Onset and Progression of Disease in Nonhuman Primates With PDE6C Cone Disorder.

Purpose: The California National Primate Research Center contains a colony of rhesus macaques with a homozygous missense mutation in PDE6C (R565Q) which causes a cone disorder similar to PDE6C achromatopsia in humans. The purposes of this study are to characterize the phenotype in PDE6C macaques in detail to determine the onset of the cone phenotype, the degree to which the phenotype progresses, if heterozygote animals have an intermediate phenotype, and if rod photoreceptor function declines over time.

Methods: We analyzed spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and electroretinography (ERG) data from 102 eyes of 51 macaques (aged 0.

Induction of in vivo-like ciliation in confluent monolayers of re-differentiated equine oviduct epithelial cells†.

We recently developed re-differentiated equine oviduct epithelial cell (REOEC) monolayers demonstrating various in vivo morphological characteristics, but lacking secondary ciliation. In this study, we evaluated the effects of fetal bovine serum, reproductive steroid hormones, Wnt- and Notch ligands and inhibitors, and different EOEC seeding densities, in both conventional wells and on microporous membranes, on EOEC morphology and, in particular, secondary ciliation. REOEC monolayers were assessed by confocal microscopy after combined staining of nuclei, cilia, and the cytoskeleton.

Effect of duration of estradiol exposure on embryo survival and endometrial gene expression in anestrous embryo recipient mares.

Previous studies indicate a positive correlation between the duration of estrus prior to ovulation and likelihood of pregnancy in embryo recipient mares. However, the mechanisms by which the duration of estrus before may affect fertility remains unclear. This study aimed to determine the effect of different durations of estradiol exposure, prior to progesterone administration, on embryo viability in anestrous recipient mares, and endometrial expression of genes thought to influence embryo survival.

De novo reconstruction of a functional in vivo-like equine endometrium using collagen-based tissue engineering.

To better understand molecular aspects of equine endometrial function, there is a need for advanced in vitro culture systems that more closely imitate the intricate 3-dimensional (3D) in vivo endometrial structure than current techniques. However, development of a 3D in vitro model of this complex tissue is challenging. This study aimed to develop an in vitro 3D endometrial tissue (3D-ET) with an epithelial cell phenotype optimized by treatment with a Rho-associated protein kinase (ROCK) inhibitor.

Ultrasound-guided fetal thorax compression to reduce post-fixation twins in the mare.

Background: Management of twin pregnancy after conceptus vesicle fixation in the horse is challenging because the reduction techniques described are either invasive, difficult to perform or associated with disappointing success rates.

Objectives: To evaluate the success of transrectal ultrasound-guided fetal thorax compression for reducing post-fixation twin pregnancy in mares.

Study Design: Retrospective clinical study.

Stepping outside national borders: International active learning educational collaboration events.

Aim: This paper discusses the benefits of international collaborations for advanced practice nursing education. It identifies new perspectives and innovative practices to enhance cultural competency.

Background: Competent, well-trained advanced practice nurses (APNs) are necessary to provide high-quality and safe patient care, improve access to care, and address health disparities that are no longer geographically bound.

Technique and outcomes of robotic-assisted retroperitoneal radical nephrectomy.

Background: Robotic retroperitoneal partial nephrectomy (rRPN) has numerous advantages over transperitoneal surgery, including direct access to the renal hilum and posterior tumors, and avoidance of the peritoneal cavity in patients with a hostile abdomen. Although the use of the retroperitoneal approach has increased over the last decade, there is little literature on robotic retroperitoneal radical nephrectomy (rRRN), which has similar benefits over the transperitoneal approach. The aim of this study was to describe our technique for robotic retroperitoneal nephrectomy (rRN) and assess its feasibility and outcomes at a high-volume center.

Immediate gemcitabine bladder instillation following bladder closure during robotic-assisted radical nephroureterectomy: a multi-institutional report of feasibility and initial outcomes.

