Imaging features of renal ectopia and fusion in 13 cats.

CASE SERIES SUMMARY: A retrospective multicenter case series of renal fusion anomalies in cats was investigated. The aim of this study was to describe the imaging characteristics (radiography, ultrasonography and CT) of renal ectopia and fusion in cats. A total of 13 feline patients (median age 9 years) were included in this multicentric retrospective study. Ultrasound was available in 12/13 cases, radiographs in 4/13 cases and CT in 3/13 cases. Of the 13 cases, seven were left to right fusions, four were right to left fusions, one was on the midline and one was in the pelvic inlet. Adopting a human classification system, there were five lump kidneys, four disc kidneys, one horseshoe kidney, one caudal ectopia, one L-shaped kidney and one pelvic kidney. In 2/13 cases, additional congenital malformations were noted, including an azygous continuation of the caudal vena cava and a peritoneal-pericardial diaphragmatic hernia. RELEVANCE AND NOVEL INFORMATION: This study provides further description of the imaging findings in feline patients with fused renal ectopia. The morphologic characteristics of the fused kidneys in cats appear similar to what is published in the human literature. Renal fusion might be an incidental finding in cats, but further investigations are necessary to determine their clinical relevance.

Pain Catastrophizing and Impact on Pelvic Floor Surgery Experience.

IMPORTANCE: Understanding patients' perceptions of symptoms and outcomes of urogynecologic surgery is essential for providing high-quality care. OBJECTIVE: The aim of the study was to assess association of pain catastrophizing with pelvic floor symptom distress and impact, postoperative pain, and voiding trial in patients undergoing urogynecologic surgery. STUDY DESIGN: Individuals whose self-identified gender was female and were undergoing surgery March 2020-December 2021 were included. Participants completed the Pain Catastrophizing Scale (range 0-52), Pelvic Floor Distress Inventory, and Pelvic Floor Impact Questionnaire preoperatively. Pain catastrophizing was score ≥30 and describes the tendency to magnify the overall threat of pain. Voiding trial failure was inability to void ≥2/3 of instilled volume (≤300 mL). The association between pain catastrophizing and symptom distress and impact was assessed with linear regression. A P < 0.05 is significant. RESULTS: Three hundred twenty patients were included (mean age, 60 years, 87% White). Forty-six of 320 participants (14%) had a pain catastrophizing score ≥30. The pain catastrophizing group had higher body mass index (33 ± 12 vs 29 ± 5), more benzodiazepine use (26% vs 12%), greater symptom distress (154 ± 58 vs 108 ± 60), and greater urogenital (59 ± 29 vs 47 ± 28), colorectal (42 ± 24 vs 26 ± 23), and prolapse (54 ± 24 vs 36 ± 24) subscale scores, all P ≤ 0.02. The pain catastrophizing group had greater impact (153 ± 72 vs 72 ± 64, P < 0.01) and urogenital (60 ± 29 vs 34 ± 28), colorectal (36 ± 33 vs 16 ± 26), and prolapse (57 ± 32 vs 22 ± 27) subscale scores, P < 0.01. Associations remained controlling for confounders ( P < 0.01). The pain catastrophizing group had higher 10-point pain scores (8 vs 6, P < 0.01) and was more likely to report pain at 2 weeks (59% vs 20%, P < 0.01) and 3 months (25% vs 6%, P = 0.01). Voiding trial failure did not differ (26% vs 28%, P = 0.98). CONCLUSIONS: Pain catastrophizing is associated with greater pelvic floor symptom distress and impact and postoperative pain but not voiding trial failure.

Multi-modality imaging and therapeutics used in a case of canine spinal nephroblastoma.

