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1.
Hum Reprod ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926156

ABSTRACT

Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health due to impaired foetal androgen production/action. However, the epidemiological evidence supporting this view is equivocal, except for certain phthalates, notably diethyl hexyl phthalate (DEHP). Maternal phthalate exposure levels associated with adverse reproductive changes in epidemiological studies are several thousand-fold lower than those needed to suppress foetal androgen production in rats, and direct studies using human foetal testis tissue show no effect of high phthalate exposure on androgen production. This conundrum is unexplained and raises fundamental questions. Human DEHP exposure is predominantly via food with highest exposure associated with consumption of a Western style (unhealthy) diet. This diet is also associated with increased exposure to the most common EDCs, whether persistent (chlorinated or fluorinated chemicals) or non-persistent (phthalates, bisphenols) compounds, which are found at highest levels in fatty and processed foods. Consequently, epidemiological studies associating EDC exposure and male reproductive health disorders are confounded by potential dietary effects, and vice versa. A Western diet/lifestyle in young adulthood is also associated with low sperm counts. Disentangling EDC and dietary effects in epidemiological studies is challenging. In pregnancy, a Western diet, EDC exposure, and maternal living in proximity to industrial sites are all associated with impaired foetal growth/development due to placental dysfunction, which predisposes to congenital male reproductive disorders (cryptorchidism, hypospadias). While the latter are considered to reflect impaired foetal androgen production, effects resulting from foetal growth impairment (FGI) are likely indirect. As FGI has numerous life-long health consequences, and is affected by maternal lifestyle, research into the origins of male reproductive disorders should take more account of this. Additionally, potential effects on foetal growth/foetal testis from the increasing use of medications in pregnancy deserves more research attention.

2.
BMC Womens Health ; 24(1): 359, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907193

ABSTRACT

BACKGROUND: Breast imaging clinics in the United States (U.S.) are increasingly implementing breast cancer risk assessment (BCRA) to align with evolving guideline recommendations but with limited uptake of risk-reduction care. Effectively communicating risk information to women is central to implementation efforts, but remains understudied in the U.S. This study aims to characterize, and identify factors associated with women's interest in and preferences for breast cancer risk communication. METHODS: This is a cross-sectional survey study of U.S. women presenting for a mammogram between January and March of 2021 at a large, tertiary breast imaging clinic. Survey items assessed women's interest in knowing their risk and preferences for risk communication if considered to be at high risk in hypothetical situations. Multivariable logistic regression modeling assessed factors associated with women's interest in knowing their personal risk and preferences for details around exact risk estimates. RESULTS: Among 1119 women, 72.7% were interested in knowing their breast cancer risk. If at high risk, 77% preferred to receive their exact risk estimate and preferred verbal (52.9% phone/47% in-person) vs. written (26.5% online/19.5% letter) communications. Adjusted regression analyses found that those with a primary family history of breast cancer were significantly more interested in knowing their risk (OR 1.5, 95% CI 1.0, 2.1, p = 0.04), while those categorized as "more than one race or other" were significantly less interested in knowing their risk (OR 0.4, 95% CI 0.2, 0.9, p = 0.02). Women 60 + years of age were significantly less likely to prefer exact estimates of their risk (OR 0.6, 95% CI 0.5, 0.98, p < 0.01), while women with greater than a high school education were significantly more likely to prefer exact risk estimates (OR 2.5, 95% CI 1.5, 4.2, p < 0.001). CONCLUSION: U.S. women in this study expressed strong interest in knowing their risk and preferred to receive exact risk estimates verbally if found to be at high risk. Sociodemographic and family history influenced women's interest and preferences for risk communication. Breast imaging centers implementing risk assessment should consider strategies tailored to women's preferences to increase interest in risk estimates and improve risk communication.


