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2.
Cancer ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524183

RESUMO

BACKGROUND: The use of herbs and supplements (HS) is common among patients with cancer, yet limited information exists about potential medication interactions (PMIs) with HS use around chemotherapy. METHODS: Patients with breast or prostate cancer who had recently finished chemotherapy at 2 academic medical centers were surveyed by telephone. Interviewers inquired about all medications, including HS, before, during, and after chemotherapy. Micromedex, Lexicomp, and Natural Medicines Comprehensive Database interaction software programs were used to determine PMIs. RESULTS: A total of 67 subjects (age range, 39-77 years) were evaluated in this study. Participants were primarily White patients (73%) with breast cancer (87%). The median number of medications was 11 (range, 2-28) during the entire study and was highest during chemotherapy (7; range, 2-22). Approximately four-fifths (84%) used HS. A total of 1747 PMIs were identified, and they represented 635 unique PMIs across all 3 timeframes, with most occurring during chemotherapy. Prescription-related PMIs (70%) were the most common type, and they were followed by HS-related (56%) and anticancer treatment-related PMIs (22%). Approximately half of the PMIs (54%) were categorized as moderate interactions, and more than one-third (38%) were categorized as major interactions. Patient use of HS increased from 51% during chemotherapy to 66% after chemotherapy, and this correlated with an increased prevalence of HS PMIs (46% to 60%). HS users were more likely to be at risk for a major PMI than non-HS users (92% vs 70%; P = .038). CONCLUSIONS: The use of HS remains prevalent among patients with cancer and may place them at risk for PMIs both during chemotherapy and after the completion of treatment. LAY SUMMARY: This study evaluates the risk of potential medication interactions for patients with breast or prostate cancer undergoing chemotherapy. The results show that patients often use herbs and supplements during treatment. Prescription medications are most often associated with medication interactions, which are followed by herb and supplement-related interactions. More than one-third of potential medication interactions are considered major. Patients should be educated about the risk of herb and supplement-related medication interactions during treatment.

3.
Arch Osteoporos ; 16(1): 21, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527160

RESUMO

We determined the extent of and reasons for non-adherence to oral bisphosphonates among veterans and conducted a pilot text message reminder application aimed at the most commonly cited reason for non-adherence. The intervention was found to be acceptable and feasible. PURPOSE: To evaluate the extent of and reasons for non-adherence to oral bisphosphonates among veterans and to assess the acceptability and feasibility of a pilot text message reminder application. METHODS: We surveyed 105 veterans initiating oral bisphosphonates for osteoporosis/osteopenia within the prior 18 months utilizing a validated self-report measure adapted for osteoporosis. Additionally, we conducted a pilot text message reminder to determine feasibility in 12 veterans who were initiating or were currently non-adherent to oral bisphosphonates. RESULTS: Of the 43 (40.9% response rate) completed surveys, the most common reasons for non-adherence were "I forgot" (37.5%), "I had other medications to take" (20.5%), "my bones are not weak" (18.4%), "I felt well" (18.4%), and "I worried about taking them for the rest of my life" (17.9%). Median MPR for the 49 (46.7%) non-adherent (MPR < 0.80) veterans was 0.35 (IQR 0.21-0.64). Of veterans offered a weekly automated text message reminder, 12 (50%) accepted. Nine of these 12 veterans reported that the text message reminders did "very well" at reminding them to take their medication and would recommend the application to other patients/family/friends. The median 6-month MPR for the reminder group was 0.96 (IQR 0.54-1.00). CONCLUSION: Half the veterans in our sample were taking insufficient doses of oral bisphosphonates to attain the full benefit of fracture risk reduction. Reasons for poor adherence included forgetfulness, polypharmacy, and misconceptions about osteoporosis. A pilot text message reminder intervention targeted to one of the most commonly cited reasons was found to be acceptable and feasible among veterans.

