Dynamics of growth differentiation factor 15 in acute heart failure

Aims: Risk stratification in acute heart failure (HF) patients can help to decide therapies and time for discharge. The potential of growth differentiation factor 15 (GDF-15) in HF has been previously shown. We aimed to study the importance of GDF-15-level variations in acute HF patients. Methods and results: We retrospectively evaluated a cohort of patients hospitalized due to acute HF. GDF-15 was measured both at admission and on the discharge day. Patients were followed-up during a 3 year period. The endpoint under analysis was all-cause mortality. GDF-15 variation is equal to [(admission GDF-15 - discharge GDF-15)∕admission GDF-15] × 100. Variation was categorized in levels of increase or decrease of GDF-15. Patients were cross-classified according to admission and discharge GDF-15 cut-off points. A Cox regression analysis was used to assess the prognostic impact of GDF-15 variation and the impact of both admission and discharge GDF-15 according to the cross-classification. We studied a group of 249 patients with high co-morbidity burden. Eighty-one patients died at 1 year and 147 within 3 years. There was a modest decrease in GDF-15 during hospitalization from a median value of 4087 to 3671 ng/mL (P = 0.02). No association existed between GDF-15 variation and mortality. In multivariate analysis, patients with admission GDF-15 ≥ 3500 ng/mL and discharge GDF-15 ≥ 3000 ng/mL had a significantly higher 1 year death risk when compared with the remaining-hazard ratio = 2.59 (95% confidence interval: 1.41-4.76)-and a 3 year 1.76 (95% confidence interval: 1.08-2.87) higher death risk compared with those with both values below the cut-off. Conclusions: Growth differentiation factor 15 decreased during an acute HF hospitalization, but its variation had no prognostic implications. The knowledge of both admission and discharge GDF-15 added meaningful information to patients' risk stratification

Impact of Pegloticase on Patient Outcomes in Refractory Gout: Current Perspectives

Gout is currently the most frequent cause of inflammatory arthritis worldwide and is responsible for poor health-related quality of life and loss of work productivity. It is caused by high levels of serum urate, leading to the deposition of monosodium urate crystals in joints and soft tissues. This condition is associated with acute flares and, if untreated or refractory, chronic and potentially destructive arthritis and tophi formation. Pegloticase is a recombinant, pegylated uricase used in the treatment of gout patients who fail conventional urate-lowering therapy. In this review, we discuss the impact of pegloticase on patient outcomes in refractory gout. We analyze different parameters, such as plasma uric acid concentration, frequency of flares, tophi reduction, pain, function, quality of life, and safety

The prognostic impact of magnesium in acute heart failure is different according to the presence of diabetes mellitus

Background: Hypermagnesemia predicts mortality in chronic heart failure (HF); however, in acute HF, magnesium does not seem to be outcome-associated. Diabetes mellitus (DM) frequently associates with altered magnesium status. We hypothesized that DM might influence the prognostic impact of magnesium in acute HF. Methods: This is a retrospective cohort study of hospitalized patients with acute HF. Patients without data on admission serum magnesium were excluded. Follow-up: 1 year from hospital admission. Primary end point: all-cause mortality. Patients were divided according to median serum magnesium (1.64 mEq/L). The Kaplan-Meier survival method was used to determine survival curves according to magnesium levels. The analysis was stratified according to the presence of DM. A multivariable Cox regression analysis was used to study the prognostic impact of magnesium. Results: We studied 606 patients. The mean age was 76 ± 12 years, 44.1% were male, 50.7% had DM, and 232 (38.3%) died during follow-up. Median magnesium was 1.64 (1.48-1.79) mEq/L. Patients with magnesium ≥1.64 mEq/L had higher 1-year mortality [141 (46.4%) vs 91 (30.1%), P < .001]. After adjustments for age, sex, history of atrial fibrillation, systolic blood pressure, heart rate, ischemic etiology, B-type natriuretic peptide, estimated glomerular filtration rate, alcohol consumption, antihyperglycaemic agents or glycated hemoglobin, admission glycemia, New York Heart Association class IV, and severe left ventricle systolic dysfunction, serum magnesium ≥1.64 mEq/L was associated with higher mortality only in patients with DM: HR 1.89 (95% confidence interval: 1.19-3.00), P = .007, and 1.27 (95% confidence interval: 0.83-1.94) and P = .26 for non-DM patients. The results were similar if magnesium was analyzed as a continuous variable. Per 0.1 mEq/L increase in magnesium levels, patients with DM had 13% increased risk of 1-year mortality. Conclusions: Higher magnesium levels were associated with worse prognosis only in HF patients with DM.info:eu-repo/semantics/publishedVersio

