Finding a New Type of Drug Candidate Using Combinatorial Library Approaches

김성건,Alex G. Cole,Connie G. Tang,윤문영 한국바이오칩학회 2007 BioChip Journal Vol.1 No.4

As the consequence of an ever-increasing trend toward bacterial antibiotic drug resistance, scientists are compelled to constantly develop a great diversity of mole-cules that can function as potent antibiotics. Using combinatorial library methods, a number of potential drugs can be selected from a sizeable pool of antibiotics. The several molecules selected and described herein, which generally inhibit specific enzymatic activities, show promise in medical applications, including inhibitors of metallo- β-lactamase in <i>B. cereus</i> and of acetohydroxyacid synthase in <i>M. tuberculosis</i>. These potential antibiotics evidence different structures than are exhibited by the currently-used inhibitors, thus raising the possibility that an entirely new class of antibiotics has been found. Combinatorial methods may also be utilized to explore inhibitor specificity, as was previously done using both metallo-β-lactamase and acetohydroxyacid synthase. The isolation of these molecules and the exploration of their specificity underlines the importance and potential of combinatorial methods in the discovery of future antibiotics to combat changing bacterial antibiotic resistance.

A comparison of healing and complication rates between common flaps utilized in total knee arthroplasty: a review of the literature

( Akhil A. Chandra ),( Filippo Romanelli ),( Alex Tang ),( Luke Menken ),( Maximilian Zhang ),( Adam Feintisch ),( Frank A. Liporace ),( Richard S. Yoon ) 대한슬관절학회 2022 대한슬관절학회지 Vol.34 No.-

Background: Flap reconstruction with perforator, fasciocutaneous, muscular, and/or free microvascular flaps is utilized to cover wound defects and improve vascularization and antibiotic/nutrient delivery. Flap use in revision procedures for total knee arthroplasty has been explored previously; however, current data are limited and studies comparing healing and complication rates between different flap types are lacking. Methods: A literature review was performed using PubMed on 13 January 2022. Studies were included if they reported healing and complication rates for either gastrocnemius, rectus abdominis, latissimus dorsi, fasciocutaneous, chimeric, or gracilis flaps in the setting of revision total knee arthroplasty (TKA). Results: The final cohort included gastrocnemius (n = 421, healing rate 73.8%, complication rate 59.9%), gracilis (n = 9, healing rate 93%, complication rate 55.6%), latissimus dorsi (n = 41, healing rate 67%, complication rate 46.3%), rectus abdominis (n = 3, healing rate 100%, complication rate 0%), fasciocutaneous (n = 78, healing rate 70%, complication rate 19.2%), and chimeric flaps (n = 4, healing rate 100%, complication rate 25%). There was no significant difference when comparing healing rates across flap types (p = 0.39). There was a significant difference when comparing complication rates across flap types (p < 0.0001), with a significant difference being noted between gastrocnemius and fasciocutaneous complication rates (p < 0.0001). All other comparisons between flap types by complication rate were not significantly different. Conclusions: Gastrocnemius flaps are the workhorse flap in the setting of revision TKA, as evidenced by this review. Healing rates did not vary significantly across flap types, which suggests that determining the appropriate flap for coverage of soft-tissue defects in revision TKA should be driven by defect size and location as well as physician experience and patient tolerance.

Survivorship Analysis in Asymptomatic COVID-19+ Hip Fracture Patients: Is There an Increase in Mortality?

Mason D. Vialonga,Luke G. Menken,Alex Tang,John W. Yurek,Li Sun,John J. Feldman,Frank A. Liporace,Richard S. Yoon 대한고관절학회 2022 Hip and Pelvis Vol.34 No.1

Purpose: Mortality rates following hip fracture surgery have been well-studied. This study was conducted to examine mortality rates in asymptomatic patients presenting for treatment of acute hip fractures with concurrent positive COVID-19(+) tests compared to those with negative COVID-19(–) tests. Materials and Methods: A total of 149 consecutive patients undergoing hip fracture surgery during the COVID-19 pandemic at two academic medical centers were reviewed retrospectively. Patients were divided into two groups for comparative analysis: one group included asymptomatic patients with COVID-19+ tests versus COVID-19– tests. The primary outcome was mortality at 30-days and 90-days. Results: COVID-19+ patients had a higher mortality rate than COVID-19– patients at 30-days (26.7% vs 6.0%, P=0.005) and 90-days (41.7% vs 17.2%, P=0.046) and trended towards an increased length of hospital stay (10.1 ±6.2 vs 6.8±3.8 days, P=0.06). COVID-19+ patients had more pre-existing respiratory disease (46.7% vs 11.2%, P=0.0002). Results of a Cox regression analysis showed an increased risk of mortality at 30-days and 90- days from COVID-19+ status alone without an increased risk of death in patients with pre-existing chronic respiratory disease. Conclusion: Factors including time to surgery, age, preexisting comorbidities, and postoperative ambulatory status have been proven to affect mortality and complications in hip fracture patients; however, a positive COVID19 test result adds another variable to this process. Implementation of protocols that will promote prompt orthogeriatric assessments, expedite patient transfer, limit operating room traffic, and optimize anesthesia time can preserve the standard of care in this unique patient population.

