Challenges in recognizing and discussing changes in a resident's condition in the palliative phase: focus group discussions with nursing staff working in nursing homes about their experiences.

BACKGROUND: Most nursing home residents have complex care needs, require palliative care and eventually die in these facilities. Timely recognition of changes in a resident's condition is crucial for providing appropriate care. Observations by nursing staff play a significant role in identifying and interpreting these changes. METHODS: Focus group discussions were conducted with nursing staff from ten nursing homes in the Netherlands to explore their experiences and challenges in recognizing and discussing changes in a resident's condition. These discussions were analysed following the principles of thematic analysis. RESULTS: The analysis of the challenges nursing staff face in identifying and interpreting changes in a resident's condition, resulted in three themes. First, that recognizing changes is considered complex, because it requires specialized knowledge and skills that is generally not part of their education and must partly be learned in practice. This also depends on how familiar the nursing staff is with the resident. Furthermore, different people observe residents through different lenses, depending on their relation and experiences with residents. This could lead to disagreements about the resident's condition. Lastly, organizational structures such as the resources available to document and discuss a resident's condition and the hierarchy between nursing home professionals often hindered discussions and sharing observations. CONCLUSION: Nursing staff's experiences highlight the complexity of recognizing and discussing changes in nursing home residents' conditions. While supporting the observational skills of nursing staff is important, it is not enough to improve the quality of care for nursing home residents with palliative care needs. As nursing staff experiences challenges at different, interrelated levels, improving the process of recognizing and discussing changes in nursing home residents requires an integrated approach in which the organization strengthens the position of nursing staff. It is important that their observations become a valued and integrated and part of nursing home care.

Meaning-making following loss among bereaved spouses during the COVID-19 pandemic (the CO-LIVE study).

This study investigates how individuals construe, understand, and make sense of experiences during the first wave of the COVID-19 pandemic. Seventeen semi-structured interviews were conducted with bereaved spouses focusing on meaning attribution to the death of their partner. The interviewees were lacking adequate information, personalized care, and physical or emotional proximity; these challenges complicated their experience of a meaningful death of their partner. Concomitantly, many interviewees appreciated the exchange of experiences with others and any last moments together with their partner. Bereaved spouses actively sought valuable moments, during and after bereavement, that contributed to the perceived meaning.

Reliability of Running Economy Measurements: Influence of Shoe Familiarisation.

The purpose was to investigate differences in reliability of running economy measurements between familiar and unfamiliar shoes. Thirty-seven runners were included who all ran in familiar and unfamiliar running shoes while running economy was measured at steady state using a treadmill. Each participant was tested on two different visits (three sessions in total), with two trials in each of the three shoe conditions completed at each visit. Coefficient of variation, standard deviation of differences, and limits of agreement of running economy were used to quantify the repeatability (within-visit variation) and reproducibility (between-visit variation). The coefficient of variation showed a marginal difference in reproducibility across shoe conditions, whereas no differences were seen in coefficient of variation, standard deviation of the differences, or limits of agreement for repeatability across shoes. All three shoe conditions showed greater repeatability than reproducibility for running economy, and enhanced repeatability at visit 3 compared to visit 2. Our results indicate that familiarisation to shoes might not be needed for reliable measurements of running economy. Based on our results, when evaluating benefits in running shoes we suggest that running economy be assessed within the same day. Further, our data suggest a beneficial effect of using multiple familiarisation sessions if small differences between shoe conditions are expected.

The correlation between posterior tibial slope and dynamic anterior tibial translation and dynamic range of tibial rotation.

