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Plasmodium vivax, a challenging species to eliminate, causes millions of malaria cases globally annually. Developing an effective vaccine is crucial in the fight against vivax malaria, but considering the limited number of studies focusing on the identification and development of P. vivax-specific vaccine candidates, exploring new antigens is an urgent need. The merozoite protein CyRPA is essential for P. falciparum growth and erythrocyte invasion and corresponds to a promising candidate antigen. In P. vivax, a single study with multiple vaccine candidates indicates PvCyRPA with strong association with protection, outperforming classic malaria vaccine candidates. However, little is known about the specific naturally acquired response in the Americas, as well as the antigen epitope mapping. For this reason, we aimed to investigate the cellular and humoral immune response elicited against PvCyRPA in Brazilian endemic areas to identify the existence of immunodominant regions and the potential of this protein as a single or even a multi-stage specific malaria vaccine candidate for P. vivax. The results demonstrated that PvCyRPA is naturally immunogenic in Brazilian Amazon individuals previously exposed to malaria, which presented anti-PvCyRPA cytophilic antibodies. Moreover, our data show that the protein also possesses important immunogenic regions with an overlap of B and T cell epitopes. These data reinforce the possibility of including PvCyRPA in vaccine formulations for P. vivax., (© 2024. The Author(s).)

Introduction: Seroma is the most common early complication following surgical breast cancer treatment. Its development is associated with pain, scar complications, adjuvant therapy delays, the need for outpatient visits, and increased care costs., Objective: Assess seroma incidence and risk factors in women undergoing mastectomies., Method: This study comprises a prospective cohort encompassing women aged 18 or over undergoing mastectomies as a breast cancer treatment. Patients underwent physiotherapy on the 1st, 7th, and 30th postoperative days for kinetic-functional, skin, and wound healing assessments and were attended to by nurses for surgical wound care, draining liquid on the 7th, 14th, and 21st postoperative days. Seroma was defined as the presence of local fluctuations requiring puncture, regardless of the punctured volume., Results: A total of 249 women were evaluated, with a mean age of 57.5 (SD = 11.8). A total of 77.1% were classified as overweight or obese, 60.2% were hypertensive, 21.3% were diabetic, 66.7% underwent neoadjuvant chemotherapy and 62.7% underwent axillary lymphadenectomies. Seroma incidence was 71.1%, requiring, on average, two aspiration punctures until condition resolution. Overweight or obese women and those who underwent axillary lymphadenectomies exhibited 1.92- and 2.06-fold higher risk for seroma development (OR = 1.92; 95% CI 1.02-3.61; p = 0.042; and OR = 2.06; 95% CI 1.17-3.63; p = 0.012), respectively., Conclusion: Seroma incidence was very high. Being overweight or obese and undergoing axillary lymphadenectomy comprise independent seroma development risk factors. This study is part of a randomized clinical trial evaluating the effectiveness of applying compressive taping to prevent post-mastectomy seroma, which was approved by the Brazilian National Cancer Institute, Research Ethics Committee (2,774,824), and it is registered in the ClinicalTrials.gov (NCT04471142, on July 15, 2020)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There are controversies regarding the impact of sex on mortality and postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG), although some studies demonstrate comparable outcomes. This study sought to evaluate sex differences regarding risk factors associated with hospital mortality and postoperative clinical outcomes among patients undergoing isolated on-pump CABG. We conducted a retrospective observational cohort study of patients who underwent isolated on-pump CABG from January 1996 to January 2020. Patients were divided into two groups (male and female) and compared regarding preoperative characteristics, surgical technical variables, and in-hospital outcomes. All-cause mortality between groups was compared using logistic regression. Risk factors for mortality, along with their respective odds ratios (OR), were separately assessed using a logistic regression model with p-values for interaction. We analyzed 4,882 patients, of whom 31.6% were female. Women exhibited a higher prevalence of age >75 years (12.2% vs 8.3%, p<0.001), obesity (22.6% vs 11.5%, p<0.001), diabetes (41.6% vs 32.2%, p<0.001), hypertension (85.2% vs 73.5%, p<0.001), and NYHA functional classes 3 and 4 (16.2% vs 11.2%, p<0.001) compared to men. Use of the mammary artery for revascularization was less frequent among women (73.8% vs 79.9%, p<0.001), who also received fewer saphenous vein grafts (2.17 vs 2.27, p = 0.002). A history of previous or recent myocardial infarction (MI) had an impact on women's mortality, unlike in men (OR 1.61 vs 0.94, p = 0.014; OR 1.86 vs 0.99, p = 0.015, respectively). After adjusting for several risk factors, mortality was found to be comparable between men and women, with an OR of 1.20 (95% CI 0.94-1.53, p = 0.129). In conclusion, female patients undergoing isolated on-pump CABG presented with a higher number of comorbidities. Previous and recent MI were associated with higher mortality only in women. In this cohort analysis, female gender was not identified as an independent risk factor for outcome after CABG., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous inflammation of the colonic mucosa. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis, and favorable response to immunosuppression. An association between IBD and AIH is uncommon, and experts have suggested that in patients with overlapping IBD and AIH, the anti-tumor necrosis factor agents can be used. Therefore, this study reports a rare case of a patient with liver cirrhosis due to AIH and UC refractory to conventional treatment and discusses the risks and benefits of using anti-tumor necrosis factor in both conditions., Patient Concerns: A 28-year-old female presented with symptoms of diarrhea, abdominal pain, asthenia, and inappetence, accompanied by abdominal collateral circulation, anemia, alteration of liver enzymes, and elevation of C-reactive protein levels., Diagnoses: The patient underwent a liver biopsy, which was consistent with liver cirrhosis due to AIH. Colonoscopy showed an inflammatory process throughout the colon, compatible with moderately active UC., Interventions: The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC. The patient presented with a clinical response and infliximab therapy was maintained., Outcomes: Eight months after starting infliximab therapy, the patient developed pneumonia with complications from disseminated intravascular coagulation and died., Lessons Subsections: AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Marmosets, Callithrix spp, are small New World monkeys that have gained importance as an experimental animal model for human. Despite its use, information on its renal morphometry, vascularization, and location are limited. Therefore, this study will supply basic anatomy for applied studies and for comparative anatomy., Methods: Fifty cadavers of Callithrix spp were collected on highways from the Atlantic Forest biome, identified and injected with a 10% formaldehyde solution. Later, the specimens were dissected and the measurements and topography of the kidneys and renal vessels were recorded. Both left and right kidneys were significantly larger in females., Results: In the specimens studied, the average body length was 20.00 ± 2.46 cm in males and 20.50 ± 1.98 cm in females (p = .43). The kidneys of the Callithrix spp. were symmetrical in shape and resembled a "bean." They were also pale brown with a smooth surface. In males, the most frequent location of the right kidney was at the L1-L2 level (92%), while the location of the left kidney was between L2 and L3 (76%). In females, the most frequent location of the right kidney was at the L1-L2 level (56%), while the location of the left kidney was between L2 and L3 (32%) (Table 1). However, in seven (28%) males and nine (36%) females, the kidneys were at the same level., Conclusions: In both sexes, there was a positive and significant linear correlation between body length and kidney length. Regardless of the variable location of the kidneys in both sides and in either sexe, the right kidney was always located more cranially than the left, similar to observations in other non-human primates., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mechanically separated meat (MSM) is widely used in the food industry, however, there is a lack of studies on its consumption in populations. The objective of this study was to identify the frequency and amount of MSM consumption, factors associated with MSM consumption, nutrient intake and preferential choice of food groups among MSM consumers. This was an observational, cross-sectional prospective study based on a probability sample of manufacturing workers, conducted in Brazil. Logistic and linear multiple regression with robust standard errors were used. 921 workers from 33 manufacturing companies were studied, with an average age of 38.2 ± 10.7 years, 55.9% males. MSM products are consumed by 28.8% and represent in average 10% of total daily caloric intake, and 47.3% of the daily kcal from ultra-processed products. Younger age and greater waist circumference are associated with MSM consumption. Younger age and lesser educational level are associated with increased contribution of MSM to total daily kcal intake. MSM consumers have greater consumption of energy, fats, carbohydrates and sodium. Their dietary patterns are characterized by lower consumption of in natura and minimally processed foods, such as tubers and roots, fruits, white and red meat, and eggs and greater consumption of ultra-processed foods and beverages., (© 2024. The Author(s).)

