Isoforms of Hsp70-binding human LDL in adult Schistosoma mansoni worms.

Schistosoma mansoni is one of the most common parasites infecting humans. They are well adapted to the host, and this parasite's longevity is a consequence of effective escape from the host immune system. In the blood circulation, lipoproteins not only help to conceal the worm from attack by host antibodies but also act as a source of lipids for S. mansoni. Previous SEM studies showed that the low-density lipoprotein (LDL) particles present on the surface of adult S. mansoni worms decreased in size when the incubation time increased. In this study, immunocytochemical and proteomic analyses were used to locate and identify S. mansoni binding proteins to human plasma LDL. Ultrathin sections of adult worms were cut transversely from the anterior, medial and posterior regions of the parasite. Immunocytochemical experiments revealed particles of gold in the tegument, muscle region and spine in male worms and around vitelline cells in females. Immunoblotting and 2D-electrophoresis using incubations with human serum, anti-LDL antibodies and anti-chicken IgG peroxidase conjugate were performed to identify LDL-binding proteins in S. mansoni. Analysis of the binding proteins using LC-MS identified two isoforms of the Hsp70 chaperone in S. mansoni. Hsp70 is involved in the interaction with apoB in the cytoplasm and its transport to the endoplasmic reticulum. However, further studies are needed to clarify the functional role of Hsp70 in S. mansoni, mainly related to the interaction with human LDL.

Dialysis parameters associated with SARS-CoV-2 infection and prognosis in end-stage kidney disease.

BACKGROUND: The Covid-19 pandemic has affected patients with end-stage kidney disease (ESKD). Whether dialysis parameters have a prognostic value in ESKD patients with Covid-19 remains unclear. MATERIALS AND METHODS: We retrospectively evaluated clinical characteristics, blood pressure (BP) and dialysis parameters in ESKD patients undergoing maintenance outpatient hemodialysis, with (Covid-ESKD) and without (No-Covid-ESKD) Covid-19, at four Brazilian hemodialysis facilities. The Covid-ESKD (n = 107; 54% females; 60.8 ± 17.7 years) and No-Covid-ESKD (n = 107; 62% females; 58.4 ± 14.6 years) groups were matched by calendar time. The average BP and dialysis parameters were calculated during the pre-infection, acute infection, and post-infection periods. The main outcomes were Covid-19 hospitalization and all-cause mortality. RESULTS: Covid-ESKD patients had greater intradialytic and postdialysis systolic BP and lower predialysis weight, postdialysis weight, ultrafiltration rate, and interdialytic weight gain during acute-illness compared to 1-week-before-illness, while these changes were not observed in No-Covid-ESKD patients. After 286 days of follow-up (range, 276-591), there were 18 Covid-19-related hospitalizations and 28 deaths among Covid-ESKD patients. Multivariable logistic regression analysis showed that increases in predialysis systolic BP from 1-week-before-illness to acute-illness (OR, 95%CI = 1.06, 1.02-1.10; p = .004) and Covid-19 vaccination (OR, 95%CI = 0.16, 0.04-0.69; p = .014) were associated with hospitalization in Covid-ESKD patients. Multivariable Cox-regression analysis showed that Covid-19-related hospitalization (HR, 95%CI = 5.17, 2.07-12.96; p < .001) and age (HR, 95%CI = 1.05, 1.01-1.08; p = .008) were independent predictors of all-cause mortality in Covid-ESKD patients. CONCLUSION: Acute Covid-19 illness is associated with variations in dialysis parameters of volume status in patients with ESKD. Furthermore, increases in predialysis BP during acute Covid-19 illness are associated with an adverse prognosis in Covid-ESKD patients.

Dialysis parameters were influenced by SARS-CoV-2 infection and may have prognostic value in patients with Covid-19.Increases in blood pressure during acute Covid-19 illness and the lack of vaccination for Covid-19 were predictors of hospitalization for Covid-19.Hospitalization for Covid-19 and age were independent risk factors for all-cause death.

Accuracy of screening strategies for masked hypertension: a large-scale nationwide study based on home blood pressure monitoring.

