Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 2 hours 19 min ago

Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis.

Thu, 11/15/2018 - 05:20
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Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis.

Mol Biol Rep. 2018 Nov 13;:

Authors: Haridas V, Shetty P, Sarathkumar E, Bargale A, Vishwanatha JK, Patil V, Dinesh US

Abstract
Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in naïve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in naïve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.

PMID: 30426384 [PubMed - as supplied by publisher]

Aircraft-Assisted Pilot Suicides in the General Aviation Increased for One-Year Period after 11 September 2001 Attack in the United States.

Thu, 11/15/2018 - 05:20
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Aircraft-Assisted Pilot Suicides in the General Aviation Increased for One-Year Period after 11 September 2001 Attack in the United States.

Int J Environ Res Public Health. 2018 Nov 12;15(11):

Authors: Vuorio A, Laukkala T, Junttila I, Bor R, Budowle B, Pukkala E, Navathe P, Sajantila A

Abstract
Pilot aircraft-assisted suicides (AAS) are rare, and there is limited understanding of copycat phenomenon among aviators. The aim of this study was to evaluate the possible effect the 11 September 2001, terrorist attacks had on pilot AASs in the U.S. Fatal aviation accidents in the National Transportation Safety Board (NTSB) database were searched using the following search words: "suicide", "murder-suicide" and "homicide-suicide". The timeline between 11 September 1996, and 11 September 2004, was analyzed. Only those accidents in which NTSB judged that the cause of the accident was suicide were included in the final analysis. The relative risk (RR) of the pilot AASs in all fatal accidents in the U.S. was calculated in order to compare the one, two, and three-year periods after the September 11 terrorist attacks with five years preceding the event. The RR of a fatal general aviation aircraft accident being due to pilot suicide was 3.68-fold (95% confidence interval 1.04⁻12.98) during the first year after 11 September 2001, but there was not a statistically significant increase in the later years. This study showed an association, albeit not determinate causal effect, of a very specific series of simultaneous terrorist murder-suicides with subsequent pilot AASs.

PMID: 30424489 [PubMed - in process]

"Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA.

Wed, 11/14/2018 - 05:16
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"Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA.

Neuropharmacology. 2018 05 01;133:171-180

Authors: Dolan SB, Chen Z, Huang R, Gatch MB

Abstract
This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in "Ecstasy" formulations, these data indicate that adulterated "Ecstasy" formulations may drive more compulsive drug use than those containing only MDMA.

PMID: 29378213 [PubMed - indexed for MEDLINE]

The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma.

Wed, 11/14/2018 - 05:16
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The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma.

Optom Vis Sci. 2018 02;95(2):155-162

Authors: Fingeret M, Dickerson JE

Abstract
SIGNIFICANCE: Noncompliance is a problem affecting glaucoma patients. Approaches to improve adherence include the use of drug-delivery systems and safer forms of surgery. Minimally invasive glaucoma surgery (MIGS) has reduced complications, particularly in combination with cataract surgery, and with its good intraocular pressure (IOP) reduction may reduce or eliminate glaucoma medications.Glaucoma is a progressive disease and a leading cause of irreversible blindness. Elevated IOP is the most important risk factor, but effective medical management is dependent on patient adherence. This review summarizes the adherence problem in glaucoma and the efforts, including MIGS, to provide effective IOP control that is not dependent on patient compliance.The current understanding of patient adherence to pharmacological treatment of glaucoma is discussed including the challenges facing glaucoma patients. Historical approaches to providing IOP control in a sustained and reliable way are presented culminating in a review of the burgeoning use of MIGS devices.It is estimated that, in the United States, 27% of prescriptions written, across all medications, are not filled or are filled but not taken. For ocular hypotensive medications, even when filled, a large percentage (which varies widely by study) are not instilled as prescribed. To address this problem, methods for sustained drug delivery have been and continue to be developed, as well as surgical and laser approaches. Most recently, MIGS devices have gained popularity because of the ease of implantation during cataract surgery, favorable safety profile, and the possibility for effective and long-lasting IOP lowering, as well as the reduction or elimination of need for IOP-lowering medication.Poor adherence to treatment is relatively common among glaucoma patients and is associated with progression of disease. Recommending MIGS implantation during cataract surgery may offer optometrists a valuable treatment option in managing glaucoma patients, particularly where good adherence is in doubt.