The Chikungunya virus (CHIKV) presents global health challenges, with Brazil experiencing outbreaks since its introduction in 2014. In 2023, following a CHIKV outbreak in Minas Gerais (MG), social media was used to optimize an entomological survey aimed at identifying vectors and viral lineages and assessing insecticide resistance. Following Instagram posts, residents with suspected CHIKV infection were able to schedule mosquito aspirations. In total, 421 mosquitoes (165 Aedes aegypti and 256 Culex quinquefasciatus ) were captured from 40 households in Salinas city (MG) and tested for the Dengue, Zika, and Chikungunya viruses through RT-qPCR. Twelve of 57 pools (10 Ae. aegypti and two Cx. quinquefasciatus ) tested positive for CHIKV RNA. Viral RNA was also detected in the heads of nine Ae. aegypti , indicating viral dissemination but not in Cx. quinquefasciatus . Genome sequencing yielded the first near-complete genome from the 2023 outbreak, unveiling that the CHIKV strain belonged to the East/Central/South African (ECSA) genotype. Additionally, genetic analyses revealed high frequencies of kdr alleles, including in CHIKV-infected mosquitoes, suggesting resistance to pyrethroid insecticides in this Ae. aegypti population. Social media was important for guiding mosquito-capture efforts in CHIKV transmission hotspots, thus optimizing the opportunity for viral detection. These findings emphasize the urgent need for innovative vector studies and control strategies, as well as interdisciplinary approaches in public health interventions.

The current sweeteners available are very efficient in providing sweet taste. However, they are associated with several chronic diseases. Some glycoproteins, such as miraculins, are extremely interesting from a biotechnological point of view because they perform the bitter into sweet taste modifying function excellently, in addition to being safer as food. In contrast, purifying and synthesizing these proteins represents a major challenge for the food industry, as these proteins are large and complex molecules, which would make the final product expensive and economically unviable. In this context, emerging techniques from computational biology and molecular modelling have been promoting a remarkable revolution in protein bioengineering. Bioinspired peptides can provide many possibilities in sweeteners development through rational design. Once these peptides are smaller molecules than an entire protein, its synthesis on a large scale tends to be much easier and more economical, besides presenting a potential for better bioavailability in the organism. The techniques discussed here allow, through sophisticated pipelines and algorithms, to perform the rational design of mimetic peptides and with smaller size, which can carry out the activation of sweet taste of miraculins and to be more viable for industrial production. In this review, the premises and tools for the elaboration of synthetic peptides bioinspired in proteins with sweetening activity that mimic this action will be emphasized.Communicated by Ramaswamy H. Sarma.

Radiopharmaceuticals have been used to diagnose several diseases, particularly because the procedure is non-invasive. However, it is important that the correct amount of radiopharmaceutical is used to avoid inaccurate diagnostic results and suboptimal therapeutic outcomes. The amount of the radiopharmaceutical is measured when produced (by the supplier) and a second time (by the receiver), before it's use. When measured at the receiver, the result is corrected for its normal radioactivity decay. Even then, it is possible that both measurements should be considered nominal different or even statistically different when compared through various statistical tools. This research combines two innovative techniques in the field of clinical metrology. The first technique is data reconciliation, which not only enhances measurement accuracy but also reduces measurement uncertainty. The second technique involves using uncertainty information to establish specification limits for compliance assessments. In this way, our proposal aimed to minimize the risk of making incorrect decisions regarding the conformity of the concentration of radiopharmaceutical activity, that is, rejecting an item or batch that is within specification or accepting an item or batch that is outside of specification. A spreadsheet, based on these metrology fundamentals, is available to help the user with the calculations, presenting numerical and graphical results for some common radioisotopes. Reliable specification limits can be calculated and used to determine if the radiopharmaceutical is in accordance with its proposed application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background and Objectives: Robotic surgical systems have rapidly become integrated into colorectal surgery practice in recent years, particularly for rectal resections, where the advantages of robotic platforms over conventional laparoscopy are more pronounced. However, as with any technological advancement, the initial high costs can be a limiting factor, leading to unequal health service access, especially in middle- and lower-income countries. Materials and Method: A narrative review was conducted with the objective of providing an overview of the escalating adoption, current training programmes, and certification process of robotic colorectal surgery in Brazil. Results: Brazil has witnessed a rapid increase in robotic platforms in recent years. Currently, there are 106 robotic systems installed nationwide. However, approximately 60% of the medical facilities which adopted robotic platforms are in the Southeast region, which is both the most populous and economically prosperous in the country. The Brazilian Society of Coloproctology recently established clear rules for the training programme and certification of colorectal surgeons in robotic surgery. The key components of the training encompass theoretical content, virtual robotic simulation, observation, assistance, and supervised procedures in colorectal surgery. Although the training parameters are well established, no colorectal surgery residency programme in Brazil has yet integrated the teaching and training of robotic surgery into its curriculum. Thus far, the training process has been led by private institutions and the industry. Conclusion : Despite the fast spread of robotic platforms across Brazil, several challenges still need to be addressed to democratise training and promote the widespread use of these platforms. It is crucial to tackle these obstacles to achieve greater integration of robotic technology in colorectal surgery throughout the country.

Tumor necrosis factor inhibitors (anti-TNFs) are widely used therapies for the treatment of inflammatory bowel diseases (IBD); however, their administration is not risk-free. Heart failure (HF), although rare, is a potential adverse event related to administration of these medications. However, the exact mechanism of development of HF remains obscure. TNFα is found in both healthy and damaged hearts. Its effects are concentration- and receptor-dependent, promoting either cardio-protection or cardiomyocyte apoptosis. Experimental rat models with TNFα receptor knockout showed increased survival rates, less reactive oxygen species formation, and improved diastolic left ventricle pressure. However, clinical trials employing anti-TNF therapy to treat HF had disappointing results, suggesting abolishment of the cardioprotective properties of TNFα, making cardiomyocytes susceptible to apoptosis and oxidation. Thus, patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy. This review aims to discuss adverse events associated with the administration of anti-TNF therapy, with a focus on HF, and propose some approaches to avoid cardiac adverse events in patients with IBD., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality., Methods: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue., Results: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023)., Conclusions: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection., (© 2023. The Author(s).)

