- Cost-Effectiveness of Scaling Up HCV Prevention and Treatment in the United States for People Who Inject Drugs. [Journal Article]
- AAddiction 2019 Jul 15
- CONCLUSIONS: Hepatitis C screening and treatment for people who inject drugs, combined with medication-assisted treatment and syringe-service programs, is a cost-effective strategy for reducing hepatitis C burden in the United States.
- Test of a clinical model of poor physical health and suicide: The role of depression, psychosocial stress, interpersonal conflict, and panic. [Journal Article]
- JAJ Affect Disord 2019 May 31; 257:404-411
- CONCLUSIONS: Firstly, the study sample was primarily Caucasian, limiting its generalizability. Secondly, causal inferences should be interpreted with caution, due to the quasi-experimental design. Thirdly, these data were self-reported, which create response biases since suicidal ideation is stigmatized.These findings highlight the importance of considering interpersonal factors as potential mediators in the relationship between poor physical health, mental illness, and suicide. Clinically, the impact of an active major depressive episode on an individual who is struggling with a serious physical illness may be strongly predictive of suicidal ideation.
- Analysis of mass transfer behavior in membrane distillation: Mathematical modeling under various conditions. [Journal Article]
- CChemosphere 2019 Jul 08; 236:124289
- Four commercially available hydrophobic membranes with different pore sizes were separately used in a direct contact membrane distillation (DCMD) apparatus to investigate the effect of fouling on the…
Four commercially available hydrophobic membranes with different pore sizes were separately used in a direct contact membrane distillation (DCMD) apparatus to investigate the effect of fouling on the mass transfer coefficient, and the dominant mass transport mode under different conditions defined by the temperature, membrane material, flow regime, and membrane pore size. Both ultrapure deionized water and simulated industrial wastewater were considered as the feed water. The results of the investigation confirmed that the fouling layer impacted the mass transport directly by resisting it, and indirectly by altering the heat transfer mechanism. In addition to the surface fouling layer, a significant number of particles were also observed to accumulate in the membrane pores. It was further determined that the contribution of Poiseuille flow to the entire mass transport was significant at higher temperatures when using a membrane with large pores. This highlighted the need for careful consideration of Poiseuille flow in the modeling and simulation of a membrane distillation (MD) mass transport process. It was also observed that the flow rate did not affect the Poiseuille flow and therefore did not directly impact the entire mass transfer. The study findings provide systematic insight for the development of a strategy for selecting an appropriate operating feed for DCMD and adjusting the permeate temperature to fit the prevailing water demand and environmental conditions.
- Initial third molar development is delayed in jaws with short distal space: An early impaction sign? [Journal Article]
- AOArch Oral Biol 2019 Jul 04; 106:104475
- CONCLUSIONS: Retromolar jaw space and M3 development are two positive correlates of M3 impaction that co-associate as early as childhood. Our results suggest that delayed initial M3 development merits investigation as a potential prognosticator for late M3 eruption relative to when jaw growth ceases - an outcome known to increase the likelihood of impaction.
- A rare TTC30B variant is identified as a candidate for synpolydactyly in a Chinese pedigree. [Journal Article]
- BONEBone 2019 Jul 12
- CONCLUSIONS: This study demonstrates for the first time that an IFT (intraflagellar transport) - related gene TTC30B is implicated with SPD.