A 4-year-old castrated male golden retriever dog was brought to a veterinary teaching hospital for evaluation of acute progressive paraparesis. Neurological examination indicated a spinal cord lesion between the third thoracic vertebra and third lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intradural, extra medullary, and/or intramedullary mass centered over the eleventh and twelfth thoracic disc space. The dog underwent cytoreductive surgery and histopathologic analysis diagnosed a nephroblastoma. Following this, the dog underwent multimodal therapy, including multiple surgeries, 2 courses of radiation, and combination chemotherapy. The dog had serial restaging using MRI, computed tomography (CT), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography throughout the course of therapy. The dog survived 350 d from date of first presentation until humane euthanasia was elected due to worsening of neurologic status. During postmortem examination, extensive infiltration of the spinal cord by nephroblastoma cells was discovered as well as pulmonary metastatic disease. Key clinical message: Based on the literature search, this is the first case in which surgery, radiation therapy, and chemotherapy were all used for the treatment of canine spinal nephroblastoma. This case report details the aggressive nature of a case of canine spinal nephroblastoma despite multi-modal therapy.

Méthode d'imagerie et de thérapies multimodales utilisées dans un cas de néphroblastome spinal canin. Un chien golden retriever mâle castré âgé de 4 ans a été présenté dans un hôpital d'enseignement vétérinaire pour l'évaluation d'une paraparésie progressive aiguë. L'examen neurologique a révélé une lésion de la moelle épinière entre la troisième vertèbre thoracique et la troisième vertèbre lombaire. L'imagerie par résonance magnétique (MRI) a révélé une masse intradurale, extra-médullaire et/ou intramédullaire centrée sur les onzième et douzième espace de disque thoracique. Le chien a subi une chirurgie de cytoréduction et une analyse histopathologique a diagnostiqué un néphroblastome. Par la suite, le chien a subi une thérapie multimodale, comprenant plusieurs interventions chirurgicales, deux cycles de radiothérapie et une chimiothérapie combinée. Le chien a subi une reclassification en série par MRI, tomodensitométrie (CT) et tomographie par émission de positrons au fluor-18 fluorodésoxyglucose/tomodensitométrie tout au long du traitement. Le chien a survécu 350 jours à partir de la date de la première présentation jusqu'à ce que l'euthanasie soit choisie en raison de l'aggravation de l'état neurologique. Au cours de l'examen post-mortem, une infiltration étendue de la moelle épinière par des cellules de néphroblastome a été découverte ainsi qu'une maladie métastatique pulmonaire.Message clinique clé :D'après la recherche documentaire, il s'agit du premier cas dans lequel la chirurgie, la radiothérapie et la chimiothérapie ont toutes été utilisées pour le traitement du néphroblastome spinal canin. Ce rapport de cas détaille la nature agressive d'un cas de néphroblastome spinal canin malgré une thérapie multimodale.(Traduit par Dr Serge Messier).

Retrospective analysis of use of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) for detection of metastatic lymph nodes in dogs diagnosed with appendicular osteosarcoma.

The purpose of this retrospective analysis was to determine if fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) could potentially be an accurate staging tool for detecting metastatic lymph nodes in dogs with appendicular osteosarcoma based on the quantitative measurement of the maximum standard uptake value (SUVmax) of lymph nodes. A total of 53 dogs were identified that presented for staging via 18F-FDG PET/CT for primary appendicular osteosarcoma. Patients were categorized according to lymph node status of having either metastatic or non-metastatic nodes based on cytological or histological analysis. Maximum standard uptake (SUVmax) values of the sampled lymph node(s) were recorded and 3/77 (3.9%) of sampled lymph nodes were confirmed metastatic. A Mann-Whitney test revealed a statistical difference in the SUVmax of the metastatic versus non-metastatic lymph nodes [median: 6.6 to 95% confidence interval (CI): 2.56 to 14.37 versus 2.18 95% CI: 2.32 to 3.17, respectively, P-value = 0.05]. This retrospective analysis revealed a significant difference in the SUVmax as measured on 18F-FDG PET/CT between metastatic lymph nodes and non-metastatic lymph nodes in canine patients afflicted with appendicular osteosarcoma, in spite of the small numbers analyzed. While these results are promising, they should be interpreted with caution and further studies are justified.