This study compared the ability of guideline-proposed office blood pressure (OBP) screening thresholds [European Society of Hypertension (ESH) guidelines: 130/85 mmHg for individuals with an OBP < 140/90 mmHg; American College of Cardiology/American Heart Association (ACC/AHA) guidelines: 120/75 mmHg for individuals with an OBP < 130/80 mmHg] and novel screening scores to identify normotensive individuals at high risk of having masked hypertension (MH) in an office setting. We cross-sectionally evaluated untreated participants with an OBP < 140/90 mmHg (n = 22,266) and an OBP < 130/80 mmHg (n = 10,005) who underwent home blood pressure monitoring (HBPM) (derivation cohort) from 686 Brazilian sites. MH was defined according to criteria suggested by the ESH (OBP < 140/90 mmHg; HBPM ≥ 135/85 mmHg), Brazilian Society of Cardiology (BSC) (OBP < 140/90 mmHg; HBPM ≥ 130/80 mmHg) and ACC/AHA (OBP < 130/80 mmHg; HBPM ≥ 130/80 mmHg). Scores were generated from multivariable logistic regression coefficients between MH and clinical variables (OBP, age, sex, and BMI). Considering the ESH, BSC, and ACC/AHA criteria, 17.2%, 38.5%, and 21.2% of the participants had MH, respectively. Guideline-proposed OBP screening thresholds yielded area under curve (AUC) values of 0.640 (for ESH criteria), 0.641 (for BSC criteria), and 0.619 (for ACC/AHA criteria) for predicting MH, while scores presented as continuous variables or quartiles yielded AUC values of 0.700 and 0.688 (for ESH criteria), 0.720 and 0.709 (for BSC criteria), and 0.671 and 0.661 (for ACC/AHA criteria), respectively. Further analyses performed with alternative untreated participants (validation cohort; n = 2807 with an OBP < 140/90 mmHg; n = 1269 with an OBP < 130/80 mmHg) yielded similar AUC values. In conclusion, the accuracy of guideline-proposed OBP screening thresholds in identifying individuals at high risk of having MH in an office setting is limited and is inferior to that yielded by scores derived from simple clinical variables.

Explaining statin inhibition effectiveness of HMG-CoA reductase by quantum biochemistry computations.

By taking advantage of the crystallographic data of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) complexed with statins, a quantum biochemistry study based on the density functional theory is performed to estimate the interaction energy for each statin when one considers binding pockets of different sizes. Assuming a correlation between statin potency and the strength of the total HMGR-statin binding energy, clinical data as well as IC(50) values of these cholesterol-lowering drugs are successfully explained only after stabilization of the calculated total binding energy for a larger size of the ligand-interacting HGMR region, one with a radius of at least 12.0 Å. Actually, the binding pocket radius suggested by classic works, which was based solely on the interpretation of crystallographic data of the HMGR-statin complex, is smaller than that necessary to achieve total binding energy convergence in our simulations. Atorvastatin and rosuvastatin are shown to be the most strongly bound HMGR inhibitors, while simvastatin and fluvastatin are the weakest ones. A binding site, interaction energy between residues and statin atoms, and residues domain (BIRD) panel is constructed, indicating clear quantum biochemistry-based routes for the development of new statin derivatives.

Impact of the COVID-19 pandemic on blood pressure control: a nationwide home blood pressure monitoring study.

There are concerns that hypertension control may decrease during the COVID-19 pandemic. This study evaluated the impact of the COVID-19 pandemic on office blood pressure (OBP) and home blood pressure monitoring (HBPM) control in a large Brazilian nationwide sample. The results of an adjusted spline analysis evaluating the trajectory of OBP and HBPM control from 01/Jan/2019 to 31/Dec/2020 among independent participants who were untreated (n = 24,227) or treated (n = 27,699) with antihypertensive medications showed a modest and transient improvement in OBP control among treated individuals, which was restricted to the early months following the COVID-19 pandemic outbreak. Furthermore, slight reductions in OBP and HBPM values were detected in the early months following the COVID-19 pandemic outbreak among treated (n = 987) participants for whom blood pressure measurements before and during the pandemic were available, but not among untreated (n = 495) participants. In conclusion, we found no major adverse influence of the COVID-19 pandemic on OBP and HBPM control in a large nationwide sample.

Discrepancies in the diagnosis of hypertension in adolescents according to available office and home high blood pressure criteria.