Prostate cancer (PCa) is one of the most prevalent types of cancer in men worldwide; however, the main diagnostic tests available for PCa have limitations and a biopsy is required for histopathological confirmation of the disease. Prostate-specific antigen (PSA) is the main biomarker used for the early detection of PCa, but an elevated serum concentration is not cancer-specific. Therefore, there is a need for the discovery of new non-invasive biomarkers that can accurately diagnose PCa. The present study used trichloroacetic acid-induced protein precipitation and liquid chromatography-mass spectrometry to profile endogenous peptides in urine samples from patients with PCa (n=33), benign prostatic hyperplasia (n=25) and healthy individuals (n=28). Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of urinary peptides. In addition, Proteasix tool was used for in silico prediction of protease cleavage sites. Five urinary peptides derived from uromodulin were revealed to be significantly altered between the study groups, all of which were less abundant in the PCa group. This peptide panel showed a high potential to discriminate between the study groups, resulting in area under the curve (AUC) values between 0.788 and 0.951. In addition, urinary peptides outperformed PSA in discriminating between malignant and benign prostate conditions (AUC=0.847), showing high sensitivity (81.82%) and specificity (88%). From in silico analyses, the proteases HTRA2, KLK3, KLK4, KLK14 and MMP25 were identified as potentially involved in the degradation of uromodulin peptides in the urine of patients with PCa. In conclusion, the present study allowed the identification of urinary peptides with potential for use as non-invasive biomarkers in PCa diagnosis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © De Souza Dutra et al.)

We hypothesized that adults with uncomplicated malaria have lower left ventricular contractile function compared to the general population and that this improves after antimalarial treatment. We examined uncomplicated malaria and the general population from the Western part of the Brazilian Amazon Basin. All persons underwent an echocardiographic examination and peripheral blood smears. Left ventricular function was assessed by speckle tracking analysis of global longitudinal strain (GLS). Logistic regression models were used to assess the association between malaria status (yes/no) and GLS and improvement in GLS by follow-up was assessed using a paired T-test. We enrolled 99 adults with uncomplicated malaria (mean age 40 years, 46% female) of whom 75 had Plasmodium vivax, 22 Plasmodium falciparum and two had both species [median 1595 (528 to 6585) parasites/mm 3 ]. Seventy adults completed a follow-up examination after standard malaria treatment (median 31 days). We examined 486 from the general population (mean age 41 years, 63% female). In persons with malaria at baseline, GLS was lower compared to the general population (18.7% vs. 19.4%, P = 0.002) and GLS improved at follow-up (19.2%, P = 0.032). In multivariable models adjusted for clinical, socioeconomic and echocardiographic confounders, baseline GLS remained significantly associated with malaria status [odds ratio 2.45 (95%CI 1.00 to 7.25), P = 0.023 per 1% increase]. Parasite density was associated with worsening in GLS [+ 16% (+ 0% to + 34%), P = 0.047 per 1 unit increase in GLS]. Adults with uncomplicated malaria had lower GLS compared to the general population and this improved after completed antimalarial treatment. Our results suggest that malaria infection may affect left ventricular contractile function, however, further studies are needed to fully elucidate such a relationship., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Iron is routinely supplemented in broiler feeds intending to prevent dietary deficiencies. The present research was conducted with the objective of assessing Fe requirements of broilers when fed supplemental phytase. A total of 1,280 1-d-old male Cobb × Cobb 500 were distributed in a 2 × 5 factorial arrangement (phytase-supplemented feeds × 5 graded increases of supplemental Fe) in 80 battery cages, eight replications of eight chicks each. The trial was replicated once. Chicks were fed a Fe-deficient diet without phytase (Fe analyzed at 31.30 ± 3.79 mg/kg) from placement to 7 d and then randomly distributed into battery cages with corresponding dieting treatments with or without phytase and graded increases of supplemental Fe. Feeds were formulated with corn and soybean meal (SBM), laboratory-grade calcium carbonate, and phosphoric acid; therefore, the vast majority of dietary Fe originated from corn and SBM (analyzed diet had 53.3 ± 1.41 mg/kg Fe). Phytase was added in excess to the producer recommendation of 1,000 FYT (4,452 ± 487 FYT/kg analyzed) such that phytate degradation was expected to be maximized. Supplemental Fe was from laboratory-grade ferrous sulfate heptahydrate (FeSO47H2O) which was increasingly added to the feeds (analyzed Fe in the supplemented feeds were: 53.3 ± 1.41, 65.5 ± 0.59, 77.2 ± 1.97, 87.6 ± 1.72, 97.7 ± 1.33 mg/kg). There were no interactions between phytase and dietary Fe for any response throughout the study (P > 0.05). Supplementing phytase had no effects on Fe intake or Fe excretion, as well as on hematocrit (Ht), hemoglobin (Hb), ferritin, Fe contents in the liver or thigh muscle color (P > 0.05). However, phytase-supplemented feeds produced better live performance as well as higher ileal digestible energy and Fe digestibility (P < 0.05). No effects were found for dietary Fe in live performance at day 28 (P > 0.05). On the other hand, increasing dietary Fe led to linear increases in Fe retention and excretion, Fe contents in livers, as well as Ht and Hb at 14 d (P < 0.05). Quadratic responses (P < 0.05) were observed for Hb at 21 d, serum ferritin on days 14, 21, and 28 (maximum responses were 83.3, 104.0, 91.9, and 88.3 mg/kg Fe, respectively). In conclusion, supplementing Fe adding to a total of 97.7 mg/kg dietary Fe did not affect live performance traits. However, the average of Fe-related blood parameters was maximized at 91.9 mg/kg dietary Fe. Supplementing phytase provided a significant increase in Fe digestibility., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy associated with high morbidity and high mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, was the first medication approved for treating aHUS in 2011., Objective: The objective of this study is to evaluate the efficacy and safety of eculizumab treatment in pediatric patients with aHUS., Data Sources: We consulted PubMed, Scopus, SciELO, and Cochrane Library databases in July 2021. The descriptors were as follows: "Atypical Hemolytic Uremic Syndrome," "aHUS," "eculizumab," "Pediatrics," "Pediatric," "Child," "Children," "Adolescent.", Study Eligibility Criteria: The study eligibility criteria are as follows: clinical trials and observational studies that included pediatric patients with aHUS diagnosis and who were treated with eculizumab., Participants and Interventions: The participants are pediatric patients, up to 18 years old, with aHUS. The intervention was eculizumab treatment., Study Appraisal: For quality assessment, we used the Newcastle-Ottawa Scale, the National Institutes of Health (NIH) quality assessment tool for case series studies, and the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool., Results: The initial search retrieved 433 studies, from which 15 were selected after complete assessment: 9 cohorts, 4 case series, and 1 clinical trial. The publication date ranged from 2015 to 2021. In total, 940 pediatric patients were included, and 682 received eculizumab. All studies reported improvements in renal and hematological parameters in most of the patients treated with eculizumab. The mortality rate was 1.6% for all patients treated with eculizumab., Limitations: The number of studies is limited, and the included studies were methodologically heterogeneous. The studies were mostly observational and many had small sample sizes., Conclusions: Eculizumab appears to be safe and effective for the treatment of aHUS in pediatric patients. More research is necessary to establish long-term efficacy, safety, and time of discontinuation., Systematic Review Registration Number: CRD42021266255., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Although infectious diseases have been associated with cardiovascular conditions, little is known about tropical disease burden and hypertension. We hypothesized that a history of tropical infections was associated with hypertension. We examined participants from outpatient clinics in the Amazon Basin who were interviewed about prior exposure to tropical diseases, including dengue, malaria hospitalization, and leishmaniasis. Hypertension was defined as a prior physician diagnosis of hypertension, treatment with anti-hypertensive medication, or a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg. We used logistic regression models to examine the relationship between tropical infectious disease and hypertension. We included 556 participants (mean age 41 ± 15 years, 61% women) of whom 214 (38%) had hypertension and 354 (64%) had a history of tropical infectious disease. The distribution of tropical diseases was: dengue 270 (76%), malaria hospitalization 104 (29%) and leishmaniasis 48 (14%). Any prior tropical infection was significantly associated with prevalent hypertension (odds ratio 1.76 [95% CI 1.22-2.54], P = 0.003) and the association remained significant after adjusting for age, sex, body mass index, diabetes, hypercholesterolemia, socioeconomic status, smoking, vegetable intake and serum creatinine. Persons with a history of ≥2 tropical infections (n = 64) had the greatest risk of hypertension (odds ratio 2.04 [95% CI 1.15-3.63], P = 0.015). In adjusted models, prior infection with dengue was associated with hypertension (P = 0.006), but no associations were found with malaria hospitalization (P = 0.39) or leishmaniasis (P = 0.98). In conclusion, a history of tropical infectious disease was associated with hypertension. This finding supports the idea that pathogen burden may be related to cardiovascular conditions., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Dengue virus can affect the cardiovascular system and men may be at higher risk of severe complications than women. We hypothesized that clinical dengue virus (DENV) infection could induce myocardial alterations of the left ventricle (LV) and that these changes could be detected by transthoracic echocardiography., Methodology/principal Findings: We examined individuals from Acre in the Amazon Basin of Brazil in 2020 as part of the Malaria Heart Study. By questionnaires we collected information on self-reported prior dengue infection. All individuals underwent transthoracic echocardiography, analysis of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). We included 521 persons (mean age 40±15 years, 39% men, 50% urban areas) of which 253 (49%) had a history of dengue infection. In multivariable models adjusted for clinical and sociodemographic data, a history of self-reported dengue was significantly associated with lower LVEF (β = -2.37, P < 0.01) and lower GLS (β = 1.08, P < 0.01) in men, whereas no significant associations were found in women (P > 0.05). In line with these findings, men with a history of dengue had higher rates of LV systolic dysfunction (LVEF < 50% = 20%; GLS < 16% = 17%) than those without a history of dengue (LVEF < 50% = 7%; GLS < 16% = 8%; P < 0.01 and 0.06, respectively)., Conclusions/significance: The findings of this study suggest that a clinical infection by dengue virus could induce myocardial alterations, mainly in men and in the LV, which could be detected by conventional transthoracic echocardiography. Hence, these results highlight a potential role of echocardiography for screening LV dysfunction in participants with a history of dengue infection. Further larger studies are warranted to validate the findings of this study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kaagaard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The genus Orthopoxvirus (OPXV) of the family Poxviridae comprises several viruses that are capable of infecting a wide range of hosts. One of the most widespread OPXVs is the Vaccinia virus (VACV), which circulates in zoonotic cycles in South America, especially in Brazil, infecting domestic and wild animals and humans and causing economic losses as well as impacting public health. Despite this, little is known about the presence and/or exposure of neotropical primates to orthopoxviruses in the country. In this study, we report the results of a search for evidence of OPVX infections in neotropical free-living primates in the state of Minas Gerais, southeast Brazil. The sera or liver tissues of 63 neotropical primates were examined through plaque reduction neutralization tests (PRNT) and real-time PCR. OPXV-specific neutralizing antibodies were detected in two sera (4.5%) from Callithrix penicillata , showing 55% and 85% reduction in plaque counts, evidencing their previous exposure to the virus. Both individuals were collected in urban areas. All real-time PCR assays were negative. This is the first time that evidence of OPXV exposure has been detected in C. penicillata , a species that usually lives at the interface between cities and forests, increasing risks of zoonotic transmissions through spillover/spillback events. In this way, studies on the circulation of OPXV in neotropical free-living primates are necessary, especially now, with the monkeypox virus being detected in new regions of the planet.

