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- BookAndrew D. Hollenbach, Ph.D., Associate Professor of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA.Contents:
Machine generated contents note: ch. 1 Ruth L. Kirschstein
The Woman and Her Legacy
1.1. Ruth L. Kirschstein
A Brief Biography
1.2. The Legacy
The Ruth L. Kirschstein NRSA Grants
ch. 2 The People Behind the Curtain
Understanding the Review Process
2.1. The Review Process
2.2. The Role of Human Nature in the Review Process
ch. 3 Who Are You?
The Fellowship Applicant
3.1. The Biosketch
3.2. Goals for Fellowship Training and Career
3.3. Selection of Sponsor and Institute
3.4. Previous Research Experience
3.5. Letters of Recommendation
3.6. Respective Contributions
3.7. Activities Planned Under This Award
ch. 4 Who's the Boss?
Sponsor, Collaborators, and Consultants
4.1. Biosketch
4.2. Sponsor and Cosponsor Information
ch. 5 Blind Them with Science
The Research Training Plan
5.1. Specific Aims
5.2. Significance
5.3. Approach
ch. 6 Last but Not Least: Institutional Environment, Training Potential, and Other Scored Items
6.1. Institutional Environment and Commitment to Training
6.2. Training Potential
6.3. Overall Impact Score
6.4. Other Scored Items
ch. 7 Details, Details, Details
Nonscored Items, Formatting, and the Cover Letter
7.1. Project Summary/Abstract
7.2. Project Narrative
7.3. Responsible Conduct of Research
7.4. Formatting
7.5. Cover Letter
ch. 8 Now What?
Resubmission
8.1. The Summary Statement
8.2. To Resubmit or Not to Resubmit
8.3. Addressing the Critiques
8.4. Introduction to the Application. - ArticleChatalic KL, Heskamp S, Konijnenberg M, Molkenboer-Kuenen JD, Franssen GM, Clahsen-van Groningen MC, Schottelius M, Wester HJ, van Weerden WM, Boerman OC, de Jong M.Theranostics. 2016;6(6):849-61.Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa). Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics-they rapidly and efficiently localize in tumor lesions. However, high tracer uptake in kidneys and salivary glands are major concerns for therapeutic applications. Here, we present the preclinical application of PSMA I&T, a DOTAGA-chelated urea-based PSMA inhibitor, for SPECT/CT imaging and radionuclide therapy of PCa. (111)In-PSMA I&T showed dose-dependent uptake in PSMA-expressing tumors, kidneys, spleen, adrenals, lungs and salivary glands. Coadministration of 2-(phosphonomethyl)pentane-1,5-dioic acid (2-PMPA) efficiently reduced PSMA-mediated renal uptake of (111)In-PSMA I&T, with the highest tumor/kidney radioactivity ratios being obtained using a dose of 50 nmol 2-PMPA. SPECT/CT clearly visualized subcutaneous tumors and sub-millimeter intraperitoneal metastases; however, high renal and spleen uptake in control mice (no 2-PMPA) interfered with visualization of metastases in the vicinity of those organs. Coadministration of 2-PMPA increased the tumor-to-kidney absorbed dose ratio during (177)Lu-PSMA I&T radionuclide therapy. Hence, at equivalent absorbed dose to the tumor (36 Gy), coinjection of 2-PMPA decreased absorbed dose to the kidneys from 30 Gy to 12 Gy. Mice injected with (177)Lu-PSMA I&T only, showed signs of nephrotoxicity at 3 months after therapy, whereas mice injected with (177)Lu-PSMA I&T + 2-PMPA did not. These data indicate that PSMA I&T is a promising theranostic tool for PCa. PSMA-specific uptake in kidneys can be successfully tackled using blocking agents such as 2-PMPA.
