Pressure pushes tRNALys3 into excited conformational states.

Conformational dynamics play essential roles in RNA function. However, detailed structural characterization of excited states of RNA remains challenging. Here, we apply high hydrostatic pressure (HP) to populate excited conformational states of tRNALys3, and structurally characterize them using a combination of HP 2D-NMR, HP-SAXS (HP-small-angle X-ray scattering), and computational modeling. HP-NMR revealed that pressure disrupts the interactions of the imino protons of the uridine and guanosine U-A and G-C base pairs of tRNALys3. HP-SAXS profiles showed a change in shape, but no change in overall extension of the transfer RNA (tRNA) at HP. Configurations extracted from computational ensemble modeling of HP-SAXS profiles were consistent with the NMR results, exhibiting significant disruptions to the acceptor stem, the anticodon stem, and the D-stem regions at HP. We propose that initiation of reverse transcription of HIV RNA could make use of one or more of these excited states.

Demulsification of Pickering Emulsions by Chemical Dissolution of Stabilizers.

Demulsification of particle-stabilized oil-in-water emulsions is crucial in diverse fields such as treatment of produce water, recovery of valuable products of Pickering emulsion catalysis, and so on. In this work, we investigated a facile method for destabilizing emulsions by dissolving stabilizer particles by the introduction of acid or base. Nanoellipsoidal hematite-stabilized decane-in-water emulsions are destabilized by dissolving hematite with oxalic or hydrochloric acid in situ. Time required for complete demulsification decreased as the acid concentration is increased. The demulsification time is typically on the order of a few hours for the chosen protocol. Similarly, the silica-stabilized decane-water emulsion is demulsified by the addition of aqueous sodium hydroxide. Demulsification kinetics is presented as the temporal change of the emulsion volume with time. Emulsion volume decreases in two stages: an initial slow decrease followed by an exponential decrease. Scanning electron microscopy analysis shows that the stabilizing particles are completely dissolved and recrystallized as salts of respective kinds. An estimate of the desorption free energy suggests that particle size should be reduced to a few nanometers for inducing destabilization. This work describes a facile method to destabilize oil-in-water emulsion, and it can be generalized to any other particle-stabilized emulsions by choosing appropriate chemical reagent for dissolution.

Evaluation of a Pharmacist-Led Implementation of Standardized Medication Administration Times for Inpatients Receiving Hemodialysis.

BACKGROUND: Missed medication doses are a common and often preventable medication-related error that have been associated with an increased length of stay and mortality. Hemodialysis is a common, relatively predictable reason that patients are unavailable, resulting in missed doses. OBJECTIVE: To evaluate the implications of a pharmacist-led intervention to standardize the medication administration times for patients requiring hemodialysis who were prescribed antihypertensives, antiepileptics, apixaban, and/or antimicrobials. METHODS: A retrospective preanalysis and postanalysis of a pharmacist-led intervention were performed at a single-center, safety net hospital. Patients receiving dialysis and prescribed one of the targeted medications were included. The primary endpoint was the composite of missed and delayed doses. RESULTS: A total of 25 patients receiving 126 dialysis sessions in the preintervention group and 29 patients receiving 80 dialysis sessions in the postintervention group were included for analysis. For the primary endpoint, 118 (18%) versus 57 (9.3%) doses were missed or delayed in the preintervention versus postintervention group, respectively (P < 0.001). The primary endpoint was driven by fewer delayed doses in the postgroup. The number of antimicrobials given on a correct schedule increased in the postintervention group (98.3% vs 99.1%, P = 0.044). CONCLUSION AND RELEVANCE: A pharmacist-led intervention for standard medication administration times in patients requiring hemodialysis increased the number of prescribed medication doses given and given on time. The intervention also led to more antimicrobials administered at appropriate times relative to dialysis sessions.

Experimental investigation of Cd (II) ion adsorption on surface-modified mixed seaweed Biosorbent: A study on analytical interpretation and thermodynamics.

