Considerations for application of benchmark dose modeling in radiation research: workshop highlights

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Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin

Structural changes in human serum albumin (HSA) induced by the pollutants 1-naphthol, 2-naphthol and 8-quinolinol were analyzed by circular dichroism, fluorescence spectroscopy and dynamic light scattering. The alteration in protein conformational stability was determined by helical content induction (from 55 to 75%) upon protein-pollutant interactions. Domain plasticity is responsible for the temperature-mediated unfolding of HSA. These findings were compared to HSA-hydrolase activity. We found that though HSA is a monomeric protein, it shows heterotropic allostericity for β-lactamase activity in the presence of pollutants, which act as K- and V-type non-essential activators. Pollutants cause conformational changes and catalytic modifications of the protein (increase in β-lactamase activity from 100 to 200%). HSA-pollutant interactions mediate other protein-ligand interactions, such as HSA-nitrocefin. Therefore, this protein can exist in different conformations with different catalytic properties depending on activator binding. This is the first report to demonstrate the catalytic allostericity of HSA through a mechanistic approach. We also show a correlation with non-microbial drug resistance as HSA is capable of self-hydrolysis of β-lactam drugs, which is further potentiated by pollutants due to conformational changes in HSA

Microalbuminuria among Type 1 and Type 2 diabetic patients of African origin in Dar Es Salaam, Tanzania

BACKGROUND: The prevalences and risk factors of microalbuminuria are not full described among black African diabetic patients. This study aimed at determining the prevalence of microalbuminuria among African diabetes patients in Dar es Salaam, Tanzania, and relate to socio-demographic features as well as clinical parameters. METHODS: Cross sectional study on 91 Type 1 and 153 Type 2 diabetic patients. Two overnight urine samples per patient were analysed. Albumin concentration was measured by an automated immunoturbidity assay. Average albumin excretion rate (AER) was used and were categorised as normalbuminuria (AER < 20 ug/min), microalbuminuria (AER 20–200 ug/min), and macroalbuminuria (AER > 200 ug/min). Information obtained also included age, diabetes duration, sex, body mass index, blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, serum creatinine, and glycated hemoglobin A(1c). RESULTS: Overall prevalence of microalbuminuria was 10.7% and macroalbuminuria 4.9%. In Type 1 patients microalbuminuria was 12% and macroalbuminuria 1%. Among Type 2 patients, 9.8% had microalbuminuria, and 7.2% had macroalbuminuria. Type 2 patients with abnormal albumin excretion rate had significantly longer diabetes duration 7.5 (0.2–24 yrs) than those with normal albumin excretion rate 3 (0–25 yrs), p < 0.001. Systolic and diastolic blood pressure among Type 2 patients with abnormal albumin excretion rate were significantly higher than in those with normal albumin excretion rate, (p < 0.001). No significant differences in body mass index, glycaemic control, and cholesterol levels was found among patients with normal compared with those with elevated albumin excretion rate either in Type 1 or Type 2 patients. A stepwise multiple linear regression analysis among Type 2 patients, revealed AER (natural log AER) as the dependent variable to be predicted by [odds ratio (95% confidence interval)] diabetes duration 0.090 (0.049, 0.131), p < 0.0001, systolic blood pressure 0.012 (0.003–0.021), p < 0.010 and serum creatinine 0.021 (0.012, 0.030). CONCLUSION: The prevalence of micro and macroalbuminuria is higher among African Type 1 patients with relatively short diabetes duration compared with prevalences among Caucasians. In Type 2 patients, the prevalence is in accordance with findings in Caucasians. The present study detects, however, a much lower prevalence than previously demonstrated in studies from sub-Saharan Africa. Abnormal AER was significantly related to diabetes duration and systolic blood pressure

Stereo-Selectivity of Human Serum Albumin to Enantiomeric and Isoelectronic Pollutants Dissected by Spectroscopy, Calorimetry and Bioinformatics

1–naphthol (1N), 2–naphthol (2N) and 8–quinolinol (8H) are general water pollutants. 1N and 2N are the configurational enantiomers and 8H is isoelectronic to 1N and 2N. These pollutants when ingested are transported in the blood by proteins like human serum albumin (HSA). Binding of these pollutants to HSA has been explored to elucidate the specific selectivity of molecular recognition by this multiligand binding protein. The association constants (Kb) of these pollutants to HSA were moderate (104–105 M−1). The proximity of the ligands to HSA is also revealed by their average binding distance, r, which is estimated to be in the range of 4.39–5.37 nm. The binding free energy (ΔG) in each case remains effectively the same for each site because of enthalpy–entropy compensation (EEC). The difference observed between ΔCpexp and ΔCpcalc are suggested to be caused by binding–induced flexibility changes in the HSA. Efforts are also made to elaborate the differences observed in binding isotherms obtained through multiple approaches of calorimetry, spectroscopy and bioinformatics. We suggest that difference in dissociation constants of pollutants by calorimetry, spectroscopic and computational approaches could correspond to occurrence of different set of populations of pollutants having different molecular characteristics in ground state and excited state. Furthermore, our observation of enhanced binding of pollutants (2N and 8H) in the presence of hemin signifies that ligands like hemin may enhance the storage period of these pollutants in blood that may even facilitate the ill effects of these pollutants

