58 results on '"Wai Ling Chan"'
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2. Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria
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Benjamin R. Taft, Fumiaki Yokokawa, Tom Kirrane, Anne-Catherine Mata, Richard Huang, Nicole Blaquiere, Grace Waldron, Bin Zou, Oliver Simon, Subramanyam Vankadara, Wai Ling Chan, Mei Ding, Sandra Sim, Judith Straimer, Armand Guiguemde, Suresh B. Lakshminarayana, Jay Prakash Jain, Christophe Bodenreider, Christopher Thompson, Christian Lanshoeft, Wei Shu, Eric Fang, Jafri Qumber, Katherine Chan, Luying Pei, Yen-Liang Chen, Hanna Schulz, Jessie Lim, Siti Nurdiana Abas, Xiaoman Ang, Yugang Liu, Iñigo Angulo-Barturen, María Belén Jiménez-Díaz, Francisco Javier Gamo, Benigno Crespo-Fernandez, Philip J. Rosenthal, Roland A. Cooper, Patrick Tumwebaze, Anna Caroline Campos Aguiar, Brice Campo, Simon Campbell, Jürgen Wagner, Thierry T. Diagana, and Christopher Sarko
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Antimalarials ,Mice ,Drug Discovery ,Plasmodium falciparum ,Molecular Medicine ,Animals ,Folic Acid Antagonists ,Mice, SCID ,QUÍMICA MÉDICA ,Malaria, Falciparum ,Malaria - Abstract
A series of 5-aryl-2-amino
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- 2022
3. NITD-688, a pan-serotype inhibitor of the dengue virus NS4B protein, shows favorable pharmacokinetics and efficacy in preclinical animal models
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Haoying Xu, Wei Lin Sandra Sim, Cheah Chen Seh, Feng Wang, Thierry T. Diagana, Wai Ling Chan, Jae-Geun Song, Kah Fei Wan, Bin Zou, Ghislain M. C. Bonamy, David Beer, David T. Barkan, Min Li, Stephanie A. Moquin, Francesca Blasco, Suresh B. Lakshminarayana, Jin Zhang, Oliver Simon, Vito G. Sasseville, Craig W. Day, Qing-Yin Wang, Chandrassegar Saravanan, Katherine Chan, Fumiaki Yokokawa, Bryan K. S. Yeung, Ratna Karuna, Hui-Quan Yeo, Colin Osborne, Christopher Sarko, Pei Yong Shi, Hongping Dong, Mei Ding, Siew Pheng Lim, Yen Liang Chen, Feng Gu, Cyrille Kounde, Gang Wang, Siyan Lu, and Wei Liu
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0301 basic medicine ,biology ,medicine.drug_class ,business.industry ,030106 microbiology ,Viremia ,General Medicine ,Dengue virus ,Pharmacology ,medicine.disease_cause ,medicine.disease ,biology.organism_classification ,Dengue fever ,Bioavailability ,03 medical and health sciences ,Flavivirus ,030104 developmental biology ,Pharmacokinetics ,medicine ,Potency ,Antiviral drug ,business - Abstract
Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to public health, yet no antiviral drug is available. We performed a high-throughput phenotypic screen using the Novartis compound library and identified candidate chemical inhibitors of DENV. This chemical series was optimized to improve properties such as anti-DENV potency and solubility. The lead compound, NITD-688, showed strong potency against all four serotypes of DENV and demonstrated excellent oral efficacy in infected AG129 mice. There was a 1.44-log reduction in viremia when mice were treated orally at 30 milligrams per kilogram twice daily for 3 days starting at the time of infection. NITD-688 treatment also resulted in a 1.16-log reduction in viremia when mice were treated 48 hours after infection. Selection of resistance mutations and binding studies with recombinant proteins indicated that the nonstructural protein 4B is the target of NITD-688. Pharmacokinetic studies in rats and dogs showed a long elimination half-life and good oral bioavailability. Extensive in vitro safety profiling along with exploratory rat and dog toxicology studies showed that NITD-688 was well tolerated after 7-day repeat dosing, demonstrating that NITD-688 may be a promising preclinical candidate for the treatment of dengue.
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- 2021
4. A Cyclic Phosphoramidate Prodrug of 2′-Deoxy-2′-Fluoro-2′-C-Methylguanosine for the Treatment of Dengue Virus Infection
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Martijn Fenaux, Andrea Leonardi, Sreehari Babu, Peck Gee Seah, Wei Liu, Pei Yong Shi, Rao P S Srinivasa, Suresh B. Lakshminarayana, Haoying Xu, Jin Zhang, Fumiaki Yokokawa, Cheah Chen Seh, Francesca Blasco, Nahdiyah Abdul Ghafar, Wai Ling Chan, Gang Wang, Ellie Growcott, Feng Gu, Weidong Zhong, Keshi Wang, Mei Ding, Ratna Karuna, Siew Pheng Lim, and Yen Liang Chen
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Male ,Hepatitis C virus ,Hepacivirus ,Pharmacology ,Dengue virus ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Antiviral Agents ,Dengue ,03 medical and health sciences ,chemistry.chemical_compound ,Dogs ,Oral administration ,medicine ,Animals ,Pharmacology (medical) ,Phosphoric Acids ,Prodrugs ,030304 developmental biology ,0303 health sciences ,Guanosine ,030306 microbiology ,Chemistry ,Phosphoramidate ,Prodrug ,Amides ,Infectious Diseases ,Nucleoside triphosphate ,Leukocytes, Mononuclear ,Female ,Nucleoside - Abstract
Monophosphate prodrug analogs of 2′-deoxy-2′-fluoro-2′-C-methylguanosine have been reported as potent inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase. These prodrugs also display potent anti-dengue virus activities in cellular assays although their prodrug moieties were designed to produce high levels of triphosphate in the liver. Since peripheral blood mononuclear cells (PBMCs) are among the major targets of dengue virus, different prodrug moieties were designed to effectively deliver 2′-deoxy-2′-fluoro-2′-C-methylguanosine monophosphate prodrugs and their corresponding triphosphates into PBMCs after oral administration. We identified a cyclic phosphoramidate, prodrug 17, demonstrating well-balanced anti-dengue virus cellular activity and in vitro stability profiles. We further determined the PBMC concentration of active triphosphate needed to inhibit virus replication by 50% (TP(50)). Compound 17 was assessed in an AG129 mouse model and demonstrated 1.6- and 2.2-log viremia reductions at 100 and 300 mg/kg twice a day (BID), respectively. At 100 mg/kg BID, the terminal triphosphate concentration in PBMCs exceeded the TP(50) value, demonstrating TP(50) as the target exposure for efficacy. In dogs, oral administration of compound 17 resulted in high PBMC triphosphate levels, exceeding the TP(50) at 10 mg/kg. Unfortunately, 2-week dog toxicity studies at 30, 100, and 300 mg/kg/day showed that “no observed adverse effect level” (NOAEL) could not be achieved due to pulmonary inflammation and hemorrhage. The preclinical safety results suspended further development of compound 17. Nevertheless, present work has proven the concept that an efficacious monophosphate nucleoside prodrug could be developed for the potential treatment of dengue virus infection.
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- 2020
5. A Cyclic Phosphoramidate Prodrug of 2’-deoxy-2’-fluoro-2’-C-methylguanosine for the Treatment of Dengue Infection
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Wei Liu, Sreehari Babu, Wai Ling Chan, Suresh B. Lakshminarayana, Ellena Growcott, Peck Gee Seah, Martijn Fenaux, Mei Ding, Nahdiyah Abdul Ghafar, Gang Wang, Ratna Karuna, Cheah Chen Seh, Haoying Xu, Feng Gu, Weidong Zhong, Pei Yong Shi, Keshi Wang, Andrea Leonardi, Francesca Blasco, Yen Liang Chen, Srinivasa P. S. Rao, Siew Pheng Lim, Fumiaki Yokokawa, and Jin Zhang
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Chemistry ,Oral administration ,Hepatitis C virus ,Toxicity ,medicine ,Phosphoramidate ,Prodrug ,Dengue virus ,Pharmacology ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Nucleoside - Abstract
Monophosphate prodrug analogs of 2’-deoxy-2’-fluoro-2’-C-methylguanosine have been reported as potent inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase. These prodrugs also display potent anti-dengue activities in cellular assays although their prodrug moieties were designed to produce high levels of triphosphate in the liver. Since peripheral blood mononuclear cells (PBMCs) are one of the major targets of dengue virus, different prodrug moieties were designed to effectively deliver 2’-deoxy-2’-fluoro-2’-C-methylguanosine monophosphate prodrugs and their corresponding triphosphates into PBMCs after oral administration. We identified a cyclic phosphoramidate prodrug 17 demonstrating a well-balanced anti-dengue cellular activity and in vitro stability profiles. In dogs, oral administration of 17 resulted in high PBMC triphosphate level, exceeding TP50 (the intracellular triphosphate concentration at which 50% of virus replication is inhibited) at 10 mg/kg. Compound 17 demonstrated 1.6- and 2.2 log viremia reduction in the dengue mouse model at 100 and 300 mg/kg twice daily, respectively. At 100 mg/kg twice daily, the terminal triphosphate concentration in PBMCs reached above TP50, defining for the first time the minimum efficacious dose for a nucleos(t)ide prodrug. In the two-week dog toxicity studies at 30 to 300 mg/kg/day, no observed adverse effect level (NOAEL) could not be achieved due to pulmonary inflammation and hemorrhage. The preclinical safety results suspended further development of 17. Nevertheless, present work has proven the concept that an efficacious monophosphate nucleoside prodrug could be developed for the potential treatment of dengue infection.
