Displaying publications 1 - 20 of 168 in total

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  1. Hor YL, Kim YJ, Ugap A, Chabrillange N, Sinniah UR, Engelmann F, et al.
    Ann Bot, 2005 Jun;95(7):1153-61.
    PMID: 15781438
    The purpose of this study was to investigate the basis of the optimal hydration status for cryopreservation of intermediate oily seeds using Citrus as a model.
  2. Radu S, Abdul Mutalib S, Rusul G, Ahmad Z, Morigaki T, Asai N, et al.
    Appl Environ Microbiol, 1998 Mar;64(3):1153-6.
    PMID: 9501454
    Twelve strains of Escherichia coli O157:H7 were isolated from 9 of 25 beef samples purchased from retail stores in Malaysia. These strains produced Shiga toxin 2 with or without Shiga toxin 1 and had the eae gene and a 60-MDa plasmid. The antibiograms and the profiles of the arbitrarily primed PCR of the strains were diverse, suggesting that the strains may have originated from diverse sources.
  3. Shu L, Sulaiman AH, Huang YS, Fones Soon Leng C, Crutel VS, Kim YS
    Asian J Psychiatr, 2014 Apr;8:26-32.
    PMID: 24655622 DOI: 10.1016/j.ajp.2013.09.009
    OBJECTIVE: This randomized, double-blind study evaluates the efficacy and tolerability of agomelatine, using fluoxetine as an active comparator, in Asian patients suffering from moderate to severe major depressive disorder (MDD).
    METHOD: Patients were randomly assigned to receive either agomelatine (25-50mg/day, n=314) or fluoxetine (20-40mg/day, n=314) during an 8-week treatment period. The main outcome measure was the change in Hamilton Depression Rating Scale 17 items (HAM-D17) scores. Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness (CGI-S) and Improvement of illness (CGI-I), patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire (LSEQ) and anxiety using the Hamilton Anxiety Rating Scale (HAM-A) scores. Tolerability and safety evaluations were based on emergent adverse events.
    RESULTS: Agomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population. Mean changes over 8 weeks were clinically relevant and similar in both groups (-14.8±7.3 and -15.0±8.1 on HAM-D17 scale in agomelatine and fluoxetine groups, respectively). The between-group difference reached statistical significance on non-inferiority test (p=0.015). Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups. The two treatments were equally effective on the symptoms of both anxiety and sleep. The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population.
    CONCLUSIONS: Agomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients.
    KEYWORDS: Agomelatine; Antidepressant; Asian population; Fluoxetine
    Study site in Malaysia: Psychiatric clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  4. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  5. Wadhwa M, Kang HN, Jivapaisarnpong T, WHO implementation workshop on guidelines on procedures and data requirements for changes to approved biotherapeutic products, Andalucia LR, Blades CDRZ, et al.
    Biologicals, 2020 May;65:50-59.
    PMID: 31959504 DOI: 10.1016/j.biologicals.2019.12.008
    The first global workshop on implementation of the WHO guidelines on procedures and data requirements for changes to approved biotherapeutic products adopted by the WHO Expert Committee in 2018 was held in June 2019. The workshop participants recognized that the principles based on sound science and the potential for risk, as described in the WHO Guidelines on post-approval changes, which constitute the global standard for product life-cycle management are providing clarity and helping national regulatory authorities in establishing guidance while improving time-lines for an efficient regulation of products. Consequently, the regulatory situation for post-approval changes and guideline implementation is changing but there is a disparity between different countries. While the guidelines are gradually being implemented in some countries and also being considered in other countries, the need for regional workshops and further training on post-approval changes was a common theme reiterated by many participants. Given the complexities relating to post-approval changes in different regions/countries, there was a clear understanding among all participants that an efficient approach for product life-cycle management at a national level is needed to ensure faster availability of high standard, safe and efficacious medicines to patients as per the World Health Assembly Resolution 67.21.
  6. Ma RC, Hu C, Tam CH, Zhang R, Kwan P, Leung TF, et al.
    Diabetologia, 2013 Jun;56(6):1291-305.
    PMID: 23532257 DOI: 10.1007/s00125-013-2874-4
    AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.

    METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.

    RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p 

  7. Jang JH, Gomez RD, Bumbea H, Nogaieva L, Wong LLL, Lim SM, et al.
    EJHaem, 2023 Feb;4(1):26-36.
    PMID: 36819188 DOI: 10.1002/jha2.632
    Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double-blind, multi-national cross-over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12-ECU or ECU-SB12. Four weekly infusions of 600 mg eculizumab were followed by fortnightly infusions of 900 mg until week 50 (ECU/SB12 cross-over at week 26). Primary endpoints were LDH at week 26 and the time-adjusted area under the effect curve (AUEC) of LDH over weeks 14‒26 and 40‒52. Among 46 patients (92%) who completed the study, the least squares mean (LSM) difference in LDH at week 26 (34·48; 95% confidence interval [CI] -47·66‒116·62 U/l) and geometric LSM ratio of time-adjusted AUEC of LDH (1·08; 90% CI 0·95‒1·23) were within pre-defined equivalence margins. Mean numbers of transfused red blood cell units, other secondary endpoints, pharmacokinetics, and pharmacodynamics were comparable. No patients developed anti-drug antibodies. Treatment-emergent adverse events were reported in 72% and 68% of patients in the SB12 and ECU treatment groups, respectively. The results demonstrate equivalence of SB12 to ECU and support SB12-use in PNH patients.
  8. Phung VLH, Oka K, Honda Y, Hijioka Y, Ueda K, Seposo XT, et al.
    Environ Res, 2023 Feb 01;218:114988.
    PMID: 36463996 DOI: 10.1016/j.envres.2022.114988
    BACKGROUND: Climate change and its subsequent effects on temperature have raised global public health concerns. Although numerous epidemiological studies have shown the adverse health effects of temperature, the association remains unclear for children aged below five years old and those in tropical climate regions.

    METHODS: We conducted a two-stage time-stratified case-crossover study to examine the association between temperature and under-five mortality, spanning the period from 2014 to 2018 across all six regions in Malaysia. In the first stage, we estimated region-specific temperature-mortality associations using a conditional Poisson regression and distributed lag nonlinear models. We used a multivariate meta-regression model to pool the region-specific estimates and examine the potential role of local characteristics in the association, which includes geographical information, demographics, socioeconomic status, long-term temperature metrics, and healthcare access by region.

    RESULTS: Temperature in Malaysia ranged from 22 °C to 31 °C, with a mean of 27.6 °C. No clear seasonality was observed in under-five mortality. We found no strong evidence of the association between temperature and under-five mortality, with an "M-" shaped exposure-response curve. The minimum mortality temperature (MMT) was identified at 27.1 °C. Among several local characteristics, only education level and hospital bed rates reduced the residual heterogeneity in the association. However, effect modification by these variables were not significant.

    CONCLUSION: This study suggests a null association between temperature and under-five mortality in Malaysia, which has a tropical climate. The "M-" shaped pattern suggests that under-fives may be vulnerable to temperature changes, even with a small temperature change in reference to the MMT. However, the weak risks with a large uncertainty at extreme temperatures remained inconclusive. Potential roles of education level and hospital bed rate were statistically inconclusive.

