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The study analyzes the development of responses to address the COVID-19 pandemic in Latin America. It is a descriptive study based on an analysis of documents, data, and policy measures adopted or announced between March and December 2020 in 14 Latin American countries. The analysis included assessment of the content, tenor, and scope of policy measures for containment and mitigation, health care, and reorganization of health services identified on government websites. In addition, quantitative demographic indicators were included, as well as those related to the epidemiological situation and the result of the Stringency index. In general, the responses of Latin American countries were heterogeneous, albeit multisectoral, characterizing the complexity and diversity of decision making when confronting a pandemic. The conclusion drawn is that there is still a great deal to reflect upon with respect to the consequences of regulatory weaknesses for the achievement of multidimensional demands during health crises.

Although arbovirus transmission and identifying target vectors may provide a baseline for planning disease control strategies, there are many gaps in knowledge regarding these mosquitoes and viral species in urban, rural, or sylvatic habitats in the Brazilian Amazon. Our goal was to screen for dengue, chikungunya, and Zika viruses in synanthropic mosquitoes and with Flinders Technology Associates (FTA) cards using insect saliva. Mosquitoes were caught using ovitraps and aspirators in the city of Porto Velho, Rondônia, Brazil. Honey-baited FTA cards were placed in mosquito cages for 15 days; whole mosquitoes and FTA cards were analysed for viral RNA using RT-qPCR assays. One pool of Aedes aegypti females was found to be infected with the Zika virus and one male mosquito was infected with dengue-4, suggesting natural vertical/venereal transmission. Our study also reported evidence of vertical/venereal transmission of ZIKV in Culex quinquefasciatus males for the first time in the Brazilian Amazon, and the feasibility of using FTA cards to detect arboviruses in the saliva of field-collected mosquitoes. Vertical/venereal transmission of viruses by atypical mosquito species reinforces the need for combined viral and entomological screening in arbovirus surveillance programs., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Postoperative pain is one of the main negative symptoms resulting from surgery and the use of new methods to control this symptom is of ever-increasing relevance. Opioid-sparing strategies, such as multimodal analgesia, are trends in this scenario. Pregabalin is a well-established treatment for neuropathic pain; however, it is still controversial in the surgical context for postoperative analgesia. This study investigated the effect of pregabalin on postoperative analgesia in patients undergoing abdominal hysterectomy. It is a prospective, randomised, double-blind, placebo-controlled clinical trial. Female patients undergoing abdominal hysterectomy were randomised to use pregabalin (group P1), 300 mg orally 2 h before surgery, or identical placebo pills (group P0). The main outcome includes the postoperative pain index by visual analogue scale (VAS) and McGill's pain questionnaire. Secondary outcomes include opioid consumption and the presence of adverse effects. A value of p < 0.05 was used to reject type I error. Fifty-five patients were randomised amongst the groups. Patients in group P1 had lower pain rates by VAS scale, both at rest and in active motion, than group P0. In McGill's questionnaire, patients from group P1 also had lower pain rates (12 × 28.5). There was approximately twice as much opioid consumption amongst patients in group P0. Regarding side effects, there was a difference between the two groups only for dizziness, being more incident in group P1. This study suggests that pregabalin is an important adjuvant drug in treating postoperative pain in patients with abdominal hysterectomy., (© 2022 John Wiley & Sons Australia, Ltd.)

Benzene, toluene, ethylbenzene and xylene (BTEX) are toxic petroleum hydrocarbons pollutants that can affect the central nervous system and even cause cancer. For that reason, studies regarding BTEX degradation are extremely important. Our study aimed evaluate the microorganism Bacillus subtilis as a tool for degrading petroleum hydrocarbons pollutants. Assays were run utilizing water or soil distinctly contaminated with gasoline and diesel oil, with and without B. subtilis. The ability of B. subtilis to degrade hydrophobic compounds was analyzed by Fourier-Transform Infrared Spectroscopy (FTIR) and gas chromatography. The FTIR results indicated, for water assays, that B. subtilis utilized the gasoline and diesel oil to produce the biosurfactant, and, as a consequence, performed a biodegradation process. In the same way, for soil assay, B. subtilis biodegraded the diesel oil. The gas chromatography results indicated, for gasoline in soil assay, the B. subtilis removed BTEX. So, B. subtilis was capable of degrading BTEX, producing biosurfactant and it can also be used for other industrial applications. Bioremediation can be an efficient, economical, and versatile alternative for BTEX contamination., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Subcutaneous and visceral adipose tissues are important body components, but their effects on the mortality in patients with liver cirrhosis remain controversial based on the current evidence., Methods: We retrospectively identified 372 eligible patients in whom subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) could be measured by computed tomography images at the third lumbar vertebra. The association of SATI and VATI with the risk of death was evaluated on a continuous scale with restricted cubic spline curves based on Cox proportional hazards models. Cumulative probability of mortality was estimated by Nelson-Aalen cumulative risk curve analyses. Independent predictors of death were evaluated by competing risk analyses after adjusting for age, sex, and model for end-stage liver disease score., Results: Majority of patients were male (69.4%) with a mean age of 55.40 ± 10.68 years. SATI had a U-shaped association with mortality (P for non-linearity <0.001). Cutoff values of SATI were 19.7 and 51.8 cm 2 /m 2 at the points where hazard ratios were just <1.2. SATI was categorized as low (<19.7 cm 2 /m 2 ), moderate (19.7-51.8 cm 2 /m 2 ), and high (>51.8 cm 2 /m 2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate SATI groups (Gray's test, P = 0.052) and high versus moderate SATI groups (Gray's test, P = 0.054). Competing risk analyses demonstrated that low SATI could increase the mortality compared with moderate SATI (subdistribution hazard ratio [sHR] = 1.66, 95% confidence interval [CI]: 0.992-2.78, P = 0.054) and was an independent predictor of death (sHR = 1.86, 95% CI: 1.059-3.28, P = 0.031). Competing risk analyses also demonstrated that high SATI could significantly increase the mortality compared with moderate SATI (sHR = 1.6, 95% CI: 1-2.54, P = 0.049), and was an independent predictor of death (sHR = 2.007, 95% CI: 1.195-3.37, P = 0.0085). VATI had an irregularly shaped association with mortality (P for non-linearity <0.001). Cutoff values of VATI were 9.8 and 40.2 cm 2 /m 2 at the points where hazard ratios were just <1.2. VATI was categorized as low (<9.8 cm 2 /m 2 ), moderate (9.8-40.2 cm 2 /m 2 ), and high (>40.2 cm 2 /m 2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate VATI groups (Gray's test, P = 0.381) and high versus moderate VATI groups (Gray's test, P = 0.787). Competing risk analyses demonstrated that neither low (sHR = 1.27, 95% CI: 0.599-2.7, P = 0.53) nor high VATI (sHR = 0.848, 95% CI: 0.539-1.34, P = 0.48) was an independent predictor of death compared with moderate VATI., Conclusions: Both excessive deficiency and accumulation of subcutaneous adipose tissues negatively influence the outcomes of cirrhotic patients., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: The epidemiological significance of wildlife infections with aetiological agents causing human infectious diseases is largely determined by their infection status, contact potential with humans (via vectors for vector-borne diseases), and their infectiousness to maintain onward transmission. This study quantified these parameters in wild and synanthropic naturally infected rodent populations in an endemic region of tegumentary leishmaniasis in northeast Brazil., Methods: Capture-mark-recapture (CMR) of rodents was conducted over 27 months in domestic/peri domestic environs, household plantations and nearby Atlantic Forest (9,920 single trap nights). Rodent clinical samples (blood and ear tissue) were tested for infection by conventional PCR and quantitative PCR (qPCR) for Leishmania (Viannia) braziliensis, and xenodiagnosis to measure infectiousness to the local sand fly vector., Results: A total 603 individuals of 8 rodent species were (re)captured on 1,051 occasions. The most abundant species were Nectomys squamipes (245 individuals, 41% of the total catch), Rattus rattus (148, 25%), and Necromys lasiurus (83, 14%). All species were captured in greater relative frequencies in plantations; R. rattus was the only species captured in all three habitats including in and around houses. Four species, comprising 22.6% of individuals captured at least twice, were geolocated in more than one habitat type; 78.6% were infected with L. (V.) braziliensis, facilitating inter-species and inter-habitat transmission. Species specific period prevalence ranged between 0%-62% being significantly higher in N. squamipes (54-62%) and Hollochillus sciureus (43-47%). Xenodiagnosis was performed on 41 occasions exposing 1,879 Nyssomyia whitmani sand flies to five rodent species (37 individuals). Similar mean levels of infectiousness amongst the more common rodent species were observed. Longitudinal xenodiagnosis of the N. squamipes population revealed a persistent level of infectiousness over 13 months follow-up, infecting a median 48% (IQR: 30.1%-64.2%) of exposed blood-fed vectors. The proportion of exposed flies infected was greater in the low compared to in the high seasonal period of vector abundance. L. (V.) braziliensis parasite loads in rodent blood quantified by qPCR were similar across rodent species but did not represent a reliable quantitative marker of infectiousness to sand flies. The standardised risk of rodent infection in plantations was 70.3% relative to 11.3% and 18.4% in peri domestic and forest habitats respectively. R. rattus was the only exception to this trend indicating greatest risk in the peri domestic environment., Conclusions: The results support the view that a collective assemblage of wild and synanthropic rodent species is an important wild reservoir of L. (V.) braziliensis in this region, with N. squamipes and R. rattus probably playing a key role in transmission within and between habitat types and rodent species. Rodents, and by implication humans, are at risk of infection in all sampled habitats, but more so in homestead plantations. These conclusions are based on one of the longest CMR study of small rodents in an American Tegumentary Leishmaniasis (ATL) foci., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Marinho-Júnior 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.)

Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare neoplastic disease of varied presentation and unspecific radiological signs in the early stages. The diagnostic delay can lead to metastatic disease, thus increasing the tumor burden and reducing the treatment options. HEHE is usually deemed a slow-growing tumor, but its speed of growth is poorly reported and still unknown., Case Description: In this case report, we documented a HEHE diagnosed in a young woman who had complaints of abdominal pain, weight loss and bloating for a long time. The typical findings observed in histological studies were not promptly recognized in the histological analyzes, even after two laparoscopic-guided liver biopsies, delaying the diagnosis until extrahepatic tumor spreading. Findings observed in computed tomography, magnetic resonance imaging and histological studies are presented. The coalescence of nodules and the rising of giant masses, occupying large parts of the liver in a specific time span, were registered and quantified. As opposed to prior reports, the results show that hepatic HEHE can grow rapidly, reinforcing the need of early diagnosis, thus avoiding the complications presented herein., Conclusions: The findings observed via radiological and histological imaging that could have avoided the diagnosis delay are depicted and discussed, showing that HEHE can rise faster than previously documented., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-22-48/coif). FGR reports that the study was funded by São Paulo Research Cientific Foundation (FAPESP; Grant No. 2017/25592-9), but only the Institution received the payments. None of them was done for the researcher. The researcher has received funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The funding is a scholarship for researchers according to their scientific production. The other authors have no conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

Ancistrus Kner, 1854, is the most diverse genus among the Ancistrini (Loricariidae) with 70 valid species showing a wide geographic distribution and great taxonomic and systematic complexity. To date, about 40 Ancistrus taxa have been karyotyped, all from Brazil and Argentina, but the statistic is uncertain because 30 of these reports deal with samples that have not yet been identified at the species level. This study provides the first cytogenetic description of the bristlenose catfish, Ancistrus clementinae Rendahl, 1937, a species endemic to Ecuador, aiming to verify whether a sex chromosome system is identifiable in the species and, if so, which, and if its differentiation is associated with the presence of repetitive sequences reported for other species of the family. We associated the karyotype analysis with the COI molecular identification of the specimens. Karyotype analysis suggested the presence of a ♂ZZ/♀ZW 1 W 2 sex chromosome system, never detected before in Ancistrus, with both W 1 W 2 chromosomes enriched with heterochromatic blocks and 18S rDNA, in addition to GC-rich repeats (W 2 ). No differences were observed between males and females in the distribution of 5S rDNA or telomeric repeats. Cytogenetic data here obtained confirm the huge karyotype diversity of Ancistrus, both in chromosome number and sex-determination systems.

For field-like environmental gas monitoring and noninvasive illness diagnostics, effective sensing materials with exceptional sensing capabilities of sensitive, quick detection of volatile organic compounds (VOCs) are required. Carbon-based nanomaterials (CNMs), like CNTs, graphene, carbon dots (Cdots), and others, have recently drawn a lot of interest for their future application as an elevated-performance sensor for the detection of VOCs. CNMs have a greater potential for developing selective sensors that target VOCs due to their tunable chemical and surface properties. Additionally, the mechanical versatility of CNMs enables the development of novel gas sensors and places them ahead of other sensing materials for wearable applications. An overview of the latest advancements in the study of CNM-based sensors is given in this comprehensive organized review., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has become a major concern contributing to increased morbidity and mortality worldwide., Objectives: Here we describe the replacement of the Gamma variant of concern (VOC) with Delta in the western Brazilian Amazon., Methods: In this study, we analysed 540 SARS-CoV-2 positive samples determined by qualitative real-time RT-PCR selected in the state of Rondônia between June and December 2021. The positive cohort was sequenced through next-generation sequencing (NGS) and each sample was quantified using real-time RT-qPCR, the whole genome sequence was obtained, SARS-CoV-2 lineages were classified using the system Pango and the maximum likelihood (ML) method was used to conduct phylogenetic analyses., Findings: A total of 540 high-quality genomes were obtained, where the Delta VOC showed the highest prevalence making up 72%, with strain AY.43 being the most abundant, while the Gamma VOC was present in 28%, where the P.1 strain was the most frequent. In this study population, only 32.96% (178/540) had completed the vaccination schedule., Main Conclusions: This study highlighted the presence of Gamma and Delta variants of SARS-CoV-2 in RO. Furthermore, we observed the replacement of the Gamma VOC with the Delta VOC and its lineages.

In this study, the effect of ultrasound processing on the properties of two packages widely used in food products was evaluated: polyamide (PA) and polyethylene (PE) multilayer packaging. Packages composed of PE/PA/PE (Film A) and PE/PA/PE/PA/PE (Film B) were filled with aqueous and fatty food simulants and treated in an ultrasound water bath (frequency 25 kHz, volumetric power of 9.74 W/L, temperature of 25 °C, and time of 30 and 60 min). Materials were evaluated in term of structure and performance properties. Ultrasound did not or induced small changes in chemical groups, crystallinity, melting temperature, and tensile strength of the films. Film A showed a reduction in heat sealing tensile strength of 25% in the machine direction and 22% in the transverse direction. Film B showed a 20% increase of water vapor transmission rate after ultrasound processing. Although ultrasound had little impact on the properties of the evaluated materials, these modifications do not compromise the use of these packages for applications in ultrasound-processed foods. Therefore, the results indicate that ultrasound can be used as a food processing technology in multilayer PA and PE packaging., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Biliobronchial fistula (BBF) is a rare abnormality resulting from congenital or acquired communication between the bile ducts and the bronchial tree. Patients often suffer from chronic cough, dyspnea, and bilioptysis, a pathognomonic symptom of this condition. Conservative methods such as less-invasive procedures are gradually consolidating. Nonetheless, surgery remains the primary treatment, especially in more complex cases. We present the case of a 44-year-old woman with a chronic cough, no verified periods of fever, cyclic jaundice, and episodes of yellowish sputum. She had undergone cholecystectomy in 2018 and had been hospitalized several times since for pneumonia treatment. All consequent investigations for mycobacteriosis were negative. When referred to our hospital, she had cyclic jaundice and parenchymal consolidation in the right lower lobe. Suspected bilioptysis motivated the search for a biliobronchial fistula. Magnetic resonance cholangiography (MRC) confirmed stenosis of the biliary tract and fistulous path, and sputum analysis indicated high bilirubin levels. External biliary bypass was performed as an initial conservative and definitive therapy due to the presence of liver cirrhosis. Although BBF is a rare condition when bilioptysis is suspected, a diagnostic investigation should be initiated. Our case study proposes two criteria for diagnosis: an imaging exam demonstrating the fistulous path and confirmation of bilirubin in the sputum or bronchoalveolar lavage (BAL). When diagnosed, surgical correction should be performed., Competing 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., (Copyright © 2022 Batalin Júnior, Zandoná, Vargas, Oliveira, Chiappetto, Oliveira, Romeiro and Tanni.)