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- 2020
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6. Effectiveness of the SIME Program for Infants and Toddlers in Center-Based Settings
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Wai Ling CHAN and Xiao Zhang
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Program evaluation ,medicine.medical_specialty ,Sociology and Political Science ,05 social sciences ,050109 social psychology ,Child development ,Family medicine ,medicine ,0501 psychology and cognitive sciences ,Center (algebra and category theory) ,Psychology ,General Psychology ,Social Sciences (miscellaneous) ,050104 developmental & child psychology - Abstract
Objective: This study evaluates the effectiveness of a center-based childcare program, namely, the stimulation, interaction, motivation, and experience (SIME) program for infants and toddlers. Method: Fifty-eight children between 1 and 2 years of age and their parents and childcare workers were recruited from two childcare centers in Hong Kong and participated in the SIME program over a 1-year period. Eighty-seven children from four other childcare centers served as controls. All children were grouped by age (1- vs. 2-year-old class). Results: The SIME program had positive effects on motor, language, cognitive and social development, parenting practices, and the quality of relationships with parents and childcare workers, especially for 1-year-old children and children from the center that served mainly families with a lower socioeconomic status (SES). Conclusion: The outcomes in 1-year-old children and children from the lower SES center confirm the success of this type of center-based infant–toddler program.
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- 2018
7. Challenges to the infant care profession: practitioners’ perspectives
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Wai Ling Chan
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Social Psychology ,Infant Care ,05 social sciences ,Professional development ,050301 education ,Pediatrics ,Child development ,Educational attainment ,Work environment ,Nursing ,Developmental and Educational Psychology ,0501 psychology and cognitive sciences ,Early childhood ,Psychology ,0503 education ,050104 developmental & child psychology - Abstract
This paper explored the challenges to the infant care profession in Hong Kong creches, with an aim to contribute to the existing early childhood care literature for reference and comparison elsewhe...
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- 2018
8. Need for and concerns about non-parental childcare programs for infants and toddlers in Hong Kong: Voices of parents
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Xiao Zhang, Wai Ling Chan, Weiyi Xie, and Nan Xiao
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Quantitative survey ,Sociology and Political Science ,Qualitative interviews ,Toileting ,Developmental and Educational Psychology ,Cognitive development ,Psychology ,Education ,Developmental psychology - Abstract
This study examined Hong Kong parents’ need for, and concerns about, the quality of non-parental childcare programs for infants and toddlers. A total of 266 Hong Kong parents whose children were enrolled in center-based childcare programs for infants and toddlers participated in a quantitative survey, and 22 parents participated in qualitative interviews. The results showed that there was a large demand for childcare programs for infants and toddlers in Hong Kong, due mainly to the number of dual working parents. Parents considered location to be the most important determinant of their program selection and also expected an upward adjustment to the teacher-child ratio in their children’s programs. Finally, parents considered mealtime (e.g., bottle feeding), self-care training (e.g., toileting), and cognitive development activities to be the three most important aspects of their children’s educational and care activities. The findings are discussed in light of the importance of developing non-parental childcare programs for infants and toddlers that address parents’ needs and concerns. This study can inform both research and policy concerning center-based childcare programs in Hong Kong.
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- 2021
9. Chinese migrant workers in action: Bringing Wal-Mart to global corporate responsibility
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Jenny Wai-ling Chan
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Wal-Mart Stores Inc. -- Social aspects ,Wal-Mart Stores Inc. -- Labor relations ,Discount stores -- Social aspects ,Discount stores -- Labor relations ,Corporate social responsibility ,Government ,Political science ,Sociology and social work - Abstract
Students and Scholars against Corporate Misbehavior (SACOM) monitors transnational corporations that violate worker's rights, feminist rights, occupational safety and health, welfare and dignity in China and in other countries. Chinese migrant worker's self-determination informs the labor activists to make a joint effort in changing the inhumane global production relation and the goal is to advance global efforts in corporate social responsibility at the local level.
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- 2005
10. Exploring the Impacts of Staff-Child Ratio on Quality of Early Childhood Care and Education – A Comparative Case Study in Hong Kong
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Wai Ling Chan
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Nursing ,Comparative case ,media_common.quotation_subject ,Quality (business) ,Early childhood ,Psychology ,media_common - Published
- 2019
11. A Systematic Approach to Assess the Quality of Centre-Based Care Services for Infants and Toddlers in Hong Kong
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Wai Ling Chan
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Nursing ,media_common.quotation_subject ,Quality (business) ,Psychology ,media_common - Published
- 2019
12. Final results of a phase I/II prospective dose escalation trial evaluating safety and efficacy of combination 177Lu PSMA 617 and NOX66 in men with end-stage metastatic castration-resistant prostate cancer (LuPIN trial)
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Megan Crumbaker, Louise Emmett, Andrew O. Yam, Lalith Ratnayake, Wai Ling Chan, Andrew Nguyen, Edmond M. Kwan, Anthony M. Joshua, Arun Azad, Peter Eu, Shikha Sharma, Christopher Rofe, Bao Ho, Kamonwan Kongrak, Adam Hickey, and Sarennya Pathmanandavel
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Oncology ,Cancer Research ,medicine.medical_specialty ,177Lu-PSMA-617 ,business.industry ,Synergistic combination ,Castration resistant ,medicine.disease ,Prostate cancer ,Phase i ii ,Internal medicine ,Dose escalation ,Medicine ,Treatment resistance ,Stage (cooking) ,business - Abstract
103 Background: 177LuPSMA – 617 is a promising therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently and synergistic combination therapy may improve outcomes. We combined 177LuPSMA – 617 with idronoxil (NOX66), an inhibitor of external NADH oxidase type 2 with radio-sensitizing properties. We present the final safety and efficacy results. Methods: Men with progressive mCRPC after androgen signalling inhibition (ASI) and taxane chemotherapy were enrolled. Key inclusion criteria were: PSMA PET/CT intensity SUV max > 15 with no discordant disease on FDG PET/CT, haemoglobin > 100g/L, platelets > 100x109/L and eGFR > 40mls/min. Enrolled patients received up to six doses of 177 Lu-PSMA 617 (7.5Gbq) day 1 every 6 weeks in combination with NOX66 days 1-10 each cycle. Cohort 1 (n = 8) received 400mg NOX66. Following safety reviews the doses were escalated in cohorts 2 (n = 24) and 3 (n = 24) to 800mg and 1200mg of NOX66, respectively. Blood samples were prospectively collected for androgen receptor splice variant 7 (ARV7) expression. PSMA and FDG PET/CT were performed at study entry and on progression. The primary outcomes were safety and tolerability; the secondary outcomes evaluated were efficacy, pain scores, and quality of life. Results: Of the 56 men enrolled, all had received prior treatment with ASI and docetaxel, and 95% (53/56) had prior cabazitaxel. 96% (54/56) patients received ≥2 cycles and 46% (26/56) completed six cycles of treatment. Adverse events are summarized in the table below. PSA responses were as follows: 86% (48/56) had any PSA reduction and 61% (34/56) had > 50% PSA reduction. 84% (47/56) have had PSA progression to date with median follow up 18.9 months (95% CI 11.9-25.8). Median PSA PFS was 7.5 months (95% CI 6.0-9.0). 55% (31/56) have died and median overall survival was 19.7 months (95% CI 10.7-28.7). 34/56 men had baseline pain scores ≥3, of whom 53% (18/34) had significant reduction in pain indicators. There was no correlation between quantitative PET results and either PSA > 50% response, PSA PFS or OS. Conclusions: The combination of 177 Lu-PSMA 617 + NOX66 appears safe and efficacious in men with heavily pre-treated mCRPC. Exploratory analysis of ARV7 expression and quantitative PET imaging markers of treatment response and resistance is in progress. Clinical trial information: ACTRN12618001073291. [Table: see text]
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- 2021
13. Teacher-child relationship quality and Chinese toddlers’ developmental functioning: A cross-lagged modelling approach
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Xiao Zhang, Wai Ling Chan, Kun Zhao, and Ting Liu
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Sociology and Political Science ,media_common.quotation_subject ,education ,05 social sciences ,050301 education ,Expressive language ,Developmentally Appropriate Practice ,behavioral disciplines and activities ,Child development ,Education ,Developmental psychology ,Comprehension ,Age groups ,Cross lagged ,Developmental and Educational Psychology ,0501 psychology and cognitive sciences ,Quality (business) ,Psychology ,Association (psychology) ,0503 education ,050104 developmental & child psychology ,media_common - Abstract
This study examined the dynamic association between teacher–child relationship quality and Chinese toddlers’ developmental functioning. The participants, located in Hong Kong, consisted of 82 Chinese toddlers and their teachers. With a two-wave longitudinal design, teachers rated the children’s developmental functioning and their own relationships with each child. The results showed that the relations between teacher-child relationships and developmental functioning differed across aspects of child development. Specifically, teacher–child relationship quality predicted and was predicted by toddlers’ comprehension and personal-social skills; teacher-child relationship quality predicted but was not predicted by motor and self-help skills; finally, expressive language skills predicted but were not predicted by teacher-child relationship quality. Follow-up analyses suggested that the observed relations operated similarly for boys and girls, but differently between younger and older age groups. We conclude by discussing the study’s limitations and offering suggestions for promoting developmentally appropriate childcare experience for toddlers.
