Publications by authors named "Craig A Smith"

96 Publications

Appraisal and coping predict health and well-being during the COVID-19 pandemic: An international approach.

Int J Psychol 2021 Jun 29. Epub 2021 Jun 29.

Peabody College, Vanderbilt University, Nashville, TN, USA.

COVID-19 has had a devastating impact on people worldwide. We conducted an international survey (n = 3646) examining the degree to which people's appraisals and coping activities around the pandemic predicted their health and well-being. We obtained subsamples from 12 countries-Bangladesh, Bulgaria, China, Colombia, India, Israel, the Netherlands, Norway, Peru, Portugal, Turkey and the United States. For each, we assessed appraisals and coping strategies as well as indicators of physical and mental health and well-being. Results indicated that, despite mean-level societal differences in outcomes, the pattern of appraisals and coping strategies predicting health and well-being was consistent across countries. Use of disengagement coping (particularly behavioural disengagement and self-isolation) was associated with relatively negative outcomes. In contrast, optimistic appraisals (particularly of high accommodation-focused coping potential and the ability to meet one's physical needs), use of problem-focused coping strategies (especially problem-solving) and accommodative coping strategies (especially positive reappraisal and self-encouragement) were associated with relatively positive outcomes. Our study highlights the critical importance of considering accommodative coping in stress and coping research. It also provides important information on how people have been dealing with the pandemic, the predictors of well-being under pandemic conditions and the generality of such relations.
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http://dx.doi.org/10.1002/ijop.12770DOI Listing
June 2021

Chickens, Sex, and Revisiting an Old Paradigm.

Endocrinology 2021 Jul;162(7)

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3168, Australia.

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http://dx.doi.org/10.1210/endocr/bqab106DOI Listing
July 2021

The Curious Case of Avian Sex Determination.

Trends Genet 2021 06 8;37(6):496-497. Epub 2021 Apr 8.

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.

Ioannidis and colleagues show that the gene DMRT1 is the master regulator of testis development in the chicken. Yet, remarkably, when this gene is deleted in genetic males and gonads form ovaries, the body remains male. This debunks the notion that somatic sex is driven primarily by hormones in birds.
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http://dx.doi.org/10.1016/j.tig.2021.03.006DOI Listing
June 2021

Anatomy, Endocrine Regulation, and Embryonic Development of the Rete Testis.

Endocrinology 2021 Jun;162(6)

Department of Anatomy and Developmental Biology, Monash Biomedical Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.

Reproduction in males requires the transfer of spermatozoa from testis tubules via the rete system to the efferent ductules, epididymis, and vas deferens. The rete therefore forms an essential bridging system between the testis and excurrent ducts. Yet the embryonic origin and molecular regulation of rete testis development is poorly understood. This review examines the anatomy, endocrine control, and development of the mammalian rete testis, focusing on recent findings on its molecular regulation, identifying gaps in our knowledge, and identifying areas for future research. The rete testis develops in close association with Sertoli cells of the seminiferous cords, although unique molecular markers are sparce. Most recently, modern molecular approaches such as global RNA-seq have revealed the transcriptional signature of rete cell precursors, pointing to at least a partial common origin with Sertoli cells. In the mouse, genes involved in Sertoli cell development or maintenance, such as Sox9, Wt1, Sf1, and Dmrt1, are also expressed in cells of the rete system. Rete progenitor cells also express unique markers, such as Pax8, E-cadherin, and keratin 8. These must directly or indirectly regulate the physical joining of testis tubules to the efferent duct system and confer other physiological functions of the rete. The application of technologies such as single-cell RNA-seq will clarify the origin and developmental trajectory of this essential component of the male reproductive tract.
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http://dx.doi.org/10.1210/endocr/bqab046DOI Listing
June 2021

Gonadal Sex Differentiation: Supporting Versus Steroidogenic Cell Lineage Specification in Mammals and Birds.

Front Cell Dev Biol 2020 18;8:616387. Epub 2020 Dec 18.

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.

The gonads of vertebrate embryos are unique among organs because they have a developmental choice; ovary or testis formation. Given the importance of proper gonad formation for sexual development and reproduction, considerable research has been conducted over the years to elucidate the genetic and cellular mechanisms of gonad formation and sexual differentiation. While the molecular trigger for gonadal sex differentiation into ovary of testis can vary among vertebrates, from egg temperature to sex-chromosome linked master genes, the downstream molecular pathways are largely conserved. The cell biology of gonadal formation and differentiation has long thought to also be conserved. However, recent discoveries point to divergent mechanisms of gonad formation, at least among birds and mammals. In this mini-review, we provide an overview of cell lineage allocation during gonadal sex differentiation in the mouse model, focusing on the key supporting and steroidogenic cells and drawing on recent insights provided by single cell RNA-sequencing. We compare this data with emerging information in the chicken model. We highlight surprising differences in cell lineage specification between species and identify gaps in our current understanding of the cell biology underlying gonadogenesis.
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http://dx.doi.org/10.3389/fcell.2020.616387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775416PMC
December 2020

Regulation of vertebrate forelimb development and wing reduction in the flightless emu.

