Recent Research Articles from UNTHSC

Reducing noise and stutter in short tandem repeat loci with unique molecular identifiers.

Tue, 01/12/2021 - 07:28
Related Articles

Reducing noise and stutter in short tandem repeat loci with unique molecular identifiers.

Forensic Sci Int Genet. 2020 Dec 25;51:102459

Authors: Woerner AE, Mandape S, King JL, Muenzler M, Crysup B, Budowle B

Abstract
Unique molecular identifiers (UMIs) are a promising approach to contend with errors generated during PCR and massively parallel sequencing (MPS). With UMI technology, random molecular barcodes are ligated to template DNA molecules prior to PCR, allowing PCR and sequencing error to be tracked and corrected bioinformatically. UMIs have the potential to be particularly informative for the interpretation of short tandem repeats (STRs). Traditional MPS approaches may simply lead to the observation of alleles that are consistent with the hypotheses of stutter, while with UMIs stutter products bioinformatically may be re-associated with their parental alleles and subsequently removed. Herein, a bioinformatics pipeline named strumi is described that is designed for the analysis of STRs that are tagged with UMIs. Unlike other tools, strumi is an alignment-free machine learning driven algorithm that clusters individual MPS reads into UMI families, infers consensus super-reads that represent each family and provides an estimate the resulting haplotype's accuracy. Super-reads, in turn, approximate independent measurements not of the PCR products, but of the original template molecules, both in terms of quantity and sequence identity. Provisional assessments show that naïve threshold-based approaches generate super-reads that are accurate (∼97 % haplotype accuracy, compared to ∼78 % when UMIs are not used), and the application of a more nuanced machine learning approach increases the accuracy to ∼99.5 % depending on the level of certainty desired. With these features, UMIs may greatly simplify probabilistic genotyping systems and reduce uncertainty. However, the ability to interpret alleles at trace levels also permits the interpretation, characterization and quantification of contamination as well as somatic variation (including somatic stutter), which may present newfound challenges.

PMID: 33429137 [PubMed - as supplied by publisher]

Identifying knowledge gaps in heart failure research among women using unsupervised machine-learning methods.

Tue, 01/12/2021 - 07:28
Related Articles

Identifying knowledge gaps in heart failure research among women using unsupervised machine-learning methods.

Future Cardiol. 2021 Jan 11;:

Authors: Alhussain K, Kido K, Dwibedi N, LeMasters T, Rose DE, Misra R, Sambamoorthi U

Abstract
Aim: To identify knowledge gaps in heart failure (HF) research among women, especially postmenopausal women. Materials & methods: We retrieved HF articles from PubMed. Natural language processing and text mining techniques were used to screen relevant articles and identify study objective(s) from abstracts. After text preprocessing, we performed topic modeling with non-negative matrix factorization to cluster articles based on the primary topic. Clusters were independently validated and labeled by three investigators familiar with HF research. Results: Our model yielded 15 topic clusters from articles on HF among women. Atrial fibrillation was found to be the most understudied topic. From articles specific to postmenopausal women, five clusters were identified. The smallest cluster was about stress-induced cardiomyopathy. Conclusion: Topic modeling can help identify understudied areas in medical research.

PMID: 33426899 [PubMed - as supplied by publisher]

Environment-wide association study on childhood obesity in the U.S.

Tue, 01/12/2021 - 07:28
Related Articles

Environment-wide association study on childhood obesity in the U.S.

Environ Res. 2020 12;191:110109

Authors: Uche UI, Suzuki S, Fulda KG, Zhou Z

Abstract
BACKGROUND: Childhood obesity is a national public health issue with increasing prevalence. It has been linked to diet, lack of physical activity, and genetic susceptibility, with more recent evidence that it could also result from environmental factors. Studies linking it to environmental factors are limited, unsystematic, incomprehensive, and inconclusive.
OBJECTIVE: To conduct an environment-wide association study (EWAS) to comprehensively investigate all the environmental factors available in a nationally representative sample of children to determine factors associated with childhood obesity.
METHODS: We utilized the 1999-2016 National Health and Nutrition Examination Survey (NHANES) datasets and included all children/adolescents (6-17 years). Obesity was measured using body mass index and waist to height ratio. A multinomial and binary logistic regression were used adjusting for age, sex, race/ethnicity, creatinine, calorie intake, physical activity, screen time, limitation to physical activities, and socioeconomic status. We then controlled for multiple hypothesis testing and validated our findings on a different cohort of children.
RESULTS: We found that metals such as beryllium (OR: 3.305 CI: 1.460-7.479) and platinum (OR: 1.346 CI: 1.107-1.636); vitamins such as gamma-tocopherol (OR: 8.297 CI: 5.683-12.114) and delta-tocopherol (OR: 1.841 CI:1.476-2.297); heterocyclic aromatic amines such as 2-Amino-9H-pyrido (2,3-b) indole (OR: 1.323 CI: 1.083-1.617) and 2-Amino-3-methyl-9H-pyriodo(2,3-b)indole (OR: 2.799 CI: 1.442-5.433); polycyclic aromatic amines such as 9- fluorene (OR: 1.509 CI: 1.230-1.851) and 4-phenanthrene (OR: 2.828 CI: 1.632-4.899); and caffeine metabolites such as 1,3,7-trimethyluric acid (OR: 1.22 CI: 1.029-1.414) and 1,3,7-trimethylxanthine (OR: 1.258 CI: 1.075-1.473) were positively and significantly associated with childhood obesity.
CONCLUSION: Following the unique concept of EWAS, certain environmental factors were associated with childhood obesity. Further studies are required to confirm these associations while investigating their mechanisms of action.

