iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines

Informatics Enhanced SNP Microarray Analysis of 30 Miscarriage Samples Compared to Routine Cytogenetics

Purpose: The metaphase karyotype is often used as a diagnostic tool in the setting of early miscarriage; however this technique has several limitations. We evaluate a new technique for karyotyping that uses single nucleotide polymorphism microarrays (SNP). This technique was compared in a blinded, prospective fashion, to the traditional metaphase karyotype. Methods: Patients undergoing dilation and curettage for first trimester miscarriage between February and August 2010 were enrolled. Samples of chorionic villi were equally divided and sent for microarray testing in parallel with routine cytogenetic testing. Results: Thirty samples were analyzed, with only four discordant results. Discordant results occurred when the entire genome was duplicated or when a balanced rearrangement was present. Cytogenetic karyotyping took an average of 29 days while microarray-based karytoyping took an average of 12 days. Conclusions: Molecular karyotyping of POC after missed abortion using SNP microarray analysis allows for the ability to detect maternal cell contamination and provides rapid results with good concordance to standard cytogenetic analysis

Incidental Bladder Cancer at the Time of Routine Cystoscopy following Laparoscopic Hysterectomy

Three patients with abnormal uterine bleeding underwent uncomplicated minimally invasive total hysterectomy with routine cystoscopy. At time of cystoscopy, the patients had unexpected findings of bladder masses and postoperatively were expeditiously referred to urology. Final pathology for all revealed low-grade urologic carcinoma. The patients were treated with transurethral excision and are currently in surveillance without concern for recurrence. All three patients were asymptomatic at time of diagnosis. If the masses were not identified at the time of hysterectomy with cystoscopy, it is unclear when the patients may have developed symptoms to warrant a workup and likely would have experienced progression of the malignancy during that time. We hope this case series showcases that abnormal bladder masses are easily identifiable by the benign gynecologist at time of cystoscopy and illustrates another benefit of routine cystoscopy at time of hysterectomy

Can people be sentinels of sustainability? Identifying the linkages among ecosystem health and human well-being

Human well-being depends on the health of ecosystems, but can human well-being also be an indicator of ecosystem health, and perhaps even sustainability? Research shows that ecosystem health and human well-being are often mutually reinforcing, whether in the direction of wellness and sustainability or poverty and degradation. However, while well-being is increasingly recognized as an important consideration when managing ecosystems, human needs and activities are often still thought of only in terms of their negative impacts on ecosystems. In this essay, we explore the proposition that there can be a mutually constitutive relationship between people’s well-being and the health of ecosystems, and discuss what such a relationship would mean for expanding the use of human well-being indicators in ecosystem-based management. Specifically, we discuss two areas of theory: ecosocial theory from social epidemiology and the marginalization–degradation thesis in political ecology; collectively, these provide a justification, in certain circumstances at least, for thinking of well-being as not just an add-on in natural resource management but as an indicator of ecosystem health and a prerequisite of social-ecological sustainability. We conclude with a discussion of future research needs to further explore how human well-being and ecosystem health interact

Intraoperative Factors Associated with More Postoperative Opioid Use after Laparoscopic Hysterectomy

Background and objectivesTo identify intraoperative factors during laparoscopic hysterectomy associated with postoperative opioid use and increased pain scores during the acute postoperative period.MethodsThis is a prospective survey-based cohort study at two teaching hospitals in the Boston metropolitan area. A total of 125 patients undergoing laparoscopic hysterectomy were enrolled. Surveys were administered by telephone at one-week postoperatively and in-person at their two-week postoperative visit to elicit opioid consumption converted to morphine milligram equivalents (MMEs) and pain scores.ResultsThe median total opioid consumption was 37.5 MME (range 0-960 MMEs). Intraoperative factors associated with increased total MME consumption were lower uterine weight and resection of endometriosis at the time of surgery. Patients with uteri less than 250 grams used twice as much opioid compared to participants with uteri greater than 250 grams (median of 49.8 MME (interquartile range [IQR] 7.5-120.5) vs. 22.5 MME (IQR 7.5-61.0). The median opioid consumption by patients with resection or ablation of endometriosis was three times that of those who did not undergo surgical treatment of endometriosis (97.0 MME (IQR 53.1-281.3) vs. 30.0 MMEs (IQR 7.5-81.3 MME)). Maximum pain scores and reported pain score at one and two-week interviews were also significantly higher in patients with these characteristics.ConclusionSeveral easily identified intraoperative factors may be correlated with opioid requirements during the acute postoperative period. This can allow surgeons to set expectations and dispense patient-specific opioid prescriptions. Individualizing prescriptions may lower the amount of excess circulating opioids and help combat the opioid epidemic

Physiomimetic Models of Adenomyosis

© 2020 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Adenomyosis remains an enigmatic disease in the clinical and research communities. The high prevalence, diversity of morphological and symptomatic presentations, array of potential etiological explanations, and variable response to existing interventions suggest that different subgroups of patients with distinguishable mechanistic drivers of disease may exist. These factors, combined with the weak links to genetic predisposition, make the entire spectrum of the human condition challenging to model in animals. Here, after an overview of current approaches, a vision for applying physiomimetic modeling to adenomyosis is presented. Physiomimetics combines a system's biology analysis of patient populations to generate hypotheses about mechanistic bases for stratification with in vitro patient avatars to test these hypotheses. A substantial foundation for three-dimensional (3D) tissue engineering of adenomyosis lesions exists in several disparate areas: epithelial organoid technology; synthetic biomaterials matrices for epithelial-stromal coculture; smooth muscle 3D tissue engineering; and microvascular tissue engineering. These approaches can potentially be combined with microfluidic platform technologies to model the lesion microenvironment and can potentially be coupled to other microorgan systems to examine systemic effects. In vitro patient-derived models are constructed to answer specific questions leading to target identification and validation in a manner that informs preclinical research and ultimately clinical trial design

Demographic data.^a

a<p>Results expressed as mean and range, with exceptions noted.</p>b<p>In 10 of the 30 cases, no fetal pole was present, with only a gestational sac visualized on ultrasound.</p

Karyotype results of 30 cases analyzed by both SNP micro arrays and cytogenetics.

*<p>Autosomal Trisomies identified (2,3,13,14,15,16,18,20,22).</p>**<p>One unbalanced translocation detected by both methods 46,XX, der (14)t(3;14)(p21;q32)mat.</p><p>One unbalanced robertsonian translocation 46,XY,+15,der(15;15)(q10;q10) was reported as trisomy 15 by SNP micro array.</p