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For birds breeding in the Arctic, nest success is affected by the timing of nest initiation, which is partially determined by local conditions such as snow cover. However, conditions during the non-breeding season can carry over to affect the timing of breeding. We used tracking and breeding data from 248 individuals of 8 species and subspecies of Arctic-breeding shorebirds to estimate how the timing of nest initiation is related to local conditions like snowmelt phenology versus prior conditions, measured by the timing and speed of migration. Using path analysis, our global model showed that local and prior conditions have similar effect sizes (Standardised Path Coefficients ± SE of 0.44 ± 0.07 and 0.43 ± 0.07 for snowmelt and arrival timing, respectively), suggesting that both influence the timing of breeding and therefore potentially reproductive output. However, the importance of each variable varied across species. Individuals that arrived later to the breeding grounds did not leave the wintering grounds later, but instead took longer to migrate, potentially reflecting differences in flight speed or time spent at stopover sites. We hypothesise that this may be due to reduced habitat quality at some stopover sites or an inability to adjust their departure timing or migration speed to match the advancing spring phenology in the North. Individuals that migrated longer distances also arrived and nested later. Our results highlight the benefits and potential conservation implications of using a full annual cycle approach to assess the factors influencing reproductive timing of birds., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Metabolic modeling is essential for understanding the mechanistic bases of cellular metabolism in various organisms, from microbes to humans, and the design of fitter microbial strains. Metabolic networks focus on the overall fluxes through biochemical reactions that implicitly rely on several biochemical processes, such as active or diffusive uptake (or export) of nutrients (or metabolites), enzymatic turnover of metabolites, and metal-cofactor enzyme interactions. Despite independent progress in biomolecular simulations, they have yet to be integrated to inform metabolic models. We explore the evolution of computational metabolic modeling approaches, starting with flux balance analysis, dynamic, kinetic delineations of metabolic shifts in single organisms within cells and across tissues, and mutually informing, community-level modeling frameworks and provide a narrative to tie in biomolecular simulations and machine learning predictions to usher the new phase of structure-guided synthetic biology applications. These additions and prospective novel ones are likely to open hitherto untapped paradigms for optimizing/understanding metabolic pathways toward improving bioproduction of protein and small molecule products with downstream applications in health, environment, energy, and sustainability., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Exposure to marketing and promotion of commercial milk formula is associated with an increased likelihood of formula-feeding. In 1981, the International Code (IC) of Marketing of Breastmilk Substitutes was adopted by the 34th World Health Assembly to restrict the promotion, marketing and advertising of commercial milk formula and protect breastfeeding., Research Aim: The current study examines mothers' exposure to violations of the IC in Newfoundland and Labrador, a province of Canada with low breastfeeding rates., Methods: A cross-sectional online survey measured exposure to IC violations (e.g., marketing, advertising and promotion of commercial milk formula) by mothers of infants less than two years old (n = 119). Data were collected on type, frequency, and location of violation., Results: Most participants (87%, n = 104/119) reported exposure to at least one IC violation. Of this group (n = 104): 94% received coupons or discount codes for the purchase of commercial milk formula; 88% received free samples of commercial milk formula from manufacturers, and 79% were contacted directly by commercial milk formula companies via email, text message, mail or phone for advertising purposes. One-third (n = 28/104, 27%) observed commercial milk formula promotional materials in health care facilities. The most frequent locations were violations occurred were doctors' offices (79%), supermarkets(75%), and pharmacies (71%)., Conclusion: The majority of mothers of young infants were exposed to violations of the IC involving the marketing, advertising and promotion of commercial milk formula. Companies producing commercial milk formula reached out directly to new mothers to offer unsolicited promotions and free samples of commercial milk formula., (© 2024. The Author(s).)