PMID: 32841636 [PubMed - indexed for MEDLINE]

Good Vibrations: The Evolution of Whisking in Small Mammals.

Tue, 01/12/2021 - 07:28
Related Articles

Good Vibrations: The Evolution of Whisking in Small Mammals.

Anat Rec (Hoboken). 2020 01;303(1):89-99

Authors: Muchlinski MN, Wible JR, Corfe I, Sullivan M, Grant RA

Abstract
While most mammals have whiskers, some tactile specialists-mainly small, nocturnal, and arboreal species-can actively move their whiskers in a symmetrical, cyclic movement called whisking. Whisking enables mammals to rapidly, tactually scan their environment to efficiently guide locomotion and foraging in complex habitats. The muscle architecture that enables whisking is preserved from marsupials to primates, prompting researchers to suggest that a common ancestor might have had moveable whiskers. Studying the evolution of whisker touch sensing is difficult, and we suggest that measuring an aspect of skull morphology that correlates with whisking would enable comparisons between extinct and extant mammals. We find that whisking mammals have larger infraorbital foramen (IOF) areas, which indicates larger infraorbital nerves and an increase in sensory acuity. While this relationship is quite variable and IOF area cannot be used to solely predict the presence of whisking, whisking mammals all have large IOF areas. Generally, this pattern holds true regardless of an animal's substrate preferences or activity patterns. Data from fossil mammals and ancestral character state reconstruction and tracing techniques for extant mammals suggest that whisking is not the ancestral state for therian mammals. Instead, whisking appears to have evolved independently as many as seven times across the clades Marsupialia, Afrosoricida, Eulipotyphla, and Rodentia, with Xenarthra the only placental superordinal clade lacking whisking species. However, the term whisking only captures symmetrical and rhythmic movements of the whiskers, rather than all possible whisker movements, and early mammals may still have had moveable whiskers. Anat Rec, 2018. © 2018 American Association for Anatomy.

PMID: 30332721 [PubMed - indexed for MEDLINE]

Bolstering geometric morphometrics sample sizes with damaged and pathologic specimens: Is near enough good enough?

Sun, 01/10/2021 - 10:08
Related Articles

Bolstering geometric morphometrics sample sizes with damaged and pathologic specimens: Is near enough good enough?

J Anat. 2021 Jan 09;:

Authors: Mitchell DR, Kirchhoff CA, Cooke SB, Terhune CE

Abstract
Obtaining coordinate data for geometric morphometric studies often involves the sampling of dry skeletal specimens from museum collections. But many specimens exhibit damage and/or pathologic conditions. Such specimens can be considered inadequate for the analyses of shape and are excluded from study. However, the influences that damaged specimens may have on the assessment of normal shape variation have only been explored in two-dimensional coordinate data and no studies have addressed the inclusion of pathological specimens to date. We collected three-dimensional coordinate data from the cranium and mandible of 100 crab-eating macaques (Macaca fascicularis). Tests typically employed to analyze shape variation were performed on five datasets that included specimens with varying degrees of damage/pathology. We hypothesized that the inclusion of these specimens into larger datasets would strengthen statistical support for dominant biological predictors of shape, such as sex and size. However, we also anticipated that the analysis of only the most questionable specimens may confound statistical outputs. We then analyzed a small sample of good quality specimens bolstered by specimens that would generally be excluded due to damage or pathologic morphology and compared the results with previous analyses. The inclusion of damaged/pathologic specimens in a larger dataset resulted in increased variation linked to allometry, sexual dimorphism, and covariation, supporting our initial hypothesis. We found that analyzing the most questionable specimens alone gave consistent results for the most dominant aspects of shape but could affect outputs for less influential principal components and predictors. The small dataset bolstered with damaged/pathologic specimens provided an adequate assessment of the major components of shape, but finer scale differences were also identified. We suggest that normal and repeatable variation contributed by specimens exhibiting damage and/or pathology emphasize the dominant components and shape predictors in larger datasets, however, the various unique conditions may be more influential for limited sample sizes. Furthermore, we find that exclusion of damaged/pathologic specimens can, in some cases, omit important demographic-specific shape variation of groups of individuals more likely to exhibit these conditions. These findings provide a strong case for inclusion of these specimens into studies that focus on the dominant aspects of intraspecific shape variation. However, they may present issues when testing hypotheses relating to more fine-scale aspects of morphology.

