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Κυριακή 25 Ιουνίου 2017

Inverse Opal Scaffolds and Their Biomedical Applications

Three-dimensional porous scaffolds play a pivotal role in tissue engineering and regenerative medicine by functioning as biomimetic substrates to manipulate cellular behaviors. While many techniques have been developed to fabricate porous scaffolds, most of them rely on stochastic processes that typically result in scaffolds with pores uncontrolled in terms of size, structure, and interconnectivity, greatly limiting their use in tissue regeneration. Inverse opal scaffolds, in contrast, possess uniform pores inheriting from the template comprised of a closely packed lattice of monodispersed microspheres. The key parameters of such scaffolds, including architecture, pore structure, porosity, and interconnectivity, can all be made uniform across the same sample and among different samples. In conjunction with a tight control over pore sizes, inverse opal scaffolds have found widespread use in biomedical applications. In this review, we provide a detailed discussion on this new class of advanced materials. After a brief introduction to their history and fabrication, we highlight the unique advantages of inverse opal scaffolds over their non-uniform counterparts. We then showcase their broad applications in tissue engineering and regenerative medicine, followed by a summary and perspective on future directions.

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Inverse opal scaffolds are characterized by a highly ordered array of uniform and interconnected pores. This new class of advanced materials offers unique opportunities for a broad spectrum of applications in tissue regeneration by serving as biomimetic substrates with precisely controlled properties.



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Pantothenate auxotrophy in Zymomonas mobilis ZM4 is due to a lack of aspartate decarboxylase activity

Abstract
The bacterium Zymomonas mobilis naturally produces ethanol at near theoretical maximum yields, making it of interest for industrial ethanol production. Z. mobilis requires the vitamin pantothenate for growth. Here we characterized the genetic basis for the Z. mobilis pantothenate auxotrophy. We found that this auxotrophy is due to the absence of a single gene, panD, encoding aspartate-decarboxylase. Heterologous expression of Escherichia coli PanD in Z. mobilis or supplementation of the growth medium with the product of PanD activity, β-alanine, eliminated the need for exogenous pantothenate. We also determined that Z. mobilis IlvC, an enzyme better known for branched-chain amino acid synthesis, is required for pantothenate synthesis in Z. mobilis, as it compensates for the absence of PanE, another pantothenate synthesis pathway enzyme. In addition to contributing to an understanding of the nutritional requirements of Z. mobilis, our results have led to the design of a more cost-effective growth medium.

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The importance of fermentative conditions for the biotechnological production of lignin modifying enzymes from white-rot fungi

Abstract
White-rot fungi are the main natural producers of lignin modifying enzymes, i.e. laccases and peroxidases, whose secretion and activity allows the depolymerization of lignin and the release of polysaccharides contained in lignocellulose. These enzymes are able to oxidize, in addition to lignin, a wide spectrum of natural and synthetic substrates, making their industrial and biotechnological application appealing. However, the complex regulation of the synthesis of lignin modifying enzymes, as well as the heterogeneous physiology of fungi in response to nutrients, make the use of white-rot fungi as production platforms challenging. Finally, yet importantly, analytical methods are not fully standardized, making evaluations and comparisons ambiguous. Consequently, robust and cost-effective fermentative processes for the production of lignin modifying enzymes by fungi have not yet been fully established, limiting their industrial exploitation. In this review, we describe the importance of both the media composition and the fermentative conditions for leveraging the fungal potential in terms of production titer and enzymatic biodiversity of lignin modifying enzymes.

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Phylogenetic diversification and developmental implications of poly-(R)-3-hydroxyalkanoate gene cluster assembly in prokaryotes

Abstract
Many polyhydroxyalkanoates (PHAs) system genes, such as phaC, phaA, phaB, phaR, phaP, and phaZ, are often found to be organized in the form of operon-like clusters. In this study, a genome survey was performed to identify such clustered PHA systems among 256 prokaryotic organisms. These data were then used to generate a comprehensive 16S rRNA species tree depicting the phylogenetic distribution of the observed clusters with diverse gene arrangements. In addition, the gene occurrences and physical linkages between PHA system genes were quantitatively estimated. From this, we identified a centrally connected hub gene, i.e. the phaC gene of PHA. Furthermore, a comparative investigation was performed between the clusters of PHA and glycogen, which decoded the role of the hub gene in the cluster organization of both systems. Together, these findings suggest that the highly-connected hub gene might contribute substantively towards the organization and maintenance of the gene network connectivity in the clusters, particularly in the storage reserve systems.

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Delays in breast cancer diagnosis after a state policy limiting Medicaid enrollment

In this issue of Cancer, Tarazi et al investigate the effects of a state policy that substantially limited Medicaid enrollment on the timeliness of breast cancer diagnosis. They observe a statistically significant increase of 3.3 percentage points in the percentage of women diagnosed with late-stage disease after the policy change among women living in low-income versus high-income areas. See also pages 000-000.



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Identifying those infected with hepatitis C virus [Letters]



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The home care conversation were not having [News]



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Medical assistance in dying: time for physicians to step up to protect themselves and patients [Commentary]



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Harms of overoxygenation in patients with exacerbation of chronic obstructive pulmonary disease [Correction]



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Influences on the start, selection and duration of treatment with antibiotics in long-term care facilities [Research]

BACKGROUND:

Understanding the extent to which current antibiotic prescribing behaviour is influenced by clinicians' historical patterns of practice will help target interventions to optimize antibiotic use in long-term care. Our objective was to evaluate whether clinicians' historical prescribing behaviours influence the start, prolongation and class selection for treatment with antibiotics in residents of long-term care facilities.

