Publications by authors named "Megan Smith"

331 Publications

Perturbations in Gut Microbiota Composition in Psychiatric Disorders: A Review and Meta-analysis.

JAMA Psychiatry 2021 Sep 15. Epub 2021 Sep 15.

Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.

Importance: Evidence of gut microbiota perturbations has accumulated for multiple psychiatric disorders, with microbiota signatures proposed as potential biomarkers. However, no attempts have been made to evaluate the specificity of these across the range of psychiatric conditions.

Objective: To conduct an umbrella and updated meta-analysis of gut microbiota alterations in general adult psychiatric populations and perform a within- and between-diagnostic comparison.

Data Sources: Cochrane Library, PubMed, PsycINFO, and Embase were searched up to February 2, 2021, for systematic reviews, meta-analyses, and original evidence.

Study Selection: A total of 59 case-control studies evaluating diversity or abundance of gut microbes in adult populations with major depressive disorder, bipolar disorder, psychosis and schizophrenia, anorexia nervosa, anxiety, obsessive compulsive disorder, posttraumatic stress disorder, or attention-deficit/hyperactivity disorder were included.

Data Extraction And Synthesis: Between-group comparisons of relative abundance of gut microbes and beta diversity indices were extracted and summarized qualitatively. Random-effects meta-analyses on standardized mean difference (SMD) were performed for alpha diversity indices.

Main Outcomes And Measures: Alpha and beta diversity and relative abundance of gut microbes.

Results: A total of 34 studies provided data and were included in alpha diversity meta-analyses (n = 1519 patients, n = 1429 control participants). Significant decrease in microbial richness in patients compared with control participants were found (observed species SMD = -0.26; 95% CI, -0.47 to -0.06; Chao1 SMD = -0.5; 95% CI, -0.79 to -0.21); however, this was consistently decreased only in bipolar disorder when individual diagnoses were examined. There was a small decrease in phylogenetic diversity (SMD = -0.24; 95% CI, -0.47 to -0.001) and no significant differences in Shannon and Simpson indices. Differences in beta diversity were consistently observed only for major depressive disorder and psychosis and schizophrenia. Regarding relative abundance, little evidence of disorder specificity was found. Instead, a transdiagnostic pattern of microbiota signatures was found. Depleted levels of Faecalibacterium and Coprococcus and enriched levels of Eggerthella were consistently shared between major depressive disorder, bipolar disorder, psychosis and schizophrenia, and anxiety, suggesting these disorders are characterized by a reduction of anti-inflammatory butyrate-producing bacteria, while pro-inflammatory genera are enriched. The confounding associations of region and medication were also evaluated.

Conclusions And Relevance: This systematic review and meta-analysis found that gut microbiota perturbations were associated with a transdiagnostic pattern with a depletion of certain anti-inflammatory butyrate-producing bacteria and an enrichment of pro-inflammatory bacteria in patients with depression, bipolar disorder, schizophrenia, and anxiety.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.2573DOI Listing
September 2021

The impact of HPV vaccination beyond cancer prevention: effect on pregnancy outcomes.

Hum Vaccin Immunother 2021 Oct;17(10):3562-3576

Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council NSW, Sydney, Australia.

While the benefits of human papillomavirus (HPV) vaccination relating to cervical cancer prevention have been widely documented, recent published evidence is suggestive of an impact on adverse pregnancy outcomes (APOs) in vaccinated mothers and their infants, including a reduction in rates of preterm births and small for gestational age infants. In this review, we examine this evidence and the possible mechanisms by which HPV vaccination may prevent these APOs. Large-scale studies linking HPV vaccination status with birth registries are needed to confirm these results. Potential confounding factors to consider in future analyses include other risk factors for APOs, and historical changes in both the management of cervical precancerous lesions and prevention of APOs. If confirmed, these additional benefits of HPV vaccination in reducing APO rates will be of global significance, due to the substantial health, social and economic costs associated with APOs, strengthening the case for worldwide HPV immunization.
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http://dx.doi.org/10.1080/21645515.2021.1936860DOI Listing
October 2021

Self-collection for HPV screening: a game changer in the elimination of cervical cancer.

Med J Aust 2021 Sep 9. Epub 2021 Sep 9.

Family Planning New South Wales, Sydney, NSW.

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http://dx.doi.org/10.5694/mja2.51262DOI Listing
September 2021

The naked truth: a comprehensive clarification and classification of current 'myths' in naked mole-rat biology.

Biol Rev Camb Philos Soc 2021 Sep 3. Epub 2021 Sep 3.

Department of Otolaryngology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, U.S.A.

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled 'Surprisingly long survival of premature conclusions about naked mole-rat biology' described 28 'myths' which, those authors claimed, are a 'perpetuation of beautiful, but falsified, hypotheses' and impede our understanding of this enigmatic mammal. Here, we re-examine each of these 'myths' based on evidence published in the scientific literature. Following Braude et al., we argue that these 'myths' fall into four main categories: (i) 'myths' that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) 'myths' that are based on incomplete understanding, where more evidence is clearly needed; (iii) 'myths' where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) 'myths' where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term 'myth' is particularly inappropriate when applied to competing, evidence-based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole-rat biology and attempt to clarify some of these misconceptions.
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http://dx.doi.org/10.1111/brv.12791DOI Listing
September 2021

Managed Care of Naked Mole-Rats.

