Minimally Invasive Treatment of Abdominal Pregnancy Implanted on the Ileocecal Junction.

We report a case of a 32-year-old gravida 1 para 0 with a copper intrauterine device in place and a newly diagnosed pregnancy at 5 weeks gestation. Serum human chorionic gonadotropin (hCG) was 23,940 mIU/mL and transvaginal ultrasound demonstrated a presumed right adnexal ectopic pregnancy with fetal cardiac activity. Upon laparoscopic entry, a 3 cm vascular mass consistent with ectopic pregnancy was noted densely adherent to the cecum, adjacent to the ileocecal junction. Given difficult tissue plane dissection and bleeding, a 4 cm mini-laparotomy was made and the mass was bluntly dissected away from the bowel implantation site. The bowel was oversewn. The patient's postoperative course was uncomplicated.

Impact of oviductal versus ovarian epithelial cell of origin on ovarian endometrioid carcinoma phenotype in the mouse.

Endometrioid carcinoma (EC) is a relatively indolent ovarian carcinoma subtype that is nonetheless deadly if detected late. Existing genetically engineered mouse models (GEMMs) of the disease, based on transformation of the ovarian surface epithelium (OSE), take advantage of known ovarian EC driver gene lesions, but do not fully recapitulate the disease features seen in patients. An EC model in which the Apc and Pten tumour suppressor genes are conditionally deleted in murine OSE yields tumours that are biologically more aggressive and significantly less differentiated than human ECs. Importantly, OSE is not currently thought to be the tissue of origin of most ovarian cancers, including ECs, suggesting that tumour initiation in Müllerian epithelium may produce tumours that more closely resemble their human tumour counterparts. We have developed Ovgp1-iCreERT2 mice in which the Ovgp1 promoter controls expression of tamoxifen (TAM)-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human Fallopian tube epithelium. Ovgp1-iCreERT2 ;Apcfl/fl ;Ptenfl/fl mice treated with TAM or injected with adenovirus expressing Cre into the ovarian bursa uniformly develop oviductal or ovarian ECs, respectively. On the basis of their morphology and global gene expression profiles, the oviduct-derived tumours more closely resemble human ovarian ECs than do OSE-derived tumours. Furthermore, mice with oviductal tumours survive much longer than their counterparts with ovarian tumours. The slow progression and late metastasis of oviductal tumours resembles the relatively indolent behaviour characteristic of so-called Type I ovarian carcinomas in humans, for which EC is a prototype. Our studies demonstrate the utility of Ovgp1-iCreERT2 mice for manipulating genes of interest specifically in the oviductal epithelium, and establish that the cell of origin is an important consideration in mouse ovarian cancer GEMMs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Differential requirements for H/ACA ribonucleoprotein components in cell proliferation and response to DNA damage.

H/ACA ribonucleoproteins (RNPs) are comprised of four conserved proteins, dyskerin, NHP2, NOP10, and GAR1, and a function-specifying, noncoding H/ACA RNA. H/ACA RNPs contribute to telomerase assembly and stabilization, and posttranscriptional processing of nascent ribosomal RNA and spliceosomal RNA. However, very little is known about the coordinated action of the four proteins in other biologic processes. As described herein, we observed a differential requirement for the proteins in cell proliferation and identified a possible reliance for these factors in regulation of specific DNA damage biomarkers. In particular, GAR1 expression was upregulated following exposure to all forms of genotoxic stress tested. In contrast, levels of the other proteins were either reduced or unaffected. Only GAR1 showed an altered subcellular localization with a shift from the nucleolus to the nucleoplasm after ultraviolet-C irradiation and doxorubicin treatments. Transient siRNA-mediated depletion of GAR1 and dyskerin arrested cell proliferation, whereas loss of either NHP2 or NOP10 had no effect. Finally, loss of dyskerin, GAR1, NHP2, and NOP10, respectively, limited the accumulation of DNA damage biomarkers. However, the individual responses were dependent upon the specific type of damage incurred. In general, loss of GAR1 had the most suppressive effect on the biomarkers tested. Since the specific responses to genotoxic stress, the contribution of each protein to cell proliferation, and the activation of DNA damage biomarkers were not equivalent, this suggests the possibility that at least some of the proteins, most notably GAR1, may potentially function independently of their respective roles within H/ACA RNP complexes.

