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Delivery models

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https://www.readbyqxmd.com/read/28350964/promoting-vaginal-distribution-of-e7-and-mcl-1-sirna-silencing-nanoparticles-for-cervical-cancer-treatment
#1
Anna Lechanteur, Tania Furst, Brigitte Evrard, Philippe Delvenne, Geraldine Piel, Pascale Hubert
There is an urgent need to develop a less aggressive and more effective treatment against cervical lesions induced by different high-risk human papillomavirus (HR-HPV). We investigated the potential of a cocktail of small interfering RNA (siRNA) directed against the oncoprotein E6 (E6), the oncoprotein E7 (E7) and/or the anti-apoptotic protein MCL-1 (MCL-1). The combination of siRNA anti-E7 and anti-MCL-1 demonstrated high efficacy on multiple HPV16 and HPV18 cell lines and no effects on healthy keratinocytes...
March 28, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28350948/bending-the-cost-curve-establishing-value-in-spine-surgery
#2
Scott L Parker, Silky Chotai, Clinton J Devin, Lindsay Tetreault, Thomas E Mroz, Darrel S Brodke, Michael G Fehlings, Matthew J McGirt
BACKGROUND: As publically promoted by all stakeholders in health care reform, prospective outcomes registry platforms lie at the center of all current evidence-driven value-based models. OBJECTIVE: To demonstrate the variability in outcomes and cost at population level and individual patient level for patients undergoing spine surgery for degenerative diseases. METHODS: Retrospective analysis of prospective longitudinal spine registry data was conducted...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28350664/human-adipose-derived-stem-cells-labeled-with-plasmonic-gold-nanostars-for-cellular-tracking-and-photothermal-cancer-cell-ablation
#3
Ronnie L Shammas, Andrew M Fales, Bridget M Crawford, Amy J Wisdom, Gayathri R Devi, David A Brown, Tuan Vo-Dinh, Scott T Hollenbeck
BACKGROUND: Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics. METHODS: To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy...
April 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28346624/association-of-group-prenatal-care-in-us-family-medicine-residencies-with-maternity-care-practice-a-cera-secondary-data-analysis
#4
Wendy B Barr, Sebastian T Tong, Nicholas M LeFevre
BACKGROUND AND OBJECTIVES: Group prenatal care has been shown to improve both maternal and neonatal outcomes. With increasing adaption of group prenatal care by family medicine residencies, this model may serve as a potential method to increase exposure to and interest in maternity care among trainees. This study aims to describe the penetration, regional and program variations, and potential impacts on future maternity care practice of group prenatal care in US family medicine residencies...
March 2017: Family Medicine
https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#5
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346416/jacie-accreditation-for-blood-and-marrow-transplantation-past-present-and-future-directions-of-an-international-model-for-healthcare-quality-improvement
#6
J A Snowden, E McGrath, R F Duarte, R Saccardi, K Orchard, N Worel, J Kuball, C Chabannon, M Mohty
Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346271/primary-and-repeat-cesarean-deliveries-a-population-based-study-in-the-united-states-1979-2010
#7
Cande V Ananth, Alexander M Friedman, Katherine M Keyes, Jessica A Lavery, Ava Hamilton, Jason D Wright
BACKGROUND: Despite the temporal increase in cesarean deliveries, the extent to which maternal age, period, and maternal birth cohorts may have contributed to these trends remains unknown. METHODS: We performed an analysis of 123 million singleton deliveries in the US (1979-2010). We estimated rate ratio (RR) with 95% confidence interval (CI) for primary and repeat cesarean deliveries. We examined changes in cesarean rates with weighted Poisson regression models across three time-scales: maternal age, year of delivery, and birth cohort (mother's birth year)...
March 23, 2017: Epidemiology
https://www.readbyqxmd.com/read/28345698/ethylcellulose-oleogels-for-lipophilic-bioactive-delivery-effect-of-oleogelation-on-in-vitro-bioaccessibility-and-stability-of-beta-carotene
#8
Chloe M O Sullivan, Maya Davidovich-Pinhas, Amanda J Wright, Shai Barbut, Alejandro G Marangoni
The in vitro lipolysis and β-carotene (BC) transfer from oil to aqueous phase of canola oil ethylcellulose (EC) oleogels were measured using a static monocompartmental model simulating oral, gastric, and duodenal digestive stages. The effects of EC oleogelation on gel in vitro digestibility were examined, using un-structured canola oil as a control. The physicochemical properties of oleogels containing BC were also measured. It was found that oleogels made with 10% 10 cP and 10% 20 cP did not differ significantly in their extent of lipolysis or BC transfer compared to canola oil; however 10% 45 cP and 15...