PURPOSE: The amount of passive anterior tibial translation (ATT) is known to be correlated to the amount of posterior tibial slope (PTS) in both anterior cruciate ligament-deficient and reconstructed knees. Slope-altering osteotomies are advised when graft failure after anterior cruciate ligament (ACL) reconstruction occurs in the presence of high PTS. This recommendation is based on studies neglecting the influence of muscle activation. On the other hand, if dynamic range of tibial rotation (rTR) is related to the amount of PTS, a "simple" anterior closing-wedge osteotomy might not be sufficient to control for tibial rotation. The purpose of this study was to evaluate the correlation between the amount of PTS and dynamic ATT and tibial rotation during high demanding activities, both before and after ACL reconstruction. We hypothesized that both ATT and rTR are strongly correlated to the amount of PTS. METHODS: Ten subjects were studied both within three months after ACL injury and one year after ACL reconstruction. Dynamic ATT and dynamic rTR were measured using a motion-capture system during level walking, during a single-leg hop for distance and during a side jump. Both medial and lateral PTS were measured on MRI. A difference between medial and lateral PTS was calculated and referred to as Δ PTS. Spearman's correlation coefficients were calculated for the correlation between medial PTS, lateral PTS and Δ PTS and ATT and between medial PTS, lateral PTS and Δ PTS and rTR. RESULTS: Little (if any) to weak correlations were found between medial, lateral and Δ PTS and dynamic ATT both before and after ACL reconstruction. On the other hand, a moderate-to-strong correlation was found between medial PTS, lateral PTS and Δ PTS and dynamic rTR one year after ACL reconstruction. CONCLUSION: During high-demand tasks, dynamic ATT is not correlated to PTS. A compensation mechanism may be responsible for the difference between passive and dynamic ATT in terms of the correlation to PTS. A moderate-to-strong correlation between amount of PTS and rTR indicates that such a compensation mechanism may fall short in correcting for rTR. These findings warrant prudence in the use of a pure anterior closing wedge osteotomy in ACL reconstruction. TRIAL REGISTRATION: Netherlands Trial Register, Trial 7686 . Registered 16 April 2016-Retrospectively registered. LEVEL OF EVIDENCE: Level 2, prospective cohort study.

Intra-and interobserver reliability of determining the femoral footprint of the torn anterior cruciate ligament on MRI scans.

BACKGROUND: Re-injury rates following reconstruction of the anterior cruciate ligament (ACL) are significant; in more than 20% of patients a rupture of the graft occurs. One of the main reasons for graft failure is malposition of the femoral tunnel. The femoral origin of the torn ACL can be hard to visualize during arthroscopy, plus many individual variation in femoral origin anatomy exists, which may lead to this malpositioning. To develop a patient specific guide that may resolve this problem, a preoperative MRI is needed to identify the patient specific femoral origin of the ACL. The issue here is that there may be a difference in the reliability of identification of the femoral footprint of the ACL on MRI between different observers with different backgrounds and level of experience. The purpose of this study was to determine the intra- and interobserver reliability of identifying the femoral footprint of the torn ACL on MRI and to compare this between orthopedic surgeons, residents in orthopedic surgery and MSK radiologists. METHODS: MR images of the knee joint were collected retrospectively from 20 subjects with a confirmed rupture of the ACL. The 2D (coronal, sagittal, transversal) proton-density (PD) images were selected for the segmentation procedure to create 3D models of the femurs. The center of the femoral footprint of the ACL on 20 MRI scans, with visual feedback on 3D models (as reference) was determined twice by eight observers. The intra- and interobserver reliability of determining the center of the femoral footprint on MRI was evaluated. Intraclass correlation coefficients (ICCs) were calculated for the X, Y and Z coordinates separately and for a 3D coordinate. RESULTS: The mean 3D distance between the first and second assessment (intraobserver reliability) was 3.82 mm. The mean 3D distance between observers (interobserver reliability) was 8.67 mm. ICCs were excellent (> 0.95), except for those between the assessments of the two MSK radiologists of the Y and Z coordinates (0.890 and 0.800 respectively). Orthopedic surgeons outscored the residents and radiologists in terms of intra- and interobserver agreement. CONCLUSION: Excellent intraobserver reliability was demonstrated (< 4 mm). However the results of the interobserver reliability manifested remarkably less agreement between observers (> 8 mm). An orthopedic background seems to increase both intra- and interobserver reliability. Preoperative planning of the femoral tunnel position in ACL reconstruction remains a surgical decision. Experienced orthopedic surgeons should be consulted when planning for patient specific instrumentation in ACL reconstruction.

Evaluation of predicted patellofemoral joint kinematics with a moving-axis joint model.