- ArticleHuang F, Zeng X, Fan Z, Xu N, Yu S, Xuan L, Liu H, Jin H, Lin R, Shi P, Zhao K, Li X, Wei X, Xu J, Wang Z, Sun J, Chai Y, Liu Q.Transplant Cell Ther. 2022 12;28(12):849.e1-849.e8.To compare the outcomes between peripheral blood stem cell (PBSC)+cord blood and PBSC+bone marrow (BM) grafts in the setting of haploidentical donor (HID) transplantation, 110 patients were enrolled in this retrospective study, including 54 recipients of haplo-PBSC+cord transplants and 56 recipients of haplo-PBSC+BM transplants. Chimerism analyses revealed that by day 30 post-transplantation, 94.3% of surviving patients in the haplo-PBSC+cord group had achieved full haploidentical chimerism and 5.7% had <10% cord chimerism, whereas 100% of surviving patients in the haplo-PBSC+BM group had achieved full donor chimerism. The cumulative incidence of platelet engraftment at 30 days was 92.6% in the haplo-PBSC+cord group versus 89.3% in the haplo-PBSC+BM group (P =.024), that of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 31.5% versus 48.2% (P =.060), and 1-year relapse was 13.0% versus 25.0% (P =.027), nonrelapse mortality was 9.3% versus 12.5% (P =.76), disease-free survival (DFS) was 77.7% versus 62.5% (P =.028), and overall survival (OS) was 81.4% versus 69.6% (P =.046). Multivariate analysis identified haplo-PBSC+cord transplantation as a protective factor for relapse (hazard ratio [HR], .31; P =.007), DFS (HR, .40; P =.007), and OS (HR, .44; P =.016). Overall, haplo-PBSC+cord transplantation led to faster platelet engraftment, lower relapse, and superior DFS and OS compared with haplo-PBSC+BM transplantation and thus might be a better transplant mode in the setting of HID transplantation.
- ArticleAlizadeh Zarei M, Rafiei Dehbidi G, Takhshid MA.Urol Oncol. 2020 11;38(11):849.e1-849.e9.OBJECTIVE: N-myc downstream regulated gene 2 (NDRG2) is identified as a promising candidate tumor suppressor in several human malignancies including prostate cancer (PCa). Here, we investigated the effect of combined NDRG2 overexpression, x-ray radiation (RTX), and docetaxel (DTX) against viability and invasiveness properties of LNCaP cells.
MATERIAL AND METHODS: A plasmid harboring NDRG2 gene under transcriptional control of prostate-specific enhancing sequence regulatory element was constructed to overexpress NDRG2 in PCa cell lines. The effects of NDRG2 overexpression in combination with RTX and DTX on viability, proliferation, and apoptosis of LNCaP cells were evaluated using MTT, colony formation, and annexin V flowcytometirc assays. Migration and invasion of NDRG2-overexpressed cells as well as expression of matrix metalloproteinses-2 (MMP2) and -9 (MMP9) were also assessed using transwell chamber assay and real-time PCR.
RESULTS: The results of fluorescence microscopy and real-time PCR showed a high and specific overexpression of NDRG2 in LNCaP cells. Overexpression of NDRG2 significantly reduced cell viability and increased apoptosis of LNCaP cell. Migration, invasion, as well as the expression of MMP2 and MMP9, was decreased following NDRG2 overexpression. Combination of NDRG2 overexpression with RTX and DTX decreased the viability, invasion, and migration of LNCaP cells synergistically.
CONCLUSION: These results indicate that a combination of NDRG2 overexpression with chemotherapy and radiotherapy can be considered for effective treatment of PCa. - ArticleShiota M, Endo S, Fujimoto N, Tsukahara S, Ushijima M, Kashiwagi E, Takeuchi A, Inokuchi J, Uchiumi T, Eto M.Urol Oncol. 2020 11;38(11):849.e11-849.e18.OBJECTIVE: Androgen metabolism is a key component in therapeutic resistance to androgen deprivation therapy (ADT). This study aimed to reveal the significance of genetic polymorphisms in genes involved in androgen metabolism, including CYP17A1, AKR1C3, and HSD17B, on serum testosterone levels during ADT, as well as the prognosis of men undergoing ADT for metastatic prostate cancer (CaP).
MATERIALS AND METHODS: This study included 104 Japanese patients with metastatic CaP, for whom serum testosterone data during ADT were available for 80 patients. The association of CYP17A1 (rs743572), AKR1C3 (rs12529), HSD17B1 (rs605059), HSD17B3 (rs2066479), and HSD17B4 (rs7737181) with serum testosterone levels during ADT and prognosis (progression-free survival and overall survival) was examined. Enzymatic activity in AKR1C3 H5Q was examined using recombinant protein.