PMID: 33421966 [PubMed - as supplied by publisher]

Monogamy as a Barrier to Human Papillomavirus Catch-Up Vaccination.

Sat, 01/09/2021 - 10:03
Related Articles

Monogamy as a Barrier to Human Papillomavirus Catch-Up Vaccination.

J Womens Health (Larchmt). 2021 Jan 08;:

Authors: Waters AV, Merrell LK, Thompson EL

Abstract
Background: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection (STI) in the United States. Although a vaccine to prevent HPV infection exists, only 53.7% of females 13-17 years of age were up-to-date on the HPV vaccination series in 2018. There is a catch-up period of vaccination for females 18-26 years of age that shows consistent underparticipation. A potential barrier to vaccination is relationship status, as long-term relationships may negatively impact HPV risk perception. This study examined monogamy as a risk factor for nonvaccination and explored how risk perception may influence this association. Materials and Methods: An electronic survey was distributed to females 18-26 years of age who attended a large public university in the mid-Atlantic region (n = 629). Multivariable and descriptive statistics were estimated using SAS 9.4 to explore the likelihood of vaccination during the catch-up period by relationship status. Results: Most participants had received the HPV vaccine, a small proportion of whom received it during the catch-up period. After adjusting for confounders, women who were in monogamous relationships were significantly less likely to have participated in HPV catch-up vaccination compared to women who were single and dating (adjusted odds ratio: 0.36, 95% confidence interval: 0.15, 0.87). Women in monogamous relationships had a lower average sexually transmitted disease (STD) risk perception compared to women who were single and dating (p < 0.0001). Conclusions: A decreased risk perception may present a barrier to participating in catch-up vaccination for monogamous women. Practitioners and the public health community should focus on communicating HPV risk to women in monogamous relationships, especially given the recently expanded age range for HPV vaccination.

PMID: 33416434 [PubMed - as supplied by publisher]

Grant application outcomes for biomedical researchers who participated in the National Research Mentoring Network's Grant Writing Coaching Programs.

Sat, 01/09/2021 - 10:03
Related Articles

Grant application outcomes for biomedical researchers who participated in the National Research Mentoring Network's Grant Writing Coaching Programs.

PLoS One. 2020;15(11):e0241851

Authors: Weber-Main AM, McGee R, Eide Boman K, Hemming J, Hall M, Unold T, Harwood EM, Risner LE, Smith A, Lawson K, Engler J, Steer CJ, Buchwald D, Jones HP, Manson SM, Ofili E, Schwartz NB, Vishwanatha JK, Okuyemi KS

Abstract
BACKGROUND: A diverse research workforce is essential for catalyzing biomedical advancements, but this workforce goal is hindered by persistent sex and racial/ethnic disparities among investigators receiving research grants from the National Institutes of Health (NIH). In response, the NIH-funded National Research Mentoring Network implemented a Grant Writing Coaching Program (GCP) to provide diverse cohorts of early-career investigators across the United States with intensive coaching throughout the proposal development process. We evaluated the GCP's national reach and short-term impact on participants' proposal submissions and funding outcomes.
METHODS: The GCP was delivered as six similar but distinct models. All models began with an in-person group session, followed by a series of coaching sessions over 4 to 12 months. Participants were surveyed at 6-, 12- and 18-months after program completion to assess proposal outcomes (submissions, awards). Self-reported data were verified and supplemented by searches of public repositories of awarded grants when available. Submission and award rates were derived from counts of participants who submitted or were awarded at least one grant proposal in a category (NIH, other federal, non-federal).
RESULTS: From June 2015 through March 2019, 545 investigators (67% female, 61% under-represented racial/ethnic minority, URM) from 187 different institutions participated in the GCP. Among them, 324 (59% of participants) submitted at least one grant application and 134 (41% of submitters) received funding. A total of 164 grants were awarded, the majority being from the NIH (93, 56%). Of the 74 R01 (or similar) NIH research proposals submitted by GCP participants, 16 have been funded thus far (56% to URM, 75% to women). This 22% award rate exceeded the 2016-2018 NIH success rates for new R01s.
CONCLUSION: Inter- and intra-institutional grant writing coaching groups are a feasible and effective approach to supporting the grant acquisition efforts of early-career biomedical investigators, including women and those from URM groups.