The main objectives of this study were to expand the moving-axis joint model concept to the patellofemoral joint and evaluate the patellar motion against experimental patellofemoral kinematics. The experimental data was obtained through 2D-to-3D bone reconstruction of EOS images and segmented MRI data utilizing an iterative closest point optimization technique. Six knee model variations were developed using the AnyBody Modeling System and subject-specific bone geometries. These models consisted of various combinations of tibiofemoral (hinge, moving-axis, and interpolated) and patellofemoral (hinge and moving-axis) joint types. The newly introduced interpolated tibiofemoral joint is calibrated from the five EOS quasi-static lunge positions. The patellofemoral axis of the hinge model was defined by performing surface fits to the patellofemoral contact area; and the moving-axis model was defined based upon the position of the patellofemoral joint at 0° and 90° tibiofemoral-flexion. In between these angles, the patellofemoral axis moved linearly as a function of tibiofemoral-flexion, while outside these angles, the axis remained fixed. When using a moving-axis tibiofemoral joint, a hinge patellofemoral joint offers (-5.12 ± 1.23 mm, 5.81 ± 0.97 mm, 14.98 ± 2.30°, -4.35 ± 1.95°) mean differences (compared to EOS) while a moving-axis patellofemoral model provides (-2.69 ± 1.04 mm, 1.13 ± 0.80 mm, 12.63 ± 2.03°, 1.74 ± 1.46°) in terms of lateral-shift, superior translation, patellofemoral-flexion, and patellar-rotation, respectively. Furthermore, the model predictive capabilities increased as a direct result of adding more calibrated positions to the tibiofemoral model (hinge-1, moving-axis-2, and interpolated-5). Overall, a novel subject-specific moving-axis patellofemoral model has been established; that produces realistic patellar motion and is computationally fast enough for clinical applications.

Gait alteration strategies for knee osteoarthritis: a comparison of joint loading via generic and patient-specific musculoskeletal model scaling techniques.

Gait modifications and laterally wedged insoles are non-invasive approaches used to treat medial compartment knee osteoarthritis. However, the outcome of these alterations is still a controversial topic. This study investigates how gait alteration techniques may have a unique effect on individual patients; and furthermore, the way we scale our musculoskeletal models to estimate the medial joint contact force may influence knee loading conditions. Five patients with clinical evidence of medial knee osteoarthritis were asked to walk at a normal walking speed over force plates and simultaneously 3D motion was captured during seven conditions (0°-, 5°-, 10°-insoles, shod, toe-in, toe-out, and wide stance). We developed patient-specific musculoskeletal models, using segmentations from magnetic resonance imaging to morph a generic model to patient-specific bone geometries and applied this morphing to estimate muscle insertion sites. Additionally, models were created of these patients using a simple linear scaling method. When examining the patients' medial compartment contact force (peak and impulse) during stance phase, a 'one-size-fits-all' gait alteration aimed to reduce medial knee loading did not exist. Moreover, the different scaling methods lead to differences in medial contact forces; highlighting the importance of further investigation of musculoskeletal modeling methods prior to use in the clinical setting.

Development and validation of a subject-specific moving-axis tibiofemoral joint model using MRI and EOS imaging during a quasi-static lunge.

The aims of this study were to introduce and validate a novel computationally-efficient subject-specific tibiofemoral joint model. Subjects performed a quasi-static lunge while micro-dose radiation bi-planar X-rays (EOS Imaging, Paris, France) were captured at roughly 0°, 20°, 45°, 60°, and 90° of tibiofemoral flexion. Joint translations and rotations were extracted from this experimental data through 2D-to-3D bone reconstructions, using an iterative closest point optimization technique, and employed during model calibration and validation. Subject-specific moving-axis and hinge models for comparisons were constructed in the AnyBody Modeling System (AMS) from Magnetic Resonance Imaging (MRI)-extracted anatomical surfaces and compared against the experimental data. The tibiofemoral axis of the hinge model was defined between the epicondyles while the moving-axis model was defined based on two tibiofemoral flexion angles (0° and 90°) and the articulation modeled such that the tibiofemoral joint axis moved linearly between these two positions as a function of the tibiofemoral flexion. Outside this range, the joint axis was assumed to remain stationary. Overall, the secondary joint kinematics (ML: medial-lateral, AP: anterior-posterior, SI: superior-inferior, IE: internal-external, AA: adduction-abduction) were better approximated by the moving-axis model with mean differences and standard errors of (ML: -1.98 ±â€¯0.37 mm, AP: 6.50 ±â€¯0.82 mm, SI: 0.05 ±â€¯0.20 mm, IE: 0.59 ±â€¯0.36°, AA: 1.90 ±â€¯0.79°) and higher coefficients of determination (R2) for each clinical measure. While the hinge model achieved mean differences and standard errors of (ML: -0.84 ±â€¯0.45 mm, AP: 10.11 ±â€¯0.88 mm, SI: 0.66 ±â€¯0.62 mm, IE: -3.17 ±â€¯0.86°, AA: 11.60 ±â€¯1.51°).