Adv Exp Med Biol 2021 ;1319:381-407

Calico Life Sciences LLC, South San Francisco, CA, USA.

Naked mole-rats are a burgeoning model species in the field of biomedical research and are also housed at many zoos throughout the world. These mammals possess many traits that have a large impact on the way that they are kept in captivity such as their eusociality, thermolability and lack of need for drinking water. This chapter outlines the captive care and unusual housing needs of these animals. Providing information and examples from our own experiences while working with naked mole-rats for many decades. While this chapter serves as a good framework for the captive care of this mammal species, it is in no way all-encompassing but simply reflects the way in which we have managed over many years to successfully sustain our colony of thousands of animals.
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http://dx.doi.org/10.1007/978-3-030-65943-1_16DOI Listing
August 2021

Comparing the clinical presentation and outcomes of dogs receiving medical or surgical treatment for osseous-associated cervical spondylomyelopathy.

Vet Rec 2021 Aug 18:e831. Epub 2021 Aug 18.

Department of Clinical Science and Services, Royal Veterinary College, University of London Hatfield, Hertfordshire, UK.

Background: This study aimed to compare the clinical presentation, short and long term outcomes of dogs treated surgically or medically for Osseous associated cervical spondylomyelopathy.

Methods: Information collected retrospectively from medical records included signalment, neurological status and treatment type. Surgical treatment consisted of dorsal laminectomy. Medical treatment involved restricted exercise and medication. Improvement or deterioration in neurological status was determined at discharge, re-examination 4-8 weeks post-treatment and by telephone interview with the referring veterinary surgeon or owner at the time of the study, which ranged from 8-54 months following the discharge (median, 16 months).

Results: Twenty-four dogs were treated surgically and 30 medically. Neurological grade at clinical presentation was significantly higher in surgically treated dogs (p = 0.004). Transient early postoperative neurological deterioration occurred in 73.1% of surgically treated dogs. For medical cases, long term improvement was seen in 15% of cases, remained static in 40% and deterioration in 45%. Surgical treatment resulted in long term improvement in 67% of cases, remained static in 29% and deterioration in 4% of cases.

Conclusion: This study suggests that surgery is a favourable treatment option, however, requires intensive post-operative care. Medical treatment was associated with a guarded prognosis but could be a viable treatment option for selected dogs.
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http://dx.doi.org/10.1002/vetr.831DOI Listing
August 2021

Understanding the association between material hardship and posttraumatic stress disorder: a test of the social selection and social causation hypotheses and an exploration of gender differences.

Soc Psychiatry Psychiatr Epidemiol 2021 Aug 12. Epub 2021 Aug 12.

Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.

Purpose: There is a well-established association between poverty and posttraumatic stress disorder (PTSD); however, little research has tested the temporality of the association.

Methods: Using data from Waves IV (2008; N = 14,800) and V (2016-2018; N = 10,685) of the National Longitudinal Study of Adolescent to Adult Health, we examined temporal associations between material hardship (a specific operationalization of poverty) and PTSD, as well as assessed for potential gender differences in associations. We conducted logistic regression and generalized structural equation modeling to examine associations between material hardship and PTSD and assess for mediation and moderation by gender.

Results: Prior PTSD diagnoses were associated with an increased likelihood of material hardship (OR = 1.64; 95% CI 1.21, 2.21). The indirect effect of gender on material hardship through PTSD diagnoses was significant. Prior material hardship was associated with an increased likelihood of PTSD diagnoses (OR = 1.81; 95% CI 1.35, 2.42). The indirect effect of gender on PTSD diagnoses through material hardship was significant. There was no evidence of moderation by gender for either association.

Conclusion: Results suggest reciprocal associations between material hardship and PTSD. Economic policies, as well as improved access to evidence-based PTSD treatments, may reduce the burden of both material hardships and PTSD.
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http://dx.doi.org/10.1007/s00127-021-02162-1DOI Listing
August 2021

Implementation of a Multifactorial Strategy Including Direct Bedding Is Associated With a Rapid and Sustained Reduction in Left Without Being Seen.

Cureus 2021 Jul 6;13(7):e16209. Epub 2021 Jul 6.

Emergency Medicine, St. Francis Hospital and Medical Center, Hartford, USA.

Objective Improve left without being seen (LWBS) in our high volume, tertiary care trauma center. Prior to intervention, our LWBS rate was 4.4%. Including a direct bedding strategy, we successfully reduced our LWBS to <1%. Design and method We utilized a retrospective before and after model. We hired a clinical documentation specialist and tracked several metrics. These included daily census, admission rates, and door to provider, door to room, average boarding, and door to disposition times. Data were collected and disseminated daily. Reports were shared at organization quality meetings. Simultaneously, we implemented the direct bedding initiative in conjunction with quick registration. To accommodate higher numbers of patients and expediate movement to care spaces, all patient spaces were clearly designated and labeled. Results Direct bedding began in September 2015 and our LWBS was 4.4%. One-year post-intervention, our LWBS was <2%. Within four years, it was <0.5%. The LWBS rate for each year, 2016 to 2019, was significantly lower than the control period (p < 0.01) (2015 up to September). Improvement was also seen in door-to-provider time and with patient experience scores. Conclusion Our multifactorial approach was associated with a profound and sustained reduction in LWBS over a short time period.
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http://dx.doi.org/10.7759/cureus.16209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341251PMC
July 2021

Twinning: Coronary Artery Disease in Monozygotic Twins.