- Investigation of the permeation enhancer strategy on benzoylaconitine transdermal patch: The relationship between transdermal enhancement strength and physicochemical properties of permeation enhancer. [Journal Article]
- EJEur J Pharm Sci 2019 Jul 12; :105009
- Permeation enhancer strategy is used to develop Benzoylaconitine (BA) of high molecular weight (603.7 Da) into transdermal patch. The present study was to achieve a patch with good analgesic and anti…
Permeation enhancer strategy is used to develop Benzoylaconitine (BA) of high molecular weight (603.7 Da) into transdermal patch. The present study was to achieve a patch with good analgesic and anti-inflammatory effects and investigate the relationship between physicochemical parameters of enhancers and enhancement strength. In vitro skin permeation study was used to evaluate the effect of enhancers, and correlation study was conducted to clarify the relationship between physicochemical parameters of enhancer and permeation amount. The enhancement molecular mechanism was characterized using FT-IR and molecular modeling. Finally, pharmacodynamic effect of BA patch was evaluated with analgesic and anti-inflammatory assessment. The correlation analysis indicated that the optimized patch containing permeation enhancer Plurol® Oleique CC497 with high surface tension (43.0 dyne/m), demonstrated the strongest skin permeation amount of 5.50 ± 0.21 μg/cm2. According to the FT-IR and molecular modeling study, the enhancer with high surface tension demonstrated maximum interaction strength (Emix = -9.20 kcal/mol) with skin lipid and affected the skin protein region, which strongly disturbed skin lipid arrangement according to the results of ATR-FTIR study (wavenumber variation of νas CH2 of skin lipid > 2.00 cm-1) and molecular modeling (Cohesive Energy Density of skin lipid bilayer = 1.04E + 08 kcal/mol). It was indicated that only based on sufficient interaction strength and disturbing of both lipophilic and hydrophilic area of stratum corneum, permeation enhancer was able to demonstrated great permeation enhancement effect. Finally, BA transdermal patch was developed and showed excellent analgesic and anti-inflammatory effect, which was a potential preparation for the treatment of inflammatory pain.
- The Glucagon-Like Peptide 2 Analog Teduglutide Reversibly Associates to Form Pentamers. [Journal Article]
- JPJ Pharm Sci 2019 Jul 12
- Glucagon-like peptide 1 and 2 (GLP-1 and GLP-2) and their analog peptide therapeutics are known to reversibly associate to form oligomers. Here we report the association properties of the GLP-2 analo…
Glucagon-like peptide 1 and 2 (GLP-1 and GLP-2) and their analog peptide therapeutics are known to reversibly associate to form oligomers. Here we report the association properties of the GLP-2 analog teduglutide at concentrations up to ∼15 mg/mL. Both sedimentation equilibrium (SE-AUC) and sedimentation velocity (SV-AUC) show that teduglutide dissociates completely to monomers below 0.1 mg/mL. SE-AUC shows that the apparent weight-average molar mass increases substantially between 0.1 and 1 mg/mL, reaching a maximum of ∼14.5 kDa (∼3.9-mer) near 2 mg/mL, and then falling at higher concentrations due to strong solution non-ideality effects (highly positive second virial coefficient). Circular dichroism spectra over the range from 0.1 to 2 mg/mL show that self-association is accompanied by significant increases in alpha-helix content, and that the associated state has a distinct tertiary structure. The SV-AUC data up to 2.2 mg/mL are fitted fairly well by an ideal rapidly-reversible monomer-pentamer association. The SE-AUC modeling included thermodynamic non-ideality effects. SE-AUC data up to ∼15 mg/ml imply a monomer-pentamer association at lower concentrations, but the pentamers also appear to weakly associate to form decamers. These results illustrate the importance of directly modeling the solution non-ideality effects, which if neglected would lead to an incorrect preferred stoichiometry.
- Early Risk Factors and Emotional Difficulties in Children at Risk of Developmental Language Disorder: A Population Cohort Study. [Journal Article]
- JSJ Speech Lang Hear Res 2019 Jul 12; :1-22
- Purpose This study evaluated the pathways between developmental language disorder (DLD), psychosocial risk factors, and the development of emotional difficulties from ages 3 to 11 years within the Mi…
Purpose This study evaluated the pathways between developmental language disorder (DLD), psychosocial risk factors, and the development of emotional difficulties from ages 3 to 11 years within the Millennium Cohort Study. Method A total of 14,494 singletons (49.4% female) from the Millennium Cohort Study were evaluated within this study. Risk of DLD (rDLD) was defined as age 5 parent-reported language problems and/or -1.5 SDs on a Naming Vocabulary subtest at the age of 5 years. Children without rDLD formed the general population comparison group. Psychosocial risk factors included 9-month temperamental traits, parental psychological distress, and maternal attachment as well as age 3 emotional regulation abilities, parent-child relationship, and peer problems. The parent report Strengths and Difficulties Questionnaire Emotional Difficulty subscale at 3, 5, 7, and 11 years of age was the outcome variable. The trajectory of emotional difficulties was evaluated within a variable-centered approach and a person-centered approach, using growth mixture modeling. Results Children with rDLD (n = 884) had increased levels of emotional problems when compared to the general population group (n = 13,344). Psychosocial risk factors were increased in children with rDLD, fully mediated the increased emotional difficulties at 3 years, and partially mediated the increased emotional difficulties at 11 years. Children with rDLD were more likely to be included in emotional trajectory subgroups with an increasing pattern of emotional problems. rDLD was an additional risk factor for lower levels of emotional self-regulation and increased peer problems when controlling for the emotional difficulties trajectory subgroup. Conclusion This article indicates that the increased emotional difficulties found in children with rDLD are likely a function of early language difficulties influencing other domains of development, specifically social interactions (parent and peer) and emotional self-regulation abilities. Clinically, this reiterates the importance of early identification and treatment of children with language delays or clinical level language disorders. Supplemental Material https://doi.org/10.23641/asha.8323598.