Le but de cette analyse rétrospective était de déterminer si la tomographie par émission de positons avec le fluor-18 fluorodésoxyglucose/tomodensitométrie (18F-FDG TEP/CT) pourrait potentiellement être un outil de stadification précis pour la détection des ganglions lymphatiques métastatiques chez les chiens atteints d'ostéosarcome appendiculaire basé sur la quantification de la valeur standard maximale d'absorption (SUVmax) des ganglions lymphatiques. Les auteurs ont identifié 53 chiens qui furent classifiés avec le 18F-FDG TEP/CT pour l'ostéosarcome appendiculaire primaire. Les patients ont été classés, selon l'état des ganglions lymphatiques, à avoir des ganglions métastatiques ou non métastatiques sur la base d'une analyse cytologique ou histologique. Les valeurs d'absorption standard maximale (SUVmax) du ou des ganglions lymphatiques échantillonnés ont été enregistrées et 3/77 (3,9 %) des ganglions lymphatiques échantillonnés ont été confirmés métastatiques. Un test de Mann-Whitney a révélé une différence statistique du SUVmax des ganglions lymphatiques métastatiques versus non métastatiques [médiane: 6,6 à 95 % intervalle de confiance (IC): 2,56 à 14,37 versus 2,18 IC à 95 %: 2,32 à 3,17, respectivement, valeur de P = 0,05]. Cette analyse rétrospective a révélé une différence significative dans le SUVmax tel que mesuré sur 18F-FDG TEP/CT entre les ganglions lymphatiques métastatiques et les ganglions lymphatiques non métastatiques chez les patients canins atteints d'ostéosarcome appendiculaire, malgré le petit nombre analysé. Bien que ces résultats soient prometteurs, ils doivent être interprétés avec prudence et des études complémentaires sont justifiées.(Traduit par Docteur Serge Messier).

Timing and Success of Postoperative Voiding Trial After Colpocleisis With and Without Concomitant Midurethral Sling.

OBJECTIVE: The aim of this study was to compare failure rates of first voiding trial (VT) within 7 days and on postoperative day (POD) 1 after colpocleisis with versus without concomitant midurethral sling (MUS). Predictors of POD 1 VT failure were also examined. METHODS: This was a retrospective cohort study of women undergoing colpocleisis from January 2012 to October 2019 comparing VT outcomes with versus without MUS. Primary outcome was first VT failure within 7 days; outcomes of VTs performed on POD 1 were also assessed. Association between MUS and VT failure and predictors of POD 1 VT failure were assessed via logistic regression. RESULTS: Of 119 women, 45.4% had concomitant MUS. First VT was performed on mean POD 3.1 ± 2.2 in the MUS group versus POD 1.8 ± 1.8 in the no MUS group (P < 0.01). The MUS group was less likely to undergo POD 1 VT (50% vs 83%, P < 0.01). Failure of the first VT did not differ (22.2% with MUS vs 32.8% without MUS, P = 0.20); no association between VT failure and MUS was noted (adjusted odds ratio [aOR], 0.6; 95% confidence interval [CI], 0.18-2.1). There were 68.1% (81/119) of participants who underwent POD 1 VT, MUS was performed in 33.3% (27/81). The POD 1 failure did not differ between those with 33.3% versus 40.7% without MUS (P = 0.52). Midurethral sling was not associated with POD 1 VT failure (aOR, 0.93; 95% CI, 0.27-3.23). In women undergoing POD 1 VT, preoperative postvoid residual was associated with VT failure (aOR, 1.39; 95% CI, 1.01-1.92). CONCLUSIONS: In women undergoing colpocleisis, MUS was not associated with VT failure within 7 days or on POD 1. Increased preoperative postvoid residual was associated with POD 1 VT failure.