Subject(s)
Breast Neoplasms , Mammography , Patient Preference , Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/psychology , Breast Neoplasms/diagnostic imaging , Cross-Sectional Studies , Middle Aged , Patient Preference/statistics & numerical data , Patient Preference/psychology , United States , Adult , Mammography/statistics & numerical data , Mammography/psychology , Risk Assessment/methods , Aged , Communication , Surveys and Questionnaires , Tertiary Care Centers , Health Knowledge, Attitudes, Practice
3.
Radiographics ; 43(12): e230100, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38032823

ABSTRACT

Contrast-enhanced mammography (CEM) is a relatively new breast imaging modality that uses intravenous contrast material to increase detection of breast cancer. CEM combines the structural information of conventional mammography with the functional information of tumor neovascularity. Initial studies have demonstrated that CEM and MRI perform with similar accuracies, with CEM having a slightly higher specificity (fewer false positives), although larger studies are needed. There are various reasons for false positives and false negatives at CEM. False positives at CEM can be caused by benign lesions with vascularity, including benign tumors, infection or inflammation, benign lesions in the skin, and imaging artifacts. False negatives at CEM can be attributed to incomplete or inadequate visualization of lesions, marked background parenchymal enhancement (BPE) obscuring cancer, lack of lesion contrast enhancement due to technical issues or less-vascular cancers, artifacts, and errors of lesion perception or characterization. When possible, real-time interpretation of CEM studies is ideal. If additional views are necessary, they may be obtained while contrast material is still in the breast parenchyma. Until recently, a limitation of CEM was the lack of CEM-guided biopsy capability. However, in 2020, the U.S. Food and Drug Administration cleared two devices to support CEM-guided biopsy using a stereotactic biopsy technique. The authors review various causes of false-positive and false-negative contrast-enhanced mammograms and discuss strategies to reduce these diagnostic errors to improve cancer detection while mitigating unnecessary additional imaging and procedures. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.


Subject(s)
Breast Neoplasms , Contrast Media , Humans , Female , Mammography/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Breast/diagnostic imaging , Diagnostic Errors/prevention & control , Magnetic Resonance Imaging/methods
4.
Radiographics ; 43(10): e230016, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37768862

ABSTRACT

High-risk lesions of the breast are frequently encountered in percutaneous biopsy specimens. While benign, these lesions have historically undergone surgical excision due to their potential to be upgraded to malignancy. However, there is emerging evidence that a tailored management approach should be considered to reduce overtreatment of these lesions. Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are two of the most commonly encountered high-risk lesions. FEA has been shown to have a relatively low rate of progression to malignancy, and some guidelines are now recommending observation over routine excision in select cases. Selective observation may be reasonable in cases where the target lesion is small and completely removed at biopsy and when there are no underlying risk factors, such as a history of breast cancer or genetic mutation or concurrent ADH. ADH has the highest potential upgrade rate to malignancy of all the high-risk lesions. Most society guidelines continue to recommend surgical excision of this lesion. More recently, some literature suggests that ADH lesions that appear completely removed at biopsy, involve limited foci (less than two or three) with no necrosis or significant atypia, manifest as a small group of mammographic calcifications, or demonstrate no enhancement at MRI may be reasonable for observation. Ultimately, management of all high-risk lesions must be based on a multidisciplinary approach that considers all patient, radiologic, clinical, and histopathologic factors. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

5.
Radiographics ; 42(3): 919-928, 2022.
Article in English | MEDLINE | ID: mdl-35333633

ABSTRACT

Kaizen process improvement is an element of lean production that is an approach to creating continuous improvement. Kaizen is based on the idea that small ongoing positive changes in workflow and elimination of waste can yield major improvements over time. A focused Kaizen event, or rapid process improvement event, can lead to sustainable process improvement in health care settings that are resistant to change. This approach has been proven to be successful in health care. These events are led by a trained facilitator and coach who provides appropriate team education and engagement. To ensure success, the team must embrace the Kaizen culture, which emphasizes the development of a "learning organization" that is focused on relentless pursuit of perfection. The culture empowers all staff to improve the work they perform, with an emphasis on the process and not the individual. Respect for individual people is key in Kaizen. In radiology, this method has been successful in empowering frontline staff to improve their individual workflows. A 5-day Kaizen event has been successful in increasing on-time starts, decreasing lead time, increasing patient and staff satisfaction, and ensuring sustainability. Sustainable success can occur when the team stays true to lean principles, engages leaders, and empowers team members with the use of timely data to drive decision making. Online supplemental material is available for this article. ©RSNA, 2022.