PMID: 33166315 [PubMed - indexed for MEDLINE]

Сardiac injury in rats with experimental posttraumatic stress disorder (ePTSD) and mechanisms of its limitation in ePTSD-resistant rats.

Fri, 01/08/2021 - 08:41
Related Articles

Сardiac injury in rats with experimental posttraumatic stress disorder (ePTSD) and mechanisms of its limitation in ePTSD-resistant rats.

J Appl Physiol (1985). 2021 Jan 07;:

Authors: Manukhina EB, Tseilikman VE, Komelkova MV, Lapshin MS, Goryacheva AV, Kondashevskaya MV, Mkhitarov VA, Lazuko SS, Tseilikman OB, Sarapultsev AP, Dmitrieva YA, Strizhikov VK, Kuzhel OP, Downey HF

Abstract
Traumatic stress causes post-traumatic stress disorder (PTSD). PTSD is associated with cardiovascular diseases and risk of sudden cardiac death in some subjects. We compared effects of predator stress (PS, cat urine scent, 10 days) on mechanisms of cardiac injury and protection in experimental PTSD-vulnerable (PTSD) and -resistant (PTSDr) rats. 14-days post-stress, rats were evaluated with an elevated plus-maze test, and assigned to PTSD and PTSDr groups according to an anxiety index calculated from the test results. Cardiac injury was evaluated by: 1) Exercise tolerance; 2) ECG; 3) Myocardial histomorphology; 4) Oxidative stress; 5) Pro- and anti-inflammatory cytokines. Myocardial heat shock protein 70 (HSP70) was also measured. Experimental PTSD developed in 40% of rats exposed to PS. Exercise tolerance of PTSD rats was 25% less than control rats and 21% less than PTSDr rats. ECG QRS, QT, and OTc intervals were longer in PTSD rats than in control and PTSDr rats. Only cardiomyocytes of PTSD rats had histomorphological signs of metabolic and hypoxic injury and impaired contractility. Oxidative stress markers were higher in PTSD than PTSDr rats. Pro-inflammatory IL-6 was higher in PTSD rats than in control and PTSDr rats, and anti-inflammatory IL-4 was lower in PTSD than in control and PTSDr rats. Myocardial HSP70 was lower in PTSD rats than PTSDr and control rats. Conclusion: Rats with PTSD developed multiple signs of cardiac injury. PTSDr rats were resistant also to cardiac injury. Factors that limit cardiac damage in PS rats include reduced inflammation and oxidative stress and increased protective HSP70.

PMID: 33411642 [PubMed - as supplied by publisher]

The Changing Landscape of Catholic Hospitals and Health Systems, 2008-2017.

Fri, 01/08/2021 - 08:41
Related Articles

The Changing Landscape of Catholic Hospitals and Health Systems, 2008-2017.

J Healthc Manag. 2021 Jan-Feb 01;66(1):33-45

Authors: Homan ME, White KR

Abstract
EXECUTIVE SUMMARY: More than 600 Catholic hospitals operating in the United States face pressures for efficiency and effectiveness as well as compliance with demands of the Roman Catholic Church. They have responded to the pressures in various ways that have led to mixed models of organizational ownership and management. The purpose of this study was to describe and analyze the status of Catholic hospital ownership and management, especially the strategic and structural features of the parent health systems. Longitudinal data (2008-2017) were acquired and analyzed using repeated-measures analysis. Descriptive statistics were prepared using cross-sectional matched pairing for 2008 and 2017 data. Of 4,253 hospitals studied, 534 changed ownership or management. More Catholic Church-operated hospitals, regardless of type of ownership (for-profit, not-for-profit, church), became decentralized to a greater degree over the 8-year period and took on more attributes of non-Catholic hospitals.The 21st century Catholic hospital is more likely to be partnered with a non-Catholic hospital or to be owned by a for-profit system than to be solely partnered with or operated by another Catholic system. Today's Catholic hospitals appear to be more similar to their non-Catholic counterparts. With the trend toward larger systems that comprise more diverse partners, an increase in lay oversight could lead to further movement away from Catholic identity and the original mission of a hospital. As systems grow in size but shrink in number, administrators must make difficult decisions about the type and scope of services offered as well as the partners they need to deliver their services.

PMID: 33411484 [PubMed - as supplied by publisher]

Increases in social support co-occur with decreases in depressive symptoms and substance use problems among adults in permanent supportive housing: an 18-month longitudinal study.

Fri, 01/08/2021 - 08:41
Related Articles

Increases in social support co-occur with decreases in depressive symptoms and substance use problems among adults in permanent supportive housing: an 18-month longitudinal study.