4.
Clin Pharmacol Ther ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33576025

RESUMO

Multidrug-resistant bacteria are causing a serious global health crisis. A dramatic decline in antibiotic discovery and development investment by pharmaceutical industry over the last decades has slowed the adoption of new technologies. It is imperative that we create new mechanistic insights based on latest technologies, and employ translational strategies to optimize patient therapy. While drug development has relied on MIC testing and established in vitro and mouse infection models, the limited understanding of outer membrane permeability in Gram-negative bacteria presents major challenges. Our team has developed a platform using the latest technologies to characterize target site penetration and receptor binding in intact bacteria that inform translational modeling and guide new discovery. Enhanced assays can quantify the outer membrane permeability of ß-lactam antibiotics and ß-lactamase inhibitors using multiplex LC-MS/MS. While ß-lactam antibiotics are known to bind to multiple different penicillin-binding proteins (PBP), their binding profiles are almost always studied in lysed bacteria. Novel assays for PBP binding in the periplasm of intact bacteria were developed and proteins identified via proteomics. To characterize bacterial morphology changes in response to PBP binding, high-throughput flow cytometry and time-lapse confocal microscopy with fluorescent probes provide unprecedented mechanistic insights. Moreover, novel assays to quantify cytosolic receptor binding and intracellular drug concentrations inform target site occupancy. These mechanistic data are integrated by quantitative and systems pharmacology modeling to maximize bacterial killing and minimize resistance in in vitro and mouse infection models. This translational approach holds promise to identify antibiotic combination dosing strategies for patients with serious infections.

5.
Clin Chem ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33582770

RESUMO

BACKGROUND: Short tandem repeat (STR)-based chimerism analysis has been widely used for chimerism monitoring after hematopoietic stem-cell transplantation (HSCT), but technical artifacts can be problematic. We designed a chimerism assay using single nucleotide polymorphisms (SNPs) adjacent and in linkage-disequilibrium (CASAL), which doubly checked for SNP pairs, and thus could reduce background errors and increase analytical sensitivity. METHODS: CASAL targeted 84 SNP pairs within 10 bp distance and in perfect linkage-disequilibrium. Using undiluted and serially diluted samples, baseline error rates, and linearity was calculated. Clinical performance of CASAL was evaluated in comparison with a conventional STR assay, using 191 posttransplant samples from 42 patients with HSCT. RESULTS: CASAL had ∼10 times lower baseline error rates compared to that of ordinary next-generation sequencing. Limit of detection and quantification of CASAL were estimated to be 0.09 and 0.39%, respectively, with a linear range of 0.1-100%. CASAL correlated well with STR assay (r2 = 0.99) and the higher sensitivity enabled detection of low-level recipient chimerism and earlier prediction of relapse. CONCLUSIONS: CASAL is a simple, analytically sensitive and accurate assay that can be used in clinical samples after HSCT with a higher performance compared to that of traditional assays. It should also be useful in other forensic and archeological testing.

7.
PLoS One ; 16(2): e0246626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571295

RESUMO

PURPOSE: To evaluate the clinical outcomes of patients with treatment-naïve diabetic macula oedema (DMO) treated with Aflibercept in routine clinic settings in ethnically diverse North West London (NWL) and compare to outcomes reported in the VIVID and VISTA clinical trials. METHODS: This was a retrospective multicentre interventional case series. Two hundred and seventy eyes of 221 treatment-naïve patients at three NWL hospitals initiated on Aflibercept and who had at least 12 months follow-up were included in the study. Visual acuity, central subfield thickness and macula volume were recorded at baseline, month 3, 6 and 12. RESULTS: There were significant differences between the NWL cohort and participants in the VIVID and VISTA trials at baseline including higher HbA1c and a higher proportion of eyes with proliferative diabetic retinopathy in the NWL cohort. The mean VA, mean CSFT and mean MV at baseline was 66.4 (± 14.6) letters, 417 (± 94) µm and 10.3 (± 1.9) mm3. The mean VA gain at 12 months was 4.0 (± 11.8) letters (p < 0.001); a total of 26% of eyes gained ≥ 10 letters, 15% of eyes gained ≥ 15 letters and 6% lost ≥15 letters. At 12-months, the mean reduction in CSFT was 108 (± 96) µm (p<0.001) and the mean reduction in MV was 1.05 (± 1.21) mm3 (p<0.001). An average of 6.2 (± 2.3) injections was given over 12 months. There was a significant association between functional and anatomical response category at 3 months and response category at 12 months (p<0.001). CONCLUSION: The effectiveness of treatment with Aflibercept for patients in NWL was meaningfully lower than was reported in the VIVID and VISTA clinical trials. A high proportion of patients with good visual acuity at baseline, poorer glycaemic control, worse diabetic retinopathy and under-treatment likely contributed to lower functional and anatomical outcomes.

