Monodispersed Bioactive Glass Nanoclusters with Ultralarge Pores and Intrinsic Exceptionally High miRNA Loading for Efficiently Enhancing Bone Regeneration

Bioactive glass nanoparticles (BGNs) have attracted much attention in drug delivery and bone tissue regeneration, due to the advantages including biodegradation, high bone-bonding bioactivity, and facile large-scale fabrication. However, the wide biomedical applications of BGNs such as efficient gene delivery are limited due to their poor pore structure and easy aggregation. Herein, for the first time, this study reports novel monodispersed bioactive glass nanoclusters (BGNCs) with ultralarge mesopores (10–30 nm) and excellent miRNA delivery for accelerating critical-sized bone regeneration. BGNCs with different size (100–500 nm) are fabricated by using a branched polyethylenimine as the structure director and catalyst. BGNCs show an excellent apatite-forming ability and high biocompatibility. Importantly, BGNCs demonstrate an almost 19 times higher miRNA loading than those of conventional BGNs. Additionally, BGNCs–miRNA nanocomplexes exhibit a significantly high antienzymolysis, enhance cellular uptake and miRNA transfection efficiency, overpassing BGNs and commercial Lipofectamine 3000. BGNCs-mediated miRNA delivery significantly improves the osteogenic differentiation of bone marrow stromal stem cells in vitro and efficiently enhances bone formation in vivo. BGNCs can be a highly efficient nonviral vector for various gene therapy applications. The study may provide a novel strategy to develop highly gene-activated bioactive nanomaterials for simultaneous tissue regeneration and disease therapy.

Monodispersed bioactive glass nanoclusters (BGNCs) with ultra-large mesopores (10–30 nm) are developed for miRNA delivery to enhance bone regeneration. BGNCs demonstrated an ultrahigh miRNA loading and transfection efficiency, overpassing commercial lipofectamine. BGNCs-mediated miRNA delivery significantly improved osteogenic differentiation of bone marrow stromal stem cells in vitro and enhanced bone formation in vivo.

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Newly Designed Silica-Containing Redox Nanoparticles for Oral Delivery of Novel TOP2 Catalytic Inhibitor for Treating Colon Cancer

Although oral drug delivery is the most common route of drug administration, the conventional polymeric nanocarriers exhibit a low drug loading capacity and low stability in the gastrointestinal (GI) environments. In this study, a newly designed silica-containing redox nanoparticle (siRNP) with reactive oxygen species (ROS) scavenging capacity is developed as an ideal oral nanocarrier for a novel hydrophobic anticancer compound BNS-22 to treat colitis-associated colon cancer in vivo. Crosslinking of silica moieties significantly enhances the stability under acidic conditions and improves BNS-22 loading capacity of siRNP compared to the conventional redox nanoparticle. After oral administration to mice, BNS-22-loaded siRNP (BNS-22@siRNP) remarkably improves bioavailability and colonic tumor distribution of BNS-22. As the result, BNS-22@siRNP significantly inhibits the tumor progression in colitis-associated colon cancer mice compared to other control treatments. It is noteworthy that no systemic absorption of siRNP carrier is observed after oral administration. Interestingly, orally administered BNS-22@siRNP significantly suppresses the adverse effects of BNS-22 owing to its ROS scavenging capacity, and no other noticeable toxicities are observed in mice treated with BNS-22@siRNP although siRNP is localized in the GI tract. Our results indicate that siRNP is a promising oral drug nanocarrier for cancer therapy.

Novel silica-containing redox nanoparticle (siRNP) is developed to enhance the stability and drug loading capacity with reactive oxygen species (ROS) scavenging activity. Oral administration of hydrophobic drug-loaded siRNP significantly improves drug bioavailability to inhibit the tumor growth in a mouse colon cancer model. By accumulating in gastrointestinal tract, ROS scavenging capacity of siRNP suppresses the systemic side effect of anticancer drug. siRNP is a promising candidate as novel nanotherapeutic and nanocarrier for a wide range of water-insoluble chemotherapeutic agents.

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Controlled Exposure of Bioactive Growth Factor in 3D Amyloid Hydrogel for Stem Cells Differentiation

Amyloid based hydrogels can mimic the extracellular matrix and serve as matrices for tissue engineering both in vitro and in vivo. A pH responsive self-assembled amyloid hydrogel system is used to encapsulate various growth factors for driving stem cell differentiation toward neuronal lineage. Diffusion studies with fluorescence recovery after photobleaching and bulk release with the model protein fluorescein isothiocyanate-bovine serum albumin show that encapsulated protein molecules can be released in a sustained fashion from the hydrogel over a considerable period of time (30 d). Moreover, by modulating the porosity of the hydrogel by the simple addition of salt, the encapsulated protein molecules can be retained for a longer period of time within the hydrogel. Mesenchymal stem cells, when cultured in 3D amyloid hydrogels with growth factors fibroblast growth factor 8 and sonic hedgehog, show more neuron specific differentiation as compared to hydrogel alone. This higher differentiation potential of growth factor encapsulated amyloid hydrogels can be due to concomitant exposure of cells to biomechanical as well as biochemical cues during the course of differentiation. The present study suggests that amyloid based hydrogel can be exploited for controlled growth factor delivery as well as directed stem cell differentiation to neuron.

Amyloid hydrogel for sustained growth factors delivery in tissue engineering applications. Amyloid based hydrogels can mimic the extracellular matrix and serve as matrices for tissue engineering applications both in vitro and in vivo. A pH responsive, self-assembled amyloid hydrogel system is used to encapsulate various growth factors for driving stem cell differentiation toward neuronal lineage.

