Mesozoic cupules and the origin of the angiosperm second integument.

The second integument of the angiosperm ovule is unique among seed plants, with developmental genetics that are distinct from those of the inner integument1. Understanding how the second integument should be compared to structures in other seed plants is therefore crucial to resolving the long-standing question of the origin of angiosperms2-6. Attention has focused on several extinct plants with recurved cupules that are reminiscent of the anatropous organization of the basic bitegmic ovules of angiosperms1-6, but interpretations have been hampered by inadequate information on the relevant fossils. Here we describe abundant exceptionally well-preserved recurved cupules from a newly discovered silicified peat dating to the Early Cretaceous epoch (around 125.6 million years ago) in Inner Mongolia, China. The new material, combined with re-examination of potentially related fossils, indicates that the recurved cupules of several groups of Mesozoic plants are all fundamentally comparable, and that their structure is consistent with the recurved form and development of the second integument in the bitegmic anatropous ovules of angiosperms. Recognition of these angiosperm relatives (angiophytes) provides a partial answer to the question of angiosperm origins, will help to focus future work on seed plant phylogenetics and has important implications for ideas on the origin of the angiosperm carpel.

Use of accelerometers in determining risk of falls in individuals post-stroke: A systematic review.

OBJECTIVE: The aim of this systematic review was to determine if the diagnostic capabilities of wearable accelerometers enhanced, provided earlier detection, or improved fall risk assessment when evaluating individuals with chronic stroke. DATA SOURCES: CINAHL and PubMed databases were searched for articles from 2015 to 2023 utilizing key terms. REVIEW METHODS: A team of researchers reviewed articles for bias via the Quality in Prognostic Studies tool, and further analyzed the data to answer the research question. RESULTS: Four studies were included in the systematic review. When utilizing an accelerometer, the vertical axis was most predictive of falls, followed by the medio-lateral axis and the anterior-posterior axis. L2-3 was the most common accelerometer placement for fall risk assessment, however no uniformity existed in the literature on placement, number of accelerometers, or type. It was determined that gait symmetry, the Timed Up and Go, Berg Balance Scale, and Longitudinal Aging Study Amsterdam best predicted falls risk. CONCLUSION: Based on limited available evidence, clinicians should continue to perform a comprehensive examination and evaluation for fall risk, that includes the use of a combination of evidence-based outcome measures and gait characteristics to develop an individualized plan of care for individuals post-stroke. However, further research is necessary to determine the added value of accelerometers as well as type, applicability of data, and placement.

A permineralized Early Cretaceous lycopsid from China and the evolution of crown clubmosses.

Lycopodiaceae are one of three surviving families of lycopsids, a lineage of vascular plants with a fossil history dating to at least the Early Devonian or perhaps the Late Silurian (c. 415 Ma). Many fossils have been linked to crown Lycopodiaceae, but the lack of well-preserved material has hindered definitive recognition of this group in the paleobotanical record. New, exceptionally well-preserved permineralized lycopsid fossils from the Early Cretaceous (125.6 ± 1.0 Ma) of Inner Mongolia, China, were examined in detail using acetate peel and micro-computed tomography techniques. The anatomy of extant Lycopodiaceae was analyzed for comparison using fluorescence microscopy. Phylogenetic relationships of the new fossil to extant Lycopodiaceae were evaluated using parsimony and maximum likelihood analyses. Lycopodicaulis oellgaardii gen. et sp. nov. provides the earliest unequivocal and best-documented evidence of crown Lycopodiaceae and Lycopodioideae, based on anatomically-preserved fossil material. Recognition of Lycopodicaulis in Asia during the Early Cretaceous indicates the presence of crown Lycopodiaceae at this time, and striking similarities of stem anatomy with extant species provide a framework for the understanding of the interaction of branching and vascular anatomy in crown-group lycopsids.

The 'Tully monster' is a vertebrate.

Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica', particularly the 'weird wonders' of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.

Transcutaneous Functional Electrical Stimulation Controlled by a System of Sensors for the Lower Limbs: A Systematic Review.

