Efficacy of treatment for hyperglycemic crisis in elderly diabetic patients in a day hospital

The purpose of this prospective cohort study was to compare the costs of day hospital (DH) care for hyperglycemic crisis in elderly diabetic patients with those of conventional hospitalization (CH). Secondary objectives were to compare these two clinical scenarios in terms of glycemic control, number of emergency and outpatient visits, readmissions, hypoglycemic episodes, and nosocomial morbidity. The study population comprised diabetic patients aged >74 years consecutively admitted to a tertiary teaching hospital in Spain for hyperglycemic crisis (sustained hyperglycemia [>300 mg/dL] for at least 3 days with or without ketosis). The patients were assigned to DH or CH care according to time of admission and were followed for 6 months after discharge. Exclusion criteria were ketoacidosis, hyperosmolar crisis, hemodynamic instability, severe intercurrent illness, social deprivation, or Katz index >D. Sixty-four diabetic patients on DH care and 36 on CH care were included, with no differences in baseline characteristics. The average cost per patient was 1,345.1±793.6 € in the DH group and 2,212.4±982.5 € in the CH group (P <0.001). There were no differences in number of subjects with mild hypoglycemia during follow-up (45.3% DH versus 33.3% CH, P =0.24), nor in the percentage of patients achieving a glycated hemoglobin (HbA) <8% (67.2% DH versus 58.3% CH, P =0.375). Readmissions for hyperglycemic crisis and pressure ulcer rates were significantly higher in the CH group. DH care for hyperglycemic crises is more cost-effective than CH care, with a net saving of 1,418.4 € per case, lower number of readmissions and pressure ulcer rates, and similar short-term glycemic control and hypoglycemia rates

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

Physical and Antimicrobial Properties of Compression-Molded Cassava Starch-Chitosan Films for Meat Preservation