PMID: 29370021 [PubMed - indexed for MEDLINE]

Genomics-guided discovery of a new and significantly better source of anticancer natural drug FK228.

Tue, 11/13/2018 - 05:11

Genomics-guided discovery of a new and significantly better source of anticancer natural drug FK228.

Synth Syst Biotechnol. 2018 Dec;3(4):268-274

Authors: Liu X, Xie F, Doughty LB, Wang Q, Zhang L, Liu X, Cheng YQ

Abstract
FK228 is an FDA-approved anticancer drug naturally produced by Chromobacterium violaceum No. 968 up to 19 mg/L in a pilot industry-scale batch fermentation. Here we report a genomics-guided discovery of Burkholderia thailandensis MSMB43 as a new and significantly better source of FK228. The genome of B. thailandensis MSMB43 was found to contain a functional biosynthetic gene cluster highly homologous to that of FK228 in C. violaceum No. 968, and the bacterium indeed produces authentic FK228. By simple fermentation in shaking flasks in a preferred M8 medium, B. thailandensis MSMB43 produced FK228 up to 67.7 mg/L; by fed-batch fermentation in a 20-L fermentor in M8 medium, B. thailandensis MSMB43 produced FK228 up to 115.9 mg/L, which is 95 fold higher than that of C. violaceum No. 968 under the same laboratory fermentation conditions. RT-PCR analysis indicated that the high FK228 yield of B. thailandensis MSMB43 was due to high expression of biosynthetic genes, represented by Bth_depA, during the fermentation process. Further genetic manipulation resulted in a recombinant strain, B. thailandensis MSMB43/pBMTL3-tdpR, which harbors a broad host-range vector expressing the thailandepsin biosynthetic pathway regulatory gene tdpR. This engineered strain produced up to 168.5 mg/L of FK228 in fed-batch fermentation in a 20-L fermentor in M8 medium. Therefore, the wild-type B. thailandensis MSMB43 or its engineered derivative could potentially be a good starting point for an industrial process to improve FK228 production for its expanding use in therapy.

PMID: 30417143 [PubMed]

Therapeutic leukocytapheresis in infants and children with leukemia and hyperleukocytosis: A single institution experience.

Sat, 11/10/2018 - 07:59
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Therapeutic leukocytapheresis in infants and children with leukemia and hyperleukocytosis: A single institution experience.

J Clin Apher. 2018 Jun;33(3):316-323

Authors: Thapa N, Pham R, Cole C, Meinershagen M, Bowman PW, Ray A

Abstract
BACKGROUND: Hyperleukocytosis, defined as white blood cell (WBC) count above 100 × 109 /L, has high early morbidity and mortality from leukostasis-related complications, namely intracranial hemorrhage and pulmonary distress. Initiating chemotherapy without prior leukocytoreduction may lead to tumor lysis syndrome (TLS). Therapeutic leukocytapheresis (TL) is used as one leukocytoreductive intervention; however, its safety and efficacy in pediatric leukemia has not been established. The purpose of this study is to evaluate safety of TL in pediatric patients and assess the efficacy of TL in reducing WBC count in pediatric leukemia.
METHODS: Retrospective chart review was conducted on 14 patients with acute lymphoblastic leukemia (ALL) and 5 with acute myeloid leukemia (AML) who underwent TL during the period 2000-2014 at a single institution.
RESULTS: Mean WBC count of 19 patients who received TL was 483.2 × 109 /L (547.1 in ALL, 304.3 in AML); a portion of patients presented with central nervous system symptoms (15%), respiratory symptoms (10%), or both (10%). TL reduced WBC count (mean 50.7% reduction after a single TL procedure; additional 17.1% reduction after a second TL procedure in 6 patients). Short-term survival immediately following TL was 100% without any major procedural complication. Mean survival time in patients with AML was 1.5 years and with ALL was 6.5 years.
CONCLUSIONS: TL significantly reduces WBC number in pediatric leukemia patients as young as 22 days old. In our retrospective study, TL was not associated with any significant complications and suggests that TL is a safe initial procedure in pediatric leukemia.

