Browsing by Subject "Humans"

Now showing 1 - 20 of 4738

Open Access
10 Years with ICH E10: Choice of Control Groups.
(Pharm Stat, 2011-09) Rockhold, Frank W; Enas, Gregory G
Open Access
18F-FDG-PET/CT Imaging for Gastrointestinal Malignancies.
(Radiologic clinics of North America, 2021-09) Howard, Brandon A; Wong, Terence Z
Gastrointestinal malignancies encompass a variety of primary tumor sites, each with different staging criteria and treatment approaches. In this review we discuss technical aspects of 18F-FDG-PET/CT scanning to optimize information from both the PET and computed tomography components. Specific applications for 18F-FDG-PET/CT are summarized for initial staging and follow-up of the major disease sites, including esophagus, stomach, hepatobiliary system, pancreas, colon, rectum, and anus.
Open Access
2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.
(Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2023-05) Ferrick, Aileen M; Raj, Satish R; Deneke, Thomas; Kojodjojo, Pipin; Lopez-Cabanillas, Nestor; Abe, Haruhiko; Boveda, Serge; Chew, Derek S; Choi, Jong-Il; Dagres, Nikolaos; Dalal, Aarti S; Dechert, Brynn E; Frazier-Mills, Camille G; Gilbert, Olivia; Han, Janet K; Hewit, Sherri; Kneeland, Christine; Mirza, Starr DeEllen; Mittal, Suneet; Ricci, Renato Pietro; Runte, Mary; Sinclair, Susan; Alkmim-Teixeira, Ricardo; Vandenberk, Bert; Varma, Niraj; Davenport, Elizabeth; Freedenberg, Vicki; Glotzer, Taya V; Huang, Jin-Long; Ikeda, Takanori; Kramer, Daniel B; Lin, David; Rojel-Martínez, Ulises; Stühlinger, Markus; Varosy, Paul D
Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.
Open Access
29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome.
(PloS one, 2012-01) Lowe, Craig B; Haussler, David
Recent research supports the view that changes in gene regulation, as opposed to changes in the genes themselves, play a significant role in morphological evolution. Gene regulation is largely dependent on transcription factor binding sites. Researchers are now able to use the available 29 mammalian genomes to measure selective constraint at the level of binding sites. This detailed map of constraint suggests that mammalian genomes co-opt fragments of mobile elements to act as gene regulatory sequence on a large scale. In the human genome we detect over 280,000 putative regulatory elements, totaling approximately 7 Mb of sequence, that originated as mobile element insertions. These putative regulatory regions are conserved non-exonic elements (CNEEs), which show considerable cross-species constraint and signatures of continued negative selection in humans, yet do not appear in a known mature transcript. These putative regulatory elements were co-opted from SINE, LINE, LTR and DNA transposon insertions. We demonstrate that at least 11%, and an estimated 20%, of gene regulatory sequence in the human genome showing cross-species conservation was co-opted from mobile elements. The location in the genome of CNEEs co-opted from mobile elements closely resembles that of CNEEs in general, except in the centers of the largest gene deserts where recognizable co-option events are relatively rare. We find that regions of certain mobile element insertions are more likely to be held under purifying selection than others. In particular, we show 6 examples where paralogous instances of an often co-opted mobile element region define a sequence motif that closely matches a transcription factor's binding profile.
Open Access
3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.
