•GLUT1 knockout does not affect erythroid differentiation and minimally affects reticulocyte membrane composition.•Metabolic adaptation facilitates reticulocyte tolerance of GLUT1 absence.
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The glucose transporter 1 (GLUT1) is 1 of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR–mediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates, to our knowledge, for the first time, generation of enucleated human reticulocytes lacking GLUT1. The GLUT1–deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1–deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMP-activated protein kinase signaling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1–deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation, or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function, and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anemia in GLUT1–deficiency syndrome.
To evaluate the association of thyroid hormones changes, including increased reverse triiodothyronine (rT3) level, with critically ill clinical patients´ mortality.
This study analyzed the ...observational data prospectively collected over 8 months (2018) in an adult intensive care unit (ICU) in Brasilia, Brazil. All consecutive ICU-admitted clinical patients were included. Thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), free triiodothyronine (fT3), rT3, and thyroid-stimulating hormone (TSH) were collected within 48 hours of ICU admission. Patients with hypothyroidism or hyperthyroidism who were previously diagnosed were excluded.
Of 353 included patients, age was 68.5 ± 19.0 years, sequential organ failure assessment (SOFA) score was 3.3 ± 2.9, and Acute Physiology and Chronic Health Evaluation II (APACHE II) was 17.1 ± 7.9. ICU mortality was 17.6% (
= 62). Non-survivor patients had a higher incidence of increased rT3 (69.3 vs 59.2%,
= 0.042), lower incidence of low T4 (4.8 vs 9.7%,
= 0.045), and increased age (75.2 ± 16.3 years vs 67.1 ± 19.3 years,
= 0.001), SOFA (3.0 ± 0.4 vs 2.8 ± 2.6,
<0.001), and APACHE II (23.5 ± 7.5 vs 15.7 ± 7.2,
<0.001). Alterations in other thyroid hormones did not show association with mortality. Increased rT3 odds ratio (OR): 2.436; 95% confidence interval (CI): 1.023-5.800;
= 0.020 and APACHE II (OR: 1.083, 95% CI: 1.012-1.158;
= 0.044) were associated with ICU mortality in the multivariate analysis.
Increased rT3 was independently associated with increased ICU mortality. In contrast, other thyroid hormone alterations did not show an association with mortality. Determining rT3 levels may be a helpful test to identify an increased risk for ICU mortality in clinical patients.
da Silveira CDG, de Vasconcelos FPJ, Moura EB, da Silveira BTG, Amorim FFP, Shintaku LS,
Thyroid Function, Reverse Triiodothyronine, and Mortality in Critically Ill Clinical Patients. Indian J Crit Care Med 2021;25(10):1161-1166.
Nitazoxanide exerts antiviral activity
and
and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.
A multicentre, randomized, double-blind, ...placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days.
Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio 95% confidence interval, 0.68 0.38-1.20,
= 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 2.21-3.43,
< 0.0001), time to hospital discharge (1.37 1.11-1.71,
= 0.005), and reduced oxygen requirements (0.77 0.64-0.94,
= 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed.
Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.
Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.
Algoritmo híbrido de otimização Glowworm-Boids Fritsche, Gian; Oliveira, Paulo Moura; Pires, Eduardo E. J. Solteiro ...
Revista Eletrônica Científica Inovação e Tecnologia,
01/2014, Letnik:
4, Številka:
9
Journal Article
Este trabalho descreve a utilização de técnicas de inspiração natural na simulação de enxames, utilizando regras comportamentais propostas nos algoritmos Boids e Glowworm. O objetivo principal do ...trabalho consiste em desenvolver uma técnica híbrida entre os algoritmos Boids e Glowworm, que permita a exploração e otimização de espaços multimodais de uma forma eficiente..
The health of the coral reefs of the Abrolhos Bank (Southwestern Atlantic) was characterized with a holistic approach using measurements of four ecosystem components: (i) inorganic and organic ...nutrient concentrations, 1 fish biomass, 1 macroalgal and coral cover and (iv) microbial community composition and abundance. The possible benefits of protection from fishing were particularly evaluated by comparing sites with varying levels of protection. Two reefs within the well-enforced no-take area of the National Marine Park of Abrolhos (Parcel dos Abrolhos and California) were compared with two unprotected coastal reefs (Sebastião Gomes and Pedra de Leste) and one legally protected but poorly enforced coastal reef (the "paper park" of Timbebas Reef). The fish biomass was lower and the fleshy macroalgal cover was higher in the unprotected reefs compared with the protected areas. The unprotected and protected reefs had similar seawater chemistry. Lower vibrio CFU counts were observed in the fully protected area of California Reef. Metagenome analysis showed that the unprotected reefs had a higher abundance of archaeal and viral sequences and more bacterial pathogens, while the protected reefs had a higher abundance of genes related to photosynthesis. Similar to other reef systems in the world, there was evidence that reductions in the biomass of herbivorous fishes and the consequent increase in macroalgal cover in the Abrolhos Bank may be affecting microbial diversity and abundance. Through the integration of different types of ecological data, the present study showed that protection from fishing may lead to greater reef health. The data presented herein suggest that protected coral reefs have higher microbial diversity, with the most degraded reef (Sebastião Gomes) showing a marked reduction in microbial species richness. It is concluded that ecological conditions in unprotected reefs may promote the growth and rapid evolution of opportunistic microbial pathogens.