PMID: 29193219 [PubMed - indexed for MEDLINE]

Perspective: Sistas In Science - Cracking the Glass Ceiling.

Fri, 11/09/2018 - 07:55
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Perspective: Sistas In Science - Cracking the Glass Ceiling.

Ethn Dis. 2018;28(4):575-578

Authors: Starlard-Davenport A, Rich A, Fasipe T, Lance EI, Adekola K, Forray A, Steed M, Fitzgerald A, Walker S, Pace BS

Abstract
In this perspective, we describe our experience as women of color scientists from diverse backgrounds and similar struggles embarking upon the National Heart, Lung and Blood Institute-funded program called PRIDE (Programs to Increase Diversity among Underrepresented Minorities Engaged in Health-Related Research). Under the leadership of our mentor and friend, Betty Pace, MD, a renowned and successful African American physician-scientist, the PRIDE Program was designed to address the difficulties experienced by junior-level minority investigators in establishing independent research programs and negotiating tenure and full professor status at academic institutions. The strength of PRIDE's innovative formula was pairing us with external senior mentors and, importantly, allowing us to serve as peer mentors to each other. We believe this "Sister's Keeper" paradigm is one solution for women to overcome their limitations and extend understandings and best practices worldwide for science, medicine, and global health.

PMID: 30405303 [PubMed - in process]

Laboratory measures of coagulation among trauma patients on NOAs: results of the AAST-MIT.

Thu, 11/08/2018 - 07:53
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Laboratory measures of coagulation among trauma patients on NOAs: results of the AAST-MIT.

Trauma Surg Acute Care Open. 2018;3(1):e000231

Authors: Kobayashi LM, Brito A, Barmparas G, Bosarge P, Brown CV, Bukur M, Carrick MM, Catalano RD, Holly-Nicolas J, Inaba K, Kaminski S, Klein AL, Kopelman T, Ley EJ, Martinez EM, Moore FO, Murry J, Nirula R, Paul D, Quick J, Rivera O, Schreiber M, Coimbra R

Abstract
Background: Warfarin is associated with poor outcomes after trauma, an effect correlated with elevations in the international normalized ratio (INR). In contrast, the novel oral anticoagulants (NOAs) have no validated laboratory measure to quantify coagulopathy. We sought to determine if use of NOAs was associated with elevated activated partial thromboplastin time (aPTT) or INR levels among trauma patients or increased clotting times on thromboelastography (TEG).
Methods: This was a post-hoc analysis of a prospective observational study across 16 trauma centers. Patients on dabigatran, rivaroxaban, or apixaban were included. Laboratory data were collected at admission and after reversal. Admission labs were compared between medication groups. Traditional measures of coagulopathy were compared with TEG results using Spearman's rank coefficient for correlation. Labs before and after reversal were also analyzed between medication groups.
Results: 182 patients were enrolled between June 2013 and July 2015: 50 on dabigatran, 123 on rivaroxaban, and 34 apixaban. INR values were mildly elevated among patients on dabigatran (median 1.3, IQR 1.1-1.4) and rivaroxaban (median 1.3, IQR 1.1-1.6) compared with apixaban (median 1.1, IQR 1.0-1.2). Patients on dabigatran had slightly higher than normal aPTT values (median 35, IQR 29.8-46.3), whereas those on rivaroxaban and apixaban did not. Fifty patients had TEG results. The median values for R, alpha, MA and lysis were normal for all groups. Prothrombin time (PT) and aPTT had a high correlation in all groups (dabigatran p=0.0005, rivaroxaban p<0.0001, and apixaban p<0.0001). aPTT correlated with the R value on TEG in patients on dabigatran (p=0.0094) and rivaroxaban (p=0.0028) but not apixaban (p=0.2532). Reversal occurred in 14%, 25%, and 18% of dabigatran, rivaroxaban, and apixaban patients, respectively. Both traditional measures of coagulopathy and TEG remained within normal limits after reversal.
Discussion: Neither traditional measures of coagulation nor TEG were able to detect coagulopathy in patients on NOAs.
Level of evidence: Level IV.