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Borealis-1: A Randomized, First Line, Placebo-Controlled Phase 2 Study Evaluating Apatorsen and Chemotherapy for Patients with Advanced Urothelial Cancer

Abstract

BackgroundFive year survival of patients with inoperable, advanced urothelial carcinoma (UC) treated with first line chemotherapy is 5 to 15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients.Patients and methodsThis placebo-controlled, double-blind phase 2 trial randomized 183 untreated UC patients (North America and Europe) to receive GC plus either placebo (N=62), apatorsen 600 mg (N= 60), or apatorsen 1000 mg (N=61). In the experimental arm, treatment included loading doses of apatorsen followed by up to 6 cycles of apatorsen plus GC. Patients receiving at least 4 cycles could continue apatorsen monotherapy as maintenance until progression or unacceptable toxicity. The primary endpoint was OSResultsOS was not significantly improved in the single or combined 600 mg or 1000 mg apatorsen arms versus placebo (hazard ratio [HR] 0.86 and 0.90, respectively). Exploratory study of specific statistical modeling showed a trend for improved survival in patients with baseline poor prognostic features treated with 600 mg apatorsen compared to placebo (HR = 0.72). Landmark analysis of serum Hsp27 (sHsp27) levels showed a trend towards survival benefit for poor-prognosis patients in apatorsen 600 mg and 1000 mg arms who achieved lower area-under-the-curve (AUC) sHsp27 levels, compared to the placebo arm (HR = 0.45, and 0.62 respectively). Higher baseline CTCs (≥5 cells/7.5 mL) was observed in patients with poor prognosis in correlation with poor survival. Treatment-emergent adverse events were manageable and more common in both apatorsen-treatment arms.ConclusionsEven though apatorsen combined with standard chemotherapy did not demonstrate a survival benefit in the overall study population, patients with poor prognostic features might benefit from this combination. Serum Hsp27 levels may act as a biomarker to predict treatment outcome. Further exploration of apatorsen in poor risk patients is warranted.

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Global Patterns of Care in Advanced Stage Mycosis Fungoides/Sezary Syndrome: A Multicenter Retrospective Follow-Up Study from the Cutaneous Lymphoma International Consortium

Abstract

BACKGROUND: Advanced-stage Mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyse the pattern of care world-wide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA vs non-USA) and whether the heterogeneity of approaches have potential impact on survival.PATIENTS AND METHODS: This study included 853 patients from 21 specialist centres (14 European, 4 USA, 1 each Australian, Brazilian and Japanese).RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving 4 or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centres, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first line treatment in USA whilst phototherapy, interferon, chlorambucil and gemcitabine in non-USA centres. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR=2.07) and polychemotherapy (SHR=1.69) showed elevated relative risks.CONCLUSION: this large multicentre retrospective study shows there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centres but these were not related to survival, whilst our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

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Risk of age-related macular degeneration in patients with prostate cancer: a nationwide, population-based cohort study

Abstract

Background: Prostate cancer (PC) can be related to increased systemic oxidative stress and dihydrotestosterone level, which are also reported to be involved in the pathogenesis of age-related macular degeneration (AMD). We conducted a cohort study to determine whether patients with PC have an increased risk of AMD.Patients and methods: Data were collected from the Taiwan Longitudinal Health Insurance Database for the 1999–2010 period. The study PC cohort comprised 22 084 patients aged ≥18 years with a first diagnosis of PC. The comparison cohort consisted of age-, occupation-, and urbanization level- matched patients at a ratio of 1:1. The primary outcome was the incidence of AMD, which was evaluated using Kaplan–Meier survival analysis and proportional hazards modeling.Results: The mean follow-up periods (standard deviation, SD) for the patients with AMD in the age-, occupation-, and urbanization level- matched PC cohort and non-PC cohorts were 4.69 (2.90) and 5.51 (2.82) years. The mean age of the PC cohort was 73.9 years and that of the non-PC cohort was 73.2 years, with approximately 85.9% of the patients aged >65 years. The PC cohort had a higher risk of AMD than did the propensity score-matched non-PC cohort with an adjusted hazard ratio (aHR) of 1.25 (95% CI = 1.12–1.39). Compared with PC cohort receiving no injection hormone therapy, the PC cohort receiving injection hormone therapy had a lower risk of AMD (aHR = 0.56, 95% CI = 0.41–0.76).Conclusion: PC is associated with an increased risk of AMD. Patients with PC receiving injected form of androgen deprivation therapy had a lower risk of AMD than patients with PC not receiving injected form of androgen-deprivation therapy.

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Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer

Abstract

Background: Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1% have characteristics similar to those with 1%≤ER<10%. We hypothesized that in patients with HER2-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pCR rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy.Patients and methods: Patients with stage II or III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence (TTR) and overall survival (OS). The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression.Results: A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95% CI = 0.986-0.994, P<0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER ≥ 10% tumors, but not those with 1%≤ER<10% tumors, adjuvant hormonal therapy was significantly associated with long TTR (HR = 0.24, 95% CI = 0.16-0.36, P<0.001) and OS (HR = 0.32, 95% CI = 0.2-0.5, P<0.001).Conclusion: Stage II or III HER2-negative primary breast cancer with ER < 10% behaves clinically like TNBC in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define TNBC as HER2-negative breast cancer with <10%, rather than <1%, of ER and/or PR expression.

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An antisense oligonucleotide targeting TGF-β2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages.

Abstract

Background: The TGF-β pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-β pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-β isoforms and not much is known about the oncogenic response to each of the isoforms. Here we studied the anti-tumor response to ISTH0047, a recently-developed locked nucleic acid (LNA)-modified antisense oligonucleotide targeting TGF-β2.Materials and Methods: We have studied the anti-cancer response to ISTH0047 using gymnotic delivery in tumor cell cultures and in in vivo preclinical orthotopic mouse models for primary tumors (breast and kidney tumors) and lung metastasis.Results: We observed that ISTH0047 is able to significantly reduce TGF-β2 mRNA and protein levels without altering the levels of TGF-β1 and TGF-β3. ISTH0047 prevented lung metastasis in syngeneic orthotopic renal cell carcinoma (RENCA) and breast cancer (4T1) tumor models. In addition, using an orthotopic xenograft model of a lung cancer cell line (CRL5807) that mainly expresses TGF-β2, we observed that ISTH0047 had an important effect on the lung microenvironment inhibiting the growth of lung lesions. ISTH0047 treatment re-educated macrophages in the lung parenchyma to express the tumor-suppressive factor, CD86.Conclusion: Overall, our data point to TGF-β2 as a therapeutic target and ISTH0047 as a novel anti-cancer drug to prevent lung metastasis by impacting on the tumor niche, in part through the induction of CD86 in tumor-associated macrophages.