RESULTS: Homozygous wild-type (GG allele; median [interquartile range], 12.0 ng/ml [8.0-19.0 ng/ml]) AKR1C3 rs12529 was associated with higher serum testosterone levels during ADT compared with variant-type (GC/CC alleles; median [interquartile range], 9.0 ng/ml [6.4-10.8 ng/ml]). Consistently, variant-type (GC/CC alleles) AKR1C3 rs12529 showed significantly lower risk of progression (hazard ratio [95% confidence interval], 0.47 [0.24-0.96], P = 0.039) compared with homozygous wild-type (GG allele) on multivariate analysis. Meanwhile, other genetic variations were associated with neither serum testosterone during ADT nor prognosis. Enzyme activity of wild-type AKR1C3 was comparable to the H5Q mutant.
CONCLUSIONS: Taken together, this study demonstrated that AKR1C3 polymorphism, which was associated with serum testosterone levels during ADT, may be a prognostic factor of the progression to castration-resistant prostate cancer in Japanese men with metastatic CaP. - ArticleDall CP, Shaw N, Egan J, Carvalho FL, Galloway LAS, Krasnow R, Stamatakis L.Urol Oncol. 2020 11;38(11):849.e19-849.e23.INTRODUCTION: Extended outpatient chemoprophylaxis (ECP) following radical cystectomy (RC) for bladder cancer is proven to reduce rates of venous thromboembolism (VTE). While ECP is commonly performed with enoxaparin, its cost-effectiveness and adherence rate has been called into question. Data from orthopedic literature suggest that ECP with direct oral anticoagulants (DOACs) may be as effective in VTE prevention as enoxaparin in patients undergoing joint surgery. Our goal is to determine how urologic oncologists employ ECP following RC.
METHODS: Members of the Society of Urologic Oncology were surveyed on practice patterns for the use of ECP after RC. Specific questions were asked regarding the use of inpatient and outpatient VTE prophylaxis, as well as perceived barriers to DOACs and enoxaparin.
RESULTS: There were 121 of 878 (13.8%) respondents and the majority were in academic practices (83%). Most respondents had at least 5 years of experience and performed greater than 10 cystectomies annually. Almost all participants utilized inpatient (97%) and extended (80%) chemoprophylaxis for VTE prevention. Of those who elected for ECP, almost all (96%) used enoxaparin. Only 3 respondents (3%) prescribed oral agents such as rivaroxaban (2) or warfarin (1). Among those using enoxaparin, financial-specific barriers to treatment such as lack of insurance coverage (38%), inability to afford the medication (51%), and need for additional insurance authorization (44%) were reported. Poor patient adherence and refusal to perform injections were reported by 20% and 18% of respondents, respectively. Among the 23 physicians who did not use ECP, cost (39%) and delivery method (26%) were cited as barriers to treatment.
CONCLUSIONS: The majority of surveyed urologic oncologists are prescribing subcutaneous enoxaparin ECP following RC. Poor patient adherence due to self-injections and financial barriers were frequently reported and represent a possible opportunity for the use of oral anticoagulants in the post-operative setting. These data will be used in the development of a proposed clinical trial of a DOAC in the post-RC setting. - ArticleHe Z, Du J, Zhang Y, Xu Y, Huang Q, Zhou Q, Wu M, Li Y, Zhang X, Zhang H, Cai Y, Ye K, Wang X, Zhang Y, Han Q, Xiao J.Theranostics. 2023;13(2):849-866.Background: Increasing evidence suggests that acute traumatic spinal cord injury (SCI)-induced defects in autophagy and autophagy-lysosomal pathway (ALP) may contribute to endothelial barrier disruption following injury. Recently, Kruppel-like factor 2 (KLF2) was reported as a key molecular switch on regulating autophagy. Whether KLF2 coordinates endothelial endothelial ALP in SCI is not known. Methods: Genetic manipulations of KLF2 were performed in bEnd.3 cells and SCI model. Western blot, qRT-PCR, immunofluorescence staining and Lyso-Tracker Red staining, Evans blue dye extravasation, behavioral assessment via Basso mouse scale (BMS), electrophysiology and footprint analysis were performed. Results: In SCI, autophagy flux disruption in endothelial cells contributes to TJ proteins degradation, leading to blood-spinal cord barrier (BSCB) impairment. Furthermore, the KLF2 level was decreased in SCI, overexpression of which alleviated TJ proteins loss and BSCB damage, which improve motor function recovery in SCI mice, while knockdown of KLF2 displayed the opposite effects. At the molecular level, KLF2 overexpression alleviated the TJ proteins degradation and the endothelial permeability by tuning the ALP dysfunction caused by SCI and oxygen glucose deprivation (OGD). Conclusions: Endothelial KLF2 as one of the key contributors to SCI-mediated ALP dysfunction and BSCB disruption. KLF2 could be a promising pharmacological target for the management and treatment of SCI.