PMID: 30402564 [PubMed]

Massively parallel sequencing-enabled mixture analysis of mitochondrial DNA samples.

Thu, 11/08/2018 - 07:53
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Massively parallel sequencing-enabled mixture analysis of mitochondrial DNA samples.

Int J Legal Med. 2018 Sep;132(5):1263-1272

Authors: Churchill JD, Stoljarova M, King JL, Budowle B

Abstract
The mitochondrial genome has a number of characteristics that provide useful information to forensic investigations. Massively parallel sequencing (MPS) technologies offer improvements to the quantitative analysis of the mitochondrial genome, specifically the interpretation of mixed mitochondrial samples. Two-person mixtures with nuclear DNA ratios of 1:1, 5:1, 10:1, and 20:1 of individuals from different and similar phylogenetic backgrounds and three-person mixtures with nuclear DNA ratios of 1:1:1 and 5:1:1 were prepared using the Precision ID mtDNA Whole Genome Panel and Ion Chef, and sequenced on the Ion PGM or Ion S5 sequencer (Thermo Fisher Scientific, Waltham, MA, USA). These data were used to evaluate whether and to what degree MPS mixtures could be deconvolved. Analysis was effective in identifying the major contributor in each instance, while SNPs from the minor contributor's haplotype only were identified in the 1:1, 5:1, and 10:1 two-person mixtures. While the major contributor was identified from the 5:1:1 mixture, analysis of the three-person mixtures was more complex, and the mixed haplotypes could not be completely parsed. These results indicate that mixed mitochondrial DNA samples may be interpreted with the use of MPS technologies.

PMID: 29468381 [PubMed - indexed for MEDLINE]

Human Papillomavirus Vaccination and School Entry Requirements: Politically Challenging, But Not Impossible.

Wed, 11/07/2018 - 07:49
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Human Papillomavirus Vaccination and School Entry Requirements: Politically Challenging, But Not Impossible.

JAMA Pediatr. 2018 Nov 05;:

Authors: Daley E, Thompson E, Zimet G

PMID: 30398530 [PubMed - as supplied by publisher]

Forensic human identification with targeted microbiome markers using nearest neighbor classification.

Tue, 11/06/2018 - 07:43
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Forensic human identification with targeted microbiome markers using nearest neighbor classification.

Forensic Sci Int Genet. 2018 Oct 05;38:130-139

Authors: Woerner AE, Novroski NMM, Wendt FR, Ambers A, Wiley R, Schmedes SE, Budowle B

Abstract
From the perspective of forensics genetics, the human microbiome is a rich, relatively untapped resource for human identity testing. Since it varies within and among people, and perhaps temporally, the potential forensic applications of the use of the microbiome can exceed that of human identification. However, the same inherent variability in microbial distributions may pose a substantial barrier to forming predictions on an individual as the source of the microbial sample unless stable signatures of the microbiome are identified and targeted. One of the more commonly adopted strategies for microbial human identification relies on quantifying which taxa are present and their respective abundance levels. It remains an open question if such microbial signatures are more individualizing than estimates of the degree of genetic relatedness between microbial samples. This study attempts to address this question by contrasting two prediction strategies. The first approach uses phylogenetic distance to predict the host individual; thus it operates under the premise that microbes within individuals are more closely related than microbes between/among individuals. The second approach uses population genetic measures of diversity at clade-specific markers, serving as a fine-grained assessment of microbial composition and quantification. Both assessments were performed using targeted sequencing of 286 markers from 22 microbial taxa sampled in 51 individuals across three body sites measured in triplicate. Nearest neighbor and reverse nearest neighbor classifiers were constructed based on the pooled data and yielded 71% and 78% accuracy, respectively, when diversity was considered, and performed significantly worse when a phylogenetic distance was used (54% and 63% accuracy, respectively). However, empirical estimates of classification accuracy were 100% when conditioned on a maximum nearest neighbor distance when diversity was used, while identification based on a phylogenetic distance failed to reach saturation. These findings suggest that microbial strain composition is more individualizing than that of a phylogeny, perhaps indicating that microbial composition may be more individualizing than recent common ancestry. One inference that may be drawn from these findings is that host-environment interactions may maintain the targeted microbial profile and that this maintenance may not necessarily be repopulated by intra-individual microbial strains.