(Br J Cancer, 1997) Vaidyanathan, G; Zhao, XG; Larsen, RH; Zalutsky, MR
An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was replaced with fluorine has been found to possess many properties similar to those of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine (FIBG) was retained in vitro by human neuroblastoma cells to a much greater extent than MIBG itself. Since alpha-emitters such as 211At could be valuable for the treatment of micrometastatic disease, an FIBG analogue in which the iodine atom is replaced by 211At would be of interest. In this study, we have evaluated the in vitro and in vivo properties of 3-[211At]astato-4-fluorobenzylguanidine ([211At]AFBG). The specific binding of [211At]AFBG to SK-N-SH human neuroblastoma cells remained fairly constant over 2- to 3-log activity range and was similar to that of [131I]MIBG. The uptake of [211At]AFBG by this cell line was reduced by desipramine, ouabain, 4 degrees C incubation, noradrenaline, unlabelled MIBG and FIBG, suggesting that its uptake is specifically mediated through an active uptake-1 mechanism. Over the 16 h period studied, the amount of [211At]AFBG retained was similar to that of [131I]FIBG, whereas the per cent of retained meta-[211At]astatobenzylguanidine ([211At]MABG) was considerably less than that of [131I]FIBG (53% vs 75%; P < 0.05). The IC50 values for the inhibition of uptake of [131I]MIBG, [211At]MABG, [125I]FIBG and [211At]AFBG by unlabelled MIBG were 209, 300, 407 and 661 nM respectively, suggesting that the affinities of these tracers for the noradrenaline transporter in SK-N-SH cells increase in that order. Compared with [211At]MABG, higher uptake of [211At]AFBG was seen in vivo in normal mouse target tissues such as heart and, to a certain extent, in adrenals. That the uptake of [211At]AFBG in these tissues was related to the uptake-1 mechanism was demonstrated by its reduction when mice were pretreated with desipramine. However, the stability of [211At]AFBG towards in vivo dehalogenation was less than that of [211At]MABG, as evidenced by the higher uptake of 211At in thyroid, spleen, lungs and stomach.
Open Access
3D refraction correction and extraction of clinical parameters from spectral domain optical coherence tomography of the cornea.
(Opt Express, 2010-04-26) Zhao, Mingtao; Kuo, Anthony N; Izatt, Joseph A
Capable of three-dimensional imaging of the cornea with micrometer-scale resolution, spectral domain-optical coherence tomography (SDOCT) offers potential advantages over Placido ring and Scheimpflug photography based systems for accurate extraction of quantitative keratometric parameters. In this work, an SDOCT scanning protocol and motion correction algorithm were implemented to minimize the effects of patient motion during data acquisition. Procedures are described for correction of image data artifacts resulting from 3D refraction of SDOCT light in the cornea and from non-idealities of the scanning system geometry performed as a pre-requisite for accurate parameter extraction. Zernike polynomial 3D reconstruction and a recursive half searching algorithm (RHSA) were implemented to extract clinical keratometric parameters including anterior and posterior radii of curvature, central cornea optical power, central corneal thickness, and thickness maps of the cornea. Accuracy and repeatability of the extracted parameters obtained using a commercial 859nm SDOCT retinal imaging system with a corneal adapter were assessed using a rigid gas permeable (RGP) contact lens as a phantom target. Extraction of these parameters was performed in vivo in 3 patients and compared to commercial Placido topography and Scheimpflug photography systems. The repeatability of SDOCT central corneal power measured in vivo was 0.18 Diopters, and the difference observed between the systems averaged 0.1 Diopters between SDOCT and Scheimpflug photography, and 0.6 Diopters between SDOCT and Placido topography.
Open Access
3D-Printed Microneedles Create Precise Perforations in Human Round Window Membrane in Situ.
(Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2020-02) Chiang, Harry; Yu, Michelle; Aksit, Aykut; Wang, Wenbin; Stern-Shavit, Sagit; Kysar, Jeffrey W; Lalwani, Anil K
Hypothesis
Three-dimensional (3D)-printed microneedles can create precise holes on the scale of micrometers in the human round window membrane (HRWM).
Background
An intact round window membrane is a barrier to delivery of therapeutic and diagnostic agents into the inner ear. Microperforation of the guinea pig round window membrane has been shown to overcome this barrier by enhancing diffusion 35-fold. In humans, the challenge is to design a microneedle that can precisely perforate the thicker HRWM without damage.
Methods
Based on the thickness and mechanical properties of the HRWM, two microneedle designs were 3D-printed to perforate the HRWM from fresh frozen temporal bones in situ (n = 18 total perforations), simultaneously measuring force and displacement. Perforations were analyzed using confocal microscopy; microneedles were examined for deformity using scanning electron microscopy.