Dev Dyn 2020 Dec 25. Epub 2020 Dec 25.

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

The vertebrate limb is a dynamic structure which has evolved into many diverse forms to facilitate complex behavioral adaptations. The principle molecular and cellular processes that underlie development of the vertebrate limb are well characterized. However, how these processes are altered to drive differential limb development between vertebrates is less well understood. Several vertebrate models are being utilized to determine the developmental basis of differential limb morphogenesis, though these typically focus on later patterning of the established limb bud and may not represent the complete developmental trajectory. Particularly, heterochronic limb development can occur prior to limb outgrowth and patterning but receives little attention. This review summarizes the genetic regulation of vertebrate forelimb diversity, with particular focus on wing reduction in the flightless emu as a model for examining limb heterochrony. These studies highlight that wing reduction is complex, with heterochronic cellular and genetic events influencing the major stages of limb development. Together, these studies provide a broader picture of how different limb morphologies may be established during development.
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http://dx.doi.org/10.1002/dvdy.288DOI Listing
December 2020

Transcriptional landscape of the embryonic chicken Müllerian duct.

BMC Genomics 2020 Oct 2;21(1):688. Epub 2020 Oct 2.

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Wellington Road, Clayton, VIC, 3800, Australia.

Background: Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract in vertebrates. Many disorders of female reproduction can be attributed to anomalies of Müllerian duct development. However, the molecular genetics of Müllerian duct formation is poorly understood and most disorders of duct development have unknown etiology. In this study, we describe for the first time the transcriptional landscape of the embryonic Müllerian duct, using the chicken embryo as a model system. RNA sequencing was conducted at 1 day intervals during duct formation to identify developmentally-regulated genes, validated by in situ hybridization.

Results: This analysis detected hundreds of genes specifically up-regulated during duct morphogenesis. Gene ontology and pathway analysis revealed enrichment for developmental pathways associated with cell adhesion, cell migration and proliferation, ERK and WNT signaling, and, interestingly, axonal guidance. The latter included factors linked to neuronal cell migration or axonal outgrowth, such as Ephrin B2, netrin receptor, SLIT1 and class A semaphorins. A number of transcriptional modules were identified that centred around key hub genes specifying matrix-associated signaling factors; SPOCK1, HTRA3 and ADGRD1. Several novel regulators of the WNT and TFG-β signaling pathway were identified in Müllerian ducts, including APCDD1 and DKK1, BMP3 and TGFBI. A number of novel transcription factors were also identified, including OSR1, FOXE1, PRICKLE1, TSHZ3 and SMARCA2. In addition, over 100 long non-coding RNAs (lncRNAs) were expressed during duct formation.

Conclusions: This study provides a rich resource of new candidate genes for Müllerian duct development and its disorders. It also sheds light on the molecular pathways engaged during tubulogenesis, a fundamental process in embryonic development.
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http://dx.doi.org/10.1186/s12864-020-07106-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532620PMC
October 2020

Subgroups of Pediatric Patients With Functional Abdominal Pain: Replication, Parental Characteristics, and Health Service Use.

Clin J Pain 2020 12;36(12):897-906

Pediatrics, Vanderbilt University Medical Center.

Objectives: Prior work in a cohort of youth with functional abdominal pain (FAP) identified patient subgroups (High Pain Dysfunctional, High Pain Adaptive, Low Pain Adaptive) that predicted differences in the course of FAP from childhood into young adulthood. We aimed to replicate these subgroups in a new sample of adolescents with FAP using the original classification algorithm and to extend subgroup characteristics to include parental characteristics and health service use.

Methods: Adolescents (n=278; ages 11 to 17 y, 66% females) presenting to a gastroenterology clinic for abdominal pain, and their parents (92% mothers) completed self-report measures; adolescents also completed a 7-day pain diary.

Results: The replicated patient subgroups exhibited distress and impairment similar to subgroups in the original sample. Moreover, in novel findings, the High Pain Dysfunctional subgroup differed from other subgroups by the predominance of mother-daughter dyads jointly characterized by high levels of anxiety, depressive symptoms, pain behavior, and pain catastrophizing. The High Pain Dysfunctional subgroup used more health care services than Low Pain Adaptive but did not differ from High Pain Adaptive.

Discussion: Findings replicate and extend the original FAP classification and suggest that the subgroups have unique patient and parent features that may reflect distinct illness mechanisms requiring different treatments.
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http://dx.doi.org/10.1097/AJP.0000000000000882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666007PMC
December 2020

Applying Single-Cell Analysis to Gonadogenesis and DSDs (Disorders/Differences of Sex Development).

Int J Mol Sci 2020 Sep 10;21(18). Epub 2020 Sep 10.

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Victoria, Australia.