PMID: 30396009 [PubMed - as supplied by publisher]

Expanding beyond the current core STR loci: An exploration of 73 STR markers with increased diversity for enhanced DNA mixture deconvolution.

Tue, 11/06/2018 - 07:43
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Expanding beyond the current core STR loci: An exploration of 73 STR markers with increased diversity for enhanced DNA mixture deconvolution.

Forensic Sci Int Genet. 2018 Oct 29;38:121-129

Authors: Novroski NMM, Wendt FR, Woerner AE, Bus MM, Coble M, Budowle B

Abstract
Current approaches to mixture deconvolution of complex biological samples at times do not have the capability to resolve component contributors in DNA evidence. Additional short tandem repeat (STR) loci were sought that may improve the forensic genetic analysis of mixtures. This study presents exploratory data of a multiplex comprised of 73 highly polymorphic STRs (referred herein as the 73Plex) that were selected because of their high diversity due to sequence variation. These STRs (or a subset of them) may be considered as candidates that may augment current core markers capabilities for DNA mixture deconvolution. Population genetics analyses were performed for each locus using DNA samples from 451 individuals comprising three U.S. populations. Sequence-based heterozygosities ranged from 72% to 98%, where only two loci (D10A97 and D6A7) fell below 80%. Mixture deconvolution capabilities for two-person mixtures were assessed based on complete allele resolution per locus (i.e., four alleles observed) of pairwise mixtures using in silico methods. A subset of 20 highly informative loci (referred herein as the 20Plex) from the 73Plex was compared to the 20 CODIS core loci on all population samples with full DNA profiles for both panels (i.e., no locus dropout; n = 443). Based on proportion of loci displaying four alleles, the 20Plex outperformed the CODIS core loci with increases of 82.6% and 89.3% using length-based and sequence-based alleles, respectively. A combination of 17 STR from the 20Plex and 3 CODIS loci gave the highest capacity for resolving allelic components per locus. These data illustrate the increased value of utilizing sequenced-based alleles of additional STR loci. Furthermore, there are a number of candidate STR loci that could notably augment the current core STR loci and enhance mixture interpretation capabilities.

PMID: 30396008 [PubMed - as supplied by publisher]

Risk Assessment of Recreational Noise-Induced Hearing Loss from Exposure through a Personal Audio System-iPod Touch.

Tue, 11/06/2018 - 07:43
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Risk Assessment of Recreational Noise-Induced Hearing Loss from Exposure through a Personal Audio System-iPod Touch.

J Am Acad Audiol. 2018 Nov 01;:

Authors: Gopal KV, Mills LE, Phillips BS, Nandy R

Abstract
BACKGROUND: Recreational noise-induced hearing loss (RNIHL) is a major health issue and presents a huge economic burden on society. Exposure to loud music is not considered hazardous in our society because music is thought to be a source of relaxation and entertainment. However, there is evidence that regardless of the sound source, frequent exposure to loud music, including through personal audio systems (PAS), can lead to hearing loss, tinnitus, difficulty processing speech, and increased susceptibility to age-related hearing loss.
PURPOSE: Several studies have documented temporary threshold shifts (TTS) (a risk indicator of future permanent impairment) in subjects that listen to loud music through their PAS. However, there is not enough information regarding volume settings that may be considered to be safe. As a primary step toward quantifying the risk of RNIHL through PAS, we assessed changes in auditory test measures before and after exposure to music through the popular iPod Touch device set at various volume levels.
RESEARCH DESIGN: This project design incorporated aspects of both between- and within-subjects and used repeated measures to analyze individual groups.
STUDY SAMPLE: A total of 40 adults, aged 18-31 years with normal hearing were recruited and randomly distributed to four groups. Each group consisted of five males and five females.
DATA COLLECTION AND ANALYSIS: Subjects underwent two rounds of testing (pre- and postmusic exposure), with a 30-min interval, where they listened to a playlist consisting of popular songs through an iPod at 100%, 75%, 50%, or 0% volume (no music). Based on our analysis on the Knowles Electronic Manikin for Acoustic Research, with a standardized 711 coupler, it was determined that listening to the playlist for 30 min through standard earbuds resulted in an average level of 97.0 dBC at 100% volume, 83.3 dBC at 75% volume, and 65.6 dBC at 50% volume. Pure-tone thresholds from 500-8000 Hz, extended high-frequency pure tones between 9-12.5 kHz, and distortion product otoacoustic emissions (DPOAE) were obtained before and after the 30-min music exposure. Analysis of variance (ANOVA) was performed with two between-subjects factors (volume and gender) and one within-subjects factor (frequency). Change (shift) in auditory test measures was used as the outcome for the ANOVA.
RESULTS: Results indicated significant worsening of pure-tone thresholds following music exposure only in the group that was exposed to 100% volume at the following frequencies: 2, 3, 4, 6 and 8 kHz. DPOAEs showed significant decrease at 2000 and 2822 Hz, also only for the 100% volume condition. No significant changes were found between pre- and postmusic exposure measures in groups exposed to 75%, 50%, or 0% volume conditions. Follow-up evaluations conducted a week later indicated that pure-tone thresholds had returned to the premusic exposure levels.
CONCLUSIONS: These results provide quantifiable information regarding safe volume control settings on the iPod Touch with standard earbuds. Listening to music using the iPod Touch at 100% volume setting for as little as 30 min leads to TTS and worsening of otoacoustic emissions, a risk for permanent auditory damage.

PMID: 30395532 [PubMed - as supplied by publisher]

Exploring college students' sexual and reproductive health literacy.

Tue, 11/06/2018 - 07:43
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Exploring college students' sexual and reproductive health literacy.

J Am Coll Health. 2018 Nov 02;:1-10

Authors: Vamos CA, Thompson EL, Logan RG, Griner SB, Perrin KM, Merrell LK, Daley EM

Abstract
OBJECTIVE: To assess college students' sexual and reproductive health (SRH) literacy experiences, specific to contraception use and STI prevention.
PARTICIPANTS: In Spring 2015, participants (n = 43) from a large institution participated in six focus groups (two male and four females groups).
METHODS: Focus groups were guided by the health literacy domains (access; understand; appraise; apply); data were analyzed in MaxQDA using the constant comparative method.
RESULTS: The Internet was the most commonly accessed source for SRH information. Participants discussed facilitators (eg, use of visuals) and barriers (eg, medical jargon) to understanding information; and personal lifestyle, advice from family/friends, symptoms, and sexual partners as appraisal factors. Participants applied information by communicating with friends/providers and seeking healthcare. However, findings were not linear nor mutually exclusive, representing the interaction of health literacy skills.
CONCLUSION: Findings suggest that a patient-centered intervention capitalizing on technology and trusted individuals (providers/peer educators) may facilitate college students' SRH literacy.

PMID: 30388946 [PubMed - as supplied by publisher]

Ligandomics: a paradigm shift in biological drug discovery.

Tue, 11/06/2018 - 07:43
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Ligandomics: a paradigm shift in biological drug discovery.

Drug Discov Today. 2018 03;23(3):636-643

Authors: Li W, Pang IH, Pacheco MTF, Tian H

Abstract
As productivity of pharmaceutical research and development (R&D) for small-molecule drugs declines, the trend in drug discovery strategies is shifting towards biologics, which predominantly target secreted or cell surface proteins. Receptors and ligands are the most-valuable drug targets. In contrast to conventional approaches of discovering one ligand at a time, the emerging technology of ligandomics can systematically map disease-selective cellular ligands in the absence of molecular probes. Biologics targeting these ligands with disease selectivity have the advantages of high efficacy, minimal adverse effects, wide therapeutic indices, and low safety-related attrition rates. Therefore, ligandomics represents a paradigm shift to address the bottleneck of target discovery for biologics development.

