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Context: Obesity is a disease with deleterious effects on the female reproductive tract, including the endometrium., Objective: We sought to understand the effects of excess adipose on the benign endometrium., Methods: A physiologic in vitro coculture system was developed, consisting of multicellular human endometrial organoids, adipose spheroids, and menstrual cycle hormones. Native human endometrial tissue samples from women with and without obesity were also analyzed. Benign endometrial tissues from premenopausal women ages 33 to 53 undergoing hysterectomy were obtained following written consent at Northwestern University Prentice Women's Hospital, Chicago, Illinois. Gene expression, protein expression, chromatin binding, and expression of DNA damage and oxidative damage markers were measured., Results: Under high adiposity conditions, endometrial organoids downregulated endometrial secretory phase genes, suggestive of an altered progesterone response. Progesterone specifically upregulated the metallothionein (MT) gene family in the epithelial cells of endometrial organoids, while high adiposity significantly downregulated the MT genes. Silencing MT genes in endometrial epithelial cells resulted in increased DNA damage, illustrating the protective role of MTs. Native endometrium from women with obesity displayed increased MT expression and oxidative damage in the stroma and not in the epithelium, indicating the cell-specific impact of obesity on MT genes., Conclusion: Taken together, the in vitro and in vivo systems used here revealed that high adiposity or obesity can alter MT expression by decreasing progesterone response in the epithelial cells and increasing oxidative stress in the stroma., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Physiologically relevant in vitro models of the human outer retina are required to better elucidate the complex interplay of retinal tissue layers and investigate their role in retinal degenerative disorders. Materials currently used to mimic the function of Bruch's membrane fail to replicate a range of important structural, mechanical, and biochemical properties. Here, we detail the fabrication of a surface-functionalized, fibrous collagen I membrane. We demonstrate its ability to better replicate a range of important material properties akin to the function of human Bruch's membrane when compared with a commonly utilized synthetic polyethylene terephthalate alternative. We further reveal the ability of this membrane to support the culture of the ARPE-19 cell line, as well as human pluripotent stem cell-derived RPE-like cells and human umbilical vein endothelial cells. This material could provide greater physiological relevance to the native Bruch's membrane than current synthetic materials and further improve the outcomes of in vitro outer retinal models.

Intracranial aneurysms (IAs) are present in 2-6% of the global population and can be catastrophic upon rupture with a mortality rate of 30-50%. IAs are commonly detected through time-of-flight magnetic resonance angiography (TOF-MRA), however, this data is rarely available for research and training purposes. The provision of imaging resources such as TOF-MRA images is imperative to develop new strategies for IA detection, rupture prediction, and surgical training. To support efforts in addressing data availability bottlenecks, we provide an open-access TOF-MRA dataset comprising 63 patients, of which 24 underwent interval surveillance imaging by TOF-MRA. Patient scans were evaluated by a neuroradiologist, providing aneurysm and vessel segmentations, clinical annotations, 3D models, in addition to 3D Slicer software environments containing all this data for each patient. This dataset is the first to provide interval surveillance imaging for supporting the understanding of IA growth and stability. This dataset will support computational and experimental research into IA dynamics and assist surgical and radiology training in IA treatment., (© 2024. The Author(s).)

Background: Hypertension is a leading cause of cardiovascular and kidney disease in the United States, yet blood pressure (BP) control at a population level is poor and worsening. Systematic home BP monitoring (HBPM) programs can lower BP, but programs supporting HBPM are not routinely used. The MyBP program deploys automated bidirectional text messaging for HBPM and disease self-management support., Objective: We aim to produce a qualitative analysis of input from providers and staff regarding implementation of an innovative HBPM program in primary care practices., Methods: Semistructured interviews (average length 31 minutes) were conducted with physicians (n=11), nurses, and medical assistants (n=6) from primary care settings. The interview assessed multiple constructs in the Consolidated Framework for Implementation Research domains of intervention characteristics, outer setting, inner setting, and characteristics of individuals. Interviews were transcribed verbatim and analyzed using inductive coding to organize meaningful excerpts and identify salient themes, followed by mapping to the updated Consolidated Framework for Implementation Research constructs., Results: Health care providers reported that MyBP has good ease of use and was likely to engage patients in managing their high BP. They also felt that it would directly support systematic BP monitoring and habit formation in the convenience of the patient's home. This could increase health literacy and generate concrete feedback to raise the day-to-day salience of BP control. Providers expressed concern that the cost of BP devices remains an encumbrance. Some patients were felt to have overriding social or emotional barriers, or lack the needed technical skills to interact with the program, use good measurement technique, and input readings accurately. With respect to effects on their medical practice, providers felt MyBP would improve the accuracy and frequency of HBPM data, and thereby improve diagnosis and treatment management. The program may positively affect the patient-provider relationship by increasing rapport and bidirectional accountability. Providers appreciated receiving aggregated HBPM data to increase their own efficiency but also expressed concern about timely routing of incoming HBPM reports, lack of true integration with the electronic health record, and the need for a dedicated and trained staff member., Conclusions: In this qualitative analysis, health care providers perceived strong relative advantages of using MyBP to support patients. The identified barriers suggest the need for corrective implementation strategies to support providers in adopting the program into routine primary care practice, such as integration into the workflow and provider education., Trial Registration: ClinicalTrials.gov NCT03650166; https://tinyurl.com/bduwn6r4., (©Julian Einhorn, Andrew R Murphy, Shari S Rogal, Brian Suffoletto, Taya Irizarry, Bruce L Rollman, Daniel E Forman, Matthew F Muldoon. Originally published in JMIR Cardio (https://cardio.jmir.org), 04.12.2023.)