Background: Recent developments in CRISPR/Cas9 genome-editing tools have facilitated the introduction of precise alleles, including genetic intervals spanning several kilobases, directly into the embryo. However, the introduction of donor templates, via homology directed repair, can be erroneous or incomplete and these techniques often produce mosaic founder animals. Thus, newly generated alleles must be verified at the sequence level across the targeted locus. Screening for the presence of the desired mutant allele using traditional sequencing methods can be challenging due to the size of the interval to be sequenced, together with the mosaic nature of founders., Methodology/principal Findings: In order to help disentangle the genetic complexity of these animals, we tested the application of Oxford Nanopore Technologies long-read sequencing at the targeted locus and found that the achievable depth of sequencing is sufficient to offset the sequencing error rate associated with the technology used to validate targeted regions of interest. We have assembled an analysis workflow that facilitates interrogating the entire length of a targeted segment in a single read, to confirm that the intended mutant sequence is present in both heterozygous animals and mosaic founders. We used this workflow to compare the output of PCR-based and Cas9 capture-based targeted sequencing for validation of edited alleles., Conclusion: Targeted long-read sequencing supports in-depth characterisation of all experimental models that aim to produce knock-in or conditional alleles, including those that contain a mix of genome-edited alleles. PCR- or Cas9 capture-based modalities bring different advantages to the analysis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LT was the recipient of a conference travel award from ONT., (Copyright: © 2024 McCabe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Alcohol is a known teratogen, and developmental exposure to ethanol results in fetal alcohol spectrum disorder (FASD). Children born with FASD can exhibit a range of symptoms including low birth weight, microcephaly, and neurobehavioral problems. Treatment of patients with FASD is estimated to cost 4 billion dollars per year in the United States alone, and 2 million dollars per affected individual's lifetime. We have established Drosophila melanogaster as a model organism for the study of FASD. Here we report that mutations in Dementin (Dmtn), the Drosophila ortholog of the Alzheimer's disease-associated protein TMCC2, convey sensitivity to developmental ethanol exposure, and provide evidence that Dmtn expression is disrupted by ethanol. In addition, we find that flies reared on ethanol exhibit mild climbing defects suggestive of neurodegeneration. Surprisingly, our data also suggest that flies reared on ethanol age more slowly than control animals, and we find that a number of slow-aging mutants are sensitive to developmental ethanol exposure. Finally, we find that flies reared on ethanol showed a persistent upregulation of genes encoding antioxidant enzymes, which may contribute to a reduced rate of central nervous system aging. Thus, in addition to the well-documented negative effects of developmental alcohol exposure on the nervous system, there may be a previously unsuspected neuroprotective effect in adult animals., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure.

Health, clinical, and regulatory factors are driving significant change in health and health care, leading to an increased emphasis on cost, quality, and results. To improve the well-being of all populations, we must focus on connectivity within a functional, community wide network of diverse partners.

Background: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms., Results: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems., Conclusions: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the mouse genome. In order to acquire robust datasets of broad based phenotypes from mouse mutants it is necessary to design and implement pipelines that incorporate standardised phenotyping platforms that are validated across diverse mouse genetics centres or mouse clinics. We describe here the rationale and methodology behind one phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale phenotyping pipelines, including the definition of parameters integral to each phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The early twentieth-century transformations of rural Chinese women’s work have received relatively little direct attention. By contrast, the former custom of footbinding continues to fascinate and is often used to illustrate or contest theories about Chinese women’s status. Arguing that for rural women at least, footbinding needs to be understood in relation to rural economic conditions, the authors focus on changes in textile production and in footbinding in two counties in Shaanxi province. Drawing on historical sources and their own interview data from rural women who grew up in this period, the authors find evidence that transformations in textile production undercut the custom of footbinding and contributed to its rapid demise.

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies.