- ArticleDhowre HS, Rajput S, Russell NA, Zelzer M.Nanomedicine (Lond). 2015;10(5):849-71.Major design aspects for novel biomaterials are driven by the desire to mimic more varied and complex properties of a natural cellular environment with man-made materials. The development of stimulus responsive materials makes considerable contributions to the effort to incorporate dynamic and reversible elements into a biomaterial. This is particularly challenging for cell-material interactions that occur at an interface (biointerfaces); however, the design of responsive biointerfaces also presents opportunities in a variety of applications in biomedical research and regenerative medicine. This review will identify the requirements imposed on a responsive biointerface and use recent examples to demonstrate how some of these requirements have been met. Finally, the next steps in the development of more complex biomaterial interfaces, including multiple stimuli-responsive surfaces, surfaces of 3D objects and interactive biointerfaces will be discussed.
- ArticleLópez-Lázaro M.Oncoscience. 2015;2(10):849-56.Cancer is, in essence, a stem cell disease. The main biological cause of cancer is that stem cells acquire DNA alterations during cell division. The more stem cell divisions a tissue accumulates over a lifetime, the higher is the risk of cancer in that tissue. This explains why cancer is diagnosed millions of times more often in some tissues than in others, and why cancer incidence increases so dramatically with age. It may also explain why taking a daily low-dose aspirin for several years reduces the risk of developing and dying from cancer. Since aspirin use reduces PGE2 levels and PGE2 fuels stem cell proliferation, aspirin may prevent cancer by restricting the division rates of stem cells. The stem cell division model of cancer may also explain why regular consumption of very hot foods and beverages increases the risk of developing esophageal cancer. Given that tissue injury activates stem cell division for repair, the thermal injury associated with this dietary habit will increase esophageal cancer risk by inducing the accumulation of stem cell divisions in the esophagus. Using these two examples, here I propose that controlling the division rates of stem cells is an essential approach to preventing cancer.
- ArticleWaringer J, Vitecek S, Martini J, Zittra C, Vieira A, Kuhlmann HC.Hydrobiologia. 2022;849(19):4259-4271.For evaluating hydraulic stress reduction strategies of caddisfly larvae, our study has three goals. First, creating a database on Reynolds numbers (Re) and drag coefficients valid for Limnephilidae larvae with cylindrical mineral cases. Second, evaluating the effects of submerged weight and biometry in cases with comparable length/width ratios. And third, collecting field data in an alpine environment for gaining insights into the hydraulic niches occupied by thirteen Drusinae species. Biometric data were subsequently combined with published Reynolds numbers and mean flow velocity data measured immediately upstream of Limnephilidae larvae at the moment of dislodgement. This provides drag coefficients for the range of Reynolds numbers obtained in the field. Data reveal that heavy cases strongly benefit from compensating drag by submerged weight, thereby enabling species to utilize high velocity spots, an important benefit for filtering species.