Background: Point-of-care and decentralized testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies., Methods: A prospective diagnostic accuracy study was conducted among close contacts of coronavirus disease 2019 (COVID-19) cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and 1 molecular method were evaluated for usability and performance against reference reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens., Results: Fifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during ≥1 visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta variants emerged increasingly during implementation. The overall sensitivity of evaluated tests ranged from 33% to 76%. Performance was higher among symptomatic cases and those with cycle threshold (Ct) values <34 and lower among oligosymptomatic or asymptomatic cases. Assuming a 24-hour time to results for RT-PCR, the cumulative sensitivity of an anterior nares swab rapid antigen test was >70% and almost 90% after 4 days., Conclusions: The near-immediate time to results for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. 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) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The present study aimed to examine the changes that occurred in vertical jump and isokinetic dynamometer (ISK) performances at the beginning of a preparatory period (PRE) and at the start of the competitive period (POST). Sixteen U-17 elite female volleyball players, from a national level (15.34 ± 1.19 years; 66.35 ± 7.95 kg; 169.22 ± 24.79 cm), performed bilateral squat jump (SJ), bilateral and unilateral countermovement jump (CMJ) and unilateral ISK tests for knee flexors (Fl) and extensors (Ex) both at 60°/s and at 300°/s. Peak torque (PT) and the hamstring-to-quadriceps (H:Q) ratio were assessed by concentric actions. Asymmetries were calculated by the percentage differences between dominant (DOM) and nondominant legs (NDOM). The paired Student's t -test was used for comparisons at a level of significance of 5%. The effect size was also calculated. A significant increase was found for both SJ (15%; p = 0.004; ES = 0.82) and CMJ (12%; p = 0.017; ES = 0.62). The PT of NDOM flexors at 60°/s was significantly lower than DOM both at PRE (4.6%; p = 0.048; ES = -0.22) and POST (6.3%; p = 0.037; ES = -0.33). The NDOM extensors at 60°/s had a significantly lower PT than DOM at POST (7.0%; p = 0.048; ES = -0.23). Both DOM and NDOM flexors at 60°/s had a PT enhancement at POST related to PRE (6.7%; p = 0.031; ES = 0.51 and 5.6%; p = 0.037; ES = 0.48, respectively). The PT of NDOM extensors at 300°/s increased at POST in comparison to PRE (7.9%; p = 0.038; ES = 0.27). The NDOM at 300°/s had a H:Q ratio higher than DOM both in PRE and POST (8.6%; p = 0.041; ES = 0.37 and 11.6%; p = 0.013; ES = 0.71, respectively), and the highest H:Q ratios were lower than the reference values (<80%). The asymmetry of the unilateral CMJ was higher at POST than at PRE (102%; p = 0.03; ES = 0.81). The PT for the flexors at 300°/s and the H:Q ratio at POST exceeded 10%. In conclusion, a training program of 15 weeks increased the neuromuscular performance of young volleyball athletes, but many H:Q ratios and asymmetries remained out of the normal recommendation. Volleyball professionals should carefully apply an adequate training program to enhance physical fitness performance without increasing the risk of lower limb injuries concurrently.

Extracellular vesicle (EV) research increasingly demands for quantitative characterisation at the single vesicle level to address heterogeneity and complexity of EV subpopulations. Emerging, commercialised technologies for single EV analysis based on, for example, imaging flow cytometry or imaging after capture on chips generally require dedicated instrumentation and proprietary software not readily accessible to every lab. This limits their implementation for routine EV characterisation in the rapidly growing EV field. We and others have shown that single vesicles can be detected as light diffraction limited fluorescent spots using standard confocal and widefield fluorescence microscopes. Advancing this simple strategy into a process for routine EV quantitation, we developed 'EVAnalyzer', an ImageJ/Fiji (Fiji is just ImageJ) plugin for automated, quantitative single vesicle analysis from imaging data. Using EVAnalyzer, we established a robust protocol for capture, (immuno-)labelling and fluorescent imaging of EVs. To exemplify the application scope, the process was optimised and systematically tested for (i) quantification of EV subpopulations, (ii) validation of EV labelling reagents, (iii) in situ determination of antibody specificity, sensitivity and species cross-reactivity for EV markers and (iv) optimisation of genetic EV engineering. Additionally, we show that the process can be applied to synthetic nanoparticles, allowing to determine siRNA encapsulation efficiencies of lipid-based nanoparticles (LNPs) and protein loading of SiO 2 nanoparticles. EVAnalyzer further provides a pipeline for automated quantification of cell uptake at the single cell-single vesicle level, thereby enabling high content EV cell uptake assays and plate-based screens. Notably, the entire procedure from sample preparation to the final data output is entirely based on standard reagents, materials, laboratory equipment and open access software. In summary, we show that EVAnalyzer enables rigorous characterisation of EVs with generally accessible tools. Since we further provide the plugin as open-source code, we expect EVAnalyzer to not only be a resource of immediate impact, but an open innovation platform for the EV and nanoparticle research communities., (© 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial., Methods: EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated., Results: Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding., Conclusions: Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored., (© 2022. Asian Pacific Association for the Study of the Liver.)

Background: Bisphosphonates are the mainstay of osteoporosis treatment, but their use for patients with esophageal varices has been avoided due to the risk of esophagitis, which may cause variceal bleeding. Since most clinical trials assessing osteoporosis treatment last 2-3 years, this study aimed to evaluate a 2-year risedronate treatment for patients with esophageal varices and liver cirrhosis., Methods: The study received Institutional Review Board approval, and the sample was divided into two groups according to bone mineral density (BMD). Cirrhosis severity and endoscopic findings at baseline were similar between the groups. The intervention group had 51 patients with osteoporosis, who received oral risedronate 35 mg weekly plus calcium and vitamin D supplements. The control group had 51 patients with osteopenia, receiving only the supplements. Scheduled esophagogastroduodenoscopies and BMD measurements were carried out., Results: The adjusted esophagitis risk was higher in the intervention group; however, none of the subjects had digestive bleeding. Lumbar spine BMD increased in the intervention group (- 3.06 ± 0.71 to - 2.33 ± 0.90; p < 0.001) and in the control group (- 1.38 ± 0.77 to - 1.10 ± 1.05; p = 0.012). Femoral neck BMD did not change in the intervention group (- 1.64 ± 0.91 to - 1.71 ± 0.95; p = 0.220), but tended to decrease in the control group (- 1.00 ± 0.74 to - 1.09 ± 0.82; p = 0.053)., Conclusion: Oral risedronate was effective and did not cause gastrointestinal bleeding in cirrhotic patients with esophageal varices under endoscopic surveillance., (© 2022. Asian Pacific Association for the Study of the Liver.)