Background: Bladder recurrence after radical nephroureterectomy (RNU) is common and randomized data supports utilization of prophylactic intravesical mitomycin to reduce recurrence. Recently, gemcitabine has been shown to be safe and effective at reducing recurrence following transurethral resection of bladder tumors. We sought to evaluate the safety and efficacy of a single, intraoperative gemcitabine instillation immediately following bladder cuff closure during RNU, and to compare outcomes with non-gemcitabine intravesical chemotherapy agents.

Robotic Partial Radical Nephrectomy for Clinical T3a Tumors: A Narrative Review.

T3a renal masses include a diverse group of tumors that invade the perirenal and/or sinus fat, pelvicaliceal system, or renal vein. The majority of cT3a renal masses represent renal cell carcinoma (RCC) and have historically been treated with radical nephrectomy (RN) given their aggressive nature. With the adoption of minimally invasive approaches to renal surgery, the combination of improved observation, pneumoperitoneum, and robotic articulation has allowed urologists to consider partial nephrectomy (PN) for more complex tumors.

Multi-institutional feasibility and safety outcomes of retroperitoneal robot-assisted partial nephrectomy in morbidly obese patients.

Background: Robotic-assisted partial nephrectomy (RAPN) is an established treatment modality for small renal masses. While retroperitoneal RAPN (rRAPN) has the benefit of avoiding the peritoneal cavity and provides more direct access to the renal hilum and posterior kidney, there is concern about the feasibility of rRAPN particularly in morbidly obese [body mass index (BMI) ≥40 kg/m] patients. We present a large scale multi-institutional study on the outcomes of rRAPN in morbidly obese patients.

In Vitro-Produced Equine Blastocysts Exhibit Greater Dispersal and Intermingling of Inner Cell Mass Cells than In Vivo Embryos.

In vitro production (IVP) of equine embryos is increasingly popular in clinical practice but suffers from higher incidences of early embryonic loss and monozygotic twin development than transfer of in vivo derived (IVD) embryos. Early embryo development is classically characterized by two cell fate decisions: (1) first, trophectoderm (TE) cells differentiate from inner cell mass (ICM); (2) second, the ICM segregates into epiblast (EPI) and primitive endoderm (PE). This study examined the influence of embryo type (IVD versus IVP), developmental stage or speed, and culture environment (in vitro versus in vivo) on the expression of the cell lineage markers, CDX-2 (TE), SOX-2 (EPI) and GATA-6 (PE).

Multiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2-, PIK3CA-mutated breast cancers.

Background: Mutations in the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), encoded by the PIK3CA gene, cause dysregulation of the PI3K pathway in 35-40% of patients with HR+/HER2- breast cancer. Preclinically, cancer cells harboring double or multiple PIK3CA mutations (mut) elicit hyperactivation of the PI3K pathway leading to enhanced sensitivity to p110α inhibitors.

Methods: To understand the role of multiple PIK3CAmut in predicting response to p110α inhibition, we estimated the clonality of multiple PIK3CAmut in circulating tumor DNA (ctDNA) from patients with HR+/HER2- metastatic breast cancer enrolled to a prospectively registered clinical trial of fulvestrant ± taselisib, and analyzed the subgroups against co-altered genes, pathways, and outcomes.

DNA barcodes reveal different speciation scenarios in the four North American Anthocharis Boisduval, Rambur, [Duménil] & Graslin, [1833] (Lepidoptera: Pieridae: Pierinae: Anthocharidini) species groups.

The mitochondrial DNA COI barcode segment sequenced from American Anthocharis specimens across their distribution ranges partitions them into four well-separated species groups and reveals different levels of differentiation within these groups. The lanceolata group experienced the deepest divergence. About 2.

Vitrifying expanded equine embryos collapsed by blastocoel aspiration is less damaging than slow-freezing.