PMID: 29326083 [PubMed - indexed for MEDLINE]

Stress and interferon signalling-mediated apoptosis contributes to pleiotropic anticancer responses induced by targeting NGLY1.

Sat, 11/03/2018 - 05:27
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Stress and interferon signalling-mediated apoptosis contributes to pleiotropic anticancer responses induced by targeting NGLY1.

Br J Cancer. 2018 Nov 02;:

Authors: Zolekar A, Lin VJT, Mishra NM, Ho YY, Hayatshahi HS, Parab A, Sampat R, Liao X, Hoffmann P, Liu J, Emmitte KA, Wang YC

Abstract
BACKGROUND: Although NGLY1 is known as a pivotal enzyme that catalyses the deglycosylation of denatured glycoproteins, information regarding the responses of human cancer and normal cells to NGLY1 suppression is limited.
METHODS: We examined how NGLY1 expression affects viability, tumour growth, and responses to therapeutic agents in melanoma cells and an animal model. Molecular mechanisms contributing to NGLY1 suppression-induced anticancer responses were revealed by systems biology and chemical biology studies. Using computational and medicinal chemistry-assisted approaches, we established novel NGLY1-inhibitory small molecules.
RESULTS: Compared with normal cells, NGLY1 was upregulated in melanoma cell lines and patient tumours. NGLY1 knockdown caused melanoma cell death and tumour growth retardation. Targeting NGLY1 induced pleiotropic responses, predominantly stress signalling-associated apoptosis and cytokine surges, which synergise with the anti-melanoma activity of chemotherapy and targeted therapy agents. Pharmacological and molecular biology tools that inactivate NGLY1 elicited highly similar responses in melanoma cells. Unlike normal cells, melanoma cells presented distinct responses and high vulnerability to NGLY1 suppression.
CONCLUSION: Our work demonstrated the significance of NGLY1 in melanoma cells, provided mechanistic insights into how NGLY1 inactivation leads to eradication of melanoma with limited impact on normal cells, and suggested that targeting NGLY1 represents a novel anti-melanoma strategy.

PMID: 30385822 [PubMed - as supplied by publisher]

Alcohol-specific social comparison as a moderator of the norms-behavior association for young adult alcohol use.

Fri, 11/02/2018 - 05:24

Alcohol-specific social comparison as a moderator of the norms-behavior association for young adult alcohol use.

Addict Behav. 2018 Oct 19;90:92-98

Authors: Litt DM, Waldron KA, Wallace EC, Lewis MA

Abstract
Research has indicated that individuals high in social comparison orientation (SCO) are more influenced by the behavior and perceived norms of others. However, despite research indicating that behavior is more closely influenced by and modeled on more socially proximal reference groups, most social comparison research to date has utilized global measures of social comparison. As such, research has not examined whether domain-specific (i.e. alcohol-specific social comparisons) and their relation with norms are more predictive of alcohol-related outcomes than global comparisons. As such, the present study aimed to determine whether the previously found relationships between global SCO, descriptive drinking norms and their interaction are still significant when accounting for alcohol-specific SCO and its interaction with descriptive norms in the prediction of drinking willingness and behavior. Results from 355 young adults age 18-20 indicated that the association of alcohol-specific SCO and its interaction with descriptive norms for drinking predicts alcohol-related outcomes (drinking willingness and alcohol consumption), but not alcohol-related negative consequences above and beyond global SCO. Thus, alcohol-specific SCO may be of particular importance when determining for whom normative based preventive interventions may be the most efficacious.

PMID: 30384190 [PubMed - as supplied by publisher]

Intermittent hypoxia training: Powerful, non-invasive cerebroprotection against ethanol withdrawal excitotoxicity.

Fri, 11/02/2018 - 05:24
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Intermittent hypoxia training: Powerful, non-invasive cerebroprotection against ethanol withdrawal excitotoxicity.