Despite advancements in wastewater treatment technologies, heavy metal contamination, especially cadmium (Cd), severely threatens human health and ecosystems. The purpose of this work is to compare the removal of Cd (II) ions from aqueous solutions by chemically modified mixed seaweed biosorbent (CMSB) and physically modified mixed seaweed biosorbent (PMSB). BET, SEM, EDAX, FTIR, and XRD techniques characterized the mixed seaweed biosorbents before and after adsorption. They are well-known for their sustainability, affordability, and biodegradability. The BET study revealed that CMSB had a surface area of 19.682 m2/g, while PMSB had a lower surface area of 14.803 m2/g. The optimum adsorption conditions were a temperature of 303 K, pH of 6.0, and biosorbent dosages of 1 g/L for CMSB and 2.5 g/L for PMSB. For CMSB and PMSB, the most efficient contact times were 40 and 80 min, respectively. The Langmuir model was demonstrated to be the best fit for the experimental data when compared to other isotherm models, with a coefficient of determination, or R2, of 0.9713 and a maximum monolayer capacity of 151.2 mg/g and 181.6 mg/g for physical and chemical activated mixed seaweed biomass. There was a significant relationship between the R2 values of chemically modified and physically modified biomass. The findings demonstrate that pseudo-second-order kinetics more accurately represent the adsorption process than pseudo-first-order and Elovich models. Thermodynamic experiments validated the endothermic, spontaneous and favourable characteristics of the removal process. According to the results of the current study, PMSB and CMSB may be used as effective adsorbents to remove Cd (II) from aqueous solutions.

Avelumab in the Treatment of Advanced Merkel Cell Carcinoma: A Systematic Review.

BACKGROUND: Avelumab, a programmed death ligand-1 inhibitor, has shown success in providing durable responses for difficult-to-treat Merkel cell carcinomas (MCCs). OBJECTIVE: Evaluate the efficacy and safety of avelumab in the treatment of advanced MCC. METHODS: Studies reporting the use of avelumab as a monotherapy or in combination with other agents in the treatment of stage III or IV (advanced) MCC were included. The primary outcomes were overall response rate, overall survival (OS), and treatment-related adverse events. RESULTS: A total of 48 studies were included, involving 1,565 patients with advanced MCC. Most patients were male (1,051, 67.3%) with stage IV MCC (517, 97.0%). The overall response rate was 46.1% (partial response-25.4% and complete response-20.7%) after a mean follow-up period of 9.5 months. Kaplan-Meier survival curves for the pooled stage III and IV group demonstrated OS rates of 58% at 1 year, 47% at 2 years, and 28% at 5 years after completion of treatment with avelumab (median OS: 23.1 months). The most common treatment-related adverse events consisted of constitutional (44%), gastrointestinal (19%), and dermatologic (12%) symptoms. CONCLUSION: Avelumab monotherapy and combination therapy have shown success in the overall response rate and survival for patients with advanced MCC.

Oil-in-Water Emulsions Stabilized by Hydrophilic Homopolymers.

Most of the polymeric emulsifiers have diblock and triblock copolymer architecture containing hydrophilic and hydrophobic domains. In this work, we show that hydrophilic homopolymers can be effective stabilizers of oil-in-water emulsions. Using polyethelyne oxide and poly(vinylpyrrolidone) as model hydrophilic homopolymers and n-decane and n-hexane as model nonpolar phases, we show that high-molecular weight polymers can stabilize emulsions over 24 h beyond a threshold concentration. We highlight the role of the molecular weight and concentration of the polymer in the stability of emulsions through kinetic measurements of emulsion volume, microscopic analysis, interfacial tension, and dilational rheology. We explain the mechanism of stabilization to stem from buoyancy-driven creaming of emulsion drops and film drainage and dilational elasticity of the interface in relation to the molecular weights and concentrations of polymers. This study demonstrates that water-soluble homopolymers can stabilize oil-in-water emulsions and open avenues for the use of eco-friendly biopolymers, which are inherently hydrophilic, as an alternative to synthetic emulsifiers.

Light-induced destabilisation of oil-in-water emulsions using light-active bolaform surfactants.