Results
HRWM thickness was determined to be 60.1 ± 14.6 (SD) μm. Microneedles separated the collagen fibers and created slit-shaped perforations with the major axis equal to the microneedle shaft diameter. Microneedles needed to be displaced only minimally after making initial contact with the RWM to create a complete perforation, thus avoiding damage to intracochlear structures. The microneedles were durable and intact after use.
Conclusion
3D-printed microneedles can create precise perforations in the HRWM without damaging intracochlear structures. As such, they have many potential applications ranging from aspiration of cochlear fluids using a lumenized needle for diagnosis and creating portals for therapeutic delivery into the inner ear.
Open Access
3Rs for innovating novel antibiotics: sharing resources, risks, and rewards.
(BMJ, 2012-04-03) So, Anthony D; Ruiz-Esparza, Quentin; Gupta, Neha; Cars, Otto
Unknown
5-α reductase inhibitors and prostate cancer prevention: where do we turn now?
(BMC Med, 2011-09-15) Hamilton, Robert J; Freedland, Stephen J
With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research.
Open Access
A 13-Year-Old Girl With Unilateral Visual Changes.
(Journal of investigative medicine high impact case reports, 2023-01) Sykes, David AW; Joseph, Suzanna L; Williams, Shannon P; Das, Samrat U
Neuroretinitis is a condition typically characterized by unilateral optic neuropathy and is most commonly a sequelae of cat scratch disease (CSD) due to infection with Bartonella henselae. Ophthalmologic examination will reveal a swollen optic nerve and may eventually reveal a canonical macular star; optical coherence tomography (OCT) will reveal flattening of the fovea, a thickened neurosensory retina, and subretinal fluid accumulation. Although CSD rarely presents with isolated neuorretinitis, it should be considered in patients presenting with unilateral visual changes. The differential diagnosis for neuroretinitis includes optic neuritis, inflammatory optic neuropathies (sarcoid, para-infectious, autoimmune), compressive, toxic, and more. We describe a pediatric patient presenting with visual changes that were initially concerning for optic neuritis and the diagnostic workup that ultimately led to a diagnosis of CSD neuroretinitis.
Open Access
A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS).
(Orphanet journal of rare diseases, 2023-11) Gentile, Luca; Coelho, Teresa; Dispenzieri, Angela; Conceição, Isabel; Waddington-Cruz, Márcia; Kristen, Arnt; Wixner, Jonas; Diemberger, Igor; Gonzalez-Moreno, Juan; Cariou, Eve; Maurer, Mathew S; Planté-Bordeneuve, Violaine; Garcia-Pavia, Pablo; Tournev, Ivailo; Gonzalez-Costello, Jose; Duarte, Alejandra Gonzalez; Grogan, Martha; Mazzeo, Anna; Chapman, Doug; Gupta, Pritam; Glass, Oliver; Amass, Leslie; THAOS investigators
Background
Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs.
Methods
Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry.
Results
This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5).
Conclusions
This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis.
Trial registration
ClinicalTrials.gov Identifier: NCT00628745.
Open Access
A 17-Year-Old Girl With Unilateral Headache and Double Vision.
(Journal of investigative medicine high impact case reports, 2019-01) Rodriguez-Homs, Larissa G; Goerlitz-Jessen, Mark; Das, Samrat U
Tolosa-Hunt syndrome is characterized by a painful ophthalmoplegia secondary to a granulomatous inflammation in or adjacent to the cavernous sinus. Magnetic resonance imaging will show enhancement of the cavernous sinus and/or the orbital apex. Although this syndrome is extremely rare in children, it should be a diagnostic consideration in patients presenting with painful ophthalmoplegia with variable involvement of cranial nerves II to VI. The differential diagnosis for unilateral cavernous sinus lesion is broad, including vascular lesions (cavernous sinus thrombosis), inflammatory processes (sarcoidosis, autoimmune), neoplastic processes (schwannoma, lymphoma), as well as infectious etiologies. We describe a pediatric patient presenting with neurological symptoms from a unilateral cavernous sinus magnetic resonance imaging abnormality and the thorough diagnostic approach to arrive at the diagnosis of Tolosa-Hunt syndrome.