This study aimed at comparing the prevalence of abnormal blood pressure (BP) phenotypes among 241 adolescents referred for hypertension (15.4 ± 1.4 years, 62% males, 40% obese) according to mostly used or available criteria for hypertension [AAP or ESH criteria for high office BP (OBP); Arsakeion or Goiânia schools' criteria for high home BP monitoring (HBPM)]. High OBP prevalence was greater when defined by AAP compared with ESH criteria (43.5% vs. 24.5%; p < .001), while high HBPM prevalence was similar between Arsakeion and Goiânia criteria (33.5% and 37.5%; p = .34). Fifty-five percent of the sample fulfilled at least one criterion for high BP, but only 31% of this subsample accomplished all four criteria. Regardless of the HBPM criteria, AAP thresholds were associated with lower prevalence of normotension and masked hypertension and greater prevalence of white-coat and sustained hypertension than ESH thresholds. These findings support the need to standardize the definition of hypertension among adolescents.

Scanning electron microscopy of the human low-density lipoprotein interaction with the tegument of Schistosoma mansoni.

The interaction between host molecules and Schistosoma mansoni has been regarded as a key feature for parasite survival. In this work, scanning electron microscopy was used to study the interaction of human low-density lipoprotein (LDL) with the tegument of the adult worm of S. mansoni. Worms were incubated in RPMI 1640 containing 10% of LPDS and 40 µg LDL/mL during 30, 60, and 120 min. Control worms were processed in the same way, without LDL. After the incubations, the samples were fixed and processed to scanning electron microscopy. The results demonstrated interaction of the LDL particles with the male parasite tegument. Male and female worms incubated without LDL from 0 (control) to 120 min did not show alterations in the tegument. It was observed a larger number of LDL particles on the dorsal region of male adult worm than others regions (anterior, posterior and gynecophoral canal). The female tegument did not show adherence of LDL. Aggregates on the tegument of the male worm were in greater number and size in the incubation times of 30 and 60 min than 120 min. The comparison between 30 and 120 min of incubation showed that the particles' size diminished from 2,650-860 nm to 634-363 nm, respectively. Such reduction can be due to the capture and the use of the lipids by the worm. Therefore, the internalization of lipids from LDL by the male worms seems to be a mechanism independent of endocytosis. Differences between males and females suggest lipid transference from male to female through gynecophoral canal.

Optimization of clavulanic acid production by Streptomyces daufpe 3060 by response surface methodology.

Clavulanic acid is a ß-lactam antibiotic which has a potent ß-lactamase inhibiting activity. In order to optimize its production by the new isolate Streptomyces DAUFPE 3060, the influence of two independent variables, temperature and soybean flour concentration, on clavulanic acid and biomass concentrations was investigated in 250 mL-Erlenmeyers according to a 2(2) central composite design. To this purpose, temperature and soybean flour (SF) concentration were varied in the ranges 26-34°C and 10-50 g/L, respectively, and the results evaluated utilizing the Response Surface Methodology. The experimental maximum production of clavulanic acid (629 mg/L) was obtained at 32°C and 40 g/L SF after 48 h, while the maximum biomass concentration (3.9 g/L) at 30°C and 50 g/L soybean flour, respectively. These values are satisfactorily close to those (640 mg/L and 3.75 g/L, respectively) predicted by the model, thereby demonstrating the validity of the mathematical approach adopted in this study.

The impact of changing home blood pressure monitoring cutoff from 135/85 to 130/80 mmHg on hypertension phenotypes.

This study investigated the impact of changing abnormal home blood pressure monitoring (HBPM) cutoff from 135/85 to 130/80 mmHg on the prevalence of hypertension phenotypes, considering an abnormal office blood pressure cutoff of 140/90 mmHg. We evaluated 57 768 individuals (26 876 untreated and 30 892 treated with antihypertensive medications) from 719 Brazilian centers who performed HBPM. Changing the HBPM cutoff was associated with increases in masked (from 10% to 22%) and sustained (from 27% to 35%) hypertension, and decreases in white-coat hypertension (from 16% to 7%) and normotension (from 47% to 36%) among untreated participants, and increases in masked (from 11% to 22%) and sustained (from 29% to 36%) uncontrolled hypertension, and decreases in white-coat uncontrolled hypertension (from 15% to 8%) and controlled hypertension (from 45% to 34%) among treated participants. In conclusion, adoption of an abnormal HBPM cutoff of 130/80 mmHg markedly increased the prevalence of out-of-office hypertension and uncontrolled hypertension phenotypes.