External stimuli-induced destabilisation of oil-in-water emulsions is of both fundamental and technological importance. In this work we synthesize light-active bolaform-type surfactants (LABSs) and show the preparation of decane-in-water emulsions over a range of surfactant and salt concentrations. Under ultraviolet (UV) illumination, LABSs undergo trans to cis isomerization affecting their interfacial activity. Therefore when stable emulsions stabilized by LABSs are exposed to UV light, they undergo partial destabilization. To induce interfacial flow, a small amount of volatile solvent (methanol, ethanol, tetrahydrofuran, etc.) is added at the emulsification stage and in this case complete phase separation is observed. This study demonstrates a facile route to induce destabilization of surfactant-stabilized emulsions using benign solvents and minimal use of energy (UV light) and this method could be of importance in wastewater treatment, enhanced oil recovery, protein separation, etc. where emulsion destabilization is desired.

Biodegradation of oil-contaminated aqueous ecosystem using an immobilized fungi biomass and kinetic study.

Remediation of environmental oil pollution with the usage of fungal organisms has proven to be a successful cleanup bioremediation method for organic contaminants. To investigate the breakdown of oil pollutants in water environments, biosurfactant-producing fungi have been isolated from oil-polluted soil samples. 16s rRNA sequencing technique was performed to identify the fungal organism and phylogenetic tree has been constructed. A variety of biosurfactant screening tests have demonstrated the better biosurfactant producing ability of fungi. The emulsion's stability, which is essential for the biodegradation process, was indicated by the emulsification index of 68.48% and emulsification activity of 1.3. In the isolated biosurfactant, important functional groups such as amino groups, lipids, and sugars were found according to thin layer chromatography analysis with a maximum retention value of 0.85. A maximum oil degradation of around 64% was observed with immobilized beads within 12 days. The half-life, and degradation removal rate constant of 20.21 days and 0.03 day-1, respectively, have been determined by the degradation kinetic analysis. GCMS analysis confirmed the highly degraded hydrocarbons such as nonanoic acid and pyrrolidine. The immobilized fungi exhibit better oil biodegradability in aqueous solutions.

Review on biopolymers and composites - Evolving material as adsorbents in removal of environmental pollutants.

The presence of pollutants and toxic contaminants in water sources makes it unfit to run through. Though various conventional techniques are on deck, development of new technologies are vital for wastewater treatment and recycling. Polymers have been intensively utilized recently in many industries owing to their unique characteristics. Biopolymers resembles natural alternative to synthetic polymers that can be prepared by linking the monomeric units covalently. Despite the obvious advantages of biopolymers, few reviews have been conducted. This review focuses on biopolymers and composites as suitable adsorbent material for removing pollutants present in environment. The classification of biopolymers and their composites based on the sources, methods of preparation and their potential applications are discussed in detail. Biopolymers have the potentiality of substituting conventional adsorbents due to its unique characteristics. Biopolymer based membranes and effective methods of utilization of biopolymers as suitable adsorbent materials are also briefly elaborated. The mechanism of biopolymers and their membrane-based adsorption has been briefly reviewed. In addition, the methods of regeneration and reuse of used biopolymer based adsorbents are highlighted. The comprehensive content on fate of biopolymer after adsorption is given in brief. Finally, this review concludes the future investigations in recent trends in application of biopolymer in various fields in view of eco-friendly and economic perspectives.

T-LAK cell-originated protein kinase (TOPK) enhances androgen receptor splice variant (ARv7) and drives androgen-independent growth in prostate cancer.