ANALYSTS' EARNINGS COVERAGE AND NON-REPORTING BIAS DURING THE ASIAN FINANCIAL CRISIS

James S Ang,Yu long Ma,Alex P Tang People&Global Business Association 2007 Global Business and Finance Review Vol.12 No.2

Analysts are known to give grossly optimistic earnings forecasts for Asian firms during the 1997-1998 financial market crises. We examine whether the absence of forecasts from analysts with the lowest expectations could contribute to the observed bias. We find evidence consistent with a non-reporting strategy, where some analysts chose not to release forecasts or updates. We find that analysts used the non-reporting earlier in Korea in 1997, and later in Indonesia, Malaysia and Thailand. The analysts seemed to follow two reporting strategies during the crisis. They would maintain or increase coverage, with over optimistic earnings forecasts, for firms that were large, and possibly influential. or for safer firms that did not fare too badly during the crisis. On the other hand, they would use the non-reporting strategy for firms that were expected to fare poorly. We verify that our evidence on the non-reporting strategy was not due to possible attrition in the number of brokerage firms or listed firms during the crisis.

Assessing the Necessity of Extra Reduction Aides in Intramedullary Nailing of Intertrochanteric Hip Fractures

John W. Yurek,Nikki A. Doerr,Alex Tang,Adam S. Kohring,Frank A. Liporace,Richard S. Yoon 대한고관절학회 2023 Hip and Pelvis Vol.35 No.3

Purpose: This study aims to determine which intertrochanteric (IT) hip fracture and patient characteristics predict the necessity for adjunct reduction aides prior to prep and drape aiming for a more efficient surgery. Materials and Methods: Institutional fracture registries from two academic medical centers from 2017-2022 were analyzed. Data on patient demographics, comorbidities, fracture patterns identified on radiographs including displacement of the lesser trochanter (LT), thin lateral wall (LW), reverse obliquity (RO), subtrochanteric extension (STE), and number of fracture parts were collected, and the need for additional aides following traction on fracture table were collected. Fractures were classified using the AO/OTA classification. Regression analyses identified significant risk factors for needing extra reduction aides. Results: Of the 166 patients included, the average age was 80.84±12.7 years and BMI was 24.37±5.3 kg/m2. Univariate regression revealed increased irreducibility risk associated with RO (odds ratio [OR] 27.917, P≤0.001), LW (OR 24.882, P<0.001), and STE (OR 5.255, P=0.005). Multivariate analysis significantly correlated RO (OR 120.74, P<0.001) and thin LW (OR 131.14, P<0.001) with increased risk. However, STE (P=0.36) and LT displacement (P=0.77) weren’t significant. Fracture types 2.2, 3.2, and 3.3 displayed elevated risk (P<0.001), while no other factors increased risk. Conclusion: Elderly patients with IT fractures with RO and/or thin LW are at higher risk of irreducibility, necessitating adjunct reduction aides. Other parameters showed no significant association, suggesting most fracture patterns can be achieved with traction manipulation alone.

Fragility Fractures of the Pelvis and Sacrum: Current Trends in Literature

Erick Heiman,Pasquale Gencarelli Jr.,Alex Tang,John M. Yingling,Frank A. Liporace,Richard S. Yoon 대한고관절학회 2022 Hip and Pelvis Vol.34 No.2

Fragility fractures of the pelvis (FFP) and fragility fractures of the sacrum (FFS), which are emerging in the geriatric population, exhibit characteristics that differ from those of pelvic ring disruptions occurring in the younger population. Treatment of FFP/FFS by a multidisciplinary team can be helpful in reducing morbidity and mortality with the goal of reducing pain, regaining early mobility, and restoring independence for activities of daily living. Conservative treatment, including bed rest, pain therapy, and mobilization as tolerated, is indicated for treatment of FFP type I and type II as loss of stability is limited with these fractures. Operative treatment is indicated for FFP type II when conservative treatment has failed and for FFP type III and type IV, which are displaced fractures associated with intense pain and increased instability. Minimally invasive stabilization techniques, such as percutaneous fixation, are favored over open reduction internal fixation. There is little evidence regarding outcomes of patients with FFP/FFS and more literature is needed for determination of optimal management. The aim of this article is to provide a concise review of the current literature and a discussion of the latest recommendations for orthopedic treatment and management of FFP/FFS.