[EN] Cassava starch-chitosan films were obtained by melt bending and compression molding, using glycerol and polyethylene glycol as plasticizers. Both the starch/chitosan and the polymer/plasticizer ratios were varied in order to analyze their effect on the physical properties of the films. Additionally, the antimicrobial activity of 70:30 polymer:plasticizer films was tested in cold-stored pork meat slices as affected by chitosan content. All film components were thermally stable up to 200 A degrees C, which guaranteed their thermostability during film processing. Starch and chitosan had limited miscibility by melt blending, which resulted in heterogeneous film microstructure. Polyethylene glycol partially crystallized in the films, to a greater extent as the chitosan ratio increased, which limited its plasticizing effect. The films with the highest plasticizer ratio were more permeable to water vapor, less rigid, and less resistant to break. The variation in the chitosan content did not have a significant effect on water vapor permeability. As the chitosan proportion increased, the films became less stretchable, more rigid, and more resistant to break, with a more saturated yellowish color. The incorporation of the highest amount of chitosan in the films led to the reduction in coliforms and total aerobic counts of cold-stored pork meat slices, thus extending their shelf-life.The authors acknowledge the financial support provided by the Spanish Ministerio de Economia y Competividad (Projects AGL2013-42989-R and AGL2016-76699-R). Author Cristina Valencia-Sullca thanks the Peruvian Grant National Program (PRONABEC Grant).Valencia-Sullca, CE.; Atarés Huerta, LM.; Vargas, M.; Chiralt, A. (2018). Physical and Antimicrobial Properties of Compression-Molded Cassava Starch-Chitosan Films for Meat Preservation. Food and Bioprocess Technology. 11(7):1339-1349. https://doi.org/10.1007/s11947-018-2094-5S13391349117Alves, V. D., Mali, S., Beleia, A., & Grossmann, M. V. (2007). Effect of glycerol and amylose enrichment on cassava starch film properties. Journal of Food Engineering, 78(3), 941–946.ASTM (1995). Standard test methods for water vapour transmission of materials. In: Standards designations: E96-95. Annual book of ASTM standards (pp. 406-413). Philadelphia, PA: American Society for Testing and Materials.ASTM (1999). Standard test method for specular gloss. In: Designation (D523). Annual book of ASTM standards, Vol. 06.01. Philadelphia, PA: American Society for Testing and Materials.ASTM (2001). Standard test method for tensile properties of thin plastic sheeting. In: Standard D882 annual book of American standard testing methods. Philadelphia, PA: American Society for Testing and Materials.Atarés, L., Bonilla, J., & Chiralt, A. (2010). Characterization of sodium caseinate-based edible films incorporated with cinnamon or ginger essential oils. Journal of Food Engineering, 100(4), 678–687.Bonilla, J., Atarés, L., Vargas, M., & Chiralt, A. (2013). Properties of wheat starch film-forming dispersions and films as affected by chitosan addition. Journal of Food Engineering, 114(3), 303–312.Bonilla, J., Fortunati, E., Atarés, L., Chiralt, A., & Kenny, J. (2014). Physical, structural and antimicrobial properties of poly vinyl alcohol-chitosan biodegradable films. Food Hydrocolloids, 35, 463–470.Bourtoom, T., & Chinnan, M. S. (2008). Preparation and properties of rice starch–chitosan blend biodegradable film. LWT-Food Science and Technology, 41(9), 1633–1641.Cano, A., Jiménez, A., Cháfer, M., González-Martínez, C., & Chiralt, A. (2014). Effect of amylose: amylopectin ratio and rice bran addition on starch films properties. Carbohydrate Polymers, 111(0), 543–555.Carvalho, A. J. F. (2008). Starch: Major sources, properties and applications as thermoplastic materials. In M. N. Belgacem & A. Gandini (Eds.), Monomers, polymers and composites from renewable resources. Amsterdam: Elsevier.Chillo, S., Flores, S., Mastromatteo, M., Conte, A., Gerschenson, L., & Del Nobile, M. A. (2008). Influence of glycerol and chitosan on tapioca starch-based edible film properties. Journal of Food Engineering, 88(2), 159–168.Commission Regulation, 2005 (EC) No 2073/2005 of 15 November 2005 on microbiological criteria for foodstuffs. In Official Journal of the European Union pp 338/1–338/26.Da Róz, A., Carvalho, A., Gandini, A., & Curvelo, A. (2006). The effect of plasticizers on thermoplastic starch compositions obtained by melt processing. Carbohydrate Polymers, 63(3), 417–424.Dang, K., & Yoksan, R. (2015). Development of thermoplastic starch blown film by incorporating plasticized chitosan. Carbohydrate Polymers, 115, 575–581.Dou, B., Dupont, V., Williams, P. T., Chen, H., & Ding, Y. (2009). Thermogravimetric kinetics of crude glycerol. Bioresource Technology, 100(9), 2613–2620.Fang, J., Fawler, P., Eserig, C., González, R., Costa, J., & Chamudis, L. (2005). Development of biodegradable laminate films derived from naturally occurring carbohydrate polymers. Carbohydrate Polymers, 60(1), 39–42.Hutchings, J. B. (1999). Food color and appearance (2nd ed.). Gaithersburg, Maryland, USA: Aspen Publishers, Inc..Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2012a). Edible and biodegradable starch films: A review. Food Bioprocessing Technology, 5(6), 2058–2076.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2012b). Effect of re-crystallization on tensile, optical and water vapour barrier properties of corn starch films containing fatty acids. Food Hydrocolloids, 26(1), 302–310.López, O., Garcia, A., Villar, M., Gentili, A., Rodriguez, M., & Albertengo, L. (2014). Thermo-compression of biodegradable thermoplastic corn starch films containing chitin and chitosan. LWT-Food Science and Technology, 57(106), 106–1515.Mali, S., Grossmann, M. V. E., García, M. A., Martino, M. N., & Zaritsky, N. E. (2006). Effects of controlled storage on thermal, mechanical and barrier properties of plasticized films from different starch sources. Journal of Food Engineering, 75(4), 453–460.Mendes, J. F., Paschoalin, R. T., Carmona, V. B., Sena Neto, A. R. A., Marques, C. P., Marconcini, J. M., Mattoso, L. H. C., Medeiros, E. S., & Oliveira, J. E. (2016). Biodegradable polymer blends based on corn starch and thermoplastic chitosan processed by extrusion. Carbohydrate Polymers, 137, 452–458.Ortega-Toro, R., Jiménez, A., Talens, P., & Chiralt, A. (2014). Properties of starch–hydroxypropyl methylcellulose based films obtained by compression molding. Carbohydrate Polymers, 109, 155–165.Ortega-Toro, R., Morey, I., Talens, P., & Chiralt, A. (2015). Active bilayer films of thermoplastic starch and polycaprolactone obtained by compression molding. Carbohydrate Polymers, 127, 282–290.Pelissari, F., Grossmann, M., Yamashita, F., & Pineda, E. (2009). Antimicrobial, mechanical and barrier properties of cassava starch-chitosan films incorporated with oregano essential oil. Journal of Agricultural and Food Chemistry, 57(16), 7499–7504.Pelissari, F. M., Yamashita, F., García, M. A., Martino, M. N., Zaritzky, N. E., & Grossmann, M. V. E. (2012). Constrained mixture design applied to the development of cassava starch-chitosan blown films. Journal of Food Engineering, 108(2), 262–267.Song, R., Xue, R., He, L. H., Liu, Y., & Xiao, Q. L. (2008). The structure and properties of chitosan/polyethylene glycol/silica ternary hybrid organic-inorganic films. Chinese Journal of Polymer Science, 26(05), 621–630.v.Su, J. F., Huang, Z., Yuan, X. Y., Wang, X. Y., & Lim, M. (2010). Structure and properties of carboxymethyl cellulose/soy protein isolate blend edible films crosslinked by Maillard reactions. Carbohydrate Polymers, 79(1), 145–153.Thunwall, M., Boldizar, A., & Rigdahl, M. (2006). Compression molding and tensile properties of thermoplastic potato starch materials. Biomacromolecules, 7(3), 981–986.Tomé, L., Fernandes, S., Sadocco, P., Causio, J., Silvertre, A., Neto, P., & Freire, C. (2012). Antibacterial thermoplastic starch- chitosan based materials prepared by melt-mixing. BioResources, 7(3), 3398–3409.Villalobos, R., Chanona, J., Hernández, P., Gutiérrez, G., & Chiralt, A. (2005). Gloss and transparency of hydroxypropyl methylcellulose films containing surfactants as affected by their microstructure. Food Hydrocolloids, 19(1), 53–61.Xu, Y. X., Kim, K. M., Hanna, M. A., & Nag, D. (2005). Chitosan–starch composite film: Preparation and characterization. Industrial Crops and Products, 21(2), 185–192.Yang, L., & Paulson, A. T. (2000). Mechanical and water vapour barrier properties of edible gellan. Food Research International, 33(7), 563–570