Despite impressive advances in the treatment of prostate cancer with various efficacious inhibitors along the androgen/androgen receptor axis, eventual development of incurable metastatic Castration-Resistant Prostate Cancer (mCRPC) is inevitable and remains a major clinical challenge. Constitutively active androgen receptor (AR) spliced variants have emerged as primary means of resistance to anti-androgens and androgen synthesis inhibitors. The alternatively spliced AR variant, ARv7, has attracted significant interest due to its constitutively active status in CRPC that drives androgen-independence. Factors that are involved in regulating ARv7 levels in CRPC are not clearly known. We recently demonstrated that a protein kinase, T-LAK cell-originated protein kinase (TOPK) level correlates with the aggressiveness of prostate cancer and its invasive behavior. In this study, we investigated whether TOPK plays a role in driving androgen-independence in prostate cancer cells. Our data demonstrate that TOPK overexpression in androgen-dependent LNCaP and VCaP induces ARv7 and drives androgen-independent growth. On the other hand, pharmacological inhibition of TOPK in androgen-independent LNCaP95 and 22Rv1 represses AR transactivation, and AR stability. In summary, this study illustrates a direct role of TOPK in regulating ARv7 and driving androgen-independence in prostate cancer cells.

Modeling analysis on the effective elimination of toxic pollutant from aquatic environment using pyrolysis assisted palmyra palm male inflorescence.

In this study adsorption of Cd(II) ions using the pyrolysis assisted Palmyra palm male inflorescence (PAPMI) was systematically examined. A batch adsorption study was carried out to determine the type of interactions and removal efficiency which is based on the surface property of PAPMI. The diverse parameters which affect the adsorption performance of PAPMI for Cd(II) ion removal were optimized: biosorbent dose - 1.25 g/L, pH - 6.0, temperature - 303 K, initial cadmium ions concentration - 50 mg/L and contact time - 40 min. Pseudo-first order kinetics and Langmuir isotherm models were more suitable to describe the adsorption kinetics and isotherm, respectively. Therefore, modeling studies portrayed the present Cd(II) ions adsorption on PAPMI as monolayer adsorption occurs on the homogeneous surface and follows the physisorption mechanism. The maximum adsorption capacity of the synthesized PAPMI was examined as 233.2 mg/g from the equilibrium isotherm investigation. Based on the calculated thermodynamic parameters (ΔGo, ΔHo and ΔSo) values, the present Cd(II) ions adsorption on PAPMI was explicated as feasible, and exothermic. The outcome proposed that Palmyra palm male inflorescence can be a suitable adsorbent for expulsion of Cd(II) ions from aqueous environment. In the interim, the utilization of pyrolysis assisted is a viable and fast uptake innovation for the removal of heavy metals from water environment.

The CALIPER-Revised Version of the Composite Physiologic Index is a Better Predictor of Survival in IPF than the Original Version.

CALIPER is a computer-based quantitative algorithm to accurately characterize and quantify pulmonary fibrosis, and a revised version of composite physiologic index (CPI) has been developed against this new algorithm. The prognostic capabilities of the original and CALIPER-revised versions of CPI were compared in a cohort of 185 patients with IPF prospectively followed in 2 centers. CALIPER-revised CPI was a significant risk factor towards lung transplant (LTx)-free survival, with enhanced hazard ratio (5.68) compared to the original CPI (5.36). Accuracy of LTx-free survival was substantially improved with CALIPER-revised CPI (area under the curve [AUC] 0.75 vs. 0.66), with much better specificity (83% vs. 55%). Six-month changes of CALIPER-revised CPI predicted survival significantly (AUC 0.65). CALIPER-revised CPI is a better predictor of LTx-free survival in patients with IPF. Since CALIPER technology is not available to all centers, this simple and easy to obtain tool may be used to guide management decisions in IPF.

A cross-country study of mis-implementation in public health practice.

