Modulation of thymidine incorporation by κ-opioid ligands in rat spinal cord-dorsal root ganglion co-cultures

β-Endorphin, met-enkephalin and several μ-selective opioid agonists were shown to decrease thymidine incorporation into DNA in various neural cell cultures. We now report that the κ-selective opioid agonists U50488, U69593 and MR2034 modulate [³H]thymidine incorporation into DNA in rat spinal cord-dorsal root ganglion co-cultures. U50488 at 10 μM increased by 60% thymidine incorporation in 6-day-old cultures. The thymidine incorporation induced by U50488 was blocked by the κ-selective antagonist nor-binaltorphimine, as well as by pertussis toxin and LiCl U50488 treatment stimulated phosphatidylinositol turnover by three-fold compared with untreated controls. These findings suggest that κ-opioid agonists modulate DNA synthesis in spinal cord-dorsal root ganglion co-cultures through a mechanism which involves pertussis toxin-sensitive GTP-binding proteins, as well as activation of phosphatidylinositol turnover.     

Dyspareunia Related to GSM: Association of Total Vaginal Thickness via Transabdominal Ultrasound

IntroductionIt has previously been suggested in the literature that ultrasound measurement of total vaginal wall thickness (TVT) differs significantly between pre- and postmenopausal women, indicating that it may be a useful and noninvasive objective assessment to correlate the degree of vaginal atrophy to patient-reported symptoms.AimThe purpose of this cross-sectional pilot study was to determine whether TVT in postmenopausal women, as measured with transabdominal ultrasound, is associated with patient-reported dyspareunia and symptoms related to genitourinary symptomatology.MethodsPostmenopausal women presenting for pelvic ultrasound had TVT and total mucosal thickness (TMT) measured via transabdominal ultrasound. A questionnaire also was administered assessing menopausal status, relevant medical history, and self-report of dyspareunia and other symptoms related to the genitourinary syndrome of menopause (GSM). This questionnaire was derived from the Vulvovaginal Symptom Questionnaire, which has been validated in the literature.Main Outcome MeasureThe main outcome measures included the average TVT and TMT for postmenopausal women reporting any symptom of GSM and average TVT and TMT of women reporting no symptoms of GSM.ResultsData from 44 postmenopausal women showed no significant association between transabdominal ultrasound-measured TVT or TMT and patient report of dyspareunia or other genitourinary symptoms. Data were stratified by individual GSM symptoms, sexual symptoms as an aggregate, and individual sexual symptoms. Neither of these subgroups showed a statistically significant difference in TVT or TMT between symptomatic and asymptomatic women.Clinical ImplicationsAlthough no statistically significant data were derived from this study, we propose that future studies investigating the longitudinal relationship between TVT and GSM symptomatology may show an association between total vaginal thickness measurement change over time as determined by ultrasound with the presence of patient-reported dyspareunia and other GSM symptoms.Strengths & LimitationsThis study is limited by its small sample size as well as the patient population, which was restricted to postmenopausal women with a clinical indication for ultrasound. A major strength of this investigation is that it is the first study to look at the relationship between sexual pain and other GSM symptoms and TVT using transabdominal ultrasound, which is a readily available, non-invasive tool in most clinical settings.ConclusionBased on the results of this small pilot study, transabdominal pelvic ultrasound cannot be used at this time to objectively quantify the presence of sexual pain or other GSM symptoms; however, future studies should continue to investigate the longitudinal relationship between these 2 variables.Balica AC, Cooper AM, McKevitt MK, et al. Dyspareunia Related to GSM: Association of Total Vaginal Thickness via Transabdominal Ultrasound. J Sex Med 2019; 16:2038–2042.     

Maternal obesity and long-term neuropsychiatric morbidity of the offspring

Archives of Gynecology and Obstetrics - To evaluate the long-term pediatric neuropsychiatric morbidity of children born to obese patients. A population-based cohort analysis was performed comparing...     

Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1

Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis.     

Targeted BRCA1/2 population screening among Ashkenazi Jewish individuals using a web-enabled medical model: An observational cohort study

PurposeThis study aimed to evaluate uptake and follow-up using internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs).MethodsAcross 4 cities in the United States, from December 2017 to March 2020, individuals aged ≥25 years with ≥1 Ashkenazi Jewish grandparent were offered enrollment. Participants consented and enrolled online with chatbot and video education, underwent BRCA1/2 AJPV GT, and chose to receive results from their primary care provider (PCP) or study staff. Surveys were conducted at baseline, at 12 weeks, and annually for 5 years.ResultsA total of 5193 participants enrolled and 4109 (79.1%) were tested (median age = 54, female = 77.1%). Upon enrollment, 35.1% of participants selected a PCP to disclose results, and 40.5% of PCPs agreed. Of those tested, 138 (3.4%) were AJPV heterozygotes of whom 21 (15.2%) had no significant family history of cancer, whereas 86 (62.3%) had a known familial pathogenic variant. At 12 weeks, 85.5% of participants with AJPVs planned increased cancer screening; only 3.7% with negative results and a significant family history reported further testing.ConclusionAlthough continued follow-up is needed, internet-enabled outreach can expand access to targeted GT using a medical model. Observed challenges for population genetic screening efforts include recruitment barriers, improving PCP engagement, and increasing uptake of additional testing when indicated.     

Axenfeld�CRieger syndrome and spectrum of PITX2 and FOXC1 mutations

Axenfeld–Rieger syndrome (ARS) is a rare autosomal dominant disorder, which encompasses a range of congential malformations affecting the anterior segment of the eye. ARS shows genetic heterogeneity and mutations of the two genes, PITX2 and FOXC1, are known to be associated with the pathogenesis. There are several excellent reviews dealing with the complexity of the phenotype and genotype of ARS. In this study, we will attempt to give a brief review of the clinical features and the relevant diagnostic approaches, together with a detailed review of published PITX2 and FOXC1 mutations.     

Automating Angle Measurements on Foot Radiographs in Young Children: Feasibility and Performance of a Convolutional Neural Network Model

Journal of Digital Imaging - Measurement of angles on foot radiographs is an important step in the evaluation of malalignment. The objective is to develop a CNN model to measure angles on...     

Using Time-delay to Improve Social Play Skills with Peers for Children with Autism

Interventions that teach social communication and play skills are crucial for the development of children with autism. The time delay procedure is effective in teaching language acquisition, social use of language, discrete behaviors, and chained activities to individuals with autism and developmental delays. In this study, three boys with autism, attending a non-public school, were taught play activities that combined a play sequence with requesting peer assistance, using a graduated time delay procedure. A multiple-baseline across subjects design demonstrated the success of this procedure to teach multiple-step social play sequences. Results indicated an additional gain of an increase in pretend play by one of the participants. Two also demonstrated a generalization of the skills learned through the time delay procedure.