers stated their farm was self-sufficient in forage. The percent of live births that resulted in weaned calves averaged 94.3%, which led to the assumption of a 5.7% calf mortality rate from birth to weaning. In the previous 12 months, 78.8% of the farms identified at least one case of calf diarrhea, 60.7% identified at least one case of respiratory disease, and 82.1% had at least one sudden, unexplained calf death. As expected, farmers that assessed a higher impact of calf losses on their annual economic revenue were also those who reported higher incidences of calf diarrhea, respiratory disease, and sudden, unexplained deaths. One-quarter of the farmers were unable to assess the economic impact of calf mortality on the farm's revenue. Herd size appears to have a predictive value on calf mortality in the first month of life, and from 30 days to weaning. The number of sudden, unexplained calf deaths seems to have a predictive value on overall calf mortality (from birth to weaning), suggesting that the farms' management practices probably play an important role in calf mortality throughout the suckling period. Further studies are needed to fully understand calf mortality in Portuguese extensive rearing systems., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Rute Santos et al.)

Insect-borne plant viruses usually alter the interactions between host plant and insect vector in ways conducive to their transmission ('host manipulation hypothesis'). Most studies have tested this hypothesis with persistently and non-persistently transmitted viruses, while few have examined semi-persistently transmitted viruses. The crinivirus Tomato chlorosis virus (ToCV) is semi-persistently transmitted virus by whiteflies, and has been recently reported infecting potato plants in Brazil, where Bemisia tabaci Middle East Asia Minor 1 (MEAM1) is a competent vector. We investigated how ToCV infection modifies the interaction between potato plants and B. tabaci in ways that increase the likelihood of ToCV transmission, in two clones, one susceptible ('Agata') and the other moderately resistant (Bach-4) to B. tabaci. Whiteflies alighted and laid more eggs on ToCV-infected plants than mock-inoculated plants of Bach-4. When non-viruliferous whiteflies were released on ToCV-infected plants near mock-inoculated plants, adults moved more intensely towards non-infected plants than in the reverse condition for both clones. Feeding on ToCV-infected plants reduced egg-incubation period in both clones, but the egg-adult cycle was similar for whiteflies fed on ToCV-infected and mock-inoculated plants. Our results demonstrated that ToCV infection in potato plants alters B. tabaci behaviour and development in distinct ways depending on the host clone, with potential implications for ToCV spread.

Importance: Yellow fever still threatens people in endemic areas, and besides conjunctival icterus, little is known about the ocular changes that occur in these patients., Objective: To characterize retinal changes in patients with confirmed yellow fever during 2 recent outbreaks of the disease in Minas Gerais, Southeastern Brazil., Design, Setting, and Participants: This cross-sectional, observational study conducted at a single referral center for infectious diseases in Southeastern Brazil collected data between January 2017 and February 2018 from 94 consecutive patients with suspicion of yellow fever who were eligible for the study., Main Outcomes and Measures: Patients underwent ophthalmic examination. Clinical findings, laboratory results, and occurrence of retinopathy and death during hospitalization were reported, including age, sex, comorbidities, disease severity, serum aspartate aminotransferase level, total bilirubin level, serum creatinine level, arterial lactate level, international normalized ratio, and platelet count at hospital admission., Results: In total, 64 patients were included who had received a confirmed diagnosis of yellow fever, with a median (interquartile range) age of 47 (38-56) years, and 12 patients (19%) were women. Twenty eyes (16%) of 13 patients (20%) had retinopathy at the same time as yellow fever. The most common fundus changes among the 20 eyes were retinal nerve fiber layer infarcts (11 [55%]), superficial hemorrhages (7 [35%]) and grayish deep lesions (6 [30%]), possibly at the level of the outer retina or choroid. Aspartate aminotransferase levels higher than 3000 U/L (odds ratio [OR], 14.2; 95% CI, 3.5-77.8; P < .001), total bilirubin levels higher than 2.3 mg/dL (OR, 20.0; 95% CI, 4.4-159.7; P < .001), serum creatinine levels higher than 2.0 mg/dL (OR, 8.2; 95% CI, 2.1-36.0; P = .003), arterial lactate levels higher than 17.1/mg/dL (OR, 4.6; 95% CI, 1.1-19.0; P = .03), platelet count lower than 94 × 103/μL (OR, 7.8; 95% CI, 1.8-59.9; P = .004), and classification of disease as severe (OR, 11.7; 95% CI, 2.0-301.0; P = .003) were associated with retinopathy. Arterial hypertension, diabetes, international normalized ratio, and death were not associated with retinopathy., Conclusions and Relevance: Retinopathy was present in 20% of patients with yellow fever and appeared to be associated with more severe systemic disease. Retinal nerve fiber layer infarcts and superficial hemorrhages, but not the grayish deep lesions, resembled those associated with other flavivirus (eg, dengue virus) infections. The clinical relevance of these findings may warrant further investigation.