BMC Psychol. 2021 Jan 06;9(1):6

Authors: Tan Z, Mun EY, Nguyen UDT, Walters ST

Abstract
BACKGROUND: Social support is a well-known protective factor against depressive symptoms and substance use problems, but very few studies have examined its protective effects among residents of permanent supportive housing (PSH), a housing program for people with a history of chronic homelessness. We utilized unconditional latent growth curve models (LGCMs) and parallel process growth models to describe univariate trajectories of social support, depressive symptoms, and substance use problems and to examine their longitudinal associations in a large sample of adults residing in PSH.
METHODS: Participants were 653 adult PSH residents in North Texas (56% female; 57% Black; mean age: 51 years) who participated in a monthly health coaching program from 2014 to 2017. Their health behaviors were assessed at baseline and tracked every six months at three follow-up visits.
RESULTS: Unconditional LGCMs indicated that over time, social support increased, whereas depressive symptoms and substance use problems decreased. However, their rates of change slowed over time. Further, in parallel process growth models, we found that at baseline, individuals with greater social support tended to have less severe depressive symptoms and substance use problems (coefficients: - 0.67, p < 0.01; - 0.52, p < 0.01, respectively). Individuals with a faster increase in social support tended to have steeper rates of reduction in both depressive symptoms (coefficient: - 0.99, p < 0.01) and substance use problems (coefficient: - 0.98, p < 0.01), respectively.
CONCLUSIONS: This study suggests that plausibly, increases in social support, though slowing over time, still positively impact depressive symptoms and substance use problems among PSH residents. Future PSH programs could emphasize social support as an early component as it may contribute to clients' overall health.

PMID: 33407857 [PubMed - in process]

mixIndependR: a R package for statistical independence testing of loci in database of multi-locus genotypes.

Fri, 01/08/2021 - 08:41
Related Articles

mixIndependR: a R package for statistical independence testing of loci in database of multi-locus genotypes.

BMC Bioinformatics. 2021 Jan 06;22(1):12

Authors: Song B, Woerner AE, Planz J

Abstract
BACKGROUND: Multi-locus genotype data are widely used in population genetics and disease studies. In evaluating the utility of multi-locus data, the independence of markers is commonly considered in many genomic assessments. Generally, pairwise non-random associations are tested by linkage disequilibrium; however, the dependence of one panel might be triplet, quartet, or other. Therefore, a compatible and user-friendly software is necessary for testing and assessing the global linkage disequilibrium among mixed genetic data.
RESULTS: This study describes a software package for testing the mutual independence of mixed genetic datasets. Mutual independence is defined as no non-random associations among all subsets of the tested panel. The new R package "mixIndependR" calculates basic genetic parameters like allele frequency, genotype frequency, heterozygosity, Hardy-Weinberg equilibrium, and linkage disequilibrium (LD) by mutual independence from population data, regardless of the type of markers, such as simple nucleotide polymorphisms, short tandem repeats, insertions and deletions, and any other genetic markers. A novel method of assessing the dependence of mixed genetic panels is developed in this study and functionally analyzed in the software package. By comparing the observed distribution of two common summary statistics (the number of heterozygous loci [K] and the number of share alleles [X]) with their expected distributions under the assumption of mutual independence, the overall independence is tested.
CONCLUSION: The package "mixIndependR" is compatible to all categories of genetic markers and detects the overall non-random associations. Compared to pairwise disequilibrium, the approach described herein tends to have higher power, especially when number of markers is large. With this package, more multi-functional or stronger genetic panels can be developed, like mixed panels with different kinds of markers. In population genetics, the package "mixIndependR" makes it possible to discover more about admixture of populations, natural selection, genetic drift, and population demographics, as a more powerful method of detecting LD. Moreover, this new approach can optimize variants selection in disease studies and contribute to panel combination for treatments in multimorbidity. Application of this approach in real data is expected in the future, and this might bring a leap in the field of genetic technology.
AVAILABILITY: The R package mixIndependR, is available on the Comprehensive R Archive Network (CRAN) at: https://cran.r-project.org/web/packages/mixIndependR/index.html .

PMID: 33407074 [PubMed - in process]

Risk Factors for Failure of Splenic Angioembolization: A Multicenter Study of Level I Trauma Centers.

Fri, 01/08/2021 - 08:41
Related Articles

Risk Factors for Failure of Splenic Angioembolization: A Multicenter Study of Level I Trauma Centers.