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BRAF mutant Colorectal Cancer: prognosis, treatment and new perspectives

Abstract

The MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also linked with less benefit when treated with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Targeting this molecular aberration has thus become a matter of particular interest in mCRC drug development. In contrast to other malignances such as BRAF mutant (mt) melanoma, efficacy observed with BRAF inhibitors in mono-therapy in mCRC is poor. Several mechanisms of resistance have been identified leading to the development of different treatment strategies that have shown promising activity in early clinical trials. Hence, rational combination of targeted therapies is expected to further increase the efficacy of selective BRAF inhibitors. Herein, we discuss the main clinical and molecular characteristics of BRAF mt colorectal cancer (CRC) and its translation into the clinic, with a focus on developmental therapeutics and combination strategies. In addition, we contextualize the available data with potential future approaches that include the extended access to next-generation sequencing platforms and gene expression strategies for molecular subtyping. These approaches will facilitate the identification of certain patient profiles providing more therapeutic possibilities.

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High Efficiency Nonfullerene Polymer Solar Cells with Thick Active Layer and Large Area

In this work, high-efficiency nonfullerene polymer solar cells (PSCs) are developed based on a thiazolothiazole-containing wide bandgap polymer PTZ1 as donor and a planar IDT-based narrow bandgap small molecule with four side chains (IDIC) as acceptor. Through thermal annealing treatment, a power conversion efficiency (PCE) of up to 11.5% with an open circuit voltage (V_oc) of 0.92 V, a short-circuit current density (J_sc) of 16.4 mA cm⁻², and a fill factor of 76.2% is achieved. Furthermore, the PSCs based on PTZ1:IDIC still exhibit a relatively high PCE of 9.6% with the active layer thickness of 210 nm and a superior PCE of 10.5% with the device area of up to 0.81 cm². These results indicate that PTZ1 is a promising polymer donor material for highly efficient fullerene-free PSCs and large-scale devices fabrication.

The nonfullerene polymer solar cells based on a wide bandgap polymer PTZ1 and a narrow bandgap acceptor IDIC exhibit weak active layer thickness and area dependence with the optimal power conversion efficiency of 11.5%, indicating that the blend of PTZ1/IDIC is potential for the practical application of polymer solar cells.

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Isoindigo-Based Polymers with Small Effective Masses for High-Mobility Ambipolar Field-Effect Transistors

So far, most of the reported high-mobility conjugated polymers are p-type semiconductors. By contrast, the advances in high-mobility ambipolar polymers fall greatly behind those of p-type counterparts. Instead of unipolar p-type and n-type materials, ambipolar polymers, especially balanced ambipolar polymers, are potentially serviceable for easy-fabrication and low-cost complementary metal-oxide-semiconductor circuits. Therefore, it is a critical issue to develop high-mobility ambipolar polymers. Here, three isoindigo-based polymers, PIID-2FBT, P1FIID-2FBT, and P2FIID-2FBT are developed for high-performance ambipolar organic field-effect transistors. After the incorporation of fluorine atoms, the polymers exhibit enhanced coplanarity, lower energy levels, higher crystallinity, and thus increased µ_e. P2FIID-2FBT exhibits n-type dominant performance with a µ_e of 9.70 cm² V⁻¹ s⁻¹. Moreover, P1FIID-2FBT exhibits a highly balanced µ_h and µ_e of 6.41 and 6.76 cm² V⁻¹ s⁻¹, respectively, which are among the highest values for balanced ambipolar polymers. Moreover, a concept "effective mass" is introduced to further study the reasons for the high performance of the polymers. All the polymers have small effective masses, indicating good intramolecular charge transport. The results demonstrate that high-mobility ambipolar semiconductors can be obtained by designing polymers with fine-tuned energy levels, small effective masses, and high crystallinity.

Three isoindigo-based polymers, PIID-2FBT, P1FIID-2FBT, and P2FIID-2FBT are developed for high-performance ambipolar organic field-effect transistor. After the incorporation of fluorine atoms, the polymers show that an obvious mobility changes from p-channel dominant to n-channel dominant transport characteristics. Especially, P1FIID-2FBT exhibits a highly balanced electron/hole mobility, resulting from the fine-tuned energy levels, high crystallinity, and relatively small effective mass.

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Nitrogen-Superdoped 3D Graphene Networks for High-Performance Supercapacitors

An N-superdoped 3D graphene network structure with an N-doping level up to 15.8 at% for high-performance supercapacitor is designed and synthesized, in which the graphene foam with high conductivity acts as skeleton and nested with N-superdoped reduced graphene oxide arogels. This material shows a highly conductive interconnected 3D porous structure (3.33 S cm⁻¹), large surface area (583 m² g⁻¹), low internal resistance (0.4 Ω), good wettability, and a great number of active sites. Because of the multiple synergistic effects of these features, the supercapacitors based on this material show a remarkably excellent electrochemical behavior with a high specific capacitance (of up to 380, 332, and 245 F g⁻¹ in alkaline, acidic, and neutral electrolytes measured in three-electrode configuration, respectively, 297 F g⁻¹ in alkaline electrolytes measured in two-electrode configuration), good rate capability, excellent cycling stability (93.5% retention after 4600 cycles), and low internal resistance (0.4 Ω), resulting in high power density with proper high energy density.

An N-superdoped 3D graphene network structure is synthesized to achieve highly conductive interconnected 3D porous structure and high N-doping level simultaneously. The supercapacitors based on this material show a remarkably high capacity, good rate capability, and excellent cycling stability.