Conserved quantities of Euler-Lagrange system via complex Lagrangian.

In this work we use complex Lagrangian technique to obtain Noether-like operators and the associated conserved quantities of an Euler-Lagrange (EL) system. We show that the three new conserved quantities namely, Noether conserved quantity, Lie conserved quantity and Mei conserved quantity reported by Fang et al. [1] for an EL-system and even more in numbers by Nucci [2] can also be obtained via complex variational formalism. Generally, a linear system of EL-equations possesses maximum 8-dimensional algebra of Noether symmetries and Noether's theorem yields related 8-first integrals. However, our methodology produces 10 Noether-like operators and 10 corresponding invariant quantities for the underlying system of equations. Among those ten first integrals, three (as named above) are reminiscent to those found in [1]. In addition, from the remaining list of conserved quantities several are similar to those reported in [2]. Moreover, the current study presents an alternative approach to compute invariant quantities of EL-systems and leads to interesting and fascinating results.

Exploring Muslim Women's Reproductive Health Needs and Preferences in the Emergency Department.

Objective: We explored individual Muslim women's reproductive healthcare experiences, preferences, beliefs, and behaviors in the emergency department (ED) and in general. Methods: This was a qualitative study conducted at a community ED using semi-structured interviews with a piloted interview guide. We interviewed participants awaiting care in the ED with the following criteria: female gender; English or Arabic speaking; aged ≥18 years; and self-identified as Muslim. We conducted interviews in both English and Arabic until thematic saturation was reached. Transcripts were coded using an iteratively developed codebook, maintaining intercoder agreement greater than 80%. We used an inductive thematic analysis to identify themes, and results were interpreted in the context of interview language and patient's age. Results: We interviewed 26 Muslim-identified female ED patients. We found that cultural representation and sensitivity among ED staff mitigated discrimination and promoted inclusion for Muslim ED patients. However, assumptions about Muslim identity also impacted the participants' healthcare. Most participants endorsed a preference for a female clinician for their reproductive healthcare in general, but not necessarily for other areas of medicine. Clinician cultural concordance was not always preferred for participants in the ED due to fears about the loss of confidentiality. Marital status impacted beliefs about reproductive and sexual health in the context of Muslim identity. Overall, family planning was acceptable and encouraged in this patient population. Conclusion: The themes elucidated in this study may guide clinicians in developing culturally sensitive practices when providing reproductive healthcare to the Muslim population.

Novel Internet of Things based approach toward diabetes prediction using deep learning models.

The integration of the Internet of Things with machine learning in different disciplines has benefited from recent technological advancements. In medical IoT, the fusion of these two disciplines can be extremely beneficial as it allows the creation of a receptive and interconnected environment and offers a variety of services to medical professionals and patients. Doctors can make early decisions to save a patient's life when disease forecasts are made early. IoT sensor captures the data from the patients, and machine learning techniques are used to analyze the data and predict the presence of the fatal disease i.e., diabetes. The goal of this research is to make a smart patient's health monitoring system based on machine learning that helps to detect the presence of a chronic disease in patient early and accurately. For the implementation, the diabetic dataset has been used. In order to detect the presence of the fatal disease, six different machine learning techniques are used i.e., Support Vector Machine (SVM), Logistic Regression, Artificial Neural Network (ANN), Convolutional Neural Network (CNN), Recurrent Neural Network (RNN), and Long Short-Term Memory (LSTM). The performance of the proposed model is evaluated by using four evaluation metrics i.e., accuracy, precision, recall, and F1-Score. The RNN outperformed remaining algorithms in terms of accuracy (81%), precision (75%), and F1-Score (65%). However, the recall (56%) for ANN was higher as compared to SVM and logistic regression, CNN, RNN, and LSTM. With the help of this proposed patient's health monitoring system, doctors will be able to diagnose the presence of the disease earlier.

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer.