J Surg Res. 2021 01;257:227-231

Authors: Bankhead-Kendall B, Teixeira P, Musonza T, Donahue T, Regner J, Harrell K, Brown CVR, Texas Trauma Study Group

Abstract
BACKGROUND: Angioembolization (AE) is an adjunct to nonoperative management (NOM) of splenic injuries. We hypothesize that failure of AE is associated with blood transfusion, grade of injury, and technique of AE.
METHODS: We performed a retrospective (2010-2017) multicenter study (nine Level I trauma centers) of adult trauma patients with splenic injuries who underwent splenic AE. Variables included patient physiology, injury grade, transfusion requirement, and embolization technique. The primary outcome was NOM failure requiring splenectomy. Secondary outcomes were mortality, complications, and length of stay.
RESULTS: A total of 409 patients met inclusion criteria; only 33 patients (8%) required delayed splenectomy. Patients who failed received more blood in the first 24 h (P = 0.009) and more often received massive transfusion (P = 0.01). There was no difference in failure rates for grade of injury, contrast blush on computed tomography, and branch embolized. After logistic regression, transfusion in the first 24 h was independently associated with failure of NOM (P = 0.02). Patients who failed NOM had more complications (P = 0.002) and spent more days in the intensive care unit (P < 0.0001), on the ventilator (P = 0.0001), and in the hospital (P < 0.0001). Patients who failed NOM had a higher mortality (15% versus 3%, P = 0.007), and delayed splenectomy was independently associated with mortality (odds ratio, 4.2; 95% confidence interval, 1.2-14.7; P = 0.03).
CONCLUSIONS: AE for splenic injury leads to effective NOM in 92% of patients. Transfusion in the first 24 h is independently associated with failure of NOM. Patients who required a delayed splenectomy suffered more complications and had higher hospital length of stay. Failure of NOM is independently associated with a fourfold increase in mortality.

PMID: 32861100 [PubMed - indexed for MEDLINE]

Comparative analysis of racial differences in breast tumor microbiome.

Fri, 01/08/2021 - 08:41
Related Articles

Comparative analysis of racial differences in breast tumor microbiome.

Sci Rep. 2020 08 24;10(1):14116

Authors: Thyagarajan S, Zhang Y, Thapa S, Allen MS, Phillips N, Chaudhary P, Kashyap MV, Vishwanatha JK

Abstract
Studies have demonstrated that environmental, host genetic, and socioeconomic factors influence the breast cancer prevalence landscape with a far-reaching influence on racial disparity to subtypes of breast cancer. To understand whether breast tissue harbors race-specific microbiota, we performed 16S rRNA gene-based sequencing of retrospective tumor and matched normal tissue adjacent to tumor (NAT) samples collected from Black non-Hispanic (BNH) and White non-Hispanic (WNH) women. Analysis of Triple Negative Breast cancer (TNBC) and Triple Positive Breast Cancer (TPBC) tissues for microbiota composition revealed significant differences in relative abundance of specific taxa at both phylum and genus levels between WNH and BNH women cohorts. Our main findings are that microbial diversity as measured by Shannon index was significantly lower in BNH TNBC tumor tissue as compared to matched NAT zone. In contrast, the WNH cohort had an inverse pattern for the Shannon index, when TNBC tumor tissue was compared to the matched NAT. Unweighted Principle Coordinates Analysis (PCoA) revealed a distinct clustering of tumor and NAT microbiota in both BNH and WNH cohorts.

PMID: 32839514 [PubMed - indexed for MEDLINE]

The long-term but not short-term use of benzodiazepine impairs motoric function and upregulates amyloid β in part through the suppression of translocator protein.

Fri, 01/08/2021 - 08:41
Related Articles

The long-term but not short-term use of benzodiazepine impairs motoric function and upregulates amyloid β in part through the suppression of translocator protein.

Pharmacol Biochem Behav. 2020 04;191:172873

Authors: Jung ME, Metzger DB, Hall J

Abstract
Many elderly American women use CNS depressant benzodiazepine (BZD) to ameliorate anxiety or insomnia. However, the chronic use of BZD (cBZD) is prevalent, causing adverse effects of BZD that include movement deficit. We previously reported that cBZD upregulates neurotoxic amyloid β42 (Aβ42) and downregulates neuroprotective translocator protein (TSPO) in the cerebellum, the brain area of movement and balance. The aim of the current study is two-fold: 1) to determine a direct effect of TSPO (inhibition) on cBZD-induced Aβ42 and Aβ-associated molecules; Aβ-producing-protein presenilin-1 (PS1) and Aβ-degrading-enzyme neprilysin and 2) to determine whether Aβ42 upregulation and motoric deficit occur upon a long-term (cBZD) rather than a short-term BZD (sBZD) treatment. Old female mice received BZD (lorazepam) for 20 days (cBZD) or 3 days (sBZD) with or without prototype TSPO ligand PK11195 and were tested for motoric performance for 3 days using Rotarod. ELISA was conducted to measure Aβ42 level and neprilysin activity in cerebellum. RT-PCR and immunoblot were conducted to measure the mRNA and protein levels of TSPO, PS1, and neprilysin. cBZD treatment decreased TSPO and neprilysin but increased Aβ42 accompanied by motoric deficit. Chronic PK11195 treatment acted as a TSPO inhibitor by suppressing TSPO expression and mimicked or exacerbated the effects of cBZD on all parameters measured except for PS1. None of the molecular and behavioral changes induced by cBZD were reproduced by sBZD treatment. These data suggest that cBZD upregulates Aβ42 and downregulates neprilysin in part through TSPO inhibition, the mechanisms distinct from sBZD, collectively contributing to motoric deficit.

