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Abstract Background Artemisinin-based combination therapy is the first-line anti-malarial treatment for uncomplicated Plasmodium falciparum infection in Angola. To date, the prevalence of polymorphisms in the pfk13 gene, associated with artemisinin resistance, and pfmdr1, associated with lumefantrine resistance, have not been systematically studied in Angola. Methods DNA was isolated from pretreatment and late treatment failure dried blood spots collected during the 2015 round of therapeutic efficacy studies in Benguela, Lunda Sul, and Zaire Provinces in Angola. The pfk13 propeller domain and pfmdr1 gene were sequenced and analysed for polymorphisms. Pfmdr1 copy number variation was assessed using a real-time PCR method. The association between pfmdr1 and pfk13 mutations and treatment failure was investigated. Results The majority of pretreatment (99%, 466/469) and all late treatment failure (100%, 50/50) samples were wild type for pfk13. Three of the pretreatment samples (1%) carried the A578S mutation commonly observed in Africa and not associated with artemisinin resistance. All 543 pretreatment and day of late treatment failure samples successfully analysed for pfmdr1 copy number variation carried one copy of pfmdr1. The NYD haplotype was the predominant pfmdr1 haplotype, present in 63% (308/491) of pretreatment samples, followed by NFD, which was present in 32% (157/491) of pretreatment samples. The pfmdr1 N86 allele was overrepresented in day of late treatment failure samples from participants receiving artemether–lumefantrine (p value 0.03). Conclusions The pretreatment parasites in patients participating in therapeutic efficacy studies in 2015 in Angola’s three sentinel sites showed genetic evidence of susceptibility to artemisinins, consistent with clinical outcome data showing greater than 99% day 3 clearance rates. The lack of increased pfmdr1 copy number is consistent with previous reports from sub-Saharan Africa. Although pfmdr1 NYD and NFD haplotypes were overrepresented in artemether–lumefantrine late treatment failure samples, their role as markers of resistance was unclear given that these haplotypes were also present in the majority of successfully treated patients in the artemether–lumefantrine treatment arms.

Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to systematically discover. We developed mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) to identify such interactions. Analysis of 33 enzymes from human carbohydrate metabolism identified 830 protein-metabolite interactions, including known regulators, substrates, and products as well as previously unreported interactions. We functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. Cell treatment with fatty acids caused a loss of pyruvate-lactate interconversion dependent on lactate dehydrogenase isoform expression. These protein-metabolite interactions may contribute to the dynamic, tissue-specific metabolic flexibility that enables growth and survival in an ever-changing nutrient environment.