Subject(s)
Quality Improvement , Radiology , Humans
6.
Differentiation ; 118: 41-71, 2021.
Article in English | MEDLINE | ID: mdl-33441255

ABSTRACT

Estrogen has always been considered the female hormone and testosterone the male hormone. However, estrogen's presence in the testis and deleterious effects of estrogen treatment during development have been known for nearly 90 years, long before estrogen receptors (ESRs) were discovered. Eventually it was learned that testes actually synthesize high levels of estradiol (E2) and sequester high concentrations in the reproductive tract lumen, which seems contradictory to the overwhelming number of studies showing reproductive pathology following exogenous estrogen exposures. For too long, the developmental pathology of estrogen has dominated our thinking, even resulting in the "estrogen hypothesis" as related to the testicular dysgenesis syndrome. However, these early studies and the development of an Esr1 knockout mouse led to a deluge of research into estrogen's potential role in and disruption of development and function of the male reproductive system. What is new is that estrogen action in the male cannot be divorced from that of androgen. This paper presents what is known about components of the estrogen pathway, including its synthesis and target receptors, and the need to achieve a balance between androgen- and estrogen-action in male reproductive tract differentiation and adult functions. The review focuses on what is known regarding development of the male reproductive tract, from the rete testis to the vas deferens, and examines the expression of estrogen receptors and presence of aromatase in the male reproductive system, traces the evidence provided by estrogen-associated knockout and transgenic animal models and discusses the effects of fetal and postnatal exposures to estrogens. Hopefully, there will be enough here to stimulate discussions and new investigations of the androgen:estrogen balance that seems to be essential for development of the male reproductive tract.


Subject(s)
Androgens/metabolism , Estrogen Receptor alpha/genetics , Estrogens/metabolism , Testosterone/metabolism , Androgens/genetics , Animals , Embryo, Mammalian , Embryonic Development/genetics , Epididymis/growth & development , Epididymis/metabolism , Estradiol/metabolism , Estrogens/genetics , Female , Genitalia, Male , Male , Mice , Mice, Knockout/genetics , Rete Testis/growth & development , Rete Testis/metabolism , Testosterone/genetics
7.
Radiology ; 298(1): E11-E18, 2021 01.
Article in English | MEDLINE | ID: mdl-32677874

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic resulted in widespread disruption to the global economy, including demand for imaging services. The resulting reduction in demand for imaging services had an abrupt and substantial impact on private radiology practices, which are heavily dependent on examination volumes for practice revenues. The goal of this report is to describe the specific experiences of radiologists working in various types of private radiology practices during the initial peak of the COVID-19 pandemic. Herein, the authors describe factors determining the impact of the pandemic on private practices, the challenges these practices faced, the cost levers leaders adjusted, and the government subsidies sought. In addition, the authors describe adjustments practices are making to their mid- and long-term strategic plans to pivot for long-term success while managing the COVID-19 pandemic. Private practices have crafted tiered strategies to respond to the impact of the pandemic by pulling various cost levers to adjust service availability, staffing, compensation, benefits, time off, and expense reductions. In addition, they have sought additional revenues, within the boundaries of their practice, to mitigate ongoing financial losses. The longer term impact of the pandemic will alter existing practices, making some of them more likely than others to succeed in the years ahead. This report synthesizes the collective experience of private-practice radiologists shared with members of the Radiological Society of North America COVID-19 Task Force, including discussions with colleagues and leaders of private-practice radiology groups from across the United States.


Subject(s)
COVID-19 , Private Practice/economics , Radiology/economics , Advisory Committees , Humans , Radiography/statistics & numerical data , Societies, Medical , Time Factors , United States
8.
AJR Am J Roentgenol ; 217(4): 855-856, 2021 10.
Article in English | MEDLINE | ID: mdl-33728971

ABSTRACT

In 17 women with newly diagnosed breast cancer who underwent contrast-enhanced mammography (CEM) and MRI, both modalities were found to be concordant for the index cancer. In six of the 17 women, CEM showed an additional lesion that was confirmed by MRI. Of these six additional lesions, three were multifocal, one was multicentric, and two were contralateral; two of the six were malignant. MRI did not identify any additional cancers that were not identified on CEM. CEM may have a role in women with breast augmentation and either a contraindication or limited access to MRI.