PMID: 32105662 [PubMed - indexed for MEDLINE]

Current Models for Development of Disease-Modifying Osteoarthritis Drugs.

Thu, 01/07/2021 - 10:49

Current Models for Development of Disease-Modifying Osteoarthritis Drugs.

Tissue Eng Part C Methods. 2021 Jan 06;:

Authors: Makarczyk MJ, Gao Q, He Y, Li Z, Gold MS, Hochberg M, Bunnell B, Tuan RS, Goodman SB, Lin H

Abstract
Osteoarthritis (OA) is a painful and disabling disease that affects millions of people worldwide. Symptom-alleviating treatments exist, although none with long-term efficacy. Furthermore, there are currently no disease-modifying OA drugs (DMOADs) with demonstrated efficacy in OA patients, which is, in part, attributed to a lack of full understanding of the pathogenesis of OA. The inability to translate findings from basic research to clinical applications also highlights the deficiencies in the available OA models at simulating the clinically relevant pathologies and responses to treatments in humans. In this review, the current status in the development of DMOADs will be first presented, with special attention to those in Phase II-IV clinical trials. Next, current in vitro, ex vivo, and in vivo OA models are summarized and the respective advantages and disadvantages of each are highlighted. Notably, the development and application of microphysiological or tissue-on-a-chip systems for modeling OA in humans are presented and the issues that need to be addressed in the future are discussed. Microphysiological systems should be given serious consideration for their inclusion in the DMOAD development pipeline, both for their ability to predict drug safety and efficacy in human clinical trials at present, as well as for their potential to serve as a test platform for personalized medicine.

PMID: 33403944 [PubMed - as supplied by publisher]

What About Mom? Health Literacy and Maternal Mortality.

Thu, 01/07/2021 - 10:49
Related Articles

What About Mom? Health Literacy and Maternal Mortality.

J Consum Health Internet. 2020;24(1):50-61

Authors: Wagner T, Stark M, Milenkov AR

Abstract
This study examined health literacy of postpartum education materials assessing readability, understandability and cultural sensitivity using common health literacy measures. Materials examined rated poorly on measures of health literacy and cultural sensitivity using evidence-based measures including the Patient Education Materials Assessment Tool (PEMAT), Fry-based Readability and National Standards for Culturally and Linguistically Appropriate Services (CLAS). Findings suggested a need for health literate and culturally sensitive postpartum education. Materials and an App were developed for new moms to help them identify postpartum warning-signs and appropriate action moms should take to address symptoms or seek emergent care.

PMID: 33402879 [PubMed]

Association of Magnesium Intake with Liver Fibrosis among Adults in the United States.

Thu, 01/07/2021 - 10:49
Related Articles

Association of Magnesium Intake with Liver Fibrosis among Adults in the United States.

Nutrients. 2021 Jan 02;13(1):

Authors: Tao MH, Fulda KG

Abstract
Liver fibrosis represents the consequences of chronic liver injury. Individuals with alcoholic or nonalcoholic liver diseases are at high risk of magnesium deficiency. This study aimed to evaluate the association between magnesium and calcium intakes and significant liver fibrosis, and whether the associations differ by alcohol drinking status. Based on the National Health and Nutrition Examination Survey (NHANES) 2017-2018, the study included 4166 participants aged >18 years who completed the transient elastography examination and had data available on magnesium intake. The median liver stiffness of 8.2 kPa was used to identify subjects with significant fibrosis (≥F2). The age-adjusted prevalence of significant fibrosis was 12.81%. Overall total magnesium intake was marginally associated with reduced odds of significant fibrosis (p trend = 0.14). The inverse association of total magnesium intake with significant fibrosis was primarily presented among those who had daily calcium intake <1200 mg. There were no clear associations for significant fibrosis with calcium intake. Findings suggest that high total magnesium alone may reduce risk of significant fibrosis. Further studies are needed to confirm these findings.

PMID: 33401667 [PubMed - in process]

Adherence and Viral Suppression Among Participants of the Patient-centered Human Immunodeficiency Virus (HIV) Care Model Project: A Collaboration Between Community-based Pharmacists and HIV Clinical Providers.

Thu, 01/07/2021 - 10:49
Related Articles

Adherence and Viral Suppression Among Participants of the Patient-centered Human Immunodeficiency Virus (HIV) Care Model Project: A Collaboration Between Community-based Pharmacists and HIV Clinical Providers.