- Back home? Uncertainties for returning seized animals to the source-areas under climate change. [Journal Article]
- GCGlob Chang Biol 2019 Jul 15
- Regardless of the economic, social and environmental impacts caused by wild animal trafficking worldwide, the suitable destination of seized specimens is one of the main challenges faced by environme…
Regardless of the economic, social and environmental impacts caused by wild animal trafficking worldwide, the suitable destination of seized specimens is one of the main challenges faced by environmental managers and authorities. In Brazil, returning seized animals to the wild has been the most frequent path in population restoration programs, and has been carried out, as a priority, in areas where the animals were captured. However, in addition to the difficulty in identifying the locations of illegal captures, little scientific knowledge is available on the future viability of the source-areas to global climate change. Thus, the current work aims to evaluate the impacts of climate change on the main source-municipalities for animal trafficking in Brazil, referred to herein as source-areas. For this, using ecological niche modeling, the environmental suitability of the source-areas for illegal animal captures was evaluated in two scenarios at two differ time horizons: optimistic (RCP 26) and a pessimistic (RCP 85) emission scenarios in both 2050 and 2070 projections. Moreover, the source-areas were compared with the Brazilian Federal protected areas, used here as the control group. According to the results, Brazilian source-municipalities are not always the best option for maintaining the most seized species in the future simulations, and, therefore, seem not be the best option for projects that aim for the return of these animals to the wild. In this sense, despite the genetic and ecological issues inherent in translocation projects, our results suggest that population restoration programs for seized species need to be rethought, and furthermore other suitable areas could be considered for truly ensuring the survival and maintenance of overexploited populations in the long-term. This article is protected by copyright. All rights reserved.
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- Circular Zymogens of Human Ribonuclease 1. [Journal Article]
- PSProtein Sci 2019 Jul 15
- The endogenous production of enzymes as zymogens provides a means to control catalytic activities. Here, we describe the heterologous production of ribonuclease 1 (RNase 1), which is the most prevale…
The endogenous production of enzymes as zymogens provides a means to control catalytic activities. Here, we describe the heterologous production of ribonuclease 1 (RNase 1), which is the most prevalent secretory ribonuclease in humans, as a zymogen. In folded RNase 1, the N and C termini flank the enzymic active site. By using intein-mediated cis-splicing, we created circular proteins in which access to the active site of RNase 1 is obstructed by an amino-acid sequence that is recognized by the HIV-1 protease. Installing a sequence that does not perturb the RNase 1 fold led to only modest inactivation. In contrast, the ancillary truncation of residues from each terminus led to a substantial decrease in the catalytic activity of the zymogen with the maintenance of thermostability. For optimized zymogens, activation by HIV-1 protease led to a > 104 -fold increase in ribonucleolytic activity at a rate comparable to that for the cleavage of endogenous viral substrates. Molecular modeling indicated that these zymogens are inactivated by conformational distortion in addition to substrate occlusion. Because protease levels are elevated in many disease states and ribonucleolytic activity can be cytotoxic, RNase 1 zymogens have potential as generalizable prodrugs. This article is protected by copyright. All rights reserved.