Open Access
A blinded study using laser induced endogenous fluorescence spectroscopy to differentiate ex vivo spine tumor, healthy muscle, and healthy bone.
(Scientific reports, 2024-01) Sperber, Jacob; Zachem, Tanner J; Prakash, Ravi; Owolo, Edwin; Yamamoto, Kent; Nguyen, Annee D; Hockenberry, Harrison; Ross, Weston A; Herndon, James E; Codd, Patrick J; Goodwin, C Rory
Ten patients undergoing surgical resection for spinal tumors were selected. Samples of tumor, muscle, and bone were resected, de-identified by the treating surgeon, and then scanned with the TumorID technology ex vivo. This study investigates whether TumorID technology is able to differentiate three different human clinical fresh tissue specimens: spine tumor, normal muscle, and normal bone. The TumorID technology utilizes a 405 nm excitation laser to target endogenous fluorophores, thereby allowing for the detection of tissue based on emission spectra. Metabolic profiles of tumor and healthy tissue vary, namely NADH (bound and free emission peak, respectively: 487 nm, 501 nm) and FAD (emission peak: 544) are endogenous fluorophores with distinct concentrations in tumor and healthy tissue. Emission spectra analyzed consisted of 74 scans of spine tumor, 150 scans of healthy normal bone, and 111 scans of healthy normal muscle. An excitation wavelength of 405 nm was used to obtain emission spectra from tissue as previously described. Emission spectra consisted of approximately 1400 wavelength intensity pairs between 450 and 750 nm. Kruskal-Wallis tests were conducted comparing AUC distributions for each treatment group, α = 0.05. Spectral signatures varied amongst the three different tissue types. All pairwise comparisons among tissues for Free NADH were statistically significant (Tumor vs. Muscle: p = 0.0006, Tumor vs. Bone: p < 0.0001, Bone vs. Muscle: p = 0.0357). The overall comparison of tissues for FAD (506.5-581.5 nm) was also statistically significant (p < 0.0001), with two pairwise comparisons being statistically significant (Tumor vs. Muscle: p < 0.0001, Tumor vs. Bone: p = 0.0045, Bone vs. Muscle: p = 0.249). These statistically significant differences were maintained when stratifying tumor into metastatic carcinoma (N = 57) and meningioma (N = 17). TumorID differentiates tumor tissue from normal bone and normal muscle providing further clinical evidence of its efficacy as a tissue identification tool. Future studies should evaluate TumorID's ability to serve as an adjunctive tool for intraoperative assessment of surgical margins and surgical decision-making.
Open Access
A blood-based biomarker panel to risk-stratify mild traumatic brain injury.
(PloS one, 2017-01) Sharma, Richa; Rosenberg, Alexandra; Bennett, Ellen R; Laskowitz, Daniel T; Acheson, Shawn K
Mild traumatic brain injury (TBI) accounts for the vast majority of the nearly two million brain injuries suffered in the United States each year. Mild TBI is commonly classified as complicated (radiographic evidence of intracranial injury) or uncomplicated (radiographically negative). Such a distinction is important because it helps to determine the need for further neuroimaging, potential admission, or neurosurgical intervention. Unfortunately, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are costly and not without some risk. The purpose of this study was to screen 87 serum biomarkers to identify a select panel of biomarkers that would predict the presence of intracranial injury as determined by initial brain CT. Serum was collected from 110 patients who sustained a mild TBI within 24 hours of blood draw. Two models were created. In the broad inclusive model, 72kDa type IV collagenase (MMP-2), C-reactive protein (CRP), creatine kinase B type (CKBB), fatty acid binding protein-heart (hFABP), granulocyte-macrophage colony-stimulating factor (GM-CSF) and malondialdehyde modified low density lipoprotein (MDA-LDL) significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.975 and a negative predictive value (NPV) of 98.6. In the parsimonious model, MMP-2, CRP, and CKBB type significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.964 and a negative predictive value (NPV) of 97.2. These results suggest that a serum based biomarker panel can accurately differentiate patients with complicated mild TBI from those with uncomplicated mild TBI. Such a panel could be useful to guide early triage decisions, including the need for further evaluation or admission, especially in those environments in which resources are limited.