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- 2020
14. Updated results of a phase I/II prospective dose escalation trial evaluating safety and efficacy of combination 177Lu PSMA 617 and idronoxil in men with mCRPC post androgen signalling inhibition and taxane chemotherapy (LuPIN trial)
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Sarennya Pathmanandavel, Peter Eu, Wai Ling Chan, Louise Emmett, Christopher Rofe, Andrew O. Yam, Megan Crumbaker, Karen Fullard, John Violet, Lalith Ratnayake, Kamonwan Kongrak, Adam Hickey, Anthony M. Joshua, Bao Ho, Shikha Sharma, Arun Azad, Andrew Nguyen, and Joanne Keane
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Standard of care ,Taxane ,177Lu-PSMA-617 ,medicine.drug_class ,business.industry ,medicine.medical_treatment ,Androgen ,Phase i ii ,Cabazitaxel ,Internal medicine ,medicine ,Dose escalation ,business ,medicine.drug - Abstract
5557 Background: There is no established standard of care post cabazitaxel in men with mCRPC. Ongoing trials in 177LuPSMA-617 have demonstrated good efficacy and safety, but synergistic combinations may further improve treatment responses. Idronoxil (NOX66) inhibits external NADH oxidase type 2 with downstream pro-apoptotic actions including radio-sensitization. Herein we present updated results and an additional cohort of a prospective single arm phase I/II dose escalation/expansion trial of LuPSMA-617 and NOX66 in mCRPC. Methods: Men with progressive mCRPC post androgen signalling inhibition (ASI) and 2 lines of taxane chemotherapy were considered eligible. Key inclusion criteria included PSMA PET/CT intensity SUV max > 15 with no discordant disease on FDG PET/CT, Hb >10, Platelets >100 and GFR >40mls/min. Enrolled patients received up to 6 doses of 177 Lu-PSMA 617 (7.5Gbq) day 1 every 6 weeks in combination with NOX66 days 1-10 each cycle. Cohort 1 (n=8) received 400mg NOX66. Cohorts 2 and 3 subsequently received 800mg and 1200mg of NOX66, respectively, following safety reviews. Data regarding safety, efficacy, pain scores, and QOL were collected. Results: 32 men were enrolled in cohorts 1&2 (November 2017 – June 2019) and 24 in cohort 3 (August 2019-February 2020). To date there have been no dose-limiting toxicities. Data for cohort 3 are immature. For cohorts 1 & 2: 31/32 men received ≥2 cycles, with 12/32 (47%) completing 6 cycles. Any PSA response was seen in 84% (27/32), with a PSA response > 50% in 62.5% (20/32). Median PSA PFS is 6.1 months Of men with increased baseline pain scores ≥3 (24/32), 50% (12/24) had a clinically significant reduction in pain indicators. Adverse events are summarized below. Updated results for cohorts 1 and 2 and preliminary results of cohort 3 will be presented. Conclusions: Combination LuPSMA-617 + NOX 66 appears safe and efficacious in men with heavily pre-treated end stage mCRPC. Clinical trial information: ACTRN12618001073291 .
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- 2020
15. Results of a phase I/II prospective dose-escalation trial evaluating safety and efficacy of combination 177LuPSMA-617 and NOX66 in men with mCRPC post androgen signalling inhibition and two lines of taxane chemotherapy (LuPIN trial)
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Andrew O. Yam, Arun Azad, Sarennya Pathmanandavel, Anthony M. Joshua, Bao Ho, Andrew Nguyen, Wai Ling Chan, Louise Emmett, Megan Crumbaker, and Karen Fullard
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Taxane ,medicine.drug_class ,business.industry ,medicine.medical_treatment ,Castrate-resistant prostate cancer ,Disease ,Androgen ,Phase i ii ,Internal medicine ,medicine ,Dose escalation ,business - Abstract
120 Background: Despite treatment advances, metastatic castrate resistant prostate cancer (mCRPC) remains a lethal disease. Trials in 177LuPSMA-617 have demonstrated good efficacy and safety, but synergistic combinations may further improve treatment responses. NOX66 inhibits external NADH oxidase type 2 with downstream pro-apoptotic actions including radio-sensitization. We present results of a prospective open label single arm phase 1/2 dose escalation/expansion trial of 177LuPSMA-617 and NOX66 in mCRPC. Methods: Men with progressive mCRPC post androgen signalling inhibition (ASI) and taxane chemotherapy were eligible. Inclusion criteria included PSMA PET/CT intensity > SUV max 15, with no discordant disease on FDG PET/CT, Hb > 100 g/L, Platelets > 90 x 106/L and GFR > 40 mL/min. Protocol allowed up to 6 doses of 177 Lu-PSMA 617 (7.5Gbq) on day 1 with NOX66 (suppository) given day 1-10 at 6-weekly intervals; the first 8 men received 400mg NOX66. After safety review, dose was escalated to 800mg. Data regarding safety, efficacy, pain scores, and QOL were collected. Results: 32/43 (26% imaging screen failures) screened men were enrolled (November 2017 – June 2019), of whom 100% had prior docetaxel and ASI, and 94% (30/32) cabazitaxel. All men received ≥ 2 cycles, with 12/32 completing 6 cycles, and 16/32 2 - 5 cycles, while 4/32 remain on treatment. Any PSA response was seen in 84% (27/32), with a PSA response > 50% in 62.5% (20/32). Median PSA PFS was 6.5 months (95%CI 3.54-9.3). To date, 72% (23/32) of patients have progressed. 34% (11/32) men have died with median OS not reached. 50% (12/24) of men with baseline pain scores ≥3 (24/32) had significant reduction in pain. Adverse events are summarized below. Conclusions: Combination 177LuPSMA-617 with NOX66 appears safe and efficacious in men with heavily pre-treated mCRPC. Clinical trial information: ACTRN12618001073291. [Table: see text]
- Published
- 2020
16. Discovery of Dengue Virus NS4B Inhibitors
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Julien Lescar, Feng Gu, Kah Fei Wan, Francesca Blasco, CongBao Kang, Wai Ling Chan, Wei Liu, Paul W. Smith, Agatha Susila, Bin Zou, Qing Yin Wang, K.L. Yeo, Mei Ding, Chao Shan, Andy M. Yip, Haoying Xu, Hongping Dong, Jing Zou, Suresh B. Lakshminarayana, Ratna Karuna, Pei Yong Shi, Peck Gee Seah, Diamond, M. S., and School of Biological Sciences
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viruses ,Immunology ,Viremia ,Viral Nonstructural Proteins ,Dengue virus ,Biology ,medicine.disease_cause ,Antiviral Agents ,Microbiology ,Cell Line ,In vivo ,Cricetinae ,Virology ,Vaccines and Antiviral Agents ,Drug Discovery ,medicine ,Animals ,Humans ,Spiro Compounds ,Replicon ,chemistry.chemical_classification ,Drug discovery ,virus diseases ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,In vitro ,Amino acid ,chemistry ,Insect Science ,Viral replication complex - Abstract
The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo . The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC 50 ], 10 to 80 nM) but not DENV-1 and -4 (EC 50 , >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo . Our results validate, for the first time, that NS4B inhibitors could potentially be developed for antiviral therapy for treatment of DENV infection in humans.