We report the first joint shipboard and airborne study focused on the chemical composition and water-uptake behavior of particulate ship emissions. The study focuses on emissions from the main propulsion engine of a Post-Panamax class container ship cruising off the central coast of California and burning heavy fuel oil. Shipboard sampling included micro-orifice uniform deposit impactors (MOUDI) with subsequent off-line analysis, whereas airborne measurements involved a number of real-time analyzers to characterize the plume aerosol, aged from a few seconds to over an hour. The mass ratio of particulate organic carbon to sulfate at the base of the ship stack was 0.23 +/- 0.03, and increased to 0.30 +/- 0.01 in the airborne exhaust plume, with the additional organic mass in the airborne plume being concentrated largely in particles below 100 nm in diameter. The organic to sulfate mass ratio in the exhaust aerosol remained constant during the first hour of plume dilution into the marine boundary layer. The mass spectrum of the organic fraction of the exhaust aerosol strongly resembles that of emissions from other diesel sources and appears to be predominantly hydrocarbon-like organic (HOA) material. Background aerosol which, based on air mass back trajectories, probably consisted of aged ship emissions and marine aerosol, contained a lower organic mass fraction than the fresh plume and had a much more oxidized organic component. A volume-weighted mixing rule is able to accurately predict hygroscopic growth factors in the background aerosol but measured and calculated growth factors do not agree for aerosols in the ship exhaust plume. Calculated CCN concentrations, at supersaturations ranging from 0.1 to 0.33%, agree well with measurements in the ship-exhaust plume. Using size-resolved chemical composition instead of bulk submicrometer composition has little effect on the predicted CCN concentrations because the cutoff diameter for CCN activation is larger than the diameter where the mass fraction of organic aerosol begins to increase significantly. The particle number emission factor estimated from this study is 1.3 x 10(16) (kg fuel)(-1), with less than 1/10 of the particles having diameters above 100 nm; 24% of particles (>10 nm in diameter) activate into cloud droplets at 0.3% supersaturation.

Understanding the functions encoded in the mouse genome will be central to an understanding of the genetic basis of human disease. To achieve this it will be essential to be able to characterize the phenotypic consequences of variation and alterations in individual genes. Data on the phenotypes of mouse strains are currently held in a number of different forms (detailed descriptions of mouse lines, first-line phenotyping data on novel mutations, data on the normal features of inbred lines) at many sites worldwide. For the most efficient use of these data sets, we have initiated a process to develop standards for the description of phenotypes (using ontologies) and file formats for the description of phenotyping protocols and phenotype data sets. This process is ongoing and needs to be supported by the wider mouse genetics and phenotyping communities to succeed. We invite interested parties to contact us as we develop this process further.

Understanding mammalian genetic systems is predicated on the determination of the relationship between genetic variation and phenotype. Several international programmes are under way to deliver mutations in every gene in the mouse genome. The challenge for mouse geneticists is to develop approaches that will provide comprehensive phenotype datasets for these mouse mutant libraries. Several factors are critical to success in this endeavour. It will be important to catalogue assay and environment and where possible to adopt standardised procedures for phenotyping tests along with common environmental conditions to ensure comparable datasets of phenotypes. Moreover, the scale of the task underlines the need to invest in technological development improving both the speed and cost of phenotyping platforms. In addition, it will be necessary to develop new informatics standards that capture the phenotype assay as well as other factors, genetic and environmental, that impinge upon phenotype outcome., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

In this correlated SEM (scanning electron microscope) and TEM (transmission electron microscope) investigation, we describe architectural details of the multiflagellated sperm cell of Psilotum nudum. Comparisons with other pteridophytes are made to (1) assess the placement of Psilotum among pteridophyte taxa and (2) evaluate structural modifications of sperm cells during land plant evolution. The released spermatozoid of Psilotum coils 2.0 revolutions and is outlined by a parallel band of up to 190 microtubules. The elongated nucleus is highly compacted and parallels the cellular coils with numerous mitochondria and starch-laden plastids distributed along its length. Along the anterior coil is an elaborate locomotory apparatus that includes ∼36 flagella that are inserted into the cell by basal bodies. Subtending the basal bodies is the multilayered structure, which consists of a long narrow lamellar strip and an overlying band of microtubules. An elongated anterior mitochondrion underlies the multilayered structure. Additional amyloplasts and mitochondria are aggregated along the anterior coil in association with the locomotory apparatus, while a fibrous band encircles the leading edge of the cell. Salient features of this cell, including details of the locomotory apparatus, structure and position of organelles, and arrangement of the spline, are shared by spermatozoids of Equisetum and ferns (including eusporangiate and leptosporangiate taxa). Thus, this study provides morphological support for the hypothesis that Psilotum nudum is a member of an assemblage that includes ferns and Equisetum. However, the less streamlined architecture of Psilotum gametes and the lack of architectural features shared with any specific taxon examined to date suggest that Psilotum is an early divergent fern, with relatively remote affinities to Ophioglossaceae and Equisetaceae.