Relationship between office isolated systolic or diastolic hypertension and white-coat hypertension across the age spectrum: a home blood pressure study.

OBJECTIVE: The current study investigated the prevalence of white-coat hypertension (WCH) and white-coat uncontrolled hypertension (WUCH) throughout the age spectrum among individuals with office isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systolic-diastolic hypertension (SDH) who were untreated or treated with antihypertensive medications, respectively. METHODS: We cross-sectionally evaluated 8809 untreated (42% males, 52.1 ±â€Š16.2 years) and 9136 treated (39% males, 59.7 ±â€Š14.5 years) individuals from two independent Brazilian populations who underwent home blood pressure monitoring. Participants were also categorized as younger (<40 years), intermediate (≥40 and <60 years) and older (≥60 years) age. RESULTS: Unadjusted and adjusted analyses showed that the frequency of WCH and WUCH was significantly greater (P < 0.05) in ISH and IDH than SDH at all age groups. Logistic regression analysis adjusted for sex, BMI and studied population showed that, compared with SDH, ISH had in average 4.1, 3.1 and 1.6-fold greater risk of WCH and 3.3, 3.6 and 2.0-fold greater risk of WUCH at younger, intermediate and older ages, whereas IDH had in average 2.3, 2.6 and 2.0-fold greater risk of WCH and 3.8, 3.2 and 3.8-fold greater risk of WUCH at younger, intermediate and older ages, respectively. CONCLUSION: ISH and IDH were associated with higher prevalence of WCH and WUCH than SDH across all age spectrum. In addition, treated and untreated ISH individuals with age less than 60 years and treated IDH individuals of all ages had the highest risk of having WCH phenotypes.

Blood pressure cutoffs for white-coat and masked effects in a large population undergoing home blood pressure monitoring.

The values used to define the presence of white-coat or masked blood pressure (BP) effects are arbitrary. The aim of this study was to investigate the accuracy of several cutoff points based on the difference between office and home BP (ΔBP) values to detect white-coat uncontrolled (WUCH) and masked uncontrolled (MUCH) hypertension, which are phenotypes with adverse prognoses, in a large cohort of treated hypertensive patients. This multicenter cross-sectional study included 6,049 treated hypertensive patients (40% males, mean age 59.1 ± 14.4 years) who underwent office and home BP monitoring. We compared the sensitivity, specificity, area under curve (AUC), and positive (PPV) and negative (NPV) predictive values of several ΔBP cutoffs to detect WUCH and MUCH. The 15/9 mmHg cutoff, which reflects a 1.0 standard deviation of the ΔBP, showed the best AUC (0.783, 95% CI = 0.772-0.794) for the detection of WUCH, particularly in individuals with office grade 1 hypertension (AUC = 0.811, 95% CI = 0.793-0.829). The -1/-1 mmHg cutoff, which considers all individuals who had lower systolic or diastolic BP levels in the office than at home, had the highest AUC (0.822, 95% CI = 0.808-0.836) for the detection of MUCH. Both cutoff values also had the best performances for identifying all patients with higher and lower office-than-home BP grades. In conclusion, the 15/9 and -1/-1 mmHg cutoffs showed the best performance for the detection of treated hypertensive patients with WUCH and MUCH, respectively, and therefore might be markers of significant white-coat and masked effects and could be useful for identifying preferential targets for more routine home BP measures.

Height-Based Equations Can Improve the Diagnosis of Elevated Blood Pressure in Children.