Patterns of biomechanical demands are associated with musculoskeletal pain in the beginning of professional life: a population-based study

Objectives This study aimed to describe patterns of occupational biomechanical demands in the beginning of professional life and to quantify their association with the presence and intensity of regional musculoskeletal pain. Methods Cross-sectional data from 21-year-old participants were collected during the third wave of the EPITeen cohort study (N=1733, 37.5% were workers). Ten different work-related biomechanical tasks were characterized. Latent class analysis was conducted to identify empirical patterns of occupational biomechanical demands. The presence and intensity of regional musculoskeletal pain in the previous year were also evaluated. Results Four patterns of occupational biomechanical demands were found: “low demands”, “sitting demands”, “repetitive and asymmetric demands”, and “high and vibrational demands”. When compared to workers with low demands, those with repetitive and asymmetric demands or high and vibrational demands presented 80% higher adjusted odds ratio (ORadj) of reporting neck/shoulder pain. High and vibrational demands occupations were significantly associated with upper-/lower-back pain in comparison to low demands [ORadj 1.80, 95% confidence interval (95% CI%) 1.09–2.96]. In addition, workers with sitting demands were more likely to report any or severe upper-/lower-back pain [ORadj 1.56 (95% CI 0.99–2.45) and 1.66 (95% CI 1.03–2.66), respectively] when compared to those with low demands. Conclusions Patterns of high work-related physical demands were associated with the presence of neck/shoulder pain and severity of upper-/lower-back pain. This emphasizes that even short-term biomechanical exposures at the workplace may be involved in the etiology of musculoskeletal complaints

Is a Combined Programme of Manual Therapy and Exercise More Effective than Usual Care in Patients with Non-Specific Chronic Neck Pain? A Randomized Controlled Trial

Objective: The aim of this study was to compare the effectiveness of a combined intervention of manual therapy and exercise (MET) versus usual care (UC), on disability, pain intensity and global perceived recovery, in patients with non-specific chronic neck pain (CNP). Design: Randomized controlled trial. Setting: Outpatient care units. Subjects: Sixty-four non-specific CNP patients were randomly allocated to MET (n = 32) or UC (n = 32) groups. Interventions: Participants in the MET group received 12 sessions of mobilization and exercise, whereas the UC group received 15 sessions of usual care in physiotherapy. Main measures: The primary outcome was disability (Neck Disability Index). The secondary outcomes were pain intensity (Numeric Pain Rating Scale) and global perceived recovery (Patient Global Impression Change). Patients were assessed at baseline, three weeks, six weeks (end of treatment) and at a three-month follow-up. Results: Fifty-eight participants completed the study. No significant between-group difference was observed on disability and pain intensity at baseline. A significant between-group difference was observed on disability at three-week, six-week and three-month follow-up (median (P25-P75): 6 (3.25-9.81) vs. 15.5 (11.28-20.75); P < 0.001), favouring the MET group. Regarding pain intensity, a significant between-group difference was observed at six-week and three-month follow-up (median (P25-P75): 2 (1-2.51) vs. 5 (3.33-6); P < 0.001), with superiority of effect in MET group. Concerning the global perceived recovery, a significant between-group difference was observed only at the three-month follow-up (P = 0.001), favouring the MET group. Conclusion: This study's findings suggest that a combination of manual therapy and exercise is more effective than usual care on disability, pain intensity and global perceived recovery.info:eu-repo/semantics/publishedVersio

Consolidated bioprocessing of corn cob-derived hemicellulose: engineered industrial Saccharomyces cerevisiae as efficient whole cell biocatalysts