The gonads are unique among the body's organs in having a developmental choice: testis or ovary formation. Gonadal sex differentiation involves common progenitor cells that form either Sertoli and Leydig cells in the testis or granulosa and thecal cells in the ovary. Single-cell analysis is now shedding new light on how these cell lineages are specified and how they interact with the germline. Such studies are also providing new information on gonadal maturation, ageing and the somatic-germ cell niche. Furthermore, they have the potential to improve our understanding and diagnosis of Disorders/Differences of Sex Development (DSDs). DSDs occur when chromosomal, gonadal or anatomical sex are atypical. Despite major advances in recent years, most cases of DSD still cannot be explained at the molecular level. This presents a major pediatric concern. The emergence of single-cell genomics and transcriptomics now presents a novel avenue for DSD analysis, for both diagnosis and for understanding the molecular genetic etiology. Such -omics datasets have the potential to enhance our understanding of the cellular origins and pathogenesis of DSDs, as well as infertility and gonadal diseases such as cancer.
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http://dx.doi.org/10.3390/ijms21186614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555471PMC
September 2020

Validation of the Health-Related Felt Stigma and Concealment Questionnaire.

J Pediatr Psychol 2020 06;45(5):509-520

Department of Psychology and Human Development, Vanderbilt University.

Objective: Stigma is associated with many health conditions, including chronic pain. Research on health-related stigma is limited by the lack of validated instruments that distinguish among various stigma-related constructs. We aimed to develop and validate such a measure for pediatric functional abdominal pain (FAP). Felt stigma (FS) was defined as comprising both perceived and internalized stigma. Stigma concealment (SC) was defined as efforts by stigmatized individuals to prevent others from learning of their condition.

Methods: Using a theory-driven approach, we adapted items from existing self-report measures of stigma to construct the health-related FS and Concealment Questionnaire (FSC-Q). Patients with FAP (N = 179, ages 11-17) completed the preliminary FSC-Q and health-related measures hypothesized to be associated with stigma. Cognitive interviewing and exploratory factor analysis (EFA) informed the final version of the measure.

Results: EFA identified a 2-factor model comprised of FS and SC. The FS and SC scales exhibited good internal consistency and construct validity. Consistent with study hypotheses, both factors were significantly associated with anxiety, depression, pain catastrophizing, pain threat, physical symptoms, and pain interference/disability. Higher FS was associated with higher mental healthcare utilization. The subset of participants meeting criteria for irritable bowel syndrome (IBS) reported higher FS and SC compared with those without IBS.

Conclusion: The FSC-Q may help advance research on health-related stigma in FAP and other chronic health conditions by allowing for assessment of distinct stigma-related constructs.
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http://dx.doi.org/10.1093/jpepsy/jsaa030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234182PMC
June 2020

Profiles of appraisal, motivation, and coping for positive emotions.

Cogn Emot 2020 05 25;34(3):481-497. Epub 2019 Jul 25.

Department of Psychology and Human Development, Peabody College, Vanderbilt University, Nashville, TN, USA.

We used a retrospective survey (= 346) to model the patterns of appraisal, motivation, and coping that uniquely correspond with 12 positive emotions (affection/love, amusement, awe, challenge/determination, compassion, gratitude, happiness/joy, hope, interest, pride, relief, and serenity/tranquillity). Generally, we conceptually replicated previously demonstrated appraisal profiles of positive emotion while also examining how additional appraisals differentiate among positive emotions. We then uncovered the motivational goals and coping processes associated with each positive emotion. We discuss the implications of our findings for future research on positive emotion.
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http://dx.doi.org/10.1080/02699931.2019.1646212DOI Listing
May 2020

Adhesion G-protein-coupled receptor, GPR56, is required for Müllerian duct development in the chick.

J Endocrinol 2020 02;244(2):395-413

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

The embryonic Müllerian ducts give rise to the female reproductive tract (fallopian tubes, uterus and upper vagina in humans, the oviducts in birds). Embryonic Müllerian ducts initially develop in both sexes, but later regress in males under the influence of anti-Müllerian hormone. While the molecular and endocrine control of duct regression in males have been well studied, early development of the ducts in both sexes is less well understood. Here, we describe a novel role for the adhesion G protein-coupled receptor, GPR56, in development of the Müllerian ducts in the chicken embryo. GPR56 is expressed in the ducts of both sexes from early stages. The mRNA is present during the elongation phase of duct formation, and it is restricted to the inner Müllerian duct epithelium. The putative ligand, Collagen III, is abundantly expressed in the Müllerian duct at the same developmental stages. Knockdown of GPR56 expression using in ovo electroporation results in variably truncated ducts, with a loss of expression of both epithelial and mesenchymal markers of duct development. Over-expression of GPR56 in vitro results in enhanced cell proliferation and cell migration. These results show that GPR56 plays an essential role in avian Müllerian duct development through the regulation of duct elongation.
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http://dx.doi.org/10.1530/JOE-19-0419DOI Listing
February 2020

Association of Functional Screening Tests and Noncontact Injuries in Division I Women Student-Athletes.

J Strength Cond Res 2020 Aug;34(8):2302-2311

Daemen College, Amherst, New York.

