Development of a magnetically stabilized fluidized bed bioreactor for enzymatic synthesis of 2-ethylhexyl oleate.

This study aimed to develop and investigate the synthesis of 2-ethylhexyl oleate catalyzed by Candida antarctica lipase immobilized on magnetic poly(styrene-co-divinylbenzene) (STY-DVB-M) particles in a magnetically stabilized fluidized bed reactor (MSFBR) operated in continuous mode. The physical properties of the copolymer were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The glass transition temperature was 85.68 °C, and the onset of thermal degradation occurred at 406.66 °C. Syntheses were performed at 50 °C using a space time of 12 h and a bed porosity of 0.892. Assays were conducted to assess the influence of magnetic field intensity (5 to 15 mT) on reaction yield, ester concentration, and productivity. The highest productivity was 0.850 ± 0.023 mmol g-1 h-1, obtained with a magnetic field intensity of 15 mT. An operational stability test was performed under these conditions, revealing a biocatalyst half-life of 2148 h (179 operation cycles) and a thermal deactivation constant of 3.23 × 10-4 h-1 (R2 = 0.9446). Computational simulations and mathematical modeling were performed using Scilab based on ping-pong bi-bi kinetics and molar balances of reaction species. The model provided consistent results of interstitial velocity and good prediction of reaction yields, with R2 = 0.926. These findings demonstrate that the studied technique can provide improvements in biocatalytic processes, representing a promising strategy for the enzymatic synthesis of 2-ethylhexyl oleate.

Thermodynamic modelling of cements clinkering process as a tool for optimising the proportioning of raw meals containing alternative materials.

The valorisation of waste or by-products in Portland clinker production is a promising alternative for developing sustainable cements. The complexity of the chemical reactions during clinkering demands an adequate dosing method that considers the effect of feedstock impurities to maximise the potential substitution of natural resources by waste or by-products, while guaranteeing the clinker reactivity requirements. This study proposes a raw meal proportioning methodology for optimising co-processing of natural feedstocks with alternative raw materials in clinker production, intending to reduce the content of natural raw materials needed, while promoting an optimal clinker reactivity. A thermodynamic modelling sequence was developed considering the variability of raw materials composition and heating temperatures. The model was then validated by comparing simulation outcomes with results reported in previous studies. An experimental case study was conducted for validation of the proposed method using a spent fluid catalytic cracking catalyst (SFCC), a by-product from the oil industry as an alternative alumina source during clinkering. The modelling simulations indicated that substitution of natural feedstocks by 15 wt% SFCC promotes the formation of reactive clinkers with more than 54% tricalcium silicate (C3S). Mixes with the potential to form the highest C3S were then produced, and heating microscopy fusibility testing was applied for evaluating the clinkers' stability. The main factors governing the reactivity and stability of the clinker phases were the melt phase content, alumina modulus, and formation of C3S and dicalcium silicate (C2S). The self-pulverisation of clinker during cooling was observed in selected mixes, and it is potentially associated with high viscosity and low Fe content in the melt phase. The proposed framework enables optimisation of the dosing of raw meals containing alternative alumina-rich feedstocks for clinker production and allows a deeper interpretation of limited sets of empirical data.

Levels of angiopoietin-2 are predictive for mortality in yellow fever virus infected patients.

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, haemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in the disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin-2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe patients and provide care to improve disease outcome.

Corrigendum: Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: a case report.

[This corrects the article DOI: 10.3389/fmed.2022.1008585.].

Immunological evaluation of young unvaccinated patients with Turner syndrome after COVID-19.

OBJECTIVES: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. METHODS: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic characterization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed. RESULTS: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-γ production by cluster of differentiation (CD)4+ and CD8+ T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phorbol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8+ and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity. CONCLUSION: Following previous reports in the literature for other conditions, our data showed that patients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: A case report.