Effects of vitrification and the superovulated environment on placental function and fetal growth in an IVF mouse model.

In studies of human IVF, as compared to frozen embryo transfer (ET), fresh ET is associated with smaller infants and higher risk of small for gestational age infants. Recent observations suggest that ET using vitrified embryos is associated with higher pregnancy and live birth rates compared to fresh ET, but increased rates of large for gestational age infants. The mechanisms underlying these associations are largely unknown, and available evidence suggests that the influence of IVF, vitrification and the superovulated (SO) uterine environment on placental function and fetal growth is complex. This warrants further investigation given the prevalent practice in human IVF of both fresh ET into a SO uterine environment, and vitrification with ET into a more physiologic uterine environment. Using a mouse model that closely resembles human IVF, we investigated if vitrification of IVF embryos better preserves placental function and results in better pregnancy outcomes as compared to fresh ET because of transfer into a more physiologic endometrium. We found that the SO environment, independent of vitrification status, reduced implantation rates, inhibited placental mechanistic target of rapamycin signaling and induced placental stress signaling, resulting in fetal growth restriction (1.080 ± 0.05 g estrous fresh (n = 17 litters), 1.176 ± 0.05 g estrous vitrified (n = 12), 0.771 ± 0.06 g SO fresh (n = 15), 0.895 ± 0.08 g SO vitrified (n = 10), P < 0.0001). In addition, our study suggests that vitrification impairs the developmental potential of IVF blastocysts that resulted in a significantly smaller litter size (2.6 ± 2.3 fresh estrous vs 2.5 ± 2.4 fresh SO vs 1.6 ± 1.7 estrous vitrified vs 1.7 ± 1.8 SO vitrified, P = 0.019), with no effect on fetal growth or placental function at term. Our findings suggest that vitrification may negatively impact early embryonic viability, while the SO maternal uterine environment impairs both placental development and fetal growth in IVF.

Impact of the T2-weighted axial oblique MRI sequence in the assessment of peroneal tendons.

AIM: To define the role of the T2-weighted axial oblique sequence for the magnetic resonance imaging (MRI) assessment of peroneal tendon pathologies. MATERIALS AND METHODS: Two radiologists interpreted 180 ankle MRI examinations using standard sequences alone and then in combination with an axial oblique sequence. The readers indicated how likely a peroneal pathology was present using a five-level confidence scale. Diagnostic confidence, interobserver agreement, and clinical correlation were compared. Changes in diagnosis were recorded. RESULTS: For both readers, the diagnostic confidence was significantly higher using the axial oblique sequence for tendinosis and inframalleolar tenosynovitis for both tendons and for peroneus brevis partial and longitudinal split tears (p<0.001). For reader 1, the diagnostic confidence was also higher using the axial oblique sequence for peroneus longus partial tears (p=0.007). Changes in diagnosis were seen for tendinosis and tenosynovitis of both tendons and for peroneus brevis partial and longitudinal split tears in 0.6-10.8% of cases. Inter-rater reliability was significantly higher with the axial oblique sequence for the diagnosis of tendinosis, inframalleolar tenosynovitis, and partial tear for both tendons, and for peroneus brevis longitudinal split tear. Amongst 105 examinations with clinical information, peroneal pathologies were most frequently diagnosed as present in cases with lateral symptoms (17% versus 14%) and absent in cases without lateral symptoms (92% versus 86%) on the axial oblique sequence. CONCLUSION: The axial oblique sequence for the assessment of peroneal tendons allows for higher diagnostic confidence, inter-rater reliability, and clinical correlation and can lead to changes in diagnosis.

The Cascading Effects of Externalizing Behaviors and Academic Achievement Across Developmental Transitions: Implications for Prevention and Intervention.