In the field of transcutaneous functional electrical stimulation (FES), open-loop and closed-loop control strategies have been developed to restore functions of the lower limbs: walking, standing up, maintaining posture, and cycling. These strategies require sensors that provide feedback information on muscle activity or biomechanics of movement. Since muscle response induced by transcutaneous FES is nonlinear, time-varying, and dependent on muscle fatigue evolution, the choice of sensor type and control strategy becomes critical. The main objective of this review is to provide state-of-the-art, emerging, current, and previous solutions in terms of control strategies. Focus is given on transcutaneous FES systems for the lower limbs. Using Compendex and Inspec databases, a total of 135 review and conference articles were included in this review. Recent studies mainly use inertial sensors, although the use of electromyograms for lower limbs has become more frequent. Currently, several researchers are opting for nonlinear controllers to overcome the nonlinear and time-varying effects of FES. More development is needed in the field of systems using inertial sensors for nonlinear control. Further studies are needed to validate nonlinear control systems in patients with neuromuscular disorders.

Update to U.S. Selected Practice Recommendations for Contraceptive Use: Self-Administration of Subcutaneous Depot Medroxyprogesterone Acetate.

U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR), adapted by CDC from global guidance developed by the World Health Organization (WHO), provides evidence-based guidance on contraceptive use for U.S. health care providers (1). During January-February, 2021, CDC evaluated the 2019 WHO recommendation on self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) (2). CDC adopted the WHO recommendation on the basis of moderate-certainty evidence that self-administered DMPA-SC is safe and effective, and has higher continuation rates compared with provider-administered DMPA. The new U.S. SPR recommendation states that self-administered DMPA-SC should be made available as an additional approach to deliver injectable contraception. Provider-administered DMPA should remain available. Self-administered DMPA-SC is a user-controlled method that has the potential to improve contraceptive access and increase reproductive autonomy. Self-administered DMPA-SC should be offered in a noncoercive manner through a shared decision-making process between patients and their health care providers, with a focus on patient preferences and equitable access to the full range of contraceptive methods.

Mission Accomplished: The ACVP/STP Coalition for Veterinary Pathology Fellows Completes Its Objectives, but Its Legacy and Spirit Live On.

After 15 years of existence, the ACVP/STP Coalition for Veterinary Pathology Fellows will dissolve, primarily due to lack of renewed financial sponsorship. While in operation, the Coalition organized 32 new training position for veterinary pathologists, supported by $7.4 M from sponsors, including pharmaceutical and biotechnology companies, contract research organizations, private individuals and allied veterinary pathology support groups. All residual funds will be donated to ACVP and STP with the understanding that the two organizations will use these funds to enhance training by collaborating on outreach efforts, thus maintaining the legacy and spirit of the Coalition.

Iron and Sulfur Precursors Affect Crystalline Structure, Speciation, and Reactivity of Sulfidized Nanoscale Zerovalent Iron.

The reactivity of sulfidized nanoscale zerovalent iron (SNZVI) is affected by the amount and species of sulfur in the materials. Here, we assess the impact of the Fe (Fe2+ and Fe3+) and S (S2O42-, S2-, and S62-) precursors used to synthesize both NZVI and SNZVI on the resulting physicochemical properties and reactivity and selectivity with water and trichloroethene (TCE). X-ray diffraction indicated that the Fe precursors altered the crystalline structure of both NZVI and SNZVI. The materials made from the Fe3+ precursor had an expanded lattice in the Fe0 body-centered-cubic (BCC) structure and lower electron-transfer resistance, providing higher reactivity with water (∼2-3 fold) and TCE (∼5-13 fold) than those made from an Fe2+ precursor. The choice of the S precursor controlled the S speciation in the SNZVI particles, as indicated by X-ray absorption spectroscopy. Iron disulfide (FeS2) was the main S species of SNZVI made from S2O42-, whereas iron sulfide (FeS) was the main S species of SNZVI made from S2-/S62-. The former SNZVI was more hydrophobic, reactive with, and selective for TCE compared to the latter SNZVI. These results suggest that the Fe and S precursors can be used to select the conditions of the synthesis process and provide selected physicochemical properties (e.g., S speciation, hydrophobicity, and crystalline structure), reactivity, and selectivity of the SNZVI materials.

