"Is It Realistic?": A Qualitative Study of the Experiences of Elite Women Athletes Considering Parenthood.

BACKGROUND AND OBJECTIVE: As the visibility and acceptance of athlete-mothers increase, so does the number of women athletes considering parenthood. Yet, many athletes struggle with the decision to become a parent while competing at the elite level due to the significant changes and uncertainties that have been reported by pregnant and parenting athletes. The experiences of women athletes considering parenthood are under-represented in the vast sport literature but are necessary for developing evidenced-based policies and practices that can support women's equitable participation in high-performance sport contexts. Thus, the purpose of this qualitative study was to describe the experiences of elite women athletes that are considering parenthood. METHODS: Participants were ten elite North American athletes (29-36 years) who are considering becoming parents in the next 5 years. Each participant self-identified as a woman and competed at the highest level in their respective sport. Data were generated via one-on-one semi-structured interviews that were audio-recorded, transcribed verbatim, and analyzed through a process of content analysis. RESULTS: The experiences of elite women athletes considering parenthood are represented by five themes: (a) calls for essential mandates and leadership, (b) how do you support yourself?, (c) hesitation of body changes, (d) age inequities, and (e) being proactive about reproductive health. Such findings support an in-depth understanding of gender-specific stressors that limit women's equitable participation in high-performance contexts. CONCLUSION: This research is grounded in the voices of elite women athletes and identifies actionable steps necessary for research and culture change. Findings provide necessary evidence to inform the development of sport policies to support those athletes that are considering becoming parents.

Diagnostic Conundrum of a Sertoli Cell Tumor in a 2-Year-Old Girl with Peripheral Precocious Puberty and a Café-au-Lait Macule: A Case Report.

INTRODUCTION: Ovarian Sertoli cell tumors represent a subset of sex cord stromal tumors and are exceedingly rare in prepubertal children. Here, we report a girl with vaginal bleeding due to a Sertoli cell tumor who was originally thought to have McCune-Albright syndrome (MAS). CASE PRESENTATION: A previously healthy girl presented at age 2 years 6 months with breast development and vaginal bleeding. On exam, she had Tanner 4 breasts, Tanner 1 pubic hair, estrogenized vaginal mucosa, and a café-au-lait macule. Laboratory studies revealed an elevated estradiol with suppressed gonadotropins and negative tumor markers. Her bone age was advanced by more than 3 years. Pelvic ultrasound (US) revealed an enlarged uterus and a slightly larger left compared to right ovary. She was started on tamoxifen for presumed MAS. A repeat pelvic US 1 month later showed a heterogenous mass in the left ovary which was subsequently resected. Pathology revealed a Sertoli cell tumor, lipid-rich variant. Germline sequencing revealed a pathogenic STK11 variant, diagnostic for Peutz-Jeghers syndrome (PJS). CONCLUSION: The findings in our patient were strikingly similar to those encountered in MAS. To our knowledge, our patient is the youngest ever reported to present with precocious puberty due to a Sertoli cell tumor in the setting of PJS.

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.

BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.

Imaging of Urinary Bladder and Ureteral Endometriosis with Emphasis on Diagnosis and Technique.

Endometriosis is a chronic inflammatory gynecological condition affecting 10-15% of women in the reproductive age group. The urinary tract is the second most common extragenital organ system affected by endometriosis, and the urinary bladder and ureter are the two most common sites involved. Involvement of the urinary bladder can cause chronic debilitating symptoms, whereas ureteral involvement may lead to asymptomatic loss of renal function. Both conditions are frequently unsuspected, leading to a delay in diagnosis. Therefore, it is important to recognize this entity early, for which knowledge of imaging appearances and techniques is helpful. In this review article, we describe (a) endometriosis background, pathogenesis, definitions and clinical symptoms, (b) imaging appearance, with emphasis on ultrasound and MRI findings of urinary bladder and ureteric endometriosis, (c) ultrasound technique and MRI sequences useful for making the correct diagnosis, (d) overview of the treatment options and key imaging findings that are important to the surgeon for surgical planning, and (e) a structured reporting template useful for multidisciplinary patient management.

Filling the evidence void: exploration of coach and healthcare provider experiences working with pregnant and postpartum elite athletes - a qualitative study.