Background: The influence of the host genome on coronavirus disease 2019 (COVID-19) susceptibility and severity is supported by reports on monozygotic (MZ) twins where both were infected simultaneously with similar disease outcomes, including several who died due to the SARS-CoV-2 infection within days apart. However, successive exposures to pathogens throughout life along with other environmental factors make the immune response unique for each individual, even among MZ twins. Case presentation and methods: Here we report a case of a young adult monozygotic twin pair, who caught attention since both presented simultaneously severe COVID-19 with the need for oxygen support despite age and good health conditions. One of the twins, who spent more time hospitalized, reported symptoms of long-COVID even 7 months after infection. Immune cell profile and specific responses to SARS-CoV-2 were evaluated as well as whole exome sequencing. Conclusion: Although the MZ twin brothers shared the same genetic mutations which may be associated with their increased risk of developing severe COVID-19, their clinical progression was different, reinforcing the role of both immune response and genetics in the COVID-19 presentation and course. Besides, post-COVID syndrome was observed in one of them, corroborating an association between the duration of hospitalization and the occurrence of long-COVID symptoms.

The 90 plus: longevity and COVID-19 survival.

The world population is getting older and studies aiming to enhance our comprehension of the underlying mechanisms responsible for health span are of utmost interest for longevity and as a measure for health care. In this review, we summarized previous genetic association studies (GWAS) and next-generation sequencing (NGS) of elderly cohorts. We also present the updated hypothesis for the aging process, together with the factors associated with healthy aging. We discuss the relevance of studying older individuals and build databanks to characterize the presence and resistance against late-onset disorders. The identification of about 2 million novel variants in our cohort of more than 1000 elderly Brazilians illustrates the importance of studying highly admixed populations of non-European ancestry. Finally, the ascertainment of nonagenarians and particularly of centenarians who were recovered from COVID-19 or remained asymptomatic opens new avenues of research aiming to enhance our comprehension of biological mechanisms associated with resistance against pathogens.

Recurrence of COVID-19 associated with reduced T-cell responses in a monozygotic twin pair.

Recurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFNγ) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19.

Men are the main COVID-19 transmitters: behavior or biology?

BACKGROUND: COVID-19 has affected millions of people worldwide. Clinical manifestations range from severe cases with lethal outcome to mild or asymptomatic cases. Although the proportion of infected individuals does not differ between sexes, men are more susceptible to severe COVID-19, with a higher risk of death than women. Also, men are pointed out as more lax regarding protective measures, mask wearing and vaccination. Thus, we questioned whether sex-bias may be explained by biological pathways and/or behavioral aspects or both. METHODS: Between July 2020 and July 2021, we performed an epidemiological survey including 1744 unvaccinated adult Brazilian couples, with there was at least one infected symptomatic member, who were living together during the COVID-19 infection without protective measures. Presence or absence of infection was confirmed by RT-PCR and/or serology results. Couples were divided into two groups: (1) both partners were infected (concordant couples) and (2) one partner was infected and the spouse remained asymptomatic despite the close contact with the COVID-19 symptomatic partner (discordant couples). Statistical analysis of the collected data was performed aiming to verify a differential transmission potential between genders in couples keeping contact without protective measures. RESULTS: The combination of our collected data showed that the man is the first (or the only) affected member in most cases when compared to women and that this difference may be explained by biological and behavioral factors. CONCLUSIONS: The present study confirmed the existence of gender differences not only for susceptibility to infection and resistance to COVID-19 but also in its transmission rate.

MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals.

Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as "discordant couples". We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners.

COVID-19 in twins: What can we learn from them

Investigations on the concordance in monozygotic (MZ) as compared to dizygotic (DZ) twins may reveal if there is a genetic component increasing the susceptibility or resistance against an infectious disease. Here, we compared the concordance rates of SARS-CoV-2 infection in MZ versus DZ young twins who shared the same bedrooms and were equally exposed to the virus. The concordance rate was higher in the MZ group supporting a complex multifactorial inheritance responsible for SARS-Cov-2 infection.

