A Drug Screen using Human iPSC-Derived Hepatocyte-like Cells Reveals Cardiac Glycosides as a Potential Treatment for Hypercholesterolemia.

Efforts to identify pharmaceuticals to treat heritable metabolic liver diseases have been hampered by the lack of models. However, cells with hepatocyte characteristics can be produced from induced pluripotent stem cells (iPSCs). Here, we have used hepatocyte-like cells generated from homozygous familial hypercholesterolemia (hoFH) iPSCs to identify drugs that can potentially be repurposed to lower serum LDL-C.

Mapping the Cell-Surface N-Glycoproteome of Human Hepatocytes Reveals Markers for Selecting a Homogeneous Population of iPSC-Derived Hepatocytes.

When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes.

Aneuploidy is permissive for hepatocyte-like cell differentiation from human induced pluripotent stem cells.

Background: The characterization of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) routinely includes analyses of chromosomal integrity. The belief is that pluripotent stem cells best suited to the generation of differentiated derivatives should display a euploid karyotype; although, this does not appear to have been formally tested. While aneuploidy is commonly associated with cell transformation, several types of somatic cells, including hepatocytes, are frequently aneuploid and variation in chromosomal content does not contribute to a transformed phenotype.

Clinical, functional, and radiographic outcomes following total knee arthroplasty with patient-specific instrumentation, computer-assisted surgery, and manual instrumentation: a short-term follow-up study.

Purpose: The purpose of this study was to evaluate clinical, functional, and radiographic outcomes following total knee arthroplasty (TKA) performed with patient-specific instrumentation (PSI), computer-assisted surgery (CAS), and manual instruments at short-term follow-up.

Methods: 122 TKAs were performed by a single surgeon: 42 with PSI, 38 with CAS, and 40 with manual instrumentation. Preoperative, 1-month, and 6-month clinical and functional outcomes were measured using the Knee Society scoring system (knee score, function score, range of motion, and pain score).

Computer-assisted versus manual TKA: no difference in clinical or functional outcomes at 5-year follow-up.

The purpose of this study was to determine whether differences in clinical, functional, or radiographic outcomes existed at 5-year follow-up between patients who underwent computer-assisted or manual total knee arthroplasty (TKA). Seventy-eight consecutive TKAs were performed by a single surgeon who had extensive experience performing computer-assisted and manual TKA. The manual group (n=40) and computer-assisted group (n=38) were similar with regard to age, sex, diagnosis, body mass index, surgical technique, implants, perioperative management, Knee Society scores, and anteroposterior mechanical axis.

Stable, dependable fixation of short-stem femoral implants at 5 years.

Conventional uncemented femoral implants provide dependable long-term fixation in patients with a wide range of clinical function. However, challenges with proximal-distal femoral mismatch, preservation of bone stock, and minimally invasive approaches have led to exploration into various other implant designs. Short-stem designs focusing on a stable metaphyseal fit have emerged to address these challenges in total hip arthroplasty (THA).

Component sizing in total knee arthroplasty: patient-specific guides vs. computer-assisted navigation.

Introduction: Patient-specific guides (PSG) and computer-assisted navigation (CAN) are technologies that have been developed to improve the accuracy and reproducibility of total knee arthroplasty (TKA). The purpose of this study is to compare the methodology by which a PSG system and an intraoperative navigation system (CAN) perform an anatomical registration and correctly predict femoral component size in TKA.

Methods: One hundred and eleven PSG TKA were performed, 30 of which were concurrently evaluated with CAN.

JD induced pluripotent stem cell-derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia.

Unlabelled: Elevated levels of low-density lipoprotein cholesterol (LDL-C) in plasma are a major contributor to cardiovascular disease, which is the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified 95 loci that associate with control of lipid/cholesterol metabolism. Although GWAS results are highly provocative, direct analyses of the contribution of specific allelic variations in regulating LDL-C has been challenging due to the difficulty in accessing appropriate cells from affected patients.

Wound complications in joint arthroplasty: comparing traditional and modern methods of skin closure.

Various methods of skin closure exist in joint replacement surgery. Although subcuticular skin closure techniques offer an aesthetic advantage over conventional skin stapling, no measurable differences have been reported. Furthermore, newer barbed sutures, such as the V-Loc absorbable suture (Covidien, Mansfield, Massachusetts), theoretically distribute tension evenly through the wound and help decrease knot-related complications.

Thyroid hormone replacement in women of reproductive age: is surgeon knowledge related to operative volume?

Background: It is not known if surgeons who place women of reproductive age on thyroid hormone replacement (levothyroxine, LT4) routinely inform them of the increased LT4 demands with future pregnancy. In addition, it is not clear whether reading the 2007 Endocrine Society's "Guidelines on the Management of Thyroid Dysfunction during Pregnancy and Postpartum" influences the role of the surgeon in patient education. The objective of this study was to identify the role of the surgeon in patient education at the time of initiation of LT4 therapy.

Sodium butyrate activates Notch1 signaling, reduces tumor markers, and induces cell cycle arrest and apoptosis in pheochromocytoma.

Background: Pheochromocytoma is a neuroendocrine (NE) tumor of the adrenal medulla for which surgical resection is the only therapy. However, 10-46% of tumors are metastatic or have malignant features, and are often inoperable. Our lab has demonstrated the importance of the Notch1 signaling pathway in NE neoplasia, indicating that this pathway could be a target for emergent treatments in pheochromocytoma.

Papillary thyroid microcarcinomas: big decisions for a small tumor.

Background: The clinical significance of papillary thyroid microcarcinoma (PTMC) is debated, and therefore the rise in incidence of PTMC creates management dilemmas. The following study evaluates factors influencing decisions to treat.

Materials And Methods: Between 1994 and 2007, 1361 patients underwent thyroid surgery at a single institution.

Valproic acid activates Notch1 signaling and induces apoptosis in medullary thyroid cancer cells.

Objective: To examine the effects of valproic acid (VPA) on Notch1 expression and cancer cell proliferation in medullary thyroid cancer (MTC) cells.

Background: Other than surgery, there are no effective treatments for MTC, a neuroendocrine malignancy that frequently metastasizes. We have previously shown that over-expression of Notch1 in MTC cells inhibits cell growth and hormone production.

Suberoyl bishydroxamic acid inhibits cellular proliferation by inducing cell cycle arrest in carcinoid cancer cells.

Carcinoid cancers arise from the neuroendocrine cell system of the gastrointestinal tract, lungs, and other organs. Hepatic metastases are common, and patients often suffer from endocrinopathies secondary to tumor secretion of various hormones and peptides. As complete surgical resection is often not possible because of widespread disease, new therapeutic and palliative treatments are needed.