Oral health education is an effective measure to prevent oral mucositis (OM) by improving self-management and effectively engaging patients in their health care. This systematic review aimed to determine the impact of oral health education interventions on the incidence and severity of OM. Bibliographical searches were carried out by two independent examiners in Medline, Scopus, Web of Science, Cochrane Library, Virtual Health Library, and SIGLE, until June 2022. The eligibility criteria were based on the PICO strategy, considering studies with pediatric oncology patients, aged 0 to 19 years, who had attended oral health education activities and had been examined for the incidence and/or severity of OM. Data were extracted for qualitative synthesis and organized in spreadsheets. The quality assessment of the selected studies was performed using the ROBINS-I tool. Meta-analysis was based on the group frequencies of OM ulcerative lesions, adopting a significance level of 5%. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to define the certainty of the evidence. The primary search retrieved 1827 articles. After removing duplicate records and screening titles and abstracts for eligibility, a total of 21 articles were selected for full-text analysis. Of these, seven eligible studies were included for data extraction and qualitative synthesis, while four studies were selected for quantitative synthesis. All studies had a longitudinal design; three performed a before-after comparison and four were controlled studies. OM was assessed by the following scales: OAG, WHO, ChIMES, and WCCNR. While data analysis of the selected studies was heterogeneous, the implementation of oral health education strategies was found to reduce the incidence and severity of OM during the follow-up period. The meta-analysis showed a favorable outcome for the educational intervention. The likelihood of patients attending oral health education activities to manifest OM ulcerative lesions was significantly lower (P = 0.002) than that of the control. The GRADE analysis presented a low certainty of the evidence. To conclude, oral health education interventions improved OM outcomes in pediatric oncology patients with a low quality of evidence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fruticulture in the Amazonian Rainforest is one of the main causes of deforestation, biodiversity loss, and soil erosion. Fruticulture plays a key role in the soil traits and soil organic matter (SOM) compartments by altering the soil ecosystem. Our aim was to assess the influence of Forest-Fruticulture conversion on soil traits, and SOM fractions in Brazil's Legal Amazon. The experiment was carried out in field conditions using four land uses as main treatments: Bixa orellana , Theobroma grandiflorum , Paullinia cupana , and the Amazon Rainforest. The soil physicochemical traits were analyzed using samples that were collected from 0-5, 5-10, and 10-20 cm soil depth by using grids (10 × 10 m) with 36 sampling points. Our results showed that the Fruticulture promoted an increase in bulk density, GMD, aggregate diameter, soil porosity, gravimetric moisture, sand, clay, carbon associated with humic acid, and, the sum of bases (K + , Ca 2+ , and Mg 2+ ), while the Amazon Rainforest showed the highest values of silt, soil P content, SOC, p-SOC, m-SOC, carbon associated with fulvic acid, humine, and soil C stock. Overall, the fruticulture farming systems have negative effects on SOM compartments. The results of our study highlight the importance of considering fruticulture with endemic plant species by promoting soil fertility and soil aggregation.

To better understand the production of enzymes of industrial interest from microorganisms with biotechnological potential using lignocellulosic biomass, we evaluated the production of endoglucanase and xylanase from Aspergillus tamarii. CAZymes domains were evaluated in the genome, and a screening of the enzymatic potential of A. tamarii in various agricultural biomasses was done. The enzymatic profile could be associated with the biomass complexity, with increased biomass recalcitrance yielding higher activity. A time-course profile defined 48 h of cultivation as the best period for cultivating A. tamarii in sugarcane bagasse reached 12.05 IU/mg for endoglucanase and 74.86 IU/mg for xylanase. Using 0.1% (w/v) tryptone as the only nitrogen source and 12 µmol/L CuSO 4 addition had an overall positive effect on the enzymatic activity and protein production. A 2 2 factorial central composite design was used then to investigate the simultaneous influence of tryptone and CuSO 4 on enzyme activity. Tryptone strongly affected enzymatic activity, decreasing endoglucanase activity but increasing xylanase activity. CuSO 4 supplementation was advantageous for endoglucanases, increasing their activity, and it had a negative effect on xylanases. But overall, the experimental design increased the enzymatic activity of all biomasses used. For the clean cotton residue, the experimental design was able to reach the highest enzyme activity for endoglucanase and xylanase, with 1.195 IU/mL and 6.353 IU/mL, respectively. More experimental studies are required to investigate how the biomass induction effect impacts enzyme production., (© 2022. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Recurrent pregnancy loss (RPL) is one of the most common reproductive failures affecting 1-5% of couples. Smad3 is an effector of signalling of the Transforming Growth Factors-β superfamily (TGF-β), regulating the transcription of several target genes of these cytokines. The objective of this study was to evaluate the influence of a variant on SMAD3 (rs17293443) in RPL. A case-control study was carried out with 149 women who experienced RPL and 159 controls, as well as bioinformatics tools to determine the role of this variant in this condition. Our study showed an allelic ( p  = 0.023) and genotypic ( p  < 0.01) association of this variant with the RPL. Our functional in silico predictions suggest that this variant causes a change in SMAD3 expression levels. Alterations in the expression of this gene can directly compromise the Smad3-dependent signalling pathway that is fundamental for key processes for gestation such as steroid hormone regulation and implantation, as demonstrated by ontologies analyses performed and the literature. Our findings regarding the involvement of Smad3 on RPL are a novelty in this field, and they seem to be promising to the clinical management of this condition.

Health care for patients with serious illnesses usually implies the need to make a large number of decisions, ranging from how information is shared to which diagnostic or therapeutic procedures will be adopted. The method of such decision-making has important implications from an individual and collective point of view and may contribute to either relieving or aggravating suffering. In this consensus document, the Bioethics Committee of the Brazilian National Academy of Palliative Care (ANCP) and the Permanent Committee on Palliative Care of the Brazilian Geriatrics and Gerontology Society (SBGG) adopt the principles of compassionate listening proposed by Saunders, of the nature of suffering proposed by Cassel, of dignity-preserving care proposed by Chochinov, and of cultural humility as a starting point for the construction of an official position of ANCP and SBGG on shared decision-making in palliative care. The position statement posits that, unlike paternalistic and consumerist models, the decision-making process in the sphere of palliative care must follow the mutualistic model of shared decision, where decisions are built based on dialogue between healthcare professionals and patients/family. The document sets forth the assumptions of this process, the limits of autonomy of patients/family and healthcare professionals and the distinction between futile and potentially inappropriate treatments, besides ratifying its incompatibility with any forms of coercion and conflict of interest foreign to the best interests of patients.

Background: Common variable immunodeficiency (CVID) is a rare disease that affects children and adults and is often difficult to diagnose. Despite being one of the most frequent causes of immunodeficiency, involving gastrointestinal (GI), respiratory, and hematological systems, the disease onset can have heterogeneous and intermittent symptoms, frequently leading to diagnostic delay. GI symptoms are common and can include diarrhea, but the asymptomatic periods lead to overlooking the recurrent pattern. The same can occur with respiratory infections, thus delaying CVID suspicion. The starting point for CVID diagnosis is the decreased gamma globulin levels in serum protein electrophoresis (SPE), also observed through direct immunoglobulin's dosage., Case Presentation: The patient is a 38 years-old man who had intermittent diarrhea and recurrent airway infections for 19 years, but the CVID diagnosis was achieved only after SPE was carried out. At that time, he was already malnourished, and developed other complications related to CVID in a short period., Conclusions: SPE is readily available and inexpensive, but is not part of the laboratory approach in diarrhea. According to the case presented herein, it can be useful for patients with recurrent infections or other clues of the disease., (© 2022. The Author(s).)

Pathogenic variants in the genes encoding serine palmitoyl transferase (SPTLC1 or SPTLC2) are the most common causes of the rare peripheral nerve disorder Hereditary Sensory Neuropathy Type 1 (HSN1). Macular telangiectasia type 2 (MacTel), a retinal disorder associated with disordered serine-glycine metabolism, has been described in some patients with HSN1. This study aims to further investigate this association in a cohort of people with HSN1. Fourteen patients with a clinically and genetically confirmed diagnosis of HSN1 from the National Hospital for Neurology and Neurosurgery (NHNN, University College London Hospitals NHS Foundation Trust, London, United Kingdom) were recruited to the MacTel Registry, between July 2018 and April 2019. Two additional patients were identified from the dataset of the international clinical registry study (www.lmri.net). Ocular examination included fundus autofluorescence, blue light and infrared reflectance, macular pigment optical density mapping and optical coherence tomography. Twelve patients had a pathogenic variant in the SPTLC1 gene, with p.Cys133Trp in 11 cases (92%) and p.Cys133Tyr in one case (8%). Four patients had a variant in the SPTLC2 gene. None of the patients showed clinical evidence of MacTel. The link between HSN1 and MacTel seems more complex than can solely be explained by the genetic variants. An extension of the spectrum of SPTLC1/2-related disease with phenotypic pleiotropy is proposed. HSN1 patients should be screened for visual symptoms and referred for specialist retinal screening, but the association of the two diseases is likely to be variable and remains unexplained., (© 2022 Peripheral Nerve Society.)