Warren, M, Lininger, M, Smith, CA, Copp, A, and Chimera, NJ. Association of functional screening tests and noncontact injuries in Division I women student-athletes. J Strength Cond Res 34(8): 2302-2311, 2020-To determine the association between functional screening tests and lower-body, noncontact injuries in Division I women basketball, soccer, and volleyball student-athletes (SA). Sixty-eight injury-free women SA (age: 19.1 ± 1.1 years, height: 171.3 ± 8.7 cm, and mass: 68.4 ± 9.5 kg) were tested preseason with single hop (SH), triple hop (TH), and crossover hop (XH) for distance, and isometric hip strength (abduction, extension, and external rotation) in randomized order. The first lower-body (spine and lower extremity), noncontact injury requiring intervention by the athletic trainer was abstracted from the electronic medical record. Receiver operating characteristic and area under the curve (AUC) were calculated to determine cut-points for each hopping test from the absolute value of between-limb difference. Body mass-adjusted strength was categorized into tertiles. Logistic regression determined the odds of injury with each functional screening test using the hopping tests cut-points and strength categories, adjusting for previous injury. Fifty-two SA were injured during the sport season. The cut-point for SH was 4 cm (sensitivity = 0.77, specificity = 0.43, and AUC = 0.53), and for TH and XH was 12 cm (sensitivity = 0.75 and 0.67, specificity = 0.71 and 0.57, AUC = 0.59 and 0.41, respectively). A statistically significant association with TH and injuries (adjusted odds ratio = 6.50 [95% confidence interval: 1.69-25.04]) was found. No significant overall association was found with SH or XH, nor with the strength tests. Using a clinically relevant injury definition, the TH showed the strongest predictive ability for noncontact injuries. This hopping test may be a clinically useful tool to help identify increased risk of injury in women SA participating in high-risk sports.
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http://dx.doi.org/10.1519/JSC.0000000000003004DOI Listing
August 2020

Utility of FMS to understand injury incidence in sports: current perspectives.

Open Access J Sports Med 2018 7;9:171-182. Epub 2018 Sep 7.

Department of Physical Therapy and Athletic Training, Northern Arizona University, Flagstaff, AZ, USA,

The Functional Movement Screen (FMS) is a popular movement screen used by rehabilitation, as well as strength and conditioning, professionals. The FMS, like other movement screens, identifies movement dysfunction in those at risk of, but not currently experiencing, signs or symptoms of a musculoskeletal injury. Seven movement patterns comprise the FMS, which was designed to screen fundamental movement requiring a balance between stability and mobility. The 7 movement patterns are summed to a composite FMS score. For an instrument to have wide applicability and acceptability, there must be high levels of reliability, validity, and accuracy. The FMS is certainly a reliable tool, and can be consistently scored within and between raters. Although the FMS has high face and content validity, the criterion validity (discriminant and convergent) is low. Additionally, the FMS does not appear to be studying a single construct, challenging the use of the summed composite FMS score. The accuracy of the FMS in screening for injury is also suspect, with low sensitivity in almost all studies, although specificity is higher. Finally, within the FMS literature, the concepts of prediction and association are conflated, combined with flawed cohort studies, leading to questions about the efficacy of the FMS to screen for injury. Future research on the use of the FMS, either the composite score or the individual movement patterns, to screen for injury or injury risk in adequately powered, well-designed studies are required to determine if the FMS is appropriate for use as a movement screen.
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http://dx.doi.org/10.2147/OAJSM.S149139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135213PMC
September 2018

Gonadal and Endocrine Analysis of a Gynandromorphic Chicken.

Endocrinology 2018 10;159(10):3492-3502

Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.

Birds have a ZZ male and ZW female sex chromosome system. The relative roles of genetics and hormones in regulating avian sexual development have been revealed by studies on gynandromorphs. Gynandromorphs are rare bilateral sex chimeras, male on one side of the body and female on the other. We examined a naturally occurring gynandromorphic chicken that was externally male on the right side of the body and female on the left. The bird was diploid but with a mix of ZZ and ZW cells that correlated with the asymmetric sexual phenotype. The male side was 96% ZZ, and the female side was 77% ZZ and 23% ZW. The gonads of this bird at sexual maturity were largely testicular. The right gonad was a testis, with SOX9+ Sertoli cells, DMRT1+ germ cells, and active spermatogenesis. The left gonad was primarily testicular, but with some peripheral aromatase-expressing follicles. The bird had low levels of serum estradiol and high levels of testosterone, as expected for a male. Despite the low percentage of ZW cells on that side, the left side had female sex-linked feathering, smaller muscle mass, smaller leg and spur, and smaller wattle than the male side. This indicates that these sexually dimorphic structures must be at least partly independent of sex steroid effects. Even a small percentage of ZW cells appears sufficient to support female sexual differentiation. Given the lack of chromosome-wide dosage compensation in birds, various sexually dimorphic features may arise due to Z-gene dosage differences between the sexes.
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http://dx.doi.org/10.1210/en.2018-00553DOI Listing
October 2018

Is Resolution of Chronic Pain Associated With Changes in Blood Pressure-related Hypoalgesia?

Ann Behav Med 2018 05;52(7):552-559

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: In healthy individuals, elevated resting blood pressure (BP) is associated with reduced pain responsiveness and lower temporal summation. Prior work indicates that this BP-related hypoalgesia is reduced in individuals with chronic pain.

Purpose: This study evaluated whether resolution of chronic pain was associated with greater BP-related hypoalgesia compared to nonresolution.