Children's behavior and achievement problems are interrelated causes of distress for individuals, schools, and families, and generate long-term individual and societal costs. Yet, little is known about how the timing and direction of relationships involving achievement and problem behaviors (1) varies by standardized versus teacher ratings of achievement and (2) changes as students enter adolescence and begin secondary school. Using data from the Study of Early Child Care and Youth Development (N = 1048, 50.05% female), we employed longitudinal structural equation modeling to examine the relationship between externalizing behaviors and two forms of achievement from third through ninth grade. Results revealed that externalizing behaviors in grades three, five, and six directly and indirectly influenced teacher ratings of school achievement in grades 5, 6, and 9, and indirectly influenced standardized assessments of achievement over time. The reciprocal relationships involving externalizing behaviors and school achievement were especially strong from grade 6 to grade 9with their contemporaneous association peaking in grade 9. Demographic and maturational factors influenced the average levels of externalizing behaviors and achievement scores over development, but none altered the timing and direction of these relationships. Our findings highlight early adolescence as an important period for implementing evidence-based interventions related to the reduction of externalizing behaviors and improvements in achievement. Implications for prevention research, practice, and policy are discussed.

Glucocorticoid regulation of amino acid transport in primary human trophoblast cells.

Excess maternal glucocorticoids reduce placental amino acid transport and fetal growth, but whether these effects are mediated directly on the syncytiotrophoblast remains unknown. We hypothesised that glucocorticoids inhibit mechanistic target of rapamycin (mTOR) signaling and insulin-stimulated System A amino acid transport activity in primary human trophoblast (PHT) cells. Syncytialised PHTs, isolated from term placentas (n = 15), were treated with either cortisol (1 µM) or dexamethasone (1 µM), ± insulin (1 nM) for 24 h. Compared to vehicle, dexamethasone increased mRNA expression, but not protein abundance of the mTOR suppressor, regulated in development and DNA damage response 1 (REDD1). Dexamethasone enhanced insulin receptor abundance, activated mTOR complex 1 and 2 signaling and stimulated System A activity, measured by Na+-dependent 14C-methylaminoisobutyric acid uptake. Cortisol also activated mTORC1 without significantly altering insulin receptor or mTORC2 read-outs or System A activity. Both glucocorticoids downregulated expression of the glucocorticoid receptor and the System A transporter genes SLC38A1, SLC38A2 and SLC38A4, without altering SNAT1 or SNAT4 protein abundance. Neither cortisol nor dexamethasone affected System L amino acid transport. Insulin further enhanced mTOR and System A activity, irrespective of glucocorticoid treatment and despite downregulating its own receptor. Contrary to our hypothesis, glucocorticoids do not inhibit mTOR signaling or cause insulin resistance in cultured PHT cells. We speculate that glucocorticoids stimulate System A activity in PHT cells by activating mTOR signaling, which regulates amino acid transporters post-translationally. We conclude that downregulation of placental nutrient transport in vivo following excess maternal glucocorticoids is not mediated by a direct effect on the placenta.

Developmental cascades of social competence, achievement in school, and achievement on standardized assessments during the transition to adolescence and secondary school.

INTRODUCTION: Social and academic functioning are cornerstones of positive youth development and important to later educational and health outcomes. Yet, little is known about how the timing and direction of relationships between social and academic functioning vary by the type of achievement assessed and how the transition to adolescence influences these relationships. METHOD: This study employs longitudinal structural equation modeling to examine the interrelationships of children's social competence, teacher ratings of school achievement, and standardized assessments of cognitive achievement in a cohort of 1048 children in the United States. RESULTS: & Conclusions: Results identify 1) direct and indirect pathways from children's social competence in grades three and five to their school achievement in grades five and six; 2) significant pathways between school and cognitive achievement across all assessment points that decline in magnitude as students enter high school; 3) the magnitude of pathways between social competence and school achievement far exceed those between social competence and cognitive achievement; and 4) social and maturational factors account for variation in these functions but do not confound the timing and direction of the pathways from one to the other function. Given the importance of social competence and academic achievement to positive development, these findings demonstrate elementary school as an optimal and foundational period to implement universal interventions to optimize social functioning and prevent later academic difficulties in secondary school.