Main Conclusion: The pUceS8.3 is a constitutive gene promoter with potential for ectopic and strong genes overexpression or active biomolecules in plant tissues attacked by pests, including nematode-induced giant cells or galls. Soybean (Glycine max) is one of the most important agricultural commodities worldwide and a major protein and oil source. Herein, we identified the soybean ubiquitin-conjugating (E2) enzyme gene (GmUBC4; Glyma.18G216000), which is significantly upregulated in response to Anticarsia gemmatalis attack and Meloidogyne incognita-induced galls during plant parasitism by plant nematode. The GmUBC4 promoter sequence and its different modules were functionally characterized in silico and in planta using transgenic Arabidopsis thaliana and G. max lines. Its full-length transcriptional regulatory region (promoter and 5´-UTR sequences, named pUceS8.3 promoter) was able to drive higher levels of uidA (β-glucuronidase) gene expression in different tissues of transgenic A. thaliana lines compared to its three shortened modules and the p35SdAMV promoter. Notably, higher β-glucuronidase (GUS) enzymatic activity was shown in M. incognita-induced giant cells when the full pUceS8.3 promoter drove the expression of this reporter gene. Furthermore, nematode-specific dsRNA molecules were successfully overexpressed under the control of the pUceS8.3 promoter in transgenic soybean lines. The RNAi gene construct used here was designed to post-transcriptionally downregulate the previously characterized pre-mRNA splicing factor genes from Heterodera glycines and M. incognita. A total of six transgenic soybean lines containing RNAi gene construct were selected for molecular characterization after infection with M. incognita pre-parasitic second-stage (ppJ2) nematodes. A strong reduction in the egg number produced by M. incognita after parasitism was observed in those transgenic soybean lines, ranging from 71 to 92% compared to wild-type control plants. The present data demonstrated that pUceS8.3 is a gene promoter capable of effectively driving dsRNA overexpression in nematode-induced giant cells of transgenic soybean lines and can be successfully applied as an important biotechnological asset to generate transgenic crops with improved resistance to root-knot nematodes as well as other pests., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Prior studies have suggested that self-rated health may be a useful indicator of cardiovascular disease. Consequently, we aimed to assess the relationship between self-rated health, cardiovascular risk factors and subclinical cardiac disease in the Amazon Basin., Design: Cross-sectional study., Setting, Participants and Interventions: In participants from the Amazon Basin of Brazil we obtained self-rated health according to a Visual Analogue Scale, ranging from 0 (poor) to 100 (excellent). We performed questionnaires, physical examination and echocardiography. Logistic and linear regression models were applied to assess self-rated health, cardiac risk factors and cardiac disease by echocardiography. Multivariable models were mutually adjusted for other cardiovascular risk factors, clinical and socioeconomic data, and known cardiac disease., Outcome Measures: Cardiovascular risk factors and subclincial cardiac disease by echocardiography., Results: A total of 574 participants (mean age 41 years, 61% female) provided information on self-rated health (mean 75±21 (IQR 60-90) points). Self-rated health (per 10-point increase) was negatively associated with hypertension (OR 0.87 (95% CI 0.78 to 0.97), p=0.01), hypercholesterolaemia (OR 0.89 (95%CI 0.80 to 0.99), p=0.04) and positively with healthy diet (OR 1.13 (95%CI 1.04 to 1.24), p=0.004). Sex modified these associations (p-interaction <0.05) such that higher self-rated health was associated with healthy diet and physical activity in men, and lower odds of hypertension and hypercholesterolaemia in women. No relationship was found with left ventricular ejection fraction <45% (OR 0.97 (95% CI 0.77 to 1.23), p=0.8), left ventricular hypertrophy (OR 0.97 (95% CI 0.76 to 1.24), p=0.81) or diastolic dysfunction (OR 1.09 (95% CI 0.85 to 1.40), p=0.51)., Conclusion: Self-rated health was positively associated with health parameters in the Amazon Basin, but not with subclinical cardiac disease by echocardiography. Our findings are of hypothesis generating nature and future studies should aim to determine whether assessment of self-rated health may be useful for screening related to policy-making or lifestyle interventions., Trial Registration Number: Clinicaltrials.gov: NCT04445103; Post-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the safety of compressive taping in patients with seroma secondary to breast cancer surgery., Methods: This study was a nonrandomized clinical study of medical devices applied to women indicated for seroma aspiration puncture after breast cancer surgery in a public reference hospital in Brazil. The intervention consisted of applying compressive taping over the seroma fluctuation area and maintained for 5 days. Evaluated outcomes comprised dermal changes caused by taping, subjective symptoms reported during the intervention period, and percent change in the punctured volume before and after the intervention., Results: A total of 35 women (mean age, 56.7 ± 12.2 years) were included. Most presented with an advanced disease stage (≥IIB; 62.9%). Although a 28.6% incidence of dermal changes caused by taping was observed, an average reduction in the aspirated volume of -28.2 mL was identified (95% confidence interval, -48.3 to -8.0; P = .008). Treatment adherence was high (91.4%), and most patients reported satisfaction with the treatment (85.7%)., Conclusions: The use of compressive taping on seroma areas can be considered safe, is well accepted by patients, and might be used as a noninvasive treatment option for seroma developing after breast cancer surgery., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Several published studies have reported an association between participation in a food assistance program and greater prevalence of overweight/obesity. Our aim was to compare nutritional status and nutrient consumption between workers from manufacturing companies participant and non-participant in the Brazilian Workers' Food Program (WFP)., Design: Cross-sectional survey, based on a probability sample of manufacturing workers in Brazil obtained by stratified two-stage sampling, comparative between WFP and non-WFP participating companies. Body mass index (BMI), waist circumference (WC), and nutrient consumption (24-hour recall) were collected by trained nutritionists. Statistical analysis was done separately in each sex with mixed effects multilevel linear regression model including sampling weights and covariate adjustment., Results: Thirty-three companies were randomly selected from all companies in three different economic activity sectors (food and beverages, non-metallic minerals, and textiles) in North-eastern Brazil, with stratification by company size, and a random sample of 929 workers (484 from non-WFP and 445 from WFP companies) was obtained from those companies. In males, the WFP group had higher BMI (+ 1.08 kg/m 2 , p < 0.001), greater WC (+ 3.27 cm, p < 0.001) and greater prevalence of obesity (OR 1.67, p < 0.001). In females, no statistical significant differences were observed in anthropometric parameters, but the WFP group had lower prevalence of obesity (OR 0.49, p = 0.05). Among workers in companies that provide lunch, males from WFP companies have greater consumption of carbohydrates (+ 39.5 kcal, p = 0.02) and protein (+ 11.1 kcal, p = 0.08), while females have lower protein consumption (- 14.2 kcal, p = 0.04) and also lower total daily consumption of carbohydrates (- 59.3 Kcal, p = 0.05) and total lipids (- 14.2 Kcal, p = 0.04)., Conclusions: Participation in the WFP is associated with increased BMI and WC among male workers; however, this association was not found in females. Compared to the non-WFP group, in the WFP group, males have greater consumption of carbohydrates and protein at lunch, while women have lower protein intake. These results indicate the need that proposals for public policies aimed to the improvement of the nutritional status of populations take into consideration the different effects of food assistance programs in males and females., (© 2022. The Author(s).)