The judicious use of perioperative antibiotic prophylaxis reduces the infectious complications of surgery. However, increased bacterial resistance within hospitals may make antibiotic prophylaxis less effective in the future and alternative strategies are needed. New immunomodulatory agents might prevent wound infections by stimulation of the host immune system. To test this hypothesis, we administered poly-[1-6]-beta-D-glucopyranosyl- [1-3] -beta-D-glucopyranose glucan (PGG glucan), which enhances neutrophil microbicidal activity, intravenously to guinea pigs in doses ranging from 0.015 to 4 mg/kg of body weight on the day before, on the day of, and on the day after intermuscular inoculation with methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. Abscesses were identified at 72 h, and median infective doses (ID50) and statistical significance were determined by logistic regression. Guinea pigs receiving PGG glucan and inoculated with methicillin-resistant S. aureus and S. epidermidis exhibited ID50 of as much as 2.5- and 60-fold higher, respectively, than those of control guinea pigs not receiving PGG glucan. Maximal protection was observed with a dose of 1 mg of PGG glucan per kg, and efficacy was reduced at higher as well as at lower PGG glucan doses. Furthermore, a single dose of PGG glucan given 24 h following bacterial inoculation was found to be effective in preventing infection. We conclude that PGG glucan reduces the risk of staphylococcal abscess formation. Neutrophil-activating agents are a novel means of prophylaxis against surgical infection and may be less likely than antibiotics to be affected adversely by the increasing antibiotic resistance of nosocomial pathogens.

The association of human immunodeficiency virus (HIV) infection and pregnancy has become more common. This virus has become a factor in the social affairs of even small, rural communities. We present a case in which the diagnosis of HIV was made during admission for Pneumocystis carinii pneumonia (PCP). The patient's condition worsened rapidly, necessitating delivery at 31 weeks' gestation by cesarean section followed by the patient's death from PCP. The infant survived and was healthy at 1 year of age.

Our laboratory has previously characterized a high affinity choline uptake system (HAChUS) in Limulus tissues and synaptosomes. We report here on the characterization of the HAChUS in synaptosomes prepared selectively from central nervous system tissues shown to be enriched for presumed cholinergic functions; namely the protocerebrum, corpora pedunculata and abdominal ganglia. Synaptosomes were prepared from these tissues by means of a modification of the subfractionation procedure developed by Dowdall and Whittaker. In our modification, we harvested a PP2L fraction exclusively from the S2 fraction. Compared to the P2L fraction, the PP2L was greater than three times more efficient in [3H]choline uptake and was significantly more sensitive to inhibition with micromolar concentrations of hemicholinium-3. The PP2L fraction HAChUS was shown to have characteristics common to the HAChUS of identified cholinergic tissues.

The results of total hip arthroplasty with the use of medial and superior bone-graft augmentation in thirty-nine hips (thirty-two patients) that had protrusio acetabuli were previously reported after two to eight years (mean, 4.7 years) of follow-up. We followed the surviving patients for 10.9 to 17.4 years (mean, 12.8 years). The average Harris hip-rating was 72 points--an average drop of 17 points since the previous report. The average was 64 points for patients who had rheumatoid arthritis and 83 points for those who had another diagnosis. Radiographic evaluation demonstrated definite, probable, and possible loosening in about 20, 10, and 60 per cent of the hips, respectively. Of the six hips that had definite loosening, four (10 per cent of the total series) had progression of the protrusion (acetabular migration); operative revision was performed on two of those four hips and on two other hips, in which progression had ceased. Hips that had progressive protrusion demonstrated superior migration more often than medial migration. The rates of loosening and revision were similar to those in hips that did not have protrusio acetabuli. We concluded that augmentation of total hip arthroplasty with bone-grafting is effective in arresting the progression of protrusio acetabuli in most hips (90 per cent in our series).