Detection of Non-Melanoma Skin Cancer by <i>in vivo</i> Fluorescence Imaging with Fluorocoxib A

Ra, Hyejun,Gonzá,lez-Gonzá,lez, Emilio,Uddin, Md. Jashim,King, Bonnie L.,Lee, Alex,Ali-Khan, Irfan,Marnett, Lawrence J.,Tang, Jean Y.,Contag, Christopher H. Neoplasia Press 2015 Neoplasia Vol.17 No.2

<P>Non-melanoma skin cancer (NMSC) is the most common form of cancer in the US and its incidence is increasing. The current standard of care is visual inspection by physicians and/or dermatologists, followed by skin biopsy and pathologic confirmation. We have investigated the use of <I>in vivo</I> fluorescence imaging using fluorocoxib A as a molecular probe for early detection and assessment of skin tumors in mouse models of NMSC. Fluorocoxib A targets the cyclooxygenase-2 (COX-2) enzyme that is preferentially expressed by inflamed and tumor tissue, and therefore has potential to be an effective broadly active molecular biomarker for cancer detection. We tested the sensitivity of fluorocoxib A in a BCC allograft SCID hairless mouse model using a wide-field fluorescence imaging system. Subcutaneous allografts comprised of 1000 BCC cells were detectable above background. These BCC allograft mice were imaged over time and a linear correlation (R<SUP>2</SUP> = 0.8) between tumor volume and fluorocoxib A signal levels was observed. We also tested fluorocoxib A in a genetically engineered spontaneous BCC mouse model (Ptch1<SUP>+/−</SUP> K14-Cre-ER2 p53<SUP>fl/fl</SUP>), where sequential imaging of the same animals over time demonstrated that early, microscopic lesions (100 μm size) developed into visible macroscopic tumor masses over 11 to 17 days. Overall, for macroscopic tumors, the sensitivity was 88% and the specificity was 100%. For microscopic tumors, the sensitivity was 85% and specificity was 56%. These results demonstrate the potential of fluorocoxib A as an <I>in vivo</I> imaging agent for early detection, margin delineation and guided biopsies of NMSCs.</P>

Enhancement of Aggregation-Induced Emission in Dye-Encapsulating Polymeric Micelles for Bioimaging

Wu, Wen-Chung,Chen, Ching-Yi,Tian, Yanqing,Jang, Sei-Hum,Hong, Yuning,Liu, Yang,Hu, Rongrong,Tang, Ben Zhong,Lee, Yi-Ting,Chen, Chin-Ti,Chen, Wen-Chang,Jen, Alex K.-Y. WILEY-VCH Verlag 2010 Advanced Functional Materials Vol.20 No.9

<P>Three amphiphilic block copolymers are employed to form polymeric micelles and function as nanocarriers to disperse hydrophobic aggregation-induced emission (AIE) dyes, 1,1,2,3,4,5-hexaphenylsilole (HPS) and/or bis(4-(N-(1-naphthyl) phenylamino)-phenyl)fumaronitrile (NPAFN), into aqueous solution for biological studies. Compared to their virtually non-emissive properties in organic solutions, the fluorescence intensity of these AIE dyes has increased significantly due to the spatial confinement that restricts intramolecular rotation of these dyes and their better compatibility in the hydrophobic core of polymeric micelles. The effect of the chemical structure of micelle cores on the photophysical properties of AIE dyes are investigated, and the fluorescence resonance energy transfer (FRET) from the green-emitting donor (HPS) to the red-emitting acceptor (NPAFN) is explored by co-encapsulating this FRET pair in the same micelle core. The highest fluorescence quantum yield (∼62%) could be achieved by encapsulating HPS aggregates in the micelles. Efficient energy transfer (>99%) and high amplification of emission (as high as 8 times) from the NPAFN acceptor could also be achieved by spatially confining the HPS/NPAFN FRET pair in the hydrophobic core of polymeric micelles. These micelles could be successfully internalized into the RAW 264.7 cells to demonstrate high-quality fluorescent images and cell viability due to improved quantum yield and reduced cytotoxicity.</P> <B>Graphic Abstract</B> <P>Highly efficient fluorescence probes are achieved through the encapsulation of aggregation-induced emission molecules, 1,1,2,3,4,5-hexaphenylsilole (HPS) and/or bis(4-(N-(1-naphthyl) phenylamino)-phenyl)fumaronitrile (NPAFN) in the core of polymeric micelles. Bright fluorescence cell images are shown with tunable colors of green directly from HPS aggregates and red through efficient fluorescence resonance energy transfer (FRET) from HPS aggregates to NPAFN aggregates. <img src='wiley_img_2010/1616301X-2010-20-9-ADFM200902043-content.gif' alt='wiley_img_2010/1616301X-2010-20-9-ADFM200902043-content'> </P>