Methods: From a prospective sample of adolescents and young adults diagnosed with chronic functional abdominal pain an average of 9 years earlier, 99 individuals in whom the condition had resolved and 51 individuals with ongoing abdominal pain were studied. Resting systolic BP was assessed, followed by evaluation of thermal pain threshold and tolerance, and assessment of temporal summation to thermal pain stimuli.

Results: Higher resting systolic BP was significantly associated with higher pain threshold and tolerance, and lower temporal summation only in the group with resolved functional abdominal pain (p < .05). Hierarchical regressions revealed that interactions between BP and resolution of chronic pain were significant only for pain tolerance (p < .05). Analyses by sex indicated that interactions between BP and resolution status were significant for the temporal summation outcome in males but not in females.

Conclusions: Results suggest that BP-related hypoalgesic mechanisms may be more effective in individuals in whom chronic pain has resolved compared to those with ongoing chronic pain. Findings hint at sex differences in the extent to which resolution of chronic pain is associated with BP-related hypoalgesia. Whether greater BP-related hypoalgesia is a consequence of, or alternatively a contributor to, resolution of chronic pain warrants further investigation.
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http://dx.doi.org/10.1093/abm/kax021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361258PMC
May 2018

Sex determination and gonadal sex differentiation in the chicken model.

Int J Dev Biol 2018 ;62(1-2-3):153-166

Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.

Our understanding of avian sex determination and gonadal development is derived primarily from the studies in the chicken. Analysis of gynandromorphic chickens and experimental chimeras indicate that sexual phenotype is at least partly cell autonomous in the chicken, with sexually dimorphic gene expression occurring in different tissue and different stages. Gonadal sex differentiation is just one of the many manifestations of sexual phenotype. As in other birds, the chicken has a ZZ male: ZW female sex chromosome system, in which the male is the homogametic sex. Most evidence favours a Z chromosome dosage mechanism underling chicken sex determination, with little evidence of a role for the W chromosome. Indeed, the W appears to harbour a small number of genes that are un-related to sexual development, but have been retained because they are dosage sensitive factors. As global Z dosage compensation is absent in birds, Z-linked genes may direct sexual development in different tissues (males having on average 1.5 to 2 times the expression level of females). In the embryonic gonads, the Z-linked DMRT1 gene plays a key role in testis development. Beyond the gonads, other combinations of Z-linked genes may govern sexual development, together with a role for sex steroid hormones. Gonadal DMRT1 is thought to activate other players in testis development, namely SOX9 and AMH, and the recently identified HEMGN gene. DMRT1 also represses ovarian pathway genes, such as FOXL2 and CYP19A1. A lower level of DMRT1 expression in the female gonads is compatible with activation of the ovarian pathway. Some outstanding questions include how the key testis and ovary genes, DMRT1 and FOXL2, are regulated. In addition, confirmation of the central role of these genes awaits genome editing approaches.
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http://dx.doi.org/10.1387/ijdb.170319csDOI Listing
April 2019

The cell biology and molecular genetics of Müllerian duct development.

Wiley Interdiscip Rev Dev Biol 2018 05 19;7(3):e310. Epub 2018 Jan 19.

Monash Biomedicine Discovery Institute, Department of Anatomy and Development Biology, Monash University, Clayton, Victoria, Australia.

The Müllerian ducts are part of the embryonic urogenital system. They give rise to mature structures that serve a critical function in the transport and development of the oocyte and/or embryo. In most vertebrates, both sexes initially develop Müllerian ducts during embryogenesis, but they regress in males under the influence of testis-derived Anti-Müllerian Hormone (AMH). A number of regulatory factors have been shown to be essential for proper duct development, including Bmp and Wnt signaling molecules, together with homeodomain transcription factors such as PAX2 and LIM1. Later in development, the fate of the ducts diverges between males and females and is regulated by AMH and Wnt signaling molecules (duct regression in males) and Hox genes (duct patterning in females). Most of the genes and molecular pathways known to be involved in Müllerian duct development have been elucidated through animal models, namely, the mouse and chicken. In addition, genetic analysis of humans with reproductive tract disorders has further defined molecular mechanisms of duct formation and differentiation. However, despite our current understanding of Müllerian duct development, some questions remain to be answered at the molecular genetic level. This article is categorized under: Early Embryonic Development > Development to the Basic Body Plan.
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http://dx.doi.org/10.1002/wdev.310DOI Listing
May 2018

Reply.

Pain 2017 Dec;158(12):2497-2498

Departments of aAnesthesiology bPediatrics and cPsychology and Human Development, Vanderbilt University, Nashville, TN, USA.

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http://dx.doi.org/10.1097/j.pain.0000000000001072DOI Listing
December 2017

Social learning pathways in the relation between parental chronic pain and daily pain severity and functional impairment in adolescents with functional abdominal pain.

Pain 2018 02;159(2):298-305

Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.