Apelin is a novel regulator of human trophoblast amino acid transport.

Apelin is an insulin-sensitizing hormone increased in abundance with obesity. Apelin and its receptor, APJ, are expressed in the human placenta, but whether apelin regulates placental function in normal body mass index (BMI) and obese pregnant women remains unknown. We hypothesized that apelin stimulates amino acid transport in cultured primary human trophoblast (PHT) cells and that maternal circulating apelin levels are elevated in obese pregnant women delivering large babies. Treating PHT cells with physiological concentrations of the pyroglutamated form [Pyr1]apelin-13 (0.1-10.0 ng/ml) for 24 h dose-dependently increased System A amino acid transport (P < 0.05) but did not affect System L transport activity. Mechanistic target of rapamycin (mTOR), extracellular signal-regulated kinase-1/2 (ERK1/2), and AMP-activated protein kinase-α (AMPKα) signaling were unaffected by apelin (P > 0.05). Plasma apelin was not different in obese women (BMI 35.8 ± 0.7, n = 21) with large babies compared with normal-BMI women (23.1 ± 0.5, n = 16) delivering normal birth weight infants. Apelin was highly expressed in placental villous tissue (20-fold higher vs. adipose), and APJ was present in syncytiotrophoblast microvillous membrane, but neither differed in abundance between normal-BMI and obese women. Phosphorylation (Thr172) of placental AMPKα strongly correlated with microvillous membrane APJ expression (P < 0.01, R = 0.63) but negatively correlated with placental apelin abundance (P < 0.01, R = -0.62). Neither placental APJ nor apelin abundance correlated with maternal BMI, plasma insulin, birth weight, or mTOR or ERK1/2 signaling (P > 0.05). Hence, apelin stimulates trophoblast amino acid uptake, establishing a novel mechanism regulating placental function. We found no evidence that apelin constitutes an endocrine link between maternal obesity and fetal overgrowth.

The Impact of Racial, Geographic, and Socioeconomic Risk Factors on the Development of Advanced-Stage Cervical Cancer.

OBJECTIVES: Despite screening, disparities exist in cervical cancer incidence and outcomes. Demographic factors are associated with diagnosis at advanced stage (AS), but less is known about geographic factors. We sought to investigate risk factors for developing AS cervical cancer in Alabama. MATERIALS AND METHODS: We identified women treated for cervical cancer from 2005 to 2015 at our institution. Stages II-IV were considered AS. ZIP codes were categorized by federal Rural-Urban Commuting Area Codes, and 16 historically underserved counties were categorized as Black Belt rural. Using data from the American College of Obstetricians and Gynecologists, we identified women's health provider locations. We explored associations between stage and multiple factors using logistic regression. RESULTS: Of 934 patients, 29.2% were black, 52.7% had AS cancer, and 63.4% lived in urban areas. Average distance to nearest American College of Obstetricians and Gynecologists Fellow in urban, rural, and Black Belt rural areas was 5.0, 10.6, and 13.7 miles, respectively. Black race, public insurance and age of older than 65 years were associated with increased risk of AS cancer. Living in a rural area trended toward higher risk but was not significant. When stratified by race, insurance status and age were associated with AS cancer in white women only. CONCLUSIONS: Living further from a women's health provider or in a rural area was not associated with a higher risk of AS cervical cancer. Black women had a higher risk of AS than white women regardless of age, insurance status, and geography. Disparities in cervical cancer are multifactorial and necessitate further research into socioeconomic, biologic, and systems causes.

OBGYN screening for environmental exposures: A call for action.