Subject(s)
Breast Neoplasms/diagnostic imaging , Contrast Media , Mammaplasty , Mammography/methods , Carcinoma in Situ/diagnostic imaging , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Lobular/diagnostic imaging , Contraindications, Procedure , Female , Humans , Magnetic Resonance Imaging/adverse effects , Retrospective Studies
9.
Radiographics ; 41(1): E1-E8, 2021.
Article in English | MEDLINE | ID: mdl-33411608

ABSTRACT

A multidisciplinary team evaluated and improved the MRI processes within the authors' integrated health care system, with the aim to increase patient access to MRI. The authors created a SMART (specific, measurable, achievable, relevant, and time-based) goal of decreasing the average number of days to wait for MRI examination by 50%, from 15 to 7.5 days, while also creating capacity to meet demand for same-day and next-day MRI appointment requests. The current performance metrics and processes were compared with available benchmarking and best practice data. Several work groups were created to empower and support frontline teams to identify and capture improvement opportunities. Across all MRI processes, teams focused on creating standard work, advancing practice to top of scope, removing waste, improving communication, reducing rework, and improving patient experience. Patient access to MRI was monitored, measured as the average number of days to wait from the time of scheduling to the MRI examination and time to the third-available appointment. The authors also monitored secondary outcomes (patient satisfaction, throughput metrics) and a balancing measure (technical repeat examination rates). The access improved after intervention: the average number of days to wait for MRI access decreased from 14.2 days to 5.8 days after the intervention (-8.4 days, -59.2%, P < .0001) and third-available appointment decreased from 18 days to 0 days. Ten to 20 same-day and next-day appointments became routinely available. The throughput metrics improved, and balancing measures were not changed. This project resulted in significant improvements in patient access to MRI examinations. The findings demonstrate the value of a multidisciplinary team applying comprehensive improvement strategies to increase patient access to complex services, such as MRI. ©RSNA, 2021.


Subject(s)
Appointments and Schedules , Patient Satisfaction , Health Services Accessibility , Humans , Magnetic Resonance Imaging
10.
Biochem Soc Trans ; 48(4): 1725-1735, 2020 08 28.
Article in English | MEDLINE | ID: mdl-32779695

ABSTRACT

Human male reproductive disorders are common and may have a fetal origin - the testicular dysgenesis syndrome (TDS) hypothesis. In rats, experimentally induced TDS disorders result from disruption of fetal androgen production/action specifically in the masculinization programming window (MPW). MPW androgen action also programs longer anogenital distance (AGD) in male versus female rats; shorter male AGD is correlated with risk and severity of induced TDS disorders. AGD thus provides a lifelong, calibrated readout of MPW androgen exposure and predicts likelihood of reproductive dysfunction. Pregnant rat exposure to environmental chemicals, notably certain phthalates (e.g. diethyl hexl phthalate, DEHP; dibutyl phthalate, DBP), pesticides or paracetamol, can reduce fetal testis testosterone and AGD and induce TDS disorders, provided exposure includes the MPW. In humans, AGD is longer in males than females and the presumptive MPW is 8-14 weeks' gestation. Some, but not all, epidemiological studies of maternal DEHP (or pesticides) exposure reported shorter AGD in sons, but this occurred at DEHP exposure levels several thousand-fold lower than are effective in rats. In fetal human testis culture/xenografts, DEHP/DBP do not reduce testosterone production, whereas therapeutic paracetamol exposure does. In humans, androgen production in the MPW is controlled differently (human chorionic gonadotrophin-driven) than in rats (paracrine controlled), and other organs (placenta, liver, adrenals) contribute to MPW androgens, essential for normal masculinization, via the 'backdoor pathway'. Consequently, early placental dysfunction, which is affected by maternal lifestyle and diet, and maternal painkiller use, may be more important than environmental chemical exposures in the origin of TDS in humans.


Subject(s)
Androgens/pharmacology , Gonadal Dysgenesis/chemically induced , Testis/drug effects , Animals , Female , Fetal Development/drug effects , Humans , Male , Maternal Exposure , Placenta/drug effects , Pregnancy , Rats
11.
AJR Am J Roentgenol ; 213(5): 1015-1020, 2019 11.
Article in English | MEDLINE | ID: mdl-31310183