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- 2015
17. Lead Optimization of Spiropyrazolopyridones: A New and Potent Class of Dengue Virus Inhibitors
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Hao Ying Xu, Wei Liu, Feng Gu, Bin Zou, Wai Ling Chan, Paul W. Smith, Kah Fei Wan, Ratna Karuna, Agatha Susila, Peck Gee Seah, Andy Yip, Pei Yong Shi, Trixie Wagner, Thierry T. Diagana, Qing Yin Wang, Alex Chao, Mei Ding, Hongping Dong, Seh Yong Leong, Francesca Blasco, Katherine Chan, Shahul Nilar, and Ina Dix
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Organic Chemistry ,virus diseases ,Viremia ,Biology ,Dengue virus ,medicine.disease ,medicine.disease_cause ,Biochemistry ,Virology ,Dengue fever ,Pharmacokinetics ,In vivo ,Drug Discovery ,medicine ,Structure–activity relationship ,Potency ,Enantiomer - Abstract
Spiropyrazolopyridone 1 was identified, as a novel dengue virus (DENV) inhibitor, from a DENV serotype 2 (DENV-2) high-throughput phenotypic screen. As a general trend within this chemical class, chiral resolution of the racemate revealed that R enantiomer was significantly more potent than the S. Cell-based lead optimization of the spiropyrazolopyridones focusing on improving the physicochemical properties is described. As a result, an optimal compound 14a, with balanced in vitro potency and pharmacokinetic profile, achieved about 1.9 log viremia reduction at 3 × 50 mg/kg (bid) or 3 × 100 mg/kg (QD) oral doses in the dengue in vivo mouse efficacy model.
- Published
- 2015
18. Angiographic and Clinical Outcomes of Everolimus-Eluting Stent in the Treatment of Extra Long Stenoses (AEETES)
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Andrew Kei-Yan Ng, Hee-Hwa Ho, Wing-Hing Chow, Kai-Hang Yiu, Chung-Wah Siu, Man-Hong Jim, and Wai-Ling Chan
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Mortality rate ,Stent ,medicine.disease ,Lesion ,Restenosis ,Sirolimus ,Internal medicine ,Angiography ,Intravascular ultrasound ,medicine ,Cardiology ,Radiology, Nuclear Medicine and imaging ,Radiology ,Myocardial infarction ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Objectives The purpose of this study was to examine the angiographic and clinical results of stent full metal jacket in treating long lesions using everolimus-eluting stents (EES). Background Data are lacking regarding the use of EES for this lesion subgroup. Methods From 2007 to 2011, 77 symptomatic patients who had severe coronary stenoses necessitating implantation of stents with total length longer than 60 mm were treated with overlapping EES. Results The mean age of patient was 61 ± 11 years with male predominance (66%). Diabetes mellitus was seen in 35 (45.5%) patients. Majority of patients had class III angina with normal heart function. On average, 3.1 stents were implanted per lesion; the mean stent size and length were 2.70 ± 0.28 mm and 82 ± 16 mm. Restudy angiography was performed on 71 patients (72 lesions) at 8.9 ± 2.5 months. Angiographic restenosis was seen in 9 (12.5%) lesions; the lesion length and late loss were 67 ± 15 mm and 0.4 ± 0.6 mm, respectively. The use of intravascular ultrasound has been found to be a predictor of less restenosis (P = 0.02; HR: 0.02; CI: 0.01–0.59). The in-hospital and 1 year major adverse cardiac event rates were 7.8% and 13%. The annual cardiac death rates were 2.6%, 3.4%, and 5.3% in the first 3 years. Conclusions The use of EES full metal jacket for long lesions is only associated with good short-term clinical and angiographic outcomes. Long-term follow-up has revealed a high cardiac death rate which may necessitate prolongation of dual antiplatelet therapy. (J Interven Cardiol 2013;26:22–28)
- Published
- 2012
19. Effectiveness of a patient/carer empowerment programme for people with hip fractures
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Kai-ming Au, Stephanie Wai-Shan Louie, Wai-ling Chan, Shuk-yiu Yu, Kam-man Wong, and Mei-yee Poon
- Subjects
medicine.medical_specialty ,Hip fracture ,Activities of daily living ,business.industry ,media_common.quotation_subject ,Rehabilitation ,Instrumental ADL ,Outcome measures ,Physical Therapy, Sports Therapy and Rehabilitation ,medicine.disease ,humanities ,Chinese version ,Physical medicine and rehabilitation ,Functional independence ,Physical therapy ,Medicine ,Knowledge test ,business ,Empowerment ,human activities ,media_common - Abstract
Aims: The study compared the effects of a patient and carer empowerment programme and conventional hip fracture protocol on hip fractures related knowledge, activity of daily living (ADL) independence, fall efficacy on ADL; and application frequency of adapted ADL skills in individuals with hip fracture. Methodology: 134 participants were recruited with 63 and 71 participants allocated to Patient and Carer Empowerment Programme (PCEP) and conventional hip fracture protocol respectively. Paired t-test was used to compare the pre-post scores of hip fracture knowledge test, Functional Independence Measures-motor scores, Lawton Instrumental ADL scales and Chinese version of Fall Efficacy Scales within groups. Independent t-test was used to compare the outcome measures and application frequency of adapted ADL skills between groups. Results: It showed that both groups have improvement on hip fracture related knowledge, ADL, instrumental ADL independence and fall efficacy on ADL (P Conclusion: It appears that participants who underwent the PCEP were more ready to build up habit on adapted ADL skills use. Further studies to investigate carers’ stress and hands-on caregiving skills after the programme were recommended.
- Published
- 2012
20. Dual-time-point 18F-FDG-PET/CT imaging in the assessment of suspected malignancy
- Author
-
Lisa Tarlinton, Adam Hickey, Robert Dura, Stuart C. Ramsay, Andy Young, Judith M Pohlen, E. Szeto, Judith Freund, and Wai-Ling Chan
- Subjects
medicine.medical_specialty ,business.industry ,Malignancy ,medicine.disease ,Text mining ,Oncology ,Likely benign ,Suspected malignancy ,Medicine ,Delayed imaging ,Radiology, Nuclear Medicine and imaging ,Fdg pet ct ,Radiology ,business ,Nuclear medicine ,Semi quantitative ,Dual time point - Abstract
Introduction (purpose of the study): The objective of this study was to assess whether dual-time-point ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management. Methods: A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images. Results: Overall, there was a significant improvement (P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point ¹⁸FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions. Conclusions:¹⁸F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point ¹⁸FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions.
- Published
- 2011
21. An adenosine nucleoside inhibitor of dengue virus
- Author
-
Wai Ling Chan, Bo Zhang, Thomas H. Keller, Wouter Schul, Min Qing, Pei Yong Shi, Andy Yip, Kristen A. Bernard, Gang Zou, Hao Ying Xu, Suresh B. Lakshminarayana, Gang Wang, Anne Goh, Wei Liu, Min Dong, Boping Liu, Hui Pen Tan, Handan He, Qing Yin Wang, Margaret Weaver, Feng Gu, Yen Liang Chen, Zheng Yin, Pornwaratt Niyomrattanakit, Chuan Young Ng, Arkadius Pichota, Christine E. Garrett, Véronique Dartois, Joanne Y.H. Lim, Ravinder Reddy Kondreddi, Jeyaraj Duraiswamy, Kai Lin, Chin Chin Lim, and Karen Beltz
- Subjects
Male ,Adenosine ,viruses ,Hepatitis C virus ,Enzyme-Linked Immunosorbent Assay ,Dengue virus ,medicine.disease_cause ,Antiviral Agents ,Virus ,Dengue fever ,Dengue ,Mice ,Dogs ,Chlorocebus aethiops ,medicine ,Animals ,Viremia ,Vero Cells ,No-Observed-Adverse-Effect Level ,Multidisciplinary ,Western equine encephalitis virus ,Molecular Structure ,biology ,virus diseases ,Nucleoside inhibitor ,biochemical phenomena, metabolism, and nutrition ,Biological Sciences ,Dengue Virus ,RNA-Dependent RNA Polymerase ,biology.organism_classification ,medicine.disease ,Virology ,Rats ,Flavivirus ,Vesicular stomatitis virus ,Female - Abstract
Dengue virus (DENV), a mosquito-borne flavivirus, is a major public health threat. The virus poses risk to 2.5 billion people worldwide and causes 50 to 100 million human infections each year. Neither a vaccine nor an antiviral therapy is currently available for prevention and treatment of DENV infection. Here, we report a previously undescribed adenosine analog, NITD008, that potently inhibits DENV both in vitro and in vivo. In addition to the 4 serotypes of DENV, NITD008 inhibits other flaviviruses, including West Nile virus, yellow fever virus, and Powassan virus. The compound also suppresses hepatitis C virus, but it does not inhibit nonflaviviruses, such as Western equine encephalitis virus and vesicular stomatitis virus. A triphosphate form of NITD008 directly inhibits the RNA-dependent RNA polymerase activity of DENV, indicating that the compound functions as a chain terminator during viral RNA synthesis. NITD008 has good in vivo pharmacokinetic properties and is biologically available through oral administration. Treatment of DENV-infected mice with NITD008 suppressed peak viremia, reduced cytokine elevation, and completely prevented the infected mice from death. No observed adverse effect level (NOAEL) was achieved when rats were orally dosed with NITD008 at 50 mg/kg daily for 1 week. However, NOAEL could not be accomplished when rats and dogs were dosed daily for 2 weeks. Nevertheless, our results have proved the concept that a nucleoside inhibitor could be developed for potential treatment of flavivirus infections.