INTRODUCTION AND OBJECTIVESNasal dermoids are uncommon midline congenital lesions in the nose, usually diagnosed in the first years of life. Imaging is mandatory to evaluate local and intracranial ...extension and treatment consists in surgical excision. This study aims to review the experience of the department in managing pediatric nasal dermoids using a dorsal rhinotomy surgical approach.MATERIAL AND METHODSRetrospective case series of pediatric nasal dermoids treated at a tertiary university teaching hospital over a period of seven years.RESULTSNine children were treated during this period. Clinical presentation was a dermoid sinus-cyst in seven cases and a cystic lesion in two. Pre-operative imaging revealed extension of the lesion to the foramen cecum in three cases. Surgery was performed via vertical dorsal rhinotomy in all patients, and associated endoscopic surgery was used in three patients. Reconstruction with autologous material was performed in three cases. No complications or recurrences were registered during the follow-up.CONCLUSIONSIn the presented series, a vertical dorsal rhinotomy incision has provided good functional and aesthetic results. The possibility of nasal dermoid intracranial extension should be accessed with imaging but remains uncommon. In its absence, this approach may be useful and can be paired with other techniques, such as nasal endoscopy, to achieve the best outcomes.
Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect ...intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6-26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
SARS-CoV-2 has a high risk of outbreak in long-term skilled nursing facilities (SNF). Coronavirus disease (COVID-19) has high mortality rates among the elderly with chronic health conditions. ...Following identification of COVID-19 index case in a SNF, serial point-prevalence was implemented with reverse transcription–polymerase chain reaction (RT-PCR) and immunochromatographic assays. Active surveillance and early isolation of infected patients were implemented. Out of 23 SNF residents and 26 healthcare workers (HCW), 18 (78%) and 12 (46%) tested positive for SARS-CoV-2, respectively. High proportion (38%) of positive patients were asymptomatic and RT-PCR was positive up to six days before symptoms. Five (21.74%) residents were hospitalized with COVID-19, and 2 (9%) died; only 1 (4%) HCW needed to be hospitalized and no staff members died. Active surveillance helped COVID-19 control and management in a SNF. Testing symptomatic individuals only may fail to identify and isolate all persons contributing to transmission. In high-risk elderly, only symptoms screening may not be enough for outbreak control.
In Latin America, Bothrops snakes account for most snake bites in humans, and the recommended treatment is administration of multispecific Bothrops antivenom (SAB--soro antibotrópico). However, ...Bothrops snakes are very diverse with regard to their venom composition, which raises the issue of which venoms should be used as immunizing antigens for the production of pan-specific Bothrops antivenoms. In this study, we simultaneously compared the composition and reactivity with SAB of venoms collected from six species of snakes, distributed in pairs from three distinct phylogenetic clades: Bothrops, Bothropoides and Rhinocerophis. We also evaluated the neutralization of Bothrops atrox venom, which is the species responsible for most snake bites in the Amazon region, but not included in the immunization antigen mixture used to produce SAB. Using mass spectrometric and chromatographic approaches, we observed a lack of similarity in protein composition between the venoms from closely related snakes and a high similarity between the venoms of phylogenetically more distant snakes, suggesting little connection between taxonomic position and venom composition. P-III snake venom metalloproteinases (SVMPs) are the most antigenic toxins in the venoms of snakes from the Bothrops complex, whereas class P-I SVMPs, snake venom serine proteinases and phospholipases A2 reacted with antibodies in lower levels. Low molecular size toxins, such as disintegrins and bradykinin-potentiating peptides, were poorly antigenic. Toxins from the same protein family showed antigenic cross-reactivity among venoms from different species; SAB was efficient in neutralizing the B. atrox venom major toxins. Thus, we suggest that it is possible to obtain pan-specific effective antivenoms for Bothrops envenomations through immunization with venoms from only a few species of snakes, if these venoms contain protein classes that are representative of all species to which the antivenom is targeted.
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