Cureus 2021 Jul 3;13(7):e16139. Epub 2021 Jul 3.

Cardiology, University of Kentucky, Bowling Green, USA.

We present the case of a patient whose monozygotic twin brother suffered a fatal myocardial infarction at the age of 40. The patient presented with similar symptoms as his brother. Given the family history, ischemic evaluation was undertaken and revealed similar coronary anatomy and severe coronary artery disease (CAD). We review the current literature regarding genetic and environmental factors regarding coronary anatomy, locations of atherosclerotic lesions, and screening in twins.
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http://dx.doi.org/10.7759/cureus.16139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330499PMC
July 2021

Population-based utility scores for HPV infection and oropharyngeal squamous cell carcinoma among Indigenous Australians.

BMC Public Health 2021 07 26;21(1):1455. Epub 2021 Jul 26.

Australian Research Centre for Population Oral Health, Adelaide Dental School, The University of Adelaide, Adelaide Health & Medical Sciences Building, Adelaide, 5005, Australia.

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is associated with high mortality. Human papillomavirus (HPV) infection is a significant risk factor for OPSCC. Utilities are fundamental values representing the strength of individuals' preferences for specific health-related outcomes. Our study aim was to work in partnership with Indigenous communities in South Australia to develop, pilot test and estimate utility scores for health states related to HPV, HPV vaccination, precursor OPSCC and its treatment, and early stage OPSCC among Indigenous Australians.

Methods: Development and pilot testing of hypothetical HPV and OPSCC health states, specifically through the lens of being Indigenous Australian, was conducted with an Indigenous Reference Group. Six health states were decided upon, with utility scores calculated using a two-stage standard gamble approach among a large convenience sample of Indigenous Australians aged 18+ years residing in South Australia. The rank, percentage of perfect health and utility score of each health state was summarised using means, and medians at 12 months and lifetime duration. Potential differences by age, sex and residential location were assessed using the Wilcox Rank Sum test.

Results: Data from 1011 participants was obtained. The mean utility scores decreased with increasing severity of health states, ranging from 0.91-0.92 in 'screened, cytology normal, HPV vaccination' and 'screened, HPV positive, endoscopy normal', to less than 0.90 (ranging from 0.87-0.88) in lower grade conditions (oral warts and oral intraepithelial neoplasia) and less than 0.80 (ranging from 0.75-0.79) in 'early stage throat cancer'. Higher utility scores were observed for 'screened, cytology normal and HPV vaccination' among younger participants (18-40 years), for 'early stage invasive throat cancer' among females, and for 'oral intraepithelial neoplasia' and 'early stage invasive throat cancer' among metropolitan-dwelling participants.

Conclusion: Among a large sample of Indigenous Australians, utility for oral HPV infection and OPSCC decreased with severity of health states. Older participants, as well as males and those residing in non-metropolitan locations, had decreased utility for high-grade cytology and early invasive cancer states. Our findings are an important contribution to cost-utility and disease prevention strategies that seek to inform policies around reducing HPV infection and OPSCC among all Australians.
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http://dx.doi.org/10.1186/s12889-021-11496-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314643PMC
July 2021

Cost-effectiveness of nonavalent HPV vaccine in Norway considering current empirical data and validation.

Prev Med 2021 09 21;150:106688. Epub 2021 Jul 21.

Harvard T.H. Chan School of Public Health, Center for Health Decision Science, Boston, MA, USA; Department of Health Management and Health Economics, University of Oslo, Oslo, Norway.

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http://dx.doi.org/10.1016/j.ypmed.2021.106688DOI Listing
September 2021

Population-based utility scores for HPV infection and cervical squamous cell carcinoma among Australian Indigenous women.

PLoS One 2021 22;16(7):e0254575. Epub 2021 Jul 22.

Adelaide Dental School, Australian Research Centre for Population Oral Health, The University of Adelaide, Adelaide, Australia.

Objective: Working in partnership with Indigenous communities in South Australia, we aimed to develop, pilot test and estimate utility scores for health states relating to cervical cancer screening, precancer, and invasive cervical cancer and precancer/cancer treatment among Indigenous women.

Methods: Development and pilot testing of hypothetical cervical cancer health states, specifically through the lens of being an Indigenous Australian woman, was done with an Indigenous Reference Group in conjunction with five female Indigenous community members. Six health states were developed. These included: (1) Screened: cytology normal; (2) human papillomaviruses (HPV) positive with cytology normal; (3) low grade cytology (LSIL);(4) high grade cytology (HSIL); (5) early stage cervical cancer and; (6) later stage cervical cancer. Utility scores were calculated using a two-stage standard gamble approach among a large cohort of Indigenous Australian women taking part in a broader study involving oral HPV infection. The mean and standard deviation (SD) of the rank, percentage of respondents with a utility = 1 (perfect health) and utility score of each health state was summarised. Mean (SD) and medians and inter-quartile range (IQR) over 12 months and lifetime duration were calculated. Potential differences by age and residential location were assessed using the Wilcox Sum Rank test.