Malaria patients are at risk of cardiopulmonary complications but diagnosis and management can be difficult in resource-limited settings. B-lines on lung ultrasound (LUS) mark changes in lung density; however, little is known about their role in malaria. We aimed to examine the prevalence of B-lines in adults with malaria at baseline and follow-up compared with controls in the Amazon Basin. We also examined the relationship between B-lines and left ventricular ejection fraction. We performed eight-zone LUS, echocardiography, and blood smears in 94 adults (mean age 40 years, 54% men) with uncomplicated malaria and 449 controls without heart failure, renal insufficiency or lung disease (mean age 41 years, 38% men). Examinations of adults with malaria were repeated after antimalarial treatment, corresponding to a median of 30 days (interquartile range [IQR] 27-39). Adults with malaria suffered from Plasmodium vivax (N = 70, median 2,823 [IQR 598-7,698] parasites/μL) or P. falciparum (N = 24, median 1,148 [IQR 480-3,128] parasites/μL). At baseline, adults with malaria more frequently had ≥ 3 B-lines (summed across eight zones) compared with controls (30% versus 2%, P value < 0.001), indicating higher lung density. When examinations were repeated, only 6% of adults with malaria had ≥ 3 B-lines at follow-up, which was significant lower compared with baseline (median reduction 3 B-line; P value < 0.001). B-lines were not significantly associated with left ventricular ejection fraction in adults with malaria. In conclusion, B-lines detected by LUS were more frequent in adults with uncomplicated malaria compared with controls and decreased after completed antimalarial treatment.