ABSTRACT

OBJECTIVE. The objective of our study was to evaluate whether the use of a clinical decision support (CDS) tool improved the appropriateness scores of orders for advanced imaging in clinical practice. MATERIALS AND METHODS. We used a stepped-wedge, cluster randomized clinical trial to evaluate the effectiveness of a CDS tool in an integrated health care system. Clinicians entered structured indications for each CT and MRI order, and the indications were electronically scored against appropriateness criteria to assign an appropriateness score. We compared the proportion of orders with adjusted appropriateness scores of 7 or greater (on a 1-9 scale) before and after activation of best practice alerts (BPAs) triggered for orders with low or marginal appropriateness scores. Secondary outcomes included the rate per month of orders for advanced imaging and the proportion of orders for which the radiology department requested changes. RESULTS. Between October 2015 and February 2016, 941 clinicians ordered 22,279 CT or MRI studies that met eligibility criteria. Before activation of the BPA, the mean proportion of appropriate orders (adjusted for time and clinic effect) was 77.0% (95% CI, 75.5-78.4%), which increased to 80.1% (95% CI, 78.7-81.5%) after activation (p = 0.001). There was no significant change in the rate of orders per month for advanced imaging. The proportion of order changes requested by the radiology department decreased from 5.7% (95% CI, 5.6-5.9%) before CDS implementation to 5.3% (95% CI, 5.1-5.5%) after CDS implementation (p < 0.001). CONCLUSION. Using an evidence-based CDS tool in clinical practice was associated with a modest but significant improvement in the appropriateness scores of advanced imaging orders.


Subject(s)
Ambulatory Care Facilities , Decision Support Systems, Clinical , Magnetic Resonance Imaging , Medical Order Entry Systems/standards , Practice Patterns, Physicians'/statistics & numerical data , Tomography, X-Ray Computed , Humans
12.
AJR Am J Roentgenol ; 213(5): 1023-1028, 2019 11.
Article in English | MEDLINE | ID: mdl-31386569

ABSTRACT

OBJECTIVE. The purpose of this quality improvement project was to create sustained improvement in the frequency of more complete imaging histories provided with imaging examinations submitted directly by ordering providers. A secondary purpose was increasing the number of characters submitted by ordering providers with imaging examinations. MATERIALS AND METHODS. A multidisciplinary team defined the components of a complete imaging history, a process that underwent several improvement cycles. Audits were regularly performed using consensus, and the project team regularly evaluated the completeness of the imaging histories. The final components of the definition of a complete imaging history included responses regarding what happened, when it happened, where the patient was experiencing pain, and the ordering provider's concern. Prompts were inserted into the electronic physician order entry process, and performance was monitored for an additional 18 months. RESULTS. A total of 10,236 orders were placed by providers in the study clinic from March 13, 2017, to December 16, 2018. Of the orders audited in the baseline period, 16.0% (64/397) of orders audited in the baseline period contained all four history components, which increased to 52.0% (2200/4234; absolute increase of 36.0%, relative increase of 225.0%; p < 0.0001) in the subsequent time periods, and improvement was sustained. The mean number of characters providers entered in the imaging histories they submitted increased from 45.4 characters per order during the baseline period to 75.4 (66.1% increase, p < 0.0001) after the intervention. CONCLUSION. By collaborating with a multidisciplinary team, we created a standardized definition of an imaging history, engineered our systems to include supportive prompts in the order entry interface, and sustainably improved the quality of imaging histories provided.


Subject(s)
Diagnostic Imaging , Medical Order Entry Systems , Practice Patterns, Physicians'/statistics & numerical data , Quality Improvement , Radiology Information Systems/standards , Systems Analysis , Cooperative Behavior , Humans
13.
Breast J ; 25(2): 262-268, 2019 03.
Article in English | MEDLINE | ID: mdl-30746809

ABSTRACT

The purpose of this study was to evaluate providers' ordering practices and perceptions of breast magnetic resonance imaging (MRI) in an academic network in order to better understand and educate a referral base. An online survey was distributed to primary care providers (PCPs) and specialists in our hospital and community practices. Questions included provider demographics, current ordering practices, challenges to ordering, and perceptions about breast MRI. Of 525 ordering providers, 134 responded (26% response rate). Of 134 providers, 57 (42%) order breast MRI in practice. Of those who do not, the most consistent reason was a lack of familiarity with the use of breast MRI (32/77 [42%] of cases). Of 57 cases, 45 (79%) order less than 10 exams annually. The most frequent indication is for high-risk screening (40/47 [84%]). PCPs order fewer breast MRI compared with specialists (P = 0.01). Both PCPs and specialists have mixed perceptions of the clinical utility of breast MRI. However, 30% of all providers are ordering more breast MRI since the enactment of breast density legislation in Massachusetts. Furthermore, 29% report they would order breast MRI more often to screen women with dense breasts if there was a low cost option. Referring provider surveys are useful tools for assessing a radiology practice. Our study suggests a growing clinical interest in breast MRI for screening; however, there is a need for provider education on the clinical utility of breast MRI. Increasing the radiologist's role in targeted educational interventions may help improve awareness and lead to more appropriate utilization of resources.