- Published
- 2009
22. N-Sulfonylanthranilic Acid Derivatives as Allosteric Inhibitors of Dengue Viral RNA-Dependent RNA Polymerase
- Author
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Wai Ling Chan, Shahul Nilar, Subhash G. Vasudevan, Wan Yen Lee, Sigmar Dressler, Gang Wang, Pei Yong Shi, Alex Chao, Ru Hui Ng, Hans Voshol, Thomas H. Keller, Daying Wen, Yen Liang Chen, J. Fraser Glickman, Joanne Y.H. Lim, Pornwaratt Niyomrattanakit, Zheng Yin, Ravinder Reddy Kondreddi, Duraiswamy Athisayamani Jeyaraj, Carsten Spanka, and Dieter Mueller
- Subjects
Models, Molecular ,Allosteric regulation ,Dengue virus ,medicine.disease_cause ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,chemistry.chemical_compound ,RNA polymerase ,Drug Discovery ,medicine ,Humans ,Structure–activity relationship ,ortho-Aminobenzoates ,Enzyme Inhibitors ,Binding site ,Polymerase ,chemistry.chemical_classification ,Binding Sites ,biology ,Chemistry ,Dengue Virus ,RNA-Dependent RNA Polymerase ,Sulfinic Acids ,biology.organism_classification ,Flavivirus ,Enzyme ,Biochemistry ,biology.protein ,Molecular Medicine - Abstract
A novel class of compounds containing N-sulfonylanthranilic acid was found to specifically inhibit dengue viral polymerase. The structural requirements for inhibition and a preliminary structure-activity relationship are described. A UV cross-linking experiment was used to map the allosteric binding site of the compound on the viral polymerase.
- Published
- 2009
23. Peptide Inhibitors of West Nile NS3 Protease: SAR Study of Tetrapeptide Aldehyde Inhibitors
- Author
-
Subhash G. Vasudevan, Wai-Ling Chan, Ngai Ling Ma, Siew Pheng Lim, Zheng Yin, Thomas H. Keller, Viral Patel, Weiling Wang, Sejal J. Patel, John E. Knox, David Beer, Xinyi Ngew, K. R. Ranga Rao, and Gang Wang
- Subjects
Models, Molecular ,Proteases ,Stereochemistry ,viruses ,medicine.medical_treatment ,Molecular Conformation ,Protein Data Bank (RCSB PDB) ,Peptide ,Structure-Activity Relationship ,Residue (chemistry) ,Drug Discovery ,medicine ,Structure–activity relationship ,Protease Inhibitors ,chemistry.chemical_classification ,Aldehydes ,NS3 ,Protease ,Tetrapeptide ,Chemistry ,Serine Endopeptidases ,virus diseases ,Stereoisomerism ,Biochemistry ,Molecular Medicine ,Oligopeptides ,West Nile virus - Abstract
A series of inhibitors related to the benzoyl-norleucine-lysine-arginine-arginine (Bz-nKRR) tetrapeptide aldehyde was synthesized. When evaluated against the West Nile virus (WNV) NS3 protease, the measured IC(50) ranges from approximately 1 to 200 microM. Concurrently, a modeling study using the recently published crystal structure of the West Nile NS3/NS2B protease complex (pdb code 2FP7) was conducted. We found that the crystal structure is relevant in explaining the observed SAR for this series of tetrapeptides, with the S1 and S2 pockets being the key peptide recognition sites. In general, a residue capable of both pi-stacking and hydrogen bonding is favored in the S1 pocket, while a positively charged residue is preferred in the S2 pocket. This study not only confirms the importance of the NS2B domain in substrate-based inhibitor binding of WNV, it also suggests that the crystal structure would provide useful guidance in the drug discovery process of related Flavivirus proteases, given the high degree of homology.
- Published
- 2006
24. Peptide inhibitors of dengue virus NS3 protease. Part 1: Warhead
- Author
-
Zheng Yin, Thomas H. Keller, Subhash G. Vasudevan, Gang Wang, Siew Pheng Lim, Viral Patel, Weiling Wang, David Beer, Sejal J. Patel, K. R. Ranga Rao, Jenefer Alam, Xinyi Ngew, Wai-Ling Chan, and Duraiswamy Athisayamani Jeyaraj
- Subjects
inorganic chemicals ,Time Factors ,Stereochemistry ,Chemistry, Pharmaceutical ,viruses ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Peptide ,Viral Nonstructural Proteins ,Dengue virus ,medicine.disease_cause ,Biochemistry ,Substrate Specificity ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Protease Inhibitors ,Enzyme Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,NS3 ,Protease ,Dose-Response Relationship, Drug ,Tetrapeptide ,biology ,Serine Endopeptidases ,Organic Chemistry ,Dengue Virus ,Ketones ,biology.organism_classification ,Boronic Acids ,Kinetics ,Flavivirus ,Models, Chemical ,chemistry ,Enzyme inhibitor ,Drug Design ,biology.protein ,Molecular Medicine ,Peptides ,RNA Helicases ,Boronic acid - Abstract
Substrate-based tetrapeptide inhibitors with various warheads were designed, synthesized, and evaluated against the Dengue virus NS3 protease. Effective inhibition was achieved by peptide inhibitors with electrophilic warheads such as aldehyde, trifluoromethyl ketone, and boronic acid. A boronic acid has the highest affinity, exhibiting a K(i) of 43 nM.
- Published
- 2006
25. Corrrection to Discovery of Tetrahydropyrazolopyrimidine Carboxamide Derivatives As Potent and Orally Active Novel Antitubercular Agents
- Author
-
Shi Hua Ang, Bee Huat Tan, Kevin Pethe, Ina Dix, Wai Ling Chan, Suresh B. Lakshminarayana, Gang Wang, Josephine Wong, Pablo Bifani, Mahesh Nanjundappa, Kelli Kuhen, Maria Tan, Pamela Thayalan, Maxime Herve, Seow Hwee Ng, Anne Goh, Thomas Dick, Paul Smith, Chen Zhang, Pei-Yu Chen, Peck Gee, Jan Jiricek, Ujjini H. Manjunatha, Cyrille Kounde, Liu Wei, Kok Sin Lee, Fumiaki Yokokawa, Richard Glynne, Sindhu Ravindran, Srinivasa P. S. Rao, Trixie Wagner, Ida Ma, and Arnab Chatterjee
- Subjects
Orally active ,Traditional medicine ,medicine.drug_class ,business.industry ,Block (telecommunications) ,Organic Chemistry ,Drug Discovery ,medicine ,Carboxamide ,business ,Biochemistry - Abstract
We recognize the contribution of Associate Prof. Dr. Thomas Dick to the research described in the manuscript (ACS Med. Chem. Lett.2013, 4 (5), pp 451–455) and therefore include him as an author. He is affiliated with the Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Block MD4A, Singapore 117597.
- Published
- 2014
26. Planar versus SPET imaging in the assessment of condylar growth
- Author
-
Carolan Mg, Wai-Ling Chan, Fernandes Vb, and Abbati Dp
- Subjects
Adult ,Male ,Study groups ,Planar Imaging ,Adolescent ,Technetium Tc 99m Medronate ,Condyle ,Mandibular asymmetry ,Unilateral condylar hyperplasia ,stomatognathic system ,Image Interpretation, Computer-Assisted ,Humans ,Medicine ,Gamma Cameras ,Radiology, Nuclear Medicine and imaging ,Child ,Retrospective Studies ,Tomography, Emission-Computed, Single-Photon ,Reproducibility ,business.industry ,Mandibular Condyle ,Mandible ,Reproducibility of Results ,General Medicine ,Normal volunteers ,Female ,Radiopharmaceuticals ,Nuclear medicine ,business - Abstract
The aim of this study was to compare two methods of quantifying 99Tc(m)-methylene diphosphonate uptake in the mandibular condyle. The study groups consisted of 23 patients with mandibular asymmetry and 16 normal volunteers aged 10-30 years. The accuracy and reproducibility of SPET using condyle-to-clivus ratios was compared with planar analysis using condyle-to-L4 (fourth lumbar vertebra) ratios. Quantitative analysis was correlated with semi-quantitative grading by three observers. Normal ranges for condyle-to-L4 and condyle-to-clivus ratios in individuals aged 11 years or over were determined. These ratios are useful in the serial monitoring of patients with condylar hyperplasia to establish when condylar growth has ceased and hence the type of surgery performed. Visual interpretation of condylar activity should use a combination of planar and SPET images and be performed in conjunction with quantitative analysis. Semi-quantitative grading on SPET images detected more subtle differences in condylar activity than planar images (using quantitative analysis as a standard).