Having a parent with chronic pain (CP) may confer greater risk of persistence of CP from childhood into young adulthood. Social learning, such as parental modeling and reinforcement, represents one plausible mechanism for the transmission of risk of CP from parents to offspring. Based on a 7-day pain diary in 154 pediatric patients with functional abdominal CP, we tested a model in which parental CP predicted adolescents' daily average CP severity and functional impairment (distal outcomes) via parental modeling of pain behaviors and parental reinforcement of adolescent's pain behaviors (mediators) and adolescents' cognitive appraisals of pain threat (proximal outcome representing adolescents' encoding of parents' behaviors). Results indicated significant indirect pathways from parental CP status to adolescent average daily pain severity (b = 0.18, SE = 0.08, 95% confidence interval: 0.04-0.31, P = 0.03) and functional impairment (b = 0.08, SE = 0.04, 95% confidence interval: 0.02-0.15, P = 0.03) over the 7-day diary period via adolescents' observations of parent pain behaviors and adolescent pain threat appraisal. The indirect pathway through parental reinforcing responses to adolescents' pain did not reach significance for either adolescent pain severity or functional impairment. Identifying mechanisms of increased risk of pain and functional impairment in children of parents with CP ultimately could lead to targeted interventions aimed at improving functioning and quality of life in families with CP. Parental modeling of pain behaviors represents a potentially promising target for family-based interventions to ameliorate pediatric CP.
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http://dx.doi.org/10.1097/j.pain.0000000000001085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889361PMC
February 2018

Modified Tuck Jump Assessment: Reliability and Training of Raters.

J Sports Sci Med 2017 Sep 8;16(3):440-442. Epub 2017 Aug 8.

Department of Physical Therapy and Athletic Training, Northern Arizona University, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592298PMC
September 2017

Sex Reversal and Comparative Data Undermine the W Chromosome and Support Z-linked DMRT1 as the Regulator of Gonadal Sex Differentiation in Birds.

Endocrinology 2017 09;158(9):2970-2987

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF). To test the association of these genes with ovarian differentiation in the chicken, we examined their expression following experimentally induced female-to-male sex reversal using the aromatase inhibitor fadrozole (FAD). Administration of FAD on day 3 of embryogenesis induced a significant loss of aromatase enzyme activity in female gonads and masculinization. However, expression levels of HINTW, FAF, and FET1 were unaltered after experimental masculinization. Furthermore, comparative analysis showed that FAF and FET1 expression could not be detected in zebra finch gonads. Additionally, an antibody raised against the predicted HINTW protein failed to detect it endogenously. These data do not support a universal role for these genes or for the W sex chromosome in ovarian development in birds. We found that DMRT1 (but not the recently identified Z-linked HEMGN gene) is male upregulated in embryonic zebra finch and emu gonads, as in the chicken. As chicken, zebra finch, and emu exemplify the major evolutionary clades of birds, we propose that Z-linked DMRT1, and not the W sex chromosome, regulates gonadal sex differentiation in birds.
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http://dx.doi.org/10.1210/en.2017-00316DOI Listing
September 2017

Genetic Manipulation of the Avian Urogenital System Using In Ovo Electroporation.

Methods Mol Biol 2017 ;1650:177-190

Department of Anatomy and Development Biology, Monash University, Clayton, VIC, 3800, USA.

One of the advantages of the avian embryo as an experimental model is its in ovo development and hence accessibility for genetic manipulation. Electroporation has been used extensively in the past to study gene function in chicken and quail embryos . Readily accessible tissues such as the neural tube, somites, and limb bud, in particular, have been targeted. However, more inaccessible tissues, such as the embryonic urogenital system , have proven more challenging to study. Here, we describe the use of in ovo electroporation of TOL2 vectors or RCASBP avian viral vectors for the rapid functional analysis of genes involved in avian sex determination and urogenital development . In the context of the developing urogenital system , these vectors have inherent advantages and disadvantages, which will be considered here. Either vector can both be used for mis-expressing a gene and for targeting endogenous gene knockdown via expression of short hairpin RNAs (shRNAs). Both of these vectors integrate into the genome and are hence spread throughout developing tissues. Going forward, electroporation could be combined with CRISPR/Cas9 technology for targeted genome editing in the avian urogenital system .
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http://dx.doi.org/10.1007/978-1-4939-7216-6_11DOI Listing
June 2018

Co-option of the cardiac transcription factor Nkx2.5 during development of the emu wing.

Nat Commun 2017 07 25;8(1):132. Epub 2017 Jul 25.

Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052, Australia.

The ratites are a distinctive clade of flightless birds, typified by the emu and ostrich that have acquired a range of unique anatomical characteristics since diverging from basal Aves at least 100 million years ago. The emu possesses a vestigial wing with a single digit and greatly reduced forelimb musculature. However, the embryological basis of wing reduction and other anatomical changes associated with loss of flight are unclear. Here we report a previously unknown co-option of the cardiac transcription factor Nkx2.5 to the forelimb in the emu embryo, but not in ostrich, or chicken and zebra finch, which have fully developed wings. Nkx2.5 is expressed in emu limb bud mesenchyme and maturing wing muscle, and mis-expression of Nkx2.5 throughout the limb bud in chick results in wing reductions. We propose that Nkx2.5 functions to inhibit early limb bud expansion and later muscle growth during development of the vestigial emu wing.The transcription factor Nkx2.5 is essential for heart development. Here, the authors identify a previously unknown expression domain for Nkx2.5 in the emu wing and explore its role in diminished wing bud development in the flightless emu, compared with three other birds that have functional wings.
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http://dx.doi.org/10.1038/s41467-017-00112-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526984PMC
July 2017

Interacting influences of gender and chronic pain status on parasympathetically mediated heart rate variability in adolescents and young adults.