METHODS:

We conducted a retrospective cohort study of all physicians who prescribed to residents in long-term care facilities in Ontario between Jan. 1 and Dec. 31, 2014. We examined variability in antibiotic prescribing among physicians for 3 measures: start of treatment with antibiotics, use of prolonged durations exceeding 7 days and selection of fluoroquinolones. Funnel plots with control limits were used to determine the extent of variation and characterize physicians as extreme low, low, average, high and extreme high prescribers for each tendency. Multivariable logistic regression was used to assess whether a clinician's prescribing tendency in the previous year predicted current prescribing patterns, after accounting for residents' demographics, comorbidity, functional status and indwelling devices.

RESULTS:

Among 1695 long-term care physicians, who prescribed for 93 132 residents, there was wide variability in the start of antibiotic treatment (median 45% of patients, interquartile range [IQR] 32%–55%), use of prolonged treatment durations (median 30% of antibiotic prescriptions, IQR 19%–46%) and selection of fluoroquinolones (median 27% of antibiotic prescriptions, IQR 18%–37%). Prescribing tendencies for antibiotics by physicians in 2014 correlated strongly with tendencies in the previous year. After controlling for individual resident characteristics, prior prescribing tendency was a significant predictor of current practice.

INTERPRETATION:

Physicians prescribing antibiotics exhibited individual, measurable and historical tendencies toward start of antibiotic treatment, use of prolonged treatment duration and class selection. Prescriber audit and feedback may be a promising tool to optimize antibiotic use in long-term care facilities.



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Natural health products should be sold separately from drugs [Editorial]



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A 44-year-old man with acute asymmetric polyarthritis and fever [Practice]



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Hepatitis C testing in Canada: dont leave baby boomers behind [Letters]



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Demodex folliculitis [Practice]



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Manitobas unique health care burdens stall federal deal [News]



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Serving two masters: the medical and political careers of Sir Charles Tupper [Humanities]



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Nigerias polio endgame impeded by Boko Haram [News]



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A gastric MANEC with an adenocarcinoma of fundic-gland type as exocrine component



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Chondrolipoma of the breast as a rare variant of myofibroblastoma: an immunohistochemical study of two cases

Abstract

Chondrolipoma of the breast is a very rare tumor whose histogenesis remains obscure. We report two cases (56-year-old and 43-year-old women) and present the results of an immunohistochemical study which strongly suggests that this tumor is a variant of myofibroblastoma. The tumors predominantly consisted of lipoma-like, mature adipose tissue, and many islands of hyaline cartilage. A proliferation of spindle cells associated with the deposition of collagen fibers was also seen. On immunohistochemical examination, spindle cells showed cytoplasmic reactivity for vimentin, desmin, bcl-2, and α-smooth muscle actin, as well as nuclear reactivity for estrogen receptor (ER) and progesterone receptor (PgR). Chondrocytes were immunoreactive for ER, PgR, S-100 protein, and Sox9. The nuclei of adipocytes, chondrocytes, and spindle cells were not immunoreactive for Rb (retinoblastoma) protein. The immunoreactivity of spindle cells for muscle markers indicates myofibroblastic differentiation, and the lack of the nuclear expression of Rb protein suggests the close relationship of this tumor with myofibroblastoma and spindle cell lipoma. The immunoreactivity of chondrocytes for ER and PgR suggests that they are derived from metaplasia of hormone-sensitive spindle cells. These findings support the concept that chondrolipoma of the breast could be a lipomatous variant of myofibroblastoma associated with cartilaginous metaplasia and that it should be added to members of the "13q/Rb family of tumors."



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Gluten and Aluminum Content in Synthroid ® (Levothyroxine Sodium Tablets)

Abstract

Introduction

Inquiries from healthcare providers and patients about the gluten and aluminum content of Synthroid® (levothyroxine sodium tablets) have increased. The objective of this study was to measure and evaluate the gluten content of the raw materials used in the manufacturing of Synthroid. Additionally, this study determined the aluminum content in different strengths of Synthroid tablets by estimating the amount of aluminum in the raw materials used in the manufacturing of Synthroid.

Methods

Gluten levels of three lots of the active pharmaceutical ingredient (API) and one lot of each excipient from different vendors were examined. The ingredients in all current Synthroid formulations (strengths) were evaluated for their quantity of aluminum.

Results

Gluten concentrations were below the lowest limit of detection (<3.0 ppm) for all tested lots of the API and excipients of Synthroid tablets. Aluminum content varied across tablet strengths (range 19–137 µg/tablet). Gluten levels of the API and excipients were found to be below the lowest level of detection and are considered gluten-free based on the US Food and Drug Administration (FDA) definition for food products. Across the various tablet strengths of Synthroid, the maximum aluminum levels were well below the FDA-determined minimal risk level for chronic oral aluminum exposure (1 mg/kg/day).

Conclusion

These data demonstrate that Synthroid tablets are not a source for dietary gluten and are a minimal source of aluminum.

Funding

AbbVie Inc.



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EMCrit 202 – Blood Bank Essentials with Joe Chaffin

US_Navy_090218-N-6326B-074_The_Naval_Med

blood bank stuff: The basics of crit care transfusion medicine

EMCrit by Scott Weingart.



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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

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In this method, human primary muscle cells are cultured in vitro to obtain differentiated myotubes and glucose uptake rates are measured. We provide a detailed protocol to quantify rates in basal and insulin-stimulated states using radiolabeled [3H] 2-deoxy-D-Glucose.

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CAPRRESI: Chimera Assembly by Plasmid Recovery and Restriction Enzyme Site Insertion

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Here, we present chimera assembly by plasmid recovery and restriction enzyme site insertion (CAPRRESI), a protocol based on the insertion of restriction enzyme sites into synonym DNA sequences and functional plasmid recovery. This protocol is a fast and low-cost method for fusing protein-coding genes.

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