- Published
- 2000
27. Angiographic and clinical outcomes of everolimus-eluting stent in the treatment of extra long stenoses (AEETES)
- Author
-
Man-Hong, Jim, Kai-Hang, Yiu, Hee-Hwa, Ho, Wai-Ling, Chan, Andrew Kei-Yan, Ng, Chung-Wah, Siu, and Wing-Hing, Chow
- Subjects
Coronary Restenosis ,Male ,Sirolimus ,Cardiotonic Agents ,Coronary Stenosis ,Myocardial Infarction ,Humans ,Drug-Eluting Stents ,Female ,Everolimus ,Middle Aged ,Coronary Angiography - Abstract
The purpose of this study was to examine the angiographic and clinical results of stent full metal jacket in treating long lesions using everolimus-eluting stents (EES).Data are lacking regarding the use of EES for this lesion subgroup.From 2007 to 2011, 77 symptomatic patients who had severe coronary stenoses necessitating implantation of stents with total length longer than 60 mm were treated with overlapping EES.The mean age of patient was 61 ± 11 years with male predominance (66%). Diabetes mellitus was seen in 35 (45.5%) patients. Majority of patients had class III angina with normal heart function. On average, 3.1 stents were implanted per lesion; the mean stent size and length were 2.70 ± 0.28 mm and 82 ± 16 mm. Restudy angiography was performed on 71 patients (72 lesions) at 8.9 ± 2.5 months. Angiographic restenosis was seen in 9 (12.5%) lesions; the lesion length and late loss were 67 ± 15 mm and 0.4 ± 0.6 mm, respectively. The use of intravascular ultrasound has been found to be a predictor of less restenosis (P = 0.02; HR: 0.02; CI: 0.01-0.59). The in-hospital and 1 year major adverse cardiac event rates were 7.8% and 13%. The annual cardiac death rates were 2.6%, 3.4%, and 5.3% in the first 3 years.The use of EES full metal jacket for long lesions is only associated with good short-term clinical and angiographic outcomes. Long-term follow-up has revealed a high cardiac death rate which may necessitate prolongation of dual antiplatelet therapy.
- Published
- 2012
28. A proteomics study to reveal the molecular response to protein misfolding in chondrocytes
- Author
-
Wai-ling Chan
- Subjects
Text mining ,business.industry ,Molecular Response ,Medicine ,Protein folding ,Computational biology ,business ,Bioinformatics ,Proteomics - Published
- 2012
29. The effectiveness of using mind mapping skills in enhancing secondary one and secondary four students' writing in a CMI school
- Author
-
Wai-ling Chan
- Subjects
business.industry ,Mathematics education ,Medicine ,business - Published
- 2012
30. Learning and teaching in Hong Kong kindergartens : a multiple case study
- Author
-
Wai-ling Chan
- Subjects
business.industry ,Mathematics education ,Multiple case ,Medicine ,business - Published
- 2012
31. Serial bone scintigraphy in a case of malignant epithelioid hemangioendothelioma
- Author
-
Ian Swainson, Wai-Ling Chan, and Donna Abbati
- Subjects
Male ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,General Medicine ,medicine.disease ,Bone and Bones ,Vascular Neoplasms ,Bone scintigraphy ,medicine ,Vascular Neoplasm ,Malignant epithelioid hemangioendothelioma ,Hemangioendothelioma, Epithelioid ,Humans ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,Radionuclide Imaging ,Epithelioid hemangioendothelioma ,Aged - Published
- 2012
32. Dual-time-point (18)F-FDG-PET/CT imaging in the assessment of suspected malignancy
- Author
-
Wai-Ling, Chan, Stuart C, Ramsay, Edwin R, Szeto, Judith, Freund, Judith M, Pohlen, Lisa C, Tarlinton, Andy, Young, Adam, Hickey, and Robert, Dura
- Subjects
Adult ,Aged, 80 and over ,Male ,Chi-Square Distribution ,Middle Aged ,Multimodal Imaging ,Sensitivity and Specificity ,Fluorodeoxyglucose F18 ,Neoplasms ,Positron-Emission Tomography ,Image Interpretation, Computer-Assisted ,Humans ,Female ,Whole Body Imaging ,Prospective Studies ,Radiopharmaceuticals ,Tomography, X-Ray Computed ,Aged - Abstract
INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management.A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images.Overall, there was a significant improvement (P0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions.(18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions.
- Published
- 2011
33. Small Molecule Inhibitors That Selectively Block Dengue Virus Methyltransferase*
- Author
-
Julien Lescar, Ru Hui Ng, Wai Ling Chan, Hongping Dong, Zheng Yin, Louis Sebastian Sonntag, Yap Li Jian, Christophe Bodenreider, Mei Ding, Shahul Nilar, Boping Liu, Ka Yan Chung, Thomas H. Keller, Paul Monaghan, Gang Wang, Pei Yong Shi, Alex Chao, Gladys Lee, Siew Pheng Lim, Gang Zou, T. R. Vedananda, and Christian G. Noble
- Subjects
S-Adenosylmethionine ,Methyltransferase ,Viral protein ,Dengue virus ,medicine.disease_cause ,Crystallography, X-Ray ,Biochemistry ,Microbiology ,Antiviral Agents ,Dengue ,Viral Proteins ,medicine ,Humans ,Binding site ,Enzyme Inhibitors ,Molecular Biology ,Binding Sites ,biology ,Cell Biology ,Methylation ,Methyltransferases ,Dengue Virus ,biology.organism_classification ,Small molecule ,Enzyme structure ,Flavivirus - Abstract
Crystal structure analysis of Flavivirus methyltransferases uncovered a flavivirus-conserved cavity located next to the binding site for its cofactor, S-adenosyl-methionine (SAM). Chemical derivatization of S-adenosyl-homocysteine (SAH), the product inhibitor of the methylation reaction, with substituents that extend into the identified cavity, generated inhibitors that showed improved and selective activity against dengue virus methyltransferase (MTase), but not related human enzymes. Crystal structure of dengue virus MTase with a bound SAH derivative revealed that its N6-substituent bound in this cavity and induced conformation changes in residues lining the pocket. These findings demonstrate that one of the major hurdles for the development of methyltransferase-based therapeutics, namely selectivity for disease-related methyltransferases, can be overcome.
- Published
- 2010
34. Inhibition of dengue virus RNA synthesis by an adenosine nucleoside
- Author
-
Min Qing, Wai Ling Chan, Boping Liu, Melissa Lo, Helen Gu, Hui Pen Tan, Wouter Schul, Handan He, Ranga Rao, Hao Ying Xu, Gang Wang, Jeyaraj Duraiswamy, Thomas H. Keller, Sarah Liung, Pei Yong Shi, Yen Liang Chen, Chin Chin Lim, Ravinder Reddy Kondreddi, Andy Yip, and Zheng Yin
- Subjects
Male ,Small interfering RNA ,Adenosine ,Adenosine kinase ,Antiviral Agents ,Polymerase Chain Reaction ,Cell Line ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Replicon ,Phosphorylation ,RNA, Small Interfering ,Rats, Wistar ,Adenosine Kinase ,Pharmacology ,biology ,Kinase ,RNA ,RNA virus ,Dengue Virus ,biology.organism_classification ,Molecular biology ,Rats ,Infectious Diseases ,Biochemistry ,biology.protein ,RNA, Viral ,Nucleoside ,medicine.drug - Abstract
We recently reported that (2 R ,3 R ,4 R ,5 R )-2-(4-amino-pyrrolo[2,3- d ]pyrimidin-7-yl)-3-ethynyl-5-hydroxy-methyl-tetrahydro-furan-3,4-diol is a potent inhibitor of dengue virus (DENV), with 50% effective concentration (EC 50 ) and cytotoxic concentration (CC 50 ) values of 0.7 μM and >100 μM, respectively. Here we describe the synthesis, structure-activity relationship, and antiviral characterization of the inhibitor. In an AG129 mouse model, a single-dose treatment of DENV-infected mice with the compound suppressed peak viremia and completely prevented death. Mode-of-action analysis using a DENV replicon indicated that the compound blocks viral RNA synthesis. Recombinant adenosine kinase could convert the compound to a monophosphate form. Suppression of host adenosine kinase, using a specific inhibitor (iodotubercidin) or small interfering RNA (siRNA), abolished or reduced the compound's antiviral activity in cell culture. Studies of rats showed that 14 C-labeled compound was converted to mono-, di-, and triphosphate metabolites in vivo . Collectively, the results suggest that this adenosine inhibitor is phosphorylated to an active (triphosphate) form which functions as a chain terminator for viral RNA synthesis.