Supplementary Information: The online version contains supplementary material available at 10.1007/s10750-022-04981-y. - ArticleOróstica MH, Wyness AJ, Monsinjon JR, Nicastro KR, Zardi GI, Barker C, McQuaid CD.Hydrobiologia. 2022;849(19):4341-4356.Recruitment of mussels is a complex process with the successful arrival of individuals hinging on the availability of suitable habitats. We examined the effects of adult mussels as settlement habitat and the degree to which the suitability of habitat they offer is species-specific by comparing the recruitment success of intertidal mussels. We hypothesised that mussel recruitment and early growth are dictated by the quality of habitat offered by conspecifics adults. We used a unique experimental arena on the south coast of South Africa, where Mytilus galloprovincialis and two lineages of Perna perna co-exist. Treatments were based on the translocation of individuals of M. galloprovincialis, western- and eastern lineage of P. perna to a single site, where artificial beds were created and sampled monthly over one year. Recruit's number, their sizes and growth were greater within beds of the western lineage of Perna than eastern lineage or Mytilus beds. The results clearly demonstrate that the quality of settlement habitat offered by adult beds differs among adult lineages/species and affects rates of settlement and the early growth of recruits. This effect extends to the intraspecific level; we found greater differences in density and growth of recruits between lineages of Perna than between either lineage and M. galloprovincialis.
Supplementary Information: The online version contains supplementary material available at 10.1007/s10750-022-04994-7. - ArticleSeelos M, Beutel M, McCord S, Kim S, Vigil K.Hydrobiologia. 2022;849(21):4803-4822.Thermal stratification of reservoirs can lead to anaerobic conditions that facilitate the microbial conversion of mercury (Hg) to neurotoxic and bioaccumulative methylmercury (MeHg). But MeHg production is just the first step in a complex set of processes that affect MeHg in fish. Of particular relevance is uptake into suspended particulate matter (SPM) and zooplankton at the base of the pelagic food web. We assessed plankton dynamics and Hg uptake into the pelagic food web of four Hg-impaired California water reservoirs. Combining water chemistry, plankton taxonomy, and stable carbon (C) and nitrogen (N) isotope values of SPM and zooplankton samples, we investigated differences among the reservoirs that may contribute to differing patterns in MeHg bioaccumulation. Methylmercury accumulated in SPM during the spring and summer seasons. Percent MeHg (MeHg/Hg*100%) in SPM was negatively associated with δ15N values, suggesting that "fresh" algal biomass could support the production and bioaccumulation of MeHg. Zooplankton δ13C values were correlated with SPM δ13C values in the epilimnion, suggesting that zooplankton primarily feed in surface waters. However, zooplankton MeHg was poorly associated with MeHg in SPM. Our results demonstrate seasonal patterns in biological MeHg uptake and how multiple data sources can help constrain the drivers of MeHg bioaccumulation.
Supplementary Information: The online version contains supplementary material available at 10.1007/s10750-022-05018-0. - ArticleSánchez-Hernández J, Vieira-Lanero R, Nachón DJ, Barca S, Del Carmen Cobo M, Cobo F.Hydrobiologia. 2022;849(6):1313-1315.
- ArticleGuedes GHS, Araújo FG.Hydrobiologia. 2022;849(5):1301-1312.A new approach for visual fish survey in reservoirs using underwater drones (remotely operated vehicle- ROV) is presented. The ROV was applied to identify abiotic gradients and to compare fish assemblages on the steep slopes in a tropical reservoir. The tested hypothesis is that fish are concentrated in the littoral zone due to the better physicochemical and habitat conditions, compared to deep and hypoxic layers. Twelve species were recorded (seven native, five exotic), with all species occurring in the littoral zone, seven species in the transition, and four in the profundal zone. A greater fish abundance and richness was found in the littoral zone corroborating the main hypothesis. The littoral zone was dominated by exotic cichlids (Cichla spp., Coptodon rendalli), while native catfish (Loricariichthys castaneus, Pimelodella lateristriga) occupied deeper areas. The fish distribution seems to be driven by local factors, such as oxygen availability and habitat structure. The preference for the littoral zone by alien cichlids may have led to the extirpation/decrease of native characids and induced catfishes to occupy deep habitats. Underwater drones can be a valuable tool for the simultaneous collection of abiotic/biotic data, especially in deep reservoirs with complex habitats, resulting in advances in the environmental monitoring.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10750-021-04790-9. - ArticleTruchado P, Van den Abbeele P, Rivière A, Possemiers S, De Vuyst L, Van de Wiele T.Benef Microbes. 