March 27, 2017: Food & Function
https://www.readbyqxmd.com/read/28345144/adapting-evaluations-of-alternative-payment-models-to-a-changing-environment
#9
Thomas W Grannemann, Randall S Brown
OBJECTIVE: To identify the most robust methods for evaluating alternative payment models (APMs) in the emerging health care delivery system environment. STUDY DESIGN (APPROACH): We assess the impact of widespread testing of alternative payment models on the ability to find credible comparison groups. We consider the applicability of factorial research designs for assessing the effects of these models. PRINCIPAL FINDINGS: The widespread adoption of alternative payment models could effectively eliminate the possibility of comparing APM results with a "pure" control or comparison group unaffected by other interventions...
March 27, 2017: Health Services Research
https://www.readbyqxmd.com/read/28345005/chronic-enzyme-replacement-to-the-brain-of-a-late-infantile-neuronal-ceroid-lipofuscinosis-mouse-has-differential-effects-on-phenotypes-of-disease
#10
Jennifer A Wiseman, Yu Meng, Yuliya Nemtsova, Paul G Matteson, James H Millonig, Dirk F Moore, David E Sleat, Peter Lobel
Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal inherited neurodegenerative disease caused by loss of lysosomal protease tripeptidyl peptidase 1 (TPP1). We have investigated the effects of chronic intrathecal (IT) administration using enzyme replacement therapy (ERT) to the brain of an LINCL mouse model, in which locomotor function declines dramatically prior to early death. Median lifespan was significantly extended from 126 days to >259 days when chronic IT treatment was initiated before the onset of disease...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28345004/homology-directed-recombination-for-enhanced-engineering-of-chimeric-antigen-receptor-t-cells
#11
Malika Hale, Baeckseung Lee, Yuchi Honaker, Wai-Hang Leung, Alexandra E Grier, Holly M Jacobs, Karen Sommer, Jaya Sahni, Shaun W Jackson, Andrew M Scharenberg, Alexander Astrakhan, David J Rawlings
Gene editing by homology-directed recombination (HDR) can be used to couple delivery of a therapeutic gene cassette with targeted genomic modifications to generate engineered human T cells with clinically useful profiles. Here, we explore the functionality of therapeutic cassettes delivered by these means and test the flexibility of this approach to clinically relevant alleles. Because CCR5-negative T cells are resistant to HIV-1 infection, CCR5-negative anti-CD19 chimeric antigen receptor (CAR) T cells could be used to treat patients with HIV-associated B cell malignancies...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344212/age-dependent-effects-of-prenatal-dexamethasone-exposure-on-immune-responses-in-male-rats
#12
Ming-Yi Chou, Li-Tung Huang, You-Lin Tain, Ho-Chang Kuo, Mao-Meng Tiao, Jiunn-Ming Sheen, Chih-Cheng Chen, Pi-Lien Hung, Kai-Sheng Hsieh, Hong-Ren Yu
Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28344166/micrornas-as-players-and-signals-in-the-metastatic-cascade-implications-for-the-development-of-novel-anti-metastatic-therapies
#13
REVIEW
Paolo Gandellini, Valentina Doldi, Nadia Zaffaroni
microRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Increasing evidence emerging from human tumor preclinical models clearly indicates that specific miRNAs, collectively termed "metastamirs," play a functional role in different steps of the metastatic cascade, by exerting either pro- or anti-metastatic functions, and behave as signaling mediators to enable tumor cell to colonize a specific organ. miRNAs also actively participate in the proficient interaction of cancer cells with tumor microenvironment, either at the primary or at the metastatic site...
March 23, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28344093/synthesis-and-characterization-of-a-novel-cationic-hydrogel-base-on-salecan-g-pmaptac
#14
Wei Wei, Xiaoliang Qi, Junjian Li, Yin Zhong, Gancheng Zuo, Xihao Pan, Ting Su, Jianfa Zhang, Wei Dong
Salecan is a biological macromolecular and biocompatible polysaccharide that have been investigated for recent years. Herein, we report a novel cationic hydrogel fabricated by graft-polymerizing 3-(methacryloylamino)propyl-trimethylammonium chloride (MAPTAC) onto salecan chains. The obtained hydrogels were transparent, solid-elastic, macro-porous, ion-sensitive, and non-cytotoxic. The swelling ratios increased with salecan content, while mechanical strength does the opposite. Moreover, drug delivery test was studied as a potential application...