Workflow assessing the effect of gait alterations on stresses in the medial tibial cartilage - combined musculoskeletal modelling and finite element analysis.

Knee osteoarthritis (KOA) is most common in the medial tibial compartment. We present a novel method to study the effect of gait modifications and lateral wedge insoles (LWIs) on the stresses in the medial tibial cartilage by combining musculoskeletal (MS) modelling with finite element (FE) analysis. Subject's gait was recorded in a gait laboratory, walking normally, with 5° and 10° LWIs, toes inward ('Toe in'), and toes outward ('Toe out wide'). A full lower extremity MRI and a detailed knee MRI were taken. Bones and most soft tissues were segmented from images, and the generic bone architecture of the MS model was morphed into the segmented bones. The output forces from the MS model were then used as an input in the FE model of the subject's knee. During stance, LWIs failed to reduce medial peak pressures apart from Insole 10° during the second peak. Toe in reduced peak pressures by -11% during the first peak but increased them by 12% during the second. Toe out wide reduced peak pressures by -15% during the first and increased them by 7% during the second. The results show that the work flow can assess the effect of interventions on an individual level. In the future, this method can be applied to patients with KOA.

Development of a grinding-specific performance test set-up.

The aim of this study was to develop a performance test set-up for America's Cup grinders. The test set-up had to mimic the on-boat grinding activity and be capable of collecting data for analysis and evaluation of grinding performance. This study included a literature-based analysis of grinding demands and a test protocol developed to accommodate the necessary physiological loads. This study resulted in a test protocol consisting of 10 intervals of 20 revolutions each interspersed with active resting periods of 50 s. The 20 revolutions are a combination of both forward and backward grinding and an exponentially rising resistance. A custom-made grinding ergometer was developed with computer-controlled resistance and capable of collecting data during the test. The data collected can be used to find measures of grinding performance such as peak power, time to complete and the decline in repeated grinding performance.

Acquiring evidence-based medicine and research skills in the undergraduate medical curriculum: three different didactical formats compared.

Medical schools have recently witnessed a call for authentic research activities that equip students with the skills required for evidence-based medicine (EBM) and research. Because it is not always possible to make such activities available as a part of the curriculum, evaluating the effectiveness of the various choices of traditional and authentic EBM and research skills courses is essential. This study's purpose was to evaluate students' perceived EBM and research skill acquisition in three different courses in a Dutch medical school. Self-reported surveys were conducted among 163 Dutch medical undergraduates who participated in an undergraduate research project, a basic EBM skills elective, or a traditional lecture-based skills course. MANCOVA was employed to test for group differences in perceived skill acquisition. Students who finished their research project perceived themselves as more experienced in writing and information retrieval skills than students who participated in the lecture-based course or basic skills elective. Students in the lecture-based course identified themselves as being the most experienced in critical judgment. No group differences were found for overall gains. Authentic research activities may have benefits over traditional lecture-based courses in the undergraduate medical curriculum, especially in terms of equipping students with writing and information retrieval skills.

Functional characterisation of a SNP in the ABCC11 allele - effects on axillary skin metabolism, odour generation and associated behaviours.

BACKGROUND: A single nucleotide polymorphism (SNP), 538G→A, leading to a G180R substitution in the ABCC11 gene results in reduced concentrations of apocrine derived axillary odour precursors. OBJECTIVE: Determine the axillary odour levels in the SNP ABCC11 genotype variants and to investigate if other parameters associated with odour production are affected. METHODS: Axillary odour was assessed by subjective quantification and gas chromatography headspace analysis. Metabolite profiles, microbiome diversity and personal hygiene habits were also assessed. RESULTS: Axillary odour in the A/A homozygotes was significantly lower compared to the G/A and G/G genotypes. However, the perception-based measures still detected appreciable levels of axillary odour in the A/A subjects. Metabolomic analysis highlighted significant differences in axillary skin metabolites between A/A subjects compared to those carrying the G allele. These differences resulted in A/A subjects lacking specific volatile odourants in the axillary headspace, but all genotypes produced odoriferous short chain fatty acids. Microbiomic analysis revealed differences in the relative abundance of key bacterial genera associated with odour generation between the different genotypes. Deodorant usage indicated a high level of self awareness of axillary odour levels with A/A individuals less likely to adopt personal hygiene habits designed to eradicate/mask its presence. CONCLUSIONS: The SNP in the ABCC11 gene results in lower levels of axillary odour in the A/A homozygotes compared to those carrying the G allele, but A/A subjects still produce noticeable amounts of axillary odour. Differences in axillary skin metabolites, bacterial genera and personal hygiene behaviours also appear to be influenced by this SNP.