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Biogeochemical gradients and microbial communities in Winogradsky columns established with polluted wetland sediments

A Winogradsky column is a miniature ecosystem established with enriched sediments that can be used to study the relationship between biogeochemical gradients, microbial diversity and pollutant transformation. Biogeochemical processes and microbial communities changed with time and depth in Winogradsky columns incubated with heavy-metal-polluted wetland sediments for 520 days. 16S rRNA surveys were complemented by geochemical analyses, including heavy metal proportioning, to evaluate gradients in the mostly anoxic columns. Oxygen was depleted below the water–sediment interface (WSI), while NH₄⁺, Fe²⁺, S²⁻ and acetate increased by one order of magnitude at the bottom. Microbial niche differentiation occurred mainly by depth and from the light-exposed surface to the interior of the columns. Gradients resulting from nutrient uptake by algae, and from iron and sulphate reduction mainly drove diversification. Heavy-metal proportioning did not significantly influence microbial diversity as Cu and Zn were immobilised at all depths. Proteobacteria were abundant in the top water and the WSI layers, whereas Firmicutes and Bacteroida dominated down-core. Together with low diversity and richness of communities at the WSI and column bottom, changes in the bacterial community coincided with algal-derived carbon sources and cellulose fermentation, respectively. We expect this study to be the starting point for the use Winogradsky columns to study microbial and geochemical dynamics in polluted sediments.

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Novel sequence types of extended-spectrum and acquired ampc beta-lactamase producing Escherichia coli and Escherichia clade V isolated from wild mammals

Abstract

The closer contact with wildlife due to the growing human population and the destruction of natural habitats emphasizes the need of gaining insight into the role of animals as source of antimicrobial resistance. Here, we aim at characterizing the antimicrobial resistance genes and phylogenetic distribution of commensal E. coli from 62 wild mammals. Isolates exhibiting resistance to ≥ 1 antibiotic were detected in 25.8% of the animals and 6.4% carried an ESBL/AmpC-producing E. coli. Genetic mechanisms involved in third-generation cephalosporin resistance were: i) hyperproduction of chromosomal AmpC (hedgehog), ii) production of acquired CMY-2 β-lactamase (hedgehog), iii) production of SHV-12 and CTX-M-14 ESBLs (n = 2, mink and roe-deer). ESBL genes were transferable by conjugation and bla_CMY-2 was mobilized by a 95kb IncI1 plasmid. The distribution of the phylogenetic groups in the E. coli collection studied was B1 (44.6%), B2 (24.6%), E (15.4%), A (4.6%) and F (3.1%). Five isolates (7.7%) were cryptic Escherichia clades (clade IV, 4 mice; clade V, 1 mink). ESBL/AmpC-E. coli isolates showed different STs: ST1128/B1, ST4564/B1 (new), ST4996/B1 (new), and a non registered ST. This study contributes to better understand the E. coli population and antimicrobial resistance flow in wildlife and reports new AmpC-E. coli sequence types and a first described ESBL-producing Escherichia clade V isolate.

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Adolescent body mass index and risk of colon and rectal cancer in a cohort of 1.79 million Israeli men and women: A population-based study

BACKGROUND

This study examined the association between the body mass index (BMI) in late adolescence and the risk of colon and rectal cancer.

METHODS

This study analyzed a cohort of 1,087,358 Jewish men and 707,212 Jewish women who underwent health examinations at the ages of 16 to 19 years between 1967 and 2002 and were followed by linkage to the national cancer registry up to 2012. Cox regression was used to estimate hazard ratios (HRs) for cancer according to age- and sex-adjusted BMI percentiles from the US Centers for Disease Control and Prevention (overweight, 85th percentile to <95th percentile; obesity, ≥95th percentile).

RESULTS

Over a median follow-up of 23 years, 2967 incidence cases of colorectal cancer, including 1977 among men (1403 in the colon and 574 in the rectum) and 990 among women (764 in the colon and 226 in the rectum), were identified. Overweight and obesity were associated with the risk for colon cancer among both men (HR for overweight, 1.53; 95% confidence interval [CI], 1.28-1.84; HR for obesity, 1.54; 95% CI, 1.15-2.06; statistically significant from a BMI of 23.4 kg/m² [spline analysis]) and women (HR for overweight, 1.54; 95% CI, 1.22-1.93; HR for obesity, 1.51; 95% CI, 0.89-2.57; significant from a BMI of 23.6 kg/m²). Obesity, but not overweight, was associated with a risk for rectal cancer among men (HR, 1.71; 95% CI, 1.11-2.65; significant from a BMI of 29.6 kg/m²) and women (HR, 2.03; 95% CI, 0.90-4.58; significant from a BMI of 30.6 kg/m²).

CONCLUSIONS

Being overweight or obese in adolescence was associated with an increased risk of subsequent colon cancers in men and women, whereas obesity was associated with rectal cancer. Cancer 2017. © 2017 American Cancer Society.

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Effect of implantoplasty on fracture resistance and surface roughness of standard diameter dental implants

Abstract

Objective

To assess the effect of implantoplasty on the fracture resistance, surface roughness, and macroscopic morphology of standard diameter (4.1 mm) external connection dental implants.

Materials and methods

An in vitro study was conducted in 20 screw-shaped titanium dental implants with an external connection. In 10 implants, the threads and surface were removed and polished with high-speed burs (implantoplasty), while the remaining 10 implants were used as controls. The final implant dimensions were recorded. The newly polished surface quality was assessed by scanning electron microscopy (SEM) and by 3D surface roughness analysis using a confocal laser microscope. Finally, all the implants were subjected to a mechanical pressure resistance test. A descriptive analysis of the data was made. Also, Student's t tests were employed to detect differences regarding the compression tests.