March 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28344013/a-self-adherent-bullet-shaped-microneedle-patch-for-controlled-transdermal-delivery-of-insulin
#15
Keum-Yong Seong, Min-Soo Seo, Dae Yeon Hwang, Eoin D O'Cearbhaill, Seamus Sreenan, Jeffrey M Karp, Seung Yun Yang
Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained...
March 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28343456/implementation-of-neurocritical-care-is-associated-with-improved-outcomes-in-traumatic-brain-injury
#16
Mypinder S Sekhon, Peter Gooderham, Brian Toyota, Navid Kherzi, Vivien Hu, Vinay K Dhingra, Morad S Hameed, Dean R Chittock, Donald E Griesdale
Background Traditionally, the delivery of dedicated neurocritical care (NCC) occurs in distinct NCC units and is associated with improved outcomes. Institution-specific logistical challenges pose barriers to the development of distinct NCC units; therefore, we developed a consultancy NCC service coupled with the implementation of invasive multimodal neuromonitoring, within a medical-surgical intensive care unit. Our objective was to evaluate the effect of a consultancy NCC program on neurologic outcomes in severe traumatic brain injury patients...
March 27, 2017: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/28343398/an-anti-programmed-death-1-antibody-a%C3%AF-pd-1-fusion-protein-that-self-assembles-into-a-multivalent-and-functional-apd-1-nanoparticle
#17
Peng Zhao, Djordje Atanackovic, Shuyun Dong, Hideo Yagita, Xiao He, Mingnan Chen
Cancer immune checkpoint therapy has achieved remarkable clinical successes in various cancers. However, current immune checkpoint inhibitors block the checkpoint of not only the immune cells that are important to cancer therapy but also the immune cells that are irrelevant to the therapy. Such an indiscriminate blockade limits the efficacy and causes the autoimmune toxicity of the therapy. It might be beneficial to use a carrier to target immune checkpoint inhibitors to cancer-reactive immune cells. Here, we explore a method to load the inhibitors into carriers...
March 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28343392/pharmacokinetic-and-biodistribution-studies-of-hpma-copolymer-conjugates-in-an-aseptic-implant-loosening-mouse-model
#18
Xin Wei, Fei Li, Gang Zhao, Yashpal Singh S Chhonker, Christine Elise Averill, Josselyn Galdamez, P Edward Purdue, Xiaoyan Wang, Edward V Fehringer, Kevin L Garvin, Steven R Goldring, Yazen Alnouti, Dong Wang
N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers were previously found to represent a versatile delivery platform for the early detection and intervention of orthopedic implant loosening. In this manuscript, we evaluated the impact of different structural parameters of the HPMA copolymeric system (e.g. molecular weight (MW), drug content) to its pharmacokinetics and biodistribution (PK/BD) profile. Using 125I, Alexa Fluor® 488 and IRDye® 800 CW-labeled HPMA copolymer-dexamethasone (P-Dex) conjugates with different MW and dexamethasone (Dex) contents, we found the MW to be the predominant impact factor on the PK/BD profiles of P-Dex, with Dex content as a secondary impact factor...
March 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28343228/focal-brain-injury-associated-with-a-model-of-severe-hypoxic-ischemic-encephalopathy-in-nonhuman-primates
#19
Ryan M McAdams, Ronald J McPherson, Raj P Kapur, Sandra E Juul
Worldwide, hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. To better understand the mechanisms contributing to brain injury and improve outcomes in neonates with HIE, better preclinical animal models that mimic the clinical situation following birth asphyxia in term newborns are needed. In an effort to achieve this goal, we modified our nonhuman primate model of HIE induced by in utero umbilical cord occlusion (UCO) to include postnatal hypoxic episodes, in order to simulate apneic events in human neonates with HIE...
March 25, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28343194/lipid-metabolism-and-feeding-habits-of-indigenous-peoples-of-the-sakha-republic-yakutia-in-today-s-socio-economic-development
#20
Vadim G Krivoshapkin, Anna I Sivtseva, Elena N Sivtseva, Svetlana S Maximova, Leonid F Timofeev, Aytalina S Golderova
INTRODUCTION: By results of a single-step epidemiological research indicators of a lipid range at 355 Evenks of the Olenyoksky District of the Republic of Sakha (Yakutia) are estimated. The aim of this research was assessment of lipid exchange and character of a delivery of Evenks of the item of Zhilinda. MATERIAL AND METHODS: 355 evenks aged over 20 years (170 men, women-185). Total cholesterol (OCHS), cholesterol (low-density lipoproteins (LDL-CHOLESTEROL), highdensity lipoprotein cholesterol ((XC-LVNP), triglycerides (TG), the calculated coefficient of haemoglobin (Ka)...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
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