BACKGROUND: Prenatal exposures have known adverse effects on maternal and neonatal outcomes. Professional societies recommend routine screening for environmental, occupational, and dietary exposures to reduce exposures and their associated sequelae. OBJECTIVE: Our objective was to determine the frequency of environmental exposure screening by obstetricians and gynecologists (OBGYNs) at initial patient visits. STUDY DESIGN: Practicing OBGYNs were approached at the University of Colorado and by social media. The survey instrument queried demographics, environmental literacy, and screening practices. Statistical analysis was performed using Chi-square and two-sample t-test. RESULTS: We received 312 online survey responses (response rate of 12%). Responding OBGYNs were predominantly female (96%), board-certified (78%), generalists (65%) with a mean age of 37.1 years. Fewer than half of physicians screened for the following factors: occupational exposures, environmental chemicals, air pollution, pesticide use, personal care products, household cleaners, water source, use of plastics for food storage, and lead and mercury exposure. Eighty five percent of respondents reported that they did not feel comfortable obtaining an environmental history and 58% respondents reported that they performed no regular screening of environmental exposures. A higher frequency of screening was associated with > 4 years of practice (p = 0.001), and having read the environmental committee opinion (p = <0.001). CONCLUSION: The majority of OBGYNs did not incorporate screening for known environmental exposures into routine practice. Reading the environmental committee opinions was strongly and significantly associated with a higher rate of screening. Improving physician comfort in counseling patients may enhance screening for exposures that affect reproductive health.

Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women.

Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.

Regulation of Placental Amino Acid Transport and Fetal Growth.

The fetus requires amino acids for the processes of protein synthesis, carbon accretion, oxidative metabolism, and biosynthesis, which ultimately determine growth rate in utero. The fetal supply of amino acids is critically dependent on the transport capacity of the placenta. System A amino acid transporters in the syncytiotrophoblast microvillous plasma membrane, directed toward maternal blood, actively accumulate amino acids, while system L exchangers mediate uptake of essential amino acids from the maternal circulation. The functional capacity and protein abundance of these transporters in the placenta are related to fetal growth in both humans and experimental animals. Maternal nutritional and endocrine signals including insulin, insulin-like growth factors, adipokines, and steroid hormones regulate placental amino acid transport, against the background of growth signals originating from the fetus. Anabolic signals of abundant maternal resource availability stimulate placental amino acid transport to optimize offspring fitness, whereas catabolic signals reduce placental amino acid transport in an attempt to ensure survival and long-term reproductive capacity of the mother when resources are scarce. These signals regulate placental amino acid transport by controlling transcription, translation, plasma membrane trafficking, and degradation of transporters. Adaptations in placental amino acid transport capacity may underlie either under- or overgrowth of the fetus when maternal nutrient and hormone levels are altered as a result of altered maternal nutrition or metabolic disease. Strategies to modulate placental amino acid transport may prove effective to normalize fetal growth in intrauterine growth restriction and fetal overgrowth.

Disability, depression and suicide ideation in people with multiple sclerosis.

INTRODUCTION: Depressive symptoms occur frequently in people with Multiple Sclerosis (MS) and rates of suicide ideation are higher than the general population. There is evidence for a direct association between disability and depression, disability and suicide ideation, and depression and suicide ideation in MS. However, the relationship between all three, i.e. the mediating role of depression between disability and suicidal ideation, has not been investigated. Exploring this relationship could highlight risk factors, alerting clinicians to the need for timely intervention. METHOD: Seventy five people with progressive MS attending two out-patient clinics took part in this cross-sectional study. Participants completed the Beck Suicide Scale, Beck Depression Inventory, Multiple Sclerosis Impact Scale and Guy's Neurological Disability Scale. RESULTS: Depressive symptoms mediated the relationship between perceived and actual disability and suicide ideation. Different types of disability were associated with suicidality, including: 'tremors' and 'taking longer to do things'. A small sub-group of participants were identified who reported suicide ideation in the presence of only mild levels of depression. LIMITATIONS: There may be a sample bias in this study as all participants were attending out-patient clinics and receiving support which may not be available to everyone with MS. CONCLUSION: It is important for clinicians to screen regularly for both depression and suicide ideation, to be alert to specific types of disability for which a higher level of suicide ideation might be present and to consider the possibility of suicidal thoughts being present in people who show minimal or no depressive symptoms.