Mission Accomplished: The ACVP/STP Coalition for Veterinary Pathology Fellows Completes Its Objectives, but Its Legacy and Spirit Live On.

After 15 years of existence, the ACVP/STP Coalition for Veterinary Pathology Fellows will dissolve, primarily due to lack of renewed financial sponsorship. While in operation, the Coalition organized 32 new training position for veterinary pathologists, supported by $7.4 M from sponsors, including pharmaceutical and biotechnology companies, contract research organizations, private individuals and allied veterinary pathology support groups. All residual funds will be donated to ACVP and STP with the understanding that the two organizations will use these funds to enhance training by collaborating on outreach efforts, thus maintaining the legacy and spirit of the Coalition.

Harnessing health plan enrollee data to boost membership in patient-powered research networks.

BACKGROUND: Patient-powered research networks (PPRNs) have been employing and exploring different methods to engage patients in research activities specific to their conditions. One way to intensify patient engagement is to partner with payer stakeholders. The objective of this study was to evaluate the effectiveness of two common payer-initiated outreach methods (postal mail versus email) for inviting prospective candidates to participate in their initiatives. METHODS: This descriptive study linked members of a nationally-representative private insurance network to four disease-specific PPRN registries. Eligible members meeting diagnostic criteria who were not registered in any of the four PPRNs by 02/28/2018 were identified, and randomly assigned to either the mail or email group. They were contacted in two outreach efforts: first on 04/23/2018, and one follow-up on 05/23/2018. New registration rates by outreach method as of 8/31/2018 were determined by relinking. We compared registrants and non-registrants using bivariate analysis. RESULTS: A total of 14,571 patients were assigned to the mail group, and 14,574 to the email group. Invitations were successfully delivered to 13,834 (94.9%) mail group and 10,205 (70.0%) email group members. A small but significantly larger proportion of mail group members, (n = 78; 0.54, 95% Confidence Interval [CI] {0.42-0.67%}) registered in PPRNs relative to the email group (n = 24; 0.16, 95% CI {0.11-0.25%}), p < 0.001. Members who registered had more comorbidities, were more likely to be female, and had marginally greater medical utilization, especially emergency room visits, relative to non-registrants (52.0% vs. 42.5%, p = 0.05). CONCLUSION: A health plan outreach to invite members to participate in PPRNs was modestly effective. Regular mail outperformed less costly email. Providing more value-add to participants may be a possible way to increase recruitment success.

The function of the ophiuroid nerve ring: how a decentralized nervous system controls coordinated locomotion.

Echinoderms lack a centralized nervous control system, yet each extant echinoderm class has evolved unique and effective strategies for locomotion. Brittle stars (Ophiuroidea) stride swiftly over the seafloor by coordinating motions of their five muscular arms. Their arms consist of many repeating segments, requiring them to use a complex control system to coordinate motions among segments and between arms. We conducted in vivo experiments with brittle stars to analyze the functional role of the nerve ring, which connects the nerves in each arm. These experiments were designed to determine how the ophiuroid nervous system performs complex decision making and locomotory actions under decentralized control. Our results show that brittle star arms must be connected by the nerve ring for coordinated locomotion, but information can travel bidirectionally around the nerve ring so that it circumvents the severance. Evidence presented indicates that ophiuroids rely on adjacent nerve ring connections for sustained periodic movements. The number of arms connected via the nerve ring is correlated positively with the likelihood that the animal will show coordinated locomotion, indicating that integrated nerve ring tissue is critical for control. The results of the experiments should provide a basis for the advancement of complex artificial decentralized systems.

Integrating morphology and in vivo skeletal mobility with digital models to infer function in brittle star arms.