Background: High blood pressure (BP) is usually underdiagnosed in children and adolescents, particularly due to its complex diagnosis process. This study describes novel height-based equations for the detection of BP disorders (BP > 90th percentile) and compares the accuracy of this approach with previously described screening methods to identify BP disorders. Methods: Height-based equations were built using the 90th percentile values for systolic and diastolic BP and respective height values from the current guideline of high-BP management in children. This guideline was also used as the gold standard method for identification of BP disorders. The equations were tested in Brazilian (n = 2,936) and American (n = 6,541) populations of children with 8-13 years old. Results: The obtained equations were 70 + 0.3 × height (in cm) for systolic BP and 35 + 0.25 × height (in cm) for diastolic BP. The new equations presented sensitivity and negative predictive value of near 100% and specificity > 91% and showed higher specificity and positive predictive value when compared with other screening tools. Importantly, height-based equations had greater agreement (kappa coefficient = 0.75-0.81) with the gold standard method than the other methods (kappa coefficient = 0.53-0.73). Further analysis showed that alternative height-based equations designed to identify hypertension (BP ≥ 95th percentile) also showed superior performance (kappa coefficient = 0.89-0.92) compared with other screening methods (kappa coefficient = 0.43-0.85). Conclusions: These findings suggest that the use of height-based equations may be a simple and feasible approach to improve the detection of high BP in the pediatric population.

Evaluating the impact of missenses mutations in CYP2D6*7 and CYP2D6*14A: does it compromise tamoxifen metabolism?

UNLABELLED: CYP2D6 is a high polymorphic enzyme from P450, responsible for metabolizing almost 25% of drugs. The distribution of different mutations among CYP2D6 alleles has been associated with poor, intermediate, extensive and ultra-metabolizers. AIM: To evaluate how missenses mutations in CYP2D6*7 and CYP2D6*14A poor metabolizer alleles affect CYP2D6 stability and function. MATERIALS & METHODS: CYPalleles database was used to collect polymorphisms data present in 105 alleles. We selected only poor metabolizers alleles that presented exclusively missenses mutations. They were analyzed through seven algorithms to predict the impact on CYP2D6 structure and function. RESULTS: H324P, the unique mutation in CYP2D6*7, has high impact in enzyme function due to its occurrence between two alpha-helixes involved in active site dynamics. G169R, a mutation that occurs only in CYP2D6*14A, leads to the gain of solvent accessibility and severe protein destabilization. CONCLUSION: Our in silico analysis showed that missenses mutations in CYP2D6*7 and CYP2D6*14A cause CYP2D6 dysfunction.

A modified blood pressure to height ratio improves accuracy for hypertension in childhood.

BACKGROUND: The blood pressure to height ratio (BP:HT) has been proposed as a simple method for identifying children with elevated BP. This procedure shows good accuracy for the screening of hypertension in adolescents but less so in younger children. Our aim in this study was to modify the BP:HT ratio and determine if this change would increase accuracy when measuring hypertension during childhood. METHODS: BP levels of 4,327 children (aged 5-12 years) were retrospectively obtained from medical charts. The modified ratio (BT:eHT13) was calculated as: BP/(HT + 7 × (13 - age in years)). Receiver operating characteristic curves were used to estimate cutoff points and the accuracy of the conventional and modified ratio to detect prehypertension and hypertension. RESULTS: The prevalences of prehypertension and hypertension were 3.91% and 5.44%, respectively. In general, BP:eHT13 showed higher sensitivity (ranging from 0.95 to 1.00) and specificity (ranging from 0.80 to 0.98) in detecting prehypertension, level I hypertension, and level II hypertension than BP:HT (sensitivity ranging from 0.91 to 1.00; specificity ranging from 0.59 to 0.89). CONCLUSIONS: The modified BP:eHT13 ratio showed better sensitivity and specificity for the screening of BP abnormalities in children aged 5-12 years.

The interaction of Vatairea macrocarca and Rhizobium tropici: net H+ efflux stimulus and alteration of extracellular Na+ concentration.

We studied the effect of a lectin isolated from seeds of the legume Vatairea macrocarpa on net H+ efflux in Rhizobium tropici, a bacterium capable of nodulating legume Phaseolus vulgaris. V. macrocarpa lectin (VML) was observed to temporarily stimulate the specific net H(+) efflux in R. tropici. When VML was present at 32 microg ml(-1), with or without 2 microM galactose (Gal), a specific net efflux >2.4 pM H+(min)(-1) mg dry biomass(-1) was induced. There was no detectable net H+ efflux when bovine serum albumin (16 microg ml(-1)) was tested. Addition of 16 microgVMLml(-1) resulted in a 700% increase of the extracellular Na+ concentration. The soluble proteins in the supernatant containing VML extract indicate a maximum immobilization of +/-10 microgVMLml(-1), with a minimum of 36,600 dimers or 8500 larger aggregates of VML binding in each bacterium. Our data suggest that VML activates Rhizobium as a bioenergetic substrate molecule, resulting in potential alterations of the external bacterial membrane.