Pain 2017 08;158(8):1509-1516

Department of Medicine, Division of Clinical Pharmacology, Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Considerable research links chronic pain to autonomic nervous system (ANS) dysfunction, specifically low heart rate variability (HRV) mediated by reduced parasympathetic activity. However, little is known about factors that influence ANS function in chronic pain. The ANS is the primary pathway for brain-gut communication, making it of particular interest in gastrointestinal disorders, such as irritable bowel syndrome, characterized by functional abdominal pain (FAP). We evaluated the relation of sex, pain severity, and psychological stress to ANS function in adolescents/young adults from a database of pediatric FAP and control participants enrolled 8 years earlier in a prospective study of pain. At follow-up in adolescence/young adulthood (Mean age = 19.46, SD = 3.48), we classified participants as Pain-Remit (n = 130), Pain-Persist (n = 96), and pain-free controls (n = 123). We recorded electrocardiogram data at rest and during laboratory stressors. Results demonstrated significantly lower HRV in Pain-Persist females compared with Pain-Remit females, female controls, and all males regardless of pain category. Spectral analysis of electrocardiogram showed that Pain-Persist females had reduced power in the high frequency domain of cardiac activity, ie, reduced parasympathetic "braking" of sympathetic activity, both at rest and during stress. Pain-Remit females exhibited levels of autonomic imbalance intermediate between those of females with persistent FAP and all other participants. Parasympathetically mediated low HRV in young women with persistent FAP may reflect a peripheral mechanism (eg, gut dysfunction) or a central nervous system mechanism (eg, pain amplification or poor emotion self-regulation) involving prolonged sympathetic activation.
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http://dx.doi.org/10.1097/j.pain.0000000000000942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528172PMC
August 2017

Intrawound Vancomycin Powder Reduces Early Prosthetic Joint Infections in Revision Hip and Knee Arthroplasty.

Surg Technol Int 2017 Feb;30:284-289

Orthopedic Surgery, Mount Carmel Health Systems, Columbus, Ohio.

Intrawound vancomycin powder has shown efficacy and safety in decreasing postoperative spine infections, but its use in arthroplasty has not been well established. The purpose of this study was to compare the rate of early prosthetic joint infections (PJI) with and without the use of intrawound vancomycin powder during joint arthroplasty. A retrospective cohort of all patients who underwent primary or revision hip or knee arthroplasty by two surgeons over a two-year period at a single hospital system was evaluated. The control group received standard systemic prophylaxis only, whereas the treatment group received 1 g of vancomycin powder in the surgical wound in addition to systemic prophylaxis. A statistically significant decrease in the overall PJI rate was found in the treatment group (4/816=0.49%) compared to the control group (13/824=1.57%; p=0.0479). Subgroup analysis demonstrated a trend toward fewer PJIs in the vancomycin group, however, only the revision procedures showed a statistically significant reduction in early PJIs after the initiation of vancomycin (7/180=3.89% to 0/134=0%; p=0.0217). The use of intrawound vancomycin powder was associated with a significant reduction in the overall incidence of early PJIs following joint arthroplasty, however, only the revision procedures demonstrated a significant reduction in the rate of early PJIs.
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February 2017

Limb patterning genes and heterochronic development of the emu wing bud.

Evodevo 2016 20;7:26. Epub 2016 Dec 20.

Environmental Futures Research Institute, Griffith University, Nathan, QLD 4111 Australia.

Background: The forelimb of the flightless emu is a vestigial structure, with greatly reduced wing elements and digit loss. To explore the molecular and cellular mechanisms associated with the evolution of vestigial wings and loss of flight in the emu, key limb patterning genes were examined in developing embryos.

Methods: Limb development was compared in emu versus chicken embryos. Immunostaining for cell proliferation markers was used to analyze growth of the emu forelimb and hindlimb buds. Expression patterns of limb patterning genes were studied, using whole-mount in situ hybridization (for mRNA localization) and RNA-seq (for mRNA expression levels).

Results: The forelimb of the emu embryo showed heterochronic development compared to that in the chicken, with the forelimb bud being retarded in its development. Early outgrowth of the emu forelimb bud is characterized by a lower level of cell proliferation compared the hindlimb bud, as assessed by PH3 immunostaining. In contrast, there were no obvious differences in apoptosis in forelimb versus hindlimb buds (cleaved caspase 3 staining). Most key patterning genes were expressed in emu forelimb buds similarly to that observed in the chicken, but with smaller expression domains. However, expression of () mRNA, which is central to anterior-posterior axis development, was delayed in the emu forelimb bud relative to other patterning genes. Regulators of Shh expression, and , also showed altered expression levels in the emu forelimb bud.