BACKGROUND: Mis-implementation (i.e., the premature termination or inappropriate continuation of public health programs) contributes to the misallocation of limited public health resources and the sub-optimal response to the growing global burden of chronic disease. This study seeks to describe the occurrence of mis-implementation in four countries of differing sizes, wealth, and experience with evidence-based chronic disease prevention (EBCDP). METHODS: A cross-sectional study of 400 local public health practitioners in Australia, Brazil, China, and the United States was conducted from November 2015 to April 2016. Online survey questions focused on how often mis-termination and mis-continuation occur and the most common reasons programs end and continue. RESULTS: We found significant differences in knowledge of EBCDP across countries with upwards of 75% of participants from Australia (n = 91/121) and the United States (n = 83/101) reporting being moderately to extremely knowledgeable compared with roughly 60% (n = 47/76) from Brazil and 20% (n = 21/102) from China (p < 0.05). Far greater proportions of participants from China thought effective programs were never mis-terminated (12.2% (n = 12/102) vs. 1% (n = 2/121) in Australia, 2.6% (n = 2/76) in Brazil, and 1.0% (n = 1/101) in the United States; p < 0.05) or were unable to estimate how frequently this happened (45.9% (n = 47/102) vs. 7.1% (n = 7/101) in the United States, 10.5% (n = 8/76) in Brazil, and 1.7% (n = 2/121) in Australia; p < 0.05). The plurality of participants from Australia (58.0%, n = 70/121) and the United States (36.8%, n = 37/101) reported that programs often mis-continued whereas most participants from Brazil (60.5%, n = 46/76) and one third (n = 37/102) of participants from China believed this happened only sometimes (p < 0.05). The availability of funding and support from political authorities, agency leadership, and the general public were common reasons programs continued and ended across all countries. A program's effectiveness or evidence-base-or lack thereof-were rarely reasons for program continuation and termination. CONCLUSIONS: Decisions about continuing or ending a program were often seen as a function of program popularity and funding availability as opposed to effectiveness. Policies and practices pertaining to programmatic decision-making should be improved in light of these findings. Future studies are needed to understand and minimize the individual, organizational, and political-level drivers of mis-implementation.

A low-cost, hands-on module to characterize antimicrobial compounds using an interdisciplinary, biophysical approach.

We have developed a hands-on experimental module that combines biology experiments with a physics-based analytical model in order to characterize antimicrobial compounds. To understand antibiotic resistance, participants perform a disc diffusion assay to test the antimicrobial activity of different compounds and then apply a diffusion-based analytical model to gain insights into the behavior of the active antimicrobial component. In our experience, this module was robust, reproducible, and cost-effective, suggesting that it could be implemented in diverse settings such as undergraduate research, STEM (science, technology, engineering, and math) camps, school programs, and laboratory training workshops. By providing valuable interdisciplinary research experience in science outreach and education initiatives, this module addresses the paucity of structured training or education programs that integrate diverse scientific fields. Its low-cost requirements make it especially suitable for use in resource-limited settings.

Exploring political influences on evidence-based non-communicable disease prevention across four countries.

Implementation of evidence-based practices can improve efficiency and effectiveness of public health efforts. Few studies have explored the political contextual factors that impact implementation of evidence-based non-communicable disease prevention (EBNCDP). This study aimed to do so in Australia, Brazil, China and the United States. Investigators conducted 10-13 qualitative, semi-structured interviews of public health practitioners working in functionally similar public health organizations in each country (total N = 50). Study participants were identified through purposive sampling and interviews were structured around an interview guide covering six domains related to EBNCDP. Interviewees from all four countries identified funding as the primary politically-influenced barrier to implementing EBNCDP. Similarly widespread barriers included government funding priorities that shift based on who is in power and the difficulty of convincing policy-makers and funders that non-communicable disease prevention is a wise investment of political capital. Policymakers who are not evidence-driven was another common barrier even in the United States and Australia, where EBNCDP is more established. Findings suggest that political contextual factors influence EBNCDP and vary to an extent by country, though certain factors seem to be universal. This can aid public health practitioners, political leaders, and policymakers in advocating for conditions and policies that encourage evidence-based practice.

A qualitative exploration of contextual factors that influence dissemination and implementation of evidence-based chronic disease prevention across four countries.