Incidence of Yellow Fever (YF) has increased in Brazil, and cardiac findings such as bradyarrhythmias and conduction abnormalities have been described. We aimed to perform a comprehensive cardiac evaluation of patients with YF, and to assess the association between cardiac involvement and disease severity. Patients hospitalized with YF from February to March 2018 underwent clinical and laboratory evaluation, focused bedside echocardiography (GE Vivid IQ), electrocardiogram and, in case of alterations, 24-hours Holter. Patients were divided into 2 groups according to YF severity. Five patients underwent magnetic resonance imaging and 3 had necropsy. Seventy patients had confirmed YF, 69% with severe form. Mean age was 48 ± 14 years, 63 (90%) were males and 5 (7%) died. Significant electrocardiogram abnormalities were present in 52% of patients with mild/moderate form of YF (G1) and 77% of those with severe form (G2), p = 0.046. Sinus bradycardia was observed in 24% (N = 17): G1 23% versus G2 25%, p = 0.67. Among 32 patients who underwent Holter, 14 (44%) had mean HR <60 beats per minute, being 8 from G2. Echocardiogram revealed left ventricular dysfunction in 4 (6%) patients, from G2. Left ventricular wall thickening with a hyper-refringent myocardial texture suggesting infiltration was observed in 17 patients (G1 18% vs G2 27%, p = 0.55). One magnetic resonance (G2) was suggestive of myocarditis, and one necropsy revealed areas of myocardial necrosis and acute myocarditis. In conclusion, cardiac involvement was observed in patients with YF, most commonly bradycardia and myocardial hyper-refringent texture suggestive of infiltration., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: The management of nonarteritic anterior ischemic optic neuropathy centers around prevention of second eye involvement, without a uniformly accepted therapy for the involved eye. Several researchers have assessed the benefit of steroids with conflicting results. This experimental study was designed to evaluate the efficacy of a single intravitreal triamcinolone acetonide injection (IVTA) in preserving retinal ganglion cells (RGCs) in a rodent model of anterior ischemic optic neuropathy (rAION)., Methods: The rAION was induced in female Wistar rats. Animals were randomized into 3 groups: 1) untreated, 2) treated with 56 μg IVTA, and 3) intravitreal saline (placebo). Procedures were performed in the left eye, with the right eye serving as control. After 30 days, animals were sacrificed and eyes were assessed histologically for RGC number., Results: The average number of RGC was significantly lower in rAION subgroups when compared with the control group (P < 0.001). No significant difference was seen between rAION eyes treated with IVTA, placebo, and untreated eyes (P > 0.05%)., Conclusions: In this rodent model for AION, no therapeutic benefit of intravitreal steroid injection was identified.

Chaetosiphon fragaefolii (Cockerell) (Hemiptera: Aphididae) is the predominant aphid in strawberry (Fragaria × ananassa Duchesne) production systems in Brazil. This pest species directly damages the plants and is also responsible for spreading viruses. Further, C. fragaefolii often renders strawberry cultivation unviable, because of its high reproductive rate, as well as the large number of individuals generated through parthenogenesis. The present study aimed to (1) evaluate the feeding behavior of C. fragaefolii in four strawberry cultivars (Albion, Aromas, Camarosa, and San Andreas) and (2) identify the resistance factors associated with the number and type of trichomes in the cultivars, and also its effect on the feeding behavior of C. fragaefolii, using the electrical penetration graph (EPG) technique. The results revealed an intrinsic relationship between the number of trichomes on the cultivar and feeding behavior of C. fragaefolii. A higher number of trichomes, both tector and glandular, was observed in Albion compared to that of other cultivars, resulting in a longer no probing (Np) period per insect, and a longer Np phase. A relatively short phloem phase and ingestion time of the phloem sieve elements were also observed in Albion. These results suggest that the trichomes act as a physical barrier creating difficulties for C. fragaefolii to feed, thereby altering its feeding behavior in the four cultivars studied.

The objective of the present study was to evaluate the antimicrobial activity of the Cc -LTP2 and Cc -GRP peptides isolated from Coffea canephora seeds and their possible synergistic activity with the azole drug fluconazole and characterize their mechanisms of action on cells of pathogenic fungi. Cc -LTP2 and Cc -GRP alone or in combination with 20  µ g/mL of fluconazole were evaluated for their antimicrobial activity on the fungus Fusarium solani , and the effects of these peptides on the permeability of membranes and the induction of oxidative stress were determined. Our results show that these peptides at a concentration of 400  µ g/mL combined with 20  µ g/mL of fluconazole were able to inhibit the growth of the tested fungi, promote changes in their growth pattern, permeabilize the membrane, and induce reactive oxygen species (ROS). Some of these results were also observed with the peptides alone or with fluconazole alone, suggesting that the peptides act synergistically, promoting the potentiation of antimicrobial action. In this study, it was shown that Cc -LTP2 and Cc -GRP in combination with fluconazole were able to inhibit the growth of the fungus F. solani , to promote permeabilization of its membrane, and to induce the production of ROS, suggesting a combinatorial activity between the peptides and fluconazole.