Men are the main COVID-19 transmitters: lessons from couples

BackgroundCOVID-19 has affected millions of people worldwide. Clinical manifestations range from severe cases with a lethal outcome to mild or asymptomatic cases. Although there is the same proportion of infected genders, men are more susceptible to severe COVID-19, with a higher risk of death than women. This sex-bias may be explained by biological pathways. MethodsWe performed an epidemiological survey from July 2020 to July 2021 including 1744 unvaccinated adult Brazilian couples with at least one infected spouse despite living together during the COVID-19 infection without protective measures. The presence or absence of infection was confirmed by RT-PCR and/or serology results. The couples were divided between groups where both partners were infected (concordant couples) or only one spouse remained asymptomatic despite the close contact with the infected one (discordant couples). Statistical analysis of the collected data was performed aiming to verify a differential transmitter potential between genders in household contact. ResultsThe combination of our data collected from concordant and discordant couples showed that the man is the first (or the only) affected in the major occurrences when compared to women. Our findings support other published surveys and are in concordance with previous studies of our group. ConclusionsThese observations support the hypothesis according to which male individuals are more efficient virus transmitters than females, independently of the use of protective masks. In short, the present study confirmed the existence of gender differences not only for susceptibility to infection and resistance to COVID-19 but also in the transmission rate. HIGHLIGHTSO_LIThere are sex differences in COVID-19 susceptibility and transmission between couples with direct contact without protective measures; C_LIO_LIMen are more efficient virus transmitters than women; C_LIO_LISex-bias in COVID-19 transmission can be explained by differences in viral load in saliva, immune response and also behavioural protective differences between genders. C_LI

Continuous production of monoacylglycerol via glycerolysis of babassu oil by immobilized Burkholderia cepacia lipase in a packed bed reactor.

This study investigated the glycerolysis of babassu oil by Burkholderia cepacia lipase immobilized on SiO2-PVA particles in a continuous packed bed reactor. Experiments were conducted in a solvent-free system at 273.15 K either in an inert atmosphere or in the presence of cocoa butter to prevent lipid oxidation. The reactor (15 × 55 mm) was run at a fixed space time of 9.8 h using different molar ratios of babassu oil to glycerol (1:3, 1:6, 1:9, 1:12, and 1:15) to assess the effects of reactant molar ratio on monoacylglycerol productivity and selectivity. Nitrogen atmosphere and cocoa butter were equally effective in inhibiting lipid oxidation, indicating that addition of cocoa butter to glycerolysis reactions may be an interesting cost-reduction strategy. An oil/glycerol molar ratio of 1:9 resulted in the highest productivity (52.3 ± 2.9 mg g-1 h-1) and selectivity (31.5 ± 1.8%). Residence time distribution data were fitted to an axial dispersion model for closed-vessel boundary conditions, giving a mass transfer coefficient (kc) of 3.4229 × 10-6 m s-1. A kinetic model based on elementary steps of the studied reaction was written in Scilab and compared with experimental data, providing standard deviations in the range of 5.5-7.5%.

Nutritional Interventions in Children with Brain Injuries: A Systematic Review.

BACKGROUND: Brain injury has several consequences throughout life, its increased incidence has caused great public concern. The aim was identifying the main nutritional therapies recommended for children with brain injuries. METHODS: A systematic review was carried out using the terms in the search strategy: "Brain Injuries", "Nutrition Therapy", and "Child" and their synonyms, from database inception up to August 2020. The search was conducted in the following databases: MEDLINE, EMBASE, Scopus, Cochrane library, LILACS, and grey literature. Two reviewers independently selected the included studies, according to the eligibility criteria and extracted data from the included articles. RESULTS: A total of 1196 studies resulted from electronic searches, and out of these, 27 studies were read in full and eight studies were included. For early enteral nutritional support (<48 h), results suggest benefit in increasing survival rates. Type of dietary protein seems to be related to decreasing gastric emptying by 40%. The use of fibers seems to reduce gastrointestinal discomfort and increase stool frequency. CONCLUSIONS: The evidence mapped was extracted from small studies analyzing different outcomes, so any decision making should be analyzed considering the context. We present the direction of the effect, but the magnitude is still unclear.