Results

Implantoplasty was carried out for a mean time of 10 min and 48 s (standard deviation (SD) of 1 min 22 s). Macroscopically, the resulting surface had a smooth appearance, although small titanium shavings and silicon debris were present. The final surface roughness (S_a values 0.1 ± 0.02 μm) was significantly lower than that of the original (0.75 ± 0.08 μm S_a) (p = .005). There was minimal reduction in the implant's inner body diameter (0.19 ± 0.03 mm), and no statistically significant differences were found between the test and control implants regarding the maximum resistance force (896 vs 880 N, respectively).

Conclusions

Implantoplasty, although technically demanding and time-consuming, does not seem to significantly alter fracture resistance of standard diameter external connection implants. A smooth surface with S_a values below 0.1 μm can be obtained through the use of silicon polishers. A larger sample is required to confirm that implantoplasty does not significantly affect the maximum resistance force of standard diameter external connection implants.

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Alveolar bone resorption after primary tooth loss has a negative impact on straightforward implant installation in patients with agenesis of the lower second premolar

Abstract

Objectives

To compare the alveolar bone dimensions in patients with lower second premolar (P2) agenesis prior to and after primary molar loss on CT scans, and assess the possibility for straightforward implant placement.

Methods

Alveolar bone dimensions were evaluated on 150 mandibular CT scans in three groups: (i) agenesis of P2, with the primary tooth in situ, and regularly erupted first premolar (P1) and molar (M1) (AW); (ii) agenesis of P2, without the primary tooth in situ for ≥3 m, but regularly erupted P1 and M1 (AWO); and (iii) P1, P2, and M1 regularly erupted (CTR). The possibility of straightforward placement of an implant 3.5 or 4.3 mm in Ø × 10 mm long was digitally simulated and compared to the actually performed treatment.

Results

Buccolingual width (7.3 ± 2.0 mm) at the coronal aspect of the ridge in the AWO group was statistically significantly smaller comparing with both the AW (9.2 ± 1.4 mm) and the CTR (9.5 ± 1.1 mm) group; width reduction appeared to be mainly due to "collapse" of the buccal aspect of the ridge. Simulated straightforward placement of implants with a diameter of 3.5 or 4.3 mm was possible in 62% and 56% of the cases in the AWO vs. 86% and 84% in the AW group (p = .006 and .002, respectively). Straightforward implant placement was actually possible in all patients (22) in the AW group, while 28% (11 of 39) of the patients in the AWO group needed additional hard tissue augmentation.

Conclusions

Significant dimensional differences exist in the alveolar ridge, especially in the coronal part, at lower P2 agenesis sites missing the primary tooth for ≥3 m, when compared to P2 agenesis sites with the primary tooth in situ. It seems thus reasonable to advise that the primary second molar should be kept as long as possible, in order to facilitate straightforward implant installation and reduce the probability of additional bone augmentation procedures.

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Cannabis use, legalization and youth health [Letters]

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Long-term stroke prevention: We can do better [Commentary]

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A national health care data network is overdue [Editorial]

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Long-term morbidity and mortality in patients without early complications after stroke or transient ischemic attack [Research]

BACKGROUND:

Secondary prevention after stroke and transient ischemic attack (TIA) has focused on high early risk of recurrence, but survivors of stroke can have substantial long-term morbidity and mortality. We quantified long-term morbidity and mortality for patients who had no early complications after stroke or TIA and community-based controls.

METHODS:

This longitudinal case–control study included all ambulatory or hospitalized patients with stroke or TIA (discharged from regional stroke centres in Ontario from 2003 to 2013) who survived for 90 days without recurrent stroke, myocardial infarction, all-cause admission to hospital, admission to an institution or death. Cases and controls were matched on age, sex and geographic location. The primary composite outcome was death, stroke, myocardial infarction, or admission to long-term or continuing care. We calculated 1-, 3- and 5-year rates of composite and individual outcomes and used cause-specific Cox regression to estimate long-term hazards for cases versus controls and for patients with stroke versus those with TIA.

RESULTS:

Among patients who were initially stable after stroke or TIA (n = 26 366), the hazard of the primary outcome was more than double at 1 year (hazard ratio [HR] 2.4, 95% confidence interval [CI] 2.3–2.5), 3 years (HR 2.2, 95% CI 2.1–2.3) and 5 years (HR 2.1, 95% CI 2.1–2.2). Hazard was highest for recurrent stroke at 1 year (HR 6.8, 95% CI 6.1–7.5), continuing to 5 years (HR 5.1, 95% CI 4.8–5.5), and for admission to an institution (HR 2.1, 95% CI 1.9–2.2). Survivors of stroke had higher mortality and morbidity, but 31.5% (1789/5677) of patients with TIA experienced an adverse event within 5 years.

INTERPRETATION:

Patients who survive stroke or TIA without early complications are typically discharged from secondary stroke prevention services. However, these patients remain at substantial long-term risk, particularly for recurrent stroke and admission to an institution. Novel approaches to prevention, potentially embedded in community or primary care, are required for long-term management of these initially stable but high-risk patients.

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SOGC urges national enquiry into maternal deaths [News]

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Neurosyphilis mimicking autoimmune encephalitis in a 52-year-old man [Practice]

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Cannabis prohibition harms Canadas youth [Letters]

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Metastatic lung cancer presenting as cutaneous nodules [Practice]

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3D printing set to revolutionize medicine [News]

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The clinical trials on gamma globulin for polio: victims of marketing success [Humanities]

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WHO guidelines on ethical public health surveillance [News]

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Neuroticism May Postpone Death for Some

Data from a longitudinal study of over 500,000 people in the United Kingdom indicate that having higher levels of the personality trait neuroticism may reduce the risk of death for individuals who report being in fair or poor health. The research, published in Psychological Science, a journal of the Association for Psychological Science, further revealed that a specific aspect of neuroticism related to worry and feelings of vulnerability was associated with lower mortality, regardless of self-reported health.

"Our findings are important because they suggest that being high in neuroticism may sometimes have a protective effect, perhaps by making people more vigilant about their health," says lead researcher Catharine R. Gale of the University of Edinburgh and University of Southampton.