Results: Data was obtained from 513 Indigenous women aged 19+ years. Mean utility scores were higher for the four non-cancer health states than for invasive cervical cancer states (p-values <0.05). Lower mean utility scores were observed for late stage cervical cancer, with 0.69 at 12 months and 0.70 for lifetime duration (Intra-class correlation coefficients = 0.425). Higher utility scores were observed for the four non-cancer health states among non-metropolitan participants (ranged from 0.93 to 0.98) compared with metropolitan participants (ranged from 0.86 to 0.93) (p-values<0.05).

Conclusion: Among a large cohort of Indigenous Australian women, the reduction in quality of life (which utilities reflect) was perceived to be greater with increasing severity of cervical cancer health states. There were differences observed by geographic location, with positive cervical screening and precursor cancer-related quality of life being much higher among non-metropolitan-dwelling participants. These utility values, from one of the largest such studies ever performed in any population will be uniquely able to inform modelled evaluations of the benefits and costs of cervical cancer prevention interventions in Indigenous women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298063PMC
July 2021

Giant Coronary Artery Aneurysms.

Cureus 2021 Jun 12;13(6):e15611. Epub 2021 Jun 12.

Interventional Cardiology, The Medical Center, Bowling Green, USA.

We present the case of a patient with giant coronary artery aneurysm. He has underlying severe coronary atherosclerosis and concomitant aneurysms of the abdominal aorta and popliteal artery. Our patient was treated surgically in the past due to underlying severe atherosclerosis. Despite bypass, his coronary aneurysms continued to enlarge. There is a lack of randomized trials regarding management to guide the decision-making process. Our case describes the work-up and treatment of a patient with giant coronary artery aneurysm requiring urgent orthopedic surgery.
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http://dx.doi.org/10.7759/cureus.15611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275069PMC
June 2021

Species Tree Inference Methods Intended to Deal with Incomplete Lineage Sorting Are Robust to the Presence of Paralogs.

Syst Biol 2021 Jul 10. Epub 2021 Jul 10.

Department of Computer Science, Rice University, 6100 Main Street, Houston, TX 77005, USA.

Many recent phylogenetic methods have focused on accurately inferring species trees when there is gene tree discordance due to incomplete lineage sorting (ILS). For almost all of these methods, and for phylogenetic methods in general, the data for each locus is assumed to consist of orthologous, single-copy sequences. Loci that are present in more than a single copy in any of the studied genomes are excluded from the data. These steps greatly reduce the number of loci available for analysis. The question we seek to answer in this study is: What happens if one runs such species tree inference methods on data where paralogy is present, in addition to or without ILS being present? Through simulation studies and analyses of two large biological data sets, we show that running such methods on data with paralogs can still provide accurate results. We use multiple different methods, some of which are based directly on the multispecies coalescent (MSC) model, and some of which have been proven to be statistically consistent under it. We also treat the paralogous loci in multiple ways: from explicitly denoting them as paralogs, to randomly selecting one copy per species. In all cases the inferred species trees are as accurate as equivalent analyses using single-copy orthologs. Our results have significant implications for the use of ILS-aware phylogenomic analyses, demonstrating that they do not have to be restricted to single-copy loci. This will greatly increase the amount of data that can be used for phylogenetic inference.
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http://dx.doi.org/10.1093/sysbio/syab056DOI Listing
July 2021

Working towards a comprehensive understanding of HPV and cervical cancer among Indigenous women: a qualitative systematic review.

BMJ Open 2021 06 30;11(6):e050113. Epub 2021 Jun 30.

Australian Research Centre for Population Oral Health, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia.

Rationale: Indigenous peoples carry a disproportionate burden of infectious diseases and cancers and are over-represented among the socially disadvantaged of most countries. Human papillomavirus (HPV) is a risk factor and causative agent of cervical, oropharyngeal and other cancers. Recent literature shows evidence of Indigenous populations being at increased risk of HPV infections and its associated cancers.

Objective: This is a qualitative systematic review. The objective of this study was to explore the experiences and barriers Indigenous women face in relation to HPV awareness, knowledge and cervical screening, in order to better understand factors that may mitigate against or facilitate prevention efforts for HPV infection and associated cancers.

Methods: Two investigators independently searched MEDLINE, PubMed, SCOPUS and Web of Science databases (for articles published from inception until 30 June 2020) using a prespecified search strategy to identify qualitative studies on narratives of Indigenous women regarding HPV infection awareness, knowledge and cervical screening, across all geographic and income-level settings. Using a 'meta-study' approach, a social ecological model of cervical screening, infection and associated cancer prevention among Indigenous populations was formulated.

Results: Five core themes were identified and formulated within the social ecological model; intrapersonal factors, interpersonal factors, institutional/organisational factors, sociocultural/community factors and public policy. These collectively formed the proposed social ecological model of HPV infection awareness and cervical cancer prevention among Indigenous women. This model has been synthesised by taking into account personal stories of Indigenous women and healthcare workers, thus offering a more nuanced, organised, structured and culturally sensitive approach to policy translation.