Country- and ethnicity-specific reference values for echocardiographic parameters are necessary for decision making. No prior studies have examined reference values in adults from the Amazon Basin of Brazil. We performed echocardiographic examinations in 290 healthy adults (mean age 37 ± 14 years, 40% male) from the Brazilian Amazon. Left ventricular (LV) dimensions and volumes were obtained and indexed to body surface area. We also assessed systolic (LV ejection fraction [LVEF] and global longitudinal strain [GLS]) and diastolic function. LV dimensions and volumes were larger in males compared to females, but after indexation only volumes remained larger (P < 0.001 for all). Parameters of systolic function, were significantly greater in females (LVEF 50 to 68%, GLS - 17 to - 24%) than in males (LVEF 50 to 67%, GLS - 15 to - 23%, P < 0.05). Upper limits of normality for cardiac dimensions (indexed and non-indexed) were markedly higher compared to contemporary guidelines (American Society of Echocardiography) and the Brazilian subgroup in the World Alliance Society of Echocardiography (WASE). Lower limit of normality for LVEF (both sex 50%) and upper limit of normality for the left atrial volume index (LAVI) (male: 31 mL/m 2 , female: 25 mL/m 2 ) were within normal range but slightly lower compared to guidelines and the WASE study. Other diastolic parameters, including E/A-ratio, E/e' ratio and peak tricuspid regurgitation velocity were compatible with present recommendations. Normal reference ranges of echocardiographic parameters in healthy adults from the Brazilian Amazon Basin may be different compared to international guidelines and data from other regions of Brazil. This applies specifically for LVEF and LAVI., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Rheumatic heart disease (RHD) continues to be a burden in low- and middle-income countries and prevalence estimates are lacking from South America. We aimed to determine the prevalence of RHD in the Brazilian Amazon Basin., Methods: We examined a random sample of adults (≥18 years) from the general population, who underwent echocardiographic image acquisition by a medical doctor. All images were analyzed according to (i) the 2012 World Heart Federation criteria and (ii) a simplified algorithm for RHD from a previously validated risk score (categories: low-, medium-, high-risk) which involved assessment of the mitral valve (leaflet thickening and excessive motion, regurgitation jet length) and aortic valve (thickening and any regurgitation)., Results: A total of 488 adults were screened (mean age 40 ± 15 years, 38% men). The prevalence of RHD was 39/1000 adults (n = 17 definite and n = 2 borderline). Fourteen (74%) had pathological mitral regurgitation, four (21%) mitral stenosis, 0 (0%) pathological aortic regurgitation and six (32%) both mitral and aortic valve disease. None had a prior diagnosis of RHD, 10 (53%) had positive cardiac auscultation and two (11%) reported a history of rheumatic fever. The simplified algorithm identified four (21%) adults as low-risk, six (32%) as intermediate, and nine (47%) as high-risk., Conclusions: The prevalence of RHD was 39/1000 in adults from the Brazilian Amazon Basin, indicating the need for screening programs in remote areas. A simplified model was only able to categorize every second case of RHD as high-risk. External validation of simplified screening models to increase feasibility in clinical practice are encouraged., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Studies have proposed that malaria may lead to electrocardiographic (ECG) changes and pericardial inflammation. We aimed to investigate the frequency of ECG alterations, determined by ECG and Holter monitoring, and pericardial effusion in patients with malaria infection. We performed a prospective observational study of adult patients with uncomplicated malaria in Amazonas, Brazil. Peripheral blood smears, ECG, and bedside echocardiography were conducted before antimalarial treatment and repeated at follow-up after completed treatment. We evaluated the diagnostic value of PR-segment depression, PR-segment elevation, and Spodick's sign for detecting pericardial effusion. A subset of patients underwent Holter monitoring at baseline. Among 98 cases of uncomplicated malaria (55% men; mean age 40 years; median parasite density 1,774/µl), 75 had Plasmodium vivax, 22 Plasmodium falciparum, and 1 had mixed infection. At baseline, 17% (n = 17) had PR-segment depression, 12% (n = 12) PR-segment elevation, 3% (n = 2) Spodick's sign, and the prevalence of pericardial effusion was 9% (n = 9). ECG alterations had sensitivities of 22% to 89% and specificities of 88% to 100% for detecting pericardial effusion at baseline. PR-segment depression had the best accuracy (sensitivity 89%, specificity 90%). Of the 25 patients, 4 patients who did not have pericardial effusion, displayed nonsustained ventricular tachycardia, determined by Holter monitoring (median duration 43 hours). Follow-up examination data were obtained for 71 patients (median 31 days), for whom PR-segment depression, elevation, and pericardial effusion had reduced significantly (p <0.05). In conclusion, our findings suggest that ECG alterations may be useful to detect pericardial effusion in malaria and that these findings decrease after completed antimalarial treatment., Competing Interests: Disclosures Dr. Dominguez receives support from grant 18-M03-KU from Danida Fellowship Center (Frederiksberg, Denmark) for Holter monitoring with Cortrium C3+ devices., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction : The Activities-specific Balance Confidence scale is the most used tool to quantify balance confidence, a psychological factor related to balance impairment among older adults. Objective : To investigate the validity and reliability of the original and short versions of the Brazilian Activities-specific Balance Confidence scales, to determine cutoff points for balance impairments and to identify the determinants of balance confidence of community-dwelling older adults. Methods : The validity of both versions of the scales was verified by correlating its results with postural balance, fear of falling and mobility (n = 105). Both scales were administered with a 30 min (interrater reliability, n = 158) and 1-week intervals (intrarater reliability, n = 105). Receiver operating characteristic curve was used to determine the cutoff points, and linear regression was applied to identify the determinants of balance confidence. Results : The Brazilian versions of the scale correlated to postural balance, fear of falling and mobility ( p < .05). Excellent interrater (α = 0.946, 95% CI: 0.902-0.976; α = 0.932, 95% CI: 0.918-0.960) and intrarater reliability (α = 0.946, 95% CI: 0.905-0.960; α = 0.952, 95% CI: 0.921-0.965) were found for the original and short versions.  Values of ≤67% (sensitivity: 81%, specificity: 77.4%) and ≤44% (sensitivity: 87.5%, specificity: 82.1%) were observed to identify balance impairments for the original and short versions of the scale. Physical inactivity, fear of falling, imbalance sensation, and number of falls are the main determinants of balance confidence. Conclusion : Both scales are valid and reliable to assess balance confidence. Cutoff points to identify balance impairments were determined and some factors may act as possible predictors of balance confidence.

Introduction: The all-inside arthroscopic repair of the anterior talofibular ligament (ATFL) is a technically challenging and still-recent procedure to treat chronic ankle instability (CAI). Favourable clinical outcomes have been shown from originator centers, but this is one of the first series from a non-originator centre. The purpose of the present study is to present the clinical and functional results of patients with CAI underwent arthroscopic all-inside ATFL repair., Methods: This is a series of cases of 18 consecutive patients who underwent the all-inside arthroscopic ATFL repair, for CAI, after the failure of conservative treatment performed for six months. The evaluation was made using the American Orthopaedic Foot and Ankle Score (AOFAS), visual analog pain scale (VAS), anterior drawer, and talar tilt tests., Results: All 18 patients were evaluated for a mean follow-up period of 12 months. There was an improvement in the AOFAS (p < 0.001), with the mean improving from 69.6 points to 98.1, standard deviation (SD) = 11.09, and in the mean VAS score (p < 0.001), from 5.0 to 0.5 points (SD = 0.78). All ankles were stable, as assessed by the anterior drawer test and talar tilt test. The only complication found was neurapraxia of the superficial fibular nerve in one patient (5%). All of the patients classified the treatment as good or excellent and returned to sports activities without limitations., Conclusion: Treatment of CAI by the all-inside arthroscopic ATFL repair was able to restore ankle stability and showed good clinical results and high satisfaction rates., (© 2021. The Author(s) under exclusive licence to SICOT aisbl.)