BACKGROUND: Little is known about the contextual factors affecting the uptake of evidence-based chronic disease interventions in the United States and in other countries. This study sought to better understand the contextual similarities and differences influencing the dissemination and implementation of evidence-based chronic disease prevention (EBCDP) in Australia, Brazil, China, and the United States. METHODS: Between February and July 2015, investigators in each country conducted qualitative, semi-structured interviews (total N = 50) with chronic disease prevention practitioners, using interview guides that covered multiple domains (e.g., use of and access to EBCDP interventions, barriers and facilitators to the implementation of EBCDP interventions). RESULTS: Practitioners across the four countries reported only a few programmatic areas in which repositories of EBCDP interventions were used within their workplace. Across countries, academic journals were the most frequently cited channels for accessing EBCDP interventions, though peers were commonly cited as the most useful. Lack of time and heavy workload were salient personal barriers among practitioners in Australia and the United States, while lack of expertise in developing and implementing EBCDP interventions was more pertinent among practitioners from Brazil and China. Practitioners in all four countries described an organizational culture that was unsupportive of EBCDP. Practitioners in Brazil, China and the United States cited an inadequate number of staff support to implement EBCDP interventions. A few practitioners in Australia and China cited lack of access to evidence. Partnerships were emphasized as key facilitators to implementing EBCDP interventions across all countries. CONCLUSIONS: This study is novel in its cross-country qualitative exploration of multilevel constructs of EBCDP dissemination and implementation. The interviews produced rich findings about many contextual similarities and differences with EBCDP that can inform both cross-country and country-specific research and practice to address barriers and improve EBCDP implementation among the four countries long-term.

Osseodensification - A novel approach in implant dentistry.

Primary stability in dental implants is an essential factor for achieving successful osseointegration. Surgical procedure and bone quality are among the most common factors that affect primary stability. It is also crucial to achieve high-insertion torque which is important for obtaining primary stability. Maintaining sufficient bone bulk and density is essential to achieve necessary bone-to-implant contact for obtaining a biomechanically stable implant. A new concept for osteotomy called osseodensification (OD) has been at the forefront of changes in surgical site preparation in implantology. This relatively new concept with universally compatible drills has been proposed to help in better osteotomy preparation, bone densification, and indirect sinus lift and also achieve bone expansion at different sites of varying bone densities. This procedure has also shown improvement in achieving better implant primary stability and better osteotomy than conventional implant drills. A systematic review was undertaken to analyze if OD procedure had any advantages over conventional osteotomy on bone density and primary stability. An electronic database search was conducted in PubMed using keywords such as "OD," "implant primary stability," "implant bone density," and "implant osteotomy." A total of 195 articles were collected and subjected to screening using inclusion and exclusion criteria. A literature review was done, following which it was seen that the use of versah drills for bone OD resulted in undersized osteotomy compared to conventional drills. It also resulted in improved bone density and increase in percentage bone volume and bone-to-implant contact, thereby improving implant stability.

Health Insurance Information-Seeking Behaviors Among the Uninsured.

As a result of the Affordable Care Act, millions of previously uninsured individuals are facing the daunting task of selecting health insurance. In order to better understand how to reach the uninsured and support their health insurance decision making, this study examined where the uninsured collect information about health insurance and the extent to which they trust those sources and media. We analyzed secondary data on health insurance information-seeking behaviors collected from a survey of 343 uninsured individuals. The Internet, mail, and television were among the most frequently used media, though all 3 had low trust scores. Participants sought information from health care providers and interpersonal sources less frequently but trusted it more than they trusted the media. Age, gender, race, and education were predictors of use and trust of different media and sources of health insurance information. Findings suggest that strategies that pair health care professionals, lay health advisors, or community liaisons with the ubiquity of the Internet may be a strong approach for delivering quality health insurance information to the uninsured. Tailoring messages might also be effective at reaching specific subgroups of the uninsured.

Single-cell control of initial spatial structure in biofilm development using laser trapping.

Biofilms are sessile communities of microbes that are spatially structured by an embedding matrix. Biofilm infections are notoriously intractable. This arises, in part, from changes in the bacterial phenotype that result from spatial structure. Understanding these interactions requires methods to control the spatial structure of biofilms. We present a method for growing biofilms from initiating cells whose positions are controlled with single-cell precision using laser trapping. The native growth, motility, and surface adhesion of positioned microbes are preserved, as we show for model organisms Pseudomonas aeruginosa and Staphylococcus aureus. We demonstrate that laser-trapping and placing bacteria on surfaces can reveal the effects of spatial structure on bacterial growth in early biofilm development.