Green tea (GT) is a natural antioxidant, sensitive to oxidation after preparation. Lyotropic liquid crystals (LLCs) are nanostructured systems used to incorporate bioactive compounds. High-intensity interval training (HIIT) is a workout modality that increases the production of reactive oxygen species (ROS). Thus, this research aimed to compare the effects of GT and GT loaded in LLC in animals subjected to HIIT, considering hematological, biochemical and histological parameters, redox status, and body mass. Monoolein, GT in infusion and Poloxamer 407 were mixed to obtain nanoparticles of LLC (NP-LLC). Healthy male rats were randomized into six groups ( n = 6/group): Control (C), GT, GT-NP-LLC, Exercise (Ex), GT+Ex, GT-NP-LLC+Ex. Body weight was significantly lower in all groups subjected to HIIT compared to C. The percentages of body mass reduction were 11.3, 13.0, 10.0 and 11.0% for Ex, GT+Ex, GT-NP-LLC and GT-NP-LLC+Ex, respectively, compared to control. GT-NP-LLC and Ex reduced triglycerides compared to C. GT and GT-NP-LLC supplementation combined with HIIT presented higher muscle hypertrophy (25 and 21%, respectively), better physical conditioning, and reduced body weight gain rate compared to HIIT by itself. Moreover, the effects of GT-NP-LLC itself on body mass and biochemical parameters are promising, suggesting NP-LLC could improve the bioavailability of GT.

A mesoscopic scale approach and the Monte Carlo (MC) method have been employed to study the exchange bias behaviour of MnFe 2 O 4 (soft)/maghemite (soft) and CoFe 2 O 4 (hard)/maghemite (soft) nanoparticles (NPs) of size ∼ 3 nm in dense and diluted assemblies at low temperatures. The analysis of our MC results clearly shows that in the powder samples the contribution to the exchange bias field ( H ex ) and the coercivity ( H c ) comes mainly from the intraparticle core/shell structure in the hard/soft sample and that the interplay between the internal characteristics and the interparticle interactions is more important in the soft/soft samples where the dipolar strength is enhanced. In the diluted frozen ferrofluid samples where interparticle exchange interactions are absent and the role of the dipolar interactions is not significant the exchange bias effects are reduced, and they come from the intra particle structure. The variation of H ex and H c with the applied cooling field well reproduces the experimental findings and sheds light on the key mechanisms of the observed magnetic behaviour. Our results demonstrate the possibility to control the magnetic behaviour of nanostructures by using properly chosen core/shell bimagnetic nanoparticles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Burnout, by definition, is related to adverse chronic workplace stressors. Life events outside the workplace have been associated with an increased risk of psychiatric morbidity. However, it is unknown whether life events outside the workplace increase the severity of burnout., Purpose: The aim of the study was to investigate the association between burnout and life events outside the workplace in nursing assistants., Methods: In an observational, cross-sectional, single-site study of 521 nursing assistants at a university hospital, we assessed burnout with the Maslach Burnout Inventory-Human Services Survey, and life events with the Social Readjustment Rating Scale. We constructed equations of multiple linear regression analyses that included each burnout subscale as the dependent variable and a domain of life events as the independent variable. Results were adjusted for potential confounders, including gender, no religion or faith, years of work, and depression., Results: An increase in the number of life events in the domain of personal changes or difficulties (e.g., personal injury or illness, sexual difficulties, change in recreation, church activities, social activities, sleeping habits, eating habits and revision of personal habits) was associated with increased severity of emotional exhaustion. An increase in the number of life events in the domain of changes in familial situation and in the domains of death of relatives or friends were associated with increased severity of depersonalization. Those associations were independent of work-related life events and other potential confounders., Conclusions: Life events outside the workplace may increase the levels of burnout in nursing assistants.

Aims: We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice., Main Methods: Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed., Key Findings: Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers., Significance: Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Low bone mineral density (BMD) is common in patients with inflammatory bowel disease. However, nutritional risk factors for low BMD in the ulcerative colitis (UC) population are still poorly understood., Aim: To investigate the association of anthropometric indicators and body composition with BMD in patients with UC., Methods: This is a cross-sectional study on adult UC patients of both genders who were followed on an outpatient basis. A control group consisting of healthy volunteers, family members, and close people was also included. The nutritional indicators evaluated were body mass index (BMI), total body mass (TBM), waist circumference (WC), body fat in kg (BFkg), body fat in percentage (BF%), trunk BF (TBF), and also lean mass. Body composition and BMD assessments were performed by dual-energy X-ray absorptiometry., Results: The sociodemographic characteristics of patients with UC ( n = 68) were similar to those of healthy volunteers ( n = 66) ( P > 0.05). Most patients (97.0%) were in remission of the disease, 58.8% were eutrophic, 33.8% were overweight, 39.0% had high WC, and 67.6% had excess BF%. However, mean BMI, WC, BFkg, and TBF of UC patients were lower when compared to those of the control group ( P < 0.05). Reduced BMD was present in 41.2% of patients with UC (38.2% with osteopenia and 2.9% with osteoporosis) and 3.0% in the control group ( P < 0.001). UC patients with low BMD had lower BMI, TBM, and BFkg values than those with normal BMD ( P < 0.05). Male patients were more likely to have low BMD (prevalence ratio [PR] = 1.86; 95% confidence interval [CI]: 1.07-3.26). Those with excess weight (PR = 0.43; 95%CI: 0.19-0.97) and high WC (PR = 0.44; 95%CI: 0.21-0.94) were less likely to have low BMD., Conclusion: Patients with UC in remission have a high prevalence of metabolic bone diseases. Body fat appears to protect against the development of low BMD in these patients., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Biodegradable cardiac patches have been able to induce improvement in left ventricular (LV) remodeling. A novel scaffold patch made with collagen and silk-fibroin (COL-SF) was further associated to polyaniline (PANi) to increase conductivity. Thus, this study investigated the safety of the association of PANi to a patch, and the improvement in LV remodeling in a myocardial infarct (MI) rat model. Wistar rats underwent MI induction. MI was confirmed with echocardiographic and after 2 weeks, animals (n = 10/group) were randomized into: (a) COL-SF hyaluronic acid patch, (b) PANi hyaluronic acid patch, (c) MI Control (just repeat thoracotomy). Healthy animals were also followed. Echocardiography was performed at pre-treatment, and at 2-, 4-, and 8-weeks post-treatment. Hearts underwent hemodynamic evaluation on Langendorff apparatus and histology for LV thickness and percent of infarct size. Liver, kidneys, and blood samples were evaluated for biochemical, hematological, oxidative stress, and histology. There was a tendency of lower %infarct size in patched animals. LV thickness was higher in the patched animals than controls. Functional echocardiographic indices %Fractional shortening and %LV ejection fraction decreased in the MI control group, but not in the patched animals. PANi presented higher %LVEF versus MI control. PANi presented higher liver transaminases; no morphological changes were observed in histology. Elevation of antioxidant markers was observed. COL-SF and PANi patches were able to induce better remodeling features compared to MI controls on %infarct size and LV thickness and have not presented echocardiographic worsening. Polyaniline may present a slight improvement on LV remodeling, despite associated to signs of hepatotoxicity and pro-oxidant effect., (© 2022 Wiley Periodicals LLC.)