The increasing gap between clinical demand for tissue or organ transplants and the availability of donated tissue highlights the emerging opportunities for lab-grown or synthetically engineered tissue. While the field of tissue engineering has existed for nearly half a century, its clinical translation remains unrealised, in part, due to a limited ability to engineer sufficient vascular supply into fabricated tissue, which is necessary to enable nutrient and waste exchange, prevent cellular necrosis, and support tissue proliferation. Techniques to develop anatomically relevant, functional vascular networks in vitro have made significant progress in the last decade, however, the challenge now remains as to how best incorporate these throughout dense parenchymal tissue-like structures to address diffusion-limited development and allow for the fabrication of large-scale vascularised tissue. This review explores advances made in the laboratory engineering of vasculature structures and summarises recent attempts to integrate vascular networks together with sophisticated in vitro avascular tissue and organ-like structures. STATEMENT OF SIGNIFICANCE: The ability to grow full scale, functional tissue and organs in vitro is primarily limited by an inability to adequately diffuse oxygen and nutrients throughout developing cellularised structures, which generally results from the absence of perfusable vessel networks. Techniques to engineering both perfusable vascular networks and avascular miniaturised organ-like structures have recently increased in complexity, sophistication, and physiological relevance. However, integrating these two essential elements into a single functioning vascularised tissue structure represents a significant spatial and temporal engineering challenge which is yet to be surmounted. Here, we explore a range of vessel morphogenic phenomena essential for tissue-vascular co-development, as well as evaluate a range of recent noteworthy approaches for generating vascularised tissue products in vitro., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Fluorescent proteins (FPs) are a powerful tool for examining tissues, cells, and subcellular components in vivo and in vitro. FusionRed is a particular FP variant mutated from mKate2 that, in addition to lower cytotoxicity and aggregation rates, has shown potential for acting as a tunable photoswitch. This was posited to stem partially from the presence of a bulky side chain at position 158 and a further stabilizing residue at position 157. In this work, we apply computational techniques including classical molecular dynamics (MD) and combined quantum mechanics/molecular mechanics simulations (QM/MM) to explore the effect of mutagenesis at these locations in FusionRed on the chromophore structure, the excited-state surface, and relative positional stability of the chromophore in the protein pocket. We find specific connections between the statistical sampling of the underlying protein structure and the nonradiative decay mechanisms from excited-state dynamics. A single mutation (C158I) that restricts the motion of the chromophore through a favorable hydrophobic interaction corresponds to an increase in fluorescence quantum yield (FQY), while a second rescue mutation (C158I-A157N) partially restores the flexibility of the chromophore and photoswitchability with favorable water interactions on the surface of the protein that counteracts the original interaction. We suggest that applying this understanding of structural features that inhibit or favor rotation on the excited state can be applied for rational design of new, tunable and red photoswitches., (© 2023 Wiley-VCH GmbH.)

African American (AA) prostate cancer associates with vitamin D 3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH) 2 D 3 -regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH) 2 D 3 -dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH) 2 D 3 -regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH) 2 D 3 -dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function., Significance: Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Each month during a woman's reproductive years, the endometrium undergoes vast changes to prepare for a potential pregnancy. Diseases of the endometrium arise for numerous reasons, many of which remain unknown. These endometrial diseases, including endometriosis, adenomyosis, endometrial cancer and Asherman syndrome, affect many women, with an overall lack of efficient or permanent treatment solutions. The challenge lies in understanding the complexity of the endometrium and the extensive changes, orchestrated by ovarian hormones, that occur in multiple cell types over the period of the menstrual cycle. Appropriate model systems that closely mimic the architecture and function of the endometrium and its diseases are needed. The emergence of organoid technology using human cells is enabling a revolution in modelling the endometrium in vitro. The goal of this Review is to provide a focused reference for new models to study the diseases of the endometrium. We provide perspectives on the power of new and emerging models, from organoids to microfluidics, which have opened up a new frontier for studying endometrial diseases., (© 2022. Springer Nature Limited.)

The journal, Higher Education (HE), was established in 1972 and is currently one of the leading international journals in higher education studies. By using bibliometric techniques, a systematic review, and a social network analysis, this review article provides an overview of the main patterns of publications in HE during its history. The findings show that (i) the volume of articles has been continuously increasing, with a particular marked uplift since 2007; (ii) while single-authored articles have dominated the publication pattern, collaborative articles have shown a particular growth over the last decade; (iii) the USA, the UK, and Australia have dominated the journal in terms of the number of articles, international collaboration, and the most prolific authors; (iv) while Chinese authors have become more evident, there has been a near-absence of contributions from Latin America, Eastern Europe, and most of Africa; (v) in the entire history of HE , there has been a gender imbalance (in favour of male authors) across the most cited articles, but this pattern has changed in the last decade and; (vi) both teaching and learning and system policy have been key research themes in the journal although internationalisation and the student experience have recently gained traction. These patterns of publication in HE , with their imbalances and absences, suggest several challenges ahead., Supplementary Information: The online version contains supplementary material available at 10.1007/s10734-022-00924-7., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: The American Association of Colleges of Pharmacy's vision statement is part of a national strategic endeavor to elevate pharmacy's professional profile. Community populations lack awareness of the unique roles and responsibilities of pharmacists. To positively influence the pipeline of future pharmacists, it is necessary to promote pharmacy as a career path. Proactively targeting younger age groups to engage in science, technology, engineering, mathematics, and health (STEM+H) educational activities will increase knowledge and understanding of the profession of pharmacy. Educational engagement is most successful when a positive relationship is established with a community alliance., Perspective: Doctor of pharmacy students established a community partnership to create the inaugural "Girl Scouting Out Pharmacy" event. Over forty pharmacy students and faculty created and led an interactive event to advocate for the betterment of our profession while simultaneously educating on various pharmacy topics. Four unique, hands-on sessions incorporated pharmacy activities for girl scouts and their parents. These activities engaged youth to imagine their future while promoting an appreciation of pharmacy careers., Implications: Creating unique events to promote STEM+H education grants early opportunities to explore pharmacy-related concepts. The combination of healthcare professional students and community outreach produces the greatest potential to spark interest. Pharmacists have a duty to inspire young individuals, ensuring the next generation meets the needs of the nation's workforce. It is the responsibility of today's pharmacists to foster intellectual curiosity and instill a progressive drive in the following generation, lest we fall behind the curve on an ever-evolving healthcare culture., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A breast cancer diagnosis can be a life-changing and stressful experience that can lead to chronic mental health conditions such as posttraumatic stress disorder (PTSD). Greater than one-third of patients initially diagnosed with PTSD after a diagnosis of breast cancer continue to have persistent or worsening PTSD symptoms after 4 years. An emerging body of literature has indicated several key environmental and biological risk factors for PTSD among survivors of breast cancer. Well-recognized risk factors include having a history of childhood trauma, being nonwhite, obesity, younger age at the time of diagnosis, diagnosis with a higher stage of breast cancer, and short time since treatment. Of the emerging risk factors related to fear circuitry in the brain, 2 pathways of particular importance are the stress-driven activation of inflammatory pathways and the long-term effect of antiendocrine therapies. These central and peripheral responses during and after stress exposure are important because increased fear and anxiety can lead to the maintenance of PTSD and worse patient outcomes. Given the poor outcomes associated with PTSD and the high prevalence of breast cancer in women, more research to identify those women at heightened risk of PTSD after breast cancer is warranted to reduce the number of diagnoses and lessen the negative impact of this chronic mental health condition., (© 2020 American Cancer Society.)