8.
Drug Discov Today ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33453364

RESUMO

The quality of lead compounds is a key factor for determining the success of chemical probe and drug discovery programs. Given that high-throughput screening (HTS) continues to be a dominant lead generation paradigm, access to high-quality screening libraries is crucial for such efforts in both industry and academia. Here, we discuss the strategy implemented a decade ago to build from scratch one of the largest compound collections in academia, containing ∼575 000 carefully annotated small molecules, and a recent multidisciplinary effort designed to further enhance the collection to meet our research demands for the next decade.

9.
JCO Oncol Pract ; : OP2000471, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33492981

RESUMO

PURPOSE: Complementary and integrative medicine (CIM) services are more prevalent in cancer centers but continue to be underutilized by patients. This study examines perspectives from patients and caregivers about these services being offered at a comprehensive cancer center. METHODS: Patients and caregivers were surveyed about their familiarity, interest, and experience with five CIM therapies: acupuncture, massage, meditation, music therapy, and yoga. Respondents were also asked about their interest when recommended by their medical team and when offered in a clinical trial as well as their willingness to pay for these services. Respondents were also asked about perceived barriers to accessing these services. Chi-squared tests were performed to explore associations between past experience, interest levels, and willingness to pay. RESULTS: A total of 576 surveys were obtained (464 patients and 112 caregivers). Most respondents identified as White or Caucasian (65.6%), female (57.2%), had been a patient for < 3 years (74.2%), had some college education (73.8%), and made > $40,000 in US dollars as their annual household income (69.1%). Respondents were most familiar with therapeutic massage (34.2%) and least familiar with acupuncture (20.0%). The average interest in these services increased from 53.3% to 64.1% when recommended by a medical professional. Respondents were most willing to pay $1-60 for therapeutic massage (62.3%) and least willing to pay for meditation (43.7%). The main barriers to accessing CIM services were cost (56.0%) and lack of knowledge (52.1%). CONCLUSION: Overall, a significant proportion of patients and caregivers were unfamiliar with these five integrative therapies. Increasing education, decreasing cost, and a recommendation by medical professionals would improve CIM usage.

10.
Ophthalmol Glaucoma ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429109

RESUMO

OBJECTIVE: To report treatment outcomes of primary transscleral cyclophotocoagulation (TSCPC) in glaucomatous eyes. DESIGN: A retrospective non-comparative study. SUBJECTS: Forty-eight eyes with a diagnosis of glaucoma and no previous incisional ocular surgery. INTERVENTION: Continuous wave TSCPC was applied to the ciliary body to lower intraocular pressure (IOP). MAIN OUTCOME MEASURES: The primary outcome measure was surgical success defined as an IOP ≤ 21 mmHg or reduced ≥ 20% from baseline, IOP > 5 mmHg, no reoperation for glaucoma, and no loss of light-perception vision. Secondary outcome measures include visual acuity (VA) and complications. RESULTS: Glaucoma eyes were stratified into two groups -1) those with pre-treatment IOP > 21mmHg (high group) and 2) those with pre-treatment IOP ≤ 21mmHg (low group). Mean±SD IOP at baseline was 30.2±6.0mmHg in the high group and 16.2±2.8mmHg in the low group. Mean±SD number of glaucoma medications at baseline was 4.0±0.9 in the high group and 3.6±1.1 in the low group. Based on our success criteria, the cumulative probability of success during the first year of follow-up was 58.3% in the high group and 28.1% in the low group (P=0.052). Post-operative mean IOP was significantly lower than baseline in the high IOP group at 1, 3, 6, 12, and 18 months post-operative visits (p<0.05). No significant change was observed in IOP at follow up visits after 1 month in the low IOP group. Throughout the first year of follow up both groups required fewer glaucoma medications compared with baseline at the 1, 3, 6, and 12 months post-operative visits (p<0.05). The most frequent cause of post-operative decrease in VA was cataract in 9 eyes. Decrease in vision due to glaucoma was observed in only 3 eyes. Complications included prolonged inflammation (11 eyes), iris neovascularization (2 eyes), cystoid macular edema (4 eyes) and hyphema (1 eye). No severe or long-term complications were observed among the study subjects. CONCLUSIONS: Continuous wave TSCPC was effective in lowering IOP in glaucoma patients without prior incisional ocular surgery who were recalcitrant to medical therapy, particularly those with baseline IOP > 21mmHg. Our minimally invasive surgical outcomes are comparable to those of conventional glaucoma surgical studies, such as the Ahmed Versus Baerveldt and Tube Versus Trabeculectomy studies.