Although the clinical and radiographic features of pigmented villonodular synovitis (PVS) have been well described, diagnosis is often delayed and high rates of recurrence after synovectomy are reported. Magnetic resonance imaging (MRI) has been shown to be useful in the diagnosis of soft tissue masses. Three patients with biopsy-proven PVS and radiographs showing only effusion underwent MRI in the axial, coronal, and sagittal planes. The margins of the diseased synovium were best demonstrated on long TR/TE (T2-weighted) images. The synovium contained areas of void signal intensity felt to be due to hemosiderin, interspersed with increased signal from both inflammation and fat. In all cases, the margins of the diseased synovium were clearly delineated, allowing classification as nodular or diffuse. No appreciable change in signal intensity was seen when comparing nodular and diffuse forms. MRI is useful but not specific for PVS, since rheumatoid synovitis may show a similar signal pattern. However, MRI in patients with suspected PVS may decrease the time until diagnosis, aid in preoperative planning and obtaining adequate margins of resection, and may be a non-invasive method of long-term follow up for possible recurrence.

Seven patients who had pain in the anterior aspect of the ankle were found to have a thickened distal fascicle of the anteroinferior tibiofibular ligament. Each patient had a history of an inversion sprain of the ankle followed by chronic pain in the anterior aspect of the ankle. The thickened distal fascicle was resected without loss of stability of the ankle. Five patients needed débridement of an area of abraded hyaline cartilage on the anterolateral aspect of the talus. Six patients were followed for a mean of thirty-nine months (range, twenty-four to fifty-nine months). Four of them had no pain in the ankle or limitation in activities, and two reported marked improvement, with only occasional pain in the ankle related to overuse. A separate distal fascicle of the anteroinferior tibiofibular ligament is present in most human ankles and can be a cause of talar impingement, abrasion of the articular cartilage, and pain in the anterior aspect of the ankle. Resection of this ligament usually will alleviate the pain caused by the impingement.

The radiographic data of 48 hips in 40 patients with painful, progressive protrusio acetabuli treated with cemented total hip arthroplasty and medial acetabular reinforcement using autologous or homologous bone grafts were reviewed. Twelve separate measurements were performed on the preoperative, postoperative, and most recent radiographs of each case to determine which measurements were the most useful in diagnosing protrusio acetabuli and in following preoperative and postoperative migration. The minimum follow-up period was 10 years (mean, 12.3 years). Vertical migration and horizontal distance, two measurements utilizing an X-Y coordinate system based on the acetabular teardrop, were found to be most useful. The cases with postoperative progression demonstrated vertical migration more often than medial migration.

Endometrial diagnostic techniques available to the family physician for office use have a high degree of accuracy in identifying intrauterine pathology. Recent refinements in endometrial sampling devices have made their use cost-effective and complication rates minimal. These methods can be utilized annually for screening asymptomatic women at high risk of developing uterine cancer. Detection of endometrial hyperplasia has improved with the newer samplers. Patient acceptance is excellent, especially with the cytologic devices.

A very unusual case of an apparent primary clear cell adenocarcinoma of the vulva in a 57-year-old female is presented. The carcinoma arose in an area of endometriosis within the canal of Nuck in the superior aspect of the right labium majus. Smooth muscle fibers presumably representing remnants of the extrapelvic round ligament were found associated with the endometriosis. Of interest is the fact that the patient underwent right herniorrhaphy 9 years earlier. Although several cases of primary adenocarcinoma arising within the vulva have been reported, none has arisen in areas of endometriosis within the canal of Nuck. No case in the literature of a primary clear cell adenocarcinoma arising from endometriosis in the canal of Nuck and in association with the extrapelvic portion of the round ligament could be found.