2015;6(6):849-60.Long-chain arabinoxylans (LC-AX) are degraded in the colon by intestinal bacteria possessing AX-degrading enzymes, such as bifidobacteria. Enzymatic activity of intestinal bacterial might vary depending on the composition of the gut microbiota. To compare the enzymatic activities of the bacterial gut communities of two healthy individuals (donors D1 and D2), these bacterial communities were inoculated into in vitro model M-SHIME(®). Differences in xylanase activities and denaturing gradient gel electrophoresis profiles, in particular a DNA-band corresponding with Bifidobacterium longum, were found in the proximal colon vessel. 16S rRNA gene sequencing analysis demonstrated the presence of two different B. longum species in these bacterial communities, showing 99% gene sequence similarity with B. longum NCC2705 and B. longum. subsp. longum KACC 91563, respectively, further referred to as B. longum D1 and B. longum D2. When grown on LC-AX as the sole added energy source, B. longum D2 displayed significantly higher activities of β-xylanase (5.3-fold), β-xylosidase (2.9-fold), and α-arabinofuranosidase (1.5-fold), respectively, compared to B. longum D1. When B. longum D2 was inoculated in the M-SHIME, inoculated with the bacterial gut communities of the individual with low AX-degrading enzyme activities, the β-xylanase activity increased (1.5-fold) in the proximal vessel. We demonstrated the presence of differences in LC-AX degrading enzyme activities of the bacterial gut communities of two individuals in the in vitro M-SHIME model, which could be linked to the presence of a potent AX-degrading B. longum (D2) strain.
- ArticleYang LX, Ma SG, Qiu YL, Zheng X.Clin Lab. 2016;62(5):849-54.BACKGROUND: The mutations in the dual oxidase maturation factor 2 (DUOXA2) and dual oxidase 2 (DUOX2) genes have been identified in patients with congenital hypothyroidism (CH). This study reports a set of dizygotic twins with CH due to the mutations in the DUOX2/DUOXA2 system.
METHODS: The dizygotic twins, a boy and a girl, both aged 7 years, were born to euthyroid nonconsanguineous parents; they were diagnosed with CH at neonatal screening and were enrolled in this study. The DUOXA2, DUOX2, paired box 8 (PAX8), thyroid peroxidase (TPO), and thyrotropin receptor (TSHR) genes were considered for mutation screening. Genomic DNA was extracted from peripheral blood leukocytes, and Sanger sequencing was used to screen for the mutations in the exon fragments. Family members of the patients were also enrolled and evaluated.
RESULTS: The fraternal twins each harbored a single heterozygous mutation, including c.738C>G (p.Y246X) in the boy inherited from the paternal DUOXA2 allele and c.2654G>A (p.R885Q) in the girl from the maternal DUOX2 allele. The two mutations have been previously reported. The boy showed enlarged thyroid lobes and a little calcification in the left lobe, while the girl's thyroid gland was severely underdeveloped and the girl had obvious complications due to irregular treatment. The germline mutations from this family were consistent with an autosomal recessive inheritance pattern. No mutations in the PAX8, TPO, and TSHR genes were detected in this study.
CONCLUSIONS: The inactivating mutations in the DUOXA2 (p.Y246X) and DUOX2 (p.R885Q) genes were identified in a set of dizygotic twins with CH. The girl was more severe in several aspects than her brother. The similar genetic defect resulted in very different outcomes. - ArticleHuang Z, Yang W, Zong Y, Qiu S, Chen X, Sun X, Zhou Y, Xie Z, Gao Q.Drug Deliv. 2016;23(3):849-57.The aim of this study was to investigate whether a periocular capsular drug delivery system (DDS) can release dexamethasone sodium phosphate (DEXP) in vitro and in vivo to the posterior segment of rabbit's eye. In vitro, the periocular capsular DDS containing 2 mg/ml or 5 mg/ml DEXP was immersed in modified Franz diffusion cell. Four-hundred microliters of liquid was aspirated at 0.5, 1, 2, 4, 8, 24 and 48 h for determination. In vivo, the DEXP-filled periocular capsular DDS was implanted into the sub-Tenon's sac of the New Zealand rabbit. DEXP concentration at the serum aqueous humor, cornea, iris, lens, ciliary body, vitreous, retina, choroids and sclera was quantified at 1, 3, 7, 14, 28 and 56 d after implantation. The DEXP concentration was determined by ultra-performance liquid chromatography-tandem mass spectrometry. In vitro, the periocular capsular DDS released the DEXP in time-dependent manner from 1/2 to 48 h. In vivo, the concentrations of the DEXP at the retina, choroids, ciliary body and iris were 123.11 (91.23, 732.61) ng/g, 362.46 ± 330.46 ng/g, 71.64 (71.35, 180.21) ng/g and 192.50 ± 42.66 ng/g, respectively, at 56 d after implantation. Minimal DEXP was found in the aqueous, serum and vitreous. Our results demonstrated that DEXP could be sustained released from the periocular capsular DDS, which indicated that the periocular capsular DDS might be a potential candidate of transscleral drug delivery for the management of posterior segment diseases.