11.
ACS Infect Dis ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471519

RESUMO

The successful treatment of Helicobacter pylori infections is becoming increasingly difficult due to the rise of resistance against current broad spectrum triple therapy regimens. In the search for narrow-spectrum agents against H. pylori, a high-throughput screen identified two structurally related thienopyrimidine compounds that selectively inhibited H. pylori over commensal members of the gut microbiota. To develop the structure-activity relationship (SAR) of the thienopyrimidines against H. pylori, this study employed four series of modifications in which systematic substitution to the thienopyrimidine core was explored and ultimately side-chain elements optimized from the two original hits were merged into lead compounds. During the development of this series, the mode of action studies identified H. pylori's respiratory complex I subunit NuoD as the target for lead thienopyrimidines. As this enzyme complex is uniquely essential for ATP synthesis in H. pylori, a homology model of the H. pylori NuoB-NuoD binding interface was generated to help rationalize the SAR and guide further development of the series. From these studies, lead compounds emerged with increased potency against H. pylori, improved safety indices, and a good overall pharmacokinetic profile with the exception of high protein binding and poor solubility. Although lead compounds in the series demonstrated efficacy in an ex vivo infection model, the compounds had no efficacy in a mouse model of H. pylori infection. Additional optimization of pharmacological properties of the series to increase solubility and free-drug levels at the sequestered sites of H. pylori infection would potentially result in a gain of in vivo efficacy. The thienopyrimidine series developed in this study demonstrates that NuoB-NuoD of the respiratory complex I can be targeted for development of novel narrow spectrum agents against H. pylori and that thienopyrimines can serve as the basis for future advancement of these studies.

12.
Sensors (Basel) ; 21(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440714

RESUMO

Detection of multiple lane markings on road surfaces is an important aspect of autonomous vehicles. Although a number of approaches have been proposed to detect lanes, detecting multiple lane markings, particularly across a large number of frames and under varying lighting conditions, in a consistent manner is still a challenging problem. In this paper, we propose a novel approach for detecting multiple lanes across a large number of frames and under various lighting conditions. Instead of resorting to the conventional approach of processing each frame to detect lanes, we treat the overall problem as a multitarget tracking problem across space and time using the integrated probabilistic data association filter (IPDAF) as our basis filter. We use the intensity of the pixels as an augmented feature to correctly group multiple lane markings using the Hough transform. By representing these extracted lane markings as splines, we then identify a set of control points, which becomes a set of targets to be tracked over a period of time, and thus across a large number of frames. We evaluate our approach on two different fronts, covering both model- and machine-learning-based approaches, using two different datasets, namely the Caltech and TuSimple lane detection datasets, respectively. When tested against model-based approach, the proposed approach can offer as much as 5%, 12%, and 3% improvements on the true positive, false positive, and false positives per frame rates compared to the best alternative approach, respectively. When compared against a state-of-the-art machine learning technique, particularly against a supervised learning method, the proposed approach offers 57%, 31%, 4%, and 9× improvements on the false positive, false negative, accuracy, and frame rates. Furthemore, the proposed approach retains the explainability, or in other words, the cause of actions of the proposed approach can easily be understood or explained.

14.
J Thorac Cardiovasc Surg ; 161(3): 1008-1009, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33451839
15.
Urology ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33482136