By definition, people with high levels of neuroticism are more likely to experience negative emotions—including irritability, frustration, nervousness, worry, and guilt—compared with their peers who have lower levels of neuroticism. Studies investigating links between neuroticism and mortality have produced inconsistent results, with some showing higher risk of death and others showing no relationship or even lower risk of death.

Drawing from existing evidence, Gale and colleagues hypothesized that the relationship between neuroticism and risk of death may depend on how people rate their health.

The researchers examined UK Biobank data collected from 502,655 people ages 37 to 73. Participants completed a validated personality assessment measuring neuroticism and indicated whether they thought they were in excellent, good, fair, or poor health overall. The data also included information on participants' health behaviors (e.g., smoking, physical activity), physical health (e.g., body mass index, blood pressure), cognitive function, and medical diagnoses (e.g., heart problems, diabetes, cancer).

Examining death certificates from the National Health Service Central Registry, the researchers found that a total of 4,497 participants had died in the follow-up period (which was about 6.25 years, on average). In general, the data showed that mortality was slightly higher among participants with higher levels of neuroticism. However, when Gale and colleagues adjusted for participants' self-rated health, they found that the direction of the relationship reversed, with higher neuroticism being linked with slightly lower risk of death from all causes and from cancer.

"When we explored this further, we found that this protective effect was only present in people who rated their health as fair or poor," explains Gale. "We also found that people who scored highly on one aspect of neuroticism related to worry and vulnerability had a reduced risk of death regardless of how they rated their health."

Intriguingly, these relationships did not seem to vary according to participants' health behaviors or medical diagnoses at the time they completed the neuroticism questionnaire, a finding which surprised the researchers.

"Health behaviors such as smoking, exercise, diet and alcohol consumption did not explain any part of the link between high scores on the worry/vulnerability facet and mortality risk. We had thought that greater worry or vulnerability might lead people to behave in a healthier way and hence lower their risk of death, but that was not the case," Gale says.

Following on these findings, Gale and colleagues plan to further investigate the different facets of neuroticism to understand why worry and vulnerability may have specific protective effects.

Co-authors on the study include Iva Čukić (University of Edinburgh), G. David Batty (University of Edinburgh and University College London), Andrew M. McIntosh (University of Edinburgh), Alexander Weiss (University of Edinburgh), and Ian J. Deary (University of Edinburgh).

This work was undertaken in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (Grant MR/K026992/1), which supports I. J. Deary. Funding from the Biotechnology and Biological Sciences Research Council and the Medical Research Council (MRC) is gratefully acknowledged. I. J. Deary, C. R. Gale, and I. Čukić are supported by the MRC (Grant MR/K025023/1). I. J. Deary and A. M. McIntosh are supported by the Wellcome Trust (Grant 104036/Z/14/Z).

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Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation

Aim

The nicotinic acid analogue acipimox is an anti-lipolytic agent, which acutely inhibits lipolysis, and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of acipimox are transient due to a counter-regulatory increase in growth hormone (GH) levels that reverse the anti-lipolytic effect of acipimox. Hypopituitary patients constitute a viable model to study the GH-independent effects of acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with acipimox acutely affects autonomic tone.

Methods

We studied heart rate variability (HRV) as a measure of autonomic tone in eight hypopituitary men with and without acipimox treatment. SDNN, RMSSD, and HF were measured as HRV parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on 2 occasions in a randomized, double blind and placebo controlled crossover study.

Results

Plasma glucose (4.7 vs. 4.9 mmol/l, P=0.02) and serum FFA (0.05 vs. 0.41 mmol/l, P<0.001) were significantly decreased during acipimox treatment. Acipimox had an inhibitory effect on SDNN (41.3 vs. 45.3 ms, P=0.01), RMSSD (23.2 vs. 11 ms, P=0.03), and HF (3.79 vs 3.60 ln(ms²), P=0.02) and these effects were reversed during clamping.

Conclusions

We showed that short-term inhibition of lipolysis by acipimox treatment lowered circulating FFA levels, improved insulin sensitivity, and was accompanied by reduced parasympathetic tone. The effect of acipimox on the parasympathetic modulation was reversed by hyperinsulinaemia.

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Changes of Blood Flux at BL21 and Points along BL Meridian Resulted from Acupuncture or Moxibustion: Case Cross Design Study

Acupuncture (Acup) and moxibustion (Moxi) are commonly used interventions in clinical practice. However, the difference between Acup and moxibustion mechanisms is unclear. In current study, blood perfusion responses resulted from Acup or Moxi at Weishu acupoint (BL21) and control points were explored, respectively. The time series of blood flux signals at BL21 and control points were transformed with Morlet wavelet, and the differences in each frequency interval were observed. The results suggested that acupoint response to different stimulation is a comprehensive process which related to all components of blood perfusion signals. Whereas the different response at control points was not observed, there has been significant difference coherence value between Acup and Moxi stimulation. The results suggested the influence of Acup and Moxi not only on the level of blood perfusion at local area; the intrinsic relevance after stimulation which can be evaluated by coherence analysis is also an appropriate index to distinguish different stimulations.

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Oil Characterization and Lipids Class Composition of Pomegranate Seeds

This study aims to investigate the physicochemical characteristics, phenolics content, and oil composition of pomegranate oil seeds (PSO). Quality indices, pigments, phenolics content, and antioxidant activity were determined. PSO was fractioned into polar lipids: glycolipids (GL) and phospholipids (PL). Sterols profile and fatty acids composition of total lipids (TL), GL, and PL were determined by GC/FID. The free acidity, the peroxide value, and the specific extinction coefficients were, respectively, 1.69%, 3.42 in milliequivalents of active oxygen per kilogram of oil, 4.15, and 3.95. PSO is rich in phenols (93.42 mg/Kg) but poor in pigments. The sterols markers were β-sitosterol (77.94%), Δ5-avenasterol (7.45%), and campesterol (6.35%). Oil content was 12.2%, wherein 23.9% were GL and 24.35% were PL. TL were rich in unsaturated fatty acids (63.17%), while saturated fatty acids were more present in PL and GL (71.97% and 66.29%, resp.). Conjugated fatty acids were about 13.30%, 2.03%, and 4.91%, respectively, in TL, PL, and GL. The cis/trans ratio of TL, PL, and GL was, respectively, 49.82%, 42.91%, and 27.39%. Monounsaturated fatty acids were more bound in PL, whereas polyunsaturated fatty acids were more bound in GL. PSO is a good source of essential fatty acids, phenolics compounds, phytosterols, and lipid-soluble fractions.