Conclusion: The social ecological model of HPV infection awareness and cervical cancer prevention among Indigenous women offers a holistic and practical approach for Indigenous health policy makers. It clearly addresses the high risk of Indigenous populations at a global level in experience of both HPV infection and HPV-related cancers.

Prospero Registration Number: CRD42020207643.
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http://dx.doi.org/10.1136/bmjopen-2021-050113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246376PMC
June 2021

A calibration equation between Δ values of carbonate and temperature.

Rapid Commun Mass Spectrom 2021 Sep;35(17):e9147

Department of Marine Geosciences, RSMAS, University of Miami, Miami, Florida.

Rationale: Information on the temperature of formation or alteration of carbonate minerals can be obtained by measuring the abundance of the isotopologues 47 and 48 (Δ and Δ values) of CO released during acid dissolution. The combination of these two proxies can potentially provide a greater insight into the temperature of formation, particularly if the carbonate minerals form by non-equilibrium processes.

Methods: We have precipitated calcium carbonates at seven temperatures between 5 and 65°C and measured their δ values using a Thermo-253 plus isotope ratio mass spectrometer. The values were transformed to Δ values in the conventional manner and then converted to the carbon dioxide equilibrium scale.

Results: Using the Δ values, we have established an empirical calibration between temperature and Δ values: [Formula: see text] CONCLUSIONS: The calibration line produced allows the determination of the temperature of natural carbonates using the Δ values and agrees with the measurements of the Δ and Δ values of some carbonates assumed to have formed under equilibrium conditions.
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http://dx.doi.org/10.1002/rcm.9147DOI Listing
September 2021

-Nitrophenyl esters provide new insights and applications for the thiolase enzyme OleA.

Comput Struct Biotechnol J 2021 21;19:3087-3096. Epub 2021 May 21.

Biotechnology Institute, University of Minnesota, St Paul, MN, USA.

The OleA enzyme is distinct amongst thiolase enzymes in binding two long (≥C) acyl chains into structurally-opposed hydrophobic channels, denoted A and B, to carry out a non-decarboxylative Claisen condensation reaction and initiate the biosynthesis of membrane hydrocarbons and β-lactone natural products. OleA has now been identified in hundreds of diverse bacteria via bioinformatics and high-throughput screening using -nitrophenyl alkanoate esters as surrogate substrates. In the present study, -nitrophenyl esters were used to probe the reaction mechanism of OleA and shown to be incorporated into Claisen condensation products for the first time. -Nitrophenyl alkanoate substrates alone were shown not to undergo Claisen condensation, but co-incubation of -nitrophenyl esters and CoA thioesters produced mixed Claisen products. Mixed product reactions were shown to initiate via acyl group transfer from a -nitrophenyl carrier to the enzyme active site cysteine, C143. Acyl chains esterified to -nitrophenol were synthesized and shown to undergo Claisen condensation with an acyl-CoA substrate, showing potential to greatly expand the range of possible Claisen products. Using -nitrophenyl 1-C-decanoate, the Channel A bound thioester chain was shown to act as the Claisen nucleophile, representing the first direct evidence for the directionality of the Claisen reaction in any OleA enzyme. These results both provide new insights into OleA catalysis and open a path for making unnatural hydrocarbon and β-lactone natural products for biotechnological applications using cheap and easily synthesized -nitrophenyl esters.
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http://dx.doi.org/10.1016/j.csbj.2021.05.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180931PMC
May 2021

Toddlers Using Tablets: They Engage, Play, and Learn.

Front Psychol 2021 31;12:564479. Epub 2021 May 31.

Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada.

Although very young children have unprecedented access to touchscreen devices, there is limited research on how successfully they operate these devices for play and learning. For infants and toddlers, whose cognitive, fine motor, and executive functions are immature, several basic questions are significant: (1) Can they operate a tablet purposefully to achieve a goal? (2) Can they acquire operating skills and learn new information from commercially available apps? (3) Do individual differences in executive functioning predict success in using and learning from the apps? Accordingly, 31 2-year-olds ( = 30.82 month, = 2.70; 18 female) were compared with 29 3-year-olds ( = 40.92 month, = 4.82; 13 female) using two commercially available apps with different task and skill requirements: (1) a shape matching app performed across 3 days, and (2) a storybook app with performance compared to that on a matched paper storybook. Children also completed (3) the Minnesota Executive Functioning Scale. An adult provided minimal scaffolding throughout. The results showed: (1) toddlers could provide simple goal-directed touch gestures and the manual interactions needed to operate the tablet (2) after controlling for prior experience with shape matching, toddlers' increased success and efficiency, made fewer errors, decreased completion times, and required less scaffolding across trials, (3) they recognized more story content from the e-book and were less distracted than from the paper book, (4) executive functioning contributed unique variance to the outcome measures on both apps, and (5) 3-year-olds outperformed 2-year-olds on all measures. The results are discussed in terms of the potential of interactive devices to support toddlers' learning.
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http://dx.doi.org/10.3389/fpsyg.2021.564479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200401PMC
May 2021

Ivacaftor-elexacaftor-tezacaftor and tacrolimus combination in cystic fibrosis.

J Cyst Fibros 2021 Jun 12. Epub 2021 Jun 12.

Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, UAB, Birmingham, AL. Electronic address:

The CFTR modulator combination elexacaftor/tezacaftor/ivacaftor (ETI) is a genetic mutation-targeted treatment in cystic fibrosis that results in profound improvements in clinical outcomes. Each of the compounds are substrates of CYP3A4/5, the cytochrome P450 enzyme family for which tacrolimus is also a substrate. The use of these compounds in an individual with a solid organ transplant has not been previously studied and there is potential for a drug interaction. In this report, we describe a pediatric liver transplant recipient with clinical decline related to cystic fibrosis who improved substantially with ETI, without significant impact on the systemic exposure of either ETI or tacrolimus.
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http://dx.doi.org/10.1016/j.jcf.2021.05.008DOI Listing
June 2021

Deletion of Fibroblast growth factor 9 globally and in skeletal muscle results in enlarged tuberosities at sites of deltoid tendon attachments.

Dev Dyn 2021 Jun 6. Epub 2021 Jun 6.

College of Engineering, University of Delaware, Newark, Delaware, USA.

Background: The growth of most bony tuberosities, like the deltoid tuberosity (DT), rely on the transmission of muscle forces at the tendon-bone attachment during skeletal growth. Tuberosities distribute muscle forces and provide mechanical leverage at attachment sites for joint stability and mobility. The genetic factors that regulate tuberosity growth remain largely unknown. In mouse embryos with global deletion of fibroblast growth factor 9 (Fgf9), the DT size is notably enlarged. In this study, we explored the tissue-specific regulation of DT size using both global and targeted deletion of Fgf9.

Results: We showed that cell hypertrophy and mineralization dynamics of the DT, as well as transcriptional signatures from skeletal muscle but not bone, were influenced by the global loss of Fgf9. Loss of Fgf9 during embryonic growth led to increased chondrocyte hypertrophy and reduced cell proliferation at the DT attachment site. This endured hypertrophy and limited proliferation may explain the abnormal mineralization patterns and locally dysregulated expression of markers of endochondral development in Fgf9 attachments. We then showed that targeted deletion of Fgf9 in skeletal muscle leads to postnatal enlargement of the DT.

Conclusion: Taken together, we discovered that Fgf9 may play an influential role in muscle-bone cross-talk during embryonic and postnatal development.
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http://dx.doi.org/10.1002/dvdy.383DOI Listing
June 2021

Cohort profile: indigenous human papillomavirus and oropharyngeal squamous cell carcinoma study - a prospective longitudinal cohort.

BMJ Open 2021 06 3;11(6):e046928. Epub 2021 Jun 3.

Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, New South Wales, Australia.

Purpose: Our aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma (OPSCC)-related HPV types (HPV 16 or 18); (3) develop HPV-related health state valuations and; (4) determine the impact on OPSCC and cervical cancers, and the cost-effectiveness of extending publicly-funded HPV vaccination among Indigenous Australians.

Participants: Participants were recruited from February 2018 to January 2019. Twelve-month follow-up occurred from March 2019 to March 2020. Participants provided socio-demographic characteristics, health-related behaviours including tobacco and alcohol use and sexual history. Health state preferences in regard to HPV vaccination, knowledge regarding HPV infection, OPSCC and cervical cancer were collected using a two-stage standard gamble approach. Participants provided saliva samples and DNA for microbial genotyping was extracted.

Findings To Date: Of the 910 participants who were positive for β-globin at baseline, 35% had any oral HPV infection. The most prevalent HPV types were 13 or 32 (Heck's disease; 23%). The second most prevalent types were associated with OPSCC (HPV 16 or 18; 3.3%). Of the 645 participants who were positive for β-globin at 12-month follow-up, 43% had any HPV infection. Of these, 33% were HPV types 13 or 32 and 2.5% were HPV 16 or 18. Some 588 participants had β-globin positive oral samples at baseline and 12-month follow-up. The prevalence of any oral HPV infection increased from 34% at baseline to 44% at 12-month follow-up; due to increases in HPV types 13 or 32 (20% at baseline and 34% at 12-month follow-up).

Future Plans: Further funding will be sought to continue follow-up of this cohort, and to include (after a full medical history) a thorough clinical examination of the external head and neck; a complete oral examination and examination of the oropharynx. Blood tests for early stage OPSCC will also be undertaken.
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http://dx.doi.org/10.1136/bmjopen-2020-046928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183277PMC
June 2021

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis.

Prev Med 2021 10 23;151:106623. Epub 2021 May 23.

Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, Australia. Electronic address:

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5-6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15-30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.
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http://dx.doi.org/10.1016/j.ypmed.2021.106623DOI Listing
October 2021

A systematic review and meta-analysis of the prevalence of human papillomavirus infection in Indigenous populations - A Global Picture.

J Oral Pathol Med 2021 May 18. Epub 2021 May 18.

Australian Research Centre for Population Oral Health, Adelaide Dental School, University of Adelaide, Adelaide, SA, Australia.

Background And Aim: Recent trends have shown a decline in the rates of human papillomavirus (HPV)-associated cervical cancer in the vaccinated population but there has been a spike in the HPV-associated oropharyngeal, anal and penile cancers in the majority of the unvaccinated population which are young and middle-aged males. Indigenous populations at an international level carry a disproportionate burden of most diseases. The aim of this meta-analysis was to ascertain the worldwide prevalence of HPV infection in Indigenous populations stratified by sex and site and to document the most commonly reported HPV types.