Background: In utero endocrine disruption is linked to increased risk of breast cancer later in life. Despite numerous studies establishing this linkage, the long-term molecular changes that predispose mammary cells to carcinogenic transformation are unknown. Herein, we investigated how endocrine disrupting compounds (EDCs) drive changes within the stroma that can contribute to breast cancer susceptibility., Methods: We utilized bisphenol A (BPA) as a model of estrogenic endocrine disruption to analyze the long-term consequences in the stroma. Deregulated genes were identified by RNA-seq transcriptional profiling of adult primary fibroblasts, isolated from female mice exposed to in utero BPA. Collagen staining, collagen imaging techniques, and permeability assays were used to characterize changes to the extracellular matrix. Finally, gland stiffness tests were performed on exposed and control mammary glands., Results: We identified significant transcriptional deregulation of adult fibroblasts exposed to in utero BPA. Deregulated genes were associated with cancer pathways and specifically extracellular matrix composition. Multiple collagen genes were more highly expressed in the BPA-exposed fibroblasts resulting in increased collagen deposition in the adult mammary gland. This transcriptional reprogramming of BPA-exposed fibroblasts generates a less permeable extracellular matrix and a stiffer mammary gland. These phenotypes were only observed in adult 12-week-old, but not 4-week-old, mice. Additionally, diethylstilbestrol, known to increase breast cancer risk in humans, also increases gland stiffness similar to BPA, while bisphenol S does not., Conclusions: As breast stiffness, extracellular matrix density, and collagen deposition have been directly linked to breast cancer risk, these data mechanistically connect EDC exposures to molecular alterations associated with increased disease susceptibility. These alterations develop over time and thus contribute to cancer risk in adulthood.

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder in reproductive aged women associated with a number of endocrine and metabolic complications, including increased risk of endometrial cancer., Objective: To study the effect of the characteristic increased androgen levels in PCOS on the endometrium, a novel scaffold-free multicellular endometrial organoid was established., Design: Human endometrial organoids were constructed using primary endometrial epithelial and stromal cells from endometrial tissues. Organoids were treated for 14 days with physiologic levels of estradiol and testosterone to mimic a normal follicular phase or PCOS hormone profiles. Organoids were harvested for immunostaining and ribonucleic acid sequencing., Setting: Academic institution., Patients: Endometrial tissues from 10 premenopausal women undergoing hysterectomy for benign pathologies were obtained following written consent., Main Outcome Measures: Organoid architecture, cell specific markers, functional markers, proliferation, and gene expression were measured., Results: A method to generate scaffold-free endometrial organoids containing epithelial and stromal cells was established. These organoids exhibited distinct organization with epithelial cells lining the outer surface and stromal cells in the center of the organoids. Epithelial cells were polarized, organoids expressed cell type specific and functional markers, as well as androgen, estrogen, and progesterone receptors. Treatment with PCOS hormones increased cell proliferation and dysregulated genes in endometrial organoids., Conclusions: A new multicellular, scaffold-free endometrial organoid system was established that resembled physiology of the native endometrium. Excess androgens in PCOS promoted cell proliferation in endometrial organoids, revealing new mechanisms of PCOS-associated with risk of endometrial neoplasia., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Retinal degenerative disorders, such as age-related macular degeneration (AMD), are one of the leading causes of blindness worldwide, however, treatments to completely stop the progression of these debilitating conditions are non-existent. Researchers require sophisticated models that can accurately represent the native structure of human retinal tissue to study these disorders. Current in vitro models used to study the retina are limited in their ability to fully recapitulate the structure and function of the retina, Bruch's membrane and the underlying choroid. Recent developments in the field of induced pluripotent stem cell technology has demonstrated the capability of retinal pigment epithelial cells to recapitulate AMD-like pathology. However, such studies utilise unsophisticated, bio-inert membranes to act as Bruch's membrane and support iPSC-derived retinal cells. This review presents a concise summary of the properties and function of the Bruch's membrane-retinal pigment epithelium complex, the initial pathogenic site of AMD as well as the current status for materials and fabrication approaches used to generate in vitro models of this complex tissue. Finally, this review explores required advances in the field of in vitro retinal modelling. STATEMENT OF SIGNIFICANCE: Retinal degenerative disorders such as age-related macular degeneration are worldwide leading causes of blindness. Previous attempts to model the Bruch's membrane-retinal pigment epithelial complex, the initial pathogenic site of age-related macular degeneration, have lacked the sophistication to elucidate valuable insights into disease mechanisms. Here we provide a detailed account of the morphological, physical and chemical properties of Bruch's membrane which may aid the fabrication of more sophisticated and physiologically accurate in vitro models of the retina, as well as various fabrication techniques to recreate this structure. This review also further highlights some recent advances in some additional challenging aspects of retinal tissue modelling including integrated fluid flow and photoreceptor alignment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