Clin Infect Dis. 2020 02 14;70(5):789-797

Authors: Byrd KK, Hou JG, Bush T, Hazen R, Kirkham H, Delpino A, Weidle PJ, Shankle MD, Camp NM, Suzuki S, Clay PG, Patient-centered HIV Care Model Team

Abstract
BACKGROUND: Human immunodeficiency virus (HIV) viral suppression (VS) decreases morbidity, mortality, and transmission risk.
METHODS: The Patient-centered HIV Care Model integrated community-based pharmacists with HIV medical providers and required them to share patient clinical information, identify therapy-related problems, and develop therapy-related action plans.Proportions adherent to antiretroviral therapy (proportion of days covered [PDC] ≥90%) and virally suppressed (HIV RNA <200 copies/mL), before and after model implementation, were compared. Factors associated with postimplementation VS were determined using multivariable logistic regression; participant demographics, baseline viral load, and PDC were explanatory variables. PDC was modified to account for time to last viral load in the year postimplementation, and stratified as <50%, 50% to <80%, 80% to <90%, and ≥90%.
RESULTS: The 765 enrolled participants were 43% non-Hispanic black, 73% male, with a median age of 48 years; 421 and 649 were included in the adherence and VS analyses, respectively. Overall, proportions adherent to therapy remained unchanged. However, VS improved a relative 15% (75% to 86%, P < .001). Higher PDC (adjusted odds ratio [AOR], 1.74 per 1-level increase in PDC category [95% confidence interval {CI}, 1.30-2.34]) and baseline VS (AOR, 7.69 [95% CI, 3.96-15.7]) were associated with postimplementation VS. Although non-Hispanic black persons (AOR, 0.29 [95% CI, .12-.62]) had lower odds of suppression, VS improved a relative 23% (63% to 78%, P < .001).
CONCLUSIONS: Integrated care models between community-based pharmacists and primary medical providers may identify and address HIV therapy-related problems and improve VS among persons with HIV.

PMID: 30953062 [PubMed - indexed for MEDLINE]

Comparison of two escalated enoxaparin dosing regimens for venous thromboembolism prophylaxis in obese hospitalized patients.

Wed, 01/06/2021 - 06:07
Related Articles

Comparison of two escalated enoxaparin dosing regimens for venous thromboembolism prophylaxis in obese hospitalized patients.

J Thromb Thrombolysis. 2021 Jan 05;:

Authors: Gibson CM, Hall C, Davis S, Schillig JM

Abstract
Standard fixed-dose enoxaparin dosing regimens may not provide adequate prophylaxis against venous thromboembolism among obese hospitalized patients. While several escalated doses have been shown to result in more frequent attainment of target anti-factor Xa levels than standard doses, few studies compare escalated doses to each other. In this prospective, multi-center trial, enoxaparin 0.5 mg/kg daily (weight-based dosing) and enoxaparin 40 mg twice daily were compared to determine if either dose resulted in more frequent attainment of anti-factor Xa levels within the goal range of 0.2-0.5 IU/mL. Eighty patients with a BMI ≥ 40 kg/m2 were enrolled. There was no difference in the percent of patients achieving goal anti-factor Xa levels (72.5% vs. 70.0%, respectively; p = 0.72). Patients were more likely to attain anti-factor Xa levels below goal range than above. No bleeding or thrombotic events occurred. Either weight-based or twice-daily escalated enoxaparin dosing regimens appear effective at achieving target anti-factor Xa levels among hospitalized patients, and no safety events were noted. Future studies are needed to determine the clinical significance of this result.

PMID: 33400099 [PubMed - as supplied by publisher]

A novel approach for visualization and localization of small amounts of DNA on swabs to improve DNA collection and recovery process.

Tue, 01/05/2021 - 07:34
Related Articles

A novel approach for visualization and localization of small amounts of DNA on swabs to improve DNA collection and recovery process.

Analyst. 2021 Jan 04;:

Authors: Kitchner E, Chavez J, Ceresa L, Bus MM, Budowle B, Gryczynski Z

Abstract
In this report, a simple and practical procedure is proposed for DNA localization on a solid matrix e.g., a collection swab. The approach is straightforward and employs spectrum decomposition using a model DNA intercalator Ethidium Bromide (EtBr). The proposed approach can detect picograms of DNA in solution and nanograms of DNA on solid surfaces (swabs) without the need for PCR amplification. The proposed technology offers the possibility for developing an inexpensive, sensitive, rapid, and practical method for localizing and recovering DNA deposited on collection swabs during routine DNA screening. Improved detection of low DNA concentrations is needed and, if feasible, will allow for better decision making in clinical medicine, biological and environmental research, and human identification in forensic investigations.

PMID: 33393553 [PubMed - as supplied by publisher]

Pages