  9. Tern PJW, Ho AKH, Sultana R, Ahn Y, Almahmeed W, Brieger D, et al.
    PMID: 32584986 DOI: 10.1093/ehjqcco/qcaa057
    The aim of this study is to gain insight into the differences in demographics of ST-elevation myocardial infarction (STEMI) patients in Asia-Pacific, as well as inter-country variation in treatment and mortality outcomes. Systematic review of published studies and reports from known registries in Australia, Japan, Korea, Singapore, and Malaysia that began data collection after the year 2000. Supplementary self-report survey questionnaire on public health data answered by representative cardiologists working in these countries. Twenty studies comprising of 158 420 patients were included in the meta-analysis. The mean age was 61.6 years. Chronic kidney disease prevalence was higher in Japan, while dyslipidaemia was low in Korea. Use of aspirin, P2Y12 inhibitors, and statins were high throughout, but ACEi/ARB and β-blocker prescriptions were lower in Japan and Malaysia. Reperfusion strategies varied greatly, with high rates of primary percutaneous coronary intervention (pPCI) in Korea (91.6%), whilst Malaysia relies far more on fibrinolysis (72.6%) than pPCI (9.6%). Similarly, mortality differed, with 1-year mortality from STEMI was considerably greater in Malaysia (17.9%) and Singapore (11.2%) than in Korea (8.1%), Australia (7.8%), and Japan (6.2%). The countries were broadly similar in development and public health indices. Singapore has the highest gross national income and total healthcare expenditure per capita, whilst Malaysia has the lowest. Primary PCI is available in all countries 24/7/365. Despite broadly comparable public health systems, differences exist in patient profile, in-hospital treatment, and mortality outcomes in these five countries. Our study reveals areas for improvements. The authors advocate further registry-based multi-country comparative studies focused on the Asia-Pacific region.
  10. Kim YB, Okuda J, Matsumoto C, Morigaki T, Asai N, Watanabe H, et al.
    FEMS Microbiol Lett, 1998 Sep 01;166(1):43-8.
    PMID: 9741083
    Escherichia coli strains isolated from patients with diarrhea or hemolytic uremic syndrome (HUS) at Pusan University Hospital, South Korea, between 1990 and 1996 were examined for traits of the O157:H7 serogroup. One strain isolated from a patient with HUS belonged to the O157:H7 serotype, possessed a 60-MDa plasmid, the eae gene, and ability to produce Shiga toxin 1 but not Shiga toxin 2. Arbitrarily primed PCR analysis suggested that this strain is genetically very close to a O157:H7 strain isolated in Japan.
  11. Ahn J, Lim J, Jusoh N, Lee J, Park TE, Kim Y, et al.
    PMID: 31380359 DOI: 10.3389/fbioe.2019.00168
    Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.
  12. Liu KT, Kueh YC, Arifin WN, Kim Y, Kuan G
    Front Psychol, 2018;9:2402.
    PMID: 30618907 DOI: 10.3389/fpsyg.2018.02402
    This study's purpose was to examine the structural relationship of the transtheoretical model (TTM) and the amount of physical activity (PA) among undergraduate students in health and medicine at Universiti Sains Malaysia. A cross-sectional study was carried out among students who took part in the co-curricular program. Co-curricular program includes activities that take place outside of the regular lectures or tutorials in the University. Students recruited through purposive sampling were informed that their participation was entirely voluntarily. Those interested completed the self-administered questionnaire, which consisted of the decisional balance, processes of change, self-efficacy, stages of change scales, and Godin leisure-time exercise questionnaire. Data were analyzed using Mplus version 8 for descriptive statistics and structural equation modeling analysis for inferential statistics. A total of 562 students participated in the study. The majority of the students was female (79.0%) and Malay (73.3%) and average of exercise sessions per week was 2.62, with a mean of 43.37 min per exercise session. The final structural model fit the data well based on several fit indices (SRMR = 0.046, RMSEA (CI: 90%) = 0.061 (0.045, 0.078), RMSEA p = 0.130). The model showed that stages of change significantly affected self-efficacy (p < 0.001), pros (benefits of exercise; p < 0.001), cons (barriers to exercise; p = 0.022), and processes of change (p < 0.001). The model also showed significant inter-relationships among the TTM constructs and supported seven hypotheses. Among all the variables examined, only processes of change significantly affected PA (p < 0.001). However, stages of change (p < 0.001) and pros (p =< 0.001) had significant indirect effects on PA via processes of change. The findings support that individuals' stages of change affect their self-efficacy level, or the ability to make positive and negative decisions and perform behavior accordingly. The study confirms that making correct decisions and taking action accordingly can increase PA levels.
  13. Kim Y, Kuan G
    PMID: 32545921 DOI: 10.3390/ijerph17124251
    The present study examines the relationship between drinking behaviour and drinking refusal self-efficacy among university students, with a focus on the influential roles of sports type and gender. A total of 354 students from Seoul National University of Science and Technology volunteered and participated in this study. The Korean Alcohol Use Disorders Identification Test (AUDIT-K), the Korean Drinking Refusal Self-Efficacy (DRSE) Questionnaire-Revised, and a questionnaire measuring participation in sports activities were administered to measure students' alcohol drinking behaviours, refusal self-efficacy and sport-related activities, respectively. The data were analysed using descriptive statistics, two-way ANOVAs, correlation analysis, and regression analysis. The subdomains of DRSE had significant influences on binge drinking. Specifically, low DRSE in situations involving social pressure played a key role in predicting increased binge drinking. There was also a significant relationship between sports type and drinking behaviour, but only for male students. Those who participated in individual sports binge drank less than those who participated in team sports. Finally, gender differences were also revealed in drinking behaviour. Male students were more likely to binge drink compared to their female counterparts. This study offers a foundation for practical interventions to help control problematic drinking behaviour among university students.
  14. Mollica MA, Mayer DK, Oeffinger KC, Kim Y, Buckenmaier SS, Sivaram S, et al.
    JCO Glob Oncol, 2020 09;6:1394-1411.
    PMID: 32955943 DOI: 10.1200/GO.20.00180
    PURPOSE: The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care.

    METHODS: We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes.

    RESULTS: Seven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care.

    CONCLUSION: This information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.