Comprehensive survey of developmental genes in the pea aphid, Acyrthosiphon pisum: frequent lineage-specific duplications and losses of developmental genes.

Aphids exhibit unique attributes, such as polyphenisms and specialized cells to house endosymbionts, that make them an interesting system for studies at the interface of ecology, evolution and development. Here we present a comprehensive characterization of the developmental genes in the pea aphid, Acyrthosiphon pisum, and compare our results to other sequenced insects. We investigated genes involved in fundamental developmental processes such as establishment of the body plan and organogenesis, focusing on transcription factors and components of signalling pathways. We found that most developmental genes were well conserved in the pea aphid, although many lineage-specific gene duplications and gene losses have occurred in several gene families. In particular, genetic components of transforming growth factor beta (TGFbeta) Wnt, JAK/STAT (Janus kinase/signal transducer and activator of transcription) and EGF (Epidermal Growth Factor) pathways appear to have been significantly modified in the pea aphid.

Moment dependency of the series elastic stiffness in the human plantar flexors measured in vivo.

The moment dependency of the series elastic stiffness (SES) in the human plantar flexors was investigated in vivo with the quick release method. At an ankle moment of 100 N m produced with either voluntary or electrical stimulation we found non-significantly different SES of 506+/-72 and 529+/-125 N m rad(-1), respectively. It has recently been proposed that the amount of series elastic tissue involved in plantar flexion changes with the moment level produced by the plantar flexors (Hof, J. Biomech 31 (1998) 793). However, our results indicate that the amount of series elastic tissue involved in plantar flexions remained constant with changing moment levels. We therefore propose that the series elastic component (SEC) in human plantar flexors act as one structure or rather one combination of anatomical structures which is engaged at all muscle activation levels, and that the mechanical properties (i.e. the stress-strain function) are determined by the combined tissue mechanical properties. Additionally, our results demonstrated that the SES in the human plantar flexors at moments levels up to about isometric maximum did not reach an asymptote where the stiffness is independent of moment, i.e. SEC of the plantar flexors is, during many daily activities, loaded for the greatest part in the non-linear part of the stress-strain function.

Developmental change in the steroid hormone signal for cell-autonomous, segment-specific programmed cell death of a motoneuron.

During metamorphosis of the hawkmoth, Manduca sexta, accessory planta retractor (APR) motoneurons undergo a segment-specific pattern of programmed cell death (PCD): e.g., APRs from abdominal segment six [APR(6)s] die at pupation in direct response to the prepupal rise in 20-hydroxyecdysone (20E), whereas APR(4)s survive through the pupal stage and die at eclosion (adult emergence). The hypothesis that the death of APR(4)s is triggered by the decline in 20E at eclosion was supported by findings that injection of 20E into developing pupae to delay the fall in 20E delayed APR(4) death. Furthermore, abdomen isolation to advance the fall in 20E caused precocious APR(4) death. In other experiments, APR(4)s were placed in primary cell culture 4 days before eclosion in medium containing 1 microg/ml 20E. A switch to hormone-free medium induced PCD in a significant proportion of APR(4)s, compared to APR(4)s that remained in 20E. Process fragmentation was a reliable early indicator of PCD. These results show that a decline in 20E triggers cell-autonomous PCD of APR(4)s, in contrast to the rise in 20E that triggers cell-autonomous PCD of APR(6)s. Thus, the PCD of homologous motoneurons in different body segments at different developmental times is triggered by different steroid hormone signals.

Dynamic viscoelastic behavior of lower extremity tendons during simulated running.

The aim of this project was to see whether the tendon would show creep during long-term dynamic loading (here referred to as dynamic creep). Pig tendons were loaded by a material-testing machine with a human Achilles tendon force profile (1.37 Hz, 3% strain, 1,600 cycles), which was obtained in an earlier in vivo experiment during running. All the pig tendons showed some dynamic creep during cyclic loading (between 0.23 +/- 0.15 and 0.42 +/- 0.21%, means +/- SD). The pig tendon data were used as an input of a model to predict dynamic creep in the human Achilles tendon during running of a marathon and to evaluate whether there might consequently be an influence on group Ia afferent-mediated length and velocity feedback from muscle spindles. The predicted dynamic creep in the Achilles tendon was considered to be too small to have a significant influence on the length and velocity feedback from soleus during running. In spite of the characteristic nonlinear viscoelastic behavior of tendons, our results demonstrate that these properties have a minor effect on the ability of tendons to act as predictable, stable, and elastic force transmitters during long-term cyclic loading.