- Published
- 2010
35. Peptide deformylase inhibitors of Mycobacterium tuberculosis: synthesis, structural investigations, and biological results
- Author
-
Arkadius Pichota, Kakoli Mukherjee, Amelia Yap, Wai Ling Chan, Thomas H. Keller, Zheng Yin, Gladys Lee, Michael H. Cynamon, Mei Ding, Mahesh Nanjundappa, Thomas Dick, David Beer, Jeanette W. P. Teo, Pamela Thayalan, Jeyaraj Duraiswamy, Wuyi Meng, James Koehn, Mark Schreiber, Carolyn Shoen, Kirk Clark, Sarah Liung, Mei Xu, Gang Wang, Xinyi Ngew, Shi-Hao Pan, Jenefer Alam, Xiaoling Xie, and Ida Ma
- Subjects
Chemistry, Pharmaceutical ,Clinical Biochemistry ,Antitubercular Agents ,Molecular Conformation ,Pharmaceutical Science ,Microbial Sensitivity Tests ,Crystallography, X-Ray ,Biochemistry ,Gatifloxacin ,Amidohydrolases ,Mycobacterium tuberculosis ,Peptide deformylase ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Drug Discovery ,Hydrolase ,Humans ,Tuberculosis ,Molecular Biology ,Antibacterial agent ,chemistry.chemical_classification ,Hydroxamic acid ,biology ,fungi ,Organic Chemistry ,Biological activity ,biology.organism_classification ,Mycobacterium bovis ,Drug Resistance, Multiple ,Enzyme ,chemistry ,Models, Chemical ,Enzyme inhibitor ,Drug Design ,biology.protein ,Molecular Medicine ,Fluoroquinolones - Abstract
Bacterial peptide deformylase (PDF) belongs to a subfamily of metalloproteases catalyzing the removal of the N-terminal formyl group from newly synthesized proteins. We report the synthesis and biological activity of highly potent inhibitors of Mycobacterium tuberculosis (Mtb) PDF enzyme as well as the first X-ray crystal structure of Mtb PDF. Structure-activity relationship and crystallographic data clarified the structural requirements for high enzyme potency and cell based potency. Activities against single and multi-drug-resistant Mtb strains are also reported.
- Published
- 2008
36. Yellow fever virus NS3 protease: peptide-inhibition studies
- Author
-
Kristina Löhr, Sejal J. Patel, John E. Knox, Thomas H. Keller, Subhash G. Vasudevan, Gang Wang, Zheng Yin, Ngai Ling Ma, Wai-Ling Chan, Weiling Wang, Wai Yee Phong, K. R. Ranga Rao, Aruna Sampath, and Siew Pheng Lim
- Subjects
Proteases ,viruses ,medicine.medical_treatment ,Molecular Sequence Data ,Dengue virus ,Viral Nonstructural Proteins ,medicine.disease_cause ,Antiviral Agents ,Virus ,Dengue fever ,Microbiology ,Substrate Specificity ,Virology ,medicine ,Amino Acid Sequence ,Enzyme Inhibitors ,NS3 ,Protease ,Binding Sites ,biology ,Serine Endopeptidases ,biology.organism_classification ,medicine.disease ,Recombinant Proteins ,NS2-3 protease ,Flavivirus ,Kinetics ,Yellow fever virus ,Oligopeptides ,Sequence Alignment ,RNA Helicases - Abstract
A recombinant form of yellow fever virus (YFV) NS3 protease, linked via a nonapeptide to the minimal NS2B co-factor sequence (CF40-gly-NS3pro190), was expressed in Escherichia coli and shown to be catalytically active. It efficiently cleaved the fluorogenic tetrapeptide substrate Bz-norleucine-lysine-arginine-arginine-AMC, which was previously optimized for dengue virus NS2B/3 protease. A series of small peptidic inhibitors based on this substrate sequence readily inhibited its enzymic activity. To understand the structure–activity relationship of the inhibitors, they were docked into a homology model of the YFV NS2B/NS3 protease structure. The results revealed that the P1 and P2 positions are most important for inhibitor binding, whilst the P3 and P4 positions have much less effect. These findings indicate that the characteristics of YFV protease are very similar to those reported for dengue and West Nile virus proteases, and suggest that pan-flavivirus NS3 protease drugs may be developed for flaviviral diseases.
- Published
- 2007
37. Peptide inhibitors of dengue virus NS3 protease. Part 2: SAR study of tetrapeptide aldehyde inhibitors
- Author
-
Sejal J. Patel, Claus Ehrhardt, Weiling Wang, John E. Knox, Thomas H. Keller, Subhash G. Vasudevan, K. R. Ranga Rao, Gang Wang, David Beer, Ngai Ling Ma, Viral Patel, Xinyi Ngew, Wai-Ling Chan, Zheng Yin, and Siew Pheng Lim
- Subjects
Models, Molecular ,Time Factors ,Stereochemistry ,medicine.medical_treatment ,Chemistry, Pharmaceutical ,Clinical Biochemistry ,Pharmaceutical Science ,Tripeptide ,Dengue virus ,Viral Nonstructural Proteins ,medicine.disease_cause ,Biochemistry ,Binding, Competitive ,Substrate Specificity ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,medicine ,Protease Inhibitors ,Enzyme Inhibitors ,Molecular Biology ,NS3 ,Aldehydes ,Dipeptide ,Protease ,Tetrapeptide ,biology ,Dose-Response Relationship, Drug ,Chemistry ,Organic Chemistry ,Serine Endopeptidases ,Hydrogen Bonding ,Dengue Virus ,Ketones ,Boronic Acids ,Protease inhibitor (biology) ,Kinetics ,Models, Chemical ,Enzyme inhibitor ,Drug Design ,biology.protein ,Molecular Medicine ,Peptides ,RNA Helicases ,medicine.drug ,Protein Binding - Abstract
With the aim of discovering potent and selective dengue NS3 protease inhibitors, we systematically synthesized and evaluated a series of tetrapeptide aldehydes based on lead aldehyde 1 (Bz-Nle-Lys-Arg-Arg-H, K(i)=5.8 microM). In general, we observe that interactions of P(2) side chain are more important than P(1) followed by P(3) and P(4). Tripeptide and dipeptide aldehyde inhibitors also show low micromolar activity. Additionally, an effective non-basic, uncharged replacement of P(1) Arg is identified.
- Published
- 2005
38. What happens after a lung scan? Management and outcome of patients in a regional hospital
- Author
-
Martin G Carolan, Richard McLean, and Wai-Ling Chan
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Scintigraphy ,Recurrence ,medicine ,Pulmonary angiography ,Humans ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,Lung ,Cause of death ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Anticoagulants ,Lung scan ,Middle Aged ,medicine.disease ,Surgery ,Pulmonary embolism ,Regional hospital ,medicine.anatomical_structure ,Treatment Outcome ,Female ,Doppler ultrasound ,Radiology ,business ,Pulmonary Embolism - Abstract
Pulmonary embolism (PE) remains a common preventable cause of death in hospitalized patients. The purpose of this study is to examine the in-hospital management, complications of treatment and clinical outcomes of inpatients undergoing lung scintigraphy for the diagnosis of PE in a regional hospital. Two hundred consecutive inpatients with suspected PE were enrolled. The results of lung scans, stratified according to the probability of pulmonary embolism, were correlated with anticoagulation status, discharge diagnosis, haemorrhagic complications and clinical outcome at 6 months. The use of complementary imaging investigations was also determined. Other imaging was performed infrequently (Doppler ultrasound in 18% of patients, CT pulmonary angiography (CT-PA) in 0.5% and conventional pulmonary angiography in 4% of patients). Long-term anticoagulation was initiated in 66 patients (33%), including 10 with intermediate probability lung scans (IPLS) who had no further investigations. Major haemorrhage occurred in 14% of all long-term anticoagulated patients followed up. The recognized recurrence rate was very low (3%) and there was no documented mortality from PE. Most patients with suspected PE are treated on the basis of the lung scan result without further tests. However, other imaging (especially CT-PA and conventional pulmonary angiography) should be performed prior to anticoagulation in patients with IPLS in whom the diagnosis is in doubt. Standard anticoagulation for 6 months appears to be effective for PE, and the recurrence rate is low. However, it has a significant risk of major haemorrhagic complications.
- Published
- 2002
39. Gallium avid breast carcinoma
- Author
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Martin G Carolan, Surjit S. Wadhwa, and Wai-Ling Chan
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Breast Neoplasms ,Gallium Radioisotopes ,Adenocarcinoma ,Breast cancer ,medicine ,Carcinoma ,Humans ,Radiology, Nuclear Medicine and imaging ,skin and connective tissue diseases ,Radionuclide Imaging ,business.industry ,Bone marrow failure ,medicine.disease ,Pancytopenia ,Lymphoma ,Thallium Radioisotopes ,medicine.anatomical_structure ,Female ,Bone marrow ,Breast carcinoma ,business ,Bone Marrow Neoplasms - Abstract
SUMMARY Primary breast carcinomas are generally thallium (Tl-201) avid but uncommonly accumulate gallium (GA-67). Therefore, GA-67 scans are not routinely performed in patients with suspected breast cancer. We report a rare case of a primary breast carcinoma with bone marrow metastases where the primary lesion was GA-67 avid but did not accumulate Tl-201. The case also illustrated an unusual presentation of aggressive metastatic breast adenocarcinoma with pancytopenia or bone marrow failure. The extensive bone marrow metastases of the primary breast carcinoma were evident on both the Tl-201 and GA-67 scans.