Methods: Published articles on HPV infection in Indigenous populations from PubMed, Scopus, EMBASE and Web of Science were systematically searched from inception until 23 December 2019.

Results: A total of 41 studies were included in the final analysis. The pooled worldwide prevalence of HPV infection (for both oral and genital sites, both males and females) in Indigenous populations was 34.2% (95% CI: 28.9%-39.8%). Subgroup analysis (geographical) showed that the pooled prevalence for African Indigenous, American Indigenous and Asian-Oceanic Indigenous populations were 33.0% (95% CI: 12.8%-57.1%), 33.0% (95% CI: 27.4%-38.9%) and 33.3% (95% CI: 0.17.5%-51.3%), respectively.

Conclusion: There are not enough data on the burden of the infection carried by males especially with respect to highly suspicious sites like oropharynx. Also, we conclude an overall high prevalence of HPV infection in the Indigenous populations and increasing their susceptibility to benign and malignant manifestations of HPV.
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http://dx.doi.org/10.1111/jop.13201DOI Listing
May 2021

Power, autonomy and interprofessional practice in dietitian clinical decision making: An interpretive study in acute hospitals.

J Hum Nutr Diet 2021 May 16. Epub 2021 May 16.

Faculty of Science, Charles Sturt University, Wagga Wagga, NSW, Australia.

Dietitians learn clinical decision making (CDM) predominantly as an autonomous cognitive process that considers the needs and preferences of the patient. Although interprofessional education is increasing in tertiary dietetic programmes, a paucity of research exists that explores the nature of how practising dietitians make decisions, independent or otherwise. This qualitative interpretative study explored the nature of experienced dietitian CDM in the acute care setting. Philosophical hermeneutic principles guided text construction and interpretation via in-depth, semi-structured interviews with practising dietitians with at least 3 years of experience. A reference focus group commented on the emerging findings, increasing the rigour of the research. Ten dietitians participated in the interviews and there were five dietitians in the reference focus group. CDM was found to be a highly social phenomenon with varying degrees of autonomy involving complex power relations with various other health professionals, in particular, medical practitioners. Dietitians respond to existing power relations in key ways, including building and maintaining relationships, advocating on behalf of the patient and negotiating decisions with other healthcare staff when in pursuit of improved health and nutrition related outcomes for patients. Strategic interprofessional communication skills are foundational to effective patient care and advancing the role of the dietitian. Power and autonomy in dietitian CDM are important concepts that could inform interprofessional education when seeking to promote both effective dietetic and interprofessional practice.
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http://dx.doi.org/10.1111/jhn.12917DOI Listing
May 2021

Improving Maternal Mental Health as a Pathway to Economic Mobility in the TANF System.

Psychiatr Serv 2021 May 17:appips202000492. Epub 2021 May 17.

Department of Psychiatry (Smith, Callinan, Holmes) and Child Study Center (Smith, Posner, Ebling), Yale University School of Medicine, New Haven, Connecticut; Department of Social and Behavioral Sciences, Yale University School of Public Health, New Haven, Connecticut (Smith); Department of Psychology, College of Staten Island, City University of New York, Staten Island (Holmes).

Objective: The authors sought to evaluate the acceptability, feasibility, and initial outcomes of the delivery of a group cognitive-behavioral therapy (CBT) mental health intervention for mothers in the Temporary Assistance for Needy Families (TANF) program.

Methods: An 8-week group CBT program was made available to parenting women (N=40) in a large, urban TANF system from April to August 2019. Participants completed baseline and endpoint measures to assess depressive symptoms, perceived stress, social support, employment, and program acceptability. TANF administrative data were examined to assess TANF engagement.

Results: TANF staff were successfully trained to deliver CBT. The participants reported significantly reduced depressive symptoms and perceived stress; perceived social support significantly increased from the beginning to the end of the intervention.

Conclusions: A model that fully embedded CBT delivery in a TANF system was acceptable to low-income parenting women and TANF staff and reduced depressive symptoms among the women. The scalability of interventions to address maternal depression among low-income women has presented a challenge. Delivering mental health interventions in the U.S. TANF system may offer a scalable method to reduce depression and increase employment in a population bearing a high mental health burden.
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http://dx.doi.org/10.1176/appi.ps.202000492DOI Listing
May 2021

Challenges in managing ST elevation myocardial infarction during the COVID-19 pandemic.

World J Cardiol 2021 Apr;13(4):76-81

Department ofCardiology, University of Kentucky College of Medicine, Bowling Green, KY 42101, United States.

Background: Coronavirus disease 2019 (COVID-19) may contribute to delayed presentations of acute myocardial infarction. Delayed presentation with late reperfusion is often associated with an increased risk of mechanical complications and adverse outcomes. Inherent delays are possible as every patient who is acutely sick is being considered a potential case or a career of COVID-19. Also, standardized personal protective equipment precautions are established for all members of the team, regardless of pending COVID-19 testing which might further add to delays.

Aim: To compare performance measures and clinical outcomes of all patients who presented to our facility with ST elevation myocardial infarction (STEMI) during the COVID-19 pandemic to same time cohort from 2019.