Estuaries in the world are affected by different contamination sources related to urbanisation and port/industrial activities. Identifying the substances responsible for the environmental toxicity in estuaries is challenging due to the multitude of stressors, both natural and anthropogenic. The Toxicity Identification and Evaluation (TIE) is a suitable way of determining causes of toxicity of sediments, but it poses difficulties since its application is labour intensive and time consuming. The aim of this study is to evaluate the diagnosis provided by a TIE based on microscale embryotoxicity tests with interstitial water (IW) to identify toxicants in estuarine sediments affected by multiple stressors. TIE showed toxicity due to different combinations of metals, apolar organic compounds, ammonia and sulphides, depending on the contamination source closest to the sampling station. The microscale TIE was able to discern different toxicants on sites subject to different contamination sources. There is good agreement between the results indicated in the TIE and the chemical analyses in whole sediment, although there are some disagreements, either due to the sensitivity of the test used, or due to the particularities of the use of interstitial water to assess the sediment toxicity. The improvement of TIE methods focused on identifying toxicants in multiple-stressed estuarine areas are crucial to discern contamination sources and subsidise management strategies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The performance of therapeutic ultrasonic (TUS) devices has a high degree of variability because of the fragility of the equipment (its transducer in particular) and its handling. These facts raise doubts about the effectiveness and safety of treatments employing such devices. Currently there is no simple way to adequately verify the performance of these devices. In our first experiments, we used a thermochromatic test body (typically a cylindrical plate 3.7 cm in diameter and 5.8 mm high) irradiated with therapeutic transducers driven by a standard radiofrequency (RF) generator. Results revealed a linear relationship between the thermal image areas, generated by the transducer's irradiation, and their respective effective radiation areas (ERAs), suggesting a good correlation. With five 3-MHz transducers, our group also observed the linear relationship using commercial TUS RF driving devices. In the present work, we used four 1-MHz transducers with their respective TUS RF driving devices and verified that there is a linear relationship between the thermal images and the ERAs at intensities of 1.0 ± 0.1 and 0.5 ± 0.05 W/cm 2 . The linear relationship obtained at both intensities confirms the suggestion that these thermochromatic test bodies can be used as the first evaluation of the ERAs and can monitor their changes with use. Moreover, if a previous assessment of the ERA and transducer intensities is performed, it is possible to follow the variation in ERA simply by monitoring the test body thermal stain., Competing Interests: Conflict of interest disclosure Potential competing interests do not exist., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: The GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity, immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with different epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3, GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of transmission, was evaluated., Methods: This study was performed using serum samples from 352 individuals from Cruzeiro do Sul and Mâncio Lima, in the state of Acre, and Guajará, in the state of Amazonas. Specific IgG, IgM, IgA and IgE antibodies and IgG subclasses were detected by Enzyme-Linked Immunosorbent Assay., Results: The results showed that GMZ2.6c protein was widely recognized by naturally acquired antibodies from individuals of the Brazilian endemic areas with different levels of transmission. The higher prevalence of individuals with antibodies against GMZ2.6c when compared to its individual components may suggest an additive effect of GLURP, MSP-3, and Pfs48/45 when inserted in a same construct. Furthermore, naturally malaria-exposed individuals predominantly had IgG1 and IgG3 cytophilic anti-GMZ2.6c antibodies, an important fact considering that the acquisition of anti-malaria protective immunity results from a delicate balance between cytophilic/non-cytophilic antibodies. Interestingly, anti-GMZ2.6c antibodies seem to increase with exposure to malaria infection and may contribute to parasite immunity., Conclusions: The data showed that GMZ2.6c protein is widely recognized by naturally acquired antibodies from individuals living in malaria-endemic areas in Brazil and that these may contribute to parasite immunity. These data highlight the importance of GMZ2.6c as a candidate for an anti-malarial vaccine., (© 2021. The Author(s).)

Background: Lung transplantation (LTx) has been discussed as an option for treating irreversible lung fibrosis post-coronavirus disease 2019 (COVID-19), in selected cases., Objectives: To report on the initial experience and management of end-stage lung disease due to COVID-19 at a national center reference in Brazil., Design and Setting: Cohort study conducted at a national reference center for lung transplantation., Methods: Medical charts were reviewed regarding patients' demographics and pre-COVID-19 characteristics, post-LTx due to COVID-19., Results: Between March 2020 and September 2021, there were 33 cases of LTx. During this period, we evaluated 11 cases of severe COVID-19-related acute respiratory distress syndrome (ARDS) that were potentially candidates for LTx. Among these, LTx was only indicated for three patients (9.1%). All of these patients were on venovenous extracorporeal membrane oxygenation (ECMO), and the procedure that they underwent was central venoarterial ECMO. All three patients were still alive after the first 30 postoperative days. However, patient #1 and patient #2 subsequently died due to fungal sepsis on the 47th and 52nd postoperative days, respectively. Patient #3 was discharged on the 30th postoperative day., Conclusions: LTx is feasible among these complex patients. Survival over the first 30 days was 100%, and this favors surgical feasibility. Nonetheless, these were critically ill patients.

Introduction: Elevated neutrophil-lymphocyte ratio (NLR) has been associated with poorer outcomes in cyanotic patients undergoing single ventricle palliation. Little is known about this biomarker on patients with tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease. Our objective is to study the impact of preoperative NLR on outcomes of TOF patients undergoing total repair., Methods: This retrospective study included 116 consecutive patients between January 2014 and December 2018. Preoperative NLR was measured from the last complete blood count test before the surgery. Using the cutoff value of 0.80, according to the receiver-operating characteristic (ROC) curve, the sample was divided into two groups (NLR < 0.80 and ≥ 0.80). The primary endpoint was hospital length of stay (LOS)., Results: ROC curves showed that higher preoperative NLR was associated with longer hospital LOS, with an area under the curve of 0.801±0.040 (95% confidence interval 0.722 - 0.879; P<0.001). High preoperative NLR was also associated with long intensive care unit (ICU) LOS (P=0.035). Preoperative NLR predicted longer hospital LOS with a sensitivity of 63% and a specificity of 81.4%., Conclusion: Higher preoperative NLR was associated with long ICU and hospital LOS in patients undergoing TOF repair.

The multiple sire system (MSS) is a common mating scheme in extensive beef production systems. However, MSS does not allow paternity identification and lead to inaccurate genetic predictions. The objective of this study was to investigate the implementation of single-step genomic BLUP (ssGBLUP) in different scenarios of uncertain paternity in the evaluation for 450-day adjusted liveweight (W450) and age at first calving (AFC) in a Nellore cattle population. To estimate the variance components using BLUP and ssGBLUP, the relationship matrix (A) with different proportions of animals with missing sires (MS) (scenarios 0, 25, 50, 75, and 100% of MS) was created. The genotyped animals with MS were randomly chosen, and ten replicates were performed for each scenario and trait. Five groups of animals were evaluated in each scenario: PHE, all animals with phenotypic records in the population; SIR, proven sires; GEN, genotyped animals; YNG, young animals without phenotypes and progeny; and YNGEN, young genotyped animals. The additive genetic variance decreased for both traits as the proportion of MS increased in the population when using the regular REML. When using the ssGBLUP, accuracies ranged from 0.13 to 0.47 for W450 and from 0.10 to 0.25 for AFC. For both traits, the prediction ability of the direct genomic value (DGV) decreased as the percentage of MS increased. These results emphasize that indirect prediction via DGV of young animals is more accurate when the SNP effects are derived from ssGBLUP with a reference population with known sires. The ssGBLUP could be applied in situations of uncertain paternity, especially when selecting young animals. This methodology is shown to be accurate, mainly in scenarios with a high percentage of MS., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Information on cardiopulmonary complications in clinical malaria is sparse and diagnosis may be difficult in resource-limited areas due to lack of proper diagnostic tools and access to medical care. A case of pericardial effusion and pulmonary alterations assessed by ultrasound in a patient with uncomplicated mixed malaria infection is described., Case Presentation: A previously healthy 23-year-old male from the Amazon Basin was diagnosed with mixed infection of Plasmodium vivax and Plasmodium falciparum by peripheral blood smear. The patient presented with mild malaria symptoms without signs of severe malaria, but reported moderate chest pain and shortness of breath. Laboratory analyses revealed thrombocytopenia and anemia. The electrocardiogram had PR depressions and bedside ultrasound of the cardiopulmonary system showed pericardial effusion (18 mm) accompanied by multiple B-lines in the lungs, identified as vertical artifacts extending from the pleural line. Cardiac biomarkers were normal. The patient was treated according to national guidelines for malaria and suspected pericarditis, respectively. At follow-up on day 5, the pericardial effusion (9mm) and B-lines had markedly decreased. By day 21 the patient was asymptomatic, had completed the treatment, and the electrocardiogram and ultrasound findings had normalized., Conclusions: This case report highlight the usefulness of bedside ultrasound to identify cardiopulmonary involvement in patients with uncomplicated malaria and relevant symptoms., (© 2021. The Author(s).)