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Surgical Approach May Influence Survival of Large-Diameter Head Metal-on-Metal Total Hip Arthroplasty: A 6- to 10-Year Follow-Up Study

Large-diameter head (LDH) metal-on-metal (MoM) total hip arthroplasty (THA) has lost popularity because of metal allergy or ALTRs (adverse local tissue reactions) in the past decade. Whether the surgical approach may influence the survival of LDH-MoM-THA has not been reported. From 2006 to 2009, we performed 96 LDH-MoM-THAs on 80 patients using an in situ head-neck assembly technique through a modified Watson-Jones approach. With a mean follow-up of 8.4 years (range, 6.3–10.1 years), the implant survival rate was 100%. All patients were satisfied with the results and the Harris Hip Score improved from 52 points to 98 points. No ALTRs were found, but 17.7% of the 96 hips (17 adverse events) experienced adverse events related to the cup, including 5 cases of outlier cup malposition, 11 cases of inadequate cup seating, and 1 acetabular fracture. The tissue tension that was improved by a muscle-sparing approach might lessen the chance of microseparation or edge-loading that is taken as the major risk for early implant failure. Further investigation of whether these LDH-MoM-THAs would fail or not would require a longer follow-up or even retrieval analysis in the future.

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MRI Texture Analysis of Background Parenchymal Enhancement of the Breast

Purpose. The purpose of this study was to determine texture parameters reflecting the background parenchymal enhancement (BPE) of the breast, which were acquired using texture analysis (TA). Methods. We investigated 52 breasts of the 26 subjects who underwent dynamic contrast-enhanced MRI. One experienced reader scored BPE visually (i.e., minimal, mild, moderate, and marked). TA, including 12 texture parameters, was performed to distinguish the BPE scores quantitatively. Relationships between the visual BPE scores and texture parameters were evaluated using analysis of variance and receiver operating characteristic analysis. Results. The variance and skewness of signal intensity were useful for differentiating between moderate and mild or minimal BPE or between mild and minimal BPE, respectively, with the cutoff value of 356.7 for variance and that of 0.21 for skewness. Some TA features could be useful for defining breast lesions from the BPE. Conclusion. TA may be useful for quantifying the BPE of the breast.

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Whole-Body SPECT/CT versus Planar Bone Scan with Targeted SPECT/CT for Metastatic Workup

Purpose. The use of SPECT/CT in bone scans has been widespread in recent years, but there are no specific guidelines concerning the optimal acquisition protocol. Two strategies have been proposed: targeted SPECT/CT for equivocal lesions detected on planar images or systematic whole-body SPECT/CT. Our aim was to compare the diagnostic accuracy of the two approaches. Methods. 212 consecutive patients with a history of cancer were referred for bone scans to detect bone metastases. Two experienced readers randomly evaluated for each patient either planar images with one-field SPECT/CT targeted on equivocal focal uptakes (targeted SPECT/CT) or a whole-body (two-field) SPECT/CT acquisition from the base of the skull to the proximal femurs (whole-body SPECT/CT). The exams were categorized as "nonmetastatic," "equivocal," or "metastatic" on both protocols. The presence or absence of any extra-axial skeletal lesions was also assessed. The sensitivity and specificity of both strategies were measured using the results of subsequent imaging follow-up as the reference standard. Results. Whole-body SPECT/CT had a significantly higher sensitivity than targeted SPECT/CT to detect bone metastases and to detect extra-axial metastases . There was no significant difference in specificity among the two approaches. Conclusion. Whole-body SPECT/CT is the optimal modality of choice for metastatic workup, including detection of extra-axial lesions, with improved sensitivity and similar specificity compared to targeted SPECT/CT.

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Syntool: A Novel Region-Based Intolerance Score to Single Nucleotide Substitution for Synonymous Mutations Predictions Based on 123,136 Individuals

Background. Synonymous mutation is the single nucleotide change that does not cause an amino acid change but can affect the rate and efficiency of translation. So recent increase in our knowledge has revealed a substantial contribution of synonymous mutations to human disease risk and other complex traits. Nevertheless, there are still rarely synonymous mutation prediction methods. Methods. Nonsynonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association. Here we defined synonymous and missense variation as single nucleotide substitution variation. And then we evaluated the intolerance of genic transcripts to single nucleotide substitution variation based on gnomAD 123136 individuals. After regressing all variations on common variations, we defined residuals of regression model as every genomics region intolerance scores. Results. We constructed a total of 24799 nonoverlapped region-based intolerance score by their intolerance to single nucleotide substitution variation (Syntool). The results show that Syntool score can discriminate synonymous disease causing mutations in Human Gene Mutation Database (HGMD Professional) and ClinVar database much better than others. Taken together, this study provides a novel prediction system for synonymous mutations, called Syntool, which could be helpful in identifying candidate synonymous disease causing mutations.