Subject(s)
Breast Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Breast Density , Female , Humans , Insurance Coverage , Massachusetts , Physicians, Primary Care
14.
Hum Reprod ; 33(4): 541-545, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29425298

ABSTRACT

Approximately 1 in 20 young men today have sperm counts low enough to impair fertility, whereas this may not have been the case historically. The cause(s) of such a decline in male reproductive health is unknown, despite it being a global health issue. Concomitantly, little progress has been made in answering fundamental questions in andrology or in developing new diagnostic tools or alternative management strategies to ICSI in infertile men. We advocate formulation of a detailed roadmap for male reproductive health to facilitate development of a research agenda that highlights the present unmet needs and key unanswered questions, and seeks to deliver effective funding and investment to address them. This vision we term 'a Male Reproductive Health Ecosystem'.


Subject(s)
Infertility, Male , Reproduction , Reproductive Health , Research , Fertility , Humans , Male
15.
Hum Reprod ; 33(11): 2107-2121, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30272154

ABSTRACT

STUDY QUESTION: Does loss of DMRT1 in human fetal testis alter testicular development and result in testicular dysgenesis? SUMMARY ANSWER: DMRT1 repression in human fetal testis alters the expression of key testicular and ovarian determining genes, and leads to focal testicular dysgenesis. WHAT IS KNOWN ALREADY: Testicular dysgenesis syndrome (TDS) is associated with common testicular disorders in young men, but its etiology is unknown. DMRT1 has been shown to play a role in the regulation of sex differentiation in the vertebrate gonad. Downregulation of DMRT1 in male mice results in trans-differentiation of Sertoli cells into granulosa (FOXL2+) cells resulting in an ovarian gonadal phenotype. STUDY DESIGN, SIZE, DURATION: To determine the effect of DMRT1 repression on human fetal testes, we developed a novel system for genetic manipulation, which utilizes a Lentivral delivered miRNA during short-term in vitro culture (2 weeks). A long-term (4-6 weeks) ex vivo xenograft model was used to determine the subsequent effects of DMRT1 repression on testicular development and maintenance. We included first and second-trimester testis tissue (8-20 weeks gestation; n = 12) in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human fetal testes were cultured in vitro and exposed to either of two DMRT1 miRNAs (miR536, miR641), or to scrambled control miRNA, for 24 h. This was followed by a further 14 days of culture (n = 3-4), or xenografting (n = 5) into immunocompromised mice for 4-6 weeks. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence and quantitative RT-PCR. Endpoints included histological evaluation of seminiferous cord integrity, mRNA expression of testicular, ovarian and germ cell genes, and assessment of cell number and protein expression for proliferation, apoptosis and pluripotency factors. Statistical analysis was performed using a linear mixed effect model. MAIN RESULTS AND THE ROLE OF CHANCE: DMRT1 repression (miR536/miR641) resulted in a loss of DMRT1 protein expression in a sub-population of Sertoli cells of first trimester (8-11 weeks gestation) human fetal testis; however, this did not affect the completion of seminiferous cord formation or morphological appearance. In second-trimester testis (12-20 weeks gestation), DMRT1 repression (miR536/miR641) resulted in disruption of seminiferous cords with absence of DMRT1 protein expression in Sertoli (SOX9+) cells. No differences in proliferation (Ki67+) were observed and apoptotic cells (CC3+) were rare. Expression of the Sertoli cell associated gene, SOX8, was significantly reduced (miR536, 34% reduction, P = 0.031; miR641 36% reduction, P = 0.026), whilst SOX9 expression was unaffected. Changes in expression of AMH (miR536, 100% increase, P = 0.033), CYP26B1 (miR641, 38% reduction, P = 0.05) and PTGDS (miR642, 30% reduction, P = 0.0076) were also observed. Amongst granulosa cell associated genes, there was a significant downregulation in R-spondin 1 expression (miR536, 76% reduction, P < 0.0001; miR641, 49% reduction, P = 0.046); however, there were no changes in expression of the granulosa cell marker, FOXL2. Analysis of germ cell associated genes demonstrated a significant increase in the expression of the pluripotency gene OCT4 (miR536, 233%, P < 0.001). We used the xenograft system to investigate the longer-term effects of seminiferous cord disruption via DMRT1 repression. As was evident in vitro for second-trimester samples, DMRT1 repression resulted in focal testicular dysgenesis similar to that described in adults with TDS. These dysgenetic areas were devoid of germ cells, whilst expression of FOXL2 within the dysgenetic areas, indicated trans-differentiation from a male (Sertoli cell) to female (granulosa cell) phenotype. LIMITATIONS, REASONS FOR CAUTION: Human fetal testis tissue is a limited resource; however, we were able to demonstrate significant effects of DMRT1 repression on the expression of germ and somatic cell genes, in addition to the induction of focal testicular dysgenesis, using these limited samples. In vitro culture may not reflect all aspects of human fetal testis development and function; however, the concurrent use of the xenograft model which represents a more physiological system supports the validity of the in vitro findings. WIDER IMPLICATIONS OF THE FINDINGS: Our findings have important implications for understanding the role of DMRT1 in human testis development and in the origin of testicular dysgenesis. In addition, we provide validation of a novel system that can be used to determine the effects of repression of genes that have been implicated in gonadal development and associated human reproductive disorders. STUDY FUNDING/COMPETING INTEREST(S): This project was funded by a Wellcome Trust Intermediate Clinical Fellowship (Grant No. 098522) awarded to RTM. LBS was supported by MRC Programme Grant MR/N002970/1. RAA was supported by MRC Programme Grant G1100357/1. RMS was supported by MRC Programme Grant G33253. This work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1. The funding bodies had no input into the conduct of the research or the production of this manuscript. The authors have declared no conflicts of interest.