This study investigates the utility of a tailored poly(ethylene glycol) diacrylate-crosslinked porous polymeric tissue engineering scaffold, with mechanical properties specifically optimised to be comparable to that of mammalian brain tissue for 3D human neural cell culture. Results obtained here demonstrate the attachment, proliferation and terminal differentiation of both human induced pluripotent stem cell- and embryonic stem cell-derived neural precursor cells (hPSC-NPCs) throughout the interconnected porous network within laminin-coated scaffolds. Phenotypic data and functional analyses are presented demonstrating that this material supports terminal in vitro neural differentiation of hPSC-NPCs to a mixed population of viable neuronal and glial cells for periods of up to 49 days. This is evidenced by the upregulation of TUBB3, MAP2, SYP and GFAP gene expression, as well as the presence of the proteins βIII-TUBULIN, NEUN, MAP2 and GFAP. Functional maturity of neural cells following 49 days 3D differentiation culture was tested via measurement of intracellular calcium. These analyses revealed spontaneously active, synchronous and rhythmic calcium flux, as well as response to the neurotransmitter glutamate. This tailored construct has potential application as an improved in vitro human neurogenesis model with utility in platform drug discovery programs. STATEMENT OF SIGNIFICANCE: The interconnected porosity of polyHIPE scaffolds exhibits the ability to support three-dimensional neural cell network formation due to limited resistance to cellular migration and re-organisation. The previously developed scaffold material displays mechanical properties similar to that of the mammalian brain. This research also employs the utility of pluripotent stem cell-derived neural cells which are of greater clinical relevance than primary neural cell lines. This scaffold material has future potential in better mimicking three-dimensional neural networks found in the human brain and may result in improved in vitro models for disease modelling and drug screening applications., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The human endometrium is one of the most hormonally responsive tissues in the body and is essential for the establishment of pregnancy. This tissue can also become diseased and cause morbidity and even death. Model systems to study human endometrial biology have been limited to in vitro culture systems of single cell types. In addition, the epithelial cells, one of the major cell types of the endometrium, do not propagate well or retain their physiological traits in culture, and thus our understanding of endometrial biology remains limited. We have generated, for the first time, endometrial organoids that consist of both epithelial and stromal cells of the human endometrium. These organoids do not require any exogenous scaffold materials and specifically organize so that epithelial cells encompass the spheroid-like structure and become polarized with stromal cells in the center that produce and secrete collagen. Estrogen, progesterone and androgen receptors are expressed in the epithelial and stromal cells and treatment with physiological levels of estrogen and testosterone promote the organization of the organoids. This new model system can be used to study normal endometrial biology and disease in ways that were not possible before.

A method has been developed for selectively patterning silk surfaces using a photolithographic process to mask off sections of silk films, which allows selective and precise patterning of features down to 40 μm. This process is highly versatile, utilizes only low-cost equipment and can be used to rapidly prototype flat silk substrates with spatially controlled chemical patterns. Here we demonstrate the usefulness of this technique to deposit fluorescent dyes, labeled proteins and conducting polymers or to modify the surface charge of the silk protein in desired regions on a silk film surface.

We report on the development of bioinspired cardiac scaffolds made from electroconductive acid-modified silk fibroin-poly(pyrrole) (AMSF+PPy) substrates patterned with nanoscale ridges and grooves reminiscent of native myocardial extracellular matrix (ECM) topography to enhance the structural and functional properties of cultured human pluripotent stem cells (hPSC)-derived cardiomyocytes. Nanopattern fidelity was maintained throughout the fabrication and functionalization processes, and no loss in conductive behavior occurred due to the presence of the nanotopographical features. AMSF+PPy substrates were biocompatible and stable, maintaining high cell viability over a 21-day culture period while displaying no signs of PPy delamination. The presence of anisotropic topographical cues led to increased cellular organization and sarcomere development, and electroconductive cues promoted a significant improvement in the expression and polarization of connexin 43 (Cx43), a critical regulator of cell-cell electrical coupling. The combination of biomimetic topography and electroconductivity also increased the expression of genes that encode key proteins involved in regulating the contractile and electrophysiological function of mature human cardiac tissue., Competing Interests: Conflicts of Interest Deok-Ho Kim is a co-founder and scientific board member at NanoSurface Biomedical Inc.

Progesterone is a steroid hormone that plays an important role in the breast. Progesterone exerts its action through binding to progesterone receptor (PR), a transcription factor. Deregulation of the progesterone signaling pathway is implicated in the formation, development, and progression of breast cancer. Next-generation selective progesterone receptor modulators (SPRMs) have potent antiprogestin activity and are selective for PR, reducing the off-target effects on other nuclear receptors. To date, there is limited information on how the newer generation of SPRMs, specifically telapristone acetate (TPA), affect PR function at the molecular level. In this study, T47D breast cancer cells were used to investigate the molecular mechanism by which TPA antagonizes PR action. Global profiling of the PR cistrome and interactome was done with chromatin immunoprecipitation sequencing (ChIP-seq) and rapid immunoprecipitation mass spectrometry. Validation studies were done on key genes and interactions. Our results demonstrate that treatment with the progestin (R5020) alone resulted in robust PR recruitment to the chromatin, and addition of TPA reduced PR recruitment globally. TPA significantly changed coregulator recruitment to PR compared with R5020. Upon conservative analysis, three proteins (TRPS1, LASP1, and AP1G1) were identified in the R5020+TPA-treated group. Silencing TRPS1 with small interfering RNA increased PR occupancy to the known PR regulatory regions and attenuated the inhibition of gene expression after TPA treatment. TRPS1 silencing alleviated the inhibition of proliferation by TPA. In conclusion, TPA decreases PR occupancy on chromatin and recruits coregulators such as TRPS1 to the PR complex, thereby regulating PR target gene expression and associated cellular responses.

Here we detail the fabrication and testing of artificial muscles fabricated from composites of the natural biopolymer silk fibroin and conducting polymers. Aligned nanofiber bundles of silk that mimic the structure of skeletal muscles were produced via electrospinning, and the fibers were infused with conducting polymers using chemical and electrochemical in situ polymerization methods. The resulting bundles of individual, electroactive fibers underwent electromechanical actuation in biologically-relevant electrolyte solutions when low potentials were applied, thus mimicking the contractile function of native muscles. The fabrication methods, bulk mechanical properties, stress and strain generation, and stability under repeated actuation for fiber bundles coated with different conducting polymer formulations are presented.