RESUMO

OBJECTIVE: To determine whether the academic achievement of Department Chairperson (DC) and Research Director (RD), when present, is associated with increased scholarly productivity and National Institutes of Health (NIH) funding of faculty members in academic urology departments. MATERIALS AND METHODS: We identified the DC, RD and faculty members of 145 academic urology departments. The scholarly productivity and NIH funding for each individual faculty member was assessed from 2018 to 2019 using an h-index extrapolated from the Scopus database and the NIH RePORTER tool, respectively. The Spearman correlation coefficient was employed to define the correlation of these parameters. Hypothesis testing was conducted using the Mann-Whitney U test. RESULTS: After excluding 13 departments due to missing faculty listing, our final sample included 132 departments and 2227 faculty members. In 2018, the NIH provided $55,243,658 in urology research grants to 24.2% of departments and 4.0% of faculty members. Of departments with NIH funding, 68.8% employed a RD. DC and RD h-index were positively correlated with departmental h-index. DC h-index positively correlated with department NIH funding. Moreover, NIH funding was significantly higher for departments with a RD vs those without a RD ($1,268,028 vs $62,941, P < .001); interestingly, NIH funding was higher for departments employing unfunded RDs vs those without a RD ($2,079,948 vs $579,055, P < .001). CONCLUSION: Academic success of a DC and RD was associated with urology departmental scholarly productivity and NIH funding. The presence of a RD, funded or unfunded, was associated with increased departmental NIH funding.

16.
J Antibiot (Tokyo) ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504919

RESUMO

Spectinomycin, an aminocyclitol antibiotic, is subject to inactivation by aminoglycoside modifying enzymes (AMEs) through adenylylation or phosphorylation of the 6-hydroxy group position. In this study, the effects of deoxygenation of the 2- and 6-hydroxy group positions on the spectinomycin actinamine ring are probed to evaluate their relationship to ribosomal binding and the antimicrobial activities of spectinomycin, semisynthetic aminomethyl spectinomycins (amSPCs), and spectinamides. To generate these analogs, an improved synthesis of 6-deoxyspectinomycin was developed using the Barton deoxygenation reaction. 6-Dehydrospectinamide was also synthesized from spectinamide 4 to evaluate the H-bond acceptor character on the C-6 position. All the synthesized analogs were tested for antibacterial activity against a panel of Gram (+) and Gram (-) pathogens, plus Mycobacterium tuberculosis. The molecular contribution of the 2- and 6-hydroxy group and the aryl functionalities of all analogs were examined by measuring inhibition of ribosomal translation and molecular dynamics experiments with MM/GBSA analysis. The results of this work indicate that the 6-hydroxy group, which is the primary target of AMEs, is a required motif for antimicrobial activity in current analogs. Removal of the 6-hydroxy group could be partially rescued by offsetting ribosomal binding contributions made by the aryl side chains found in the spectinamide and amSPCs. This study builds on the knowledge of the structure-activity relationships of spectinomycin analogs and is being used to aid the design of next-generation spectinomycins.

17.
J Gastroenterol Hepatol ; 36(2): 490-497, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33448489

RESUMO

BACKGROUND AND AIM: Endoscopist directed nurse administered propofol sedation (EDNAPS) is widely considered to be safe and efficient, but there are limited data from the Australian health-care setting, and Australian sedation guidelines do not support the practice. Thus, we report data from a prospective audit of EDNAPS over a 6.5-year period in an Australian referral hospital. METHODS: Consecutive endoscopic procedures performed between January 2013 and June 2019. Sedation protocol was an initial dose of midazolam 1-3 mg intravenously (i.v.) and propofol 10-50 mg i.v.. Further aliquots of propofol 10-30 mg i.v. were given as required. ProvationMD® endoscopic reporting system was used to prospectively record patient demographics, medication and dose, American Society of Anesthesiologist's (ASA) class, and sedation-related complications. RESULTS: During the 78-month period, 28 051 eligible procedures were performed; 3093 procedures performed with anesthetic support or without EDNAPS were excluded. In total, 24 958 procedures with EDNAPS were analyzed including 7563 gastroscopies, 12 941 colonoscopies, 2932 gastroscopy and colonoscopy, 1440 flexible sigmoidoscopies, and 82 combined gastroscopy and flexible sigmoidoscopy. Of these, 9539 were ASA 1 (38.2%), 13 680 were ASA 2 (54.8%), 1733 were ASA 3 (6.9%), and 4 were ASA 4 (0.02%). Sedation-related complications occurred in 66 patients (0.26%), predominantly transient hypoxic episodes. No patient required intubation for an airway emergency, and there was no sedation-related mortality. Sedation-related complications increased with ASA class and were significantly more common with gastroscopy. CONCLUSIONS: Endoscopist directed nurse administered propofol sedation is a safe way of performing endoscopic sedation in low-risk patients in the hospital setting.