The cryotolerance of equine blastocysts larger than 300 μm can be improved by aspirating blastocoele fluid prior to vitrification; however, it is not known whether blastocoele aspiration also enables successful slow-freezing. The aim of this study was therefore to determine whether slow-freezing of expanded equine embryos following blastocoele collapse was more or less damaging than vitrification. Grade 1 blastocysts recovered on day 7 or 8 after ovulation were measured (>300-550 μm, n = 14 and > 550 μm, n = 19) and blastocoele fluid was aspirated prior to slow-freezing in 10% glycerol (n = 14), or vitrification (n = 13) in 16.

ER+, HER2- advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes.

Taselisib is a potent β-sparing phosphatidylinositol 3-kinase (PI3K) inhibitor that, with endocrine therapy, improves outcomes in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated (PIK3CAmut) advanced breast cancer. To understand alterations associated with response to PI3K inhibition, we analysed circulating tumour DNA (ctDNA) from participants enrolled in the SANDPIPER trial. Participants were designated as either PIK3CAmut or PIK3CA no mutation was detected (NMD) per baseline ctDNA.

In vitro aging of stallion spermatozoa during prolonged storage at 5°C.

Artificial insemination with chilled stallion semen is hampered by a limited period of maximum fertility maintenance (24-48 h). This study used multiparametric flow cytometry to simultaneously measure reactive oxygen species (ROS) production, mitochondrial function or [Ca ] and plasma membrane fluidity in viable, acrosome-intact spermatozoa, with the aim of providing insight into changes in sperm function during storage at 5°C. High proportions of viable and acrosome-intact spermatozoa (71 ± 8%) remained after 96 h of storage demonstrating that the basic integrity of the cells was well preserved (n = 17 stallions).

Comparison of Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations.

Purpose: Understanding the differences in biomarker prevalence that may exist among diverse populations is invaluable to accurately forecast biomarker-driven clinical trial enrollment metrics and to advance inclusive research and health equity. This study evaluated the frequency and types of mutations (mut) detected in predicted genetic ancestry subgroups across breast cancer (BC) subtypes.

Methods: Analyses were conducted using real-world genomic data from adult patients with BC treated in an academic or community setting in the United States and whose tumor tissue was submitted for comprehensive genomic profiling.

Insulin-like growth factor system components expressed at the conceptus-maternal interface during the establishment of equine pregnancy.

In many species, the insulin-like growth factors (IGF1 and IGF2), their receptors and IGF binding proteins play important roles in preparing the endometrium for implantation, and regulating conceptus growth and development. To determine whether the IGF system may contribute to conceptus-maternal interaction during equine pre-implantation development, we evaluated mRNA expression for IGF system components in conceptuses, and endometrium recovered from pregnant and cycling mares, on days 7, 14, 21 and 28 after ovulation. We also investigated expression of IGF1, IGF2 and their receptors 6 and 11 days after transfer of day 8 embryos to synchronous (day 8) or asynchronous (day 3) recipient mares.

Growth-rate model predicts in vivo tumor response from in vitro data.

A major challenge in oncology drug development is to elucidate why drugs that show promising results in cancer cell lines in vitro fail in mouse studies or human trials. One of the fundamental steps toward solving this problem is to better predict how in vitro potency translates into in vivo efficacy. A common approach to infer whether a model will respond in vivo is based on in vitro half-maximal inhibitory concentration values (IC ), but yields limited quantitative comparison between cell lines and drugs, potentially because cell division and death rates differ between cell lines and in vivo models.

Atmospheric turbulence effects on shaped and unshaped sonic boom signatures.

Atmospheric turbulence is known to randomly distort the "N-wave" sonic boom signature emitted by conventional, unshaped supersonic aircraft. To predict the effect of turbulence on the signature from shaped aircraft, a numerical model has been developed based on the nonlinear Khokhlov-Zabolotskaya-Kuznetzov (KZK) propagation equation coupled with an approximate atmospheric turbulence model. The effects of turbulence on an archetypal N-wave and a shaped signature are compared via a series of numerical experiments propagating the signatures through multiple random realizations of turbulence in varying atmospheric and propagation conditions.