Respir Physiol Neurobiol. 2018 10;256:67-78

Authors: Jung ME, Mallet RT

Abstract
Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca2+ loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence. Although the brain is heavily dependent on blood-borne O2 to sustain its aerobic ATP production, brief, cyclic episodes of moderate hypoxia and reoxygenation, when judiciously applied over the course of days or weeks, evoke adaptations that protect the brain from ethanol withdrawal-induced glutamate excitotoxicity, mitochondrial damage, oxidative stress and amyloid β accumulation. This review summarizes evidence from ongoing preclinical research that demonstrates intermittent hypoxia training to be a potentially powerful yet non-invasive intervention capable of affording robust, sustained neuroprotection during ethanol withdrawal.

PMID: 28811138 [PubMed - indexed for MEDLINE]

Challenges in investigation of diabetes-related aviation fatalities-an analysis of 1491 subsequent aviation fatalities in USA during 2011-2016.

Thu, 11/01/2018 - 05:20
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Challenges in investigation of diabetes-related aviation fatalities-an analysis of 1491 subsequent aviation fatalities in USA during 2011-2016.

Int J Legal Med. 2018 Nov;132(6):1713-1718

Authors: Junttila IS, Vuorio A, Budowle B, Laukkala T, Sajantila A

Abstract
Diabetes mellitus (DM) could cause pilot incapacitation and result in aviation fatalities. The mechanisms could be directly as a consequence of acute hypoglycemia/subacute diabetic ketoacidosis (DKA) or indirectly as an acute cardiovascular event by contributing to the development of atherosclerosis in coronary or carotid and cerebral arteries. In this study, DM-related fatal flight accidents in the US National Transport Bureau's database between years 2011-2016 were analyzed with special emphasis on postmortem (PM) glucose levels and correlation of toxicological reports with anamnestic information on DM. Additionally, autopsy results on coronary arteries were reviewed. In 43 out of 1491 (~ 3%) fatal accidents pilots had DM. Postmortem glucose or glycated hemoglobin percentage (Hb1Ac) was measured in 12 of the 43 cases; while antidiabetic medication was found in 14 of the cases (only two of the cases had both glucose measurements and medication). With the increasing prevalence of DM, a possibility of pilot incapacitation due to DM or complications of DM should be actively studied, even if no anamnestic information of DM was available. While PM hypoglycemia is difficult to assess, we propose a systematic investigation based on measurement of glucose, Hb1Ac%, and ketone bodies, and documentation of atherosclerotic lesions in major arteries to identify or rule out DM as a cause of pilot incapacitation.

PMID: 29974235 [PubMed - indexed for MEDLINE]

"The devil's in the detail": Release of an expanded, enhanced and dynamically revised forensic STR Sequence Guide.

Thu, 11/01/2018 - 05:20
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"The devil's in the detail": Release of an expanded, enhanced and dynamically revised forensic STR Sequence Guide.

Forensic Sci Int Genet. 2018 05;34:162-169

Authors: Phillips C, Gettings KB, King JL, Ballard D, Bodner M, Borsuk L, Parson W

Abstract
The STR sequence template file published in 2016 as part of the considerations from the DNA Commission of the International Society for Forensic Genetics on minimal STR sequence nomenclature requirements, has been comprehensively revised and audited using the latest GRCh38 genome assembly. The list of forensic STRs characterized was expanded by including supplementary autosomal, X- and Y-chromosome microsatellites in less common use for routine DNA profiling, but some likely to be adopted in future massively parallel sequencing (MPS) STR panels. We outline several aspects of sequence alignment and annotation that required care and attention to detail when comparing sequences to GRCh37 and GRCh38 assemblies, as well as the necessary matching of MPS-based allele descriptions to previously established repeat region structures described in initial sequencing studies of the less well known forensic STRs. The revised sequence guide is now available in a dynamically updated FTP format from the STRidER website with a date-stamped change log to allow users to explore their own MPS data with the most up-to-date forensic STR sequence information compiled in a simple guide.

PMID: 29486434 [PubMed - indexed for MEDLINE]

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