18.
Br J Haematol ; 192(2): 375-384, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33338291

RESUMO

Immune thrombocytopenia (ITP) is thought to result from an aberrant adaptive autoimmune response, involving autoantibodies, B and T lymphocytes, directed at platelets and megakaryocytes. Previous reports have demonstrated skewed CD4+ T-helper subset distribution and enhanced production of pro-inflammatory cytokines such as interleukin 17A and interferon gamma. The role of monocytes (MCs) in ITP is less widely described, but innate immune cells have a role in shaping CD4+ T-cell phenotypes. Glucocorticoids (GCs) are commonly used for first-line ITP treatment and modulate a broad range of immune cells including T cells and MCs. Using multiparameter flow cytometry analysis, we demonstrate the expansion of intermediate MCs (CD14++ CD16+ ) in untreated patients with newly diagnosed ITP, with these cells displaying a pro-inflammatory phenotype, characterised by enhanced expression of CD64 and CD80. After 2 weeks of prednisolone treatment (1 mg/kg daily), the proportion of intermediate MCs reduced, with enhanced expression of the anti-inflammatory markers CD206 and CD163. Healthy control MCs were distinctly different than MCs from patients with ITP before and after GC treatment. Furthermore, the GC-induced phenotype was not observed in patients with chronic ITP receiving thrombopoietin receptor agonists. These data suggest a role of MCs in ITP pathogenesis and clinical response to GC therapy.

19.
Antimicrob Agents Chemother ; 65(3)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33361293

RESUMO

Zinc is an essential micronutrient for mycobacteria, and its depletion induces multiple adaptive changes in cellular physiology, the most remarkable of which are remodeling and hibernation of ribosomes. Ribosome remodeling, induced upon relatively moderate depletion of zinc, involves replacement of multiple ribosomal proteins containing the zinc-binding CXXC motif (called C+ r proteins) by their motif-free C- paralogs. Severe zinc depletion induces binding of mycobacterial protein Y (Mpy) to the 70S C- ribosome, thereby stabilizing the ribosome in an inactive state that is also resistant to kanamycin and streptomycin. Because the Mpy binding region on the ribosome is proximal to the binding pocket of spectinamides (Spa), the preclinical drug candidates for tuberculosis, we addressed the impact of remodeling and hibernation of ribosomes on Spa sensitivity. We report here that while Mpy binding has no significant effect on Spa sensitivity to the ribosome, replacement of S14C+ with its C- counterpart reduces the binding affinity of the drug by ∼2-fold, causing increased Spa tolerance in Mycobacterium smegmatis and Mycobacterium tuberculosis cells harboring the C- ribosome. The altered interaction between Spa and ribosomes likely results from new contact points for D67 and R83 residues of S14C- with U1138 and C1184 of 16S rRNA helix 34, respectively. Given that M. tuberculosis induces ribosome remodeling during progression from the acute to chronic phase of lung infection, our findings highlight new considerations in the development of Spa as effective drugs against tuberculosis.

20.
Adv Mater ; 33(4): e2003778, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33325594

RESUMO

Development of inflammation modulating polymer scaffolds for soft tissue repair with minimal postsurgical complications is a compelling clinical need. However, the current standard of care soft tissue repair meshes for hernia repair is highly inflammatory and initiates a dysregulated inflammatory process causing visceral adhesions and postsurgical complications. Herein, the development of an inflammation modulating biomaterial scaffold (bioscaffold) for soft tissue repair is presented. The bioscaffold design is based on the idea that, if the excess proinflammatory cytokines are sequestered from the site of injury by the surgical implantation of a bioscaffold, the inflammatory response can be modulated, and the visceral adhesion formations and postsurgical complications can be minimized. The bioscaffold is fabricated by 3D-bioprinting of an in situ phosphate crosslinked poly(vinyl alcohol) polymer. In vivo efficacy of the bioscaffold is evaluated in a rat ventral hernia model. In vivo proinflammatory cytokine expression analysis and histopathological analysis of the tissues have confirmed that the bioscaffold acts as an inflammation trap and captures the proinflammatory cytokines secreted at the implant site and effectively modulates the local inflammation without the need for exogenous anti-inflammatory agents. The bioscaffold is very effective in inhibiting visceral adhesions formation and minimizing postsurgical complications.

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