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]. BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS o

Efektifitas Pemberian Rotifera (Brachionus Rotundiformis) yang Diperkaya dengan Taurin dan Glutamin terhadap Kelangsungan Hidup dan Pertumbuhan Larva Ikan Kerapu Sunu (Plectropomus Leopardus)

Ikan Kerapu merupakan salah satu Ikan laut yang berekonomis penting yang banyak ditangkap dan diekspor. Rendahnya kelangsungan hidup pada stadia larva menjadi penyebab pengembangan budidaya kerapu sunu masih mengalami kendala sehingga masih sulit pengadaan benih secara cukup dan berkelanjutan. Pemberian pakan alami pada stadia larva merupakan langkah yang penting dalam meningkatkan kelangsungan hidup larva. Jenis pakan alami yang sering digunakan dalam kegiatan pembenihan ikan laut yaitu rotifer (B. rotundiformis). Rotifer menjadi pakan pada stadia larva karena rotifer mempunyai ukuran yang kecil dan sesuai dengan bukaan mulut larva kerapu sunu. Namun pemberian rotifer masih belum cukup untuk meningkatkan kelangsungan hidup larva, sehingga perlu dilakukan pengayaan rotifer dengan asam amino. Asam amino yang diduga dapat mengkatkan kelangsungan hidup larva adalah Taurin dan Glutamin. Tujuan penelitian ini adalah untuk mengetahui pengaruh pemberian rotifer yang diperkaya dengan taurin dan glutamin dalam menunjang kelangsungan hidup larva kerapu sunu. Penelitian ini akan dilaksanakan di Balai Besar Riset Budidaya Laut dan Penyuluhan Perikanan di Gondol, Bali pada bulan september 2017. Metode yang digunakan terdiri dari 4 perlakuan dan 4 kali ulangan: (A) tanpa Taurin dan Glutamin; (B) 0,5 taurin per 10 L media pengkaya; (C) 0,5 Glutamin per 10 L media pengkaya; (D) 0,5 Taurin dan 0,5 Glutamin per 10 L media pengkaya. Pemeliharaan larva menggunakan bak berukuran 1000 L dan di pelihara selama 10 hari. Pemberian rotifer mulai dari D-2 sampai D-10. Parameter yang diamati adalah kelangsungan hidup, pertumbuhan, dan kualitas air

Experimental Evaluation of Interfacial Surface Cracks in Friction Welded Dissimilar Metals through Image Segmentation Technique (IST)

Surface cracks on the friction welded interface of dissimilar metals are one of the earliest indications of degradation of the joint, which is a critical aspect for the welding strength. By manual inspection of the friction welded joint, observations of irregularities, porosity voids, crack lengths, cracked surfaces, and depth penetrations of two dissimilar metals can be made. Manual inspection purely depends on a quality expert&#8217;s experience of quantitative analysis and knowledge. In this research, an attempt has been made to effectively utilize the image segmentation technique (IST) in the estimation of the welded surface quality of a dissimilar joint by friction welding. The bonding strength between dissimilar metals in friction welding is more dependent on the coefficient of friction between the metallic surfaces. To demonstrate the capability of the image segmentation technique, experiments were conducted with various parameters, such as friction pressure, friction time, coefficient of friction, and torque speed of the rotating work piece. The effect of the coefficient of friction on friction welded surface quality by considering process parameters is estimated by using the proposed technique. Experiments were validated and the results claimed that the proposed image processing approach is efficient in fractured surface crack detection, reducing the computation cost, and providing a high-speed method with greater accuracy in the identification of welded surface defects. It was found that the friction coefficient is dependent mostly on the friction pressure and friction time. Its values range from 0.21 to 0.71, with the highest value of friction pressure at 120 MPa and 500 rpm. The present work deals with the detection of welding defects by means of segmentation based analysis of the welded interface. This method has a significant improvement in the fractured surface, crack detection, and non-welded areas&#8217; detection in terms of pixels at the desired region, and is easy when compared to conventional detection techniques by using an operator&#8217;s decisions