Process optimization and mechanistic studies of lead (II): Aspergillus caespitosus interaction for industrial effluent treatment

The lead (II) accumulation potential of various biosorbent had been widely studied in the last few years, but an outstanding Pb(II) accumulating biomass still seems crucial for bringing the process to a successful application stage. This investigation describes the use of non-living biomass of Aspergillus caespitosus for removal of Pb from Pb(NO3)2 solution in a batch system under different experimental conditions. The highest Pb(II) sorption (351.7 ± 5.7 mg/g biomass) was observed at 600 µg/ml initial Pb concentration. Biosorption data were well defined by pseudo-second order, saturation mixed order and Langmuir isotherm models. The thermodynamic parameters: G (303 K), H and S were determined to be 4.64 kJ/mol, 75.4 kJ/mol and 26.2 J/mol-K respectively. The Pb uptake from binary solution was inhibited in the order of copper > nickel > zinc > manganese. Fourier transform infrared spectroscopy (FT-IR) characterization of Pb biosorption revealed the involvement of –SO3 and –CN groups along with other groups. The biosorbed Pb was stripped out (85.5%) using 0.01 M HCl and about 12% loss in Pb(II) sorption capacity was observed after five sorption-desorption cycles. High Pb (II) uptake (351.7 ± 5.7 mg/g biomass) by A. caespitosus proved it to be an outstanding biomaterial until now reported in literature for accumulating from solutions.Key words: Aspergillus caespitosus, Pb, Langmuir isotherm, pseudo-second-order kinetic model, FTIR, SEM, EDAX

Influence of nitrogen sources on production of &#946b-galactosidase by Aspergillus niger

The study was undertaken to enhance the production of b-galactosidase using five organic nitrogen sources with wheat bran as a substrate under solid state fermentation. The microbial source Aspergillus niger and its DG-resistant mutant that were grown in medium with initial pH of 5.5 in 250 ml flasks at 30°C for 144 h and sample was harvested after every 24 h and analysed for substrate consumption, cell mass formation and enzyme production. All the nitrogen sources, ammonium sulphate, corn steep liquor, diammonium phosphate, fish meal and urea showed significant results. However, higher values of enzyme activity of 168.0 and 371.15 IU/l/h, parent and mutant, respectively, was obtained from sample in which corn steep liquor was used as a nitrogen source as compared tocontrol (73.1 and 176.3 IU/l/h in parent and mutant, respectively). The effect of nitrogen sources was also found significant in both the organisms but higher in mutant organism (2.2 fold). It is concluded that enzyme production enhanced 2.7 fold by use of suitable production medium under optimum cultural conditions and that the mutant derivative of A. niger can be exploited for hyper production of this enzyme

Gastrointestinal complaints in runners are not due to small intestinal bacterial overgrowth

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal complaints are common among long distance runners. We hypothesised that small intestinal bacterial overgrowth (SIBO) is present in long distance runners frequently afflicted with gastrointestinal complaints.</p> <p>Findings</p> <p>Seven long distance runners (5 female, mean age 29.1 years) with gastrointestinal complaints during and immediately after exercise without known gastrointestinal diseases performed Glucose hydrogen breath tests for detection of SIBO one week after a lactose hydrogen breath test checking for lactose intolerance. The most frequent symptoms were diarrhea (5/7, 71%) and flatulence (6/7, 86%). The study was conducted at a laboratory.</p> <p>In none of the subjects a pathological hydrogen production was observed after the intake of glucose. Only in one athlete a pathological hydrogen production was measured after the intake of lactose suggesting lactose intolerance.</p> <p>Conclusions</p> <p>Gastrointestinal disorders in the examined long distance runners were not associated with small intestinal bacterial overgrowth.</p

Targeted physiotherapy for patellofemoral joint osteoarthritis: A protocol for a randomised, single-blind controlled trial

<p>Abstract</p> <p>Background</p> <p>The patellofemoral joint (PFJ) is one compartment of the knee that is frequently affected by osteoarthritis (OA) and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA.</p> <p>Methods</p> <p>90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA) will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week) compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks). Physiotherapy treatment will consist of (i) quadriceps muscle retraining; (ii) quadriceps and hip muscle strengthening; (iii) patellar taping; (iv) manual PFJ and soft tissue mobilisation; and (v) OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction.</p> <p>Conclusion</p> <p>This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the potential to reduce the personal and societal burden of this increasing public health problem.</p> <p>Trial Registration</p> <p>Australia New Zealand Clinical Trials Registry ACTRN12608000288325</p

Addressing Recruitment Challenges in the Engage-HU Trial in Young Children with Sickle Cell Disease