The titanium alloy composition and microdesign affect the dynamic interplay between the bone cells and titanium surface in the osseointegration process. The current study aimed to evaluate the surface physicochemical properties, electrochemical stability, and the metabolic response of the MC3T3-E1 cells (pre-osteoblast cell line) cultured onto titanium-15molybdenum (Ti-15Mo) discs treated with phosphoric acid (H 3 PO 4 ) and sodium hydroxide (NaOH) and/or strontium-loading by the hydrothermal method. The x-ray dispersive energy spectroscopy (EDS) and x-ray diffraction (XRD) analysis showed no trace of impurities and the possible formation of hydrated strontium oxide (H 2 O 2 Sr), respectively. The confocal laser microscopy (CLSM) analysis indicated that titanium samples treated with strontium (Sr) showed greater surface roughness. The acid/alkali treatment prior to the hydrothermal Sr deposition improved the surface free energy and resistance to corrosion of the Ti-15Mo alloy. The acid/alkali treatment also provided greater retention of the Sr particles on the Ti-15Mo surfaces accordingly with inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. The AlamarBlue and fluorescence analysis indicated noncytotoxic effects against the MC3T3-E1 cells, which allowed cells' adhesion and proliferation, with greater cells' spreading in the Sr-loaded Ti-15Mo samples. These findings suggest that Sr deposition by the hydrothermal method has the potential to enhance the physicochemical properties of the Ti-15Mo previously etched with H 3 PO 4 and NaOH, and also improve the initial events related to cell-mediated bone deposition., (© 2022 IOP Publishing Ltd.)

Cannabis cultivation for medical purposes in Brazil has been increased in the last years. While cannabis crops are prohibited, hundreds patients have been granted with judicial authorizations and there is little information about the cultivation conditions, yields and chemical profiles of the plants. Cannabis plants contain hundreds of compounds, with cannabinoids and terpenes the main drivers of their toxicological and pharmacological properties. Besides the cannabinoids, terpene contents are useful for the chemotaxonomic classification of different varieties, and their role in forensic analyses should be further delineated. The present study monitored cannabis crops of fifteen participants who were granted special licenses by the Brazilian Courts in Rio de Janeiro and São Paulo. The cultivation conditions were monitored and five cannabinoids (tetrahydrocannabinol acid-THCA, tetrahydrocannabinol-THC, cannabidiolic acid-CBDA, cannabidiol-CBD and cannabinol-CBN) and nineteen terpenes were quantified in cannabis flowers. The total grow cycle of thirty-five cannabis plants ranged from 10 to 24 weeks. The dry flower yields ranged 22-90 g per plant. Most cannabis specimens were CBD-rich varieties (CBD levels from 1.6% to 16.7%, and THC levels from 0.0% to 2.6%, n = 22) used to treat epileptic patients. The THC-rich varieties contained CBD levels ranging from 0.03% to 0.8%, and THC levels from 0.7% to 20.1%, n = 11. Fewer of the samples contained THC:CBD ratios of approximately 1:1 (CBD levels of 3.3-3.8% and THC levels of 2.2-3.7%, n = 2). The most abundant terpenes in the cannabis flowers were beta-caryophyllene, alpha-humulene, guaiol and alpha-bisabolol. CBD-rich varieties showed significant higher levels of beta-caryophyllene and alpha-humulene in comparison with THC-rich varieties. Overall, the study herein provides data concerning medical cannabis crops grown in a region of Brazil that not only guide individual medical cannabis cultivation methods but also aid forensic analyses., Competing Interests: Declaration of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ammonia (NH[Formula: see text]) from manure is a concern in raising broiler due to possible damages to production and the environment. Brazil is the main exporter of chicken meat in the world and is also responsible for large waste of poultry litter. The country, likewise, figures as top 5 producers of green coconut, which results in considerable volumes of waste, since 80%-85% of the fruit is unusable. This work analyzes the ammonia concentration profile of two bedding substrates for raising broiler, to know, coir-husk fiber and a commonly used pine wood shavings in a Brazilian climate. A differential home-made photoacoustic cell combined with a diode laser was employed for sensing ammonia at trace levels. Such combination confers selectivity as well as lower limits of detection to the system. The chemical compositions pH, N, C, Ca, Mg, P[Formula: see text]O[Formula: see text] and K[Formula: see text]O were also determined, in addition to the moisture, dry matter and mineral content of substrates and litters. NH[Formula: see text] concentrations varied from (0.9 ± 0.3) ppmv to (19 ± 3) ppmv and from (2.1 ± 0.5) ppmv to (21 ± 3) ppmv for the coir-husk fiber and wood shavings substrates, respectively. Results showed the feasibility of using coconut fiber as poultry litter in regions where this material is a common waste. Moreover, as NH[Formula: see text] concentrations were lower for coconut fiber bedding compared to shavings, this coir-husk fiber is a potential residue to guarantee the environmental sustainability by Brazilian poultry farming. Coir-husk fibers presented significantly higher amounts of P and K in comparison to pine wood. NH[Formula: see text] profiles revealed that coir-husk fiber emitted lower quantities than wood shavings. Besides, a delay on the NH[Formula: see text] emission pattern was clearly seen when the coconut waste was the bedding material. Such a tendency was confirmed by the logistic model. Our findings, in turn, make the coir-husk an environmentally friendly alternative low-cost product for poultry litter as well as its potential use as natural fertilizer. The later deserves attention since there is a need to accurately assess the emissions of methane, nitrous oxide, and carbon dioxide during the composting process. In Brazil, the waste generated by the high production of green coconut is an environmental liability. The cost of poultry production has been high, reducing the profit of producers, who seek to make production cheaper. Measuring NH[Formula: see text] from poultry activity in Brazil, a tropical country, aims to control management and reduce production losses, since NH[Formula: see text] is a harmful gas to birds. The measurement of NH[Formula: see text] concentrations at trace levels from raising broilers by photoacoustic diode laser spectroscopy, to the best of our knowledge, has been reported for the very first time., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The systemic inflammatory response elicited by acute Zika virus (ZIKV) infection during pregnancy plays a key role in the clinical outcomes in mothers and congenitally infected offspring. The present study aimed to evaluate the serum levels of GDF-3 and inflammasome-related markers in pregnant women during acute ZIKV infection. Serum samples from pregnant (n = 18) and non-pregnant (n = 22) women with acute ZIKV infection were assessed for NLRP3, IL-1β, IL-18, and GDF3 markers through an enzyme-linked immunosorbent assay. ZIKV-negative pregnant (n = 18) and non-pregnant women (n = 15) were used as control groups. All serum markers were highly elevated in the ZIKV-infected groups in comparison with control groups (p < 0.0001). Among the ZIKV-infected groups, the serum markers were significantly augmented in the pregnant women in comparison with non-pregnant women (NLRP3 p < 0.001; IL-1β, IL-18, and GDF3 p < 0.0001). The IL-18 marker was found at significantly higher levels (p < 0.05) in the third trimester of pregnancy. Bivariate and multivariate analyses showed a strong positive correlation between GDF3 and NLRP3 markers among ZIKV-infected pregnant women (r = 0.91, p < 0.0001). The findings indicated that acute ZIKV infection during pregnancy induces the overexpression of GDF-3 and inflammasome-related markers, which may contribute to congenital disorders and harmful pregnancy outcomes.

Background: Bradyrhizobium japonicum strain SEMIA 5079 (= CPAC 15) is a nitrogen-fixing symbiont of soybean broadly used in commercial inoculants in Brazil. Its genome has about 50% of hypothetical (HP) protein-coding genes, many in the symbiosis island, raising questions about their putative role on the biological nitrogen fixation (BNF) process. This study aimed to infer functional roles to 15 HP genes localized in the symbiosis island of SEMIA 5079, and to analyze their expression in the presence of a nod-gene inducer., Results: A workflow of bioinformatics tools/databases was established and allowed the functional annotation of the HP genes. Most were enzymes, including transferases in the biosynthetic pathways of cobalamin, amino acids and secondary metabolites that may help in saprophytic ability and stress tolerance, and hydrolases, that may be important for competitiveness, plant infection, and stress tolerance. Putative roles for other enzymes and transporters identified are discussed. Some HP proteins were specific to the genus Bradyrhizobium, others to specific host legumes, and the analysis of orthologues helped to predict roles in BNF., Conclusions: All 15 HP genes were induced by genistein and high induction was confirmed in five of them, suggesting major roles in the BNF process., (© 2022. The Author(s).)