Conclusions: These data reveal heterochronic but otherwise normal expression of most patterning genes in the emu vestigial forelimb. Delayed expression may be related to the small and vestigial structure of the emu forelimb bud. However, the genetic mechanism driving retarded emu wing development is likely to rest within the forelimb field of the lateral plate mesoderm, predating the expression of patterning genes.
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http://dx.doi.org/10.1186/s13227-016-0063-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5168868PMC
December 2016

FUNCTIONAL HOP TESTS AND TUCK JUMP ASSESSMENT SCORES BETWEEN FEMALE DIVISION I COLLEGIATE ATHLETES PARTICIPATING IN HIGH VERSUS LOW ACL INJURY PRONE SPORTS: A CROSS SECTIONAL ANALYSIS.

Int J Sports Phys Ther 2016 Dec;11(6):945-953

Athletic Department, Daemen College.

Background: Although functional tests including the single leg hop (SLH), triple hop (TH), cross over hop (COH) for distance, and the tuck jump assessment (TJA) are used for return to play (RTP) criteria for post anterior cruciate ligament (ACL) injury, sport-specific baseline measurements are limited.

Purpose: The purpose of this study was to examine differences in SLH, TH, and COH distance and limb symmetry index (LSI), as well as total scores, number of jumps, and individual flaws of the TJA in 97 injury-free Division I (DI) collegiate female student athletes participating in ACL injury prone vs. non ACL injury prone sports. The hypothesis was that significant mean differences and asymmetries (LSI) would exist between the two groups in SLH, TH, COH and TJA.

Study Design: Cross sectional.

Methods: Due to research suggesting inherent ACL injury risk associated with specific sport involvement, participants were grouped into high (HR, n=57) and low (LR, n=40) ACL injury risk based on participating in a sport with high or low ACL injury rates. The HR group was composed of athletes participating in soccer, basketball, and volleyball, while the LR group athletes participated in diving, cross country, and track and field. Participants performed all standard functional tests (SFT) and side-to-side differences for each participant as well as between group differences were assessed for the hop tests. The LSI, a ratio frequently used to gauge athletes' readiness for RTP post injury, was also assessed for between group differences. The TJA was compared between the groups on individual flaws, overall scores, and number of jumps performed.

Results: No between group differences for hop distances were found, with medium to large effect sizes for SLH, TH, and COH. The HR group had a higher TJA score, number of jumps, and higher proportion of the flaw of 'foot placement not shoulder width apart'.

Conclusion: Although most SFT's showed no significant differences between athlete groups, some differences were seen in the TJA; the HR group showed an increase in 'foot placement not shoulder width apart' flaw, higher overall flaw scores, and overall jumped more times compared to the LR group. These results may warrant caution in relying solely on SFT for RTP decisions, due to potential asymmetries seen in an uninjured population with baseline testing.

Level Of Evidence: 4.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095946PMC
December 2016

Sex Reversal in Birds.

Sex Dev 2016 17;10(5-6):288-300. Epub 2016 Aug 17.

Department of Anatomy and Developmental Biology, Monash University, Melbourne, Vic., Australia.

Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal.
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http://dx.doi.org/10.1159/000448365DOI Listing
November 2017

Comparison of Female Collegiate Athletes and College Age Cohort in Tuck Jump Assessment.

J Strength Cond Res 2017 Apr;31(4):1048-1054

1Department of Physical Therapy and Athletic Training, Northern Arizona University, Flagstaff, Arizona; 2Smith Performance Center, Tucson, Arizona; 3Select Physical Therapy, Peoria, Arizona; and 4Department of Athletic Training, Daemen College, Amherst, New York.

Smith, CA, Olson, BK, Olson, LA, Chimera, NJ, and Warren, M. Comparison of female collegiate athletes and college age cohort in tuck jump assessment. J Strength Cond Res 31(4): 1048-1054, 2017-The tuck jump assessment (TJA) is a plyometric jumping assessment with 10 flaw criteria against which technique is assessed over a 10-second interval. The TJA has been reported as a tool for identifying neuromuscular deficits that increase risk for anterior cruciate ligament injury, but group specific data on female TJA scores are limited. No cut point has been developed for groups with different activity levels or participation in athletics. This study investigated the association between TJA score and athletic participation in college-aged females. One hundred twenty-one females (53 collegiate athletes and 68 college students) completed the TJA. TJA score was the sum of flaws for the 10 criteria observed, and the number of jumps was recorded. Poisson regression was used to assess the association between TJA score and number of jumps. The association between each of the 10 flaws between groups was assessed with the chi-square test. No significant association was found between groups for TJA score (mean ± SD: 4.66 ± 1.07 athletes; 5.45 ± 1.05 college cohort; p = 0.06; β = 0.82). Athletes jumped significantly more times (12.23 ± 1.04 athletes; 9.35 ± 1.04 college cohort). Athletes had a lower proportion of 2 flaws: "thighs do not reach parallel" and "pause between jumps." Lower statistical power may limit interpretation of the remaining flaws. The lack of control of the number of jumps may impact TJA score. To improve the TJA usefulness on the field and clinic, the protocol may need to standardize the number of jumps.
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http://dx.doi.org/10.1519/JSC.0000000000001573DOI Listing
April 2017
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