Background: Despite completion of the vaccine schedule for hepatitis B virus (HBV), children may display levels of HBV surface antibodies (anti-HBs) that are considered inadequate for sufficient protection (<10 IU/L)., Aims: Our aim was to investigate if age and gap time between HBV vaccine doses may negatively affect the levels of anti-HBs in children, and if these relationships are modified by sex., Methods: In a high-endemic HBV region of the western Brazilian Amazon we enrolled children who had completed the HBV vaccine schedule. All children underwent analysis of anti-HBs and a clinical examination., Results: We included 522 children (mean age 4.3 ± 0.8 years; 50% male). Median anti-HBs was 28.4 [interquartile range (IQR) 5.4 to 128.6] IU/L and 32% had anti-HBs <10 IU/L. The median gap time from last to preceding dose was 2.4 [IQR 2.1 to 3.3] months. Levels of anti-HBs decreased with higher age (-42% per year increase [95%CI -56% to -24%], p<0.001), but not with longer gap time (+23% per month increase [95%CI -16% to +62%], p = 0.249). After adjusting for relevant confounders, gap time became significant (p = 0.032) and age remained a significant predictor of anti-HBs (p<0.001)., Conclusion: One third of assessed children displayed anti-HBs <10 IU/L. Levels of anti-HBs decreased with higher age and increased with longer gap time between the last two doses., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Li-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer., Materials and Methods: We determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil., Results: The TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria., Conclusion: The identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation., Competing Interests: Maurício Fernando Silva Almeida RibeiroTravel, Accommodations, Expenses: Foundation Medicine Rodrigo Medeiros BovolinStock and Other Ownership Interests : Abbott Laboratories (ABT), Johnson & Johnson (JNJ), Novo Nordisk A/S (NVO), Edwards Lifesciences (EW), Zoetis Inc (ZTS), Gilead Sciences (GILD), Varian Medical Systems Inc. (VAR), Varex Imaging Corporation (VREX) Fernando Costa SantiniHonoraria: Merck Sharp & Dohme, Roche, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, Wyeth, AmgenConsulting or Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Roche, Bayer, Lilly, AmgenSpeakers' Bureau: Roche, Merck Sharp & Dohme, AstraZeneca, BayerTravel, Accommodations, Expenses: Bayer, Merck Sharp & Dohme, Bristol Myers Squibb Rodrigo Ramella MunhozHonoraria: Bristol Myers Squibb, MSD, Roche, Novartis, Sanofi, Merck SeronoConsulting or Advisory Role: Roche, Merck Serono, Sanofi, Bristol Myers SquibbSpeakers' Bureau: Bristol Myers Squibb, MSD, Novartis, RocheResearch Funding: Lilly, Roche, Bristol Myers Squibb, Novartis, MSDTravel, Accommodations, Expenses: Bristol Myers Squibb, MSD, Roche, Sanofi Denis Leonardo Fontes JardimHonoraria: Janssen-Cilag, Roche/Genentech, Astellas Pharma, MSD Oncology, BMS Brazil, Pfizer, Libbs, MerckConsulting or Advisory Role: Janssen-Cilag, Pfizer, MSDTravel, Accommodations, Expenses: MSD, BMS Brazil, Janssen-Cilag Gustavo dos Santos FernandesHonoraria: Roche, MSD Oncology, BayerResearch Funding: Roche, Memorial Sloan-Kettering Cancer Center, BMS BrazilTravel, Accommodations, Expenses: Roche Maria Isabel AchatzConsulting or Advisory Role: RocheSpeakers' Bureau: AstraZeneca, MSD Oncology, Merck Sharpe & DohmeNo other potential conflicts of interest were reported.

In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.

Introduction: Several studies have reported increased cardiometabolic risk among workers assisted by food assistance public policies. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its individual components among manufacturing workers and their relationship to the Brazilian Workers' Food Program (WFP)., Methods: It was a prospective, cross-sectional, two-stage survey comparative of manufacturing workers from companies adherent and non-adherent to the WFP stratified by sector of activity and company size. The workers were interviewed in the workplace, and data on waist circumference (WC), blood pressure, and 12-hours fasting blood glucose (FBG), serum triglycerides (TG), and total and HDL-cholesterol were obtained. Mixed effects multilevel regression was used to compare WFP and non-WFP groups separately in each sex. All subjects gave written informed consent., Results: The survey included 332 workers from 16 WFP companies and 344 workers from 17 non-WFP companies. The general prevalence of MetS, according to IDF/AHA/NHLBI criteria, was high but not statistically different between sexes (39.8% in females versus 28.5% for males, p=0.16). Statistically significant differences were found between sexes in the prevalence of individual components: WC (77.8% in females versus 38.3% in males, p=0.002), TG (27.3% in females versus 40.8% in males, p=0.07), and HDL-C (52.2% in females versus 43.1% in males, p=0.05). Among males, MetS prevalence was significantly higher in the WFP group (33.0% versus 23.9%, p=0.008), and, in the individual components, the WFP group had higher prevalence of increased WC (47.0% versus 29.4%, p<0.001) and elevated FBG (8.9% versus 6.3%, p<0.001), as well as greater average levels of TG, HDL-C and FBG. Among female workers, no statistically significant differences between groups were observed in MetS prevalence and its individual components, but WFP female worker presented lower systolic and diastolic blood pressure., Conclusion: In a low-income population, male manufacturing workers participating in a food assistance program are at increased risk of MetS, an effect that was not identified among female workers., Competing Interests: The authors declare no conflicts of interest., (© 2020 Pereira et al.)

Aim: This study investigated whether time-estimation task exposure influences the severity of Attention Deficit Hyperactivity Disorder (ADHD), as well as theta band activity in the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex., Material and Methods: Twenty-two patients with ADHD participated in a crossover experiment with a visual time-estimation task under control conditions (without exposure to time estimation tasks) and experimental (thirty days exposure to time-estimation tasks) in association with electroencephalographic analysis of theta band., Results: ADHD patients with thirty days of time-estimation task exposure presented a worse performance of the time-estimation task, as revealed by the measurements of the absolute error and relative error ( p  ≤ 0.05). However, our findings show the improvement of self-reported symptoms of attention, impulsivity, and emotional control in patients after the time-estimation task exposure ( p  = 0.0001). Moreover, the theta band oscillations in the right dorsolateral prefrontal cortex and in the ventrolateral prefrontal increased with thirty days of time-estimation task exposure ( p  ≤ 0.05)., Conclusion: We propose that the decrease in EEG theta power may indicate an efficient accumulation of temporal pulses, which could be responsible for the improvement in the patient cognitive aspects as demonstrated by the current study. Time-estimation task improves ADHD cognitive symptoms, with a substantial increase in cortical areas activity related to attention and memory, suggesting its use as a tool for cognitive timing function management and non-invasive therapeutic aid in ADHD.