Open Access
A bony Chance fracture through L1 following posterior spinal fusion for adolescent idiopathic scoliosis: a case report.
(Spine deformity, 2021-05) Rocos, Brett; Kato, So; Lebel, David; Lewis, Stephen
Study design
Case report.
Introduction
Instrumented posterior fusion using pedicle screws has been the mainstay of the surgical correction of adolescent idiopathic scoliosis since it was popularised by Roy-Camille in the 1970s. The aim of this case report is to describe the occurrence and salvage of an L1 chance fracture occurring through the lower instrumented vertebra following pedicle screw placement for posterior spinal instrumented fusion in the treatment of adolescent idiopathic scoliosis (AIS).
Case report
A 15-year-old female patient underwent T2-L1 posterior instrumented fusion for a Lenke 1b deformity. The selection of fusion levels was made based upon standing and bending radiographs which showed a non-structural lumbar curve. Early recovery was uneventful. At 6 months post-operatively, the patient reported new deformity and pain. A chance fracture at L1 was diagnosed and subsequent extension of instrumentation to L3 was carried out. Final post-operative recovery was uneventful and the patient returned to an active lifestyle.
Conclusion
Several factors can contribute to the occurrence of a fracture through an instrumented pedicle. This case shows that there must be due consideration of the small pedicle at L1 when it is chosen as the LIV.
Open Access
A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins.
(Proc Natl Acad Sci U S A, 1998-07-21) Hall, RA; Ostedgaard, LS; Premont, RT; Blitzer, JT; Rahman, N; Welsh, MJ; Lefkowitz, RJ
The Na+/H+ exchanger regulatory factor (NHERF) binds to the tail of the beta2-adrenergic receptor and plays a role in adrenergic regulation of Na+/H+ exchange. NHERF contains two PDZ domains, the first of which is required for its interaction with the beta2 receptor. Mutagenesis studies of the beta2 receptor tail revealed that the optimal C-terminal motif for binding to the first PDZ domain of NHERF is D-S/T-x-L, a motif distinct from those recognized by other PDZ domains. The first PDZ domain of NHERF-2, a protein that is 52% identical to NHERF and also known as E3KARP, SIP-1, and TKA-1, exhibits binding preferences very similar to those of the first PDZ domain of NHERF. The delineation of the preferred binding motif for the first PDZ domain of the NHERF family of proteins allows for predictions for other proteins that may interact with NHERF or NHERF-2. For example, as would be predicted from the beta2 receptor tail mutagenesis studies, NHERF binds to the tail of the purinergic P2Y1 receptor, a seven-transmembrane receptor with an intracellular C-terminal tail ending in D-T-S-L. NHERF also binds to the tail of the cystic fibrosis transmembrane conductance regulator, which ends in D-T-R-L. Because the preferred binding motif of the first PDZ domain of the NHERF family of proteins is found at the C termini of a variety of intracellular proteins, NHERF and NHERF-2 may be multifunctional adaptor proteins involved in many previously unsuspected aspects of intracellular signaling.
Open Access
A case of frontal neuropsychological and neuroimaging signs following multiple primary-blast exposure.
(Neurocase, 2012-06) Hayes, Jasmeet Pannu; Morey, Rajendra A; Tupler, Larry A
Blast-related traumatic brain injury (TBI) from the Afghanistan and Iraq wars represents a significant medical concern for troops and veterans. To better understand the consequences of primary-blast injury in humans, we present a case of a Marine exposed to multiple primary blasts during his 14-year military career. The neuropsychological profile of this formerly high-functioning veteran suggested primarily executive dysfunction. Diffusion-tensor imaging revealed white-matter pathology in long fiber tracks compared with a composite fractional-anisotropy template derived from a veteran reference control group without TBI. This study supports the existence of primary blast-induced neurotrauma in humans and introduces a neuroimaging technique with potential to discriminate multiple-blast TBI.