Subject(s)
Gonadal Dysgenesis/embryology , Gonadal Dysgenesis/genetics , Testis/embryology , Transcription Factors/metabolism , Animals , Down-Regulation , Gene Knockdown Techniques , Humans , Male , Mice , Mice, Nude , MicroRNAs , Sertoli Cells/metabolism
16.
Reproduction ; 155(3): S1-S16, 2018 02.
Article in English | MEDLINE | ID: mdl-29269516

ABSTRACT

Reproduction is our biological reason for being. Our physiology has been shaped via countless millennia of evolution with this one purpose in mind, so that at birth we are 'programmed for sex', although this will not kick-start functionally until puberty. Our development from an early embryo is focused on making us fit to reproduce and is intimately connected to nutrition and energy stores. Fluctuations in food supply has probably been a key evolutionary shaper of the reproductive process, and this review hypothesizes that we have developed rapid, non-genomic adaptive mechanisms to such fluctuations to better fit offspring to their perceived (nutritional) environment, thus giving them a reproductive advantage. There is abundant evidence for this notion from 'fetal programming' studies and from experimental 'inter-generational' studies involving manipulation of parental (especially paternal) diet and then examining metabolic changes in resulting offspring. It is argued that the epigenetic reprogramming of germ cells that occurs during fetal life, after fertilisation and during gametogenesis provides opportunities for sensing of the (nutritional) environment so as to affect adaptive epigenetic changes to alter offspring metabolic function. In this regard, there may be adverse effects of a modern Western diet, perhaps because it is deficient in plant-derived factors that are proven to be capable of altering the epigenome, folate being a prime example; we have evolved in tune with such factors. Therefore, parental and even grandparental diets may have consequences for health of future generations, but how important this might be and the precise epigenetic mechanisms involved are unknown.


Subject(s)
Epigenesis, Genetic , Fetal Development , Maternal Nutritional Physiological Phenomena , Reproduction , Sexual Maturation , Animals , Diet , Female , Humans , Pregnancy
18.
AJR Am J Roentgenol ; 211(5): 949-956, 2018 11.
Article in English | MEDLINE | ID: mdl-30207788

ABSTRACT

OBJECTIVE: The aim of this study was to compare the efficacy of a peer learning program to score-based peer review in a radiology department. MATERIALS AND METHODS: Our score-based peer review program was transitioned to an open, inclusive, education- and improvement-oriented peer learning program. Program performance was evaluated by learning opportunity submissions, program participation, number of learning opportunity distributions to radiologists, number of practice improvement projects resulting from program, and radiologist survey results before and after interventions. RESULTS: Outcomes for the score-based peer review program compared with those of the peer learning program were as follows. The mean number of radiologists participating monthly increased from 5.0 to 35.2 (p < 0.01); submissions increased from 3.0 discrepancies per month to 36.0 learning opportunities per month (p < 0.01); the mean monthly learning opportunity distributions to radiologists increased from 18 to 352 (p < 0.01); improvement projects performed during the study periods increased from 5 to 61 (p < 0.01); and mean monthly continuing medical education credits earned by radiologists increased from 7.7 to 50.6 (p < 0.01). Radiologists felt peer learning accomplished goals better than did score-based peer review. CONCLUSION: In transitioning our score-based peer review program to a peer learning program, our radiologists identified, discussed, and converted more learning opportunities into practice improvement and perceived peer learning to be of higher value than score-based peer review.