- Published
- 2002
40. Retropharyngeal abscess on a Ga-67 scan: a case report
- Author
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Martin G. Carolan, Wai-Ling Chan, and Vivian B. Fernandes
- Subjects
medicine.medical_specialty ,Gallium Radioisotopes ,Scintigraphy ,Sensitivity and Specificity ,Sepsis ,Diagnosis, Differential ,medicine ,Sore throat ,Humans ,Radiology, Nuclear Medicine and imaging ,Abscess ,Radionuclide Imaging ,medicine.diagnostic_test ,business.industry ,Pharynx ,Retropharyngeal abscess ,General Medicine ,Semiology ,medicine.disease ,Retropharyngeal Abscess ,Dysphagia ,Surgery ,Anti-Bacterial Agents ,medicine.anatomical_structure ,Child, Preschool ,Injections, Intravenous ,Female ,Radiology ,medicine.symptom ,Radiopharmaceuticals ,business ,Tomography, X-Ray Computed ,Follow-Up Studies - Abstract
A retropharyngeal abscess is a potentially fatal deep neck infection. Classical symptoms include fever, neck swelling, sore throat, dysphagia, and cervical rigidity. Sometimes small children present with nonspecific symptoms. We report a rare case whereby the Ga-67 citrate scan was the first investigation to reveal an inflammatory process in the retropharyngeal or submastoid region of a 3-year-old child with sepsis. This directed the line of investigation to a more precise anatomic imaging modality, CT scanning, to localize the abscess. With prompt administration of intravenous antibiotics, the child recovered quickly and did not require surgery. The Ga-67 scan is thus a useful screening test to detect inflammatory foci because of its high sensitivity. It is also valuable in the follow-up of the patient's response to therapy.
- Published
- 1999
41. 54. What happens after a lung scan? Management and outcome of patients in a regional hospital
- Author
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R. McLean, M. G. Carolan, and Wai-Ling Chan
- Subjects
Regional hospital ,medicine.medical_specialty ,business.industry ,Emergency medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,General Medicine ,Lung scan ,Intensive care medicine ,business ,Outcome (game theory) - Published
- 2001
42. Bony Metastases Seen on Scintigraphy with Samarium-153
- Author
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Surjit Singh-Wadhwa, Naresh Verma, and Wai-Ling Chan
- Subjects
medicine.medical_treatment ,Mammary gland ,Bone Neoplasms ,Breast Neoplasms ,Scintigraphy ,Metastasis ,Organophosphorus Compounds ,Organometallic Compounds ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,Bone pain ,Radioisotopes ,Samarium ,medicine.diagnostic_test ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Radiation therapy ,medicine.anatomical_structure ,Bone scintigraphy ,Female ,Intractable pain ,Radiopharmaceuticals ,medicine.symptom ,business ,Nuclear medicine ,Breast carcinoma - Abstract
The authors present a case of bony metastases secondary to breast carcinoma demonstrated on bone scintigraphy and scintigraphy using samarium-153 (Sm-153) lexidronam. Sm-153 is used as to palliate bone pain. Images of comparable quality on bone and Sm-153 scintigraphy have been described but are uncommon.
- Published
- 2002
43. Effectiveness of a patient/carer empowerment programme for people with hip fractures.
- Author
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Wai-Shan Louie, Stephanie, Mei-Yee Poon, Shuk-Yiu Yu, Wai-Ling Chan, Kai-Ming Au, and Kam-Man Wong
- Subjects
ACCIDENTAL fall prevention ,CAREGIVER education ,CHI-squared test ,CONFIDENCE intervals ,BONE fractures ,HIP joint injuries ,INTELLECT ,OCCUPATIONAL therapy ,HEALTH outcome assessment ,PATIENT education ,PROBABILITY theory ,SCALES (Weighing instruments) ,SELF-efficacy ,T-test (Statistics) ,ACTIVITIES of daily living ,RANDOMIZED controlled trials ,HUMAN services programs ,PRE-tests & post-tests - Abstract
The article discusses a comparative study on the effects of patient and carer empowerment programme (PCEP) and conventional hip fracture protocol. The factors included hip fractures related knowledge, activity of daily living (ADL) independence, and fall efficacy on ADL. The study findings revealed that the PCEP allowed patients to promote skills and knowledge of hip fractures and ADL.
- Published
- 2012
- Full Text
- View/download PDF
44. Dual-time-point 18F-FDG-PET/CT imaging in the assessment of suspected malignancy.
- Author
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Wai-Ling Chan, Ramsay, Stuart C., Szeto, Edwin R., Freund, Judith, Pohlen, Judith M., Tarlinton, Lisa C., Young, Andy, Hickey, Adam, and Dura, Robert
- Subjects
- *
CANCER patients , *MEDICAL imaging systems , *PRECANCEROUS conditions , *INCURABLE diseases , *CARCINOGENS , *CARCINOMA in situ - Abstract
Introduction (purpose of the study): The objective of this study was to assess whether dual-time-point 18F-fluoro-2-deoxyglucose (18F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management. Methods: A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images. Results: Overall, there was a significant improvement ( P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point 18FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions. Conclusions: 18F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point 18FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
45. The transition from kindergarten to primary school, as experienced by teachers, parents and children in Hong Kong.
- Author
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Wai Ling Chan
- Subjects
- *
KINDERGARTEN , *PARENT-child relationships , *PRIMARY school teachers , *PRIMARY school teaching , *CURRICULUM , *PRIMARY education , *ACTIVITY programs in education - Abstract
This study investigates the transition from kindergarten to primary school through the experiences of the teachers, parents and children involved. Emphasis is given to the transitional activities participated in by the stakeholders and the effectiveness of these activities. These experiences of children's transition to school will inform further research into the design of effective transition programmes in the local context. The means of investigation in this study include questionnaires, semi-structured interviews and observations. The results show that the teachers and parents generally believed that the children performed quite well academically, although the primary school teachers reported that they were average in discipline. The findings from both the questionnaires and the interviews show that most of the respondents agreed that strong connections between kindergarten, primary school and parents could facilitate a smoother transition to school. However, in reality, both kindergarten and primary school teachers showed ignorance of each other's teaching practices and curriculum. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
46. An adenosine nucleoside inhibitor of dengue virus.
- Author
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Zheng Yin, Yen-Liang Chen, Wouter Schul, Qing-Yin Wang, Feng Gu, Jeyaraj Duraiswamy, Ravinder Reddiy Kondreddi, Pornwaratt Niyomrattanakit, Suresh B. Lakshminarayana, Anne Goh, Hao Ying Xu, Wei Liu, Boping Liu, Joanne V. H. Lim, Chuan Young Ng, Min Qing, Chin Chin Lim, Andy Yip, Gang Wang, and Wai Ling Chan
- Subjects
DENGUE viruses ,ADENOSINES ,DENGUE ,RNA polymerases ,PHARMACOKINETICS ,VIREMIA ,CYTOKINES ,FLAVIVIRAL diseases ,PREVENTION - Abstract
Dengue virus (DENV), a mosquito-borne flavivirus. is a major public health threat. The virus poses risk to 2.5 billion people worldwide and causes 50 to 100 million human infections each year. Neither a vaccine nor an antiviral therapy is currently available for prevention and treatment of DENV infection. Here, we report a previously undescribed adenosine analog, NIT0008, that potently inhibits DENV both in vitro and in vivo.. In addition to the 4 serotypes of DENV, NITD008 inhibits other flaviviruses, including West Nile virus, yellow fever virus, and Powassan virus. The compound also suppresses hepatitis (virus, but it does not inhibit nonflaviviruses, such as Western equine encephalitis virus and vesicular stomatitis virus. A triphosphate form of NITD008 directly inhibits the RNA-dependent RNA polymerase activity of DENV, indicating that the compound functions as a chain terminator during viral RNA synthesis. NITD008 has good in vivo pharmacokinetic properties and is biologically available through oral administration. Treatment of DENV-infected mice with NITD008 suppressed peak viremia, reduced cytokine elevation, and completely prevented the infected mice from death. No observed adverse effect level (NOAEL) was achieved when rats were orally dosed with NITD008 at 50 mg/kg daily for 1 week. However, NOAEL could not be accomplished when rats and dogs were dosed daily for 2 weeks. Nevertheless, our results have proved the concept that a nucleoside inhibitor could be developed for potential treatment of flavivirus infections. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
47. 《「敢」問「感」學:課程設計與推行》
- Author
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Wai Ling CHAN and To-Chan, Sing Pui Tikky
48. 《幼兒創意之天與地》
- Author
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Cheung, Lai Ha Lily and Wai Ling CHAN
49. English immersion experience for Hong Kong preschoolers: What can we hear from children's voices?
- Author
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Ng, Mei Lee and Wai Ling CHAN
50. 教師篇
- Author
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Wong-Tsui, King Yuk Anita and Wai Ling CHAN
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