  15. Zhu L, Kim Y, Yang Z
    J Acupunct Meridian Stud, 2018 Dec;11(6):343-354.
    PMID: 30195824 DOI: 10.1016/j.jams.2018.08.209
    Auriculotherapy has been extensively used for chronic spontaneous urticaria in China. However, the evidence of its effectiveness and safety for the treatment of chronic spontaneous urticaria is insufficient. Hence, we conducted this study to compare auriculotherapy or auriculotherapy joint treatment with Western medicine for the cure of chronic spontaneous urticaria. This meta-analysis of seven randomized controlled trials showed that auriculotherapy or auriculotherapy joint treatment was significantly superior to Western medicine in curing clinical signs and symptoms of chronic spontaneous urticaria [odds ration (OR), 2.61; 95% confidence interval (CI), 1.54-4.43; p = 0.0004) and also better in total effect rate (OR, 3.81; 95% CI, 2.07-7.01; p<0.0001). But, auriculotherapy or auriculotherapy joint treatment was similar to Western medicine in improving clinical signs and symptoms of chronic spontaneous urticaria (OR, 0.74; 95% CI, 0.35-1.56; p = 0.42). Auriculotherapy or auriculotherapy joint treatment was safer than Western medicine for curing chronic spontaneous urticaria (OR, 0.26; 95% CI, 0.09-0.80; p = 0.02). Auriculotherapy alone or auriculotherapy joint treatment appears to be more effective and safer than Western medicine that contains antihistamines in the treatment of chronic spontaneous urticaria. However, these findings should be interpreted with caution due to the unclear risk bias of methodological quality, and further studies with large-scale, better, and more rigorously designed protocol are necessary to prove these findings.
  16. Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, et al.
    J Clin Oncol, 2023 Sep 10;41(26):4208-4217.
    PMID: 37379502 DOI: 10.1200/JCO.23.00515
    PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1.

    RESULTS: Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116). Observed safety of both treatments was consistent with their previously reported safety profiles.

    CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

  17. Mohamed M, Tandon N, Kim Y, Kopp I, Tanaka N, Mikamo H, et al.
    PMID: 37475682 DOI: 10.1177/19322968231186402
    Globally, health care workers (HCWs) are at a high risk of occupational exposure to needlestick injuries (NSIs). Needlestick injuries not only are associated with an increased risk of infections caused by bloodborne pathogens but are also a primary source of emotional distress and job burnout for HCWs and patients. Insulin injection-related NSIs are common among HCWs working in hospitals in the Asia-Pacific (APAC) region and impose a significant burden. Insulin pen needles have a high risk of transmitting infections (at both the patient-end and cartridge end of the sharp) after use. Recapping a needle after administering an insulin injection poses a major risk to HCWs. Currently, several safety-engineered needle devices (SENDs) are available with active or passive safety mechanisms. Passive insulin safety pen needles with dual-ended protection and automatic recapping capabilities have resulted in a significant drop in accidental punctures to HCWs while administering insulin to patients with diabetes. In this article, we have reviewed the burden and common causes of NSIs with insulin injections among HCWs in the APAC region. We have discussed current approaches to address the issues associated with NSIs and the benefits of introducing SENDs in health care settings, including long-term care facilities, nursing homes, and home care settings where patients may require assisted insulin injections. This review also summarizes key strategies/recommendations to prevent NSIs in HCWs and patients with diabetes in the APAC region.
  18. Jasuja S, Gallieni M, Jha V, Vachharajani T, Bhalla AK, Tan J, et al.
    Nephrology (Carlton), 2023 Dec;28(12):672-681.
    PMID: 37697492 DOI: 10.1111/nep.14236
    AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA).

    METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey.

    RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel.

    CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

  19. Kim Y, Griffin JM, Nor MNM, Zhang J, Freestone PS, Danesh-Meyer HV, et al.
    Neurotherapeutics, 2017 Oct;14(4):1148-1165.
    PMID: 28560708 DOI: 10.1007/s13311-017-0536-9
    The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion. Tonabersat inhibited connexin43 hemichannel-mediated ATP release during both ischemia and reperfusion phases, with direct channel block confirmed using electrophysiology. Tonabersat also reduced connexin43 gap junction coupling in vitro, but only at higher concentrations, with junctional plaques internalized and degraded via the lysosomal pathway. Systemic delivery of tonabersat in a rat bright-light retinal damage model (a model for dry age-related macular degeneration) resulted in significantly improved functional outcomes assessed using electroretinography. Tonabersat also prevented thinning of the retina, especially the outer nuclear layer and choroid, assessed using optical coherence tomography. We conclude that tonabersat, already given orally to over 1000 humans in clinical trials (as a potential treatment for, and prophylactic treatment of, migraine because it was thought to inhibit cortical spreading depression), is a connexin hemichannel inhibitor and may have the potential to be a novel treatment of central nervous system injury and chronic neuroinflammatory disease.
  20. Bornstein J, Roux S, Kjeld Petersen L, Huang LM, Dobson SR, Pitisuttithum P, et al.
    Pediatrics, 2021 01;147(1).
    PMID: 33386332 DOI: 10.1542/peds.2019-4035
    BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9-14 years) receiving 2-dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16-26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36.

    METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36.

    RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%-100%; IgG-LIA: 91%-100%) and young women who received 3 doses (cLIA: 78%-98%; IgG-LIA: 91%-100%) remained seropositive 2 to 2.5 years after the last regimen dose.

    CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.

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