Subject(s)
Education, Medical, Continuing , Peer Review, Health Care , Quality Assurance, Health Care/standards , Radiology/education , Radiology/standards , Clinical Competence , Humans , Private Practice , Program Evaluation , Quality Improvement
19.
Breast J ; 24(3): 319-324, 2018 05.
Article in English | MEDLINE | ID: mdl-28833841

ABSTRACT

Performance benchmarks exist for mammography (MG); however, performance benchmarks for magnetic resonance imaging (MRI) are not yet fully developed. The purpose of our study was to perform an MRI audit based on established MG and screening MRI benchmarks and to review whether these benchmarks can be applied to an MRI practice. An IRB approved retrospective review of breast MRIs was performed at our center from 1/1/2011 through 12/31/13. For patients with biopsy recommendation, core biopsy and surgical pathology results were reviewed. The data were used to derive mean performance parameter values, including abnormal interpretation rate (AIR), positive predictive value (PPV), cancer detection rate (CDR), percentage of minimal cancers and axillary node negative cancers and compared with MG and screening MRI benchmarks. MRIs were also divided by screening and diagnostic indications to assess for differences in performance benchmarks amongst these two groups. Of the 2455 MRIs performed over 3-years, 1563 were performed for screening indications and 892 for diagnostic indications. With the exception of PPV2 for screening breast MRIs from 2011 to 2013, PPVs were met for our screening and diagnostic populations when compared to the MRI screening benchmarks established by the Breast Imaging Reporting and Data System (BI-RADS) 5 Atlas® . AIR and CDR were lower for screening indications as compared to diagnostic indications. New MRI screening benchmarks can be used for screening MRI audits while the American College of Radiology (ACR) desirable goals for diagnostic MG can be used for diagnostic MRI audits. Our study corroborates established findings regarding differences in AIR and CDR amongst screening versus diagnostic indications.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Magnetic Resonance Imaging/standards , Benchmarking , Biopsy/methods , Female , Humans , Magnetic Resonance Imaging/methods , Mammography , Mass Screening/statistics & numerical data , Retrospective Studies
20.
Radiology ; 283(1): 231-241, 2017 04.
Article in English | MEDLINE | ID: mdl-27673509

ABSTRACT

In September 2015, the Institute of Medicine (IOM) published a report titled "Improving Diagnosis in Health Care," in which it was recommended that "health care organizations should adopt policies and practices that promote a nonpunitive culture that values open discussion and feedback on diagnostic performance." It may seem counterintuitive that a report addressing a highly technical skill such as medical diagnosis would be focused on organizational culture. The wisdom becomes clearer, however, when examined in the light of recent advances in the understanding of human error and individual and organizational performance. The current dominant model for radiologist performance improvement is scoring-based peer review, which reflects a traditional quality assurance approach, derived from manufacturing in the mid-1900s. Far from achieving the goals of the IOM, which are celebrating success, recognizing mistakes as an opportunity to learn, and fostering openness and trust, we have found that scoring-based peer review tends to drive radiologists inward, against each other, and against practice leaders. Modern approaches to quality improvement focus on using and enhancing interpersonal professional relationships to achieve and maintain high levels of individual and organizational performance. In this article, the authors review the recommendations set forth by the recent IOM report, discuss the science and theory that underlie several of those recommendations, and assess how well they fit with the current dominant approach to radiology peer review. The authors also offer an alternative approach to peer review: peer feedback, learning, and improvement (or more succinctly, "peer learning"), which they believe is better aligned with the principles promoted by the IOM. © RSNA, 2016.


Subject(s)
Diagnostic Errors/prevention & control , Formative Feedback , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Peer Review/methods , Quality Improvement , Radiology/standards , Humans , Organizational Culture , United States
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