Clomiphene Citrate and Enclomiphene Hydrochloride Exposure Is Associated With Interfrontal Suture Fusion in Zebrafish

Plastic Surgery ◽

10.1177/22925503211057526 ◽

2021 ◽

pp. 229255032110575

Author(s):

Tamara A. Franz-Odendaal ◽

Michael Bezuhly

Keyword(s):

Clomiphene Citrate ◽

Population Based ◽

Craniofacial Development ◽

Zebrafish Larvae ◽

Fertility Drugs ◽

Signaling Mechanisms ◽

Key Points ◽

Whole Mount ◽

Suture Fusion ◽

Metopic Craniosynostosis

Background: The last several decades have witnessed an increase in metopic craniosynostosis incidence. Population-based studies suggest that pharmacological exposure in utero may be responsible. This study examined effects of the fertility drug clomiphene citrate (CC) on calvarial development in an established model for craniofacial development, the zebrafish Danio rerio. Results: Zebrafish larvae were exposed to clomiphene citrate or its isomer enclomiphene for five days at key points during calvarial development. Larvae were then raised to adulthood in normal rearing water. Zebrafish were analyzed using whole-mount skeletal staining. We observed differential effects on survivability, growth and suture formation depending on the treatment. Treatments with CC or enclomiphene at 5.5 mm SL led to increased fusion of the interfrontal suture (p < .01) compared to controls. Conclusions: Exposure to fertility drugs appears to affect development of the cranial vault, specifically the interfrontal suture, in zebrafish. Further research is required to identify the signaling mechanisms at play. This work suggests that fertility drug treatment may contribute to the increased incidence of metopic craniosynostosis observed globally.

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The Pleiotropic Intricacies of Hedgehog Signaling: From Craniofacial Patterning to Carcinogenesis

FACE ◽

10.1177/27325016211024326 ◽

2021 ◽

pp. 273250162110243

Author(s):

Mikhail Pakvasa ◽

Andrew B. Tucker ◽

Timothy Shen ◽

Tong-Chuan He ◽

Russell R. Reid

Keyword(s):

Intracellular Signaling ◽

Limb Development ◽

Hedgehog Signaling ◽

Target Genes ◽

Craniofacial Development ◽

Signaling Cascade ◽

Signaling Mechanisms ◽

Intracellular Signaling Cascade ◽

And Function

Hedgehog signaling was discovered more than 40 years ago in experiments demonstrating that it is a fundamental mediator of limb development. Since that time, it has been shown to be important in development, homeostasis, and disease. The hedgehog pathway proceeds through a pathway highly conserved throughout animals beginning with the extracellular diffusion of hedgehog ligands, proceeding through an intracellular signaling cascade, and ending with the activation of specific target genes. A vast amount of research has been done elucidating hedgehog signaling mechanisms and regulation. This research has found a complex system of genetics and signaling that helps determine how organisms develop and function. This review provides an overview of what is known about hedgehog genetics and signaling, followed by an in-depth discussion of the role of hedgehog signaling in craniofacial development and carcinogenesis.

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Fertility Drugs Associated with Thyroid Cancer Risk: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2018/7191704 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

QingAn Yu ◽

XiaoYing Lv ◽

KunPeng Liu ◽

DaKun Ma ◽

YaoHua Wu ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Risk ◽

Clomiphene Citrate ◽

Positive Association ◽

Female Infertility ◽

Cochrane Library ◽

Significant Positive Association ◽

Fertility Drugs ◽

Increased Risk ◽

Thyroid Cancer Risk

Associations have been demonstrated between fertility drugs and a variety of hormone-sensitive carcinomas. The purpose of this study was to determine the relationship between fertility drugs used in the treatment of female infertility and the risk of thyroid cancer. To investigate the clinical significance of fertility drugs used for the treatment of female infertility and the risk associated with thyroid cancer, we performed a literature search using PubMed, MEDLINE, the Cochrane Library, the Web of Science, and EBSCOHOST for comparative studies published any time prior to July 21, 2017. The studies included women who were treated for infertility with fertility drugs, such as clomiphene citrate, gonadotropins, or other unspecified fertility agents, which reported the incidence of thyroid cancer as the main outcome. Eight studies were included in the meta-analyses. Among women with infertility, there was a significant positive association between thyroid cancer risk and the use of fertility drugs (relative risk [RR] = 1.35; 95% confidence interval [CI] 1.12–1.64; P=0.002). Additionally, among women with infertility, the use of clomiphene citrate was associated with an increased risk of thyroid cancer compared to women who did not use fertility drugs (RR = 1.45; 95% CI 1.12–1.88; P=0.005). After pooling results, we found that the parity status of infertile women using fertility drugs was not associated with thyroid cancer risk (RR = 0.99; 95% CI 0.61–1.58, P=0.95). In summary, clomiphene citrate (the most commonly used fertility drug) and other fertility drugs are associated with an increased risk of thyroid cancer.

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Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry

Blood ◽

10.1182/blood-2013-04-495598 ◽

2013 ◽

Vol 122 (7) ◽

pp. 1284-1292 ◽

Cited By ~ 74

Author(s):

Martin Höglund ◽

Fredrik Sandin ◽

Karin Hellström ◽

Mats Björeman ◽

Magnus Björkholm ◽

...

Keyword(s):

Health Care ◽

Treatment Outcome ◽

Tyrosine Kinase Inhibitor ◽

Care Setting ◽

Kinase Inhibitor ◽

Relative Survival ◽

Population Based ◽

Prognostic Scores ◽

Key Points ◽

Eutos Score

Key Points Patients up to age 70 years with CML treated within a decentralized health care setting had a relative survival close to 1.0. Sokal, but not EUTOS, score at diagnosis predicted overall and relative survival in a population-based cohort of patients with CML.