Brittle stars (Phylum Echinodermata, Class Ophiuroidea) have evolved rapid locomotion employing muscle and skeletal elements within their (usually) five arms to apply forces in a manner analogous to that of vertebrates. Inferring the inner workings of the arm has been difficult as the skeleton is internal and many of the ossicles are sub-millimeter in size. Advances in 3D visualization and technology have made the study of movement in ophiuroids possible. We developed six virtual 3D skeletal models to demonstrate the potential range of motion of the main arm ossicles, known as vertebrae, and six virtual 3D skeletal models of non-vertebral ossicles. These models revealed the joint center and relative position of the arm ossicles during near-maximal range of motion. The models also provide a platform for the comparative evaluation of functional capabilities between disparate ophiuroid arm morphologies. We made observations on specimens of Ophioderma brevispina and Ophiothrix angulata. As these two taxa exemplify two major morphological categories of ophiuroid vertebrae, they provide a basis for an initial assessment of the functional consequences of these disparate vertebral morphologies. These models suggest potential differences in the structure of the intervertebral articulations in these two species, implying disparities in arm flexion mechanics. We also evaluated the differences in the range of motion between segments in the proximal and distal halves of the arm length in a specimen of O. brevispina, and found that the morphology of vertebrae in the distal portion of the arm allows for higher mobility than in the proximal portion. Our models of non-vertebral ossicles show that they rotate further in the direction of movement than the vertebrae themselves in order to accommodate arm flexion. These findings raise doubts over previous hypotheses regarding the functional consequences of ophiuroid arm disparity. Our study demonstrates the value of integrating experimental data and visualization of articulated structures when making functional interpretations instead of relying on observations of vertebral or segmental morphology alone. This methodological framework can be applied to other ophiuroid taxa to enable comparative functional analyses. It will also facilitate biomechanical analyses of other invertebrate groups to illuminate how appendage or locomotor function evolved.

Effects of continuous bisphenol A exposure from early gestation on 90 day old rat testes function and sperm molecular profiles: A CLARITY-BPA consortium study.

Bisphenol A (BPA) is a ubiquitous industrial chemical that has been identified as an endocrine disrupting compound (EDC). There is growing concern that early life exposures to EDCs, such as BPA, can adversely affect the male reproductive tract and function. This study was conducted as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) to further delineate the toxicities associated with continuous exposure to BPA from early gestation, and to comprehensively examine the elicited effects on testes and sperm. NCTR Sprague Dawley rat dams were gavaged from gestational day (GD) 6 until parturition, and their pups were directly gavaged daily from postnatal day (PND) 1 to 90 with BPA (2.5, 25, 250, 2500, 25,000, 250,000 µg/kg/d) or vehicle control. At PND 90, the testes and sperm were collected for evaluation. The testes were histologically evaluated for altered germ cell apoptosis, sperm production, and altered spermiation. RNA and DNA isolated from sperm were assessed for elicited changes in global mRNA transcript abundance and altered DNA methylation. Effects of BPA were observed in changes in body, testis and epididymis weights only at the highest administered dose of BPA of 250,000 µg/kg/d. Genome-wide transcriptomic and epigenomic analyses failed to detect robust alterations in sperm mRNA and DNA methylation levels. These data indicate that prolonged exposure starting in utero to BPA over a wide range of levels has little, if any, impact on the testes and sperm molecular profiles of 90 day old rats as assessed by the histopathologic, morphometric, and molecular endpoints evaluated.

Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Angiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1-3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer. METHODS: In this randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we randomly assigned patients aged 18 years or older with relapsed platinum-sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain, and the UK. Participants received up to six cycles of platinum-based chemotherapy (once every 3 weeks) then entered a maintenance phase. Participants were randomly allocated (2:3:3), with five stratification factors and in alternating blocks, to receive placebo alongside chemotherapy and then placebo only maintenance (arm A; reference), cediranib 20 mg once-daily alongside chemotherapy then placebo only maintenance (arm B; concurrent), or cediranib 20 mg once-daily alongside chemotherapy then cediranib 20 mg once-daily maintenance (arm C; maintenance). Patients continued treatment to progression or excessive toxic effects. The primary efficacy endpoint was progression-free survival between arms A and C. Efficacy analysis was by intention to treat. Safety was assessed in all patients who received the allocated study drug. This trial is registered with ClinicalTrials.gov, number NCT00532194; the ISRCTN registry, number ISRCTN68510403; and ANZ Clinical Trials Registry, number ACTRN1261000016003. FINDINGS: We randomly assigned 486 [corrected] women between Nov 13, 2007, and Dec 23, 2011; results presented are for 456 patients randomly assigned subsequent to the 30mg safety phase. During a median of 19·5 months (IQR 14-26) follow-up, 113 (96%) of 118 women assigned to arm A and 141 (86%) of 164 assigned to arm C had disease progression. Median progression-free survival was 11·0 months (95% CI 10·4-11·7) in arm C and 8·7 months (7·7-9·4) in arm A (hazard ratio 0·56, 0·44-0·72, p<0·0001). 156 (90%) of 174 patients in arm B had disease progression, and median progression-free survival was 9·9 months (95% CI 9·4-10·5). Diarrhoea, neutropenia, hypertension, and voice changes were significantly more common, during chemotherapy with cediranib, and diarrhoea, hypothyroidism and voice changes were more common during maintenance. Poor compliance with cediranib was noted during maintenance treatment with toxic effects being the most common cause for discontinuation. INTERPRETATION: Cediranib, when given orally with chemotherapy and continued as maintenance, yielded a meaningful improvement [corrected] in progression-free survival in women with recurrent platinum-sensitive ovarian cancer, albeit with added toxic effects. The positive results in ICON6 could provide women with a new therapeutic option for recurrent ovarian cancer. Assessment of the secondary endpoint of overall survival will need longer follow-up. FUNDING: Medical Research Council, Cancer Research UK, Canadian Cancer Society Research Institute, Cancer Australia, National Gynecological Cancer Centre, and AstraZeneca.

Water vascular system architecture in an Ordovician ophiuroid.

Understanding the water vascular system (WVS) in early fossil echinoderms is critical to elucidating the evolution of this system in extant forms. Here we present the first report of the internal morphology of the water vascular system of a stem ophiuroid. The radial canals are internal to the arm, but protected dorsally by a plate separate to the ambulacrals. The canals zig-zag with no evidence of constrictions, corresponding to sphincters, which control pairs of tube feet in extant ophiuroids. The morphology suggests that the unpaired tube feet must have operated individually, and relied on the elasticity of the radial canals, lateral valves and tube foot musculature alone for extension and retraction. This arrangement differs radically from that in extant ophiuroids, revealing a previously unknown Palaeozoic configuration.

A qualitative investigation of decision making during help-seeking for adult hearing loss.

OBJECTIVE: The Any Qualified Provider framework in the National Health Service has changed the way adult audiology services are offered in England. Under the new rules, patients are being offered a choice in geographical location and audiology provider. This study aimed to explore how choices in treatment are presented and to identify what information patients need when they are seeking help with hearing loss. DESIGN: This study adopted qualitative methods of ethnographic observations and focus group interviews to identify information needed prior to, and during, help-seeking. Observational data and focus group data were analysed using the constant comparison method of grounded theory. STUDY SAMPLE: Participants were recruited from a community Health and Social Care Trust in the west of England. This service incorporates both an Audiology and a Hearing Therapy service. Twenty seven participants were involved in focus groups or interviews. RESULTS: Participants receive little information beyond the detail of hearing aids. Participants report little information that was not directly related to uptake of hearing aids. CONCLUSIONS: Participant preferences were not explored and limited information resulted in decisions that were clinician-led. The gaps in information reflect previous data on clinician communication and highlight the need for consistent information on a range of interventions to manage hearing loss.

Concise review: MicroRNA function in multipotent mesenchymal stromal cells.