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Baseline Characteristics of the Paediatric Observation Priority Score in Emergency Departments outside Its Centre of Derivation

Objectives and Background. Scoring systems in Emergency Departments (EDs) are rarely validated. This study aimed to examine the Paediatric Observation Priority Score (POPS), a method of quantifying patient acuity, in EDs in the United Kingdom, and determine baseline performance characteristics. Methods. POPS was implemented in 4 EDs for children (ages of 0 to 16) with participants grouped into 3 categories: discharged from ED, discharged but with return within 7 days, and admitted for less or more than 24 hours. Results. 3323 participants with POPS scores ranging from 0 to 11 (mean = 2.33) were included. The proportion of each POPS score varied between sites with approximately 10–20% being POPS 0 and 12–25% POPS greater than 4. Odds ratio of readmission with POPS 5–9 against 0–4 was 2.05 (CI 1.20 to 3.52). POPS 0–4 showed no significant difference (p = 0.93) in relation to admission/discharge rates between sites with a significant difference found (p 5. Conclusion. It is feasible to implement POPS into EDs with similar performance characteristics to the original site of development. There is now evidence to support a wider health service evaluation to refine and improve the performance of POPS.

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Valve Calcification in Aortic Stenosis: Etiology and Diagnostic Imaging Techniques

Aortic stenosis is the most common valvulopathy in the Western world. Its prevalence has increased significantly in recent years due to population aging; hence, up to 8% of westerners above the age of 84 now have severe aortic stenosis (Lindroos et al., 1993). This causes increased morbidity and mortality and therein lies the importance of adequate diagnosis and stratification of the degree of severity which allows planning the best therapeutic option in each case. Long understood as a passive age-related degenerative process, it is now considered a rather more complex entity involving mechanisms and factors similar to those of atherosclerosis (Stewart et al., 1997). In this review, we summarize the pathophysiological mechanisms underlying the onset and progression of the disease and analyze the current role of cardiac imaging techniques for diagnosis.

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FDA Clears First Neonatal Magnetic Resonance Imaging Device

July 20, 2017 -- Today, the U.S. Food and Drug Administration cleared the first magnetic resonance imaging (MRI) device specifically for neonatal brain and head imaging in neonatal intensive care units (NICU). "Although we can use traditional MRI...

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FXa inhibition by Rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms.

Abstract

Aim

To evaluate if Rivaroxaban, an oral factor Xa (FXa) inhibitor, could in vitro modify the expression of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus.

Methods

AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol/L Rivaroxaban.

Results

AAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 (IL-6) levels released from AAA (IL-6: Control: medians: 23.45 (25^th:16.17-75^th:37.15) vs AAA: median: 153.07 (25^th:100.80-75^th:210.69) pg/ml/mg tissue. P<0.05) and the expression levels of nitric oxide synthase 2 (NOS2) were significantly higher in AAA than in control. The protein expression level of NADPH oxidase subunits gp67-and gp91-phox, but did not gp47-phox, were also significantly higher in the AAA sites than in control. Addition of Rivaroxaban to AAA sites explants significantly reduced the release of IL-6 (medians: 51.61 (25^th:30.87-75^th:74.03) pg/ml/mg tissue P<0.05 with respect to AAA alone) and the content of NOS2, gp67 and gp91-phox NADPH subunits. The content of matrix metallopeptidase 9 (MMP9) was significantly higher in the AAA sites as compare to control. Rivaroxaban also reduced MMP9 content in AAA sites to similar levels to control.

Conclusions

FXa inhibition by Rivaroxaban exerted anti-inflammatory and anti-oxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA.

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Response to R-warfarin anticoagulant effect

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Can the possibility of transverse iliosacral screw fixation for first sacral segment be predicted preoperatively? Results of a computational cadaveric study

Publication date: Available online 23 July 2017
Source:Injury
Author(s): Jin-Hoon Jeong, Jin Woo Jin, Byoung Youl Kang, Gu-Hee Jung
ObjectivesThe purpose of this study was to predict the possibility of transverse iliosacral (TIS) screw fixation into the first sacral segment (S1) and introduce practical anatomical variables using conventional computed tomography (CT) scans.Materials and MethodsA total of 82 cadaveric sacra (42 males and 40 females) were used for continuous 1.0-mm slice CT scans, which were imported into Mimics^® software to produce a three-dimensional pelvis model. The anterior height (BH) and superior width (BW) of the elevated sacral segment was measured, followed by verification of the safe zone (SZS1 and SZS2) in a true lateral view. Their vertical (VDS1 and VDS2) and horizontal (HDS1 and HDS2) distances were measured. VDS1 less than 7mm was classified as impossible sacrum, since the transverse fixation of 7.0 mm-sized IS screw could not be done safely.ResultsFourteen models (16.7%; six females, eight males) were assigned as the impossible sacrum. There was no statistical significance regarding gender (p=0.626) and height (p=0.419). The average values were as follows: BW, 31.4mm (SD 2.9); BH, 16.7mm (SD 6.8); VDS1, 13.4mm (SD 6.1); HDS1, 22.5mm (SD 4.5); SZS1, 239.5mm² (SD 137.1); VDS2, 15.5mm (SD 3.0); HDS2, 18.3mm (SD 2.9); and SZS2, 221.1mm² (SD 68.5). Logistic regression analysis identified BH (p=0.001) and HDS1 (p=0.02) as the only statistically significant variables to predict the possibility. Receiver operating characteristic curve analysis established a cut-off value for BH and HDS1 of impossible sacrum of 20.6mm and 18.6mm, respectively.ConclusionBH and HDS1 could be used to predict the possibility of TIS screw fixation. If the BH exceeds 20.6mm or HDS1 is less than 18.6mm, TIS screw fixation for S1 should not be undertaken because of narrowed SZ.



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Purification of Biotinylated Cell Surface Proteins from Rhipicephalus microplus Epithelial Gut Cells

A modified density centrifugation gradient-based methodology was utilized to isolate epithelial cells from Rhipicephalus microplus gut tissue. Surface-bound proteins were biotinylated and purified through streptavidin magnetic beads for utilization in downstream applications.

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Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice

This protocol demonstrates murine islet isolation and seeding onto a decellularized scaffold. Scaffold-supported islets were transplanted into the epididymal fat pad of streptozotocin (STZ)-induced diabetic mice. Islets survived at the transplantation site and reversed the hyperglycemic condition.

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