Volatile Organic Compounds and Pulmonary Function in the Third National Health and Nutrition Examination Survey, 1988–1994

BACKGROUND: Volatile organic compounds (VOCs) are present in much higher concentrations indoors, where people spend most of their time, than outdoors and may have adverse health effects. VOCs have been associated with respiratory symptoms, but few studies address objective respiratory end points such as pulmonary function. Blood levels of VOCs may be more indicative of personal exposures than are air concentrations; no studies have addressed their relationship with respiratory outcomes. OBJECTIVE: We examined whether concentrations of 11 VOCs that were commonly identified in blood from a sample of the U.S. population were associated with pulmonary function. METHODS: We used data from 953 adult participants (20–59 years of age) in the Third National Health and Nutrition Examination Survey (1988–1994) who had VOC blood measures as well as pulmonary function measures. Linear regression models were used to evaluate the relationship between 11 VOCs and measures of pulmonary function. RESULTS: After adjustment for smoking, only 1,4-dichlorobenzene (1,4-DCB) was associated with reduced pulmonary function. Participants in the highest decile of 1,4-DCB concentration had decrements of −153 mL [95% confidence interval (CI), −297 to −8] in forced expiratory volume in 1 sec and −346 mL/sec (95% CI, −667 to −24) in maximum mid-expiratory flow rate, compared with participants in the lowest decile. CONCLUSIONS: Exposure to 1,4-DCB, a VOC related to the use of air fresheners, toilet bowl deodorants, and mothballs, at levels found in the U.S. general population, may result in reduced pulmonary function. This common exposure may have long-term adverse effects on respiratory health

Thermostability-based binding assays reveal complex interplay of cation, substrate and lipid binding in the bacterial DASS transporter, VcINDY

The divalent anion sodium symporter (DASS) family of transporters (SLC13 family in humans) are key regulators of metabolic homeostasis, disruption of which results in pro- tection from diabetes and obesity, and inhibition of liver cancer cell proliferation. Thus, DASS transporter inhibitors are attractive targets in the treatment of chronic, age-related metabolic diseases. The characterisation of several DASS transporters has revealed vari- ation in the substrate selectivity and flexibility in the coupling ion used to power transport. Here, using the model DASS co-transporter, VcINDY from Vibrio cholerae, we have exam- ined the interplay of the three major interactions that occur during transport: the coupling ion, the substrate, and the lipid environment. Using a series of high-throughput thermo- stability-based interaction assays, we have shown that substrate binding is Na+-depend- ent; a requirement that is orchestrated through a combination of electrostatic attraction and Na+-induced priming of the binding site architecture. We have identified novel DASS ligands and revealed that ligand binding is dominated by the requirement of two carb- oxylate groups in the ligand that are precisely distanced to satisfy carboxylate interaction regions of the substrate-binding site. We have also identified a complex relationship between substrate and lipid interactions, which suggests a dynamic, regulatory role for lipids in VcINDY’s transport cycle

Solvent accessibility changes in a Na+-dependent C4-dicarboxylate transporter suggest differential substrate effects in a multistep mechanism

The divalent anion sodium symporter (DASS) family (SLC13) play critical roles in metabolic homeostasis, influencing many processes including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyse the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrate-induced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested are modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na+ and succinate. We also observe separable effects of Na+ and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na+ binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate binding site-associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structural-characterised representative of the entire DASS family

Improved clinical outcome measures of knee pain and function with concurrent resolution of subchondral Bone Marrow Edema Lesion and joint effusion in an osteoarthritic patient following Pentosan Polysulphate Sodium treatment: a case report