Ester synthesis catalyzed by Mucor miehei lipase immobilized on magnetic polysiloxane-polyvinyl alcohol particles.

Mucor miehei lipase was immobilized on magnetic polysiloxane-polyvinyl alcohol particles by covalent binding with high activity recovered. The performance of the resulting immobilized biocatalyst was evaluated in the synthesis of flavor esters using heptane as solvent. The impact on reaction rate was determined for enzyme concentration, molar ratio of the reactants, carbon chain length of the reactants, and alcohol structure. Ester synthesis was maximized for substrates containing excess acyl donor and lipase loading of 25 mg/mL. The biocatalyst selectivity for the carbon chain length was found to be different concerning the organic acids and alcohols. High reaction rates were achieved for organic acids with 8 or 10 carbons, whereas increasing the alcohol carbon chain length from 4 to 8 carbons gave much lower esterification yields. Optimal reaction rate was determined for the synthesis of butyl caprylate (12 carbons). Esterification performance was also dependent on the alcohol structure, with maximum activity occurring for primary alcohol. Secondary and tertiary alcohols decreased the reaction rates by more than 40%.

Antibiotic prophylaxis in bariatric surgery with continuous infusion of cefazolin: determination of concentration in adipose tissue.

BACKGROUND: The aim of this study was to evaluate the concentration of cefazolin in adipose tissue of patients undergoing bariatric surgery. METHODS: Eighteen patients undergoing bariatric surgery were evaluated during the period from October 2011 to May 2012. All patients had a dosage schedule of antibiotic prophylaxis with cefazolin administered as follows: first, 2 g in anesthetic induction, followed by continuous infusion of 1 g diluted in 250 ml of saline solution. Adipose samples, collected soon after the incision (initial) and before the skin synthesis (final), were analyzed using reverse phase high-pressure liquid chromatography. The level of significance adopted was 5 %. RESULTS: The cefazolin concentration in the adipose tissue samples at the beginning of surgery was an average of 6.66 ± 2.56 ug/ml. The mean concentration before the skin synthesis was 7.93 ± 2.54 ug/ml. Patients with BMI < 40 kg/m(2) had higher initial and final sample concentrations of cefazolin than patients with BMI ≥ 40 kg/m(2). There was no surgical site infection (SSI) in any of the patients. CONCLUSIONS: In bariatric surgeries, addition of a 1 g increase of cefazolin, administered through continuous intravenous infusion, to the currently recommended dose of 2 g administered in anesthetic induction provided a concentration in the adipose tissue above the minimum inhibitory concentration (MIC) of the main causal agents of SSI. An inverse correlation between BMI and concentration of cefazolin in adipose tissue was observed.

Screening of wild type Streptomyces isolates able to overproduce clavulanic acid.

The selection of new microorganisms able to produce antimicrobial compounds is hoped for to reduce their production costs and the side effects caused by synthetic drugs. Clavulanic acid is a ß-lactam antibiotic produced by submerged culture, which is widely used in medicine as a powerful inhibitor of ß-lactamases, enzymes produced by bacteria resistant to antibiotics such penicillin and cephalosporin. The purpose of this work was to select the best clavulanic acid producer among strains of Streptomyces belonging to the Microorganism Collection of the Department of Antibiotics of the Federal University of Pernambuco (DAUFPE). Initially, the strains were studied for their capacity to inhibit the action of ß-lactamases produced by Klebsiella aerogenes ATCC 15380. From these results, five strains were selected to investigate the batch kinetics of growth and clavulanic acid production in submerged culture carried out in flasks. The results were compared with the ones obtained by Streptomyces clavuligerus ATCC 27064 selected as a control strain. The best clavulanic acid producer was Streptomyces DAUFPE 3060, molecularly identified as Streptomyces variabilis, which increased the clavulanic acid production by 28% compared to the control strain. This work contributes to the enlargement of knowledge on new Streptomyces wild strains able to produce clavulanic acid by submerged culture.