Orthotopic tumor modeling is a valuable tool for pre-clinical prostate cancer research, as it has multiple advantages over both subcutaneous and transgenic genetically engineered mouse models. Unlike subcutaneous tumors, orthotopic tumors contain more clinically accurate vasculature, tumor microenvironment, and responses to multiple therapies. In contrast to genetically engineered mouse models, orthotopic models can be performed with lower cost and in less time, involve the use of highly complex and heterogeneous mouse or human cancer cell lines, rather that single genetic alterations, and these cell lines can be genetically modified, such as to express imaging agents. Here, we present a protocol to surgically injecting a luciferase- and mCherry-expressing murine prostate cancer cell line into the anterior prostate lobe of mice. These mice developed orthotopic tumors that were non-invasively monitored in vivo and further analyzed for tumor volume, weight, mouse survival, and immune infiltration. Further, orthotopic tumor-bearing mice were surgically castrated, leading to immediate tumor regression and subsequent recurrence, representing castration-resistant prostate cancer. Although technical skill is required to carry out this procedure, this syngeneic orthotopic model of both androgen-dependent and castration-resistant prostate cancer is of great use to all investigators in the field.

Multi-faceted immunomodulatory and tissue-tropic clinical bacterial isolate potentiates prostate cancer immunotherapy.

Immune checkpoint inhibitors have not been effective for immunologically "cold" tumors, such as prostate cancer, which contain scarce tumor infiltrating lymphocytes. We hypothesized that select tissue-specific and immunostimulatory bacteria can potentiate these immunotherapies. Here we show that a patient-derived prostate-specific microbe, CP1, in combination with anti-PD-1 immunotherapy, increases survival and decreases tumor burden in orthotopic MYC- and PTEN-mutant prostate cancer models. CP1 administered intra-urethrally specifically homes to and colonizes tumors without causing any systemic toxicities. CP1 increases immunogenic cell death of cancer cells, T cell cytotoxicity, and tumor infiltration by activated CD8 T cells, Th17 T cells, mature dendritic cells, M1 macrophages, and NK cells. CP1 also decreases intra-tumoral regulatory T cells and VEGF. Mechanistically, blocking CP1-recruited T cells from infiltrating the tumor inhibits its therapeutic efficacy. CP1 is an immunotherapeutic tool demonstrating how a tissue-specific microbe can increase tumor immunogenicity and sensitize an otherwise resistant cancer type to immunotherapy.

Organoids model distinct Vitamin E effects at different stages of prostate cancer evolution.

Vitamin E increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) through unknown mechanisms while Selenium showed no efficacy. We determined the effects of the SELECT supplements on benign (primary), premalignant ( RWPE-1) and malignant (LNCaP) prostate epithelial organoids. While the supplements decreased proliferation and induced cell death in cancer organoids, they had no effect on the benign organoids. In contrast, Vitamin E enhanced cell proliferation and survival in the premalignant organoids in a manner that recapitulated the SELECT results. Indeed, while Vitamin E induced a pro-proliferative gene expression signature, Selenium alone or combined with Vitamin E produced an anti-proliferative signature. The premalignant organoids also displayed significant downregulation of glucose transporter and glycolytic gene expression pointing to metabolic alterations. Detached RWPE-1 cells had low ATP levels due to diminished glucose uptake and glycolysis which was rescued by Vitamin E through the activation of fatty acid oxidation (FAO). FAO inhibition abrogated the ATP rescue, diminished survival of the inner matrix detached cells, restoring the normal hollow lumen morphology in Vitamin E treated organoids. Organoid models therefore clarify the paradoxical findings from SELECT and demonstrate that Vitamin E promotes tumorigenesis in the early stages of prostate cancer evolution.

Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation.

Identification of defined cell populations with stem/progenitor properties is key for understanding prostate development and tumorigenesis. Here we show that the polycomb repressor protein Bmi1 marks a population of castration-resistant luminal epithelial cells enriched in the mouse proximal prostate. We employ lineage tracing to show that these castration-resistant Bmi1-expressing cells (or CARBs) are capable of tissue regeneration and self-renewal. Notably, CARBs are distinct from the previously described luminal castration-resistant Nkx3.1-expressing cells (CARNs). CARBs can serve as a prostate cancer cell-of-origin upon Pten deletion, yielding luminal prostate tumours. Clonal analysis using the R26R-confetti allele indicates preferential tumour initiation from CARBs localized to the proximal prostate. These studies identify Bmi1 as a marker for a distinct population of castration-resistant luminal epithelial cells enriched in the proximal prostate that can serve as a cell of origin for prostate cancer.