Background: A difference in maximum tolerance to mechanical pain (MTMP) between the sexes is widely studied but there is still no consensus on whether the level of physical activity (PA) influences pain., Objectives: To compare the MTMP between men and women with different levels of PA., Methods: Sixty five individuals were divided in female (n = 35) and male group (n = 30). The main outcome measures were PA level and MTMP by pressure algometry. Pressure was applied three times on both sides at the following points: cervical (5 th and 7 th ) and lumbar (3 th and 5 th ) vertebrae; trapezius, rhomboid, gluteus, gastrocnemius, pectoralis major, tibialis anterior, and deltoid muscles, elbow, hand, knee, and ankle., Results: It was observed that the PA level has little influence on the MTMP at all the assessed points and that men have greater MTMP than women., Conclusion: Sex, not the PA level, influences the MTMP., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: To compare the immediate analgesic effect of transcutaneous nerve stimulation (TENS) and interferential current (IFC), with different combinations of parameters, in individuals with chronic low back pain (CLBP)., Methodology: 280 individuals with CLBP were included in the study, both genders, randomized in 8 groups: GI2KHz/100Hz, GI2KHz/2Hz, GI4KHz/100Hz, GI4KHz/2Hz, placebo interferential group (GIP), GT100Hz, GT2Hz, and placebo TENS group (GTP). All individuals underwent a single application of TENS or IFC for 30min. The assessments were carried out prior to the intervention, as well as immediately after, with the following outcomes: pain intensity (Numeric Pain Rating Scale-NPRS), qualitative pain characteristics (McGill Pain Questionnaire-MPQ), and pressure pain threshold (PPT) by pressure algometry (PA) in 4 points of the low back region., Results: In the intergroup comparison of NPRS, all intervention groups showed greater pain reduction compared to GTP (p < 0.05). In the total MPQ score, the groups that obtained significant results (p < 0.05) when compared to GTP were GT100Hz and GT2Hz, while the groups GT100Hz and GI4KHz/100Hz were significant when compared to GIP. In the PA, GI4KHz/100Hz showed an increase in the PPT in all points compared to GTP and GI2KHz/100Hz., Conclusion: Both TENS and IFC presented immediate analgesic effect in CLBP, with emphasis on the interferential current of 4 KHz modulated at 100Hz., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest”, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: to map the scientific knowledge about COVID-19 in older adults., Method: this is a scoping review literature review. A search was performed in the PubMed, CINAHL, Web of Science and LILACS databases. Original articles that answered the guiding question were included: what scientific knowledge is available in the world about COVID-19 in older adults?, Results: thirty-one articles were included, most of them carried out in China (n=23) and with a retrospective design (n=13) and case studies/case series (n=13). Based on the findings, six thematic categories emerged: clinical signs and symptoms (n=12), other information (n=9), adverse outcomes/complications resulting from COVID-19 (n=8), age relationship and greater severity of COVID-19 (n=8), variables related to death by COVID-19 (n=8), and diagnostic findings (n=8)., Conclusion: the findings reinforce older adults' greater vulnerability to the worsening of COVID-19, as well as to complications resulting from the disease, including the greater occurrence of death.

Fumarate hydratases (FHs, fumarases) catalyze the reversible conversion of fumarate into l-malate. FHs are distributed over all organisms and play important roles in energy production, DNA repair and as tumor suppressors. They are very important targets both in the study of human metabolic disorders and as potential therapeutic targets in neglected tropical diseases and tuberculosis. In this study, human FH (HsFH) was characterized by using enzyme kinetics, differential scanning fluorimetry and X-ray crystallography. For the first time, the contribution of both substrates was analyzed simultaneously in a single kinetics assay allowing to quantify the contribution of the reversible reaction for kinetics. The protein was crystallized in the spacegroup C222 1 , with unit-cell parameters a = 125.43, b = 148.01, c = 129.76. The structure was solved by molecular replacement and refined at 1.8 Å resolution. In our study, a HEPES molecule was found to interact with HsFH at the C-terminal domain (Domain 3), previously described as involved in allosteric regulation, through a set of interactions that includes Lys 467. HsFH catalytic efficiency is higher when in the presence of HEPES. Mutations at residue 467 have already been implicated in genetic disorders caused by FH deficiency, suggesting that the HEPES-binding site may be important for enzyme kinetics. This study contributes to the understanding of the HsFH structure and how it correlates with mutation, enzymatic deficiency and pathology., (© 2019 Federation of European Biochemical Societies.)

This work aimed to prepare chitosan/clay microspheres, by the precipitation method, for use in drug carrier systems. The influence of the process parameters, particularly two airflows of the drag system (2.5 and 10 L·min -1 ) on the microspheres physical dimensions and properties, such as microstructure, degree of swelling and porosity were evaluated. The samples were characterized by optical microscopy (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Water absorption and porosity tests were also performed. The results showed that the process parameters affected the size of the microspheres. The diameter, volume and surface area of the chitosan/clay microspheres decreased when they were prepared with the higher airflow of the drag system. The microspheres presented a porous microstructure, being the pore size, percentage of porosity and degree of swelling affected not only by the process parameters but also by the type of clay. Hybrids (chitosan/clay) with intercalated morphology were obtained and the hybrid prepared with montmorillonite clay at higher airflows of the drag system presented the greatest interlayer spacing and a more disordered morphology. Thus, it is certain that the chitosan/clay nanocomposite microspheres prepared with montmorillonite (CL clay) at higher airflows of the drag system can have good drug-controlled release properties.