RBR ligase–mediated ubiquitin transfer: a tale with many twists and turns

RBR ligases are an enigmatic class of E3 ubiquitin ligases that combine properties of RING and HECT-type E3s and undergo multilevel regulation through autoinhibition, post-translational modifications, multimerization and interaction with binding partners. Here, we summarize recent progress in RBR structures and function, which has uncovered commonalities in the mechanisms by which different family members transfer ubiquitin through a multistep process. However, these studies have also highlighted clear differences in the activity of different family members, suggesting that each RBR ligase has evolved specific properties to fit the biological process it regulates

Activation of Latent HIV Using Drug-Loaded Nanoparticles

Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the HDAC inhibitor sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. Taken together these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy

Respiratory syncytial virus infection induces higher Toll-like receptor-3 expression and TNF-α production than human metapneumovirus infection

published_or_final_versio

Minnelide effectively eliminates CD133+ side population in pancreatic cancer

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is a devastating disease hallmarked by limited patient survival. Resistance to chemotherapy, a major cause of treatment failure in PDAC patients, is often attributed to Cancer Stem Cells (CSCs). Pancreatic CSCs are a small subset of quiescent cells within a tumor represented by surface markers like CD133. These cells are responsible not only for tumor recurrence, but also poor prognosis based on their “stem-like” characteristics. At present, conventional therapy is directed towards rapidly dividing PDAC cells and thus fails to target the CSC population. METHODS: MIA PaCa-2, S2-013 and AsPC-1 were treated with 12.5 nM triptolide (12 T cells) for 7 days. The surviving cells were recovered briefly in drug-free growth media and then transferred to Cancer Stem cell Media (CSM). As a control, untreated cells were also transferred to CSM media (CSM). The 12 T and CSM cells were tested for stemness properties using RNA and protein markers. Low numbers of CSM and 12 T cells were implanted subcutaneously in athymic nude mice to study their tumorigenic potential. 12 T and CSM cells were sorted for CD133 expression and assayed for their colony forming ability and sphere forming ability. Invasiveness of 12 T cells, CSM and MIA PaCa-2 were compared using Boyden chamber assays. RESULTS: Treated 12 T cells displayed increased expression of the surface marker CD133 and the drug transporter ABCG2 compared to untreated cells (CSM cells). Both 12 T and CSM cells formed subcutaneous tumors in mice confirming their tumor-initiating properties. When tested for invasion, 12 T cells had increased invasiveness compared to CSM cells. CD133(+) cells in both CSM and 12 T showed greater colony and sphere forming ability compared to CD133(−) cells from each group. Consistent with these data, when injected subcutaneously in mice, CD133(−) cells from CSM or 12 T did not form any tumors whereas CD133(+) cells from both groups showed tumor formation at a very low cell number. Despite pre-exposure to triptolide in 12 T CD133(+) cells, treatment of tumors formed by these cells with Minnelide, a triptolide pro-drug, showed significant tumor regression. CONCLUSION: Our results indicated that triptolide enhanced and enriched the “stemness” in the PDAC cell lines at a low dose of 12.5 nM, but also resulted in the regression of tumors derived from these cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0470-6) contains supplementary material, which is available to authorized users

Peer-based behavioral health program for drug users in China: a pilot study

<p>Abstract</p> <p>Background</p> <p>Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.</p> <p>Methods</p> <p>A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).</p> <p>Results</p> <p>Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.</p> <p>Conclusions</p> <p>This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.</p

Peer-based behavioral health program for drug users in China: a pilot study

<p>Abstract</p> <p>Background</p> <p>Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.</p> <p>Methods</p> <p>A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).</p> <p>Results</p> <p>Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.</p> <p>Conclusions</p> <p>This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.</p