In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities. We found that BPA treatment occurring before mammary bud invasion into the mesenchyme [embryonic day (E)12.5] incompletely resulted in the measured phenotypes of mammary gland defects. Exposing mice up to the point at which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype and exposure during epithelial extension (E15.5 to E18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposure windows highlight the substantial correlations between early-life molecular changes (estrogen receptor-α and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes., (Copyright © 2017 Endocrine Society.)

Lead (Pb) has been known to be a cause of human poisoning since ancient times, but despite this, it was a widely used metal in the European colonial period. In this study, the relationship between Pb exposure and the demographic variables ancestry and age was explored by comparing the bone Pb levels of individuals that were of either African or European ancestry, excavated from a British Royal Navy hospital cemetery (1793-1822 CE) at English Harbour in Antigua, West Indies. More direct comparisons of Pb levels between the two ancestral groups were possible in this study because of the unsegregated nature of this cemetery. Inductively coupled plasma mass spectrometry was used to determine bulk Pb levels in cortical bone samples from the fibular diaphyses of 23 male individuals. No significant difference was found between the distributions of the Pb levels of the ancestral groups ( p  = 0.94). Further, no positive correlations or significant differences were found in relation to the individuals' ages and their Pb levels ( p  = 0.24). Levels of Ba, Ca and rare earth elements support a largely biogenic origin of lead. This is bolstered by Pb deposition patterns, generated by synchrotron X-ray fluorescence imaging for another study. The data suggest that naval personnel, regardless of ancestry at English Harbour, had very similar experiences with regard to Pb exposure. Their exposure to the toxic metal was likely not consistent over time as steady exposure would have resulted in accumulation of Pb with age. This study contributes to addressing historical questions regarding the prevalence of Pb poisoning within the British Royal Navy during the colonial period., (© 2017 The Authors International Journal of Osteoarchaeology Published by John Wiley & Sons Ltd.)

Self-assembly of a tetrapeptide covalently attached to a thiophene-based monomer produced a gel with a fibrous, porous structure. Conditions were identified in which the thiophene end groups could undergo polymerization while retaining the 3D structure, resulting in the formation of nanofibrous gels with conductivities averaging 10 -4 S cm -1 .

Objective: This study identifies the types of patient-related information problems (PIPs) that patient-care teams encounter during morning rounds, and how those PIPs are identified and managed. PIPs are any issues related to patient information (e.g., wrong, missing, incomplete information) that affect the patient-care team's ability to perform their work. Not addressing PIPs can lead to workflow challenges, delayed patient-care decisions, and negative impacts to the patient., Materials and Methods: We employed qualitative data collection methods by shadowing patient-care teams during 29 morning rounds resulting in 155h of observation. We observed the interactions between the rounding physicians and other patient-care team members, including: nurses, consulting physicians, care coordinators, pharmacists, social workers, and therapists., Results: This study resulted in identifying seven types of PIPs that occur during morning rounds. Additionally, the study presents the different ways that participants identified and managed the PIPs., Discussion: We discuss the potential negative effects of PIPs on the patient-care workflow. We also discuss socio-technical recommendations for organizational policies and training, as well as electronic health record (EHR) design improvements that could help patient-care teams more effectively identify and manage PIPs., Conclusion: Hospital teams rely on accurate, available, and up-to-date information in order to make informed decisions on patient care. However, PIPs exist in EHR systems, paper documents, and verbal conversations. This study identifies a set of PIPs and how they are currently being identified and managed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Understanding how neurodegenerative disorders develop is not only a key challenge for researchers but also for the wider society, given the rapidly aging populations in developed countries. Advances in this field require new tools with which to recreate neural tissue in vitro and produce realistic disease models. This in turn requires robust and reliable systems for performing 3D in vitro culture of neural lineage cells. This review provides a state of the art update on three-dimensional culture systems for in vitro development of neural tissue, employing a wide range of scaffold types including hydrogels, solid porous polymers, fibrous materials and decellularised tissues as well as microfluidic devices and lab-on-a-chip systems. To provide some context with in vivo development of the central nervous system (CNS), we also provide a brief overview of the neural stem cell niche, neural development and neural differentiation in vitro. We conclude with a discussion of future directions for this exciting and important field of biomaterials research., Statement of Significance: Neurodegenerative diseases, including dementia, Parkinson's and Alzheimer's diseases and motor neuron diseases, are a major societal challenge for aging populations. Understanding these conditions and developing therapies against them will require the development of new physical models of healthy and diseased neural tissue. Cellular models resembling neural tissue can be cultured in the laboratory with the help of 3D scaffolds - materials that allow the organization of neural cells into tissue-like structures. This review presents recent work on the development of different types of scaffolds for the 3D culture of neural lineage cells and the generation of functioning neural-like tissue. These in vitro culture systems are enabling the development of new approaches for modelling and tackling diseases of the brain and CNS., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Bacteria that inhabit the rhizosphere of agricultural crops can have a beneficial effect on crop growth. One such mechanism is the microbial-driven solubilization and remineralization of complex forms of phosphorus (P). It is known that bacteria secrete various phosphatases in response to low P conditions. However, our understanding of their global proteomic response to P stress is limited. Here, exoproteomic analysis of Pseudomonas putida BIRD-1 (BIRD-1), Pseudomonas fluorescens SBW25 and Pseudomonas stutzeri DSM4166 was performed in unison with whole-cell proteomic analysis of BIRD-1 grown under phosphate (Pi) replete and Pi deplete conditions. Comparative exoproteomics revealed marked heterogeneity in the exoproteomes of each Pseudomonas strain in response to Pi depletion. In addition to well-characterized members of the PHO regulon such as alkaline phosphatases, several proteins, previously not associated with the response to Pi depletion, were also identified. These included putative nucleases, phosphotriesterases, putative phosphonate transporters and outer membrane proteins. Moreover, in BIRD-1, mutagenesis of the master regulator, phoBR, led us to confirm the addition of several novel PHO-dependent proteins. Our data expands knowledge of the Pseudomonas PHO regulon, including species that are frequently used as bioinoculants, opening up the potential for more efficient and complete use of soil complexed P., (© 2016 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

High rates of human immunodeficiency virus (HIV) exist among urban African American youth. There is a need to provide HIV information to youth prior to the onset of sexual activity. The Stomping Out HIV intervention combines a health fair and step show to increase awareness and healthy behaviors among this population. Questionnaires were administered to youth and parents before and after Stomping Out, and focused on health knowledge, satisfaction with Stomping Out, intended behavior changes and self-efficacy to make healthier choices related to HIV and STI prevention. Youth and adults reported increased knowledge and self-efficacy after Stomping Out. These findings suggest that health initiatives focusing on sociocultural issues can greatly impact adults and youth.