Methods: All patients who presented to our facility with STEMI during the pandemic were compared to a matched cohort during the same time period in 2019. STEMI with unknown time of symptom onset and inpatient STEMI patients were excluded. Primary outcome was major adverse cardiac events (MACE) in-hospital and up to 14 d after STEMI, including death, myocardial infarction, cardiac arrest, or stroke. Significant differences among groups for continuous variables were tested through ANOVA, using SYSTAT, version 13. Chi-square tests of association were used to compare patient characteristics among groups using SYSTAT. Relative risk scores and associated tests for significance were calculated for discrete variables using MedCalc (MedCalc Software, Ostend, Belgium).

Results: There was a significantly longer time interval from symptom onset to first medical contact (FMC) in the COVID-19 group ( < 0.02). Time to first electrocardiogram, door-to-balloon time, and FMC to balloon time were not significantly affected. The right coronary artery was the most common culprit for STEMI in both the cohorts. Over 60% of patients had one or more obstructive (> 50%) lesion(s) remote from the culprit site. In-hospital and 14 d MACE were more prevalent in the COVID-19 group ( < 0.01 and < 0.001).

Conclusion: This single academic center study in the United States suggests that there is a delay in patients with STEMI seeking medical attention during the COVID-19 pandemic which could be translating into worse clinical outcomes.
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http://dx.doi.org/10.4330/wjc.v13.i4.76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069518PMC
April 2021

Mental Health and Wealth: Depression, Gender, Poverty, and Parenting.

Annu Rev Clin Psychol 2021 05;17:181-205

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA; email:

Depression is a common and debilitating condition that adversely affects functioning and the capacity to work and establish economic stability. Women are disproportionately burdened by depression, and low-income pregnant and parenting women have particularly high rates of depression and often lack access to treatment. As depression can be treated, it is a modifiable risk factor for poor economic outcomes for women, and thus for children and families. Recent national and state health care policy changes offer the opportunity for community-based psychological and economic interventions that can reduce the number of pregnant and parenting women with clinically significant depressive symptoms. Moreover, there is strong evidence that in addition to benefiting women's well-being, such reforms bolster children's emotional and social development and learning and help families rise out of poverty. This review summarizes the mental health and economic literature regarding how maternal depression perpetuates intergenerational poverty and discusses recommendations regarding policies to treat maternal depression in large-scale social services systems.
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http://dx.doi.org/10.1146/annurev-clinpsy-071219-022710DOI Listing
May 2021

Cervical screening during the COVID-19 pandemic: optimising recovery strategies.

Lancet Public Health 2021 07 30;6(7):e522-e527. Epub 2021 Apr 30.

Centre for Health Policy and Management, School of Medicine, Trinity College Dublin, Dublin, Ireland.

Disruptions to cancer screening services have been experienced in most settings as a consequence of the COVID-19 pandemic. Ideally, programmes would resolve backlogs by temporarily expanding capacity; however, in practice, this is often not possible. We aim to inform the deliberations of decision makers in high-income settings regarding their cervical cancer screening policy response. We caution against performance measures that rely solely on restoring testing volumes to pre-pandemic levels because they will be less effective at mitigating excess cancer diagnoses than will targeted measures. These measures might exacerbate pre-existing inequalities in accessing cervical screening by disregarding the risk profile of the individuals attending. Modelling of cervical screening outcomes before and during the pandemic supports risk-based strategies as the most effective way for screening services to recover. The degree to which screening is organised will determine the feasibility of deploying some risk-based strategies, but implementation of age-based risk stratification should be universally feasible.
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http://dx.doi.org/10.1016/S2468-2667(21)00078-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087290PMC
July 2021

Anticoagulation in a Patient With Mechanical Prosthetic Valves and Calcific Uremic Arteriolopathy on Warfarin.

Cureus 2021 Mar 30;13(3):e14196. Epub 2021 Mar 30.

Cardiology, University of Kentucky, Bowling Green, USA.

Calciphylaxis, or calcific uremic arteriolopathy (CUA), is a rare vascular calcific disease that is most often associated with renal dysfunction and warfarin, particularly end-stage renal disease (ESRD). This condition causes debilitatingly painful skin lesions, oftentimes plaques, throughout areas of cutaneous and subcutaneous adiposity. The progression of these lesions to black eschar with ulceration is the hallmark of CUA. In this report, we present the case of a Caucasian female with a past medical history of nephrogenic systemic fibrosis (NSF), ESRD, and mechanical aortic and mitral valves, anticoagulated with warfarin, who developed CUA. In the setting of mechanical prosthetic valves, vitamin K antagonists (VKA) and aspirin are the only evidence-based antithrombotic therapies. This case presents challenging decision-making when managing anticoagulant therapy in the absence of applicable guidelines.
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http://dx.doi.org/10.7759/cureus.14196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085035PMC
March 2021

Incidental Cardiac Arrhythmia Identification with Consumer Grade Heart Rate Monitors: A Case Study.

Curr Sports Med Rep 2021 May;20(5):255-258

School of Kinesiology and Recreation, Illinois State University, Normal, IL.

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http://dx.doi.org/10.1249/JSR.0000000000000842DOI Listing
May 2021
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