Background Consolidated bioprocessing, which combines saccharolytic and fermentative abilities in a single microorganism, is receiving increased attention to decrease environmental and economic costs in lignocellulosic biorefineries. Nevertheless, the economic viability of lignocellulosic ethanol is also dependent of an efficient utilization of the hemicellulosic fraction, which contains xylose as a major component in concentrations that can reach up to 40% of the total biomass in hardwoods and agricultural residues. This major bottleneck is mainly due to the necessity of chemical/enzymatic treatments to hydrolyze hemicellulose into fermentable sugars and to the fact that xylose is not readily consumed by Saccharomyces cerevisiaethe most used organism for large-scale ethanol production. In this work, industrial S. cerevisiae strains, presenting robust traits such as thermotolerance and improved resistance to inhibitors, were evaluated as hosts for the cell-surface display of hemicellulolytic enzymes and optimized xylose assimilation, aiming at the development of whole-cell biocatalysts for consolidated bioprocessing of corn cob-derived hemicellulose. Results These modifications allowed the direct production of ethanol from non-detoxified hemicellulosic liquor obtained by hydrothermal pretreatment of corn cob, reaching an ethanol titer of 11.1 g/L corresponding to a yield of 0.328 g/g of potential xylose and glucose, without the need for external hydrolytic catalysts. Also, consolidated bioprocessing of pretreated corn cob was found to be more efficient for hemicellulosic ethanol production than simultaneous saccharification and fermentation with addition of commercial hemicellulases. Conclusions These results show the potential of industrial S. cerevisiae strains for the design of whole-cell biocatalysts and paves the way for the development of more efficient consolidated bioprocesses for lignocellulosic biomass valorization, further decreasing environmental and economic costs.This work has been carried out at the Biomass and Bioenergy Research Infrastructure (BBRI)-LISBOA-01-0145-FEDER-022059, supported by Operational Programme for Competitiveness and Internationalization (PORTUGAL2020), by Lisbon Portugal Regional Operational Programme (Lisboa 2020) and by North Portugal Regional Operational Programme (Norte 2020) under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and has been supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020, the “Contrato-Programa” UIDB/04050/2020, the MIT-Portugal Program (Ph.D. Grant PD/BD/128247/2016 to Joana T. Cunha) and through Project FatVal (POCI-01-0145-FEDER-032506) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing

Evaluation of the QuEChERS Method and Gas Chromatography–Mass Spectrometry for the Analysis Pesticide Residues in Water and Sediment

A method for the determination of pesticide residues in water and sediment was developed using the QuEChERS method followed by gas chromatography – mass spectrometry. The method was validated in terms of accuracy, specificity, linearity, detection and quantification limits. The recovery percentages obtained for the pesticides in water at different concentrations ranged from 63 to 116%, with relative standard deviations below 12%. The corresponding results from the sediment ranged from 48 to 115% with relative standard deviations below 16%. The limits of detection for the pesticides in water and sediment were below 0.003 mg L−1 and 0.02 mg kg−1, respectively

Prognosis of chronic low back pain: design of an inception cohort study

BACKGROUND: Although clinical guidelines generally portray chronic low back pain as a condition with a poor prognosis this portrayal is based on studies of potentially unrepresentative survival cohorts. The aim of this study is to describe the prognosis of an inception cohort of people with chronic low back pain presenting for primary care. METHODS/DESIGN: The study will be an inception cohort study with one year follow-up. Participants are drawn from a cohort of consecutive patients presenting with acute low back pain (less than 2 weeks duration) to primary care clinics in Sydney, Australia. Those patients who continue to experience pain at three months, and are therefore classified as having chronic back pain, are invited to participate in the current study. The cohort will be followed up by telephone at baseline, 9 months and 12 months after being diagnosed with chronic low back pain. Recovery from low back pain will be measured by sampling three different outcomes: pain intensity, interference with function due to pain, and work status. Life tables will be generated to determine the one year prognosis of chronic low back pain. Prognostic factors will be assessed using Cox regression. DISCUSSION: This study will determine the prognosis of chronic non-specific low back pain in a representative cohort of patients sourced from primary care. The results of this study will improve understanding of chronic low back pain, allowing clinicians to provide more accurate prognostic information to their patients