The attitude and heading reference system (AHRS) is an important concept in the area of navigation, image stabilization, and object detection and tracking. Many studies and works have been conducted in this regard to estimate the accurate orientation of rigid bodies. In most research in this area, low-cost MEMS sensors are employed, but since the system's response will diverge over time due to integration drift, it is necessary to apply proper estimation algorithms. A two-step extended Kalman Filter (EKF) algorithm is used in this study to estimate the orientation of an IMU. A 9-DOF device is used for this purpose, including a 6-DOF IMU with a three-axis gyroscope and a three-axis accelerometer, and a three-axis magnetometer. In addition, to have an accurate algorithm, both IMU and magnetometer biases and disturbances are modeled and considered in the real-time filter. After applying the algorithm to the sensor's output, an accurate orientation as well as unbiased angular velocity, linear acceleration, and magnetic field were achieved. In order to demonstrate the reduction of noise power, fast Fourier transform (FFT) diagrams are used. The effect of the initial condition on the response of the system is also investigated.

The COVID-19 epidemic in Brazil experienced two major lineage replacements until mid-2021. The first was driven by lineage P.2, in late 2020, and the second by lineage Gamma, in early 2021. To understand how these SARS-CoV-2 lineages spread in Brazil, we analyzed 11,724 genomes collected throughout the country between September 2020 and April 2021. Our findings indicate that lineage P.2 probably emerged in July 2020 in the Rio de Janeiro state and Gamma in November 2020 in the Amazonas state. Both states were the main hubs of viral disseminations to other Brazilian locations. We estimate that Gamma was 1.56-3.06 times more transmissible than P.2 in Rio de Janeiro and that the median effective reproductive number (Re) of Gamma varied according to the geographic context (Re = 1.59-3.55). In summary, our findings support that lineage Gamma was more transmissible and spread faster than P.2 in Brazil., Competing Interests: The authors declare no competing interests, (© 2022 The Author(s).)

This integrative review examined factors associated with hepatitis C treatment adherence. The articles included were published in English, Spanish and Portuguese in the Lilacs, Medline, PsycINFO, Web of Science, Scopus and CINAHL databases, between 2000 and 2019. Initially, 540 publications were found and, after applying the study inclusion criteria, 22 articles were selected. Percentage non-adherence to treatment ranged from 12% to 32%. The variables identified as facilitating adherence were: receiving treatment for psychiatric disorders identified during treatment; knowing about medications and disease; receiving less complex treatment with greater likelihood of cure; fewer adverse events; social support; doctor-patient communication; and/or being in relationships. Barriers to adherence identified were: presence of depressive symptoms and other mental disorders; abuse of alcohol and psychoactive substances; education; age; ethnicity; unemployment; not having a steady partner; stigma; distance from health services; and the complexity and adverse effects of treatment. This review identified gaps in research on adherence.

Introduction: Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). The role of inflammation and nitric oxide (NO) pathways in the pathophysiology of the LU is not understood., Objective: The aim of this study was to verify the association between inflammatory molecules and nitric oxide metabolites (NOx) and the occurrence of the LU in patients with SCA., Method: It was a cross-sectional study on adult participants with SCA followed at Fundação Hemominas, a public blood center in Brazil. Eligible participants were recruited and included in one of two groups: Group 1, comprised of cases with SCA (Hb SS) and at least one LU at the time of inclusion in the study and Group 2, comprised of controls with SCA without a history of LU, matched by sex and age to cases. Participants were interviewed to obtain sociodemographic data and blood samples were collected. Clinical and laboratory data were abstracted from medical records. Nitric oxide metabolites (NOx) and inflammatory molecules were quantified using an immunoassay and Multiplex xMAP® technology, respectively. Eighty-seven individuals were included, ranging in age from 17 to 61 years (mean 40 ± 10.7 years); 30 had LU and 57 were controls without LU., Results: Participants with LU had significantly higher levels of interleukin 8 (IL-8), IL-10, IL-15, NOx and platelet and white blood cell (WBC) counts, when compared to those without LU. Participants with LU had a significantly higher risk of having a history of osteomyelitis and a higher use of antiseptic soap in bathing, when compared to those without LU., Conclusion: In conclusion, our results showed that NOx, inflammatory molecules and hematological features were associated with LU in Brazilian adults with SCA., (Copyright © 2020 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nano-sized EVs from therapy-grade human placental-expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology. Scalable EV separation from cell-secreted soluble factors via tangential flow-filtration (TFF) and subtractive tandem mass-tag (TMT) proteomics revealed significant enrichment of predominantly immunomodulatory and proangiogenic proteins. Western blot, calcein-based flow cytometry, super-resolution and electron microscopy verified EV identity. PLX-EVs partly protected corona proteins from protease digestion. EVs significantly ameliorated human skin regeneration and angiogenesis in vivo, induced differential signalling in immune cells, and dose-dependently inhibited T cell proliferation in vitro. Corona removal by size-exclusion or ultracentrifugation abrogated angiogenesis. Re-establishing an artificial corona by cloaking EVs with fluorescent albumin as a model protein or defined proangiogenic factors was depicted by super-resolution microscopy, electron microscopy and zeta-potential shift, and served as a proof-of-concept. Understanding EV corona formation will improve rational EV-inspired nano-therapy design., (© 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: Setting up new liver transplant (LT) centers is essential for countries with organ shortages. However, good outcomes require experience, because LT learning depends on a high number of surgeries. This study aims to describe how a new center was set up from a partnership between the new center and an experienced one. The step-by-step preparation process, the time needed and the results of the new center are depicted., Material and Methods: The mentoring process lasted 40 months, in which half of the 52 patients included on the transplant list received LT. After the mentorship, a 22-month period was also analyzed, in which 46 new patients were added to the waiting list and nine were operated on., Results: The 30-day survival rates during (92.3%) and after (66.7%) the partnership were similar to the other LT centers in the same region, as well as the rates of longer periods. The waiting time on the LT list, the characteristics of the donors and the ischemia times did not differ during or after the mentorship., Conclusion: The partnership between universities is a suitable way to set up LT centers, achieving good results for the institutions and the patients involved., Competing Interests: The authors declare that they have no conflicts of interest to declare.

Bots have become active contributors in maintaining open-source repositories. However, the definitions of bot activity in open-source software vary from a more lenient stance encompassing every non-human contributions vs frameworks that cover contributions from tools that have autonomy or human-like traits ( i.e ., Devbots). Understanding which of those definitions are being used is essential to enable (i) reliable sampling of bots and (ii) fair comparison of their practical impact in, e.g ., developers' productivity. This paper reports on an empirical study composed of both quantitative and qualitative analysis of bot activity. By analysing those two bot definitions in an existing dataset of bot commits, we see that only 10 out of 54 listed tools (mainly dependency management) comply with the characteristics of Devbots. Moreover, five of those Devbots have similar patterns of contributions over 93 projects, such as similar proportions of merged pull-requests and days until issues are closed. Our analysis also reveals that most projects (77%) experiment with more than one bot before deciding to adopt or switch between bots. In fact, a thematic analysis of developers' comments in those projects reveal factors driving the discussions about Devbot adoption or removal, such as the impact of the generated noise and the needed adaptation in development practices within the project., Competing Interests: Philipp Leitner is an Academic Editor for PeerJ CS., (© 2022 Erlenhov et al.)

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS-CoV-2 lineages may impact COVID-19 disease progression and provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS-CoV-2 lineages are currently well phylogenetically defined, but two main factors have precluded major coinfection/codetection and recombination analysis thus far: (i) the low diversity of SARS-CoV-2 lineages during the first year of the pandemic, which limited the identification of lineage defining mutations necessary to distinguish coinfecting/recombining viral lineages; and the (ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we assembled a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. This approach enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations, representing 0.61 % of all samples investigated. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming its plausibility with the cocirculating lineages at the timeframe investigated. Our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, although it is certainly a lower bound estimate considering the difficulty to detect coinfections with very similar SARS-CoV-2 lineages and the low number of samples sequenced from the total number of infections.