Purpose: We examined the role of privacy in collaborative clinical work and how it is understood by hospital IT staff. The purpose of our study was to identify the gaps between hospital IT staff members' perceptions of how electronic health record (EHR) users' protect the privacy of patient information and how users actually protect patients' private information in their daily collaborative activities. Since the IT staff play an important role in implementing and maintaining the EHR, any gaps that exist between the IT staff's perceptions of user work practices and the users' actual work practices can result in a number of problems in the configuration, implementation, or customization of the EHR, which can lead to collaboration challenges, interrupted workflow, and privacy breaches., Methods: We used qualitative data collection methods for this study. We conducted semi-structured interviews with 20 hospital IT staff members. We also conducted observations of EHR users in the in-patient units of the same hospital., Results: We identified gaps in IT staff's understandings of users' work activities, especially in regards to privacy-compromising workarounds that are used by users and why they are used., Discussion: We discuss the reasons why this gap may exist between IT staff and users and ways to improve IT staff's understanding of why users perform certain privacy-compromising workarounds., Conclusion: A hospital's IT staff face a daunting task in ensuring users' collaborative work practices are supported by the system while providing effective privacy mechanisms. In order to achieve both goals, the IT staff must have a clear understanding of their users' practices. However, as this study highlights, there may be a mismatch between the IT staff's understandings of how users protect patient privacy and how users actually protect privacy., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Flexible and conductive biocompatible materials are attractive candidates for a wide range of biomedical applications including implantable electrodes, tissue engineering, and controlled drug delivery. Here, we demonstrate that chemical and electrochemical polymerization techniques can be combined to create highly versatile silk-conducting polymer (silk-CP) composites with enhanced conductivity and electrochemical stability. Interpenetrating silk-CP composites were first generated via in situ deposition of polypyrrole during chemical polymerization of pyrrole. These composites were sufficiently conductive to serve as working electrodes for electropolymerization, which allowed an additional layer of CP to be deposited on the surface. This sequential method was applied to both 2D films and 3D sponge-like silk scaffolds, producing conductive materials with biomimetic architectures. Overall, this two-step technique expanded the range of available polymers and dopants suitable for the synthesis of mechanically robust, biocompatible, and highly conductive silk-based materials.

A delivery platform was developed using silk-based hydrogels, and sustained delivery of the cationic chemokine CXCL12 at therapeutically relevant doses is demonstrated. Hydrogels were prepared from plain silk and silk that had been chemically modified with sulfonic acid groups. CXCL12 was mixed with the silk solution prior to gelation, resulting in 100% encapsulation efficiency, and both hydrated and lyophilized gels were compared. By attaching a fluorescein tag to CXCL12 using a site-specific sortase-mediated enzymatic ligation, release was easily quantified in a high-throughput manner using fluorescence spectroscopy. CXCL12 continually eluted from both plain and acid-modified silk hydrogels for more than 5 weeks at concentrations ranging from 10 to 160 ng per day, depending on the gel preparation method. Notably, acid-modified silk hydrogels displayed minimal burst release yet had higher long-term release rates compared to those of plain silk hydrogels. Similar release profiles were observed over a range of loading capacities, allowing dosage to be easily varied.

Curcumin, a natural phenolic compound derived from the plant Curcuma longa, was physically entrapped and stabilized in silk hydrogel films, and its influence on human bone marrow-derived mesenchymal stem cells (hBMSC) was assessed related to adipogenic differentiation. The presence of curcumin significantly reduced the silk gelation time and changed the porous morphology of gel matrix, but did not change the formation of the silk beta-sheet structure. Based on spectrofluorimetric analysis, curcumin most likely interacted with hydrophobic residues in silk, interacting with the beta-sheet domains formed in the hydrogels. The antioxidant activity of silk film-associated curcumin remained functional over at least one month in both the dry and hydrated state. Negligible curcumin was released from silk hydrogel films over 48 h incubation in aqueous solution. For hBMSC cultured on silk films containing more than 0.25 mg ml(-1) curcumin, cell proliferation was inhibited, while adipogenesis was significantly promoted based on transcripts as well as Oil Red O staining. When hBMSC were cultured in media containing free curcumin, both proliferation and adipogenesis of hBMSC were inhibited when curcumin concentrations exceeded 5 μM, which is more than 1000 times higher than the level of curcumin released from the films in aqueous solution. Thus, silk film-associated curcumin exhibited different effects on hBMSC proliferation and differentiation compared with curcumin in solution., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Patient-care teams frequently encounter information problems during their daily activities. These information problems include wrong, outdated, conflicting, incomplete, or missing information. Information problems can negatively impact the patient-care workflow, lead to misunderstandings about patient information, and potentially lead to medical errors. Existing research focuses on understanding the cause of these information problems and the impact that they can have on the hospital's workflow. However, there is limited research on how patient-care teams currently identify and manage information problems that they encounter during their work. Through qualitative observations and interviews in an emergency department (ED), we identified the types of information problems encountered by ED staff, and examined how they identified and managed the information problems. We also discuss the impact that these information problems can have on the patient-care teams, including the cascading effects of information problems on workflow and the ambiguous accountability for fixing information problems within collaborative teams.