OBJECTIVE: Recent research grounded in the experiences of elite female athletes has shed light on the complex challenges of navigating sport environments that do not support or value pregnant or postpartum athletes. The purpose of this study was to explore the unique experiences of coaches and healthcare providers working with pregnant and postpartum elite athletes, and to identify actionable steps for research, policy and culture change to support them. METHODS: Sixteen participants (five coaches, three physicians and eight physiotherapists), who have worked with pregnant and/or postpartum elite athletes within the last 5 years, participated in this qualitative study. Thirteen participants self-identified as women, and three as men. Data were generated via semistructured one-on-one interviews that were audiorecorded, transcribed verbatim and analysed through a process of content analysis. RESULTS: The findings of this research are represented by five main themes: (a) lack of female athlete reproductive research, (b) need for evidence-informed education and training, (c) need to develop evidence-based progression for sport participation in pregnancy and postpartum, (d) open communication to support athlete-centred care and (e) essential supports and changes required for pregnant/postpartum athletes. CONCLUSION: Findings from this study, which are grounded in the unique perspectives of coaches and healthcare providers, outline specific recommendations to inform policy and practices that support athletes through the perinatal period, such as developing evidence-based return-to-sport protocols.

Long-term experience with the use of a single histrelin implant beyond one year in patients with central precocious puberty.

OBJECTIVES: The histrelin implant has been used to treat central precocious puberty (CPP) for more than 15 years. Although approved for annual use, limited published reports suggest that a single implant is efficacious well beyond a year. Our objective was to report our long-term experience using a single histrelin implant for more than 12 months in children with CPP. METHODS: We performed a retrospective study of 170 children with central precocious puberty treated with a single histrelin implant for more than 1 year. RESULTS: Implants were left in situ for an average of 24 months. Pubertal development regressed or remained stable in the vast majority of patients and biochemical suppression was maintained. No correlation between time since an implant was placed and complications such as implant breakage or a second incision was seen. CONCLUSIONS: A single histrelin implant provides excellent pubertal suppression well beyond a year. Extended use of a single histrelin implant should be considered standard of care in children with CPP.

We're not Superhuman, We're Human: A Qualitative Description of Elite Athletes' Experiences of Return to Sport After Childbirth.

BACKGROUND: A growing number of athletes return to elite sport following childbirth. Yet, they face significant barriers to do so safely and successfully. The experiences of elite athletes returning to sport following delivery are necessary to support evidence-informed policy. OBJECTIVE: The purpose of this qualitative description was to describe the experiences of elite athletes as they returned to sport following childbirth, and to identify actionable steps for research, policy and culture-change to support elite athlete mothers. METHODS: Eighteen elite athletes, primarily from North America, who had returned to sport following childbirth in the last 5 years were interviewed. Data were generated via one-on-one semi-structured interviews that were audio-recorded, transcribed verbatim, and analyzed through a process of content analysis. RESULTS: The findings of this study are represented by one overarching theme: Need for More Time, and five main themes: (a) Training "New Bodies" Postpartum, (b) Injuries and Safe Return to Sport, (c) Breastfeeding While Training, (d) Critical Supports for Return to Sport, (e) Navigating Motherhood and Sport. The athletes identified the urgent need to develop best-practice policies and funding to support return to sport, as well as develop evidence-based return-to-sport protocols to support a safe and injury-free return. CONCLUSION: Athletes shared detailed stories highlighting the challenges, barriers and successes elite athletes experience returning to elite-level sport following childbirth. Participants provided clear recommendations for policy and research to better support the next generation of elite athlete mothers.

Pushing for change: a qualitative study of the experiences of elite athletes during pregnancy.