Serum Creatinine Trajectories for Community- versus Hospital-Acquired Acute Kidney Injury.

BACKGROUND: Patterns of acute kidney injury (AKI) can be distinguished by the rate of changes in the serum creation concentrations during hospitalizations. We hypothesized that the timing and values of minimum and maximum serum creatinine (sCr) could be used to distinguish between transient hospital-associated AKI (THA-AKI) and hospital-acquired AKI (HA-AKI). MATERIALS AND METHODS: We evaluated adults admitted to 2 regionally distinct academic medical centers. Peak sCr during the hospitalization was used to define AKI, using absolute changes and timing from the minimum sCr. sCr trajectories were derived based on the rate of change between the minimum and peak creatinine concentrations. RESULTS: Peak creatinine followed the minimum creatinine for HA-AKI, while the peak creatinine preceded the minimum creatinine for THA-AKI. There were 82,403 patients included in the analyses, and 53,882 (65%) did not have AKI during the index hospitalization. There were 2,611 inpatient deaths; HA-AKI had a 4.8-fold increased risk relative to those without AKI (p < 0.01), and transient AKI had a 1.6-fold increased risk for inpatient mortality relative to inpatients without AKI (p < 0.01). CONCLUSIONS: Patients with hospital-associated AKI are at an increased risk for inpatient mortality. Creatinine trajectories can be used to describe the rate of development as well as recovery from inpatient AKI. The 24- and 48-hour interval slopes may be early indicators of developing AKI. © 2016 S. Karger AG, Basel.

IFPA meeting 2015 workshop report III: nanomedicine applications and exosome biology, xenobiotics and endocrine disruptors and pregnancy, and lipid.

Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) nanomedicine applications and exosome biology; 2) xenobiotics and endocrine disruptors and pregnancy; 3) lipid mediators and placental function.

The neurodevelopmental differences of increasing verbal working memory demand in children and adults.

Working memory (WM) - temporary storage and manipulation of information in the mind - is a key component of cognitive maturation, and structural brain changes throughout development are associated with refinements in WM. Recent functional neuroimaging studies have shown that there is greater activation in prefrontal and parietal brain regions with increasing age, with adults showing more refined, localized patterns of activations. However, few studies have investigated the neural basis of verbal WM development, as the majority of reports examine visuo-spatial WM. We used fMRI and a 1-back verbal WM task with six levels of difficulty to examine the neurodevelopmental changes in WM function in 40 participants, twenty-four children (ages 9-15 yr) and sixteen young adults (ages 20-25 yr). Children and adults both demonstrated an opposing system of cognitive processes with increasing cognitive demand, where areas related to WM (frontal and parietal regions) increased in activity, and areas associated with the default mode network decreased in activity. Although there were many similarities in the neural activation patterns associated with increasing verbal WM capacity in children and adults, significant changes in the fMRI responses were seen with age. Adults showed greater load-dependent changes than children in WM in the bilateral superior parietal gyri, inferior frontal and left middle frontal gyri and right cerebellum. Compared to children, adults also showed greater decreasing activation across WM load in the bilateral anterior cingulate, anterior medial prefrontal gyrus, right superior lateral temporal gyrus and left posterior cingulate. These results demonstrate that while children and adults activate similar neural networks in response to verbal WM tasks, the extent to which they rely on these areas in response to increasing cognitive load evolves between childhood and adulthood.

IFPA meeting 2015 workshop report I: placental mitochondrial function, transport systems and epigenetics.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops covered areas of placental regulation and nutrient handling: 1) placental epigenetics; 2) placental mitochondrial function; 3) placental transport systems.