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91.
N. S. Hari Narayana Moorthy Sergio F. Sousa Maria J. Ramos Pedro A. Fernandes 《Medicinal chemistry research》2016,25(7):1340-1357
Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets. 相似文献
92.
Stelter K. Theodoraki M. N. Becker S. Tsekmistrenko V. Olzowy B. Ledderose G. 《European archives of oto-rhino-laryngology》2015,272(3):639-639
European Archives of Oto-Rhino-Laryngology - 相似文献
93.
94.
95.
Dan Azagury Tara E Mokhtari Luis Garcia Ulysses S Rosas Trit Garg Homero Rivas John Morton 《Surgery》2019,165(3):565-570
Background
Laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding all lead to substantial weight loss in obese patients. Long-term weight loss can be highly variable beyond 1-year postsurgery. This study examines and compares the frequency distribution of weight loss and lack of treatment effect rates after laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding.Methods
A total of 1,331 consecutive patients at a single academic institution were reviewed from a prospectively collected database. Preoperative data collected included demographics, body mass index, and percent excess weight loss. Postoperative BMI and %EWL were collected at 12, 24, and 36 months. Percent excess weight loss was analyzed by the percentiles of excess weight lost, and the distribution of percent excess weight loss was evaluated in 10% increments. Lack of a successful treatment effect was defined as <25% excess weight loss.Results
Of the 1,331 patients, 72.4% (963) underwent laparoscopic Roux-en-Y gastric bypass, 18.3% (243) laparoscopic sleeve gastrectomy, and 9.4%(125) laparoscopic adjustable gastric banding. Mean percent excess weight loss was greatest for laparoscopic Roux-en-Y gastric bypass, followed by laparoscopic sleeve gastrectomy, and then by laparoscopic adjustable gastric banding at every time point: at 2 years mean percent excess weight loss was 77.9± 24.4 for laparoscopic Roux-en-Y gastric bypass, 50.8 ± 25.8 for laparoscopic sleeve gastrectomy, and 40.8± 25.9 for laparoscopic adjustable gastric banding (P < .0001). The rates of a successful treatment effect s for laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding were 0.9%, 5.2%, and 24.3% at 1 year; 0.3%, 11.1%, and 26.0% at 2 years; and 1.0%, 25.3%, and 30.2% at 3 years. At 1 year, the odds ratio of lack of a successful treatment effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass was 6.305 (2.125–19.08; P?=?.0004), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass was 36.552 (15.64–95.71; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy was 5.791 (2.519–14.599; P < .0001). At 2 years, the odds ratio for laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass increased to 70.7 (9.4–531.7; P < .0001), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass increased to 128.1 (16.8–974.3; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy decreased to 1.8 (0.9–3.6; P?=?.09).Conclusion
This study emphasizes the existing variability in weight loss across bariatric procedures as well as in the lack of a treatment effect for each procedure. Although laparoscopic adjustable gastric banding has the greatest rate of a lack of a successful treatment effect, the rate remained stable over 3 years postoperatively. Laparoscopic sleeve gastrectomy showed a doubling in the rate of a lack of a successful treatment effect every year reaching 25% at year 3. The rates for lack of a successful treatment effect for laparoscopic Roux-en-Y gastric bypass remained stable at about 1% for the first 3 years postoperatively. 相似文献96.
Rosario Gulias-Cañizo Anell Lagunes-Guillén Arturo González-Robles Erika Sánchez-Guzmán Federico Castro-Muñozledo 《Burns : journal of the International Society for Burn Injuries》2019,45(2):398-412
Background
Since recent reports have shown that (-)-Epigallocatechin-3-gallate (EGCG) could be used for treating proliferative and inflammatory disorders, we explored its use for the management of corneal chemical burns.Materials and methods
Initially, EGCG was assayed on the rabbit corneal epithelial cell line RCE1(5T5) to establish the best testing conditions, and to avoid unwanted outcomes in the experimental animals. Then, we studied its effects on cell proliferation, cell cycle progression and cell differentiation. Afterwards, we instilled EGCG in experimental grade II corneal alkali burns in mice, three times a day up to 21 days, and evaluated by slit lamp examination and histological sections of corneal epithelial, corneal endothelial and stromal edema, as well as the presence of inflammatory cells and neovascularization.Results
EGCG reduced cell growth and led to a decline in the proportion of proliferative cells in a concentration dependent manner. At 10 μM, EGCG promoted cell differentiation, an effect not related with apoptosis or cytotoxicity. When 10 μM EGCG was instilled in corneal alkali burns in mice three times a day up to 21 days, EGCG significantly reduced corneal opacity and neovascularization. The improved clinical appearance of the cornea was associated to a controlled epithelial growth; epithelial morphology was similar to that observed in normal epithelium and contrasted with the hyperproliferative, desquamating epithelium observed in control burn wounds. EGCG reduced corneal, stromal and endothelial edema, and wound inflammation.Conclusion
This work constitutes the first evidence for the use of EGCG in the acute phase of a corneal alkali burn, representing a possible novel alternative to improve patient outcomes as an add-on therapy. 相似文献97.