OBJECTIVES: Athletes train and compete at the elite level during their reproductive years, yet sport policies that support pregnant athletes are lacking. The experiences of elite athletes during pregnancy are vastly under-represented, and such voices are needed to support evidence-informed policy. Thus, the purpose of this qualitative study was to describe the experiences of elite female athletes as they navigate pregnancy, and to identify sport policy considerations regarding participation during pregnancy. METHODS: Twenty athletes (mean age 35±5 years) who, within the last 5 years, had trained or competed at the elite level immediately prior to becoming pregnant were included. Data were generated via one-on-one semistructured interviews that were audio-recorded, transcribed verbatim and analysed through a process of content analysis. RESULTS: The findings of this study are represented by one overarching message: mother versus athlete, and five main themes: (1) pregnancy planning and fertility, (2) pregnancy disclosure and discrimination, (3) training pregnant athletic bodies, (4) safety concerns, and (5) supportive network and equitable funding. CONCLUSION: In-depth stories shared by participants highlight the many significant decisions athletes must make as they navigate pregnancy alongside elite sport participation. The shared experiences of pregnant athletes highlight clear challenges that should be considered in the development of sport policy and practices that are inclusive and supportive of female athletes.

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units.

Type I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of α, ß-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemically-synthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual ß-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues.

A Peptidyl-Transesterifying Type†I Thioesterase in Salinamide Biosynthesis.

Salinamide A belongs to a rare class of bicyclic depsipeptide antibiotics in which the installation of a (4-methylhexa-2,4-dienoyl)glycine handle across a hexadepsipeptide core contributes to its chemical complexity and biological properties. Herein, we report the genetic and biochemical basis for salinamide construction in the marine bacterium Streptomyces sp. CNB-091, which involves a novel intermolecular transesterification reaction catalyzed by a type I thioesterase. Heterologous expression studies revealed the central role of the nonribosomal peptide synthetase Sln9 in constructing and installing the distinctive acylglycine "basket handle" of salinamide. Biochemical characterization of the Sln9 thioesterase domain established that transesterification of the serine residue of desmethylsalinamide E with acylated glycyl thioesters yields desmethylsalinamide C.

Recent advances in the biosynthesis of unusual polyketide synthase substrates.

This highlight provides an overview of recent advances in understanding the diversity of polyketide synthase (PKS) substrate building blocks. Substrates functioning as starter units and extender units contribute significantly to the chemical complexity and structural diversity exhibited by this class of natural products. This article complements and extends upon the current comprehensive reviews that have been published on these two topics (Moore and Hertweck, Nat. Prod. Rep., 2002, 19, 70; Chan et al., Nat. Prod. Rep., 2009, 1, 90; Wilson and Moore, Nat. Prod. Rep., 2012, 29, 72).

Chemoenzymatic Synthesis of Acyl Coenzyme A Substrates Enables in Situ Labeling of Small Molecules and Proteins.

A chemoenzymatic approach to generate fully functional acyl coenzyme A molecules that are then used as substrates to drive in situ acyl transfer reactions is described. Mass spectrometry based assays to verify the identity of acyl coenzyme A enzymatic products are also illustrated. The approach is responsive to a diverse array of carboxylic acids that can be elaborated to their corresponding coenzyme A thioesters, with potential applications in wide-ranging chemical biology studies that utilize acyl coenzyme A substrates.

Environmental and endocrine correlates of tactic switching by nonterritorial male tree lizards (Urosaurus ornatus).

Animals often exhibit individual variation in their behavioral responses to the same stimuli in the biotic or abiotic environment. To elucidate the endocrine mechanisms mediating such behavioral variation, we have been studying a species of lizard with two distinct male phenotypes. Here we document behavioral variation across years in one of the two male phenotypes of the tree lizard, Urosaurus ornatus, and present hormone data that support an endocrine mechanism underlying this behavioral variation. Nonterritorial male tree lizards appear to be nomadic rovers in some years and sedentary satellites in others, whereas territorial males are always territorial. This behavioral variation by nonterritorial males was correlated with environmental conditions. In environmentally harsher years (as assessed by rainfall), nonterritorial males appear to behave as nomads, whereas in more benign years they are more site-faithful. A between-year comparison of levels of corticosterone and testosterone for the two male phenotypes supports a model for how hormones underlie the males' reproductive tactics, particularly the nonterritorial males' behavioral plasticity. In an environmentally harsher (drier) year, both types of males had higher corticosterone levels than in a milder (wetter) year, but only nonterritorial males had lower testosterone in the relatively harsher year. We propose that disruptive selection for individual variation in hormonal responses to environmental cues may be a common mechanism underlying the evolution of alternative male reproductive tactics in this and other species.