Open Access
A case study of inclusion of rural populations in research: Implications for science and health equity.
(Clinical and translational science, 2024-08) Noonan, Devon; Lam, Wendy KK; Goodrich, James; Sullivan, Sydney; Bentley-Edwards, Keisha; Koeberl, Dwight; Palipana, Anushka; McClernon, F Joseph
Prior research highlights that rural populations have been historically underrepresented/excluded from clinical research. The primary objective of this study was to describe the inclusion of rural populations within our research enterprise using Clinical Research Management System demographic information at a large academic medical center in the Southeast. This was a cross-sectional study using participant demographic information for all protocols entered into our Clinical Research Management System between May 2018 and March 2021. Descriptive statistics were used to analyze the representation of rural and non-rural participants and demographic breakdown by age, sex, race, and ethnicity for our entire enterprise and at the state level. We also compared Material Community Deprivation Index levels between urban and rural participants. Results indicated that 19% of the research population was classified as rural and 81% as non-rural for our entire sample, and 17.5% rural and 82.5% urban for our state-level sample. There were significant differences in race, sex, and age between rural and non-rural participants and Material Community Deprivation Indices between rural and non-rural participants. Lessons learned and recommendations for increasing the inclusion of rural populations in research are discussed.
Open Access
A case-control study of airways obstruction among construction workers.
(Am J Ind Med, 2015-10) Dement, John; Welch, Laura; Ringen, Knut; Quinn, Patricia; Chen, Anna; Haas, Scott
BACKGROUND: While smoking is the major cause of chronic obstructive pulmonary disease (COPD), occupational exposures to vapors, gases, dusts, and fumes (VGDF) increase COPD risk. This case-control study estimated the risk of COPD attributable to occupational exposures among construction workers. METHODS: The study population included 834 cases and 1243 controls participating in a national medical screening program for older construction workers between 1997 and 2013. Qualitative exposure indices were developed based on lifetime work and exposure histories. RESULTS: Approximately 18% (95% CI = 2-24%) of COPD risk can be attributed to construction-related exposures, which are additive to the risk contributed by smoking. A measure of all VGDF exposures combined was a strong predictor of COPD risk. CONCLUSIONS: Construction workers are at increased risk of COPD as a result of broad and complex effects of many exposures acting independently or interactively. Control methods should be implemented to prevent worker exposures, and smoking cessation should be promoted.
Open Access
A cellular genome-wide association study reveals human variation in microtubule stability and a role in inflammatory cell death.
(Mol Biol Cell, 2014-01) Salinas, Raul E; Ogohara, Cassandra; Thomas, Monica I; Shukla, Kajal P; Miller, Samuel I; Ko, Dennis C
Pyroptosis is proinflammatory cell death that occurs in response to certain microbes. Activation of the protease caspase-1 by molecular platforms called inflammasomes is required for pyroptosis. We performed a cellular genome-wide association study (GWAS) using Salmonella typhimurium infection of human lymphoblastoid cell lines as a means of dissecting the genetic architecture of susceptibility to pyroptosis and identifying unknown regulatory mechanisms. Cellular GWAS revealed that a common human genetic difference that regulates pyroptosis also alters microtubule stability. An intergenic single-nucleotide polymorphism on chromosome 18 is associated with decreased pyroptosis and increased expression of TUBB6 (tubulin, β 6 class V). TUBB6 is unique among tubulin isoforms in that its overexpression can completely disrupt the microtubule network. Cells from individuals with higher levels of TUBB6 expression have lower microtubule stability and less pyroptosis. Reducing TUBB6 expression or stabilizing microtubules pharmacologically with paclitaxel (Taxol) increases pyroptosis without affecting the other major readout of caspase-1 activation, interleukin-1β secretion. The results reveal a new role for microtubules and possibly specific tubulin isoforms in the execution of pyroptosis. Furthermore, the finding that there is common diversity in TUBB6 expression and microtubule stability could have broad consequences for other microtubule-dependent phenotypes, diseases, and pharmacological responses.

Browsing by Subject "Humans"

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