Multipotent mesenchymal stromal cells (MSCs) are ideal candidates for different cellular therapies due to their simple isolation, extensive expansion potential, and low immunogenicity. For various therapeutic approaches, such as bone and cartilage repair, MSCs are expected to contribute by direct differentiation to replace the damaged tissue, while many other applications rely on the secretion of paracrine factors which modulate the immune response and promote angiogenesis. MicroRNAs (miRNAs), which target messenger RNA for cleavage or translational repression, have recently been shown to play critical functions in MSC to regulate differentiation, paracrine activity, and other cellular properties such as proliferation, survival, and migration. The global miRNA expression profile of MSC varies according to the tissue of origin, species, and detection methodology, while also certain miRNAs are consistently found in all types of MSC. The function in MSC of more than 60 different miRNAs has been recently described, which is the subject of this review. A special emphasis is given to miRNAs that have demonstrated a function in MSC in vivo. We also present in detail miRNAs with overlapping effects (i.e., common target genes) and discuss future directions to deepen our understanding of miRNA biology in MSC. These recent discoveries have opened the possibility of modulating miRNAs in MSC, in order to enhance their proregenerative, therapeutic potential.

Intussusceptive-like angiogenesis in human fetal lung xenografts: Link with bronchopulmonary dysplasia-associated microvascular dysangiogenesis?

BACKGROUND: Human fetal lung xenografts display an unusual pattern of non-sprouting, plexus-forming angiogenesis that is reminiscent of the dysmorphic angioarchitecture described in bronchopulmonary dysplasia (BPD). The aim of this study was to determine the clinicopathological correlates, growth characteristics and molecular regulation of this aberrant form of graft angiogenesis. METHODS: Fetal lung xenografts, derived from 12 previable fetuses (15 to 22 weeks' gestation) and engrafted in the renal subcapsular space of SCID-beige mice, were analyzed 4 weeks posttransplantation for morphology, vascularization, proliferative activity and gene expression. RESULTS: Focal plexus-forming angiogenesis (PFA) was observed in 60/230 (26%) of xenografts. PFA was characterized by a complex network of tortuous nonsprouting vascular structures with low endothelial proliferative activity, suggestive of intussusceptive-type angiogenesis. There was no correlation between the occurrence of PFA and gestational age or time interval between delivery and engraftment. PFA was preferentially localized in the relatively hypoxic central subcapsular area. Microarray analysis suggested altered expression of 15 genes in graft regions with PFA, of which 7 are known angiogenic/lymphangiogenic regulators and 5 are known hypoxia-inducible genes. qRT-PCR analysis confirmed significant upregulation of SULF2, IGF2, and HMOX1 in graft regions with PFA. CONCLUSION: These observations in human fetal lungs ex vivo suggest that postcanalicular lungs can switch from sprouting angiogenesis to an aberrant intussusceptive-type of angiogenesis that is highly reminiscent of BPD-associated dysangiogenesis. While circumstantial evidence suggests hypoxia may be implicated, the exact triggering mechanisms, molecular regulation and clinical implications of this angiogenic switch in preterm lungs in vivo remain to be determined.

A human fetal prostate xenograft model of developmental estrogenization.

Prostate cancer is a common disease in older men. Rodent models have demonstrated that an early and later-life exposure to estrogen can lead to cancerous lesions and implicated hormonal dysregulation as an avenue for developing future prostate neoplasia. This study utilizes a human fetal prostate xenograft model to study the role of estrogen in the progression of human disease. Histopathological lesions were assessed in 7-, 30-, 90-, 200-, and 400-day human prostate xenografts. Gene expression for cell cycle, tumor suppressors, and apoptosis-related genes (ie, CDKN1A, CASP9, ESR2, PTEN, and TP53) was performed for 200-day estrogen-treated xenografts. Glandular hyperplasia was observed in xenografts given both an initial and secondary exposure to estradiol in both 200- and 400-day xenografts. Persistent estrogenic effects were verified using immunohistochemical markers for cytokeratin 10, p63, and estrogen receptor α. This model provides data on the histopathological state of the human prostate following estrogenic treatment, which can be utilized in understanding the complicated pathology associated with prostatic disease and early and later-life estrogenic exposures.