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A population-based longitudinal study on the implication of demographic changes on blood donation and transfusion demand

Blood Advances ◽

10.1182/bloodadvances.2017005876 ◽

2017 ◽

Vol 1 (14) ◽

pp. 867-874 ◽

Cited By ~ 15

Author(s):

Andreas Greinacher ◽

Kerstin Weitmann ◽

Linda Schönborn ◽

Ulf Alpen ◽

Doris Gloger ◽

...

Keyword(s):

Longitudinal Study ◽

Blood Supply ◽

Blood Donation ◽

Population Based ◽

Demographic Changes ◽

Direct Impact ◽

Key Points ◽

The Future

Key Points Demographic changes have a direct impact on the blood supply, and demography can be used to predict blood donation rates in the future. The transfusion demand cannot be predicted from demography.

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Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study

Blood Advances ◽

10.1182/bloodadvances.2017014944 ◽

2018 ◽

Vol 2 (8) ◽

pp. 895-903 ◽

Cited By ~ 16

Author(s):

Lori Muffly ◽

Elysia Alvarez ◽

Daphne Lichtensztajn ◽

Renata Abrahão ◽

Scarlett Lin Gomez ◽

...

Keyword(s):

Lymphoblastic Leukemia ◽

Population Based ◽

Adolescent And Young Adult ◽

Front Line ◽

Population Based Study ◽

Key Points ◽

Adult Acute Lymphoblastic Leukemia ◽

Pediatric All ◽

Cancer Setting ◽

Cancer Settings

Key Points Two-thirds of AYA ALL are treated in the adult cancer setting; one-quarter of AYAs in this setting receive front-line pediatric ALL therapy. Survival was superior for AYA ALL patients treated in pediatric cancer settings and in NCI-designated cancer centers.

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Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

Blood Advances ◽

10.1182/bloodadvances.2017007609 ◽

2017 ◽

Vol 1 (24) ◽

pp. 2186-2192 ◽

Cited By ~ 13

Author(s):

Marianna Thordardottir ◽

Ebba K. Lindqvist ◽

Sigrun H. Lund ◽

Rene Costello ◽

Debra Burton ◽

...

Keyword(s):

Body Mass Index ◽

Multiple Myeloma ◽

Body Mass ◽

Monoclonal Gammopathy ◽

High Body Mass Index ◽

Population Based ◽

Population Based Study ◽

Increased Risk ◽

Key Points ◽

Undetermined Significance

Key PointsObesity is not associated with MGUS or LC-MGUS. High body mass index during midlife is associated with increased risk of progressing from MGUS and LC-MGUS to MM and other LP diseases.

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Assessing the Role of Selection Bias in the Protective Relationship Between Caregiving and Mortality

American Journal of Epidemiology ◽

10.1093/aje/kwz173 ◽

2019 ◽

Vol 188 (11) ◽

pp. 1961-1969

Author(s):

Meghan L Smith ◽

Timothy C Heeren ◽

Lynsie R Ranker ◽

Lisa Fredman

Keyword(s):

Selection Bias ◽

Osteoporotic Fractures ◽

Mortality Rates ◽

Sociodemographic Factors ◽

Population Based ◽

Ancillary Study ◽

Participation Bias ◽

Hazard Ratios ◽

Key Points

Abstract Caregivers have lower mortality rates than noncaregivers in population-based studies, which contradicts the caregiver-stress model and raises speculation about selection bias influencing these findings. We examined possible selection bias due to 1) sampling decisions and 2) selective participation among women (baseline mean age = 79 years) in the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF) (1999–2009), an ancillary study to the Study of Osteoporotic Fractures (SOF). Caregiver-SOF includes 1,069 SOF participants (35% caregivers) from 4 US geographical areas (Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley, Pennsylvania; and Portland, Oregon). Participants were identified by screening all SOF participants for caregiver status (1997–1999; n = 4,036; 23% caregivers) and rescreening a subset of caregivers and noncaregivers matched on sociodemographic factors 1–2 years later. Adjusted hazard ratios related caregiving to 10-year mortality in all women initially screened, subsamples representing key points in constructing Caregiver-SOF, and Caregiver-SOF. Caregivers had better functioning than noncaregivers at each screening. The association between caregiving and mortality among women invited to participate in Caregiver-SOF (41% died; adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI): 0.61, 0.88) was slightly more protective than that in all initially screened women (37% died; aHR = 0.83, 95% CI: 0.73, 0.95), indicating little evidence of selection bias due to sampling decisions, and was similar to that in Caregiver-SOF (39% died; aHR = 0.71, 95% CI: 0.57, 0.89), indicating no participation bias. These results add to a body of evidence that informal caregiving may impart health benefits.

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Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study

Blood ◽

10.1182/blood-2014-01-549733 ◽

2014 ◽

Vol 123 (25) ◽

pp. 3972-3978 ◽

Cited By ~ 100

Author(s):

Cheng E. Chee ◽

Aneel A. Ashrani ◽

Randolph S. Marks ◽

Tanya M. Petterson ◽

Kent R. Bailey ◽

...

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Recurrence Risk ◽

Population Based ◽

Secondary Prophylaxis ◽

Cancer Type ◽

Patients With Cancer ◽

Key Points ◽

Venous Thromboembolism Recurrence ◽

Active Cancer

Key Points VTE recurrence risk in patients with cancer can be stratified by cancer type, stage, stage progression, and presence of leg paresis. Patients with cancer at high VTE recurrence risk should be considered for secondary prophylaxis.

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