M. Simons R. Kimble S. McPhail Z. Tyack 《Burns : journal of the International Society for Burn Injuries》2019,45(8):1792-1809
BackgroundThe measurement of health-related quality of life (HRQoL) provides information about the perceived burden of the health condition and treatments from a lived experience. The Brisbane Burn Scar Impact Profile (caregiver report for young children, BBSIP0–8), developed in 2013, is a proxy-report measure of burn scar-specific HRQoL. The aim of this study was to report its psychometric properties in line with an evaluative purpose.MethodsCaregivers of children up to 8 years of age at risk of burn scarring were recruited into a prospective, longitudinal cohort study. Caregivers completed the BBSIP0–8, Pediatric Quality of Life Inventory and Patient Observer Scar Assessment Scale at baseline (approximately ≥85% of the total body surface area re-epithelialised), 1–2 weeks after baseline and 1-month after baseline. Psychometric properties measured included internal consistency, test–retest reliability, validity and responsiveness.ResultsEighty-six caregivers of mostly male children (55%), of a median age (IQR) of 1 year, 10 months (2 years, 1 month) and total body surface area burn of 1.5% (3.0%) were recruited. Over one third of participants were grafted and 15% had contractures or skin tightness at baseline. Internal consistency of ten item groups ranged from 0.73 to 0.96. Hypothesised correlations of changes in the BBSIP0–8 items with changes in criterion measures supported longitudinal validity (ρ ranging from ?0.73 to 0.68). The majority of item groups had acceptable reproducibility (ICC = 0.65–0.83). The responsiveness of five item groups was supported (AUC = 0.71–0.90).ConclusionThe psychometric properties tested support the use of the BBSIP0–8 as an evaluative measure of burn scar-related health-related quality of life for children aged below eight years in the early post-acute period of rehabilitation. Further investigation at longer time period after burn injury is indicated. 相似文献
98.
Sathiyavelavan Gopalan Jagadesh Chandra Bose S. Periasamy 《The Indian journal of surgery》2015,77(3):232-236
The aim of this study is to review the literature to find out the exact etiology of anastomotic cancers of colon post resection and differentiate them between a recurrence, second primary, and metastatic disease (local manifestation of systemic disease). Web-based literature search was done, and datas collected. We searched PubMed for papers using the keywords colon cancer recurrence, anastomotic recurrence, and recurrent colon carcinoma. We also searched for systematic review in the same topic. In addition, we used our personal referrence archive. Anastomotic recurrences of colon are postulated to arise due to inadequate margins, tumor implantation by exfoliated cells, altered biological properties of bowel anastomosis, and missed synchronous lesions. Some tumors are unique with repeated recurrence after repeated resection. Duration after primary surgery plays a major role in differentiating recurrent and second primary lesions. Repeated recurrences after repeated resections have to be considered a manifestation of systemic disease or metastatic disease due to the virulence of the disease. A detailed analysis and study of patients with colonic anastomotic lesion are required to differentiate it between a recurrent, a second primary lesion, and a metastatic disease (local manifestation of a systemic disease). The nomenclature is significant to study the survival of these patients, as a second primary lesion will have different survival compared to that of recurrent lesions. 相似文献
99.
ObjectivesTo fill an empirical gap in the literature by examining changes in quality of care measures occurring when multispecialty clinic systems were acquired by hospital-owned, vertically integrated health care delivery systems in the Twin Cities area.ConclusionsMoving a clinic system into a vertically integrated delivery system resulted in limited increases in quality of care indicators. Caution is warranted when the acquisition causes disruption in referral patterns. 相似文献
100.
Michael L. Goodman Miriam S. Mutambudzi Stanley Gitari Philip H. Keiser Sarah E. Seidel 《Vulnerable children and youth studies》2016,11(4):366-378
There are an estimated 56 million orphans and vulnerable children across sub-Saharan Africa. Communities typically care for orphan children through informal caring arrangements – either within or outside of kinship networks. Within Kenya, an estimated 250,000 children live on the streets. There is less research related to fostering attitudes of this special population than orphans and vulnerable children generally. Important research over the past decade has illuminated multiple ways in which children are made more vulnerable because of HIV, including parental death and street-migration from HIV-affected households. As HIV transitions from a terminal illness to a chronic, manageable one, research is also required to establish how parents living with HIV can be an asset to children. In this study, we assess whether mothers living with HIV were very willing to foster biologically-related children, and street-involved children, how these fostering attitudes differed from mothers not living with HIV, and whether differences in fostering attitudes by reported HIV status were mediated by social support, family functioning and general self-rated health. Approximately 40% of mothers living with HIV were very willing to provide long-term foster care to biologically-related or street-involved children. This was less than the percentage of mothers not living with HIV, who were very willing to foster biologically-related children (61%) or street-involved children (58%). Significant portions of these differences were explained by social support, family functioning and general self-rated health. Multi-sectoral approaches are suggested by these findings in order to improve the child-fostering capacity of mothers living with HIV. Improving social support, family functioning and general self-rated health among HIV-infected mothers may not only provide protective benefits for the mothers and their children, but also expand the community’s capacity to care for orphan and vulnerable children. 相似文献