We investigated the componential structure of event-related potentials elicited while participants use the P300 BCI. Six healthy participants "typed" all characters in a 6 × 6 matrix twice in a random sequence. A principal component analysis indicated that in addition to the P300, target flashes elicited an earlier frontal positivity, possibly a Novelty P3. The amplitudes of both P300 and the Novelty P3 varied with the matrix row in which the target character was located. However, the P300 elicited by row flashes was largest for targets in the lower part of the matrix, whereas the Novelty P3 elicited by column flashes was largest in the top part. Classification accuracy using stepwise linear discriminant analysis mirrored the pattern in the Novelty P3 (an accuracy difference of 0.1 between rows 1 and 6). When separate classifiers were generated to rely solely on the P300 or solely on the Novelty P3, the latter function led to higher accuracy (a mean accuracy difference of about 0.2 between classifiers). A possible explanation is that some nontarget flashes elicit a P300, leading to lower selection accuracy of the respective classifier. In an additional set of data from six different participants we replicated the ERP structure of the initial analyses and characterized the spatial distributions more closely by using a dense electrode array. Overall, our findings provide new insights in the componential structure of ERPs elicited in the P300 speller paradigm and have important implications for optimizing the speller's selection accuracy.

To produce conductive, biocompatible, and mechanically robust materials for use in bioelectrical applications, we have developed a new strategy to selectively incorporate poly(pyrrole) (Ppy) into constructs made from silk fibroin. Here, we demonstrate that covalent attachment of negatively charged, hydrophilic sulfonic acid groups to the silk protein can selectively promote pyrrole absorption and polymerization within the modified films to form a conductive, interpenetrating network of Ppy and silk that is incapable of delamination. To further increase the conductivity and long-term stability of the Ppy network, a variety of small molecule sulfonic acid dopants were utilized and the properties of these silk-conducting polymer composites were monitored over time. The composites were evaluated using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), optical microscopy, energy-dispersive X-ray (EDX) spectroscopy, cyclic voltammetry, a 4-point resistivity probe and mechanical testing. In addition, the performance was evaluated following exposure to several biologically relevant enzymes. Using this strategy, we were able to produce mechanically robust polymer electrodes with stable electrochemical performance and sheet resistivities on the order of 1 × 10(2) Ω/sq (conductivity ∼1 S/cm).

The development of biomaterials that mimic the physiological binding of growth factors to the extracellular matrix (ECM) is an appealing strategy for advanced growth factor delivery systems. In vivo, fibroblast growth factor 2 (FGF-2) binds to the sulfated glycosaminoglycan heparan sulfate, which is a major component of the ECM. Therefore, we tested whether silk fibroin (SF) decorated with a sulfonated moiety could mimic the natural ECM environment and lead to advanced delivery of this heparin-binding growth factor. Using a diazonium coupling reaction, modified SF derivatives containing approximately 20, 40, 55 and 70 sulfonic acid groups per SF molecule were obtained. Films of the SF derivative decorated with 70 sulfonic acid groups per SF molecule resulted in a 2-fold increase in FGF-2 binding as compared to native SF. More than 99% of bound FGF-2 could be retained on all SF derivatives. However, protection of FGF-2 potency was only achieved with at least 40 sulfonic acid groups per SF molecule, as observed by reduced metabolic activity and enhanced levels of phosphorylated extracellular signal-regulated kinases (pERK1/2) in cultured human mesenchymal stem cells (hMSCs). This study introduces a first step towards the development of an ECM-mimicking biomaterial for sustained, non-covalent binding, controlled delivery and preserved potency of biomolecules., ((c) 2009 Elsevier Ltd. All rights reserved.)

Silk proteins belong to a class of unique, high molecular weight, block copolymer-like proteins that have found widespread use in biomaterials and regenerative medicine. The useful features of these proteins, including self-assembly, robust mechanical properties, biocompatibility and biodegradability can be enhanced through a variety of chemical modifications. These modifications provide chemical handles for the attachment of growth factors, cell binding domains and other polymers to silk, expanding the range of cell and tissue engineering applications attainable. This review focuses on the chemical reactions that have been used to modify the amino acids in silk proteins, and describes their utility in biomedical applications.

A simple chemical modification method using diazonium coupling chemistry was developed to tailor the structure and hydrophilicity of silk fibroin protein. The extent of modification using several aniline derivatives was characterized using UV-vis and 1H NMR spectroscopies, and the resulting protein structure was analyzed with ATR-FTIR spectroscopy. Introduction of hydrophobic functional groups facilitated rapid conversion of the protein from a random coil to a beta-sheet structure, while addition of hydrophilic groups inhibited this process. hMSCs were grown on these modified silks to assess the biocompatibility of these materials. The hydrophilicity of the silk derivatives was found to affect the growth rate and morphology, but hMSCs were able to attach, proliferate and differentiate into an osteogenic lineage on all of the silk derivatives.

The thin film microstructure development of functionalized oligothiophenes with branched, thermally removable groups at each end of conjugated cores with five, six, and seven thiophene rings was monitored during their thermal conversion from solution processible precursors to insoluble semiconductor products. The change in end group character provides a comparison of branched vs linear end group functionalization in oligothiophenes. Near edge X-ray absorption fine structure (NEXAFS) spectroscopy confirmed that branched alpha-, omega-substitutions of the precursors strongly influenced the packing of the conjugated core. The quinque- and sexithiophene precursors oriented perpendicular to the substrate, whereas the septithiophene precursor oriented parallel to the substrate, providing one of the first examples of length dependence in oligothiophene orientation. This dependence may be due to a packing mismatch between the conjugated cores and the branched end groups. The convertible septithiophene exhibits four distinct microstructures as it converts from precursor to product that correlate strongly with its field-effect hole mobility in field-effect transistors. The extent of septithiophene order and the surface-relative orientation of its ordered phases clearly influence field-effect transistor performance.