Objective: To determine the demographic and health factors related to the frailty syndrome in older adults., Methods: This is a longitudinal quantitative study carried out with 262 older adults aged 65 years and older, of both sexes, living at home. Data collection was carried out in Period 1 between October 2007 and February 2008, and in Period 2 between July and December 2013. For data collection, we used the sociodemographic profile instrument, the Edmonton Frail Scale, the Mini-Mental State Examination, the number of falls in the last 12 months, the number of self-reported diseases and used drugs, the Functional Independence Measure, and the Lawton and Brody Scale. We used descriptive statistics for data analysis, in the comparison of the means between periods, the nonparametric Wilcoxon test, and the method of Generalized Estimating Equations, which is considered an extension of the Generalized Linear Models with p ≤ 0.05., Results: Of the 515 participants, 262 completed the follow-up, with a predominance of females, older individuals, and those who had no partner; there was an increase in frail older adults. In the Generalized Estimating Equations analysis, frailty score was related to sociodemographic (increase in age, no partner, and low education level) and health variables (more diseases, drugs, falls, and decrease in functional capacity). There was an association between the variables of age (older), marital status (no partner), and loss of functional capacity., Conclusions: Frailty syndrome was associated with increasing age, having no partner, and decreased functional capacity over time, and investments are required to prevent this syndrome and promote quality in aging.

Objective: to investigate the association between frailty with hospitalization and institutionalization in a follow-up study of elderly residents., Method: the follow-up study was performed in 2008 and 2013 with elderly of both genders, aged 65 years and older who were living in the community-dwelling. The sampling procedure performed was probabilistic, with dual-stage clustering. In 2008, 515 elderly people were interviewed and, in 2013, 262. We used the socioeconomic and demographic data, self-reported morbidity, specific data of hospitalization and institutionalization. Frailty was measured by the Edmonton Frail Scale (EFS), and functional capacity through the Functional Independence Measure., Results: we found the mean gross EFS score was higher among resident elderly who were hospitalized and institutionalized and was statistically significant in both investigated years., Conclusion: the confirmation of association between frailty and hospitalization and institutionalization reinforces the importance of the subject, and highlights frailty as an important tool for risk estimates for these adverse events.

Objective: To describe the scientific knowledge produced about trauma in the elderly caused by traffic accidents in healthcare area studies. METHODS :Integrative review of studies from 2003 to 2013 searched in LILACS, SciELO, PubMed and CINHAL databases. We used combination of the descriptors injuries, wounds and accidents, in English, Portuguese and Spanish languages., Results: 32 studies were selected. In the thematic analysis, three categories emerged: epidemiological data from traffic accidents involving elderly; traffic accidents with elderly pedestrians; and trauma care in the elderly. We observed increased incidence of trauma in most countries and pedestrians represented a large part of the victims. Among these, the elderly are the most vulnerable group., Conclusion: Studies showed that trauma care in the elderly need protocols and professionals with training in gerontology specialized in trauma care services.

The filamentous fungus Aspergillus terreus secretes both invertase and β-glucosidase when grown under submerged fermentation containing rye flour as the carbon source. The aim of this study was to characterize the co-purified fraction, especially the invertase activity. An invertase and a β-glucosidase were co-purified by two chromatographic steps, and the isolated enzymatic fraction was 139-fold enriched in invertase activity. SDS-PAGE analysis of the co-purified enzymes suggests that the protein fraction with invertase activity was heterodimeric, with subunits of 47 and 27 kDa. Maximal invertase activity, which was determined by response surface methodology, occurred in pH and temperature ranges of 4.0-6.0 and 55-65 °C, respectively. The invertase in co-purified enzymes was stable for 1 h at pH 3.0-10.0 and maintained full activity for up to 1 h at 55 °C when diluted in water. Invertase activity was stimulated by 1 mM concentrations of Mn²⁺ (161 %), Co²⁺ (68 %) and Mg²⁺ (61 %) and was inhibited by Al³⁺, Ag⁺, Fe²⁺ and Fe³⁺. In addition to sucrose, the co-purified enzymes hydrolyzed cellobiose, inulin and raffinose, and the apparent affinities for sucrose and cellobiose were quite similar (K(M) = 22 mM). However, in the presence of Mn²⁺, the apparent affinity and V(max) for sucrose hydrolysis increased approximately 2- and 2.9-fold, respectively, while for cellobiose, a 2.6-fold increase in V(max) was observed, but the apparent affinity decreased 5.5-fold. Thus, it is possible to propose an application of this multifunctional extract containing both invertase and β-glucosidase to degrade plant biomass, thus increasing the concentration of monosaccharides obtained from sucrose and cellobiose.