- ArticleMoslehi S, Rowland C, Smith JH, Watterson WJ, Griffiths W, Montgomery RD, Philliber S, Marlow CA, Perez MT, Taylor RP.Adv Neurobiol. 2024;36:849-875.Imagine a world in which damaged parts of the body - an arm, an eye, and ultimately a region of the brain - can be replaced by artificial implants capable of restoring or even enhancing human performance. The associated improvements in the quality of human life would revolutionize the medical world and produce sweeping changes across society. In this chapter, we discuss several approaches to the fabrication of fractal electronics designed to interface with neural networks. We consider two fundamental functions - stimulating electrical signals in the neural networks and sensing the location of the signals as they pass through the network. Using experiments and simulations, we discuss the favorable electrical performances that arise from adopting fractal rather than traditional Euclidean architectures. We also demonstrate how the fractal architecture induces favorable physical interactions with the cells they interact with, including the ability to direct the growth of neurons and glia to specific regions of the neural-electronic interface.
- ArticleZhang MJ, Zhang GL, Yuan WB, Gao C.Hepatogastroenterology. 2014 May;61(131):849-52.BACKGROUND/AIMS: To investigate the possible clinical risk factors contributing to PGS after subtotal gastrectomy.
METHODOLOGY: The clinical data of 422 patients administering subtotal gastrectomy in our hospital were reviewed retrospectively from Jan, 1, 2005 to May, 1, 2012.
RESULTS: The higher morbility of PGS were found in the patients whose age were over 65 years, combining with anxiety disorder or diabetes mellitus, with low-albuminemia in perioperative period or having pyloric obstruction in preoperative period, administering Billroth II gastroenterostomy, whose operation time over 4 hours, using patient-controlled analgesia, injecting liquid per day over 3500 ml.
CONCLUSION: The clinical factors referred previously maybe the identified risk factors of PGS after subtotal gastrectomy, avoiding these clinical factors in perioperative period would reduce the occurrences of PGS after subtotal gastrectomy. - ArticleKe BC, Huang XX, Li Y, Li LY, Xu QX, Gao Y, Liu Y, Luo J.Neuroreport. 2016 08 03;27(11):849-57.Recent studies suggest that peripheral nerve injury converts resting spinal cord astroglial cells into an activated state, which is required for the development and maintenance of neuropathic pain. However, the underlying mechanisms of how resting astrocytes are activated after nerve injury remain largely unknown. Astroglial cell proliferation and activation could be affected by endogenous factors including chemokines, growth factors, and neurotropic factor. Chemokine (C-C motif) ligand 7 (Ccl7) is essential in facilitating the development of neuropathic pain; however, the mechanism is unknown. In the present study, we found that Ccl7 promoted astrocyte proliferation and thus contributed toward neuropathic pain. Spinal nerve ligation increased the expression in the spinal cord of neuronal Ccl7. Behavioral analyses showed that knockdown of Ccl7 alleviated spinal nerve ligation-induced neuropathic pain. Further in-vitro study showed that neuronal-derived Ccl7 was sufficient for the proliferation and activation of astroglial cells. We found a novel mechanism of Ccl7 stimulating the proliferation and activation of spinal cord astrocytes that contributes toward neuropathic pain.