The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we did not find an increased incidence of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sublineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting more infectious variants or antibody evasion mutations is expected to increase. IMPORTANCE The continuous evolution of SARS-CoV-2 is an expected phenomenon that will continue to happen due to the high number of cases worldwide. The present study analyzed how a Variant of Concern (VOC) could still circulate in a population hardly affected by two COVID-19 waves and with vaccination in progress. Our results showed that the answer behind that was a new generation of Gamma-like viruses, which emerged locally carrying mutations that made it more transmissible and more capable of spreading, partially evading prior immunity triggered by natural infections or vaccines. With thousands of new cases daily, the current pandemics scenario suggests that SARS-CoV-2 will continue to evolve and efforts to reduce the number of infected subjects, including global equitable access to COVID-19 vaccines, are mandatory. Thus, until the end of pandemics, the SARS-CoV-2 genomic surveillance will be an essential tool to better understand the drivers of the viral evolutionary process.

On 24 th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses., Competing Interests: Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. J.Z. and G.S. declare the Israel patent application no. 23/09/2020—277,546 and United States patent application no. 16/12/2020—63/125,984, entitled methods and compositions for treating coronaviral infections. Oxford University holds intellectual property related to the Oxford-Astra Zeneca vaccine. A.J.P. is Chair of UK Dept. Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee, and is a member of the WHO’s SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. The University of Oxford has protected intellectual property disclosed in this publication. S.C.G. is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine (PCT/GB2012/000467). T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project during the conduct of the study. S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In healthy adults, Nordic walking (NW) is known to increase the external mechanical energy fluctuations, though the external work is unaltered due to an improved pendulum-like recovery in comparison with free walking (FW). We aimed to compare mechanical, pendulum-like, and spatiotemporal parameters of gait at different speeds with and without NW poles in people with Parkinson's disease and healthy controls. The study included 11 people (aged 65.6 ± 7.0 years) with idiopathic Parkinson's disease, scoring between 1 and 1.5 on the Hoehn and Yahr scale (H&Y), and nine healthy controls (aged 70.0 ± 5.6 years). All the people were experienced Nordic walkers. Walking tests were performed at 1.8 km h -1 and 4.7 km h -1 , on eight 3D force platforms on a walkway. We found greater pendulum-like energy recovery (p < 0.05) in the Parkinson group during NW than in FW, while external mechanical work remained similar (p > 0.05). People with Parkinson's disease showed a major increase in vertical and forward energy fluctuations using poles than in healthy controls. In addition, the Parkinson group showed increased stride frequency and reduced stride length compared to controls in the NW and FW conditions. Our findings partly justify the lower walking economy in Parkinson's disease due to reduced pendulum-like mechanism at commonly used speeds. NW alters gait mechanics similarly in Parkinson group and healthy control, increasing the total mechanical work. Therefore, NW can be a compelling strategy for rehabilitation because of its potential for improving functional mobility, increasing pendulum-like mechanism in Parkinson's disease., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Platelet-rich plasma is a promising regenerative therapeutic with controversial efficacy. We and others have previously demonstrated regenerative functions of human platelet lysate (HPL) as an alternative platelet-derived product. Here we separated extracellular vesicles (EVs) from soluble factors of HPL to understand the mode of action during skin-organoid formation and immune modulation as model systems for tissue regeneration. HPL-EVs were isolated by tangential-flow filtration (TFF) and further purified by size-exclusion chromatography (SEC) separating EVs from (lipo)protein-enriched soluble fractions. We characterized samples by tunable resistive pulse sensing, western blot, tandem mass-tag proteomics and super-resolution microscopy. We evaluated EV function during angiogenesis, wound healing, organoid formation and immune modulation. We characterized EV enrichment by TFF and SEC according to MISEV2018 guidelines. Proteomics showed three major clusters of protein composition separating TSEC-EVs from HPL clustering with TFF soluble fractions and TFF-EVs clustering with TSEC soluble fractions, respectively. HPL-derived TFF-EVs promoted skin-organoid formation and inhibited T-cell proliferation more efficiently than TSEC-EVs or TSEC-soluble fractions. Recombining TSEC-EVs with TSEC soluble fractions re-capitulated TFF-EV effects. Zeta potential and super-resolution imaging further evidenced protein corona formation on TFF-EVs. Corona depletion on SEC-EVs could be artificially reconstituted by TSEC late fraction add-back. In contrast to synthetic nanoparticles, which commonly experience reduced function after corona formation, the corona-bearing EVs displayed improved functionality. We conclude that permissive isolation technology, such as TFF, and better understanding of the mechanism of EV corona function are required to realize the complete potential of platelet-based regenerative therapies.

One of the most remarkable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) features is the significant number of mutations they acquired. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we describe a new SARS-CoV-2 P.1 sub-lineage circulating in Brazil, denoted here as Gamma-like-II, that as well as the previously described lineage Gamma-like-I shares several lineage-defining mutations with the VOC Gamma. Reconstructions of ancestor sequences support that most lineage-defining mutations of the Spike (S) protein, including those at the receptor-binding domain (RBD), accumulated at the first P.1 ancestor. In contrast, mutations outside the S protein were mostly fixed at subsequent steps. Our evolutionary analyses estimate that P.1-ancestral strains carrying RBD mutations of concern probably circulated cryptically in the Amazonas for several months before the emergence of the VOC Gamma. Unlike the VOC Gamma, the other P.1 sub-lineages displayed a much more restricted dissemination and accounted for a low fraction (<2 per cent) of SARS-CoV-2 infections in Brazil in 2021. The stepwise diversification of lineage P.1 through multiple inter-host transmissions is consistent with the hypothesis that partial immunity acquired from natural SARS-CoV-2 infections in heavily affected regions might have been a major driving force behind the natural selection of some VOCs. The lag time between the emergence of the P.1 ancestor and the expansion of the VOC Gamma and the divergent epidemic trajectories of P.1 sub-lineages support a complex interplay between the emergence of mutations of concern and viral spread in Brazil., (© The Author(s) 2021. Published by Oxford University Press.)

Recurrent pregnancy loss (RPL) is the most common reproductive failure, reaching 1-5% of women throughout their lives, and having unknown etiology in 50% of the cases. In humans, EGF-CFC1 ( E pidermal G rowth F actors & C ripto/ F RL-1/ C ryptic) gene family is composed by TDGF1 and CFC1 , two developmental genes. The aim of this study was to investigate the role of EGF-CFC on RPL. To this, multiple approaches were performed; we conducted an expression analysis of TDGF1 and CFC1 using publicly available data from Gene Omnibus Expression (GEO), systems biology analyses and functional prediction; and a molecular analysis carried out in a case-control study. Our GEO analysis showed a decrease in TDGF1 expression in the endometrium (p=0.049) and CFC1 expression in placenta (p=0.015) of women with RPL. Network analysis, gene ontology and literature pointed to a strong connection between EGF-CFC1 gene family to pathways that play key roles during pregnancy, including TGF-β, c-Src/MAPK/AKT, Notch, TNFα, IFNγ and IL-6. A pathogenicity score developed for this gene family showed that the c.-14+1429T>C (rs3806702) variant in the TDGF1 and the p.Arg47Gln (rs201431919) variant in CFC1 gene would be the ones with the highest deleterious effect for RPL. In the case-control study, which involved 149 women with RPL and 159 controls, no statistical difference was observed in the allele and genotype distributions of the variants studied in the two groups. In this study, we performed extensive bioinformatics analysis for biomarker prioritization followed by experimental validation of proposed selected markers. Although there is no statistical difference in the frequencies of these variants between RPL and controls, the expression analysis results suggest that TDGF1 and CFC1 genes might play a role in RPL. In addition, systems biology analyzes raise the hypothesis that genes in other signaling pathways that may be related to RPL as good candidates for future studies. Abbreviations RPL: recurrent pregnancy loss; EGF-CFC1 : E pidermal G rowth F actors - C ripto/ F RL-1; GEO: Gene Omnibus Expression; KEGG: Kyoto Encyclopedia of Genes and Genomes.