Background: Sickle cell disease (SCD) is a genetic disorder that causes significant medical and neurologic morbidity in children. Hydroxyurea (HU) is the primary medication used to prevent these complications. National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend offering HU to children as young as 9 months of age with SCD (HbSS or HbSB0 thalassemia) using a shared decision-making approach. Although HU has proven efficacious it remains underutilized and caregivers report that they are not always actively involved in the decision to initiate this therapy. Reasons for limited HU uptake likely include lack of clinician knowledge and training and negative caregiver perceptions. Thus, we developed the Engage-HU trial as a novel approach to address HU utilization barriers. A critical consideration for this trial was that SCD primarily affects individuals of African and Hispanic/Latino descent. In these minority populations, intervention trials are sometimes terminated early because of recruitment difficulties related to mistrust of research, caregiver burden, and transportation issues. As such, the Engage-HU trial design included best-practice strategies for recruiting people of color in research. This study describes these strategies, the initial recruitment plan, preliminary recruitment outcomes and strategies, and our procedural adaptations. Study Design and Methods: Engage-HU is a randomized control trial (NCT03442114) to assess how clinicians can engage caregivers in a shared discussion that considers their values and preferences and includes evidence that supports HU. Engage-HU compares two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD: 1) the American Society of Hematology Pocket Guide, and 2) the HU Shared-Decision Making (H-SDM) Toolkit. The study aims to recruit 174 caregivers and evaluate the effectiveness of the dissemination methods on patient-centered outcomes (caregiver confidence in decision-making and perceptions of experiencing shared decision-making) as well as HU uptake and child health outcomes. Eligible children are aged 0 to 5 years, candidates for HU, and their caregiver has not made a decision about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a stepped-wedge design. Data will be analyzed based on the intent-to-treat principle. All participants will remain in the arm of the study to which they were randomized, regardless of whether or not they receive the assigned dissemination method. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using a linear mixed effects regression model with a robust variance estimator and maximum likelihood estimation with observations clustered within site. The Engage-HU trial includes adaptations to increase recruitment such as tailored messaging, a relational recruitment approach, streamlined data collection, and a Stakeholder Advisory Committee. However, even with these adaptations, the first 6-months of the trial yielded lower than anticipated recruitment. Rather than terminate the trial or accept low enrollment, the research team implemented a series of recruitment strategies to address barriers including helping to improve research coordinator knowledge of the study purpose and adjusting no-show and follow-up procedures (e.g., calls to families after missed appointments and reminder calls before appointments). Site clinicians and clinic staff were provided with additional training so they could give more context about Engage-HU to caregivers and the study principal investigator led monthly "all coordinator" calls to provide support by sharing updates and experiences about successful recruitment. Implementation of these strategies resulted in triple the number of enrollments over the next 7-months compared to the previous 6-months (Table 1). Our goal in sharing this information is to provide lessons learned that can be implemented in future trials with the systematically underserved SCD population. It is also anticipated that methods described here may also inform clinical approaches to better engage caregivers of young children around critical clinical conversations, such as initiating medications like HU. Disclosures King: Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; RiverVest: Consultancy; Novimmune: Research Funding; Celgene: Consultancy; Tioma Therapuetics: Consultancy; Amphivena Therapeutics: Research Funding; WUGEN: Current equity holder in private company; Cell Works: Consultancy; Incyte: Consultancy. Smith-Whitley:Prime: Other: Education material; Celgene: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Neumayr:Emmaus: Consultancy; Bayer: Consultancy; CTD Holdings: Consultancy; Pfizer: Consultancy; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Micelle: Other: Site principal investigator; GBT: Other: Site principal investigator; PCORI: Other: site principal investigator; Novartis: Other: co-investigator; Bluebird Bio: Other: co-investigator; Sangamo Therapeutics: Other; Silarus: Other; Celgene: Other; La Jolla Pharmaceuticals: Other; Forma: Other; Imara: Other; National Heart, Lung, and Blood Institute: Other; Health Resources and Services Administration: Other; Centers for Disease Control and Prevention: Other; Seattle Children's Research: Other. Yates:Novartis: Research Funding. Thompson:Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Research Funding; BMS: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding. </jats:sec

A dual function TAR Decoy serves as an anti-HIV siRNA delivery vehicle

The TAR RNA of HIV was engineered as an siRNA delivery vehicle to develop a combinatorial therapeutic approach. The TAR backbone was found to be a versatile backbone for expressing siRNAs. Upon expression in human cells, pronounced and specific inhibition of reporter gene expression was observed with TARmiR. The resulting TARmiR construct retained its ability to bind Tat and mediate RNAi. TARmiR was able to inhibit HIV gene expression as a TAR decoy and by RNA interference when challenged with infectious proviral DNA. The implications of this dual function therapeutic would be discussed

Cleavage of pyrene-stabilized RNA bulge loops by trans-(±)-cyclohexane-1,2-diamine

Chemical agents that cleave HIV genome can be potentially used for anti-HIV therapy. In this report, the cleavage of the upper stem-loop region of HIV-1 TAR RNA was studied in a variety of buffers containing organic catalysts. trans-(±)-Cyclohexane-1,2-diamine was found to cleave the RNA with the highest activity (31%, 37°C, 18 h). Cleavage of the RNA in trans-(±)-cyclohexane-1,2-diamine buffer was also studied when the RNA was hybridized with complementary DNAs. A pyrene-modified C3 spacer was incorporated to the DNA strand to facilitate the formation of a RNA bulge loop in the RNA/DNA duplex. In contrast, unmodified DNAs cannot efficiently generate RNA bulge loops, regardless of the DNA sequences. The results showed that the pyrene-stablized RNA bulge loops were efficiently and site-specifically cleaved by trans-(±)-cyclohexane-1,2-diamine