Immunogenetics of resistance to SARS-CoV-2 infection in discordant couples

BackgroundDespite the high number of individuals infected by SARS-CoV-2 who develop COVID-19 symptoms worldwide, many exposed individuals remain asymptomatic and/or stay uninfected. This could be explained by a combination of environmental (exposure, previous infection), epigenetic, and genetic factors. Aiming to identify genetic variants involved in SARS-CoV-2 resistance, we analyzed 86 discordant Brazilian couples where one was infected and symptomatic while the partner remained asymptomatic and seronegative despite sharing the same bedroom during the infection. The discordant partners had comparable ages, and genetic ancestry proportions. MethodsWhole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic MHC and LRC. ResultsWe observed a minor impact in antigen-presentation genes and KIR genes associated with resistance. Interestingly, genes related to immune modulation, mainly involved in NK cell killing activation/inhibition harbor variants potentially contributing to infection resistance. We hypothesize that individuals prone to produce higher amounts of MICA (possibly soluble), LILRB1, LILRB2, and low amounts of MICB, would be more susceptible to infection. ConclusionAccording to this hypothesis, quantitative differences in these NK activity-related molecules could contribute to resistance to COVID-19 down regulating NK cell cytotoxic activity in infected individuals but not in resistant partners.

Addressing the impact of COVID-19 lockdown on energy use in municipal buildings: A case study in Florianópolis, Brazil.

COVID-19 has spread quickly to several countries following the initial outbreak of the disease. As a consequence, several measures have been taken to mitigate the virus spread worldwide. In the city of Florianópolis, in southern Brazil, a strict lockdown was implemented on 16 March 2020. Although commercial activities were allowed to resume 21 April, a complete lockdown of municipal public buildings (e.g., administrative buildings and schools) lasted up to 5 August 2020. Reports in the literature emphasize the influence of occupant presence and actions on energy use in buildings. Therefore, the objective of this study was to assess the impact of the COVID-19 lockdown on the electric energy use of municipal buildings in Florianópolis. A large database with monthly electric energy use data was provided by the City Hall and analyzed. Firstly, the consumer units were grouped into three categories: systems, services and buildings. This revealed that buildings were directly affected by the lockdown measures, but systems and services were not. Therefore, an in-depth evaluation of health centers, administrative buildings, elementary schools and nursery schools was conducted and mean electric energy reductions of 11.1 %, 38.6 %, 50.3 %, and 50.4 %, respectively, were observed. Although it may initially seem unexpected, municipal health centers had a small electric energy use reduction, because they were not directly responsible for COVID-19 treatment, as patients were forwarded to specific facilities. Walkthroughs and energy audits were performed in an administrative building, an elementary school, and a nursery school, to gain a deeper understanding of the consumption trends. It was observed that municipal buildings present a basal energy use intensity even when the buildings are unoccupied. Energy audits verified that stand-by loads and vital loads, such as lighting for safety and computer servers, play a key role in this share of energy use.

Monozygotic twins discordant for severe clinical recurrence of COVID-19 show drastically distinct T cell responses to SARS-Cov-2

BackgroundClinical recurrence of COVID-19 in convalescent patients has been reported, which immune mechanisms have not been thoroughly investigated. Presence of neutralizing antibodies suggests other types of immune response are involved. MethodsWe assessed the innate type I/III IFN response, T cell responses to SARS-CoV-2 with IFN{gamma} ELISPOT, binding and neutralizing antibody assays, in two monozygotic twin pairs with one COVID-19 recurrence case. ResultsIn pair 1, four months after a first mild episode of infection for both siblings, one displayed severe clinical recurrence of COVID-19. Twin pair 2 of siblings underwent non-recurring asymptomatic infection. All fours individuals presented similar overall responses, except for remarkably difference found in specific cellular responses. Recurring sibling presented a reduced number of recognized T cell epitopes as compared to the other three including her non-recurring sibling. ConclusionsOur results suggest that an effective SARS-CoV-2-specific T cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19. Besides, adaptive immunity can be distinct in MZ twins. Given the rising concern about SARS-CoV-2 variants that evade neutralizing antibodies elicited by vaccination or infection, our study stresses the importance of T cell responses in protection against recurrence/reinfection. Key pointsImmune parameters leading to COVID-19 recurrence/reinfection are incompletely understood. A COVID-19 recurrence case in a monozygotic twin pair is described with an intact antibody and innate type I/III Interferon response and drastically reduced number of recognized SARS-CoV-2 T cell epitopes.