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background At present, there are no registered products for the treatment of subchondral Bone Marrow Edema Lesion (BML) and associated knee pain. Patients who do not respond to current anti-inflammatory therapies are left with limited treatment options, and may resort to operative management with Total Knee Arthroplasty (TKA). We report the use of Pentosan Polysulphate Sodium (PPS) for the treatment of BMLs of the knee. Case presentation We report the case of a 70-year-old female with knee osteoarthritis presenting with a high level of knee pain, scoring 8 on the Numerical Rating Scale (NRS), and functional limitation demonstrating a poor Lysholm Knee Score of 37. MRI scans of the knee revealed subchondral BML in the medial femoral condyle and medial tibial plateau. The patient was administered a course of Pentosan Polysulphate Sodium (PPS) intramuscularly twice weekly, for 3 weeks. MRI scans 2 weeks post-treatment showed complete resolution of the bone marrow edema at the medial femoral condyle and medial tibial plateau with concomitant recovery from pain (NRS pain score of 0), and a 43% improvement of the Lysholm Knee Score. In addition, marked reduction in joint effusion was also demonstrated in the MRI scan post PPS therapy. Conclusion The MRI interpretations demonstrate improved clinical outcome measures ensuing therapeutic intervention with PPS, and warranting further investigation into the efficacy of PPS in the treatment of BML associated pain and dysfunction in the osteoarthritic population via randomized controlled trial, or equivalent rigorous methodological technique

Fusion Assessment by MRI in Comparison With CT in Anterior Lumbar Interbody Fusion: A Prospective Study

Copyright The Author(s) 2018 Creative Commons Non Commercial No Derivs CC BY-NC-ND: This article is distributed under the terms of the Creative Commons Attribution-Non Commercial-NoDerivs 4.0 License (http://www.creativecommons.org/licenses/by-nc-nd/4.0/) which permits non-commercial use, reproduction and distribution of the work as published without adaptation or alteration, without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Study Design: Prospective cohort study. Objectives: To evaluate the role of magnetic resonance imaging (MRI) in evaluation of fusion status following anterior lumbar interbody fusion (ALIF) and compare agreement and confidence in assessing fusion or its absence on MRI to the current standard computed tomography (CT). Methods: A prospective follow up of patients undergoing surgery by 2 spine surgeons between 2012 and 2015 at a single institution. Fusion was assessed at different time points in these patients by 2 independent musculoskeletal radiologists. Fusion was analyzed in coronal and sagittal planes using both imaging modalities, with confidence being attributed on a scale of 0 to 3. Assessors were blinded to patient data. Results: Fourteen patients (25 levels) with mean follow-up of 10.2 months (range 2.4-20.3 years) and age of 41 years (range 20.7-61.5 years) were assessed. MRI within the interbody cage in coronal (κ = .58) and sagittal (κ = .50) planes had the highest interobserver agreement. CT anterior to the cage in coronal (κ = .48) and sagittal (κ = .44) planes, as well as within the cage in coronal (κ = .50) and sagittal planes (κ = .44) showed moderate agreement. Confidence anterior to the interbody cage using MRI scan was reduced when compared with remaining angles and imaging modalities. Conclusions: The study demonstrates that MRI may be a useful tool in the assessment of fusion following ALIF with results comparable to CT, and that it may have a useful role in select patients especially considering marked radiation exposure reduction

The Variation of Mechanical Properties of M300 Maraging Steel Manufactured with Varying Process Parameters in Laser Powder Bed Fusion

Laser power bed fusion (L-PBF) is a type of additive manufacturing (AM) that uses layers of powdered metal and a laser to manufacture a part in a layer-by-layer fashion. L-PBF uses a variety of process parameters that ultimately determine the overall quality and mechanical properties of a print. The ability to alter parameters allows for the utilization of various metals in this form of AM. Maraging 300 steel (M300) is a material of particular interest due to its combined tensile strength and high strength-to-weight ratio. By using an assortment of parameters and comparing the resulting mechanical properties it can be determined which process parameters result in a more favorable part to be used in a variety of applications. A favorable process parameter set was selected for future use. This study aims to determine which process parameters result in the best overall mechanical properties of M300 manufactured using L-PBF.Mechanical Engineerin

Predictive validity and correlates of selfâ assessed resilience among U.S. Army soldiers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142339/1/da22694.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142339/2/da22694_am.pd

Alcohol Misuse and Coâ Occurring Mental Disorders Among New Soldiers in the U.S. Army

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135492/1/acer13269_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135492/2/acer13269.pd