Live bacterial delivery systems for development of mucosal vaccines.

By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed rational development of new and improved bacterial carriers and more effective gene expression systems. These advances have improved the performance and versatility of these delivery systems to induce mucosal immunity to recombinant antigens in animal models. Application of these (improved) technologies for development of human vaccines is still limited and awaits further exploration.

Profound differences in the transport of steroids by two mouse P-glycoproteins.

There are two mouse P-glycoproteins that convey multidrug resistance, mdr1 (mdr1b) and mdr3 (mdr1a), by serving as drug efflux transporters. These proteins each exhibit tissue-specific expression. There is relatively high expression of the mdr1 gene in the adrenals, the site of glucocorticoid and mineralocorticoid hormone synthesis. We previously demonstrated that mdr1 gene expression in murine thymoma cells correlated well with a decrease in their ability to accumulate the glucocorticoid dexamethasone and their increased resistance to glucocorticoid-induced apoptosis. Additional evidence is presented that supports the proposition that the mdr1 P-glycoprotein can transport glucocorticoids. Specifically, introduction and expression of the mouse mdr1 gene in the human HEK 293T cell line conveys a multidrug resistance phenotype that includes a reduced capacity to accumulate dexamethasone. Moreover, isolation of additional mdr1-expressing mouse lymphoid cells, without using steroids in the selection, confirms the linkage between multidrug resistance conveyed by the mdr1 P-glycoprotein and resistance to dexamethasone. In contrast, two newly isolated lymphoid lines, selectively expressing the mdr3 gene, were not found to have increased dexamethasone resistance or the capacity to accumulate significantly lower levels of hormone. The results support the concept that the mdr1 and mdr3 P-glycoproteins may serve alternative roles in the transport of endogenous substances such as steroids.

Relevance of aquatic biodegradation tests for predicting degradation of polymeric materials during biological solid waste treatment.

The aquatic biodegradability of cellulose and cellulose acetate with degrees of substitution (d.s.) in the range of 1.5 to 3.0, was compared with the mineralization under laboratory controlled composting conditions. In line with previous observations, it was found that cellulose acetates with d.s. < or = 2.5 were readily mineralized to CO2 in the controlled composting test. The degradation rate was clearly affected by the degree of substitution (d.s. 1.5 > d.s. 2.5 > d.s. 3.0). Surprisingly, however, biodegradation of cellulose acetate materials was not observed in the aquatic Strum test. Modifications of the pH and the inoculum source in an attempt to improve the activity of fungi and actinomycetes in the aquatic environment, did not increase CO2-evolution. It is concluded that the relevance of modified Strum tests is limited for predicting complete biodegradation of polymeric materials during biological waste processing. For evaluation of the compostability of polymeric products or packaging materials, more relevant laboratory controlled composting tests should be used.

Estrogen receptor-dependent sexual differentiation of dopaminergic neurons in the preoptic region of the mouse.

Although it has been known for some time that estrogen exerts a profound influence on brain development a definitive demonstration of the role of the classical estrogen receptor (ERalpha) in sexual differentiation has remained elusive. In the present study we used a sexually dimorphic population of dopaminergic neurons in the anteroventral periventricular nucleus of the hypothalamus (AVPV) to test the dependence of sexual differentiation on a functional ERalpha by comparing the number of tyrosine hydroxylase (TH)-immunoreactive neurons in the AVPV of wild-type (WT) mice with that of mice in which the ERalpha had been disrupted by homologous recombination (ERKOalpha). Only a few ERalpha-immunoreactive neurons were detected in the AVPV of ERKOalpha mice, and the number of TH-immunoreactive neurons was three times that of WT mice, suggesting that disruption of the ERalpha gene feminized the number of TH-immunoreactive neurons. In contrast, the AVPV contains the same number of TH-immunoreactive neurons in testicular feminized male mice as in WT males, indicating that sexual differentiation of this population of neurons is not dependent on an intact androgen receptor. The number of TH-immunoreactive neurons in the AVPV of female ERKOalpha mice remained higher than that of WT males, but TH staining appeared to be lower than that of WT females. Thus, the sexual differentiation of dopamine neurons in the AVPV appears to be receptor specific and dependent on the perinatal steroid environment.