Objective: to verify the inter and intra-rater reproducibility of the Brazilian adapted version of the Edmonton Frail Scale (EFS) in an elderly group of residents., Method: in order to test the inter-rater reproducibility, two assessments were independently conducted by two researchers on the same day but at different times, in a sample of 103 elderly. Concerning the intra-rater reproducibility, the instrument was administered to 83 elderly (80.6% of the initial sample) by the same researcher in a time gap of 15 days between the two assessments., Results and Discussion: in relation to the inter-rater test, the Kappa was 0.81 (CI 0.61-1.00) and the Intraclass Correlation Coefficient (ICC) corresponded to 0.87 (CI 0.82-0.91, p<0.001). In relation to the intra-rater test, the Kappa was 0.83 (CI 0.72-0.94) and the ICC 0.87 (CI 0.81-1.00, p<0.001)., Conclusion: the results show that the EFS is reliable and can be used as a tool to improve geriatric nursing care in Brazil.

Objective: To describe the socio-demographic characteristics and quality of life of elderly patients with systemic arterial hypertension; to correlate the quality of life with the time of diagnosis and number of medication, as well as to compare the quality of life with the type of medication., Method: In this cross sectional home survey design, 460 elderly people from rural areas were involved. The data was collected with the use of the following instruments: World Health Organization Quality of Life-bref and World Health Organization Quality of Life Olders. A descriptive analysis, Pearson correlation and t-Student test (p<0.05) were undertaken., Results: Predominant patient characteristics were: women between the age of 60 and 70, married, four to eight years of formal education, income of one minimum wage, living with their partners. The time of diagnosis was associated with lower quality of life in the physical domain. Elderly patients who used Inhibitors and Angiotensin Converting Enzyme and who did not use AT1 blocker had lower scores in relation to functioning of the senses. Those who used calcium channel blocker scored higher in relation to autonomy., Conclusion: there is a need for actions to control systemic arterial hypertension and its associated complications, with the purpose of improving quality of life.

The filamentous fungus Paecylomices variotii was able to produce high levels of cell extract and extracellular invertases when grown under submerged fermentation (SbmF) and solid-state fermentation, using agroindustrial products or residues as substrates, mainly soy bran and wheat bran, at 40°C for 72 h and 96 h, respectively. Addition of glucose or fructose (≥1%; w/v) in SbmF inhibited enzyme production, while the addition of 1% (w/v) peptone as organic nitrogen source enhanced the production by 3.7-fold. However, 1% (w/v) (NH(4))(2)HPO(4) inhibited enzyme production around 80%. The extracellular form was purified until electrophoretic homogeneity (10.5-fold with 33% recovery) by DEAE-Fractogel and Sephacryl S-200 chromatography. The enzyme is a monomer with molecular mass of 102 kDa estimated by SDS-PAGE with carbohydrate content of 53.6%. Optima of temperature and pH for both, extracellular and cell extract invertases, were 60°C and 4.0-4.5, respectively. Both invertases were stable for 1 h at 60°C with half-lives of 10 min at 70°C. Mg(2+), Ba(2+) and Mn(2+) activated both extracellular and cell extract invertases from P. variotii. The kinetic parameters K(m) and V(max) for the purified extracellular enzyme corresponded to 2.5 mM and 481 U/mg prot(-1), respectively.