The structural and mechanical properties of Langmuir-Blodgett monolayer and multilayer films of 3",4""-didecyl-5,2'; 5',2"; 5",2'''; 5''',2""; 5"",2'''''; 5''''',2"""-heptathiophene-4'''-acetic acid on mica have been studied by atomic force microscopy (AFM) as a function of humidity, temperature, and applied force. The molecules orient with the carboxylic acid group pointing toward the mica surface and expose the alkyl side chains to the air interface. As the load applied by the AFM tip increases, the film is compressed easily from an initial height of 2 to 1.2 nm. After compression the films can support much higher loads without loss of height. The state of aggregation of the molecules was found to be sensitive to the environmental humidity, which induced reversible changes. Annealing the samples with monolayer or multilayer films resulted in irreversible changes when the temperature exceeded approximately 100 degrees C.

The oligothiophene derivative 4-(5' " '-decyl-[2,2';5',2' ';5' ',2' ";5' ",2' " '] pentathiophen-5-yl)-butyric acid (D5TBA) was synthesized by Stille cross-coupling methods using functionalized thiophene monomers. The structural and mechanical properties of D5TBA self-assembled monolayers on mica have been studied by atomic force microscopy (AFM). The self-assembled films were prepared by immersing the mica in dilute chloroform or tetrahydrofuran (THF) solutions. The films were predominantly of monolayer thickness with molecules packed in nearly upright orientations. In regions covered with multilayers, the molecules in each monolayer were oriented opposite to those in the neighboring ones, that is, with COOH-COOH and CH3-CH3 contact. The nature of the end group in contact with the substrate depended on the solvent used and the degree of hydration of the substrate, with hydrophobic chloroform solvent favoring the methyl end down and hydrophilic THF favoring the acid group end down. The orientation could also be controlled by dipping using the Langmuir-Blodgett technique.

A symmetrical alpha,omega-substituted sexithiophene derivative containing thermally removable branched ester solubilizing groups has been prepared. These oligomers can be solution cast into thin films and then thermolyzed to remove the solubilizing group, leaving short pendant alkene groups on the oligomer. Device testing of thin film transistors shows an increase in hole mobility from 1 x 10-5 cm2/(V s) with on/off ratios of approximately 100 before thermolysis to 5 x 10-2 cm2/(V s) with on/off ratios >105 after thermolysis. This method offers an attractive route to easily processed and highly performing thiophene oligomers.

Background: Arginine is an agent commonly used to evaluate adequacy of growth hormone (GH) secretion. Because arginine is a simple amino acid, it is considered safe and rarely causes adverse reactions., Objective: To report the second anaphylactoid reaction to arginine in a child undergoing stimulation testing with arginine for assessing GH secretion., Methods: Allergy skin testing to arginine was performed with a protocol similar to penicillin testing 4 weeks after the anaphylactoid reaction., Results: Testing revealed a positive response to the arginine., Conclusions: The use of intravenous arginine as a test of GH reserve remains safe and effective, but it is prudent to have the equipment and medication available to treat an allergic reaction.

Insulin resistance is a strong predictor of the development of type 2 diabetes mellitus and cardiovascular disease. Girls with premature adrenarche (PA) or obesity may be at an increased risk for the development of insulin resistance. Recently, in prepubertal girls with PA, a fasting glucose to insulin ratio (FGIR) of less than 7 was found to be predictive of insulin resistance as determined by the frequently sampled iv glucose tolerance test. We sought to compare the FGIR with 2 insulin sensitivity measures, SiM (an adjusted mean measure of insulin sensitivity based on fasting and 2 h post glucose load insulin sensitivity measures) and the composite whole body insulin sensitivity index, ISI(comp), both derived from the 2-h oral glucose tolerance test in 2 groups of children at risk: girls with PA and obese girls. We studied 25 prepubertal girls with PA and/or obesity and further classified them as insulin resistant (IR) or insulin sensitive (IS) based on the FGIR. Four simple measures of insulin sensitivity [FGIR, quantitative insulin sensitivity check index (QUICKI), fasting insulin resistance index, and fasting insulin] were compared with SiM and ISI(comp). Additionally, we characterized the subjects in terms of risk factors associated with insulin resistance according to their insulin resistance status based on the FGIR. In our subjects the strongest correlations overall appeared to be between FGIR and SiM, FGIR and ISI(comp), QUICKI and SiM, and QUICKI and ISI(comp) [correlations (r) ranged from 0.81--0.84]. Furthermore, the IR group had higher body mass index and body mass index z-scores and triglyceride levels than the IS group and were over 3 times more likely to have triglycerides greater than the 95th percentile compared with national norms. We conclude that the FGIR and QUICKI are highly correlated with oral glucose tolerance test measures of insulin sensitivity. An FGIR less than 7 in young girls with PA or obesity may be helpful in the early identification of children at risk for complications of insulin resistance.

A number of isolates of Saccharomyces cerevisiae have been associated with disease in immunocompromised individuals. Such isolates display a variety of characteristics that enable colonization and persistence in the host. The aim of the work presented here was to establish whether clinical isolates of S. cerevisiae were capable of adhering to epithelial tissue. Adherence to host tissue has been shown to be crucial to the virulence of the pathogenic yeast Candida albicans, and identification of this ability in S. cerevisiae might indicate a role for adherence in tissue colonization by this emerging pathogen. Clinical S. cerevisiae isolates were found to be capable of adhering to exfoliated buccal epithelial cells (BECs) but to a lesser degree than C. albicans. In contrast to the situation evident with C. albicans, the adherence of S. cerevisiae isolates to BECs was not influenced by the carbon source in which the yeast was grown. Treatment of S. cerevisiae with trypsin or proteinase K resulted in a significant reduction in adherence ability while adherence was unaffected by treatment of cells with mannosidase, thus indicating a possible role for proteins rather than mannoproteins in the adherence of S. cerevisiae to BECs.

Tumors of the cranial nerves are uncommon, and are usually schwannomas or neurofibromas. The authors describe a case of a fibroblastic tumor involving the sixth cranial nerve. Based upon electron microscopy and immunohistochemistry, the tumor was not of nerve-sheath origin, but was comprised of fibroblasts. Clinical, radiographic, and pathological material are presented, and the literature is discussed. This represents the third case report of a tumor of the abducens nerve, and the first report of a fibroma of a cranial or peripheral nerve.